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, Michael Thiede
Published: 10 October 2017
Frontiers in Pharmacology, Volume 8; https://doi.org/10.3389/fphar.2017.00715

Abstract:
Pharmacoeconomics is receiving increasing attention globally as a set of tools ensuring efficient use of resources in health systems, albeit with different applications depending on the contextual, cultural and development stages of each country. The factors guiding design, implementation and optimisation of pharmacoeconomics as a steering tool under the universal health coverage paradigm are explored using case studies of Germany and South Africa. Findings German social health insurance is subject to the efficiency precept. Pharmaco-regulatory tools reflect the respective framework conditions under which they developed at particular points in time. The institutionalisation of pharmacoeconomics and its integration into the remit of the Institute for Quality and Efficiency in Health Care occurred only rather recently. The road has not been smooth, requiring political discourse and complex processes of negotiation. Although enshrined in the National Drug Policy of 1996, South Africa, has had a more fragmented approach to medicine selection and pricing with different policies in private and public sectors. The regulatory reform for use of pharmacoeconomic tools is ongoing and will be further shaped by the introduction of National Health Insurance. Conclusion A clear vision or framework is essential as the introduction of pharmacoeconomics into regulation is not a single event but rather a growing momentum. The path will always be subject to influences of politics, economics and market forces beyond the healthcare system so delays and modifications to pharmacoeconomic tools are to be expected. Health systems are dynamic and pharmacoeconomic reforms needs to be sufficiently flexible to evolve alongside.
Taleen S. Der-Ghazarian, Tanessa Call, Samantha N. Scott, Kael Dai, Samuel J. Brunwasser, Sean N. Noudali, Nathan S. Pentkowski,
Frontiers in Systems Neuroscience, Volume 11; https://doi.org/10.3389/fnsys.2017.00073

Abstract:
5-HT1B receptors (5-HT1BRs) modulate behavioral effects of cocaine. Here we examined the effects of the 5-HT1BR agonist 5-propoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-pyrrolo[3,2-b]pyridine (CP94253) on spontaneous and cocaine-induced locomotion and on cocaine-primed reinstatement of conditioned place preference (CPP) in male mice given daily repeated injections of either saline or cocaine (15 mg/kg, IP) for 20 days. In the locomotor activity experiment, testing occurred both 1 and 20 days after the final injection. In the CPP experiment, mice underwent conditioning procedures while receiving the last of their daily injections, which were given either during or ≥2 h after CPP procedures. The CPP procedural timeline consisted of baseline preference testing (days 12–13 of the chronic regimen), conditioning (days 14–19, 2 daily 30-min sessions separated by 5 h), CPP test (day 21), extinction (days 22–34; no injections), CPP extinction test (day 35), and reinstatement test (day 36). Mice that had not extinguished received additional extinction sessions prior to reinstatement testing on day 42. On test days, mice were pretreated with either saline or CP94253 (10 mg/kg, IP). Testing began 30 min later, immediately after mice were primed with either saline or cocaine (5 mg/kg for locomotion; 15 mg/kg for reinstatement). We found that CP94253 increased spontaneous locomotion in mice receiving repeated injections of either saline or cocaine when tested 1 day after the last injection, but had no effect on spontaneous locomotion after 20 days abstinence from repeated injections. Surprisingly, cocaine-induced locomotion was sensitized regardless of whether the mice had received repeated saline or cocaine. CP94253 attenuated expression of the sensitized locomotion after 20 days abstinence. A control experiment in noninjected, drug-naïve mice showed that CP94253 had no effect on spontaneous or cocaine-induced locomotion. Mice reinstated cocaine-CPP when given a cocaine prime, and CP94253 pretreatment attenuated cocaine reinstatement.The findings suggest that stress from repeated saline injections and/or co-housing with cocaine-injected mice may cross-sensitize with cocaine effects on locomotion and that CP94253 attenuates these effects, as well as reinstatement of cocaine-CPP. This study supports the idea that 5-HT1BR agonists may be useful anti-cocaine medications.
Frontiers in Aging Neuroscience, Volume 9; https://doi.org/10.3389/fnagi.2017.00330

Abstract:
Parkinson’s disease (PD), the most common neurodegenerative disorder is characterized by abnormal accumulation of α-synuclein aggregates known as Lewy bodies (LB) and loss of nigrostriatal dopaminergic neurons. Recent neuroimaging studies suggest that in the early phases of PD, synaptic and axonal damage anticipate the onset of a frank neuronal death. Paralleling, even post mortem studies on the brain of affected patients and on animal models support that synapses might represent the primary sites of functional and pathological changes. Indeed, α-synuclein microaggregation and spreading at terminals, by dysregulating the synaptic junction, would block neurotransmitter release, thus triggering a retrograde neurodegenerative process ending with neuronal cell loss by proceeding through the axons. Rather than neurodegeneration, loss of dopaminergic neuronal endings and axons could thus underlie the onset of connectome dysfunction and symptoms in PD and parkinsonisms. However, the manifold biases deriving from the interpretation of human brain imaging data hinder the validation of this hypothesis. Here, we present pivotal evidence supporting that novel comparative brain imaging studies, in patients and experimental models of PD in preliminary stages of disease, could be instrumental for proving whether synaptic endings are the sites where degeneration begins and initiating the factual achievement of disease modifying approaches. The need for such investigations is timely to define an early therapeutic window of intervention to attempt disease halting by terminal and/or axonal healing.
, Anne S. B. Johansen,
Published: 10 October 2017
Frontiers in Microbiology, Volume 8; https://doi.org/10.3389/fmicb.2017.01961

Abstract:
Bacterial biofilm formation is one of the main reasons for a negative treatment outcome and a high recurrence rate for many chronic infections in humans. The optimal way to study both the biofilm forming bacteria and the host response simultaneously is by using discriminative, reliable and reproducible animal models of the infections. In this review, the advantages of in vivo studies are compared to in vitro studies of biofilm formation in infectious diseases. The pig is the animal of choice when developing and applying large animal models of infectious diseases due to its similarity of anatomy, physiology and immune system to humans. Furthermore, conventional pigs spontaneously develop many of the same chronic bacterial infections as seen in humans. Therefore, in this review porcine models of five different infectious diseases all associated with biofilm formation and chronicity in humans are described. The infectious diseases are: chronic wounds, endocarditis, pyelonephritis, hematogenous osteomyelitis and implant-associated osteomyelitis.
Adrien Labriet, , , Éric Lévesque, Derek Jonker, Félix Couture, Angela Buonadonna, Mario D’Andrea, Lyne Villeneuve, , et al.
Published: 10 October 2017
Frontiers in Pharmacology, Volume 8, pp 712-712; https://doi.org/10.3389/fphar.2017.00712

Abstract:
Hepatocyte nuclear factor 1-alpha (HNF1A) is a liver-enriched transcription factor that plays a key role in many aspects of hepatic functions including detoxification processes. We examined whether HNF1A polymorphisms are associated with clinical outcomes in two independent cohorts combining 417 European ancestry patients with metastatic colorectal cancer (mCRC) treated with irinotecan-based chemotherapy. The intronic rs2244608A>G marker was predictive of an improved progression-free survival with a trend in the Canadian cohort and reaching significance in the Italian cohort, with hazard ratios (HR) of 0.74 and 0.72, P = 0.076 and 0.038, respectively. A strong association between rs2244608A>G and improved PFS was found in the combined analysis of both cohorts (HR = 0.72; P = 0.002). Consistent with an altered HNF1A function, mCRC carriers of the rs2244608G minor allele displayed enhanced drug exposure by 45% (P = 0.032) compared to non-carriers. In Caucasians, rs2244608A>G is in strong linkage with the coding variant rs1169288c.79A>C (HNF1A p.I27L). In healthy donors, we observed an altered hepatic (ABCC1, P = 0.009, ABCC2, P = 0.048 and CYP3A5, P = 0.001; n = 89) and intestinal (TOP1, P = 0.004; n = 75) gene expression associated with the rs1169288C allele. In addition, the rs1169288C polymorphism could significantly increase the ABCC1 promoter activity by 27% (P = 0.008) and 15% (P = 0.041) in the human kidney HEK293 and the human liver HepG2 cell lines, respectively. Our findings suggest that the HNF1A rs2244608, or the tightly linked functional coding variant p.I27L, might be a potential prognostic marker with irinotecan-based regimens.
Published: 10 October 2017
Frontiers in Psychology, Volume 8; https://doi.org/10.3389/fpsyg.2017.01767

