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Published: 12 July 2020
by MDPI
Abstract:
The protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease. This neglected tropical disease causes severe morbidity and mortality in endemic regions. About 30% of T. cruzi infected individuals will present with cardiac complications. Invasive trypomastigotes released from infected cells can be carried in the vascular endothelial system to infect neighboring and distant cells. During the process of cellular infection, the parasite induces host cells, to increase the levels of host thrombospondin-1 (TSP-1), to facilitate the process of infection. TSP-1 plays important roles in the functioning of vascular cells, including vascular endothelial cells with important implications in cardiovascular health. Many signal transduction pathways, including the yes-associated protein 1 (YAP)/transcriptional coactivator, with PDZ-binding motif (TAZ) signaling, which are upstream of TSP-1, have been linked to the pathophysiology of heart damage. The molecular mechanisms by which T. cruzi signals, and eventually infects, heart endothelial cells remain unknown. To evaluate the importance of TSP-1 expression in heart endothelial cells during the process of T. cruzi infection, we exposed heart endothelial cells prepared from Wild Type and TSP-1 Knockout mouse to invasive T. cruzi trypomastigotes at multiple time points, and evaluated changes in the hippo signaling cascade using immunoblotting and immunofluorescence assays. We found that the parasite turned off the hippo signaling pathway in TSP-1KO heart endothelial cells. The levels of SAV1 and MOB1A increased to a maximum of 2.70 ± 0.23 and 5.74 ± 1.45-fold at 3 and 6 h, respectively, in TSP-1KO mouse heart endothelial cells (MHEC), compared to WT MHEC, following a parasite challenge. This was accompanied by a significant continuous increase in the nuclear translocation of downstream effector molecule YAP, to a maximum mean nuclear fluorescence intensity of 10.14 ± 0.40 at 6 h, compared to wild type cells. Furthermore, we found that increased nuclear translocated YAP significantly colocalized with the transcription co-activator molecule pan-TEAD, with a maximum Pearson’s correlation coefficient of 0.51 ± 0.06 at 6 h, compared to YAP-Pan-TEAD colocalization in the WT MHEC, which decreased significantly, with a minimum Pearson’s correlation coefficient of 0.30 ± 0.01 at 6 h. Our data indicate that, during the early phase of infection, upregulated TSP-1 is essential for the regulation of the hippo signaling pathway. These studies advance our understanding of the molecular interactions occurring between heart endothelial cells and T. cruzi, in the presence and absence of TSP-1, providing insights into processes linked to parasite dissemination and pathogenesis.
Published: 12 July 2020
by MDPI
Abstract:
We introduce and shortly summarize a variety of more recent aspects of lyotropic liquid crystals (LLCs), which have drawn the attention of the liquid crystal and soft matter community and have recently led to an increasing number of groups studying this fascinating class of materials, alongside their normal activities in thermotopic LCs. The diversity of topics ranges from amphiphilic to inorganic liquid crystals, clays and biological liquid crystals, such as viruses, cellulose or DNA, to strongly anisotropic materials such as nanotubes, nanowires or graphene oxide dispersed in isotropic solvents. We conclude our admittedly somewhat subjective overview with materials exhibiting some fascinating properties, such as chromonics, ferroelectric lyotropics and active liquid crystals and living lyotropics, before we point out some possible and emerging applications of a class of materials that has long been standing in the shadow of the well-known applications of thermotropic liquid crystals, namely displays and electro-optic devices.
Published: 12 July 2020
by MDPI
Abstract:
Tensor network methods are powerful and efficient tools for studying the properties and dynamics of statistical and quantum systems, in particular in one and two dimensions. In recent years, these methods have been applied to lattice gauge theories, yet these theories remain a challenge in ( 2 + 1 ) dimensions. In this article, we present a new (decorated) tensor network algorithm, in which the tensors encode the lattice gauge amplitude expressed in the fusion basis. This has several advantages—firstly, the fusion basis does diagonalize operators measuring the magnetic fluxes and electric charges associated to a hierarchical set of regions. The algorithm allows therefore a direct access to these observables. Secondly the fusion basis is, as opposed to the previously employed spin network basis, stable under coarse-graining. Thirdly, due to the hierarchical structure of the fusion basis, the algorithm does implement predefined disentanglers. We apply this new algorithm to lattice gauge theories defined for the quantum group SU ( 2 ) k and identify a weak and a strong coupling phase for various levels k . As we increase the level k , the critical coupling g c decreases linearly, suggesting the absence of a deconfining phase for the continuous group SU ( 2 ) . Moreover, we illustrate the scaling behaviour of the Wilson loops in the two phases.
