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Yanni Zhang, Rongxi Li, Hexin Huang, Tian Gao, , Bangsheng Zhao, Xiaoli Wu, Ahmed Khaled
Published: 15 September 2021
Frontiers in Earth Science, Volume 9; https://doi.org/10.3389/feart.2021.729710

Abstract:
The shale of the Wulalike Formation developed in the northwestern Ordos Basin is considered to be an effective marine hydrocarbon source rock. One of the key factors for successful shale gas exploration in the Wufeng–Longmaxi Formation in the Sichuan Basin is the high content of biogenic silica. However, few people have studied the siliceous origin of the Wulalike shale. In this study, we used petrographic observation and element geochemistry to analyze the origin of silica in the Wulalike shale. The results show that the siliceous minerals are not affected by hydrothermal silica and mainly consist of biogenic and detrital silica. A large number of siliceous organisms, such as sponge spicules, radiolarians, and algae, are found under the microscope. It has been demonstrated that total organic carbon has a positive correlation with biogenic silica and a negative correlation with detrital silica, and biogenic silica is one of the effective indicators of paleoproductivity. Therefore, the enrichment of organic matter may be related to paleoproductivity. Through the calculation of element logging data in well A, it is found that biogenic silica is mainly distributed in the bottom of the Wulalike Formation, and the content of biogenic silica decreases, while the content of detrital silica increases upward of the Wulalike Formation. Biogenic silica mainly exists in the form of microcrystalline quartz, which can form an interconnected rigid framework to improve the hardness and brittleness of shale. Meanwhile, biogenic microcrystalline quartz can protect organic pores from mechanical compaction. Therefore, it may be easier to fracture the shale gas at the bottom of the Wulalike Formation in well A.
, Petra Imhof, Petra Hellwig
Published: 15 September 2021
Frontiers in Chemistry, Volume 9; https://doi.org/10.3389/fchem.2021.762612

Abstract:
Editorial on the Research Topic Computational and Experimental Insights in Redox-Coupled Proton Pumping in Proteins Elementary electron and proton transfer reactions commonly occur in chemistry and biology. Proteins involved in oxidative- and photo-phosphorylation carry out these reactions to generate energy in the form of ATP. Despite the simplicity of electron and proton transfer reactions, these pose extreme challenge to study either by experimental or computational approaches. In this special issue, we present a collection of reviews, original research articles as well as perspectives written by top-level experimental and computational experts working in the field of redox-active enzymes and associated fields. The special issue presents a current state-of-the-art in our understanding of the mechanism of bioenergetic enzymes, and at the same time provides important glimpses of theoretical and experimental methodological advances in the field. The respiratory complex I, NADH:quinone (Q) oxidoreductase, is the first electron acceptor of the electron transport chain (ETC) in many organisms and pumps protons by conserving energy from the reduction of quinone to quinol (Parey et al., 2020). Despite recent major advances in structural characterization of this large complex (500–1 MDa), the molecular mechanism of redox-coupled proton pumping remains largely unknown and among other questions, the role of quinone/quinol binding in the electrostatic and conformational control of enzyme remains unclear (Hielscher et al., 2013; Haapanen and Sharma, 2021). One of the central elements of the coupling mechanism is the interface between the peripheral “arm” catalysing electron transfer and a membrane “arm” responsible for proton translocation. In this special issue, Yoga et al. and Nuber et al. have reviewed and discussed interesting aspects of quinone/quinol binding and its coupling to the conformational changes in this critical region of complex I. Yoga et al. reviewed the latest structural and computational data on the binding of quinone in the unique ∼30 Å long quinone-binding tunnel of complex I, and discussed recent mechanistic models of proton pumping. Nuber et al. have highlighted the importance of movement of quinol (QH−) anion in the quinone tunnel and protonation/deprotonation reactions in the redox-coupled proton pumping mechanism of complex I. The third complex in the ETC is complex III and is described by a well-known Q cycle (Crofts et al., 2017). Husen and Solov’yov gave new insights into the side-reactions of complex III, and by performing multiscale computational simulations they suggest how superoxide forms by reaction between dioxygen and semiquinone, and how it is released to the membrane-solvent environment. Thus, shedding light on the ROS (reactive oxygen species) generation by complex III of the ETC. Sarewicz et al. by performing site-directed mutagenesis of heme bL ligand and spectroscopic measurements provided new insights into the redox reactions of Qo site of complex III. The final electron acceptor, complex IV, acts as an electron sink in the ETC of many organisms, and efficiently pumps protons by conserving the free energy of oxygen reduction (Wikström and Sharma, 2018). The functional importance of a tyrosyl radical in the catalytic cycle of complex IV has been emphasized based on computations and experiments (Voicescu et al., 2009; Sharma et al., 2013). Blomberg, based on hybrid density functional theory calculations (Blomberg) discusses how highly conserved redox-active tyrosine remains deprotonated until the last steps of the catalytic cycle, a notion that is central to drive proton pumping even at high proton motive force. Baserga et al. performed advanced FTIR spectroelectrochemical titrations and provided a quantitative description of the changes in electric field at the active site of complex IV during its redox reactions. Kaur and colleagues provide a holistic view on the proton binding motifs of the redox-active proton pumps. They highlight the central role played by proton loading sites (sites in protein that uptake and release protons) in maintaining pumping even at high proton motive force. Relatedly, Bondar presents a comparison of several proton translocating enzymes and their proton binding motifs, and emphasizes the importance of these in understanding mechanism of proton pumping enzymes. In the study of Calisto and Pereira, sequence and structural analysis of NrfD-like subunits is presented and their role in ion-translocation and quinone binding is discussed. Other complex electron and proton translocating enzymes are presented, completing the picture on the complexity of coupled electron and proton translocation in biological systems. Wu et al. reveal the complex electron transfer in NADPH oxidase 5 (NOX5), a member of a family of enzymes, dedicated to the production of reactive oxygen species. By computer simulations, they analysed the O2 movement and electron tunneling pathways in the inter-heme electron-transfer steps that ultimately lead to production of superoxide in NOX5. Finally, Dale-Evans et al. describe the mechanism of HypD from E. coli by means of theoretical and computational studies on the voltametric current. Their data allowed them to specifically estimate the kinetic parameter and reveal a step-wise one-electron, one-proton transfer mechanism rather than a concerted two-electron redox reaction. The work presented in this special issue highlights how experimental (spectroscopy, biochemistry, etc.) and computational (classical and quantum chemical simulations) studies in concert have greatly advanced our knowledge of proton-coupled electron transfer processes. Even with the broad range of exciting results and mechanistic understanding already obtained, the complexity of the systems involved in redox-coupled proton pumping is so high that novel developments at all levels will...
, Beate Winner, Franziska Richter, Gabriela Caraveo
Frontiers in Cell and Developmental Biology, Volume 9; https://doi.org/10.3389/fcell.2021.752378

Abstract:
Editorial on the Research Topic Intracellular Mechanisms of α-Synuclein Processing The aggregation of the protein α-synuclein (aSyn) is the pathological hallmark of the group of neurodegenerative disorders, collectively known as synucleinopathies. These include Parkinson's disease (PD), PD-Dementia, Dementia with Lewy Bodies (DLB), and Multiple Systems Atrophy (MSA). While all of these neurodegenerative disorders present with distinctive clinical features, they all converge in one pathological characteristic: intracellular aSyn aggregation into Lewy Bodies (Mezey et al., 1998; Spillantini et al., 1998; Goedert et al., 2017; Riederer et al., 2019). Lewy Body pathology can occur at the soma and neurites of neurons, but it can also occur within glial cells as in MSA [called glial cytoplasmic inclusions (GCI)]. To complicate matters, there is increasing evidence for extracellular aSyn conformers, that might be responsible for the spreading of pathological protein aggregates and hence disease pathology (Kordower et al., 2008; Li et al., 2008), as first demonstrated in patients following fetal midbrain transplants. This findings have led to the hypothesis that sporadic PD might progress in six states that follow a caudo-rostral pattern (Braak et al., 2003), with peripheral non-motor symptoms occurring before the diagnosis of the full blown disease. Despite the central role of aSyn in all of these disorders, little is known about the initial mechanisms that lead to its aggregation, disruption of cellular functions and extracellular spread, as suggested via the gut-brain axis (Kim et al., 2019; Derkinderen et al., 2020). Articles within this Research Topic seek to shed light into these mechanisms. aSyn is typically degraded by both the lysosome and the proteasome (Cuervo et al., 2004; Shin et al., 2005). It is of no surprise that mutations in genes associated with lysosomal pathways are major genetic risk factors for the development of PD (Klein and Mazzulli, 2018). These include the lysosomal enyzmes β-glucocerebrosidase (GBA1), galactocerebrosidase (GALC), and the lysosomal cathepsins (CTSD and CTSB), as well as lysosomal membrane proteins like SCARB2, TMEM175, LAMP3, and components of the lysosomal acidification machinery (ATP13A2 and ATP6V0A1) (Sidransky et al., 2009; Chang et al., 2017; Robak et al., 2017). As shown in longitudinal studies, GBA1-associated PD patients undergo faster disease progression and shorter survival, underlying the need for novel and genotype-specific therapeutic strategies (Brockmann). GBA1 degrades the lysosomal sphingolipid glucosylceramide into glucose and ceramide. Mutations in GBA1 linked to PD, yield deficits in ceramide metabolism and result in inefficient aSyn degradation within the lysosome. Accumulation of the GBA1 substrate, glucosylceramide can lead to the conversion of physiologic to pathologic aSyn (Zunke et al., 2018), indicating lipids as one of the key factors in aSyn conformation (Kiechle et al.) (Figure 1, no. 1, 5). Figure 1. Overview of intra- and extracellular routes of aSyn aggregation and pathology pathways as highlighted within this Research Topic: (1) Intracellular aSyn aggregation can be triggered by overexpression, post translational modifications (PTMs), or mutations within aSyn (e.g., A53T, A30P). (2–5) Pathological aSyn conformers comprising oligomers and fibrils block the autophagic/lysosomal pathway by interfering with BAG5 and the autophagic adaptor protein p62 (2), the lysosomal enzymes β-glucocerebrosidase (GBA1; 3) and cathepsin D (CTSD; 4), all critical for aSyn degradation. Dysfunction of GBA1 causes glycosphingolipids (glucosylceramide, GluCer) to increase (5). These lipids further drive aSyn aggregation. Pathological aSyn conformers also affect mitochondrial function, the lysosomal-mitochondrial crosstalk (6), vesicle recycling, and endocytosis (7), as well as formation and function of the actin cytoskeleton (8). Moreover, aSyn accumulation induces microRNAs involved in cell cycle activation (9). (10) Effects of aSyn-mediated pathologies were analyzed and summarized within different models (human, murine, C. elegans), exhibiting important roles of aSyn within the hippocampus. Additionally, aSyn is capable of escaping neurons causing cell-to-cell propagation and hence spreading of disease, which causes pathological effects on peripheral immune cells (11) and the gastro intestinal tract (GIT). The gut-brain-axis contributes to the spread of pathological aSyn conformers and disease pathology (12, 13). This illustration contains images from Servier Medical Art (smart.servier.com). Further emphasizing the importance of lysosomal degradation processes in synucleinopathies (Figure 1, no. 2-5), as well as the bidirectional loop between degradative function of lysosomes and aSyn proteoforms (Wildburger et al.), lysosomal cathepsin D variants associated with neurodegenerative disorders were analyzed (Bunk et al.) (Figure 1, no. 4). Given that lysosomal cathepsins have been shown to directly process aSyn (Mcglinchey and Lee, 2015), the study of Bunk et al. also suggests enhanced aSyn proteolysis as a potential therapeutic strategy. Since the lysosome is the key organelle involved in autophagy, defects in autophagic function have been implicated in numerous neurodegenerative diseases including synucleinopathies. Highlighting the link between lysosomal autophagic pathways and aSyn accumulation, Friesen et al. describe that the co-chaperone BAG5 can promote aSyn oligomer formation, as well as regulate the levels and subcellular distribution of p62, an important autophagic adaptor protein (Friesen et al.) (Figure 1, no. 2). The structural properties and posttranslational modifications (PTMs) of aSyn play an important role in toxicity and its seeding capacity (Figure 1, no. 1, 12). To this end, Ray et al. revises the importance of aSyn structure and mutations on the biophysics of its aggregation, cell...
Christina Pettan-Brewer, Andreza Francisco Martins, Daniel Paiva Barros de Abreu, Ana Pérola Drulla Brandão, David Soeiro Barbosa, Daniela P. Figueroa, Natalia Cediel Becerra, Laura H. Kahn, Daniel Friguglietti Brandespim, Juan Carlos Carrascal Velásquez, et al.
Published: 14 September 2021
Frontiers in Public Health, Volume 9; https://doi.org/10.3389/fpubh.2021.687110