Abstract:
Editorial on the Research TopicDiversity and Universality in Causal Cognition The capacity to acquire and use causal knowledge belongs to the central cognitive competencies that allow us to orient in the world, and this knowledge shapes our cognitive, affective, and behavioral responses. Its central role renders causal cognition a core topic for the social and cognitive sciences. But is causal cognition a universal and uniform phenomenon, or are there cultural differences in the way people represent the causal texture of the world? In spite of extensive research on causal cognition in the past decades (Waldmann, 2017), little is known about cultural diversity in how people perceive, represent, and reason about causal relationships (Bender et al., 2017). The main goal of this research topic is therefore to compile evidence for both diversity and universality in causal cognition, with the aim of pushing the field forward. One set of the contributions to this topic addresses questions revolving around people's conceptualization of causality and agency, with a focus on situations that involve a human agent. To this end, Le Guen et al. investigate how rural Mayan Yucatec and Tseltal speakers from Mexico and urban students from Mexico and Germany account for events for which the relations between intention, action, and outcome are varied. The groups converge in recognizing explicit links between actions and outcomes as causal, but differ in how they interpret non-law-like relations. Specifically, the notion of “chance” proved sensitive to task characteristics, cultural background, and language used. Another topic that has attracted interest is the phenomenon of “causal deviance,” which refers to situations in which an outcome satisfies an agent's intention, but is not brought about by this agent's action. For such cases, studies with US American participants have repeatedly reported a higher readiness to attribute intentionality to immoral than to amoral actions. For example, in a causally deviant situation the amoral action of “hitting a bull's eye” is not considered intentional in contrast to the immoral action of “hitting the aunt's heart.” Seeking a more fine-grained understanding of this phenomenon, Sousa et al. find the asymmetry to be fairly robust across varying degrees of causal deviance, even if mediated by judgments of action and blame, which they interpret as evidence for the existence of multiple concepts linked to intentional action. While these authors consider intentionality to be a basic and universal concept, Astuti and Bloch explore the possibility of cross-cultural variation by investigating the extent to which Malagasy people take intentionality into account when assessing acts of wrongdoing. They conclude that, while intentionality is indeed considered important in mundane cases of wrongdoing, its relevance decreases for events with more severe consequences for society, thereby pointing at both cross-cultural commonalities and differences (for a continuation of the debate, see also Sousa and Swiney, 2016). A further factor that may tune people's attention to agency and intentionality is language. Agency information can be encoded in different ways, for instance through word order, case marking, or verb type. That these linguistic cues affect the assignment of causal roles has been demonstrated by Bender and Beller with speakers of German and Tongan. An important area of causal cognition is reasoning about complex systems. Research reviewed here focuses on cases of economic decision-making, complex problem solving, and ethnomedical beliefs. In the first of these studies, Tucker et al. investigate the causal models Malagasy farmers, foragers, and fishermen use when explaining success and failure. Tucker and colleagues find that biological and economic events are attributed primarily to natural causes, whereas individuals' success and failure tend to be attributed to “supernatural” factors. As natural and supernatural factors represent distinct sets within a single explanatory framework—with the supernatural forces driving the natural ones—the Malagasy data suggest a type of “integrative thinking” that the authors consider to be common in unpredictable environments. A suitable context for testing this hypothesis is the large-scale project described in Bennardo's contribution, which seeks to identify the main causal forces in cultural models of nature across a broad range of populations. Both economic decisions under uncertainty and cognitive models of nature are paradigmatic test cases for investigating causal reasoning about complex systems. Simulations of systems (microworlds) are used to study complex problem solving, with participants being responsible for retaining a balance between several interconnected factors. Complex systems are characterized by non-transparent relations and non-linear processes, which pose substantial challenges for problem-solving and management (Funke). Because successful problem-solving typically involves updating a cognitive model of the interactions, microworlds can be used to diagnose causal perception, reasoning, understanding, and intervention. As argued by Güss and Robinson, participants' models and strategies may be affected by cultural background on several levels: knowledge, problem-solving heuristics, and perceptions of control by culturally mediated experiences; priorities in problem-solving by culture-specific values; and the temporal horizon for planning and decision-making by the cultural learning environment. To what extent microworlds are useful for cross-cultural research, whether problems of different complexity require different types of causal cognition, or whether they constitute qualitatively different phenomena is discussed both within the research topic (Funke; Greiff and Martin) and beyond (Dörner and Funke, 2017). A particularly relevant example of reasoning about complex causal relations is the diagnosis of mental disorders. Taking causal model theory as the starting point, Hagmayer and Engelmann derive predictions for systems of causal beliefs, applied here to lay theories of depression. Their analysis of data from a systematic literature review reveals cross-cultural convergence about relevant observable causes (e.g., stress), but substantially less cross-cultural agreement for hidden, especially supernatural causes. The third set of contributions to the present research topic addresses methodological problems typically encountered in cross-cultural research, and discusses possible solutions and their relevance for theoretical advances in the field. Beer and Bender investigate how people in an unfamiliar socio-cultural setting account for the behavior of others conditional upon their category membership. Setting off as an attempt to explore information search strategies among the Wampar in Papua New Guinea, the contribution turns into a discussion of the difficulties with parallelizing cognitive tasks across cultures. Not only designing new tasks for cross-cultural investigations of causal cognition is challenging—even the attempt to interpret available evidence is tricky. Ethnographic fieldwork has gathered a plethora of potentially relevant data that can be reconstructed as examples of causal reasoning (e.g., reasoning about witchcraft). However, in these studies the data are often not described in terms of abstract causal theories. Thus, relevant information is hard to localize and difficult to identify as relevant. How ethnographic descriptions can still be used to investigate causal reasoning is laid out by Widlok, pointing to culture-specific notions of time and extensions of personhood and agency as essential components of causal understanding (see also Peeters, 2015). The malleability of cultural perspectives over time and the inalienability of contextual information, a critical point raised by Widlok, is emphasized further by Iliev and ojalehto who call for diachronic analyses within single cultures as an essential complement to synchronic investigations across cultures. They introduce automated text analyses as a valuable tool for tracking how the concern with causality, the usage of causal vocabulary, and causal concepts themselves have changed over time. Extending this historic perspective to the evolutionary roots of causal cognition, Haidle scrutinizes archaeological findings as evidence of causal cognition in our ancestors. Based on the idea that tool construction presupposes considerations of cause-effect relations, she uses data on the composition of tool remains to infer, by way of reverse-engineering, which components of causal cognition allowed our ancestors to invent these tools. Finally, Kronenfeld in his theoretical piece reverts the usual reading of causal cognition to explore possible ways in which cognition may be considered causal, focusing in particular on collective practices. In summary, the 15 contributions to this research topic address a broad range of aspects of causal cognition: from perceptions and representations of causal relations through judgments of blameworthiness and punishment to ways in which illnesses are explained and treated. The articles describe approaches from a broad range of disciplines—including anthropology, archaeology, linguistics, philosophy, and psychology—and provide evidence for both the universality and diversity of causal cognition. Jointly, they support the assumption that core components of causal cognition are widely shared across historic and cultural contexts, but are also refined, shaped, and occasionally altered through processes of cultural elaboration and transmission that are characteristic for our species. Thus, these contributions highlight the need for more in-depth investigations of the cultural impacts in this domain, preferably through concerted efforts across disciplines, timescales, and levels of analyses (Bender and Beller, 2016). All authors listed have made a substantial and direct intellectual contribution to the work and approved it for publication. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. This topic originated from joint work of the international Research Group “The cultural constitution of causal cognition: Re-integrating anthropology into the cognitive sciences,” funded by the Centre for Interdisciplinary Research (ZiF) at Bielefeld University, Germany. Additional support was provided by the Deutsche Forschungsgemeinschaft (DFG) through grant Be 2178/5-1 to SB and AB, and by the Strategic Programme for International Research and Education (SPIRE, 2014) of the University of Bergen. Bender, A., and Beller, S. (2016). Probing the cultural constitution of causal cognition—a research program. Front. Psychol. 7:245. doi: 10.3389/fpsyg.2016.00245 PubMed Abstract | CrossRef Full Text | Google Scholar Bender, A., Beller, S., and Medin, D. L. (2017). “Causal cognition and culture,” in The Oxford Handbook of Causal Reasoning, ed M. R. Waldmann (New York: Oxford University Press), 717–738. Google Scholar Dörner, D., and Funke, J. (2017). Complex problem solving: what it is and what it is not. Front. Psychol. 8:1153. doi: 10.3389/fpsyg.2017.01153 CrossRef Full Text | Google Scholar Peeters, G. (2015). Commentary on: “Agency, time, and causality”. Front. Psychol. 6:329. doi: 10.3389/fpsyg.2015.00329 CrossRef Full Text | Google Scholar Sousa, P., and Swiney, L. (2016). Intentionality, morality, and the incest taboo in Madagascar. Front. Psychol. 7:494. doi: 10.3389/fpsyg.2016.00494 PubMed Abstract | CrossRef Full Text | Google Scholar Waldmann, M. R. (ed.). (2017). The Oxford Handbook of Causal Reasoning. New York, NY: Oxford University Press. Google Scholar Keywords: causal cognition, agency, culture, language, methods, interdisciplinary approach Citation: Beller S, Bender A and Waldmann MR (2017) Editorial: Diversity and Universality in Causal Cognition. Front. Psychol. 8:1767. doi: 10.3389/fpsyg.2017.01767 Received: 17 July 2017; Accepted: 25 September 2017; Published: 10 October 2017. Edited and reviewed by: Snehlata Jaswal, LM Thapar School of Management, India Copyright © 2017 Beller, Bender and Waldmann. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. *Correspondence: Sieghard Beller, [email protected] Andrea Bender, [email protected] Michael R. Waldmann, [email protected]
Manuel Alcaraz-Iborra, , Elisa Rodr´´íguez-Ortega, Leticia De La Fuente, ,
Frontiers in Behavioral Neuroscience, Volume 11, pp 186-186; https://doi.org/10.3389/fnbeh.2017.00186

Abstract:
Ethanol (EtOH) research has focused on stages of dependence. It is of paramount importance to more deeply understand the neurobehavioral factors promoting increased risk for EtOH binge drinking during the early stages of the addiction cycle. The first objective of this study was to evaluate whether C57BL/6J mice showing high drinking in the dark (DID) exhibit neurobehavioral traits known to contribute to EtOH binge-drinking disorders. Comparing high vs. low drinkers (HD/LD), we evaluated different types of basal anxiety-like responses, ethanol preference and sensitivity to the reinforcing properties of EtOH, and basal mRNA expression of the OX1/OX2 receptors (OX1r/OX2r) within the prefrontal cortex (PFC) and the nucleus accumbens (NAcc). Additionally, we tested binge drinking by LD/HD in response to a selective OX1r antagonist following intermittent episodes of DID (iDID). We report that DID consistently segregates two neurobehavioral endophenotypes, HD vs. LD, showing differences in neophobia and/or impulsivity/compulsivity traits. Additionally, HD mice show decreased basal OX1r and OX2r mRNA expression within the NAcc and elevated OX1r within the PFC. Exposure to several intermittent episodes of EtOH DID triggered a rapid increase in EtOH intake over time in LD mice matching that observed in HD mice. Despite HD/LD endophenotypes did not show differences in EtOH intake, they still predicted the response to a pharmacological challenge with a selective OX1r antagonist. The present data underscore the relevance of HD/LD endophenotypes stemming from DID procedures for exploring neurobehavioral processes underlying the early stages of the addiction cycle and EtOH binge-drinking disorders.
, Sonia Q. Doi
Published: 10 October 2017
Frontiers in Medicine, Volume 4; https://doi.org/10.3389/fmed.2017.00168

Abstract:
Editorial on the Research TopicBiomarkers in CKD The prevalence of chronic kidney disease (CKD) is increasing worldwide and consequently the risks for renal replacement therapies, such as dialysis and transplantation and the incidence of cardiovascular events are also increasing (1, 2). The goal of the present Research Topic, “Biomarkers in CKD” is to highlight the importance of identifying novel and more efficient biomarkers for predicting the decline of glomerular filtration rate (GFR) and the progression of renal disease, as well as to provide tools for more efficient treatments for patients with CKD. We are thankful to all the authors for their invaluable contribution to this topic, and the reviewers for their in-depth service. The collection of papers in this topic demonstrates the complexity of this field and emphasizes new methods and approaches on biomarker discovery with a potential to stratify patients in future clinical studies, help in diagnostics, and reveal new targets for more efficient therapeutic strategies. Currently, the estimation of GFR by serum creatinine-based equations is the most precise method to estimate the decline of renal function with the progression of kidney disease or the effect of a treatment (3). However, as emphasized by Wilkinson et al., serum creatinine can be affected by a variety of factors that are particularly variable in CKD patients, including muscle mass, dietary protein, and exercise. Therefore, the estimating equations may over- or underestimate GFR in a large population study. The authors highlight the importance of taking in consideration these factors when using the standard formulas for risk assessment of cardiovascular events and mortality in population-based cohorts. Albuminuria is the classic sensitive marker of early renal dysfunction but excludes many patients that will only have proteinuria when GFR is already significantly decreased. Albuminuria is also utilized as a marker of risk for CKD progression. However, strategies that decrease albuminuria do not always prevent the progression of kidney disease. In this regard, studies have reported various biomarkers that precede changes in albuminuria (4–6). In their comprehensive review of recent clinical studies, Argyropoulos et al. highlight the potential of β2M (beta-2 microglobulin) as a promising marker to assess glomerular and tubular function in a wide spectrum of renal diseases and to predict cardiovascular morbidity and mortality. Prakoura and Chatziantoniou refer to periostin as another candidate. The expression of this protein is low in normal kidneys, increasing with progression of CKD in several animal models or decreasing with regression of the disease upon treatment. These authors also suggest that discoidin domain receptor 1, an integral membrane receptor that is overexpressed in kidney disease, could be a promising therapeutic target for CKD. The diverse etiological causes and the different rate of progression in patients with CKD have led to the assumption that a multi-biomarker approach has a better potential to provide information with higher accuracy than the analysis of individual biomarkers. The development of new computer-based modeling analyses of transcriptomes and proteomics allow for interpretation of data sets from various sources to identify potential biomarkers in specific population studies. A pilot study conducted by Subasi et al. used mass spectrometry (SELDI-TOF) data to determine patterns of protein expression that predict rapid or slow progression in CKD patients in the African American Study of Kidney Disease and Hypertension (AASK) trial. The authors used a combinatorial Logical Analysis of Data methodology to discriminate the risk groups and to predict the risk for progression of renal disease in that population, demonstrating that this new method outperforms the classic predictor proteinuria, with higher sensitivity, specificity, and accuracy. In the past two decades, an increasing effort has been applied for the discovery of novel biomarkers, but the potential utility of these markers in the clinical setting is still an area of intense investigation. Therefore, advancing studies on new technology for biomarker discovery is essential to allow the establishment of non-invasive and more accurate markers that can diagnose CKD at its early stages, which can predict or correlate better with the decline of GFR, and which provide more efficient therapeutic targets in the diverse settings of CKD. The authors reviewed manuscripts submitted to the research topic and the final version of this Editorial. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer PS and handling editor declared their shared affiliation. 1. The United States Renal Data System. 2016 USRDS Annual Data Report: Epidemiology of Kidney Disease in Teh United States. Bethesda, MD: National Institutes of Health, NIDDK (2016). Google Scholar 2. Jha V, Garcia-Garcia G, Iseki K, Li Z, Naicker S, Plattner B, et al. Chronic kidney disease: global dimension and perspectives. Lancet (2013) 382(9888):260–72. doi:10.1016/S0140-6736(13)60687-X PubMed Abstract | CrossRef Full Text | Google Scholar 3. Stevens LA, Coresh J, Greene T, Levey AS. Assessing kidney function – measured and estimated glomerular filtration rate. N Engl J Med (2006) 354(23):2473–83. doi:10.1056/NEJMra054415 CrossRef Full Text | Google Scholar 4. Keirstead ND, Wagoner MP, Bentley P, Blais M, Brown C, Cheatham L, et al. Early prediction of polymyxin-induced nephrotoxicity with next-generation urinary kidney injury biomarkers. Toxicol Sci (2014) 137(2):278–91. doi:10.1093/toxsci/kft247 PubMed Abstract | CrossRef Full Text | Google Scholar 5. Sabbisetti VS, Waikar SS, Antoine DJ, Smiles A, Wang C, Ravisankar A, et al. Blood kidney injury molecule-1 is a biomarker of acute and chronic kidney injury and predicts progression to ESRD in type I diabetes. J Am Soc Nephrol (2014) 25(10):2177–86. doi:10.1681/ASN.2013070758 PubMed Abstract | CrossRef Full Text | Google Scholar 6. Zhou H, Cheruvanky A, Hu X, Matsumoto T, Hiramatsu N, Cho ME, et al. Urinary exosomal transcription factors, a new class of biomarkers for renal disease. Kidney Int (2008) 74(5):613–21. doi:10.1038/ki.2008.206 PubMed Abstract | CrossRef Full Text | Google Scholar Keywords: biomarkers, chronic kidney diseases, diagnosis, progression disease, treatment Citation: Araujo M and Doi SQ (2017) Editorial: Biomarkers in CKD. Front. Med. 4:168. doi: 10.3389/fmed.2017.00168 Received: 14 July 2017; Accepted: 25 September 2017; Published: 10 October 2017 Edited by: Reviewed by: Copyright: © 2017 Araujo and Doi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. *Correspondence: Magali Araujo, [email protected]
Published: 10 October 2017
Frontiers in Microbiology, Volume 8, pp 1908-1908; https://doi.org/10.3389/fmicb.2017.01908

