Mechanosensitive Adaptation of E-Cadherin Turnover across adherens Junctions

In the natural and technological world, multi-agent systems strongly depend on how the interactions are ruled between their individual components, and the proper control of time-scales and synchronization is a key issue. This certainly applies to living tissues when multicellular assemblies such as epithelial cells achieve complex morphogenetic processes. In epithelia, because cells are known to individually generate actomyosin contractile stress, each individual intercellular adhesive junction line is subjected to the opposed stresses independently generated by its two partner cells. Contact lines should thus move unless their two partner cells mechanically match. The geometric homeostasis of mature epithelia observed at short enough time-scale thus raises the problem to understand how cells, if considered as noisy individual actuators, do adapt across individual intercellular contacts to locally balance their time-average contractile stress. Structural components of adherens junctions, cytoskeleton (F-actin) and homophilic bonds (E-cadherin) are quickly renewed at steady-state. These turnovers, if they depend on forces exerted at contacts, may play a key role in the mechanical adaptation of epithelia. Here we focus on E-cadherin as a force transducer, and we study the local regulation and the mechanosensitivity of its turnover in junctions. We show that E-cadherin turnover rates match remarkably well on either side of mature intercellular contacts, despite the fact that they exhibit large fluctuations in time and variations from one junction to another. Using local mechanical and biochemical perturbations, we find faster turnover rates with increased tension, and asymmetric rates at unbalanced junctions. Together, the observations that E-cadherin turnover, and its local symmetry or asymmetry at each side of the junction, are mechanosensitive, support the hypothesis that E-cadherin turnover could be involved in mechanical homeostasis of epithelia.     

Application paléoécologique de la méthode d'analyse factorielle en composantes principales: interprétation des microfaunes de foraminifères planctoniques quaternaires en méditerranée. II. Étude des espèces de méditerranée orientale

The principal component analysis method is applied to the study of associations of different Pleistocene and Holocene planktonic Foraminifera in five cores from the eastern Mediterranean. Comparison of the fossil foraminiferal distribution with the distribution of living species leads to grouping of the fossil microfauna on the basis of paleoecological controls. Factor 1 is interpreted as representing thermal control. We recognize as warm-water species Globigerinoides trilobus, Globigerinoides trilobus sacculifer, Orbulina universa, Globigerinella siphonifera, Globigerinoides ruber. Cold-water species are Globigerina pachyderma, Globorotalia scitula, Globigerina quinqueloba, Globigerinita glutinata. Species considered to be of intermediate character are Globigerina bulloides, Globorotalia inflata and Globorotalia truncatulinoides. Factor 2 also leads to the grouping of these last species and may reflect the contributing influence of productivity phenomena. A quadratic liaison interpreted as the “Guttman effect” relates factors 1 and 2. Factor 3 introduces complications resulting from apparently sporadic, irregular events affecting the distribution of certain species, notably Globoratalia inflata, Globorotalia truncatulinoides and Globigerina dutertrei.     

Co-culture of human fibroblasts,smooth muscle and endothelial cells promotes osteopontin induction in hypoxia

Arteriovenous fistulas (AVFs) are the preferred vascular access for haemodialysis of patients suffering from end-stage renal disease, a worldwide public health problem. However, they are prone to a high rate of failure due to neointimal hyperplasia and stenosis. This study aimed to determine if osteopontin (OPN) was induced in hypoxia and if OPN could be responsible for driving AVF failure. Identification of new factors that participate in remodelling of AVFs is a challenge. Three cell lines representing the cells of the three layers of the walls of arteries and veins, fibroblasts, smooth muscle cells and endothelial cells, were tested in mono- and co-culture in vitro for OPN expression and secretion in normoxia compared to hypoxia after silencing the hypoxia-inducible factors (HIF-1α, HIF-2α and HIF-1/2α) with siRNA or after treatment with an inhibitor of NF-kB. None of the cells in mono-culture showed OPN induction in hypoxia, whereas cells in co-culture secreted OPN in hypoxia. The changes in oxygenation that occur during AVF maturation up-regulate secretion of OPN through cell-cell interactions between the different cell layers that form AVF, and in turn, these promote endothelial cell proliferation and could participate in neointimal hyperplasia.     

Synthesis,Antimicrobial Activity and Molecular Docking Study of Novel α‐(Diphenylphosphoryl)‐ and α‐(Diphenylphosphorothioyl)cycloalkanone Oximes

A series of novel α‐(diphenylphosphoryl)‐ and α‐(diphenylphosphorothioyl)cycloalkanone oximes have been synthesized in search for novel bioactive molecules. Their structures were characterized by various spectroscopic methods including IR, NMR (¹H, ³¹P, ¹³C), mass spectrometry and single crystal X‐ray diffraction. The newly synthesized phosphorus‐containing oximes were screened for their in vitro antimicrobial activity against Gram‐positive bacteria (Staphylococcus aureus and Bacillus subtilis), Gram‐negative bacteria (Escherichia coli and Salmonella typhimurium) and fungal strains (Candida albicans and Candida glabrata). The biological assays showed that all the studied compounds exhibited high antibacterial and antifungal activities at only 0.1–2.1 μg/mL. In silico molecular docking studies in FabH enzyme active site were performed in order to predict the possible interaction modes and binding energies of the drug candidates at the molecular level.     