Abstract:
Professionals throughout the world have been working to assess the interdisciplinary interaction and interdependence between health and wellbeing in a constantly changing environment. The One Health concept was developed to encourage sustainable collaborative partnerships and to promote optimal health for people, animals, plants, the environment, and the whole planet. The dissemination of scientific discoveries and policies, by working directly with diverse communities, has been one of the main goals for Global One Health. The One Health concept has also been referred or related to as “One Medicine, One Medicine-One Health, One World-One Health, EcoHealth,” and Planetary Health,” depending on each fundamental view and approach. In Latin America, despite the concept still being discussed among health professionals and educators, several One Health initiatives have been used daily for more than decades. One Health action has been applied especially in rural and underserved urban areas where low socioeconomic status, lack of health professionals, and scarcity of medical resources may require professionals to work together. Local communities from diverse social and economic statuses, including indigenous populations have been working with institutions and social organizations for many years, accomplishing results through grassroots movements. These “bottom-up” socio-community approaches have also been tools for the prevention and control of diseases, such practice has preceded the One Health concepts in Latin American countries. It is strongly believed that collaborative, multidisciplinary, political, and economic initiatives with prosocial focus may become investments toward obtaining significant results in the face of global, economic and health challenges; working for a healthier world with inclusivity, equity, and equality. In this study, it is briefly presented how the One Health approach has been initiated and developed in Latin America, highlighting the events and actions taken in Brazil, Chile, and Colombia.
Lucas Albuquerque Freire, Michele Andrade de Brito, Natã Sant’Anna Esteves, Márcio Tannure, Maamer Slimani, Hela Znazen, Nicola Luigi Bragazzi, Ciro José Brito, Dany Alexis Sobarzo Soto, Daniel Gonçalves, et al.
Published: 14 September 2021
Frontiers in Psychology, Volume 12; https://doi.org/10.3389/fpsyg.2021.708725

Abstract:
This study aimed to determine the impact of a soccer game on the creatine kinase (Ck) response and recovery and the specific Global Positioning System (GPS)-accelerometry-derived performance analysis during matches and comparing playing positions. A sample composed of 118 observations of 24 professional soccer teams of the Brazil League Serie A was recruited and classified according to playing positions, i.e., Left/Right Defenders (D = 30, age: 25.2 ± 5.8 years, height: 187 ± 5.5 cm, weight: 80 ± 5.8 kg), Offensive Midfielders (OM = 44, age: 25.1 ± 0.2 years, height: 177 ± 0.3 cm, weight: 73 ± 1.2 kg), Forwards (F = 9, age: 25.1 ± 0.2 years, height: 176.9 ± 4.3 cm, weight: 74.5 ± 2.1 kg), Left/Right Wingers (M = 23, age: 24.5 ± 0.5 years, height: 175 ± 1.1 cm, weight: 74 ± 4.4 kg), and Strikers (S = 12, age: 28 ± 0.2 years, height: 184 ± 1.0 cm, weight: 80 ± 1.4 kg). Blood Ck concentration was measured pre-, immediately post-, and 24 h postgame, and the GPS-accelerometry parameters were assessed during games. Findings demonstrated that Ck concentrations were higher at all postgame moments when compared with pregame, with incomplete recovery markers being identified up to 24 h after the game (range: 402–835 U/L). Moreover, Midfielders (108.6 ± 5.6 m/min) and Forwards (109.1 ± 8.3 m/min) had a higher relative distance vs. other positions (100.9 ± 10.1 m/min). Strikers [8.2 (8.1, 9.05) load/min] and Defenders [8.45 (8, 8.8) load/min] demonstrated lower load/min than Wingers [9.5 (9.2, 9.8) load/min], Midfielders [10.6 (9.9, 11.67) load/min], and Forwards [11 (10.65, 11, 15) load/min]. These results could be used to adopt specific training programs and recovery strategies after match according to the playing positions.
Leila Methnani, Andrea Aler Tubella, Virginia Dignum, Andreas Theodorou
Frontiers in Artificial Intelligence, Volume 4; https://doi.org/10.3389/frai.2021.737072

Abstract:
As Artificial Intelligence (AI) continues to expand its reach, the demand for human control and the development of AI systems that adhere to our legal, ethical, and social values also grows. Many (international and national) institutions have taken steps in this direction and published guidelines for the development and deployment of responsible AI systems. These guidelines, however, rely heavily on high-level statements that provide no clear criteria for system assessment, making the effective control over systems a challenge. “Human oversight” is one of the requirements being put forward as a means to support human autonomy and agency. In this paper, we argue that human presence alone does not meet this requirement and that such a misconception may limit the use of automation where it can otherwise provide so much benefit across industries. We therefore propose the development of systems with variable autonomy—dynamically adjustable levels of autonomy—as a means of ensuring meaningful human control over an artefact by satisfying all three core values commonly advocated in ethical guidelines: accountability, responsibility, and transparency.
Zhi-Jie Xia, Xin-Xin I. Zeng, Mitali Tambe, Bobby G. Ng, P. Duc S. Dong,
Frontiers in Cell and Developmental Biology, Volume 9; https://doi.org/10.3389/fcell.2021.720688

Abstract:
Saul–Wilson syndrome (SWS) is a rare, skeletal dysplasia with progeroid appearance and primordial dwarfism. It is caused by a heterozygous, dominant variant (p.G516R) in COG4, a subunit of the conserved oligomeric Golgi (COG) complex involved in intracellular vesicular transport. Our previous work has shown the intracellular disturbances caused by this mutation; however, the pathological mechanism of SWS needs further investigation. We sought to understand the molecular mechanism of specific aspects of the SWS phenotype by analyzing SWS-derived fibroblasts and zebrafish embryos expressing this dominant variant. SWS fibroblasts accumulate glypicans, a group of heparan sulfate proteoglycans (HSPGs) critical for growth and bone development through multiple signaling pathways. Consistently, we find that glypicans are increased in zebrafish embryos expressing the COG4 p.G516R variant. These animals show phenotypes consistent with convergent extension (CE) defects during gastrulation, shortened body length, and malformed jaw cartilage chondrocyte intercalation at larval stages. Since non-canonical Wnt signaling was shown in zebrafish to be related to the regulation of these processes by glypican 4, we assessed wnt levels and found a selective increase of wnt4 transcripts in the presence of COG4 p.G516R . Moreover, overexpression of wnt4 mRNA phenocopies these developmental defects. LGK974, an inhibitor of Wnt signaling, corrects the shortened body length at low concentrations but amplifies it at slightly higher concentrations. WNT4 and the non-canonical Wnt signaling component phospho-JNK are also elevated in cultured SWS-derived fibroblasts. Similar results from SWS cell lines and zebrafish point to altered non-canonical Wnt signaling as one possible mechanism underlying SWS pathology.
Published: 14 September 2021
Frontiers in Tropical Diseases, Volume 2; https://doi.org/10.3389/fitd.2021.709907

Abstract:
The enterotoxigenic Escherichia coli (ETEC) are a diverse and genetically plastic pathologic variant (pathovar) of E. coli defined by their production of heat-labile (LT) and heat-stable (ST) enterotoxins. These pathogens, which came to recognition more than four decades ago in patients presenting with severe cholera-like diarrhea, are now known to cause hundreds of millions of cases of symptomatic infection annually. Children in low-middle income regions of the world lacking access to clean water and basic sanitation are disproportionately affected by ETEC. In addition to acute diarrheal morbidity, these pathogens remain a significant cause of mortality in children under the age of five years and have also been linked repeatedly to sequelae of childhood malnutrition and growth stunting. Vaccines that could prevent ETEC infections therefore remain a high priority. Despite several decades of effort, a licensed vaccine that protects against the breadth of these pathogens remains an aspirational goal, and the underlying genetic plasticity of E. coli has posed a fundamental challenge to development of a vaccine that can encompass the complete antigenic spectrum of ETEC. Nevertheless, novel strategies that include toxoids, a more complete understanding of ETEC molecular pathogenesis, structural details of target immunogens, and the discovery of more highly conserved antigens essential for virulence should accelerate progress and make a broadly protective vaccine feasible.
Published: 14 September 2021
Frontiers in Psychology, Volume 12; https://doi.org/10.3389/fpsyg.2021.726685

Abstract:
The COVID-19 health and economic crisis has also brought a rise in people being unable to cope with their existing medical conditions and other issues such as domestic violence, drugs, and alcohol among others. Suicidal tendencies have been on the rise. Feelings of isolation causing emotional distress in place-confined settings have put additional pressure on the healthcare systems demanding that we find additional and complementary means of support for those in need. This is important not only in the current pandemic but also in the post-pandemic world. The goal is to collectively contribute and address the recurring calls for actions to maintain global well-being and public health. An important discussion to bring on the table is the need to promote interventions for people to cope with the pandemic and to adjust to the post-pandemic world. Promoting affective attitudes toward place can foster well-being outcomes. This has important benefits and is of relevance to governments, policymakers, and healthcare professionals in delivering better healthcare equipping people with coping mechanisms both throughout the pandemic and in the long run. However, the key challenge is how to foster these place affect attitudes meeting the changing demands in the post-pandemic world. It is in the middle of a crisis that the conversation needs to start about how to strategically plan for the recovery.
, Andre Krouwel, Marisol Palacios-Gálvez, Elena Morales-Marente, Iván Rodríguez-Pascual, E. Begoña García-Navarro
Published: 14 September 2021
Frontiers in Psychology, Volume 12; https://doi.org/10.3389/fpsyg.2021.727225

