The emergency of SARS-CoV-2 in China started a novel challenge to the scientific community. As the virus turns pandemic, scientists try to map the cellular mechanisms and pathways of SARS-CoV-2 ...related to the pathogenesis of Coronavirus Disease 2019 (Covid-19). After transmembrane angiotensin-converting enzyme 2 (ACE2) has been found to be SARS-CoV-2 receptor, we hypothesized an immune-hematological mechanism for Covid-19 based on renin-angiotensin system (RAS) imbalance to explain clinical, laboratory and imaging findings on disease course. We believe that exaggerated activation of ACE/Angiotensin II (Ang II)/Angiotensin Type 1 (AT1) receptor RAS axis in line with reduction of ACE2/Angiotensin-(1-7)/Mas receptor may exert a pivotal role in the pathogenesis of Covid-19. In this perspective, we discuss potential mechanisms and evidence on this hypothesis.
The upcoming Large Synoptic Survey Telescope (LSST) will detect many strongly lensed Type Ia supernovae (LSNe Ia) for time-delay cosmography. This will provide an independent and direct way for ...measuring the Hubble constant H0, which is necessary to address the current 4.4σ tension in H0 between the local distance ladder and the early Universe measurements. We present a detailed analysis of different observing strategies (also referred to as cadence strategy) for the LSST, and quantify their impact on time-delay measurement between multiple images of LSNe Ia. For this, we simulated observations by using mock LSNe Ia for which we produced mock-LSST light curves that account for microlensing. Furthermore, we used the free-knot splines estimator from the software PyCS to measure the time delay from the simulated observations. We find that using only LSST data for time-delay cosmography is not ideal. Instead, we advocate using LSST as a discovery machine for LSNe Ia, enabling time delay measurements from follow-up observations from other instruments in order to increase the number of systems by a factor of 2–16 depending on the observing strategy. Furthermore, we find that LSST observing strategies, which provide a good sampling frequency (the mean inter-night gap is around two days) and high cumulative season length (ten seasons with a season length of around 170 days per season), are favored. Rolling cadences subdivide the survey and focus on different parts in different years; these observing strategies trade the number of seasons for better sampling frequency. In our investigation, this leads to half the number of systems in comparison to the best observing strategy. Therefore rolling cadences are disfavored because the gain from the increased sampling frequency cannot compensate for the shortened cumulative season length. We anticipate that the sample of lensed SNe Ia from our preferred LSST cadence strategies with rapid follow-up observations would yield an independent percent-level constraint on H0.
In order to model the adsorption of organic corrosion inhibitors on ultrathin oxide layers on aluminum, the formation of a self-assembled layer of gallic acid, the smallest tannin molecule, at the ...surface of an Al2O3 ultrathin layer supported by Al(111) was studied using periodic density functional theory including dispersion forces (DFT-D). A dense self-assembled layer (SAM) was formed with a density of 3.6 molecules/nm2, adsorbed in a monodentate way by ligand exchange, with an adsorption energy of 2.27 eV/molecule. The electronic analysis shows that the oxide levels are significantly stabilized by the covalent bonding with the COOH moiety of the molecule. The permittivity of the surface layers falls from 109 for the ultrathin Al2O3 film to 4 for the joint oxide and organic film. The permittivity of the surface constrained gallic acid SAM is 1.4, a value slightly lower than that of the free hexagonal compact, SAM (2.4). The organic layer forms an efficient barrier against electron transfer to dioxygen, thus providing good cathodic inhibition. The potential drop at the edge of the oxide and organic layer is found to be around 2 V. Studies of benzoates derivatives (benzoic acid and nitrobenzoic acid) show that the potential drop and the electronic work function difference (with respect to the nonfunctionalized oxide film) induced by the organic SAM increase linearly with the charge of the adsorbed molecules. The reported results give indications for the rational design of corrosion inhibitors.
Adhesive bonding is used to fabricate structures of complex shape that could not be manufactured in one piece. In many high performance structures, joints between composite materials with other light ...metals such as aluminium are required for structural optimization. This work numerically and experimentally addresses adhesive joints between aluminium and carbon–epoxy composites, considering different adhesives and value of overlap length (LO). Numerically, the Finite Element Method (FEM) coupled with cohesive zone models (CZM) is used to perform a detailed stress analysis that enables the comparison between different planes in the joint and LO values. A damage analysis during damage and crack growth is also considered to fully describe the failure process. The use of the proposed numerical technique enables predicting the joint strength and creating a simple and rapid methodology that can be used in the design of hybrid structures, e.g. in the selection of the joint geometry and adhesive. The joints’ strength and failure modes were highly dependent on the adhesive, and this behaviour was successfully modelled numerically. Using a brittle adhesive resulted in a negligible maximum load (Pm) improvement with LO. The joints bonded with the ductile adhesive showed a nearly linear improvement of Pm with LO.
Systemic insulin availability is determined by a balance between beta-cell secretion capacity and insulin clearance (IC). Insulin-degrading enzyme (IDE) is involved in the intracellular mechanisms ...underlying IC. The liver is a major player in IC control yet the role of hepatic IDE in glucose and lipid homeostasis remains unexplored.
We hypothesized that IDE governs postprandial IC and hepatic IDE dysfunction amplifies dysmetabolic responses and prediabetes traits such as hepatic steatosis.