Abstract:
Editorial on the Research TopicAbout the Foodborne Pathogen Campylobacter The name “Campylobacter” comes from ancient Greek meaning “curved rod” which describes the shape of this microorganism. Campylobacter was firstly isolated as a Vibrio species from epizootic ovine abortion in 1906 by McFadyean and Stockman (1913), and renamed in 1973 as the neotype strain Campylobacter after showing significant biological differences with Vibrio species (Véron and Chatelain, 1973). Rather than a curved rod, the shape looks more like to a spiral and can develop in to filamentous or coccoid forms under stressful conditions (Tangwatcharin et al., 2006; Ghaffar et al., 2015; Rodrigues et al., 2016). Nowadays, Campylobacter spp. are classified among the ε-proteobacteria in the family of Campylobacteriaceae (Vandamme et al., 1991). Campylobacter has emerged as the leading cause of bacterial foodborne infections in developed countries, having surpassed Salmonella several years ago, and represents a significant economic burden (EFSA and ECDC, 2016). Although new species of Campylobacter have been recently discovered, human cases of campylobacterosis are dominated by two main species, Campylobacter jejuni and, to a lesser extent, Campylobacter coli. Quantitative epidemiology reports reveal high rates of contamination for broiler chickens and carcasses by Campylobacter (Hue et al., 2010; Lawes et al., 2012; Powell et al., 2012). The presence of Campylobacter was also detected in other farm animals or foodstuffs due to cross contamination (EFSA and ECDC, 2016). Campylobacter in poultry remains a problem with no effective control measures available that can be recommended for microbial food/farm safety guidelines to mitigate the risk of flock colonization. Campylobacter also remains a puzzle as to how an obligate microaerobic bacterium can survive from farm to retail outlets. The underlying molecular mechanisms of persistence, survival and pathogenesis appear to represent a combination peculiar to this pathogen, which are not shared with other foodborne bacterial pathogens such as Listeria monocytogenes, Salmonella enterica, Escherichia coli, and Staphylococcus aureus. This topic includes 18 published articles describing original studies of C. jejuni and C. coli that deal with (1) epidemiology and animal carriage, (2) host interaction, (3) control strategies, (4) metabolism and regulation specificities of these two pathogen species, (5) methodology to improve cultural technique and (6) chicken gut microbiota challenged with Campylobacter. Organic animal production schemes differ in many ways (antibiotic use, herd structure, feeding regimes, access to outdoor areas, space allowance) from conventional rearing systems, and therefore can have an impact in the occurrence, transmission and pathogenicity of foodborne pathogens, including Campylobacter spp. In this research topic, is however shown that organic pig production schemes have a minor impact on the epidemiology of C. coli. Kempf et al. monitored the prevalence and antimicrobial resistance of C. coli isolated from conventional and organic pigs in farms from France and Sweden and observed no significant difference in prevalence between pigs in organic and conventional productions. They however observed in France a higher occurrence of antimicrobial resistant C. coli isolates (particularly against the antibiotics tetracycline and erythromycin) from conventional rearing systems. Denis et al. characterized C. coli isolates obtained from 19 organic pig farms and 24 conventional pig farms through pulsed field gel electrophoresis, multilocus sequence typing, detection of nine virulence-associated genes and evaluation of the adhesion and invasion capacity on Caco-2 cells. They concluded that pig farm management strategies did not influence the diversity and virulence of C. coli. Ayllón et al. used a proteomic approach to examine relative differences in protein expression levels between C. jejuni interacting with human (INT-407) and porcine (IPEC-1) cell lines. The study revealed 366 differentially expressed proteins after 3 h infection and 485 after 24 h. The identities of the protein enabled analysis of the response pathways that indicate differences in the timing of inflammatory responses between the cell lines and comparative down regulation of the signaling pathways that control cell migration, endocytosis and cell cycle progression in the porcine cell line. The authors attribute the differences in the cellular pathway responses to C. jejuni exposure as indicative of the processes that establish either infective or commensal behavior respectively in human or porcine hosts. Upadhyay et al. examined the potential of three phytochemicals generally recognized as safe (GRAS) and applied at sub-inhibitory concentrations to bacterial growth, to prevent or reduce the severity of human infection. Phytochemical treatments of C. jejuni resulted in reduced motility and a reduction in the expression of cytolethal distending toxin that could result in favorable effects on human infection. Using human intestinal epithelial (Caco-2) cell-based assays the authors demonstrated the abilities of trans-cinnamaldehyde (0.01%), carvacrol (0.002%), and eugenol (0.01%) to reduce the processes of attachment, invasion and translocation of C. jejuni. Effective control of Campylobacter on commercial broiler chicken farms is proving more than challenging. Microbiological risk assessments suggest that if reductions in the intestinal loads carried by chickens could be translated on to poultry meat then these measures could make a significant impact on the cases of human campylobacterosis (Boysen...
Xunan Hai, Houshuang Zhang, Zhonghua Wang, Haiyan Gong, Jie Cao, Yongzhi Zhou,
Published: 10 October 2017
Frontiers in Microbiology, Volume 8; https://doi.org/10.3389/fmicb.2017.01959

Abstract:
Peroxiredoxins (Prxs) are a family of antioxidant enzymes that reduce peroxides in the presence of thioredoxin, thioredoxin reductase, and nicotinamide adenine dinucleotide phosphate (NADPH) to resist oxidative stress. In this study, we identified and isolated a 2-Cys Prx designated as ‘Prx2’ from Babesia microti, with a full-length cDNA of 826 bp and an open reading frame (ORF) of 756 bp, which encodes a 251-amino acid protein. BLAST analysis demonstrated that Prx2 shows the typical features of members of the 2-Cys Prx family, which includes harboring two conserved VCP motifs with Cys101 and Cys221 conserved cysteine residues. Recombinant Prx2 was expressed in Escherichia coli and analyzed by western blot. The antioxidant activity of Prx2 was demonstrated using a mixed-function oxidation (MFO) system and oxidation of NADPH. Furthermore, Prx2 mRNA expression level in parasites at the erythrocytes and tick stages were analyzed by real-time fluorescence quantitative PCR. Peak Prx2 mRNA transcription was detected eight days after infection at the erythrocyte stage, but not at the tick stage. Taken together, this study characterized Prx2 from B. microti as an antioxidant molecule that was specifically transcribed at the erythrocyte stage.
Lingli Zhou,
Frontiers in Computational Neuroscience, Volume 11; https://doi.org/10.3389/fncom.2017.00092

Abstract:
Molecular signal transmission in cell is very crucial for information exchange. How to understand its transmission mechanism has attracted many researchers. In this paper, we prove that signal transmission problem between cancer cell and drug molecules can be achieved by synchronous control. To achieve our purpose, we derive the Fokker-Plank equation by using the Langevin equation and theory of random walk, this is model which can express the concentration change of drug molecules. Second, according to the biological character which vesicles in cell can be combined with cell membrane to release the cargo which plays a role of signal transmission. Third, we propose the the view of synchronous control which the process of vesicle docking with their target membrane is a synchronization process, so we can achieve the precise treatment of disease by using synchronous control. We believe this synchronous control mechanism is reasonable and two examples are given to illustrate the correctness of our results obtained in this paper
, Ousama AlZahal, Nicola Walker, Brian McBride
Published: 10 October 2017
Frontiers in Microbiology, Volume 8, pp 1943-1943; https://doi.org/10.3389/fmicb.2017.01943

Abstract:
Sub-acute ruminal acidosis (SARA) is a gastrointestinal functional disorder in livestock characterized by low rumen pH, which reduces rumen function, microbial diversity, host performance, and host immune function. Dietary management is used to prevent SARA, often with yeast supplementation as a pH buffer. Almost nothing is known about the effect of SARA or yeast supplementation on ruminal protozoal and fungal diversity, despite their roles in fiber degradation. Dairy cows were switched from a high-fiber to high-grain diet abruptly to induce SARA, with and without active dry yeast (ADY, Saccharomyces cerevisiae) supplementation, and sampled from the rumen fluid, solids, and epimural fractions to determine microbial diversity using the protozoal 18S rRNA and the fungal ITS1 genes via Illumina MiSeq sequencing. Diet-induced SARA dramatically increased the number and abundance of rare fungal taxa, even in fluid fractions where total reads were very low, and reduced protozoal diversity. SARA selected for more lactic-acid utilizing taxa, and fewer fiber-degrading taxa. ADY treatment increased fungal richness (OTUs) but not diversity (Inverse Simpson, Shannon), but increased protozoal richness and diversity in some fractions. ADY treatment itself significantly (P < 0.05) affected the abundance of numerous fungal genera as seen in the high-fiber diet: Lewia, Neocallimastix, and Phoma were increased, while Alternaria, Candida Orpinomyces, and Piromyces spp. were decreased. Likewise, for protozoa, ADY itself increased Isotricha intestinalis but decreased Entodinium furca spp. Multivariate analyses showed diet type was most significant in driving diversity, followed by yeast treatment, for AMOVA, ANOSIM, and weighted UniFrac. Diet, ADY, and location were all significant factors for fungi (PERMANOVA, P = 0.0001, P = 0.0452, P = 0.0068, Monte Carlo correction, respectively, and location was a significant factor (P = 0.001, Monte Carlo correction) for protozoa. Diet-induced SARA shifts diversity of rumen fungi and protozoa and selects against fiber-degrading species. Supplementation with ADY mitigated this reduction in protozoa, presumptively by triggering microbial diversity shifts (as seen even in the high-fiber diet) that resulted in pH stabilization. ADY did not recover the initial community structure that was seen in pre-SARA conditions.
, , Ronaldo B. Gobbi, , Nayara P. Almeida,
Published: 10 October 2017
Frontiers in Physiology, Volume 8, pp 755-755; https://doi.org/10.3389/fphys.2017.00755

Abstract:
Total anaerobic contribution (TAn) con be assessed by accumulated oxygen deficit, and through sum of glycolytic and phosphagen contribution which enable the evaluation of TAn without influences on mechanical parameters. However, little is known about the difference of TAn within swimming distances. Therefore, the objective of the present study was to determine and compare the TAn in different performances using the backward extrapolation technique and amount of lactate accumulated during exercise, and relate it with swimming performance. Fourteen competitive swimmers performed five maximal front crawl swims of 50, 100, 200, 400, and 800 m. The total phosphagen (AnAl) and glycolytic (AnLa) contributions were assumed as the fast component of post-exercise oxygen consumption (EPOCFAST) and amount of blood lactate accumulated during exercise, respectively. TAn was the sum of AnAl and AnLa. Significantly lower values of AnLa were observed in the 800 m (p 0.13). The TAn was significantly higher in the 200 and 400 m performances than observed at 50 and 800 m (p < 0.01). Anaerobic contributions were correlated with 50, 100, 200, and 400 m performances (p < 0.01). The AnAl contribution was not correlated with 400m performance. Anaerobic parameters were not correlated with 800 m performance. In conclusion, the highest values of anaerobic contribution were observed in the 200 and 400 m distances. Moreover, TAn is important to performances below 400 m, and may be used in training routines.
Published: 10 October 2017
Frontiers in Psychology, Volume 8, pp 1739-1739; https://doi.org/10.3389/fpsyg.2017.01739

Abstract:
In this paper we argue that a synthesis of findings across the various sub-areas of research in complex problem solving and consequently progress in theory building is hampered by an insufficient differentiation of complexity and difficulty. In the proposed framework of person, task and situation (PTS), complexity is conceptualized as a quality that is determined by the cognitive demands that the characteristics of the task and the situation impose. Difficulty represents the quantifiable level of a person’s success in dealing with such demands. We use the well-documented “semantic effect” as an exemplar for testing some of the conceptual assumptions derived from the PTS framework. We demonstrate how a differentiation between complexity and difficulty can help take CPS beyond a potentially too narrowly defined psychometric perspective and subsequently gain a better understanding of the cognitive mechanisms behind this effect. In an empirical study a total of 240 university students were randomly allocated to one of four conditions. The four conditions resulted from contrasting the semanticity level of the variable labels used in the CPS system (high vs. low) and two instruction conditions for how to explore the CPS system’s causal structure (starting with the assumption that all relationships between variables existed vs. starting with the assumption that none of the relationships existed). The variation in the instruction aimed at inducing knowledge acquisition processes of either (1) systematic elimination of presumptions, or (2) systematic compilation of a mental representation of the causal structure underpinning the system. Results indicate that (a) it is more complex to adopt a “blank slate” perspective under high semanticity as it requires processes of inhibiting prior assumptions, and (b) it seems more difficult to employ a systematic heuristic when testing against presumptions. In combination, situational characteristics, such as the semanticity of variable labels, have the potential to trigger qualitatively different tasks. Failing to differentiate between ‘task’ and ‘situation’ as independent sources of complexity and treating complexity and difficulty synonymously threaten the validity of performance scores obtained in CPS research.
Kai Li, Charlotte Lindauer, , Heinz Rüdiger, Heinz Reichmann, Ulrike Reuner,
Published: 10 October 2017
Frontiers in Physiology, Volume 8; https://doi.org/10.3389/fphys.2017.00778