Abstract:
This article describes patterns of compliance with social distancing measures among the Spanish population during the coronavirus disease-2019 (COVID-19) pandemic. It identifies several factors associated with higher or lower compliance with recommended measures of social distancing. This research is part of a 67-country study, titled the International COVID-19 study on Social & Moral Psychology, in which we use a Spanish dataset. Participants were residents in Spain aged 18 or above. The sample comprises 1,090 respondents, weighted to be representative of the Spanish population. Frequencies, correlations, bivariate analysis, and six models based on hierarchical multiple regressions were applied. The main finding is that most Spaniards are compliant with established guidelines of social distance during the pandemic (State of Alarm, before May 2020). Variables associated more with lower levels of compliance with these standards were explored. Six hierarchical multiple regression models found that compliance with social distance measures has a multifactorial explanation (R 2 between 20.4 and 49.1%). Sociodemographic factors, personal hygiene patterns, and the interaction between personal hygiene patterns and the support for political measures related to the coronavirus brought significant effects on the regression models. Less compliance was also associated with beliefs in some specific conspiracy theories with regard to COVID-19 or general conspiracy mentality (Conspiracy Mentality Questionnaire, CMQ), consumption patterns of traditional mass media (television, paper newspapers, magazines, and radio) and modern means to get informed (online digital newspapers, blogs, and social networks), political ideology, vote, trust in institutions, and political identification. Among the future lines of action in preventing the possible outbreak of the virus, we suggest measures to reinforce trust in official information, mainly linked to reducing the influence of disinformation and conspiracy theories parallel to the pandemic.
Hao Zhang, Zeyu Wang, Ziyu Dai, Wantao Wu, Hui Cao, Shuyu Li, Nan Zhang,
Published: 14 September 2021
Frontiers in Immunology, Volume 12; https://doi.org/10.3389/fimmu.2021.694490

Abstract:
Tumor-infiltrating immune cells (TIICs) have become an important source of markers for predicting the clinical outcomes of cancer patients. However, measurements of cellular heterogeneity vary due to the frequently updated reference genomes and gene annotations. In this study, we systematically collected and evaluated the infiltration pattern of 65 immune cells. We constructed the Immune Cell Pair (ICP) score based on the cell pair algorithm in 3,715 samples and across 12 independent cancer types, among which, the ICP score from six cancer types was further validated in 2,228 GEO samples. An extensive tumorigenic and immunogenomic analysis was subsequently conducted. As a result, the ICP score showed a robust reliability and efficacy in predicting the survival of patients with gliomas, in pan-cancer samples, and six independent cancer types. Notably, the ICP score was correlated with the genomic alteration features in gliomas. Moreover, the ICP score exhibited a remarkable association with multiple immunomodulators that could potentially mediate immune escape. Finally, the ICP score predicted immunotherapeutic responses with a high sensitivity, allowing a useful tool for predicting the overall survival and guiding immunotherapy for cancer patients.
, Douglas Cost, Christine P. Villano
Frontiers in Ecology and Evolution, Volume 9; https://doi.org/10.3389/fevo.2021.695534

Abstract:
Community and citizen science on climate change-influenced topics offers a way for participants to actively engage in understanding the changes and documenting the impacts. As in broader climate change education, a focus on the negative impacts can often leave participants feeling a sense of powerlessness. In large scale projects where participation is primarily limited to data collection, it is often difficult for volunteers to see how the data can inform decision making that can help create a positive future. In this paper, we propose and test a method of linking community and citizen science engagement to thinking about and planning for the future through scenarios story development using the data collected by the volunteers. We used a youth focused wild berry monitoring program that spanned urban and rural Alaska to test this method across diverse age levels and learning settings. Using qualitative analysis of educator interviews and youth work samples, we found that using a scenario stories development mini-workshop allowed the youth to use their own data and the data from other sites to imagine the future and possible actions to sustain berry resources for their communities. This process allowed youth to exercise key cognitive skills for sustainability, including systems thinking, futures thinking, and strategic thinking. The analysis suggested that youth would benefit from further practicing the skill of envisioning oneself as an agent of change in the environment. Educators valued working with lead scientists on the project and the experience for youth to participate in the interdisciplinary program. They also identified the combination of the berry data collection, analysis and scenarios stories activities as a teaching practice that allowed the youth to situate their citizen science participation in a personal, local and cultural context. The majority of the youth groups pursued some level of stewardship action following the activity. The most common actions included collecting additional years of berry data, communicating results to a broader community, and joining other community and citizen science projects. A few groups actually pursued solutions illustrated in the scenario stories. The pairing of community and citizen science with scenario stories development provides a promising method to connect data to action for a sustainable and resilient future.
Akane Shinohara, , Takehiko Iijima
Frontiers in Cardiovascular Medicine, Volume 8; https://doi.org/10.3389/fcvm.2021.730298

Abstract:
The endothelial glycocalyx (GCX) plays a key role in the development of organ failure following sepsis. Researchers have investigated GCX degradation caused by pathological conditions. Nonetheless, the GCX restoration process remains poorly understood. Herein, we developed a model in which GCX restoration could be reproduced in mice using in vivo imaging and a dorsal skinfold chamber (DSC). The severity of sepsis was controlled by adjusting the dose of lipopolysaccharide (LPS) used to trigger GCX degradation in BALB/c mice. We evaluated the GCX thickness, leukocyte-endothelial interactions, and vascular permeability using in vivo imaging through DSC under intravital microscopy. The plasma concentration of syndecan-1(Sdc-1), a GCX structural component, was also determined as a marker of GCX degradation. Thus, we developed a reproducible spontaneous GCX recovery model in mice. Degraded GCX was restored within 24 h by the direct visualization of the endothelial GCX thickness, and leukocyte-endothelial interactions. In contrast, indirectly related indicators of recovery from sepsis, such as body weight and blood pressure, required a longer recovery time. This model can be used to study intractable angiopathy following sepsis.
, Meibao Feng, Minhong Wang, Liang Zhang, Meirong Li, Chencui Huang
Published: 14 September 2021
Frontiers in Oncology, Volume 11; https://doi.org/10.3389/fonc.2021.689136

Abstract:
Purpose This study established and verified a radiomics model for the preoperative prediction of the Ki67 index of gastrointestinal stromal tumors (GISTs). Materials and Methods A total of 344 patients with GISTs from three hospitals were divided into a training set and an external validation set. The tumor region of interest was delineated based on enhanced computed-tomography (CT) images to extract radiomic features. The Boruta algorithm was used for dimensionality reduction of the features, and the random forest algorithm was used to construct the model for radiomics prediction of the Ki67 index. The receiver operating characteristic (ROC) curve was used to evaluate the model’s performance and generalization ability. Results After dimensionality reduction, a feature subset having 21 radiomics features was generated. The generated radiomics model had an the area under curve (AUC) value of 0.835 (95% confidence interval(CI): 0.761–0.908) in the training set and 0.784 (95% CI: 0.691–0.874) in the external validation cohort. Conclusion The radiomics model of this study had the potential to predict the Ki67 index of GISTs preoperatively.
Cheng Li, Kangning Li, Xinyi Liu, Hui Ruan, Mingming Zheng, Zhijie Yu, Junyi Gai, Shouping Yang
Published: 14 September 2021
Frontiers in Plant Science, Volume 12; https://doi.org/10.3389/fpls.2021.700651

Abstract:
Phosphorus (P) is one of the essential macronutrients, whose deficiency limits the growth and development of plants. In this study, we investigated the possible role of GmWRKY46 in the phosphate (Pi) starvation stress tolerance of soybean. GmWRKY46 belonged to the group III subfamily of the WRKY transcription factor family, which was localized in the nucleus and had transcriptional activator activity. GmWRKY46 could be strongly induced by Pi starvation, especially in soybean roots. Overexpression of GmWRKY46 significantly enhanced tolerance to Pi starvation and lateral root development in transgenic Arabidopsis. RNA-seq analysis showed that overexpression of GmWRKY46 led to change in many genes related to energy metabolisms, stress responses, and plant hormone signal transduction in transgenic Arabidopsis. Among these differential expression genes, we found that overexpression of AtAED1 alone could enhance the tolerance of transgenic Arabidopsis to Pi starvation. Y1H and ChIP-qPCR analyses showed that GmWRKY46 could directly bind to the W-box motif of the AtAED1 promoter in vitro and in vivo. Furthermore, results from intact soybean composite plants with GmWRKY46 overexpression showed that GmWRKY46 was involved in hairy roots development and subsequently affected plant growth and Pi uptake. These results provide a basis for the molecular genetic breeding of soybean tolerant to Pi starvation.
Qian Zhao, Yanxia Shi, Yuhong Wang, Xuewen Xie, Lei Li, Liyun Guo, ,
Published: 14 September 2021
Frontiers in Microbiology, Volume 12; https://doi.org/10.3389/fmicb.2021.716758

Abstract:
Target leaf spot (TLS), caused by Corynespora cassiicola, is an emerging and high-incidence disease that has spread rapidly on the global scale. Aerospores released by infected plants play a significant role in the epidemiology of cucumber TLS disease; however, no data exist concerning the infectiousness and particle size of C. cassiicola aerospores, and the experimental evidence for the aerospores transmission was lacking. In the present study, highly effective approaches to collect and quantify aerospores were developed for exposure chamber and greenhouse studies. Quantifiable levels of C. cassiicola aerospores were detected in 27 air samples from nine naturally infested greenhouses, ranging from 198 to 5,969 spores/m3. The C. cassiicola strains isolated from air samples were infective to healthy cucumber plants. Exposure chambers were constructed to study the characteristics of C. cassiicola aerospores released by artificially infested cucumber plants. The particle size of C. cassiicola ranged predominately from 2.1 to 4.7 μm, accounting for 71.97% of the total amount. In addition, the transmission dynamics of C. cassiicola aerospores from donor cucumber plants to recipient cucumber plants were confirmed in exposure chambers and greenhouses. The concentration of C. cassiicola aerospores was positively associated with cucumber TLS disease severity. This study suggested that aerospore dispersal is an important route for the epidemiology of plant fungal disease, and these data will contribute to the development of new strategies for the effective alleviation and control of plant diseases.
Marc Sauchelli Toran, Patricia Fernández Labrador, Juan Francisco Ciriza, Yeray Asensio, André Reigersman, Juan Arevalo, Frank Rogalla,
Frontiers in Chemical Engineering, Volume 3; https://doi.org/10.3389/fceng.2021.734233

