ACE2 coding variants in different populations and their potential impact on SARS-CoV-2 binding affinity

The susceptibility of different populations to SARS-CoV-2 infection is not yet understood. Here, we combined ACE2 coding variants' analysis in different populations and computational chemistry calculations to probe the effects on SARS-CoV-2/ACE2 interaction. ACE2-K26R; which is most frequent in Ashkenazi Jewish population decreased the SARS-CoV-2/ACE2 electrostatic attraction. On the contrary, ACE2-I468V, R219C, K341R, D206G, G211R increased the electrostatic attraction; ordered by binding strength from weakest to strongest. The aforementioned variants are most frequent in East Asian, South Asian, African and African American, European, European and South Asian populations, respectively

Structure of a dimeric photosystem II complex from a cyanobacterium acclimated to far-red light

Photosystem II (PSII) is the water-splitting enzyme central to oxygenic photosynthesis. To drive water oxidation, light is harvested by accessory pigments, mostly chlorophyll (Chl) a molecules, which absorb visible light (400–700 nm). Some cyanobacteria facultatively acclimate to shaded environments by altering their photosynthetic machinery to additionally absorb far-red light (FRL, 700–800 nm), a process termed far-red light photoacclimation or FaRLiP. During far-red light photoacclimation, FRL-PSII is assembled with FRL-specific isoforms of the subunits PsbA, PsbB, PsbC, PsbD, and PsbH, and some Chl-binding sites contain Chls d or f instead of the usual Chl a. The structure of an apo-FRL-PSII monomer lacking the FRL-specific PsbH subunit has previously been determined, but visualization of the dimeric complex has remained elusive. Here, we report the cryo-EM structure of a dimeric FRL–PSII complex. The site assignments for Chls d and f are consistent with those assigned in the previous apo-FRL-PSII monomeric structure. All sites that bind Chl d or Chl f at high occupancy exhibit a FRL-specific interaction of the formyl moiety of the Chl d or Chl f with the protein environment, which in some cases involves a phenylalanine sidechain. The structure retains the FRL-specific PsbH2 subunit, which appears to alter the energetic landscape of FRL-PSII, redirecting energy transfer from the phycobiliprotein complex to a Chl f molecule bound by PsbB2 that acts as a bridge for energy transfer to the electron transfer chain. Collectively, these observations extend our previous understanding of the structure-function relationship that allows PSII to function using lower energy FRL

Probing the Water Stability Limits and Degradation Pathways of Metal-Organic Frameworks (MOFs)

A comprehensive model to describe the water stability of prototypical metal–organic frameworks (MOFs) is derived by combining different types of theoretical and experimental approaches. The results provide an insight into the early stages of water-triggered destabilization of MOFs and allow detailed pathways to be proposed for the degradation of different MOFs under aqueous conditions. The essential elements of the approach are computing the pKa values of coordinated water molecules and geometry relaxations. Variable-temperature and pH infrared spectroscopy techniques are used to corroborate the main findings. The model developed herein helps to explain stability limits observed for several prototypical MOFs, including MOF-5, HKUST-1, UiO-66, and MIL-101-Cr, in aqueous solutions, and thus, provides an insight into the possible degradation pathways in acidic and basic environments. The formation of a metal hydroxide through the autoprotolysis of metal-coordinated water molecules and the strength of carboxylate–metal interactions are suggested to be two key players that govern stability in basic and acidic media, respectively. The methodology presented herein can effectively guide future efforts, which are especially significant for in silico screening, for developing novel MOFs with enhanced aqueous stability

Tuning the Chemical Environment within the UiO-66-NH2 Nanocages for Charge-Dependent Contaminant Uptake and Selectivity

The remarkable water stability of Zr-carboxylatebased metal-organic frameworks (MOFs) stimulated considerable interest toward their utilization in aqueous phase applications. The origin of such stability is probed here through pH titration and plc modeling. A unique feature of the Zr-6(mu 3OH)(4)(mu O-3)(4)(RCO2)(12) cluster is the Zr-bridging oxo/hydroxyl groups, demonstrating several pK(a) values that appear to provide for the water stability at a wide range of pH. Accordingly, the tunability of the cage/surface charge of the MOF can feasibly be controlled through careful adjustment of solution pH. Such high stability, and facile control over cage/surface charge, can additionally be augmented through introducing chemical functionalities lining the cages of the MOF, specifically amine groups in the UiO-66-NH2 presented herein. The variable protonation states of the Zr cluster and the pendant amino groups, their H-bond donor/acceptor characteristics, and their electrostatic interactions with guest molecules were effectively utilized in controlled experiments to demonstrate high uptake of model guest molecules (137 mg/g for Cr(VI), 1275 mg/g for methylene blue, and 909 mg/g for methyl orange). Additionally, a practical form of the silica-supported MOF, UiO-66-NH2 @SiO2, constructed in under 2 h reaction time, is described, generating a true platform microporous sorbent for practical use in demanding applications

Comparison of zebrafish and mice knockouts for Megalencephalic Leukoencephalopathy proteins indicates that GlialCAM/MLC1 forms a functional unit