Abstract:
Objectives Wilson’s disease is reported to have autonomic dysfunction, but comprehensive evaluation of autonomic function is lacking. Additionally, little is known about the change of autonomic function of Wilson’s disease during continuous therapy. We assumed that patients with Wilson’s disease had both sympathetic and parasympathetic autonomic impairments, and the autonomic dysfunction might be stable across a three-year follow-up after years of optimal treatment. Methods Twenty-six patients with Wilson’s disease and twenty-six healthy controls were recruited. Twenty patients in the Wilson’s disease group were examined again after a three-year follow-up. All the participants were evaluated by a questionnaire on dysautonomia symptoms, 24-hour blood pressure and heart rate monitoring, and cardiovascular autonomic function examination in various conditions including at rest, deep breathing, Valsalva manoeuvre, isometric handgrip test and passive tilting. Baroreflex sensitivity and spectral analyses were performed via trigonometric regressive spectral analysis. Results Patients with Wilson’s disease showed autonomic dysfunction mainly in the following aspects: 1.the heart rate was higher than the controls. 2. Valsalva ratio was lower in patients with Wilson’s disease compared with the controls. 3. Heart rate increase during isometric hand gripping was smaller in the Wilson’s disease patients than the controls. 4. Baroreflex sensitivity was lower during nearly all the cardiovascular autonomic function examinations compared with healthy controls. When tested three years later, baroreflex sensitivity at rest decreased compared with baseline. 5. There were mild declines of resting DBP and low frequency component of heart rate variability during the follow-up examination compared with baseline. 6. Subgroup analysis showed that patients initially presenting with neurological symptoms had a higher night-time heart rate, lower expiration: inspiration RR interval ratio (E/I ratio), lower expiration: inspiration RR interval difference (E-I difference), less increase of heart rate and diastolic blood pressure during the handgrip test, and lower baroreflex sensitivity during deep breathing than the control group. 6. Correlation analysis showed that the severity of neurological symptoms was associated with E/I ratio, E-I difference, Valsalva ratio, heart rate change during the handgrip test, and baroreflex sensitivity during deep breathing. Conclusions The present study reveals cardiovascular autonomic dysfunction involving both sympathetic and parasympathetic branches in
Juan Song, Hui Liu, Huifu Zhuang, Chunxia Zhao, , Shibo Wu, Jinfeng Qi, Jing Li, ,
Published: 10 October 2017
Frontiers in Plant Science, Volume 8; https://doi.org/10.3389/fpls.2017.01738

Abstract:
Maize (Zea mays L.) is a staple crop worldwide with extensive genetic variations. Various insects attack maize plants causing large yield loss. Here, we investigated the responses of maize B73, a susceptible line, and Mo17, a resistant line, to the aphid Rhopalosiphum padi on metabolite and transcriptome levels. R. padi feeding had no effect on the levels of the defensive metabolites benzoxazinoids (Bxs) in either line, and Mo17 contained substantially greater levels of Bxs than did B73. Profiling of the differentially expressed genes revealed that B73 and Mo17 responded to R. padi infestation specifically, and importantly, these two lines showed large gene expression differences even without R. padi herbivory. Correlation analysis identified four transcription factors (TFs) that might account for the high Bx levels in Mo17. Similarly, genome-wide alternative splicing (AS) analyses indicated that both B73 and Mo17 had temporally specific responses to R. padi infestation, and these two lines also exhibited large differences of AS regulation under normal condition, and 340 genes, including 10 TFs, were constantly differentially spliced. This study provides large-scale resource datasets for further studies on the mechanisms underlying maize-aphid interactions, and highlights the phenotypic divergence in defense against aphids among maize varieties.
Published: 10 October 2017
Frontiers in Psychology, Volume 8, pp 1708-1708; https://doi.org/10.3389/fpsyg.2017.01708

Abstract:
Defined as increased sensitivity to losses, loss aversion is often conceptualized as a cognitive bias. However, findings that loss aversion has an attentional or emotional regulation component suggest that it may instead reflect differences in information processing. To distinguish these alternatives, we applied the drift-diffusion model (DDM) to choice and response time data in a card gambling task with unknown risk distributions. Loss aversion was measured separately for each participant. Dividing the participants into terciles based on loss aversion estimates, we found that the most loss-averse group showed a significantly lower drift rate than the other two groups, indicating overall slower uptake of information. In contrast, neither the starting bias nor the threshold separation (barrier) varied by group, suggesting that decision thresholds are not affected by loss aversion. These results shed new light on the cognitive mechanisms underlying loss aversion, consistent with an account based on information accumulation.
Qiong Duan, Yang Yang Wang, Ling Qiu, Tian Heng Ren, Zhi Li, Shu Lan Fu, Zong Xiang Tang
Published: 10 October 2017
Frontiers in Plant Science, Volume 8, pp 1716-1716; https://doi.org/10.3389/fpls.2017.01716

Abstract:
Rye (Secale cereale L.) 4R chromosome contains elite genes that are applicable for application in wheat (Triticum aestivum L.) cultivar improvement. PCR-based 4R-specific markers can facilitate benefit the detection of elite genes on 4R in wheat backgrounds. In this study, a new fluorescence in situ hybridization (FISH) map of the 4RKu chromosome of Kustro rye Kustro has been built. A set of 4RKu dissection lines were was obtained and 301 new 4RKu-specific markers were developed using sSpecific lLength aAmplified fFragment sSequencing (SLAF-seq) technology. The 301se markers were combined with the 99 4RKu-specific markers previously developed, and by us previously were physically mapped to 4RKu chromosome using the new FISH map of 4RKu chromosome and the 4RKu dissection lines. A total of 338 of the 400 markers have been successfully mapped to six regions of 4RKu chromosome. In additionAdditionally, the powdery mildew resistance gene(s) on the 4RLKu arm has beenwas located to the segment between L.4 and L.8, and the same region where the 115 4RLKu-specific markers were mapped. The markers developed in this study can be used to identify a given specific segment of 4R chromatin in wheat backgrounds, to help to construct a high-density physical map of 4R chromosome, and to facilitateaccelerate the utilization of elite genes on 4R chromosome in wheat breeding programs.
, Laura M. Griffin
Published: 10 October 2017
Frontiers in Psychology, Volume 8; https://doi.org/10.3389/fpsyg.2017.01775

Abstract:
A Book Review onSelf and Social Identity in Educational ContextsEdited by Kenneth I. Mavor, Michael J. Platow, and Boris Bizumic (Abingdon, Routledge), 2017, 378 pages, ISBN-10: 1138815136; ISBN-13: 978-1138815131.Books that are insightful, thoughtful provoking, and written in a way that is accessible to multiple reader types are hard to come by; this, we believe, is one of them. Mavor, Platow, and Bizumic (2017) have provided us with a book that is equally as important in education as it is in psychology. We would strongly encourage academics, educators, and students, who are interested in extending their knowledge of educational practice and research, to keep a copy of this book on their desk for easy access! The “self” and “social identity” are two core principles that have long fascinated psychologists and sociologists. This broad list of interested academics, researchers, and practitioners ranges from Jung, who aimed to understand the “self” through the interpretation of the unconscious and symbolism (Jung and Shamdasani, 2010), to Tajfel and Turner (1979), who proposed that an individual's perception of who they are is heavily influenced by their membership(s) of a group (or groups). Tajfel and Turner (1986) suggest that, because there are key differences between an individual's personal and social identity, the differences are determined by perceived experiences within interpersonal and group situations. While some theorists have recognized that social identity theory can be limited in its differentiation of groups (Turner et al., 1987; Brown, 2000), other academics across the social sciences have attested to the use of social identity theory in generating hypotheses for the study of group behavior (Huddy, 2001; Bradford, 2014; Jenkins, 2014). While the above is, undoubtedly, a non-exhaustive list of those currently working within the area of “self” and “social identity,” Mavor, Platow, and Bizumic's book “Self and Social Identity in Educational Contexts” (2017) utilizes social identity theory (Tajfel and Turner, 1979) combined with self-categorization (Turner et al., 1987), referred throughout as the “social identity approach,” to highlight the importance of developing “new and creative forms of practice in educational settings” (p. i). In addition to the wealth of knowledge and experience of 44 academics, researchers, and practitioners, this book is viewed as an invitation for others to explore the “social and psychological processes by which learners' personal and social self-concepts shape and enhance learning and teaching” (p. i). While this book is targeting advanced students and educational researchers across the social sciences, the introductory chapters are written in a way that, one would argue, could certainly appeal to a much wider audience. The first Chapters (Ch1 and Ch2) are given the monumental task of introducing what the contextualizing of the self and social identity within education looks like to paint a picture of how the book will progress. The challenge of this chapter, as is identified, is the diversity in the later chapters; how does one clearly articulate so many specialized areas of social identity and self-categorization? Taking a broadened operational approach, the authors note structuring the chapters by context, stages, and mechanisms associated with the identity and aid the reader by offering themes in which readers should view each chapter: (i) Promoting Change, (ii) Managing Conflict, and (iii) Facilitating Change. The way in which the various sections of this book are placed guides the reader along a linear pathway of information that concludes with the applied chapters (Ch16, Ch17, and Ch18) and concluding Chapter (Ch19). Among the central Chapters “Between the Classroom and Beyond” (Ch5, Ch6, Ch7, and Ch8) and “Student Life” (Ch9, Ch10, and Ch11) for example, the authors provide insight into how life transitions can involve moments of change regarding social identity and that the personal self can be affected in this process. There is evidence and arguments that call for a type of reformation of educational practice to account student engagement extending past quality teaching and adopting methods that enhance group and classroom cohesiveness and dynamics. It is evident, in the way this book is written, that most authors are both academics and practitioners. This interplay of two worlds provides readers with a unique insight into research and theory that is practice-orientated and succeeds in “opening and explaining novel integrations between psychology and education for the mutual benefit of both” (p. 16). Although the theoretical aspects are explained in intricate detail, they are done so in a way that is comprehensive and understandable. Initially, there was some concern regarding the specificity of certain chapters, such as Chapter 6 which focuses on “Insights and Applications from Medical Education” (as this is not necessarily a personal research interest), but found that, after this review, these chapters had a higher number of post-it notes ranging from “interesting” and “never thought of that” to “that's incredible” and “oooh, look this up.” As mentioned above, this book appeals on multiple levels. One of the resounding statements comes from Chapter 12 to 15, “Approaches to Learning and Academic Performance,” where the authors highlight that focusing on the way students learn is no longer as important as how students learn; that there is need to account for the holistic learner in terms of ontology and epistemology. The book is addressing and highlighting critical research areas within the combined fields of education and psychology. While some of the chapter foci can often be considered niche, such as “bullying,” “group identity,” or “socio-economic status,” the applied nature of the writing, combined with the wealth of experience from the authors, packages the content into a digestible one-inch thick book. This review was completed in a number of steps. First, both authors read and independently reviewed this book. Second, using an interview style process, the lead author (DM) asked the second author (LG) a series of questions related to the content, quality, and style, of each Chapter within the book. Finally, the lead author (DM) compiled both reviews, compared these reviews against the interview data, and wrote the final document. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Bradford, B. (2014). Policing and social identity: procedural justice, inclusion and cooperation between police and public. Policing Soc. 24, 22–43. doi: 10.1080/10439463.2012.724068 CrossRef Full Text | Google Scholar Brown, R. (2000). Social identity theory: past achievements, current problems and future challenges. Eur. J. Soc. Psychol. 30, 745–778. doi: 10.1002/1099-0992(200011/12)30:63.0.CO;2-O CrossRef Full Text | Google Scholar Huddy, L. (2001). From social to political identity: a critical examination of social identity theory. Polit. Psychol. 22, 127–156. doi: 10.1111/0162-895X.00230 CrossRef Full Text | Google Scholar Jenkins, R. (2014). Social Identity. New York, NY: Routledge. Google Scholar Jung, C. G., and Shamdasani, S. (2010). The Undiscovered Self: With Symbols and the Interpretation of Dreams, Vol. 20. Princeton, NJ: Princeton University Press. Google Scholar Tajfel, H., and Turner, J. C. (1979). “An integrative theory of intergroup conflict,” in The Social Psychology of Intergroup Relations, eds W. G. Austin and S. Worchel (Michigan, IN: Brooks/Cole Publishers). Google Scholar Tajfel, H., and Turner, J. C. (1986). “The social identity theory of inter group behavior,” in Psychology of Intergroup Relations, eds S. Worchel and W. G. Austin (Chicago, IL: Nelson). Turner, J. C., Hogg, M. A., Oakes, P. J., Reicher, S. D., and Wetherell, M. S. (1987). Rediscovering the Social Group: A Self-Categorization Theory. Oxford: Blackwell. Google Scholar Keywords: social identity, educational practice, psychology of education, practice based research, educational context Citation: McDonnell DP and Griffin LM (2017) Book Review: Self and Social Identity in Educational Contexts. Front. Psychol. 8:1775. doi: 10.3389/fpsyg.2017.01775 Received: 26 August 2017; Accepted: 25 September 2017; Published: 10 October 2017. Edited and reviewed by: Jesus de la Fuente, University of Almería, Spain Copyright © 2017 McDonnell and Griffin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. *Correspondence: Dean P. McDonnell, [email protected]
Published: 10 October 2017
Frontiers in Psychology, Volume 8, pp 1707-1707; https://doi.org/10.3389/fpsyg.2017.01707