Abstract:
Water reuse is a safe and often the least energy-intensive method of providing water from non-conventional sources in water stressed regions. Although public perception can be a challenge, water reuse is gaining acceptance. Recent advances in membrane technology allow for reclamation of wastewater through the production of high-quality treated water, including potable reuse. This study takes an in-depth evaluation of a combination of membrane-based tertiary processes for its application in reuse of brewery wastewater, and is one of the few studies that evaluates long-term membrane performance at the pilot-scale. Two different advanced tertiary treatment trains were tested with secondary wastewater from a brewery wastewater treatment plant (A) ultrafiltration (UF) and reverse osmosis (RO), and (B) ozonation, coagulation, microfiltration with ceramic membranes (MF) and RO. Three specific criteria were used for membrane comparison: 1) pilot plant optimisation to identify ideal operating conditions, 2) Clean-In-Place (CIP) procedures to restore permeability, and 3) final water quality obtained. Both UF and Micro-Filtration membranes were operated at increasing fluxes, filtration intervals and alternating phases of backwash (BW) and chemically enhanced backwash (CEB) to control fouling. Operation of polymeric UF membranes was optimized at a flux of 25–30 LMH with 15–20 min of filtration time to obtain longer production periods and avoid frequent CIP membrane cleaning procedures. Combination of ozone and coagulation with ceramic MF membranes resulted in high flux values up to 120 LMH with CEB:BW ratios of 1:4 to 1:10. Coagulation doses of 3–6 ppm were required to deal with the high concentrations of polyphenols (coagulation inhibitors) in the feed, but higher concentrations led to increasing fouling resistance of the MF membrane. Varying the ozone concentration stepwise from 0 to 25 mg/L had no noticeable effect on coagulation. The most effective cleaning strategy was found to be a combination of 2000 mg/L NaOCl followed by 5% HCl which enabled to recover permeability up to 400 LMH·bar−1. Both polymeric UF and ceramic MF membranes produced effluents that fulfil the limits of the national regulatory framework for reuse in industrial services (RD 1620/2007). Coupling to the RO units in both tertiary trains led to further water polishing and an improved treated water quality.
Zi Wang, Xinfang Xie, Jingyi Li, Xue Zhang, Jiawei He, Manliu Wang, , Hong Zhang
Published: 14 September 2021
Frontiers in Immunology, Volume 12; https://doi.org/10.3389/fimmu.2021.676919

Abstract:
Introduction Crescents, especially those found at a percentage greater than 50%, are often associated with rapid progression of kidney disease in IgA nephropathy (IgAN). The mechanism of crescents forming in IgAN is still unclear. In this study, we aimed to evaluate whether excess complement activation participates in the formation of crescents in IgAN. Methods One hundred IgAN patients with various proportions of crescents—24 with 1%–24%, 27 with 25%–49%, 21 with 50%–74% 12 with more than 75%, and 16 without crescents—were included. Urinary concentrations of mannose-binding lectin (MBL), Bb, C4d, C3a, C5a, and soluble C5b-9 (sC5b-9) were measured at the time of biopsy. Receiver operating characteristic (ROC) curves were performed to evaluate predictive ability of renal survival for urine complement activation. In addition, historical C4d, C5b-9, and C3d were stained by immunohistochemistry. Results IgAN patients with more than 50% crescent formation showed higher complement activation levels than the other patients (urinary C3a/creatinine (C3a/Cr): 6.7295 ng/mg, interquartile range (IQR) 1.4652–62.1086 ng/mg vs. 0.1055 ng/mg, IQR 0–1.4089 ng/mg; urinary C5a/Cr: 15.6202 ng/mg, 4.3127–66.7347 ng/mg vs. 0.3280 ng/mg, IQR 0.0859–2.4439 ng/mg; urinary sC5b-9/Cr: 98.6357 ng/mg, 8.8058–1,087.4578 ng/mg vs. 1.4262 ng/mg, 0.0916–11.0858 ng/mg, all p-values <0.001). The levels of urinary MBL and C4d representing lectin complement pathway showed a linear association with the proportion of crescents (r = 0.457 and 0.562, respectively, both p-values <0.001). Combined urine complement products could increase the predictive ability compared with crescents alone from 0.904 to 0.944 (p = 0.062) with borderline significance. Moreover, the glomerular C4d deposition rate elevated with the increase of proportions of crescents. Conclusion Excess complement activation may be involved in the formation of crescents, especially diffuse crescent formation, in patients with IgAN. Urinary C4d correlated with the proportion of crescents and was a potential biomarker for disease monitoring in crescentic IgAN.
Yun Bai, Tao Yu, Jiezhong Deng, Yusheng Yang, Jiulin Tan, Qijie Dai, Zehua Zhang, , Jianzhong Xu
Frontiers in Cell and Developmental Biology, Volume 9; https://doi.org/10.3389/fcell.2021.730095

Abstract:
The periosteum is critical for bone healing. Studies have shown that the periosteum contains periosteal stem cells (PSCs) with multidirectional differentiation potential and self-renewal ability. PSCs are activated in early fracture healing and are committed to the chondrocyte lineage, which is the basis of callus formation. However, the mechanism by which PSCs are activated and committed to chondrocytes in bone regeneration remains unclear. Here, we show that tartrate acid phosphatase (TRAP)-positive monocytes secrete CTGF to activate PSCs during bone regeneration. The loss function of TRAP-positive monocytes identifies their specific role during bone healing. Then, the secreted CTGF promotes endochondral ossification and activates PSCs in mouse bone fracture models. The secreted CTGF enhances PSC renewal by upregulating the expression of multiple pluripotent genes. CTGF upregulates c-Jun expression through αVβ5 integrin. Then, c-Jun transcription activates the transcription of the pluripotent genes Sox2, Oct4, and Nanog. Simultaneously, CTGF also activates the transcription and phosphorylation of Smad3 through αVβ5 integrin, which is the central gene in chondrogenesis. Our study indicates that TRAP-positive monocyte-derived CTGF promotes bone healing by activating PSCs and directing lineage commitment and that targeting PSCs may be an effective strategy for preventing bone non-union.
Ziyan Yan, Wenfeng Deng, Yuchen Wang, Yanna Liu, Hengbiao Sun, Renfei Xia, Wenli Zeng, Jian Geng, Gui Chen, Xiaolong He, et al.
Published: 14 September 2021
Frontiers in Medicine, Volume 8; https://doi.org/10.3389/fmed.2021.721145

Abstract:
Background: Colonization of Cryptococcus rarely occurs in a graft. This study reports a case of malacoplakia and cryptococcoma caused by E. coli and Cryptococcus albidus in a transplanted kidney, with detailed pathology and metagenome sequencing analysis. Case Presentation: We presented a case of cryptococcoma and malacoplakia in the genitourinary system including the transplant kidney, bladder, prostate, and seminal vesicles caused by Cryptococcus albidus and Escherichia coli in a renal-transplant recipient. Metagenome sequencing was conducted on a series of samples obtained from the patient at three different time points, which we termed Phase I (at the diagnosis of cryptococcoma), Phase II (during perioperative period of graftectomy, 3 months after the diagnosis), and Phase III (2 months after graftectomy). Sequencing study in the Phase I detected two and four sequences of C. albidus respectively in cerebrospinal fluid (CSF) and feces, with resistant Escherichia coli 09-02E presented in urine and renal mass. A 3-month antibiotic treatment yielded a smaller bladder lesion but an enlarged allograft lesion, leading to a nephrectomy. In the Phase II, two sequences of C. albidus were detected in CSF, while the E. coli 09-02E continued as before. In the Phase III, the lesions were generally reduced, with one C. albidus sequence in feces only. Conclusions: The existence and clearance of Cryptococcus sequences in CSF without central nervous system symptoms may be related to the distribution of infection foci in vivo, the microbial load, and the body's immunity. Overall, this study highlights the need for enhanced vigilance against uncommon types of Cryptococcus infections in immunocompromised populations and increased concern about the potential correlation between E. coli and Cryptococcus infections.
Xiao-Ai Zhang, Rui-Qiu Zhao, Jin-Jin Chen, Yang Yuan, Xiang Tang, Zi-Wei Zhou, Luo Ren, Qin-Bin Lu, Yu-Na Wang, Hai-Yang Zhang, et al.
Published: 14 September 2021
Frontiers in Microbiology, Volume 12; https://doi.org/10.3389/fmicb.2021.709849

Abstract:
Human parechoviruses (HPeVs) are important causes of infection in children. However, without a comprehensive and persistent surveillance, the epidemiology and clinical features of HPeV infection remain ambiguous. We performed a hospital-based surveillance study among three groups of pediatric patients with acute respiratory infection (Group 1), acute diarrhea (Group 2), and hand, foot and mouth disease (Group 3) in Chongqing, China, from 2009 to 2015. Among 10,212 tested patients, 707 (6.92%) were positive for HPeV, with the positive rates differing significantly among three groups (Group 1, 3.43%; Group 2, 14.94%; Group 3, 3.55%; P < 0.001). The co-infection with other pathogens was detected in 75.2% (531/707) of HPeV-positive patients. Significant negative interaction between HPeV and Parainfluenza virus (PIV) (P = 0.046, OR = 0.59, 95% CI = 0.34–0.98) and positive interactions between HPeV and Enterovirus (EV) (P = 0.015, OR = 2.28, 95% CI = 1.23–4.73) were identified. Among 707 HPeV-positive patients, 592 (83.73%) were successfully sequenced, and 10 genotypes were identified, with HPeV1 (n = 396), HPeV4 (n = 86), and HPeV3 (n = 46) as the most frequently seen. The proportion of genotypes differed among three groups (P < 0.001), with HPeV1 and HPeV4 overrepresented in Group 2 and HPeV6 overrepresented in Group 3. The spatial patterns of HPeV genotypes disclosed more close clustering of the currently sequenced strains than those from other countries/regions, although they were indeed mixed. Three main genotypes (HPeV1, HPeV3, and HPeV4) had shown distinct seasonal peaks, highlighting a bi-annual cycle of all HpeV and two genotypes (HPeV 1 and HPeV 4) with peaks in odd-numbered years and with peaks in even-numbered years HPeV3. Significantly higher HPeV1 viral loads were associated with severe diarrhea in Group 2 (P = 0.044), while associated with HPeV single infection than HPeV-EV coinfection among HFMD patients (P = 0.001). It’s concluded that HPeV infection was correlated with wide clinical spectrum in pediatric patients with a high variety of genotypes determined. Still no clinical significance can be confirmed, which warranted more molecular surveillance in the future.
, Abhay B. Ramachandra, Jonas C. Schupp, Cristina Cavinato, Micha Sam Brickman Raredon, Thomas Bärnthaler, Carlos Jr. Cosme, Inderjit Singh, George Tellides, Naftali Kaminski, et al.
Published: 14 September 2021
Frontiers in Physiology, Volume 12; https://doi.org/10.3389/fphys.2021.726253

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Hypoxia adversely affects the pulmonary circulation of mammals, including vasoconstriction leading to elevated pulmonary arterial pressures. The clinical importance of changes in the structure and function of the large, elastic pulmonary arteries is gaining increased attention, particularly regarding impact in multiple chronic cardiopulmonary conditions. We establish a multi-disciplinary workflow to understand better transcriptional, microstructural, and functional changes of the pulmonary artery in response to sustained hypoxia and how these changes inter-relate. We exposed adult male C57BL/6J mice to normoxic or hypoxic (FiO2 10%) conditions. Excised pulmonary arteries were profiled transcriptionally using single cell RNA sequencing, imaged with multiphoton microscopy to determine microstructural features under in vivo relevant multiaxial loading, and phenotyped biomechanically to quantify associated changes in material stiffness and vasoactive capacity. Pulmonary arteries of hypoxic mice exhibited an increased material stiffness that was likely due to collagen remodeling rather than excessive deposition (fibrosis), a change in smooth muscle cell phenotype reflected by decreased contractility and altered orientation aligning these cells in the same direction as the remodeled collagen fibers, endothelial proliferation likely representing endothelial-to-mesenchymal transitioning, and a network of cell-type specific transcriptomic changes that drove these changes. These many changes resulted in a system-level increase in pulmonary arterial pulse wave velocity, which may drive a positive feedback loop exacerbating all changes. These findings demonstrate the power of a multi-scale genetic-functional assay. They also highlight the need for systems-level analyses to determine which of the many changes are clinically significant and may be potential therapeutic targets.
Ye-Eun Yoo, Seungjoon Lee, Woohyun Kim, Hyosang Kim, Changuk Chung, Seungmin Ha, Jinsu Park, Yeonseung Chung, Hyojin Kang,
Frontiers in Molecular Neuroscience, Volume 14; https://doi.org/10.3389/fnmol.2021.712576