Published: 12 July 2020
by MDPI
Abstract:
Influenza continues to be a public health threat despite the availability of annual vaccines. While vaccines are generally effective at inducing strain-specific immunity, they are sub-optimal or ineffective when drifted or novel pandemic strains arise due to sequence changes in the major surface glycoprotein hemagglutinin (HA). The discovery of a large number of antibodies targeting the highly conserved stem region of HAs that are capable of potently neutralizing a broad range of virus strains and subtypes suggests new ways to protect against influenza. The structural characterization of HA stem epitopes and broadly neutralizing antibody paratopes has enabled the design of novel proteins, mini-proteins, and peptides targeting the HA stem, thus providing a foundation for the design of new vaccines. In this narrative, we comprehensively review the current knowledge about stem-directed broadly neutralizing antibodies and the structural features contributing to virus neutralization.
Published: 12 July 2020
by MDPI
Abstract:
The massive sulfide ores of the Pobeda hydrothermal fields are grouped into five main mineral microfacies: (1) isocubanite-pyrite, (2) pyrite-wurtzite-isocubanite, (3) pyrite with minor isocubanite and wurtzite-sphalerite microinclusions, (4) pyrite-rich with framboidal pyrite, and (5) marcasite-pyrite. This sequence reflects the transition from feeder zone facies to seafloor diffuser facies. Spongy, framboidal, and fine-grained pyrite varieties replaced pyrrhotite, greigite, and mackinawite “precursors”. The later coarse and fine banding oscillatory-zoned pyrite and marcasite crystals are overgrown or replaced by unzoned subhedral and euhedral pyrite. In the microfacies range, the amount of isocubanite, wurtzite, unzoned euhedral pyrite decreases versus an increasing portion of framboidal, fine-grained, and spongy pyrite and also marcasite and its colloform and radial varieties. The trace element characteristics of massive sulfides of Pobeda seafloor massive sulfide (SMS) deposit are subdivided into four associations: (1) high temperature—Cu, Se, Te, Bi, Co, and Ni; (2) mid temperature—Zn, As, Sb, and Sn; (3) low temperature—Pb, Sb, Ag, Bi, Au, Tl, and Mn; and (4) seawater—U, V, Mo, and Ni. The high contents of Cu, Co, Se, Bi, Te, and values of Co/Ni ratios decrease in the range from unzoned euhedral pyrite to oscillatory-zoned and framboidal pyrite, as well as to colloform and crystalline marcasite. The trend of Co/Ni values indicates a change from hydrothermal to hydrothermal-diagenetic crystallization of the pyrite. The concentrations of Zn, As, Sb, Pb, Ag, and Tl, as commonly observed in pyrite formed from mid- and low-temperature fluids, decline with increasing crystal size of pyrite and marcasite. Coarse oscillatory-zoned pyrite crystals contain elevated Mn compared to unzoned euhedral varieties. Framboidal pyrite hosts maximum concentrations of Mo, U, and V probably derived from ocean water mixed with hydrothermal fluids. In the Pobeda SMS deposit, the position of microfacies changes from the black smoker feeder zone at the base of the ore body, to seafloor marcasite-pyrite from diffuser fragments in sulfide breccias. We suggest that the temperatures of mineralization decreased in the same direction and determined the zonal character of deposit.
Published: 12 July 2020
by MDPI
Abstract:
Perturbations of glycosaminoglycan metabolism lead to mucopolysaccharidoses (MPS)—lysosomal storage diseases. One type of MPS (type VI) is associated with a deficiency of arylsulfatase B (ARSB), for which we previously established a cellular model using pulmonary artery endothelial cells with a silenced ARSB gene. Here, we explored the effects of silencing the ARSB gene on the growth of human pulmonary artery smooth muscle cells in the presence of different concentrations of dermatan sulfate (DS). The viability of pulmonary artery smooth muscle cells with a silenced ARSB gene was stimulated by the dermatan sulfate. In contrast, the growth of pulmonary artery endothelial cells was not affected. As shown by microarray analysis, the expression of the arylsulfatase G (ARSG) in pulmonary artery smooth muscle cells increased after silencing the arylsulfatase B gene, but the expression of genes encoding other enzymes involved in the degradation of dermatan sulfate did not. The active site of arylsulfatase G closely resembles that of arylsulfatase B, as shown by molecular modeling. Together, these results lead us to propose that arylsulfatase G can take part in DS degradation; therefore, it can affect the functioning of the cells with a silenced arylsulfatase B gene.