Abstract:
Preliminary studies of strength-based parenting (SBP), a style of parenting that seeks to build strengths knowledge and strengths use in one’s child, have reported benefits such as higher life satisfaction, subjective wellbeing, and positive emotions together with lower stress in children and teens. Two proximal mediators conveying these effects have been identified: teen’s own use of strengths and strength-based coping, along with a small moderating effect of growth mindsets relating to strengths. The current study tests the potential mediating effect of self-efficacy, a sense of agency in life, in the relationship between SBP and mental health (wellbeing and illbeing) in teens. Self efficacy has been linked to wellbeing and strengths processes in past studies and is classed as a basic human need and form of eudaimonic happiness. This study reconfirmed the adaptive benefits of SBP in a large sample of Australian adolescents (N=11,368; 59% male; Mage=14.04, SDage=1.99) sourced from 28 schools. Using structural equation modelling, SBP significantly and directly predicted higher happiness and lower depression, with direct effects falling into the 85th and 95th percentile of meta-analytically derived individual differences effect sizes. In addition, self-efficacy was a significant partial mediator, accounting for 40.0% of the total effect on happiness and 52.7% of the total effect on distress. Self-efficacy was also a full mediator in the case of anxiety, with a strong indirect effect. Results suggest that building strengths in teens can also build self-efficacy, and given the large effect sizes, that SBP is a promising leverage point for increasing teen wellbeing.
Published: 10 October 2017
Frontiers in Psychology, Volume 8; https://doi.org/10.3389/fpsyg.2017.01558

Abstract:
Making music at the highest international standards can be rewarding, but it is also challenging, with research highlighting pernicious ways in which practicing and performing can affect performers’ health and wellbeing. Several studies indicate that music students’ perceptions, attitudes, and behaviors toward health and healthy living are less than optimal, especially considering the multiple physical and psychological demands of their day-to-day work. This article presents the results of a comprehensive screening protocol that investigated lifestyle and health-related attitudes and behaviors among 483 undergraduate and postgraduate students (mean age=21.29 years ±3.64; 59% women) from ten leading conservatoires. The protocol included questionnaires measuring wellbeing, general health, health-promoting behaviors, perfectionism, coping skills, sleep quality, and fatigue. On each measure, the data were compared with existing published data from similar age groups. The results indicate that music students have higher levels of wellbeing and lower fatigue than comparable samples outside of music. However, they also reveal potentially harmful perceptions, attitudes, and behaviors toward health. Specifically, engagement in health responsibility and stress management was low, which along with high perfectionistic strivings, limited use of coping skills, poor sleep quality, and low self-rated health, paints a troubling picture both for the music students and for those who support their training. The findings point to the need for more (and more effective) health education and promotion initiatives within music education; in particular, musicians should be better equipped with mental skills to cope with constant pressure to excel and high stress levels. In part, this calls for musicians themselves to engage in healthier lifestyles, take greater responsibility for their own health, and be aware of and act upon health information in order to achieve and sustain successful practice and performance. For that to happen, however, music educators, administrators, and policy makers must play an active role in providing supportive environments where health and wellbeing is considered integral to expert music training.
Jie Chen, Haoqiang Zhang, Xinlu Zhang,
Published: 10 October 2017
Frontiers in Plant Science, Volume 8, pp 1739-1739; https://doi.org/10.3389/fpls.2017.01739

Abstract:
Soil salinization and the associated land degradation are major and growing ecological problems. Excess salt in soil impedes plant photosynthetic processes and root uptake of water and nutrients such as K+. Arbuscular mycorrhizal (AM) fungi can mitigate salt stress in host plants. Although numerous studies demonstrate that photosynthesis and water status are improved by mycorrhizae, the molecular mechanisms involved have received little research attention. In the present study, we analyzed the effects of AM symbiosis and salt stress on photosynthesis, water status, concentrations of Na+ and K+, and the expression of several genes associated with photosynthesis (RppsbA, RppsbD, RprbcL and RprbcS) and genes coding for aquaporins or membrane transport proteins involved in K+ and/or Na+ uptake, translocation or compartmentalization homeostasis (RpSOS1, RpHKT1, RpNHX1 and RpSKOR) in black locust. The results showed that salinity reduced the net photosynthetic rate, stomatal conductance and relative water content in both non-mycorrhizal (NM) and AM plants; the reductions of these three parameters were less in AM plants compared with NM plants. Under saline conditions, AM fungi significantly improved the net photosynthetic rate, quantum efficiency of photosystem II photochemistry and K+ content in plants, but evidently reduced the Na+ content. AM plants also displayed a significant increase in the relative water content and an evident decrease in the shoot/root ratio of Na+ in the presence of 200 mM NaCl compared with NM plants. Additionally, mycorrhizal colonization upregulated the expression of three chloroplast genes (RppsbA, RppsbD and RprbcL) in leaves, and three genes (RpSOS1, RpHKT1 and RpSKOR) encoding membrane transport proteins involved in K+/Na+ homeostasis in roots. Expression of several aquaporin genes was regulated by AM symbiosis in both leaves and roots depending on soil salinity. This study suggests that the beneficial effects of AM symbiosis on the photosynthetic capacity, water status and K+/Na+ homeostasis lead to the improved growth performance and salt tolerance of black locust exposed to salt stress.
Jinmei Ding, Ronghua Dai, Lingyu Yang, , Ke Xu, Shuyun Liu, Wenjing Zhao, Lu Xiao, Lingxiao Luo, , et al.
Published: 10 October 2017
Frontiers in Microbiology, Volume 8; https://doi.org/10.3389/fmicb.2017.01967

Abstract:
In mammals, the microbiota can be transmitted from the placenta, uterus, and vagina of the mother to the infant. Unlike mammals, development of the avian embryo is a process isolated from the mother and thus in the avian embryo the gut microbial developmental process remains elusive. To explore the establishment and inheritance of the gut microbiome in the avian embryo, we used the chicken as the model organism to investigate the gut microbial composition in embryos, chicks and maternal hens. We observed: (1) 28 phyla and 162 genera of microbes in embryos where the dominated genus was Halomonas (79%). (2) 65 genera were core microbiota in all stages with 42% and 62% gut microbial genera of embryo were found in maternal hen and chick, respectively. There was a moderate correlation (0.40) between the embryo and maternal, and 0.52 between the embryo and chick at the family level. (3) Gut microbes that are involved in substance metabolism, infectious disease, and environmental adaptation are enriched in embryos, chicks, and maternal hens, respectively. (4) 94% genera of gut microbial composition were similar among three different chicken breeds which were maintained under similar conditions. Our findings provide evidence to support the hypothesis that part of the microbial colonizers harbored in early embryos were inherited from maternal hens, and the gut microbial abundance and diversity were influenced by environmental factors and host genetic variation during development.
, Catherine Dejean,
Frontiers in Molecular Neuroscience, Volume 10; https://doi.org/10.3389/fnmol.2017.00320

Abstract:
Connexins (Cx) are largely represented in the central nervous system (CNS) with eleven Cx isoforms forming intercellular channels. Moreover, in the CNS, Cx43 can form hemichannels (HCs) at non-functional membrane as related channel-forming Pannexin1(Panx1) and Panx2. Opening of Panx1 channels and Cx43 HCs appears to be involved in inflammation and has been documented in various CNS pathologies. These last years, evidence accumulated supporting a link between inflammation and cerebral neuropathies (migraine, Alzheimer’s disease, Parkinson’s disease, major depressive disorder, autism spectrum disorder, epilepsy, schizophrenia, bipolar disorder). Involvement of Panx channels and Cx43 HCs has been also proposed in pathophysiology of neurological diseases and psychiatric disorders. Other studies showed that following inflammatory injury of the CNS, Panx1 activators are released and prolonged opening of Panx1 channels triggers neuronal death. In neuropsychiatric diseases, comorbidities are frequently present and can aggravate the symptoms and make therapeutic management more complex. The high comorbidity between some neuropathies can be partially understood by the fact that these diseases share a common etiology involving inflammatory pathways and Panx1 channels or Cx43 HCs. Thus, anti-inflammatory therapy opens perspectives of targets for new treatments and could have real potential in controlling a cerebral neuropathy and some of its comorbidities. The purpose of this minireview is to provide information of our knowledge on the link between Cx43- and Panx-based channels, inflammation and cerebral neuropathies.
, Marina M. Schoemaker, Egbert Otten, Leonora J. Mouton,
Published: 10 October 2017
Frontiers in Psychology, Volume 8; https://doi.org/10.3389/fpsyg.2017.01774

Abstract:
The Dynamic Systems Approach (DSA) to development has been shown to be a promising theory to understand developmental changes. In this perspective, we use the example of mid-childhood (6- to 10-years of age) reaching to show how using the DSA can advance the understanding of development. Mid-childhood is an important developmental period that has often been overshadowed by the focus on the acquisition of reaching during infancy. This underrepresentation of mid-childhood studies is unjustified, as earlier studies showed that important developmental changes in mid-childhood reaching occur that refine the skill of reaching. We review these studies here for the first time and show that different studies revealed different developmental trends, such as non-monotonic and linear trends, for variables such as movement time and accuracy at target. Unfortunately, proposed explanations for these developmental changes have been tailored to individual studies, limiting their scope. Also, explanations were focused on a single component or process in the system that supposedly causes developmental changes. Here, we propose that the DSA can offer an overarching explanation for developmental changes in this research field. According to the DSA, motor behavior emerges from interactions of multiple components entailed by the person, environment and task. Changes in all these components can potentially contribute to the emerging behavior. We show how the principles of change of the DSA can be used as an overarching framework by applying these principles not only to development, but also the behavior itself. This underlines its applicability to other fields of development.
, Xuliang Gao, Daxun Wang,
Published: 10 October 2017
Frontiers in Psychology, Volume 8; https://doi.org/10.3389/fpsyg.2017.01768

Abstract:
To obtain accurate, valid and rich information from the questionnaires for internet addiction, a diagnostic classification test for internet addiction (the DCT-IA) was developed using diagnostic classification models (DCMs), a cutting-edge psychometric theory, based on DSM-5. A calibration sample and a validation sample were recruited in this study to calibrate the item parameters of the DCT-IA and to examine the sensitivity and specificity. The DCT-IA had high reliability and validity based on both CTT and DCMs, and had a sensitivity of 0.935 and a specificity of 0.817 with AUC=0.919. More important, different from traditional questionnaires, the DCT-IA can simultaneously provide general-level diagnostic information and the detailed symptom criteria-level information about the posterior probability of satisfying each symptom criterion in DMS-5 for each patient, which gives insight into tailoring individual-specific treatments for internet addiction.
, Sara Arganda, Corrie S. Moreau, James F. A. Traniello
Frontiers in Systems Neuroscience, Volume 11; https://doi.org/10.3389/fnsys.2017.00074

Abstract:
Neuromodulators are conserved across insect taxa, but how biogenic amines and their receptors in ancestral solitary forms have been co-opted to control behaviors in derived socially complex species is largely unknown. Here we explore patterns associated with the functions of octopamine, serotonin, and dopamine in solitary ancestral insects and their derived functions in eusocial ants, bees, wasps, and termites. Synthesizing current findings that reveal potential ancestral roles of monoamines in insects, we identify physiological processes and conserved behaviors under aminergic control, consider how biogenic amines may have evolved to modulate complex social behavior, and present focal research areas that warrant further study.
, Mauro D'onofrio,
Frontiers in Astronomy and Space Sciences, Volume 4; https://doi.org/10.3389/fspas.2017.00020

Abstract:
Phylogenetic approaches have proven to be useful in astrophysics. We have recently published a Maximum Parsimony (or cladistics) analysis on two samples of 215 and 85 low-z quasars (z < 0.7) which offer a satisfactory coverage of the Eigenvector 1-derived main sequence. Cladistics is not only able to group sources radiating at higher Eddington ratios, to separate radio-quiet (RQ) and radio-loud (RL) quasars and properly distinguishes core-dominated and lobe-dominated quasars, but it suggests a black hole mass threshold for powerful radio emission as already proposed elsewhere. An interesting interpretation from this work is that the phylogeny of quasars may be represented by the ontogeny of their central black hole, i.e. the increase of the black hole mass. However these exciting results are based on a small sample of low-z quasars, so that the work must be extended. We are here faced with two difficulties. The first one is the current lack of a larger sample with similar observables. The second one is the prohibitive computation time to perform a cladistic analysis on more that about one thousand objects. We show in this paper an experimental strategy on about 1500 galaxies to get around this difficulty. Even if it not related to the quasar study, it is interesting by itself and opens new pathways to generalize the quasar findings.
Zhenyong Wu, Sathish Thiyagarajan, Ben O’Shaughnessy,
Frontiers in Molecular Neuroscience, Volume 10; https://doi.org/10.3389/fnmol.2017.00315

Abstract:
Calcium-triggered exocytotic release of neurotransmitters and hormones from neurons and neuroendocrine cells underlies neuronal communication, motor activity, and endocrine functions. The core of the neuronal exocytotic machinery is composed of soluble N-ethyl maleimide sensitive factor receptors (SNAREs). Formation of complexes between vesicle attached v- and plasma-membrane anchored t-SNAREs in a highly regulated fashion brings the membranes into close apposition. Small, soluble proteins called Complexins and calcium-sensing Synaptotagmins cooperate to block fusion at low resting calcium concentrations, but trigger release upon calcium increase. A growing body of evidence suggests that the transmembrane domains (TMDs) of SNARE proteins play important roles in regulating the processes of fusion and release, but the mechanisms involved are only starting to be uncovered. Here we review recent evidence that SNARE TMDs exert influence by regulating the dynamics of the fusion pore, the initial aqueous connection between the vesicular lumen and the extracellular space. Even after the fusion pore is established, hormone release by neuroendocrine cells is tightly controlled, and the same may be true of neurotransmitter release by neurons. The dynamics of the fusion pore can regulate the kinetics of cargo release and the net amount released, and can determine the mode of vesicle recycling. Manipulations of SNARE TMDs were found to affect fusion pore properties profoundly, both during exocytosis and in biochemical reconstitutions. To explain these effects, TMD flexibility, and interactions among TMDs or between TMDs and lipids have been invoked. Exocytosis has provided the best setting in which to unravel the underlying mechanisms, being unique among membrane fusion reactions in that single fusion pores can be probed using high-resolution methods. An important role will likely be played by methods that can probe single fusion pores in a biochemically defined setting which have recently become available. Finally, computer simulations are valuable mechanistic tools because they have the power to access small length scales and very shorttimes that are experimentally inaccessible.
, , , Joanna Rączaszek-Leonardi, Katharina J. Rohlfing
Published: 10 October 2017
Frontiers in Psychology, Volume 8; https://doi.org/10.3389/fpsyg.2017.01656