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Shank2 is an excitatory postsynaptic scaffolding protein strongly implicated in autism spectrum disorders (ASDs). Shank2-mutant mice with a homozygous deletion of exons 6 and 7 (Shank2-KO mice) show decreased NMDA receptor (NMDAR) function and autistic-like behaviors at juvenile [∼postnatal day (P21)] and adult (>P56) stages that are rescued by NMDAR activation. However, at ∼P14, these mice show the opposite change – increased NMDAR function; moreover, suppression of NMDAR activity with early, chronic memantine treatment during P7–21 prevents NMDAR hypofunction and autistic-like behaviors at later (∼P21 and >P56) stages. To better understand the mechanisms underlying this rescue, we performed RNA-Seq gene-set enrichment analysis of forebrain transcriptomes from wild-type (WT) and Shank2-KO juvenile (P25) mice treated early and chronically (P7–21) with vehicle or memantine. Vehicle-treated Shank2-KO mice showed upregulation of synapse-related genes and downregulation of ribosome- and mitochondria-related genes compared with vehicle-treated WT mice. They also showed a transcriptomic pattern largely opposite that observed in ASD (reverse-ASD pattern), based on ASD-related/risk genes and cell-type–specific genes. In memantine-treated Shank2-KO mice, chromatin-related genes were upregulated; mitochondria, extracellular matrix (ECM), and actin-related genes were downregulated; and the reverse-ASD pattern was weakened compared with that in vehicle-treated Shank2-KO mice. In WT mice, memantine treatment, which does not alter NMDAR function, upregulated synaptic genes and downregulated ECM genes; memantine-treated WT mice also exhibited a reverse-ASD pattern. Therefore, early chronic treatment of Shank2-KO mice with memantine alters expression of chromatin, mitochondria, ECM, actin, and ASD-related genes.
Published: 14 September 2021
Frontiers in Psychology, Volume 12; https://doi.org/10.3389/fpsyg.2021.746871

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The emergent respect for the prominence of engagement in the present education has made it one of the most widespread inquiry issues that it has been regarded as the ultimate target of learning. In the language teaching field, the idea of student activities for learning is intensely rooted in the prevailing standards of effective language learning, which considers language communication and interaction as analytical for language improvement. Moreover, teachers as center of learning process is the most prominent research attention, and teachers play a key role in regulating the education process as well as students’ learning achievement. However, there is an absence of research which have considered teachers’ care and praise among all positive interpersonal behavior and its significant effect on students’ engagement. So, the present review attempts to focus on teacher care and praise, and their effects on student engagement in EFL classrooms. Subsequently, some implications are presented to clarify the practice of teachers, students, teacher educators, and materials developers.
Chang Ki Kim, Hyun-Seok Cho, Wonchul Cho, Hyun-Goo Kim
Published: 14 September 2021
Frontiers in Chemistry, Volume 9; https://doi.org/10.3389/fchem.2021.732582

Abstract:
A photovoltaic–electrolysis–PEM hybrid model was developed for a feasibility study, and simulations of several scenarios in Korea were performed. The solar irradiance was derived from the University of Arizona solar irradiance based on satellite–Korea Institute of Energy Research model which provides the satellite imagery over the Korean peninsula every 15 min. In Korea, the annual average solar irradiance is 1,310 kWh m−2 with a maximum of 1,440 kWh m−2 in 2017. Electricity load and solar irradiance information were used to test the performance model of the photovoltaic–electrolysis–PEM hybrid system for baseload and several peak load shave runs. When the baseload was set at 4200 MW, the total capacity of the Photovoltaic plants was 58.5 GWp. In contrast, the hybrid system reduced the peak load more efficiently during daytime. In particular, the capacity factor of the Proton Exchange Membrane system increased in winter because the solar irradiance is relatively weak in that season. These results provide useful insights for the development of control logic models for the PV–electrolysis–PEM system in micro-grid setups.
, Diana Camidge, Fiona Croden, Catherine Gibbons, R. James Stubbs, John Blundell, Graham Finlayson, Nicola Buckland
Published: 14 September 2021
Frontiers in Nutrition, Volume 8; https://doi.org/10.3389/fnut.2021.688295

Abstract:
Introduction: Free-living movement (physical activity [PA] and sedentary behavior [SB]) and eating behaviors (energy intake [EI] and food choice) affect energy balance and therefore have the potential to influence weight loss (WL). This study explored whether free-living movement and/or eating behaviors measured early (week 3) in a 14-week WL programme or their change during the intervention are associated with WL in women. Methods: In the study, 80 women (M ± SD age: 42.0 ± 12.4 years) with overweight or obesity [body mass index (BMI): 34.08 ± 3.62 kg/m2] completed a 14 week WL program focused primarily on diet (commercial or self-led). Body mass (BM) was measured at baseline, and again during week 2 and 14 along with body composition. Free-living movement (SenseWear Armband) and eating behavior (weighed food diaries) were measured for 1 week during week 3 and 12. Hierarchical multiple regression analyses examined whether early and early-late change in free-living movement and eating behavior were associated with WL. The differences in behavior between clinically significant weight losers (CWL; ≥5% WL) and non-clinically significant weight losers (NWL; ≤ 3% WL) were compared. Results: The energy density of food consumed [β = 0.45, p < 0.001] and vigorous PA [β = −0.30, p < 0.001] early in the intervention (regression model 1) and early-late change in light PA [β = −0.81 p < 0.001], moderate PA [β = −1.17 p < 0.001], vigorous PA [β = −0.49, p < 0.001], total energy expenditure (EE) [β = 1.84, p < 0.001], and energy density of food consumed [β = 0.27, p = 0.01] (regression model 2) significantly predicted percentage change in BM. Early in the intervention, CWL consumed less energy dense foods than NWL [p = 0.03]. CWL showed a small but significant increase in vigorous PA, whereas NWL showed a slight decrease in PA [p = 0.04]. Conclusion: Both early and early-late change in free-living movement and eating behaviors during a 14 week WL program are predictors of WL. These findings demonstrate that specific behaviors that contribute to greater EE (e.g., vigorous PA) and lower EI (e.g., less energy-dense foods) are related to greater WL outcomes. Interventions targeting these behaviors can be expected to increase the effectiveness of WL programs.
, Jianying Yuan, Yanpeng Sun, HongBin Wang, Dengfa He, Yanjun Wang, Shuxin Pan, Jian Cui
Published: 14 September 2021
Frontiers in Earth Science, Volume 9; https://doi.org/10.3389/feart.2021.664092

Abstract:
Because of the influence of the far field effect of the collision between Euro-Asian and India plates during the Late Cenozoic, the Tian Shan orogenic belt underwent intense reactivation, forming the Southern Junggar fold-and-thrust belt (SJ-FTB) to the north and the Kuqa fold-and-thrust belt to the south. Most previous research focuses on the deformation features and mechanisms during the Late Cenozoic. However, little research has been done on deformation features and mechanisms during the Late Jurassic. In this paper, we conducted geometric and kinematic analyses of seismic profiles and outcrop data to reveal the Late Jurassic deformation characteristics in SJ-FTB. Furthermore, we carried out sandbox modeling experiments to reproduce the regional structural evolution since the Early Jurassic. Angular unconformity between the Cretaceous and Jurassic is well preserved in the Qigu anticline belt. This unconformity also exists in the Huoerguosi–Manasi–Tugulu (HMT) anticline belt, which is the second fold belt of the SJ-FTB, indicating that the HMT anticline belt started to become active during the Late Jurassic. The Qigu anticline belt reactivated intensively during the Late Cenozoic, and the displacement was transferred to the HMT anticline belt along the Paleogene Anjihaihe Formation mudstone detachment. Therefore, the present-day SJ-FTB forms because of the two-stage compressional deformation from both the Late Jurassic and Late Cenozoic (ca. 24 Ma).
, Philipp Maier
Published: 14 September 2021
Frontiers in Earth Science, Volume 9; https://doi.org/10.3389/feart.2021.710000

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To quantify submarine groundwater discharge, we developed an inexpensive automated seepage meter that applies a tracer injection and the computation of the mean residence time. The SGD-MRT is designed to measure a wide range of discharge rates from about 30 to 800 cm³/min and allows minimizing backpressures caused by pipe friction or flow sensors. By modifying the inner volume of the flow-through unit, the range of measurement is adjustable to lower or higher discharge rates. For process control and data acquisition, an Arduino controller board is used. In addition, components like temperature, conductivity, and pressure sensors or pumps extend the scope of the seepage meter. During field tests in the Wadden Sea, covering tidal cycles, discharge rates of more than 700 cm³/min were released from sand boils. Based on the measured discharge rates and numerical integration of the time series data, a water volume of about 400 dm3 with a seawater content of less than 12% was released from the sand boil within 7 h.
Lingling Wang, Jingmin Li, Hailing Liu, Zhongpeng Wang, , Li An
Published: 14 September 2021
Frontiers in Psychology, Volume 12; https://doi.org/10.3389/fpsyg.2021.693879

Abstract:
Impaired decision-making has been observed in suicide attempters during the Iowa Gambling Task (IGT). Decision-making performance is influenced by somatic markers and explicit knowledge, but it is still unclear of the influencing role on decision-making performance in suicidal individuals. We aimed to investigate whether there is a decision-making deficit in suicide attempters, suicide ideators, as well as the distinct roles of somatic markers and explicit knowledge wherein. Thirteen suicide attempters, 23 suicide ideators, and 19 healthy controls performed the IGT. Both somatic markers (by the skin conductance responses, SCRs) and explicit knowledge (by the subjective experience rating and a list of questions) were recorded. No significant differences were found among the three groups on IGT performance, explicit knowledge, and anticipatory SCRs. IGT Performance of suicide attempters was positively correlated with explicit knowledge index while behavior performance was positively associated with the SCRs in healthy controls. These results indicate that the suicide attempters seem to apply a compensatory strategy by mostly utilizing explicit knowledge to perform normally as healthy controls in the IGT.
Jing Tang, Qian-Min Ge, Rong Huang, Hui-Ye Shu, Ting Su, Jie-Li Wu, Yi-Cong Pan, Rong-Bin Liang, Li-Juan Zhang, Yi Shao, et al.
Frontiers in Cardiovascular Medicine, Volume 8; https://doi.org/10.3389/fcvm.2021.670594