The importance of naturally attenuated SARS-CoV-2in the fight against COVID-19

The current SARS-CoV-2 pandemic is wreaking havoc throughout the world and has rapidly become a global health emergency. A central question concerning COVID-19 is why some individuals become sick and others not. Many have pointed already at variation in risk factors between individuals. However, the variable outcome of SARS-CoV-2 infections may, at least in part, be due also to differences between the viral subspecies with which individuals are infected. A more pertinent question is how we are to overcome the current pandemic. A vaccine against SARS-CoV-2 would offer significant relief, although vaccine developers have warned that design, testing and production of vaccines may take a year if not longer. Vaccines are based on a handful of different designs (i), but the earliest vaccines were based on the live, attenuated virus. As has been the case for other viruses during earlier pandemics, SARS-CoV-2 will mutate and may naturally attenuate over time (ii). What makes the current pandemic unique is that, thanks to state-of-the-art nucleic acid sequencing technologies, we can follow in detail how SARS-CoV-2 evolves while it spreads. We argue that knowledge of naturally emerging attenuated SARS-CoV-2 variants across the globe should be of key interest in our fight against the pandemic.     

Discriminant haplotypes of avirulence genes of Phytophthora sojae lead to a molecular assay to predict phenotypes

The soybean–Phytophthora sojae interaction operates on a gene-for-gene relationship, where the product of a resistance gene (Rps) in the host recognizes that of an avirulence gene (Avr) in the pathogen to generate an incompatible reaction. To exploit this form of resistance, one must match with precision the appropriate Rps gene with the corresponding Avr gene. Currently, this association is evaluated by phenotyping assays that are labour-intensive and often imprecise. To circumvent this limitation, we sought to develop a molecular assay that would reveal the avirulence allele of the seven main Avr genes (Avr1a, Avr1b, Avr1c, Avr1d, Avr1k, Avr3a, and Avr6) in order to diagnose with precision the pathotypes of P. sojae isolates. For this purpose, we analysed the genomic regions of these Avr genes in 31 recently sequenced isolates with different virulence profiles and identified discriminant mutations between avirulence and virulence alleles. Specific primers were designed to generate amplicons of a distinct size, and polymerase chain reaction conditions were optimized in a final assay of two parallel runs. When tested on the 31 isolates of known virulence, the assay accurately revealed all avirulence alleles. The test was further assessed and compared to a phenotyping assay on 25 isolates of unknown virulence. The two assays matched in 97% (170/175) of the interactions studied. Interestingly, the sole cases of discrepancy were obtained with Avr3a, which suggests a possible imperfect interaction with Rps3a. This molecular assay offers a powerful and reliable tool to exploit and study with greater precision soybean resistance against P. sojae.     

In Situ Fe and S isotope analyses in pyrite from the 3.2 Ga Mendon Formation (Barberton Greenstone Belt,South Africa): Evidence for early microbial iron reduction

On the basis of phylogenetic studies and laboratory cultures, it has been proposed that the ability of microbes to metabolize iron has emerged prior to the Archaea/Bacteria split. However, no unambiguous geochemical data supporting this claim have been put forward in rocks older than 2.7–2.5 giga years (Gyr). In the present work, we report in situ Fe and S isotope composition of pyrite from 3.28‐ to 3.26‐Gyr‐old cherts from the upper Mendon Formation, South Africa. We identified three populations of microscopic pyrites showing a wide range of Fe isotope compositions, which cluster around two δ⁵⁶Fe values of ?1.8‰ and +1‰. These three pyrite groups can also be distinguished based on the pyrite crystallinity and the S isotope mass‐independent signatures. One pyrite group displays poorly crystallized pyrite minerals with positive Δ³³S values > +3‰, while the other groups display more variable and closer to 0‰ Δ³³S values with recrystallized pyrite rims. It is worth to note that all the pyrite groups display positive Δ³³S values in the pyrite core and similar trace element compositions. We therefore suggest that two of the pyrite groups have experienced late fluid circulations that have led to partial recrystallization and dilution of S isotope mass‐independent signature but not modification of the Fe isotope record. Considering the mineralogy and geochemistry of the pyrites and associated organic material, we conclude that this iron isotope systematic derives from microbial respiration of iron oxides during early diagenesis. Our data extend the geological record of dissimilatory iron reduction (DIR) back more than 560 million years (Myr) and confirm that micro‐organisms closely related to the last common ancestor had the ability to reduce Fe(III).