Published: 12 July 2020
by MDPI
Abstract:
With the increase of drought and flood frequency, the drought-flood abrupt alternation events occur frequently. Due to the coexistence and rapid transformation of drought and flood, the drought-flood abrupt alternation events is often more harmful and threatening than the single drought or flood event to the security of the society. This study is to synthetically evaluate the evolving characteristics of drought, flood, and drought-flood abrupt alternation events under climate change, which are identified by using the Standard Weighted Average Precipitation (SWAP) index. The variability of drought, flood, and drought-flood abrupt alternation events in the future is predicted by using GCM projections, whose outputs are corrected by using a daily bias correction method. The results show that: (1) The SWAP index has the capability to judge reliably the onset, duration, and intensity over the study areas, and can be used to monitor drought-flood abrupt alternation events efficiently; (2) In the reference period (1961–2005), for the drought-flood abrupt alternation events, the frequency has a downward trend in the upper reaches and an upward trend in the lower reaches, and the spatial distribution of intensity shows a contrary law to that of frequency; (3) The frequency and intensity of drought-flood abrupt alternation events show an upward trend in the whole basin in the future period (2021-2095), under the RCP4.5 and RCP8.5 scenarios. These results indicate that drought-flood abrupt alternation events can be more frequent, and the intensity will significantly increase in the 21st century, which may likely pose a serious impact on this basin.
Published: 12 July 2020
by MDPI
Abstract:
The jumping side volley has created breathtaking moments and cherished memories for soccer fans. Regrettably, scientific studies on the skill cannot be found in the literature. Relying on the talent of athletes to improvise on the fly can hardly be considered a viable learning method. This study targeted to fill this gap by quantifying the factors of the jumping side volley and to contribute to the development of a coaching method for it. Using 3D motion capture (12 cameras, 200 Hz) and full-body biomechanical modeling, our study aimed to identify elements that govern the entrainment of skill execution. Given the rarity of players who have acquired this skill and the low success rate of the kick (even in professional games), we were able to achieve and review 23 successful trials from five college-level subjects and quantify them for the study. The results unveiled the following key elements: (1) the control of trunk rotation during jumping, (2) the angle between thighs upon take-off, (3) the whip-like control of the kicking leg while airborne, (4) timing between ball motion and limb coordination, and (5) damping mechanism during falling. An accurate kick can normally be achieved through repetitive training. This underlines the need for athletes to master a safe landing technique that minimizes risk of injury during practice. Therefore, training should begin with learning a safe falling technique.
Published: 12 July 2020
by MDPI
Abstract:
Chemical diversification of type II topoisomerase (Topo II) inhibitors remains indispensable to extend their anti-tumor therapeutic values which are limited by their side effects. Herein, we designed and synthesized a novel series of benzimidazole-chalcone hybrids (BCHs). These BCHs showed good inhibitory effect in the Topo II mediated DNA relaxation assay and anti-proliferative effect in 4 tumor cell lines. 4d and 4n were the most potent, with IC50 values less than 5 μM, superior to etoposide. Mechanistic studies indicated that the BCHs functioned as non-intercalative Topo II catalytic inhibitors. Moreover, 4d and 4n demonstrated versatile properties against tumors, including inhibition on the colony formation and cell migration, and promotion of apoptosis of A549 cells. The structure-activity relationship and molecular docking analysis suggested possible contribution of the chalcone motif to the Topo II inhibitory and anti-proliferative potency. These results indicated that 4d and 4n could be promising lead compounds for further anti-tumor drug research.
Published: 12 July 2020
by MDPI
Abstract:
In recent years, the chaotic habits of modern life have favored the consumption of quickly prepared meals, using ready-to-eat (RTE) foods and condiments. The aim of this study was to establish the microbiological safety of RTE sauces and pesto from markets analyzed at different stages of shelf life. In the bacterial investigation, all samples were shown to be acceptable, although differences were observed concerning shelf life times. On the other hand, the fungal investigation showed frequent positive results, with concentrations higher than threshold values. Detected microbial diffusion was the lowest when products were far from the expiry date and had just been opened, while high microbial proliferation was observed when analyzing the same package after 48 h, higher than for a product close to the end of its shelf life. This study highlights the discreet microbiological quality of processed and RTE foods, underlining the importance of hygienic–sanitary surveillance of these foods to their shelf life. Consequently, it is necessary to: (1) implement a food control plan for all food categories to carry out risk analysis associated with their consumption; and (2) better adapt the regulations relating to microbiological analysis, and understand the biological significance of each microbial parameter throughout the shelf life of foods.
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