Abstract:
Purpose: To detect lung metastases, we conducted a retrospective study to improve patient prognosis. Methods: Hypertension patients with ocular metastases (OM group; n = 58) and without metastases (NM group; n = 1,217) were selected from individuals with lung cancer admitted to our hospital from April 2005 to October 2019. The clinical characteristics were compared by Student's t-test and chi-square test. Independent risk factors were identified by binary logistic regression, and their diagnostic value evaluated by receiver operating characteristic curve analysis. Results: Age and sex did not differ significantly between OM and NM groups; There were significant differences in pathological type and treatment. Adenocarcinoma was the main pathological type in the OM group (67.24%), while squamous cell carcinoma was the largest proportion (46.43%) in the NM group, followed by adenocarcinoma (34.10%). The OM group were treated with chemotherapy (55.17%), while the NM group received both chemotherapy (39.93%) and surgical treatment (37.06%). Significant differences were detected in the concentrations of cancer antigen (CA)−125, CA-199, CA-153, alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), cytokeratin fraction 21-1 (CYFRA21-1), total prostate-specific antigen, alkaline phosphatase, and hemoglobin (Student's t-test). Binary logistic regression analysis indicated that CA-199, CA-153, AFP, CEA, and CYRFA21-1 were independent risk factors for lung cancer metastasis. AFP (98.3%) and CEA (89.3%) exhibited the highest sensitivity and specificity, respectively, while CYRFA21-1 had the highest area under the ROC curve value (0.875), with sensitivity and specificity values of 77.6 and 87.0%, respectively. Hence, CYFRA21-1 had the best diagnostic value.
Jyoti Mathur, P. B. Khare, Apurva Panwar, S. A. Ranade
Frontiers in Ecology and Evolution, Volume 9; https://doi.org/10.3389/fevo.2021.613847

Abstract:
Pteris vittata L. is very common and a widely distributed species belongs to the family Pteridaceae. Various cytotypes from diploid to octaploid is available in this fern species. The present work has been carried out for genetic diversity in this fern both within and between the cytotypes. The molecular analysis at inter- as well as intra-species has been carried out with 57 accessions of P. vittata as well as of other species of Pteris with Microsorium punctatum considered as an out group taxon. For the present study 48 P. vittata (36 tetraploid and 12 pentaploid) and five of other species (four P. cretica, one P. pellucida, one P. tremula, one P. quadriaurita, and two P. ensiformis) accessions were used. The UPGMA (unweighted pair group method with arithmetic mean) dendrograms were generated for each method separately, as well as for all methods cumulatively, after a 1000 replicate bootstrap analysis. In order to determine the utility of each of the method, a comparative statistical assessment was done and marker index (MI), expected average heterozygosity, fraction of polymorphic loci and effective multiplex ratio (EMR) were calculated in case of each of the methods used in the present study. At the level of individual methods highest MI was obtained for directed amplification of minisatellites DNA (DAMD) method. Our findings of the present study concluded that out of the three methods Random Amplified Polymorphic DNA (RAPD), Inter-Simple Sequence Repeat (ISSR), and Directed Amplification of Minisatellite DNA (DAMD), DAMD was the best in term of polymorphism and heterozygosity as scores exhibited highest MI. The different accessions of P. vittata collected from different phytogeographical regions falls into six groups. Out of six clusters, one cluster is of pentaploid cytotype, four clusters are of tetraploid cytotype and one for outgroup taxon (M. punctatum). The result thus showed that within tetraploid, heterozygosity with variable genomic structure exists.
, T. Candela, S. Osinga, E. Peters, L. Buijze, P. A. Fokker, J. D. Van Wees
Published: 14 September 2021
Frontiers in Earth Science, Volume 9; https://doi.org/10.3389/feart.2021.685841

Abstract:
This paper describes and deploys a workflow to assess the evolution of seismicity associated to injection of cold fluids close to a fault. We employ a coupled numerical thermo-hydro-mechanical simulator to simulate the evolution of pressures, temperatures and stress on the fault. Adopting rate-and-state seismicity theory we assess induced seismicity rates from stressing rates at the fault. Seismicity rates are then used to derive the time-dependent frequency-magnitude distribution of seismic events. We model the seismic response of a fault in a highly fractured and a sparsely fractured carbonate reservoir. Injection of fluids into the reservoir causes cooling of the reservoir, thermal compaction and thermal stresses. The evolution of seismicity during injection is non-stationary: we observe an ongoing increase of the fault area that is critically stressed as the cooling front propagates from the injection well into the reservoir. During later stages, models show the development of an aseismic area surrounded by an expanding ring of high seismicity rates at the edge of the cooling zone. This ring can be related to the “passage” of the cooling front. We show the seismic response of the fault, in terms of the timing of elevated seismicity and seismic moment release, depends on the fracture density, as it affects the temperature decrease in the rock volume and thermo-elastic stress change on the fault. The dense fracture network results in a steeper thermal front which promotes stress arching, and leads to locally and temporarily high Coulomb stressing and seismicity rates. We derive frequency-magnitude distributions and seismic moment release for a low-stress subsurface and a tectonically active area with initially critically stressed faults. The evolution of seismicity in the low-stress environment depends on the dimensions of the fault area that is perturbed by the stress changes. The probability of larger earthquakes and the associated seismic risk are thus reduced in low-stress environments. For both stress environments, the total seismic moment release is largest for the densely spaced fracture network. Also, it occurs at an earlier stage of the injection period: the release is more gradually spread in time and space for the widely spaced fracture network.
, Monika Daseking
Published: 14 September 2021
Frontiers in Psychology, Volume 12; https://doi.org/10.3389/fpsyg.2021.710929

Abstract:
With the exception of a recently published study and the analyses provided in the test manual, structural validity is mostly uninvestigated for the German version of the Wechsler Intelligence Scale for Children - Fifth Edition (WISC-V). Therefore, the main aim of the present study was to examine the latent structure of the 10 WISC-V primary subtests on a bifurcated extended population-representative German standardization sample (N=1,646) by conducting both exploratory (EFA; n=823) and confirmatory (CFA; n=823) factor analyses on the original data. Since no more than one salient subtest loading could be found on the Fluid Reasoning (FR) factor in EFA, results indicated a four-factor rather than a five-factor model solution when the extraction of more than two suggested factors was forced. Likewise, a bifactor model with four group factors was found to be slightly superior in CFA. Variance estimation from both EFA and CFA revealed that the general factor dominantly accounted for most of the subtest variance and construct reliability estimates further supported interpretability of the Full Scale Intelligence Quotient (FSIQ). In both EFA and CFA, most group factors explained rather small proportions of common subtest variance and produced low construct replicability estimates, suggesting that the WISC-V primary indexes were of lower interpretive value and should be evaluated with caution. Clinical interpretation should thus be primarily based on the FSIQ and include a comprehensive analysis of the cognitive profile derived from the WISC-V primary indexes rather than analyses of each single primary index.
, V. Génot, S. Aizawa, A. Milillo, J. Zender, G. Murakami, J. Benkhoff, I. Zouganelis, T. Alberti, N. André, et al.
Frontiers in Astronomy and Space Sciences, Volume 8; https://doi.org/10.3389/fspas.2021.718024

Abstract:
The investigation of multi-spacecraft coordinated observations during the cruise phase of BepiColombo (ESA/JAXA) are reported, with a particular emphasis on the recently launched missions, Solar Orbiter (ESA/NASA) and Parker Solar Probe (NASA). Despite some payload constraints, many instruments onboard BepiColombo are operating during its cruise phase simultaneously covering a wide range of heliocentric distances (0.28 AU–0.5 AU). Hence, the various spacecraft configurations and the combined in-situ and remote sensing measurements from the different spacecraft, offer unique opportunities for BepiColombo to be part of these unprecedented multipoint synergistic observations and for potential scientific studies in the inner heliosphere, even before its orbit insertion around Mercury in December 2025. The main goal of this report is to present the coordinated observation opportunities during the cruise phase of BepiColombo (excluding the planetary flybys). We summarize the identified science topics, the operational instruments, the method we have used to identify the windows of opportunity and discuss the planning of joint observations in the future.
Joaquin Gaete-Silva, Alfredo Gaete
Published: 14 September 2021
Frontiers in Psychology, Volume 12; https://doi.org/10.3389/fpsyg.2021.740856

Abstract:
Responding to disruptive behavior has become increasingly problematic in current Westernized societies, impacting people’s well-being globally. In the context of the current Special Issue, in this article, we advance the concept of problematic disruptive behavior (PDB) as a suitable “window” to better understand some aspects of the deep interdependence of social participation, citizenship, justice, and well-being. To do so, we also advance the notion of postdisciplinary society to account both for the apparent rise of problematic disruptive experiences, and the increased social conflict within which such experiences get often entangled. More specifically, we argue that formerly morally acceptable responses to problematic disruption, such as punishment and discipline, have lost social legitimacy and, to that extent, they aggravate the problems they were intended to resolve. We provide a genealogical account of the surge of such postdisciplinary order with a focus on the moral transition on ideas of justice, of personal entitlements, and authority. We conclude outlining an alternative way to respond to disruptive behaviors that we anticipate will be both more effective and acceptable in the current postdisciplinary milieu.
Kai-Di Ni,
Published: 14 September 2021
Frontiers in Pharmacology, Volume 12; https://doi.org/10.3389/fphar.2021.716801

Abstract:
The cytochrome P450 (CYP) ω-hydroxylases are a subfamily of CYP enzymes. While CYPs are the main metabolic enzymes that mediate the oxidation reactions of many endogenous and exogenous compounds in the human body, CYP ω-hydroxylases mediate the metabolism of multiple fatty acids and their metabolites via the addition of a hydroxyl group to the ω- or (ω-1)-C atom of the substrates. The substrates of CYP ω-hydroxylases include but not limited to arachidonic acid, docosahexaenoic acid, eicosapentaenoic acid, epoxyeicosatrienoic acids, leukotrienes, and prostaglandins. The CYP ω-hydroxylases-mediated metabolites, such as 20-hyroxyleicosatrienoic acid (20-HETE), 19-HETE, 20-hydroxyl leukotriene B4 (20-OH-LTB4), and many ω-hydroxylated prostaglandins, have pleiotropic effects in inflammation and many inflammation-associated diseases. Here we reviewed the classification, tissue distribution of CYP ω-hydroxylases and the role of their hydroxylated metabolites in inflammation-associated diseases. We described up-regulation of CYP ω-hydroxylases may be a pathogenic mechanism of many inflammation-associated diseases and thus CYP ω-hydroxylases may be a therapeutic target for these diseases. CYP ω-hydroxylases-mediated eicosanods play important roles in inflammation as pro-inflammatory or anti-inflammatory mediators, participating in the process stimulated by cytokines and/or the process stimulating the production of multiple cytokines. However, most previous studies focused on 20-HETE,and further studies are needed for the function and mechanisms of other CYP ω-hydroxylases-mediated eicosanoids. We believe that our studies of CYP ω-hydroxylases and their associated eicosanoids will advance the translational and clinal use of CYP ω-hydroxylases inhibitors and activators in many diseases.
Lingling Wang, Ling Zhou, Yuhao Zhou, Lu Liu, Weiling Jiang, Huojun Zhang,
Published: 14 September 2021
Frontiers in Pharmacology, Volume 12; https://doi.org/10.3389/fphar.2021.737129