Abstract:
Dynamical systems approaches to social coordination underscore how participants’ local actions give rise to and maintain global interactive patterns and how, in turn, they are also shaped by them. Developmental research can deliver important insights into both processes: (1) the stabilization of ways of interacting, and (2) the gradual shaping of the agentivity of the individuals. In this article we propose that infants’ agentivity develops out of participation, i.e. acting a part in an interaction system. To investigate this development this article focuses on the ways in which participation in routinized episodes may shape infant’s agentivity in social events. In contrast to existing research addressing more advanced forms of participating in social routines, our goal was to assess infants’ early participation as evidence of infants grasping of their behavior as agentive. In our study, 19 Polish mother–infant dyads were filmed playing peekaboo when the infants were 4 and 6 months of age. We operationalized infants’ participation in the peekaboo in terms of their use of various behaviors across modalities during specific phases of the game: We included smiles, vocalizations, and attempts to cover and uncover themselves or their mothers. We hypothesized that infants and mothers would participate actively in the routine by regulating their behavior so as to adhere to the routine format. Furthermore, we hypothesized that infants who experienced more scaffolding would be able to adopt a more active role in the routine. We operationalized scaffolding by analyzing mothers’ use of specific peekaboo structures that allowed infants to anticipate when it was their turn to act. Results suggested that infants as young as 4 months of age engaged in peekaboo and took up turns in the game, and that their participation increased at 6 months of age. Crucially, our results suggest that infants’ behavior was organized by the global structure of the peekaboo game, because smiles, vocalizations, and attempts to uncover occurred significantly more often during specific phases rather than being evenly distributed across the whole interaction. Furthermore, the way mothers structured the game at 4 months predicted infant participation at both 4 and 6 months of age.
Adrien Corot, Hanaé Roman, Odile Douillet, Hervé Autret, Maria-Dolores Perez-Garcia, Sylvie Citerne, , Soulaiman Sakr, Nathalie LeDuc,
Published: 10 October 2017
Frontiers in Plant Science, Volume 8; https://doi.org/10.3389/fpls.2017.01724

Abstract:
Bud outgrowth is a key process in the elaboration of yield and visual quality in rose crops. Although light intensity is well known to affect bud outgrowth, little is known on the mechanisms involved in this regulation. The objective of this work was to test if the control of bud outgrowth pattern along the stem by photosynthetic photon flux density (PPFD) is mediated by sugars, cytokinins and/or abscisic acid in intact rose plants. Rooted cuttings of Rosa hybrida ‘Radrazz’ were grown in growth chambers under high PPFD (520 µmol.m−2.s−1) until the floral bud visible stage. Plants were then either placed under low PPFD (90 µmol.m−2.s−1) or maintained under high PPFD. Bud outgrowth inhibition by low PPFD was associated with lower cytokinin and sugar contents and a higher abscisic acid content in the stem. Interestingly, cytokinin supply to the stem restored bud outgrowth under low PPFD. On the other hand, abscisic acid supply inhibited outgrowth under high PPFD and antagonized bud outgrowth stimulation by cytokinins under low PPFD. In contrast, application of sugars did not restore bud outgrowth under low PPFD. These results suggest that PPFD regulation of bud outgrowth in rose involves a signaling pathway in which cytokinins and abscisic acid play antagonistic roles. Sugars can act as nutritional and signaling compounds and may be involved too, but do not appear as the main regulator of the response to PPFD.
, Konrad Rempel, Marcos E. Gómez,
Published: 10 October 2017
Frontiers in Psychology, Volume 8; https://doi.org/10.3389/fpsyg.2017.01755

Abstract:
Materialistic values may be detrimental for people’s well-being. However, we know little about why (i.e. explaining mechanisms) and when (i.e. boundary conditions) this is the case. Although low satisfaction of the psychological needs is said to play a key role in this process, a recent meta-analysis indicates that the explaining power of need satisfaction is limited and suggests that need frustration may be more important. Moreover, although materialism may be detrimental in some life domains, studies in materialistic contexts such as work are lacking, particularly in the non-Western world. In response, we put need frustration to the fore and examine both need satisfaction and frustration as the underlying processes in the relation between materialism and employee attitudes and well-being in two Latin-American countries. The Chilean sample (N = 742) shows that materialism at work is associated with less positive (work satisfaction and engagement) and more negative (burnout and turnover intentions) outcomes, even when controlling for workers’ income. Notably, need frustration explained the detrimental effects of materialism alongside need satisfaction in a unique manner, showing that it is essential to distinguish both constructs. Results were replicated in Paraguay (N = 518) using different positive (organizational commitment and meaning at work) and negative (negative emotions and job insecurity) outcomes, adding to the generalizability of our results across samples of different nations.
Xinjiong Fan, Mingjun Liang, Lei Wang, Ruo Chen, He Li,
Published: 10 October 2017
Frontiers in Microbiology, Volume 8, pp 1950-1950; https://doi.org/10.3389/fmicb.2017.01950

Abstract:
The pathogen Pseudomonas aeruginosa uses quorum sensing (QS) to control virulence and biofilm formation. Enzymatic disruption of quorum sensing is a promising anti-infection therapeutic strategy that does not rely on antibiotics. Here, a novel gene (aii810) encoding an N-acylhomoserine lactonase was isolated from the Mao-tofu metagenome for the first time. Aii810 encoded a protein of 269 amino acids and was expressed in Escherichia coli BL21 (DE3) in soluble form. It showed the highest activity at 20 ˚С, and it maintained 76.5% of activity at 0 ˚С and more than 50% activity at 0–40 ˚С. The optimal pH was 8.0. It was stable in both neutral and slightly alkaline conditions and at temperatures below 40 ˚С. The enzyme hydrolyzed several ρ-nitrophenyl esters, but its best substrate was ρ-nitrophenyl acetate. Its kcat and Km values were 347.7 S−1 and 205.1 μM, respectively. It efficiently degraded N-butyryl-L-homoserine lactone and N-(3-oxododecanoyl)-L-homoserine lactone, exceeding hydrolysis rates of 72.3% and 100%, respectively. Moreover, Aii810 strongly attenuated P. aeruginosa virulence and biofilm formation. This enzyme with high anti-QS activity was the most cold-adapted N-acylhomoserine lactonase reported, which makes it an attractive enzyme for use as a therapeutic agent against P. aeruginosa infection.
Xiaorui Chen, Matthew D. Hitchings, José E. Mendoza, Virginia Balanza, , , Pablo Bielza,
Published: 10 October 2017
Frontiers in Microbiology, Volume 8, pp 1969-1969; https://doi.org/10.3389/fmicb.2017.01969

Abstract:
Pest control in agriculture employs diverse strategies, among which the use of predatory insects has steadily increased. The use of several species within the genus Orius in pest control is widely spread, particularly in Mediterranean Europe. Commercial mass rearing of predatory insects is costly, and research efforts have concentrated on diet manipulation and selective breeding to reduce costs and improve efficacy. The characterisation and contribution of microbial symbionts to Orius sp. fitness, behaviour and potential impact on human health has been neglected. This paper provides the first genome sequence level description of the predominant culturable facultative bacterial symbionts associated with five Orius species (O. laevigatus, O. niger, O. pallidicornis, O. majusculus and O. albidipennis) from several geographical locations. Two types of symbionts were broadly classified as members of the genera Serratia and Leucobacter, while a third constitutes a new genus within the Erwiniaceae. These symbionts were found to colonise all the insect specimens tested, which evidenced an ancestral symbiotic association between these bacteria and the genus Orius. Pangenome analyses of the Serratia sp. isolates offered clues linking Type VI secretion system effector-immunity proteins from the Tai4 sub-family to the symbiotic lifestyle.
, Gudi S. Krishna, Sravani Alla, Tony D. Kurian, Justin Kurian, Madhan Ramesh, M. Kishor
Published: 10 October 2017
Frontiers in Pharmacology, Volume 8; https://doi.org/10.3389/fphar.2017.00722

Abstract:
Background: Bipolar Affective Disorder (BPAD) is one of the leading causes of disability globally. Medication non-adherence and low quality of life (QOL) are the major challenges associated with the treatment of BPAD patients. Objective: Aim of this study was to assess the impact of pharmacist-psychiatrist collaborative patient education on medication adherence and QOL of BPAD patients. Methodology: A prospective randomized control study was conducted in the psychiatry outpatient department in a tertiary care setting. The eligible patients were enrolled and randomized into test (collaborative care) and control (usual care) groups. Patient education was provided by pharmacists to the test group patients, along with the usual care provided to all the patients. Patients were followed for three follow-ups of nearly one month intervals. Medication adherence and QOL were assessed by Medication Adherence Rating Scale and WHOQOL-BREF questionnaire respectively. T-test was used and P-values < 0.05 were considered statistically significant. Results: Out of 75 patients enrolled, 73 patients were followed for all the three follow-ups and completed the study. Thirty-eight patients belonged to test and 35 were in control group. The mean age of patients was 34.21 ± 10.91 years. Forty-eight (65.75%) patients belonged to age group of 18-39 years. There were 41 males (56.16%) and 32 female patients (43.83 %) in the study. Mean improvement in medication adherence and QOL of the test and control groups were found to be 2.06 ± 0.15 (< 0.001) and 13.8 ± 10.5 (<0.05) respectively. Conclusions: This study concluded that pharmacist-psychiatrist collaborative patient education can significantly improve the medication adherence and QOL of the BPAD patients. Statistically significant results indicating improved patient care and outcomes were possible when pharmacists worked as a team with psychiatrists.
Seda Onder, , , Lawrence M. Schopfer,
Published: 10 October 2017
Frontiers in Pharmacology, Volume 8; https://doi.org/10.3389/fphar.2017.00713

Abstract:
Hupresin is a new affinity resin that binds butyrylcholinesterase (BChE) in human plasma and acetylcholinesterase (AChE) solubilized from red blood cells (RBC). Hupresin is available from the CHEMFORASE company. BChE in human plasma binds to Hupresin and is released with 0.1 M trimethylammonium bromide (TMA) with full activity and 10–15% purity. BChE immunopurified from plasma by binding to immobilized monoclonal beads has fewer contaminating proteins than the one-step Hupresin-purified BChE. However, when affinity chromatography on Hupresin follows ion exchange chromatography at pH 4.5, BChE is 99% pure. The membrane bound AChE, solubilized from human RBC with 0.6% Triton X-100, binds to Hupresin and remains bound during washing with sodium chloride. Human AChE is not released in significant quantities with non-denaturing solvents, but is recovered in 1% trifluoroacetic acid. The denatured, partially purified AChE is useful for detecting exposure to nerve agents by mass spectrometry. Our goal was to determine whether Hupresin retains binding capacity for BChE and AChE after Hupresin is washed with 0.1 M NaOH. A 2 mL column of Hupresin equilibrated in 20 mM TrisCl pH 7.5 was used in seven consecutive trials to measure binding and recovery of BChE from 100 mL human plasma. Between each trial the Hupresin was washed with 10 column volumes of 0.1 M sodium hydroxide. A similar trial was conducted with red blood cell AChE in 0.6% Triton X-100. It was found that the binding capacity for BChE and AChE was unaffected by washing Hupresin with 0.1 M sodium hydroxide. Hupresin could be washed with sodium hydroxide at least seven times without losing binding capacity.
, Maria Camprubí-Robles, Rüdiger Schweigreiter, , , Richard L. Proia, Christine E. Bandtlow, ,
Frontiers in Molecular Neuroscience, Volume 10; https://doi.org/10.3389/fnmol.2017.00317

Abstract:
The bioactive lipid sphingosine-1-phosphate (S1P) is an important regulator in the nervous system. Here, we explored the role of S1P and its receptors in vitro and in preclinical models of peripheral nerve regeneration. Adult sensory neurons and motor neuron-like cells were exposed to S1P in an in vitro assay, and virtually all neurons responded with a rapid retraction of neurites and growth cone collapse which were associated with RhoA and ROCK activation. The S1P1 receptor agonist SEW2871 neither activated RhoA or neurite retraction, nor was S1P-induced neurite retraction mitigated in S1P1-deficient neurons. Depletion of S1P3 receptors however resulted in a dramatic inhibition of S1P-induced neurite retraction and was on the contrary associated with a significant elongation of neuronal processes in response to S1P. Opposing responses to S1P could be observed in the same neuron population, where S1P could activate S1P1 receptors to stimulate elongation or S1P3 receptors and retraction. S1P was, for the first time in sensory neurons, linked to the phosphorylation of collapsin response-mediated protein-2 (CRMP2), which was inhibited by ROCK inhibition. The improved sensory recovery after crush injury further supported the relevance of a critical role for S1P and receptors in fine-tuning axonal outgrowth in peripheral neurons.
Zhouqing He, Tingting Huang, Kevin Ao, Xiaofang Yan, Yan Huang
Published: 10 October 2017
Frontiers in Plant Science, Volume 8; https://doi.org/10.3389/fpls.2017.01682