[Abstract] Background: Megalencephalic Leukoencephalopathy with subcortical Cysts (MLC) is a rare type of leukodystrophy characterized by astrocyte and myelin vacuolization, epilepsy and early-onset macrocephaly. MLC is caused by mutations in MLC1 or GLIALCAM, coding for two membrane proteins with an unknown function that form a complex specifically expressed in astrocytes at cell-cell junctions. Recent studies in Mlc1−/− or Glialcam−/− mice and mlc1−/− zebrafish have shown that MLC1 regulates glial surface levels of GlialCAM in vivo and that GlialCAM is also required for MLC1 expression and localization at cell-cell junctions. Methods: We have generated and analysed glialcama−/− zebrafish. We also generated zebrafish glialcama−/− mlc1−/− and mice double KO for both genes and performed magnetic resonance imaging, histological studies and biochemical analyses. Results: glialcama−/− shows megalencephaly and increased fluid accumulation. In both zebrafish and mice, this phenotype is not aggravated by additional elimination of mlc1. Unlike mice, mlc1 protein expression and localization are unaltered in glialcama−/− zebrafish, possibly because there is an up-regulation of mlc1 mRNA. In line with these results, MLC1 overexpressed in Glialcam−/− mouse primary astrocytes is located at cell-cell junctions. Conclusions: This work indicates that the two proteins involved in the pathogenesis of MLC, GlialCAM and MLC1, form a functional unit, and thus, that loss-of-function mutations in these genes cause leukodystrophy through a common pathway.Ministerio de Ciencia e Innovación; SAF2015–70377Ministerio de Ciencia e Innovación; RTI2018–093493-B-I00Generalitat de Catalunya; SGR2014–1178Generalitat de Catalunya; SGR014–2016Instituto de Salud Carlos III; PI16/00267-R-Fede

The Effect of Surface Texture on the Joint Shear Strength of AR500 Steel and AA7075 / M. N. Muhamed...[et al.]

AA7075 aluminium alloy brazing joint panels caused by shear loading. The use of steel and aluminium laminated metal composite is increasingly popular since they are well known for lightweight application and stiffness properties and this makes them the material of choice in automotive industry. However, the formation of reaction layer phases has limited the application of this method of joining due to the adverse effect of these phases on the strength of the joint. In this work, AR500 steel and AA7075 aluminium alloy interface joint were fabricated by torch brazing method using Al-Si-Zn base material as its filler metal for different types of surface conditions. The joining was evaluated for shear strength performance. The experimental results showed that the highest shear strength for the panel was recorded at 8010 N. Fractures were mostly seen at the joint interface area. In general, the torch brazing process with different surface joining conditions, had facilitated the joining of these dissimilar metals while improving the mechanical properties of the joint

Active wetting of epithelial tissues

Development, regeneration and cancer involve drastic transitions in tissue morphology. In analogy with the behavior of inert fluids, some of these transitions have been interpreted as wetting transitions. The validity and scope of this analogy are unclear, however, because the active cellular forces that drive tissue wetting have been neither measured nor theoretically accounted for. Here we show that the transition between 2D epithelial monolayers and 3D spheroidal aggregates can be understood as an active wetting transition whose physics differs fundamentally from that of passive wetting phenomena. By combining an active polar fluid model with measurements of physical forces as a function of tissue size, contractility, cell-cell and cell-substrate adhesion, and substrate stiffness, we show that the wetting transition results from the competition between traction forces and contractile intercellular stresses. This competition defines a new intrinsic lengthscale that gives rise to a critical size for the wetting transition in tissues, a striking feature that has no counterpart in classical wetting. Finally, we show that active shape fluctuations are dynamically amplified during tissue dewetting. Overall, we conclude that tissue spreading constitutes a prominent example of active wetting --- a novel physical scenario that may explain morphological transitions during tissue morphogenesis and tumor progression

Prevalence of group A streptococcal carriage in school children from Cape Town: A cross- sectional study and systematic review

Background. Asymptomatic children can be a major reservoir of pharyngeal group A streptococcus (GAS). The role of GAS carriage causing subsequent infections resulting in the manifestation of clinical symptoms, or being associated with transmission to uninfected individuals, is not entirely clear. Furthermore, data on GAS carriage from countries in Africa remain scant with only a few studies reporting carriage. Objectives. We performed a cross-sectional study to determine the prevalence of asymptomatic pharyngeal carriage of group A streptococci in school children in Cape Town. We considered our results in the context of a meta-analysis of data of GAS carriage in Africa. Methods. We conducted a school-based cross-sectional study from 2009 to 2011 in two Cape Town peri-urban communities, enrolling 950 healthy learners. Pharyngeal swabs were obtained from learners and processed at the National Health Laboratory Service (NHLS) microbiology laboratory at Groote Schuur Hospital, Cape Town. Thereafter, we conducted a systematic review through a comprehensive literature search among several sources. Prevalence estimates with 95% confidence intervals (CIs) were determined using a random-effects meta-analysis model. Results. GAS was isolated from 31 participants corresponding to a carrier rate of 3% (95% CI 2% - 4%). Combining our results with 18 other studies revealed a pooled prevalence of 9% (95% CI 6% - 11%). Regional pooled rates were similar across southern, eastern and northern Africa, of between 9% (95% CI 6% - 11%) and 11% (95% CI 4% - 21%) while countries within Central Africa had a pooled estimate of 7% (95% CI 5% - 9%). Western Africa had the lowest pooled estimate of 2% (95% CI 1% - 2%). Conclusion. There was a relatively low rate of carriage of GAS in asymptomatic school children residing in South Africa. Pooled prevalence rates revealed regional differences across the African continent as regards the rate of GAS carriage, with the western and northern African regions having rates of GAS carriage that were lower and higher respectively than those of East, Central and southern African countries, which demonstrated similar rates of carriage