Abstract:
In the past decades, apoptosis has been the most well-studied regulated cell death (RCD) that has essential functions in tissue homeostasis throughout life. However, a novel form of RCD called necroptosis, which requires receptor-interacting protein kinase-3 (RIPK3) and mixed-lineage kinase domain-like pseudokinase (MLKL), has recently been receiving increasing scientific attention. The phosphorylation of RIPK3 enables the recruitment and phosphorylation of MLKL, which oligomerizes and translocates to the plasma membranes, ultimately leading to plasma membrane rupture and cell death. Although apoptosis elicits no inflammatory responses, necroptosis triggers inflammation or causes an innate immune response to protect the body through the release of damage-associated molecular patterns (DAMPs). Increasing evidence now suggests that necroptosis is implicated in the pathogenesis of several human diseases such as systemic inflammation, respiratory diseases, cardiovascular diseases, neurodegenerative diseases, neurological diseases, and cancer. This review summarizes the emerging insights of necroptosis and its contribution toward the pathogenesis of lung diseases.
Qingsong Li, Fei Liu, Yuqi Tang, Sharen Lee, Chao Lang, Lan Bai,
Frontiers in Cardiovascular Medicine, Volume 8; https://doi.org/10.3389/fcvm.2021.695454

Abstract:
Introduction: Understanding the epidemiology of cardiovascular disease (CVD) related comorbidity is a key strategy for improving the outcomes of patients with cancer. Therefore, this study aimed to assess the distribution of cardiovascular comorbidities and cardiovascular risk factors (CVRF) among five cancer sites. Methods: This is a single-centered, cross-sectional study performed in Dalian, China. Between 2008 and 2018, all newly diagnosed cancer in the First Affiliated Hospital of Dalian Medical University, China were screened. Clinical data were extracted from a comprehensive electronic health record system. Results: 35861 patients with lung, colorectal, gastric, breast, and thyroid cancer were collected retrospectively. The most prevalent CVDs in descending order were hypertension (21.9%), followed by coronary heart disease (6.5%), atrial fibrillation (2.9%), and heart failure (1%). The prevalence of hypertension significantly varies between lung (21.3%), colorectal (27.3%), gastric (22.5%), breast (16.7%), and thyroid cancer (22.4%) (P < 0.001). CVRF varies with cancer sites. Age, sex, total cholesterol, triglyceride, low-density lipoprotein cholesterol, systolic blood pressure, smoking, alcohol use, and diabetes mellitus (DM) are common risk factors associated with CVD at different cancer sites. The association between DM and presence of CVD was strong in breast (odds ratio [OR] = 4.472, 95% confidence interval [CI]: 3.075–6.504, P < 0.001), lung (OR = 3.943; 95% CI: 3.270–4.754, P < 0.001), colorectal (OR = 3.049; 95% CI: 2.326–3.996, P < 0.001), and gastric (OR = 2.508; 95% CI: 1.927–3.264, P < 0.001) cancer. Conclusion: Cancer patients had a significant burden of CVD and increased CVRF. The prevalence of CVRF and CVD comorbidity differ for cancer types. DM remains significantly associated with CVD at different cancer sites except for thyroid cancer.
Liam J. O’Neil, Christopher B. Oliveira, Donavon Sandoval-Heglund, Ana Barrera-Vargas, Javier Merayo-Chalico, Eduardo Aguirre-Aguilar, ,
Published: 14 September 2021
Frontiers in Immunology, Volume 12; https://doi.org/10.3389/fimmu.2021.715997

Abstract:
Objective Antibodies against carbamylated proteins (anti-CarP) are associated with poor prognosis and the development of bone erosions in rheumatoid arthritis (RA). RA neutrophils externalize modified autoantigens through the formation of neutrophil extracellular traps (NETs). Increased levels of the cathelicidin LL37 have been documented in the synovium of RA patients, but the cellular source remains unclear. We sought to determine if post-translational modifications of LL37, specifically carbamylation, occur during NET formation, enhance this protein’s autoantigenicity, and contribute to drive bone erosion in the synovial joint. Methods ELISA and Western blot analyses were used to identify carbamylated LL37 (carLL37) in biological samples. Anti-carLL37 antibodies were measured in the serum of HLA-DRB1*04:01 transgenic mice and in human RA synovial fluid. Results Elevated levels of carLL37 were found in plasma and synovial fluid from RA patients, compared to healthy controls. RA NETs release carLL37 and fibroblast-like synoviocytes (FLS) internalized NET-bound carLL37 and loaded it into their MHCII compartment. HLA-DRB1*04:01 transgenic mice immunized with FLS containing NETs developed autoantibodies against carLL37. Anti-carLL37 antibodies were present in RA sera and synovial fluid and they correlated with radiologic bone erosion scores of the hands and feet in RA patients. CarLL37-IgG immune complexes enhanced the ability of monocytes to differentiate into osteoclasts and potentiated osteoclast-mediated extracellular matrix resorption. Conclusions NETs are a source of carLL37 leading to induction of anti-carbamylated autoantibody responses. Furthermore, carLL37-IgG immune complexes may be implicated in the bone damage characteristic of RA. These results support that dysregulated NET formation has pathogenic roles in RA.
Mingxing Tang, Shuo Li, Lan Wei, Zhaohua Hou, ,
Published: 14 September 2021
Frontiers in Immunology, Volume 12; https://doi.org/10.3389/fimmu.2021.684605

Abstract:
Engineered nanomaterials (ENMs) have been widely exploited in several industrial domains as well as our daily life, raising concern over their potential adverse effects. While in general ENMs do not seem to have detrimental effects on immunity or induce severe inflammation, their indirect effects on immunity are less known. In particular, since the gut microbiota has been tightly associated with human health and immunity, it is possible that ingested ENMs could affect intestinal immunity indirectly by modulating the microbial community composition and functions. In this perspective, we provide a few pieces of evidence and discuss a possible link connecting ENM exposure, gut microbiota and host immune response. Some experimental works suggest that excessive exposure to ENMs could reshape the gut microbiota, thereby modulating the epithelium integrity and the inflammatory state in the intestine. Within such microenvironment, numerous microbiota-derived components, including but not limited to SCFAs and LPS, may serve as important effectors responsible of the ENM effect on intestinal immunity. Therefore, the gut microbiota is implicated as a crucial regulator of the intestinal immunity upon ENM exposure. This calls for including gut microbiota analysis within future work to assess ENM biocompatibility and immunosafety. This also calls for refinement of future studies that should be designed more elaborately and realistically to mimic the human exposure situation.
, Claus Barkmann, Bonnie Adema, Anne Daubmann, Reinhold Kilian, Maja Stiawa, Mareike Busmann, Sibylle M. Winter, Martin Lambert, Karl Wegscheider, et al.
Published: 14 September 2021
Frontiers in Psychology, Volume 12; https://doi.org/10.3389/fpsyg.2021.705400

Abstract:
Offspring of mentally ill parents is at heightened risk for psychological symptoms. The identification of environmental factors that predict their mental health is crucial for the development of preventive and therapeutic measures. In the current study, we addressed the combined role of family functioning and social support by taking mentally ill patients’, their partners’, and children’s perspectives into account. The cross-sectional sample included n=195 families (195 patients, 127 partners, and 295 children). Family members completed questionnaires related to family functioning, social support as well as parental and child psychopathology. We conducted multilevel analyses to investigate the associations with internalizing and externalizing problems in children. Family functioning and social support were significantly associated with child internalizing and externalizing problems. However, results varied depending on the rating perspective. We found significant interaction effects of family functioning and social support on child psychopathology. The findings point to the importance of family functioning and social support as potential targets for interventions. Findings should be replicated in future longitudinal studies.
Nathan Chan, Zeli Shen, Anthony Mannion, Susanna Kurnick, Ioana S. Popescu, Frederic J. Burton, Paul P. Calle,
Frontiers in Ecology and Evolution, Volume 9; https://doi.org/10.3389/fevo.2021.676682

Abstract:
Blue iguanas (Cyclura lewisi) are endangered reptiles found only on Grand Cayman. Previously, DNA for a novel Helicobacter species GCBI1 was detected in sick and dead iguanas. In the current study, fecal and cloacal swab samples were obtained from 25 iguanas. Through molecular and microbiological techniques, a novel Helicobacter species was cultured from feces and characterized, for whom we propose the name Helicobacter cyclurae. This novel helicobacter had a prevalence of 56% by PCR and 20% by culture in samples analyzed. The type strain MIT 16-1353 was catalase, oxidase, and gamma-glutamyl transpeptidase positive. By electron microscopy, H. cyclurae has a curved rod morphology and a single sheathed polar flagellum. Phylogenetic analysis using 16S rRNA, gyrB, and hsp60 indicated that these strains were most closely related to Helicobacter sp. 12502256-12 previously isolated from lizards. H. cyclurae has a 1.91-Mb genome with a GC content of 33.37%. There were 1,969 genes with four notable virulence genes: high temperature requirement-A protein-secreted serine protease, gamma-glutamyl transpeptidase, fibronectin/fibrinogen binding protein, and neutrophil-activating protein. Whole-genome phylogeny, average nucleotide identity, and digital DNA–DNA hybridization analysis confirmed that H. cyclurae is a novel species, and the first helicobacter cultured and characterized from blue iguanas.
Jinhao Zeng, Xiao Ma, Ziyi Zhao, Yu Chen, Jundong Wang, Yanwei Hao, Junrong Yu, Zhongzhen Zeng, Nianzhi Chen, Maoyuan Zhao, et al.
Published: 14 September 2021
Frontiers in Pharmacology, Volume 12; https://doi.org/10.3389/fphar.2021.682713

Abstract:
Background: Seeking novel and effective therapies for gastric precancerous lesions (GPL) is crucial to reducing the incidence of gastric cancer. Ginsenoside Rb1 (GRb1) is a major ginsenoside in ginseng and has been proved to possess multiple bioactivities. However, whether GRb1 could protect against GPL and the underlying mechanisms have not been explored. Methods: We evaluated the effects of GRb1 on gastric precancerous lesions in rats on macroscopic, microscopic and ultramicroscopic levels. Then, an antibody array was employed to screen differential expression proteins (DEPs). Validation for the targeting DEP and investigation for the possible mechanism was conducted using immunohistochemistry, qRT-PCR, TUNEL apoptosis assay, immunoprecipitation and immunoblotting. Results: GRb1 was found to reverse intestinal metaplasia and a portion of dysplasia in the MNNG-induced GPL rats. The antibody array assay revealed seven DEPs in GPL rats as compared to control rats (5 DEPs were up-regulated, while two DEPs were down-regulated). Among the DEPs, β-catenin, beta-NGF and FSTL1 were significantly down-regulated after GRb1 administration. Our validation results revealed that enhanced protein expression and nuclear translocation of β-catenin were present in animal GPL samples. In addition, analysis of human gastric specimens demonstrated that β-catenin up-regulation and nuclear translocation were significantly associated with advanced GPL pathology. GRb1 intervention not only decreased protein expression and nuclear translocation of β-catenin, but interfered with β-catenin/TCF4 interaction. Along with this, declined transcriptional and protein expression levels of downstream target genes including c-myc, cyclin D1 and Birc5 were observed in GRb1-treated GPL rats. Conclusion: GRb1 is capable of preventing the occurrence and progression of GPL, which might be contributed by diminishing protein expression and nuclear translocation of β-catenin and interfering with β-catenin/TCF4 interaction.
Ting Jiang, Gulijianati Wumaier, Xue Li, Xu Yang,
Published: 14 September 2021
Frontiers in Psychiatry, Volume 12; https://doi.org/10.3389/fpsyt.2021.737228