Abstract:
Ubiquitination-mediated protein degradation plays a crucial role in the turnover of immune proteins through rapidly altering protein levels. Specifically, the over-accumulation of immune proteins and consequent activation of immune responses in uninfected cells is prevented through degradation. Protein post-translational modifications can influence and affect ubiquitination. There is accumulating evidence that suggests sumoylation, phosphorylation and acetylation differentially affect the stability of immune-related proteins, so that control over the accumulation or degradation of proteins is fine-tuned. In this paper, we review the function and mechanism of sumoylation, phosphorylation, acetylation and ubiquitination in plant disease resistance responses, focusing on how ubiquitination reacts with sumoylation, phosphorylation and acetylation to regulate plant disease resistance signaling pathways. Future research directions are suggested in order to provide ideas for signaling pathway studies, and to advance the implementation of disease resistance proteins in economically important crops.
Mickael Vourc’H, Antoine Roquilly, , Gaelle David, Philippe Hulin, Cedric Jacqueline, Jocelyne Caillon, Christelle Retiere,
Published: 10 October 2017
Frontiers in Immunology, Volume 8, pp 1283-1283; https://doi.org/10.3389/fimmu.2017.01283

Abstract:
Pseudomonas aeruginosa (PA) expresses the type III secretion system (T3SS) and effector exoenzymes that interfere with intracellular pathways. Natural killer (NK) cells play a key role in anti-bacterial immunity and their activation is highly dependent on IL-12 produced by myeloid cells. We studied PA and NK cell interactions and the role of IL-12 using, human peripheral blood mononuclear cells, sorted human NK cells and a human NK cell line (NK92). We used a wild-type (WT) strain of PA (PAO1) or isogenic PA deleted strains to delineate the role of T3SS and exoenzymes. Our hypotheses were tested in vivo in a PA-pneumonia mouse model. Human NK cells or NK92 cell line produced low levels of IFN-g in response to PA without IL-12 stimulation, whereas PA significantly increased IFN-g after IL-12 priming. The modulation of IFN-g production by PA required bacteria-to-cell contact. Among Type III secretion system (T3SS) effectors, exoenzyme T (ExoT) up-regulates IFN-g production and control ERK activation. In vivo, ExoT also increases IFN-g levels and the percentage of IFN-g+ NK cells in lungs during PA pneumonia, confirming in vitro data. In conclusion, our results suggest that T3SS could modulate the production of IFN-g by NK cells after PA infection through ERK activation.
Ken Soderstrom, Eman Soliman,
Published: 10 October 2017
Frontiers in Pharmacology, Volume 8; https://doi.org/10.3389/fphar.2017.00720

Abstract:
Cannabinoids include the active constituents of Cannabis or are molecules that mimic the structure and/or function of these Cannabis-derived molecules. Cannabinoids produce many of their cellular and organ system effects by interacting with the well-characterized CB1 and CB2 receptors. However, it has become clear that not all effects of cannabinoid drugs are attributable to their interaction with CB1 and CB2 receptors. Evidence now demonstrates that cannabinoid agents produce effects by modulating activity of the entire array of cellular macromolecules targeted by other drug classes, including: other receptor types; ion channels; transporters; enzymes, and other protein- and non-protein cellular structures. This review summarizes evidence for these interactions in the CNS and in cancer, and is organized according to the cellular targets involved. The CNS represents a well-studied area and cancer is emerging in terms of understanding mechanisms by which cannabinoids modulate their activity. Considering the CNS and cancer together allows identification of non-cannabinoid receptor targets that are shared and divergent in both systems. This comparative approach allows the identified targets to be compared and contrasted, suggesting potential new areas of investigation. It also provides insight into the diverse sources of efficacy employed by this interesting class of drugs. Obtaining a comprehensive understanding of the diverse mechanisms of cannabinoid action may lead to the design and development of therapeutic agents with greater efficacy and specificity for their cellular targets.
Published: 10 October 2017
Frontiers in Pharmacology, Volume 8, pp 718-718; https://doi.org/10.3389/fphar.2017.00718

Abstract:
Sunitinib, a multityrosine kinase inhibitor, is currently the standard first-line therapy in metastatic renal cell carcinoma and is also used in treating patients with pancreatic neuroendocrine and imatinib-resistant gastrointestinal stromal tumours. Nevertheless, most patients eventually relapse secondary to intrinsic or acquired sunitinib resistance. Autophagy has been reported to contribute to both chemo-sensitivity and -resistance. However, over the last few years, controversial regulatory effects of sunitinib on autophagy have been reported. Since gaining insights into the underlying molecular insights and clinical implications is indispensible for achieving optimum therapeutic response, this minireview article sheds light on the role of a network of prosurvival signaling pathways recently identified as key mediators of sunitinib resistance with established and emerging functions as autophagy regulators. Furthermore, we underscore putative prognostic biomarkers of sunitinib responsiveness that could guide clinicians towards patient stratification and more individualized therapy. Importantly, innovative therapeutic strategies/approaches to overcome sunitinib resistance both evaluated in preclinical studies and perspective clinical trials are discussed which could ultimately be translated to better clinical outcome.
Christopher A. De Solis, Anna A. Morales, Matthew P. Hosek, Alex C. Partin,
Frontiers in Molecular Neuroscience, Volume 10; https://doi.org/10.3389/fnmol.2017.00314

Abstract:
There have been several attempts to identify which RNAs are localized to dendrites; however, no study has determined which RNAs localize to the dendrites following the induction of synaptic activity. We sought to identify all RNA transcripts that localize to the distal dendrites of dentate gyrus granule cells following unilateral high frequency stimulation of the perforant pathway (pp-HFS) using Sprague Dawley rats. We then utilized laser microdissection (LMD) to very accurately dissect out the distal 2/3rds of the molecular layer (ML), which contains these dendrites, without contamination from the granule cell layer (GCL), 2 and 4 hrs post pp-HFS. Next, we purified and amplified RNA from the ML and performed an unbiased screen for 27,000 RNA transcripts using Affymetrix microarrays. We determined that Activity Regulated Cytoskeletal Protein (Arc/Arg3.1) mRNA, exhibited the greatest fold increase in the ML at both timepoints (2 hr and 4 hr). In total, we identified 31 transcripts that increased their levels within the ML following pp-HFS across the two timepoints. Of particular interest is that one of these identified transcripts was an unprocessed micro-RNA (pri-miR132). Fluorescent in situ hybridization (FISH) and qRT-PCR were used to confirm some of these candidate transcripts. Our data indicates Arc is a unique activity dependent gene, due to the magnitude that its activity dependent transcript localizes to the dendrites. Our study determined other activity dependent transcripts likely localize to the dendrites following neural activity, but do so with lower efficiency compared to Arc.
, , Filipe C. Matheus, , Elizabeth S. Yamada, Cristiane S. F. Maia,
Frontiers in Aging Neuroscience, Volume 9; https://doi.org/10.3389/fnagi.2017.00327

Abstract:
Periodontitis is an oral chronic infection/inflammatory condition, identified as a source of mediators of inflammation into the blood circulation, which may contribute to exacerbate several diseases. There is increasing evidence that inflammation plays a key role in the pathophysiology of Alzheimer’s disease (AD). Although inflammation is present in both diseases, the exact mechanisms and crosslinks between periodontitis and AD are poorly understood. Therefore, this paper aims to review possible comorbidity between periodontitis and AD. Here, the authors discuss the inflammatory aspects of periodontitis, how this oral condition produces a systemic inflammation and, finally, the contribution of this systemic inflammation for worsening neuroinflammation in the progression of AD.
, Simon Schindler, Marc-André Reinhard
Published: 10 October 2017
Frontiers in Psychology, Volume 8; https://doi.org/10.3389/fpsyg.2017.01770

Abstract:
According to the just-world theory, people need to – or rather want to – believe that they live in a just world where they will receive what they earn and consequently earn what they receive. In the present work, we examined the influence of people’s general and personal beliefs in a just world (BJW) on their (dis)honest behavior. Given that general BJW was found to be linked to antisocial tendencies, we expected stronger general BJW to be linked to more dishonesty. Given that personal BJW was found to be correlated with trust and justice striving, a negative link with dishonesty could be assumed. In one study (N = 501), we applied a common coin-toss paradigm to assess dishonesty. General BJW significantly predicted the probability of tossing the target outcome, that is, higher general BJW was linked to more dishonest behavior. This effect was found to be independent from personal BJW and self-reported importance of religion. Unexpectedly, there was no significant relationship between personal BJW and levels of dishonesty. These findings imply that although BJW normally serves an adaptive function, at least the facet general BJW has maladaptive side-effects.
, Syed B. Jamal, , Paulo V. S. D. Carvalho, Sintia Almeida, , , Artur Silva, ,
Published: 10 October 2017
Frontiers in Microbiology, Volume 8, pp 1878-1878; https://doi.org/10.3389/fmicb.2017.01878

Abstract:
The bacterial communities in a wide range of environmental niches sense and respond to numerous external stimuli for their survival. Primarily, a source they require to follow up this communication is the two-component signal transduction system (TCS), which typically comprises a sensor Histidine kinase for receiving external input signals and a response regulator that conveys a proper change in the bacterial cell physiology. For numerous reasons, TCSs have ascended as convincing targets for antibacterial drug design. Several studies have shown that TCSs are essential for the coordinated expression of virulence factors and, in some cases, for bacterial viability and growth. It has also been reported that the expression of antibiotic resistance determinants may be regulated by some TCSs. In addition, as a mode of signal transduction, phosphorylation of histidine in bacteria differs from normal serine/threonine and tyrosine phosphorylation in higher eukaryotes. Several studies have shown the molecular mechanisms by which TCSs regulate virulence and antibiotic resistance in pathogenic bacteria. In this review, we list some of the characteristics of the bacterial TCSs and their involvement in virulence and antibiotic resistance. Furthermore, this review lists and discusses inhibitors that have been reported to target TCSs in pathogenic bacteria.
, Karoline H. Jæger, Miroslav Kuchta, , Marie E. Rognes
Published: 10 October 2017
Frontiers in Physics, Volume 5; https://doi.org/10.3389/fphy.2017.00048

Abstract:
In this paper, we study a mathematical model of cardiac tissue based on explicit representation of individual cells. In this EMI model, the extracellular (E) space, the cell membrane (M) and the intracellular (I) space are represented as separate geometrical domains. This representation introduces modelling flexibility needed for detailed representation of the properties of cardiac cells including their membrane. In particular, we will show that the model allows ion channels to be non-uniformly distributed along the membrane of the cell. Such features are difficult to include in classical homogenized models like the monodomain and bidomain models frequently used in computational analyses of cardiac electrophysiology. The EMI model is solved using a finite difference method (FDM) and two variants of the finite element method (FEM). We compare the three schemes numerically, reporting on CPU-efforts and convergence rates. Finally, we illustrate the distinctive capabilities of the EMI model compared to classical models by simulating monolayers of cardiac cells with heterogeneous distributions of ionic channels along the cell membrane. Because of the detailed representation of every cell, the computational problems that result from using the EMI model are much larger than for the classical homogenized models, and thus represent a computational challenge. However, our numerical simulations indicate that the FDM scheme is optimal in the sense that the computational complexity increases proportionally to the number of cardiac cells in the model. Moreover, we present simulations, based on systems of equations involving ~ 117 million unknowns, representing up to ~ 16000 cells. We conclude that collections of cardiac cells can be simulated using the EMI model, and that the EMI model enable greater modeling flexibility than the classical monodomain and bidomain models.
Published: 10 October 2017
Frontiers in Physics, Volume 5; https://doi.org/10.3389/fphy.2017.00043

Abstract:
In the recent years experiments have established the existence of neutrino oscillations and most of the oscillation parameters have been measured with a good accuracy. However, in spite of many interesting ideas, no real illumination was sparked on the problem of flavor in the lepton sector. In this review, we discuss the state of the art of models for neutrino masses and mixings formulated in the context of flavor symmetries, with particular emphasis on the role played by grand unified gauge groups.
Márcio L. Jr. Aumond, Artur T. Jr. De Araujo, Camila F. De Oliveira Junkes, Márcia R. De Almeida, Hélio N. Matsuura, , , Márcio L. Jr. Aumond, Artur T. Jr. De Araujo, Camila F. De Oliveira Junkes, et al.
Published: 10 October 2017
Frontiers in Plant Science, Volume 8, pp 1734-1734; https://doi.org/10.3389/fpls.2017.01734

Abstract:
The development of adventitious roots is affected by several factors, including the age of the cutting donor plant, which negatively affects rooting capacity. Eucalyptus globulus quickly loses rooting capacity of cuttings as the donor plant ages, although the molecular and biochemical mechanisms behind this process are still unclear. To better understand the bases of rooting competence loss in E. globulus, the time required for a significant decline in rhizogenic ability without exogenous auxin was determined in microcuttings derived from donor plants of different ages after sowing. Tip cuttings of donor plants were severed before and after loss of rooting competence of microcuttings to test the hypothesis that auxin and carbohydrate homeostasis regulate rooting competence decline. There were no significant changes in concentration of carbohydrates, flavonoids, or proteins before and after the loss of rooting capacity. Peroxidase (EC 1.11.1.7) total activity increased with loss of rooting competence. Auxin concentration showed the opposite pattern. In good agreement, TAA1, a key gene in auxin biosynthesis, had lower expression after loss of rooting capacity. The same applied to the auxin receptor gene TIR1, suggesting reduced auxin sensitivity. On the other hand, genes associated with auxin response repression (TPL, IAA12) or with the action of cytokinins, the rhizogenesis inhibitor-related ARR1, showed higher expression in plants with lower rooting competence. Taken together, data suggest that age negatively affects E. globulus rooting by a combination of factors. Decreased endogenous auxin concentration, possibly caused by less biosynthesis, lower auxin sensitivity, higher expression of genes inhibiting auxin action, as well as of genes related to the action of cytokinins, appear to play roles in this process.
Published: 10 October 2017
Frontiers in Psychology, Volume 8, pp 1719-1719; https://doi.org/10.3389/fpsyg.2017.01719

Abstract:
As papers about consciousness are so often introduced, consciousness was until few decades ago considered a philosophical problem only, and the current interest in empirical consciousness research was unforeseen. This development was of course influenced by the technological advancements in neuroscience during those decades, but more important and fundamental was a new openness to interdisciplinary integration of research questions, methods and arguments. Cognitive scientists and neuroscientists agreed that the philosophical problems of why and how there is consciousness are also their problems. Philosophers agreed that empirical evidence may resolve or at least influence this debate. Scientists across disciplines generally agree that consciousness is subjective, characterized by a kind of privileged first-person access. Consciousness research has proven to be an actual and functioning discipline able to provide meaningful and reproducible results. Nevertheless, it has yet only scratched the surface in the attempt to solve some its bigger challenges, e.g., its many underlying questions of metaphysics (i.e., why does consciousness exist?) and questions of mechanisms (how does consciousness exist?). One major obstacle for consciousness research is the lacking consensus of how to optimally measure consciousness empirically. Another major challenge is how to identify neural correlates of consciousness. This challenge clearly relates to the first as one needs to apply a measure of consciousness in order to identify its correlates. Current consciousness research is already occupied with these questions that may even be said to dominate the scientific debate. As it will be argued below, consciousness research may face problems in the future that are currently less debated but which are logical extensions of the challenges above. It is a natural ambition when developing a measure of consciousness to be able to determine whether non-reporting subjects or even machines are conscious and of what. And it is a natural ambition when finding neural correlates of consciousness to understand how these correlates relate to a deeper metaphysical understanding of the relation between subjective experience and the physical substrate of the brain. Historically, the attempt to “measure” consciousness has unfolded as a debate between direct and indirect approaches. Direct approaches, at least intuitively, are the most informative as participating experimental subjects here simply report about their own experiences. As subjective reports however have demonstrable limits (e.g., lack of insights into personal bias, memory problems etc.), many scientists have refrained from their use and insisted on the use of objective measures only (e.g., Nisbett and Wilson, 1977; Johansson et al., 2006). Experiments on consciousness that are based on objective measures—the “indirect” approach—typically involve asking subjects to choose between alternatives, e.g., in forced-choice tasks. Although such methods may stay clear of classical limitations of subjective methods, they are confronted with other problems, which, according to some scientists, are greater. For one thing, objective measures must assume that the “threshold” of giving a correct response is the same as the “threshold” of having a subjective experience of the same content (Fu et al., 2008; Timmermans and Cleeremans, 2015). Furthermore, in order to arrive at any one particular objective method, one must have “calibrated it” to something else in order to know that this particular behavior can be considered a measure of consciousness—and not something else. This would typically involve associating a subjective report with a particular behavior—a process by which one would “import” all the weaknesses related to subjective reports that one tried to avoid in the first place (Overgaard, 2010). Proponents of the “direct” approach have attempted to develop precise and sensitive scales to capture minor variations in subjective experience, e.g., the Perceptual Awareness Scale and gradual confidence ratings (Ramsøy and Overgaard, 2004; Sandberg and Overgaard, 2015). Although different approaches to this idea disagree about what consistutes the optimal measure (Dienes and Seth, 2010; Timmermans et al., 2010; Szczepanowski et al., 2013), they share the view that a detailed subjective report may be imprecise yet better than an indirect measure. In recent years, the arsenal of indirect measures have been supplied with what is named “no-report paradigms.” Essentially, all paradigms using objective measures only are without report, so in a certain sense, paradigms labeled “no-report paradigms” have not introduced anything new. Nevertheless, experiments of this kind attempt first to associate a particular objective measure (e.g., a behavior or a brain activation) with conscious experience, and then to apply this measure as a measure of consciousness so that no direct report is needed (e.g., Frässle et al., 2014; Pitts et al., 2014). Such methods intuitively seem to circumvent some of the criticism mentioned above. However, and as mentioned above, the only way one may associate a phenomenon as nystagmus with conscious experience is by the direct use of introspection (to establish the “correlation”) (Overgaard and Fazekas, 2016). It has been proposed that the best and most practical way forward is to combine methods and learn what we can from the results we get (Tsuchiya et al., 2016). Whereas this is most likely what is necessary, it is important to notice that different methods seem to generate different results, so that some methods are associated with the finding that the neural correlates of visual consciousness involve prefrontal activity, whereas other methods are associated with the finding that visual consciousness mainly involve occipital/parietal activity but not prefrontal. Most neuroscientific research on consciousness has had the explicit aim to identify the neural correlates of consciousness. Although it is rarely debated what we mean with a “neural correlate of consciousness,” most experiments aim to identify the minimal neural activations that are sufficient for a specific content of consciousness (Chalmers, 2000). Contrary to this, other scientists are preoccupied with finding neural correlates of consciousness “as such”—i.e., neural correlates that mark the difference between being dead, asleep, awake, etc., and which are not content-specific in the sense above. With regards to the attempt to isolate neural correlates of conscious content, one central debate in recent years has been whether neural correlates of consciousness should primarily be associated with prefrontal cortex (“late” activations) or whether (visual) consciousness should be associated with occipital/parietal activations (“early” activations). According to most recent reviews and articles, evidence is lending support toward the latter view (Andersen et al., 2016; Koch et al., 2016; Hurme et al., 2017). According to this view, “late” activations are not actual correlates of consciousness, but are confounds associated with metacognition and report (e.g., Aru et al., 2012). Nevertheless, proponents of the opposite view—that consciousness is associated with prefrontal cortex activity—argue that “early” activations in fact represent preconscious states—i.e., information that is not yet conscious (e.g., Lau and Rosenthal, 2011). According to other perspectives, this debate is partially misunderstood. Block (2005) argues that there may be two neural correlates of consciousness: One relating to phenomenal consciousness (the “early” activations), and one relating to access consciousness (the “late” activations). Others suggests that there is an identity between subjective experience and certain causal properties of physical systems rather than an identity between experience and particular brain parts (Tononi et al., 2016). According to the REF-CON model of consciousness, subjective experience is intrinsically related to a particular kind of “strategy” that makes information available for action (Overgaard and Mogensen, 2014; Mogensen and Overgaard, 2017). From this perspective, there need not be any “universal” correlate of consciousness at all. But even in such theoretical models according to which finding neural correlates of consciousness is very different from explaining consciousness, neural correlates of consciousness are essential as evidence to show how and if they work in practice. There has been relatively more research into the neural correlates of the contents of consciousness than into “consciousness as such.” Research attempting to identify particular “levels” of consciousness obviously also face many methodological challenges, not least relating to contrastive analysis. Some studies have attempted to contrast healthy subjects with patients in vegetative state or minimally conscious state (Boly et al., 2013), although there are a number of problems: Some experiments indicate that not all such patients are unconscious (Owen et al., 2006), and—at the same time—most brain injured patients have many different lesions and, consequently, massive reorganization, which makes comparisons very difficult. The “upsurge” of interest in a science of consciousness did not begin but certainly took off with the publications of Chalmers (1995, 1996) and the Tucson-based conference series “Toward a Science of Consciousness”—soon to be further strengthened by the annual conferences organized by the ASSC (Association for the Scientific Study of Consciousness). Since then, much has happened in the attempt to discover neural and cognitive correlates of consciousness. It is however as uncertain today as it was then how exactly to apply these findings. In principle, there are many potential applications of consciousness research, but whereas some are extensions of the more fundamental questions (e.g., ethics and law), others are close to the heart of what consciousness research is (arguably) about, i.e., the mind-brain or mind-body problem. One such fundamental problem relates to the fact that consciousness is subjective and in this way accessible from the first person only. Whereas we still have no universally accepted measures of consciousness, much progress has been made with regards to how one may grasp the content of an experience in the context of an experiment. One major future challenge will be how to measure consciousness “from the outside.” This problem is currently being faced in coma and vegetative state patients who either do not respond or respond in a minimal or strange fashion. It will very likely be an even greater challenge for a future science of consciousness to consider how to evaluate whether artificial systems (e.g., computers or robots) can be conscious or whether experience is a privilege for biological creatures. Essentially, these questions force us to try to make scientifically based decisions about how to measure conscious experience in highly different situations: In coma/vegetative state patients, there are little or no responses, yet a neural (however altered) system. In artificial systems, there may be high responsiveness (even, in principle, explicit expressions of being conscious) but no neural (biological) system. One possibly even greater challenge will be to reintegrate the philosophical metaphysical debate into the scientific work. It will be a challenge to the future science of consciousness to demonstrate that empirical work on consciousness directly aids an understanding of the fundamental questions about consciousness. This challenge may seem unavoidable as the current preoccupation with cognitive functions and neural activations associated with subjective experience in most cases seems so directly linked to and motivated by the mind-brain problem. Existing data, however, seems to fit easily into every theoretical understanding of this problem. In and of itself, it seems not to be the case that evidence that perceptual experience is associated with—say—activity in primary visual cortex also provides evidence to determine whether consciousness should be seen as—say—identical to or metaphysically different from brain activity. Accordingly, it will require something “extra” to answer this challenge. Either, if possible, experimental investigations must be designed in order to “test” theoretical positions that currently are stated within the framework of philosophy of mind. Alternatively, experimental consciousness research must work even closer with theoretical consciousness research in order to make empirical data available as arguments. The challenges highlighted above obviously only represent a few of the many scientific and theoretical issues that scientists in this area face. Consciousness remains one of the biggest scientific challenges among all disciplines as the most fundamental questions are not simply unanswered—it is still highly unclear how one should even begin to answer them. Currently, consciousness research is often considered a “topic”—or even “niche”—under the umbrella of cognitive neuroscience. Nevertheless, consciousness researchers often point out that subjective experience is the underlying and fundamental reason for many questions in neuroscience. Scientists interested in the brain are often seeking answers to questions such as why we become addicted, how we remember, perceive, or solve problems. Such questions arguably presume conscious experience and make little sense without. Terms such as “memory” or “perception” do not solely refer to behavior, but also to particular kinds of conscious content which we know about from introspection. For this reason, one future ambition for consciousness research could be to become a more integral part of the overall ambition to understand the brain, and as such become part of the basic curriculum for any neuroscientist. The author confirms being the sole contributor of this work and approved it for publication. The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Andersen, L. M., Pedersen, M. N., Sandberg, K., and Overgaard, M. (2016). Occipital MEG activity in the early time range (<300 ms) predicts graded changes in perceptual consciousness. Cereb. Cortex 26, 2677–2688. doi: 10.1093/cercor/bhv108 PubMed Abstract | CrossRef Full Text |
Open Access
Published: 10 October 2017
Frontiers in Plant Science, Volume 8; https://doi.org/10.3389/fpls.2017.01735

Abstract:
The plant hormone auxin is a vital component for plant reproduction as it regulates the development of both male and female reproductive organs, including ovules and gynoecia. Furthermore, auxin plays important roles in the development and growth of seeds and fruits. Auxin responses can be detected in ovules shortly after fertilization, and it has been suggested that this accumulation is a prerequisite for the developmental reprogramming of the ovules to seeds, and of the gynoecium to a fruit. However, the roles of auxin at the final stages of ovule development, and the sources of auxin leading to the observed responses in ovules after fertilization have remained elusive. Here we have characterized the auxin readout in Arabidopsis ovules, at the pre-anthesis, anthesis and in the immediate post-fertilization stages, using the R2D2 auxin sensor. In addition we have mapped the expression of auxin biosynthesis and conjugation genes, as well as that of auxin transporting proteins, during the same developmental stages. These analyses reveal specific spatiotemporal patterns of the different auxin homeostasis regulators. Auxin biosynthesis genes and auxin transport proteins define a pre-patterning of vascular cell identity in the pre-anthesis funiculus. Furthermore, our data suggests that auxin efflux from the ovule is restricted in an anther-dependent manner, presumably to synchronize reproductive organ development and thereby optimizing the chances of successful fertilization. Finally, de novo auxin biosynthesis together with reduced auxin conjugation and transport result in an enhanced auxin readout throughout the sporophytic tissues of the ovules soon after fertilization. Together, our results suggest a sophisticated set of regulatory cascades that allow successful fertilization and the subsequent transition of the female reproductive structures into seeds and fruits.
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