Abstract:
Background: This study investigated the relationship between occupational stress and the mental health of people working in oil fields in the arid desert environment of Xinjiang, and revealed the causal relationship between occupational stress and psychological disorders, while furthermore exploring the relationship between psychological disorders and genetic levels. Methods: The participants of this study included oil field company workers from the Xinjiang Petroleum Administration of Karamay City, Xinjiang, who underwent occupational health examinations. The Occupational Stress Inventory Revised Edition (OSI-R) was used to measure the occupational stress of the oil workers. The mental health status of oil workers was evaluated using the Symptoms Checklist-90. Results: Occupational tasks: The total scores of the personal strain and mental health questionnaires were positively correlated with somatization, obsessive-compulsive symptoms, interpersonal sensitivity, depression, anxiety, hostility, terror, paranoia, and psychosis (P < 0.05). Individual coping resources and the mental health total score was negatively correlated with somatization, obsessive-compulsive symptoms, interpersonal sensitivity, anxiety, hostility, terror, paranoia, and psychosis. The following factors were identified as mental health risk factors: female gender; age 45 and above (relative to ≤30 years old); high scores on the personal strain questionnaire; occupational stress; external effort; internal investment; and high effort-low return. The following factors were identified as protective factors for mental health: Han nationality; oil transportation (relative to drilling); individual resilience; and work returns. In respect to the abnormal psychological group and the normal psychological group, statistically significant differences were found in the distribution of genotypes and allele frequencies at the rs1800497 locus (P < 0.05). The depression and paranoia scores observed between different genotype groups at the rs1800497 locus were statistically significant (P < 0.05). Conclusions: This study shows that occupational stress and the D2 dopamine receptor (DRD2) gene have an impact on the mental health of oil field workers in the arid desert environment of Xinjiang. Effort-reward imbalance and occupational stress were identified as risk factors for mental health, while rewards for work were protective factors. Higher levels of occupational stress may lead to depression and other psychological disorders, adversely affecting mental health. In oil field operators in the arid desert environment of Xinjiang, the AA genotype of the DRD2 gene in the rs1800497 locus was identified as a genotype specific to susceptibility to mental health problems, and a correlation was found between the A allele and an increased risk of psychological problems. Therefore, it is necessary to devise relevant measures to alleviate occupational stress among oil workers and increase their job rewards, so as to improve their mental health.
Published: 14 September 2021
Frontiers in Physics, Volume 9; https://doi.org/10.3389/fphy.2021.730685

Abstract:
Quantum annealing is a global optimization algorithm that uses the quantum tunneling effect to speed-up the search for an optimal solution. Its current hardware implementation relies on D-Wave’s Quantum Processing Units, which are limited in terms of number of qubits and architecture while being restricted to solving quadratic unconstrained binary optimization (QUBO) problems. Consequently, previous applications of quantum annealing to real-life use cases have focused on problems that are either native QUBO or close to native QUBO. By contrast, in this paper we propose to tackle inequality constraints and non-quadratic terms. We demonstrate how to handle them with a realistic use case-a bus charging scheduling problem. First, we reformulate the original integer programming problem into a QUBO with the penalty method and directly solve it on a D-Wave machine. In a second approach, we dualize the problem by performing the Hubbard-Stratonovich transformation. The dual problem is solved indirectly by combining quantum annealing and adaptive classical gradient-descent optimizer. Whereas the penalty method is severely limited by the connectivity of the realistic device, we show experimentally that the indirect approach is able to solve problems of a larger size, offering thus a better scaling. Hence, the implementation of the Hubbard-Stratonovich transformation carried out in this paper on a scheduling use case suggests that this approach could be investigated further and applied to a variety of real-life integer programming problems under multiple constraints to lower the cost of mapping to QUBO, a key step towards the near-term practical application of quantum computing.
, Catharina Schuetz, Ulrich Baumann, Christian Klemann, Dorothee Viemann, Simona Ursu, Eva-Maria Jacobsen, Klaus-Michael Debatin, Ansgar Schulz, Manfred Hoenig, et al.
Published: 14 September 2021
Frontiers in Immunology, Volume 12; https://doi.org/10.3389/fimmu.2021.739675

Abstract:
DNA damage occurs constantly in every cell triggered by endogenous processes of replication and metabolism, and external influences such as ionizing radiation and intercalating chemicals. Large sets of proteins are involved in sensing, stabilizing and repairing this damage including control of cell cycle and proliferation. Some of these factors are phosphorylated upon activation and can be used as biomarkers of DNA damage response (DDR) by flow and mass cytometry. Differential survival rates of lymphocyte subsets in response to DNA damage are well established, characterizing NK cells as most resistant and B cells as most sensitive to DNA damage. We investigated DDR to low dose gamma radiation (2Gy) in peripheral blood lymphocytes of 26 healthy donors and 3 patients with ataxia telangiectasia (AT) using mass cytometry. γH2AX, p-CHK2, p-ATM and p53 were analyzed as specific DDR biomarkers for functional readouts of DNA repair efficiency in combination with cell cycle and T, B and NK cell populations characterized by 20 surface markers. We identified significant differences in DDR among lymphocyte populations in healthy individuals. Whereas CD56+CD16+ NK cells showed a strong γH2AX response to low dose ionizing radiation, a reduced response rate could be observed in CD19+CD20+ B cells that was associated with reduced survival. Interestingly, γH2AX induction level correlated inversely with ATM-dependent p-CHK2 and p53 responses. Differential DDR could be further noticed in naïve compared to memory T and B cell subsets, characterized by reduced γH2AX, but increased p53 induction in naïve T cells. In contrast, DDR was abrogated in all lymphocyte populations of AT patients. Our results demonstrate differential DDR capacities in lymphocyte subsets that depend on maturation and correlate inversely with DNA damage-related survival. Importantly, DDR analysis of peripheral blood cells for diagnostic purposes should be stratified to lymphocyte subsets.
Yumeng Zhu, Xiaochao Wang, Yanqing Xu, Lu Chen, Peipei Ding, Jianfeng Chen,
Published: 14 September 2021
Frontiers in Oncology, Volume 11; https://doi.org/10.3389/fonc.2021.736725

Abstract:
Background C5AR2 (GPR77, C5L2) is the second receptor for C5a that is a potent protein generated by complement activation. C5AR2 can mediate its own signaling events and exert significant immunomodulatory effects through those events. However, research of C5AR2 in cancer is limited, and its function remains unclear in breast cancer. Methods The expression of C5AR2 and its correlations with prognosis, immune infiltration, tumor mutation burden (TMB), and microsatellite instability (MSI) in more than thirty types of cancers were described through GTEx, TCGA, PrognoScan, TIMER2.0, CCLE, HPA, and TISIDB database. C5AR2 showed strong relationships to those immune marker sets in breast cancer. Otherwise, CCK8 assay and Transwell assay were conducted to illustrate the role of C5AR2 in migration, invasion, and proliferation of breast cancer cells. Results Generally, C5AR2 expression differed across most cancerous and noncancerous tissues, and high C5AR2 expression significantly related to poor prognosis in BRCA, GBM, KICH, LAML, LGG, LIHC, PAAD, and STAD. Moreover, C5AR2 expression levels were dramatically correlated with recognized immune infiltration, especially the polarization of macrophages in breast cancer. Gene set enrichment analysis confirmed that C5AR2 participates in regulating multiple signaling pathways involved in tumorigenesis as well as tumor immunity. C5AR2 overexpression facilitated the functions such as migration, invasion, and proliferation in breast cancer cells, which is consistent with bioinformatics analysis. Conclusions C5AR2 is involved in immune infiltration and malignant characteristics of breast cancer, which may be a prospective biomarker for breast cancer.
, Lori Letts, Briano Di Rezze, Michelle Phoenix
Frontiers in Rehabilitation Sciences, Volume 2; https://doi.org/10.3389/fresc.2021.709977

Abstract:
Participation of children in rehabilitation services is associated with positive functional and developmental outcomes for children with disabilities. Participation in therapy is at risk when the personal and environmental contexts of a child create barriers to accessing services. The International Classification of Functioning, Disability and Health (ICF) provides a framework for conceptualizing the personal and environmental factors linked to a child. However, it does not facilitate critical examination of the person–environment relationship and its impact on participation in children's rehabilitation. This perspective study proposes the use of intersectionality theory as a critical framework in complement with the ICF to examine the impact of systemic inequities on the participation in therapy for children with disabilities. Clinicians are called to be critical allies working alongside children and families to advocate for inclusive participation in children's rehabilitation by identifying and transforming systemic inequities in service delivery.
Published: 14 September 2021
Frontiers in Chemistry, Volume 9; https://doi.org/10.3389/fchem.2021.742565

Abstract:
Fast and reliable industrial production of ammonia (NH3) is fundamentally sustaining modern society. Since the early 20th Century, NH3 has been synthesized via the Haber–Bosch process, running at conditions of around 350–500°C and 100–200 times atmospheric pressure (15–20 MPa). Industrial ammonia production is currently the most energy-demanding chemical process worldwide and contributes up to 3% to the global carbon dioxide emissions. Therefore, the development of more energy-efficient pathways for ammonia production is an attractive proposition. Over the past 20 years, scientists have imagined the possibility of developing a milder synthesis of ammonia by mimicking the nitrogenase enzyme, which fixes nitrogen from the air at ambient temperatures and pressures to feed leguminous plants. To do this, we propose the use of highly reconfigurable molecular metal oxides or polyoxometalates (POMs). Our proposal is an informed design of the polyoxometalate after exploring the catabolic pathways that cyanobacteria use to fix N2 in nature, which are a different route than the one followed by the Haber–Bosch process. Meanwhile, the industrial process is a “brute force” system towards breaking the triple bond N-N, needing high pressure and high temperature to increase the rate of reaction, nature first links the protons to the N2 to later easier breaking of the triple bond at environmental temperature and pressure. Computational chemistry data on the stability of different polyoxometalates will guide us to decide the best design for a catalyst. Testing different functionalized molecular metal oxides as ammonia catalysts laboratory conditions will allow for a sustainable reactor design of small-scale production.
Mattia Emanuela Ligotti, Fanny Pojero, Giulia Accardi, Anna Aiello, , Giovanni Duro, Giuseppina Candore
Frontiers in Cell and Developmental Biology, Volume 9; https://doi.org/10.3389/fcell.2021.725606

Abstract:
The outcomes of Coronavirus disease-2019 (COVID-19) vary depending on the age, health status and sex of an individual, ranging from asymptomatic to lethal. From an immunologic viewpoint, the final severe lung damage observed in COVID-19 should be caused by cytokine storm, driven mainly by interleukin-6 and other pro-inflammatory cytokines. However, which immunopathogenic status precedes this “cytokine storm” and why the male older population is more severely affected, are currently unanswered questions. The aging of the immune system, i.e., immunosenescence, closely associated with a low-grade inflammatory status called “inflammageing,” should play a key role. The remodeling of both innate and adaptive immune response observed with aging can partly explain the age gradient in severity and mortality of COVID-19. This review discusses how aging impacts the immune response to the virus, focusing on possible strategies to rejuvenate the immune system with stem cell-based therapies. Indeed, due to immunomodulatory and anti-inflammatory properties, multipotent mesenchymal stem cells (MSCs) are a worth-considering option against COVID-19 adverse outcomes.
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