In a European/Portuguese population-based cohort, IDE SNPs were strongly associated with postprandial IC in normoglycemic men but to a considerably lesser extent in women or in subjects with prediabetes. Liver-specific knockout-mice (LS-IDE KO) under normal chow diet (NCD), showed reduced postprandial IC with glucose intolerance and under high fat diet (HFD) were more susceptible to hepatic steatosis than control mice. This suggests that regulation of IC by IDE contributes to liver metabolic resilience. In agreement, LS-IDE KO hepatocytes revealed reduction of Glut2 expression levels with consequent impairment of glucose uptake and upregulation of CD36, a major hepatic free fatty acid transporter.
Together these findings provide strong evidence that dysfunctional IC due to abnormal IDE regulation directly impairs postprandial hepatic glucose disposal and increases susceptibility to dysmetabolic conditions in the setting of Western diet/lifestyle.
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•IDE polymorphisms strongly associate with postprandial IC in NGT men.•IDE polymorphisms association with IC is weaken in women and prediabetes.•Liver-specific IDE KO display reduced postprandial IC.•Liver-specific IDE KO display glucose intolerance correlated with reduced glut2.•Liver-specific IDE KO exacerbates hepatic steatosis induced by high fat diet.
It is estimated that around 70% of Type 2 Diabetes Mellitus patients (T2DM) have Non-Alcoholic Fatty Liver Disease (NAFLD). Awareness and education are amongst the major shortcomings of the public ...health response to the increasing threat of NAFLD. Characterizing the specific NAFLD-related information needs of particular high-risk metabolic communities, for instance, T2DM patients, might aid in the development of evidence-based health promotion strategies, ultimately promoting NAFLD-awareness, treatment adherence and therapeutic success rates.
Semi-structured interviews with T2DM patients were conducted to gain insight into their awareness of NAFLD, including its relationship with insulin resistance and T2DM.
Awareness of NAFLD as a disease entity, as well as its progression to end-stage liver disease or its relationship with other metabolic conditions, including insulin resistance and T2DM was low. Surveillance behaviours were also suboptimal and perceptions on the self-management knowledge and praxis regarding lifestyle intervention components of T2DM treatment seemed detached from those of NAFLD.
Our findings could inform the integration of NAFLD-related content in T2DM health promotion strategies. Rising awareness on NAFLD progression and its relationship with T2DM using culturally and community-relevant constructs might facilitate the development of primary and secondary prevention programmes to promote the adherence to lifestyle interventions by influencing NAFLD threat perceptions.
Abstract
The recently discovered ring around the dwarf planet (136108) Haumea is located near the 1:3 resonance between the orbital motion of the ring particles and the spin of Haumea. In the current ...work, we study the dynamics of individual particles in the region where the ring is located. Using the Poincaré surface of section technique, the islands of stability associated with the 1:3 resonance are identified and studied. Throughout its existence, this resonance is shown to be doubled, producing pairs of periodic and quasi-periodic orbits. The fact of being doubled introduces a separatrix, which generates a chaotic layer that reduces the size of the stable regions of the 1:3 resonance significantly. The results also show that there is a minimum equivalent eccentricity (e1$\colon$3) required for the existence of such a resonance. This value seems to be too high to keep a particle within the borders of the ring. On the other hand, the Poincaré surface of sections shows the existence of much larger stable regions, but associated with a family of first-kind periodic orbits. They exist with equivalent eccentricity values lower than e1$\colon$3, covering a large radial distance, which encompasses the region of Haumea’s ring. Therefore, this analysis suggests that Haumea’s ring is in a stable region associated with a first-kind periodic orbit instead of the 1:3 resonance.
The interest in high-rate anaerobic (pre-)treatment of sewage using UASB reactors is steadily growing since its introduction in the mid-1980s. Today there are hundreds of full-scale plants in ...operation in various parts of the tropical world, notably in Latin America and India. The main advantage of UASB technology is the very low or even zero energy demand, leading to an up to tenfold drop in operational costs compared to activated sludge. This paper presents a literature review focussing on current design criteria and post-treatment options, alongside discussing the centralized and decentralized approach. The current limitations and constraints regarding temperature, nutrients, pathogen removal, odour nuisance, operational constrictions and methane emissions are also presented and discussed. Further, recent challenges in relation to energy recovery from biogas, sludge and scum are discussed, alongside with advances related to recovery of dissolved methane and sludge management. Finally, the paper provides some outlooks for upcoming developments.
Environmental manganese (Mn) toxicity causes an extrapyramidal, parkinsonian-type movement disorder with characteristic magnetic resonance images of Mn accumulation in the basal ganglia. We have ...recently reported a suspected autosomal recessively inherited syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia in cases without environmental Mn exposure. Whole-genome mapping of two consanguineous families identified SLC30A10 as the affected gene in this inherited type of hypermanganesemia. This gene was subsequently sequenced in eight families, and homozygous sequence changes were identified in all affected individuals. The function of the wild-type protein and the effect of sequence changes were studied in the manganese-sensitive yeast strain Δpmr1. Expressing human wild-type SLC30A10 in the Δpmr1 yeast strain rescued growth in high Mn conditions, confirming its role in Mn transport. The presence of missense (c.266T>C p.Leu89Pro) and nonsense (c.585del p.Thr196Profs∗17) mutations in SLC30A10 failed to restore Mn resistance. Previously, SLC30A10 had been presumed to be a zinc transporter. However, this work has confirmed that SLC30A10 functions as a Mn transporter in humans that, when defective, causes Mn accumulation in liver and brain. This is an important step toward understanding Mn transport and its role in neurodegenerative processes.
Network theory methods are being increasingly applied to proteins to investigate complex biological phenomena. Residues that are important for signaling processes can be identified by their condition ...as critical nodes in a protein structure network. This analysis involves modeling the protein as a graph in which each residue is represented as a node and edges are drawn between nodes that are deemed connected. In this paper, we show that the results obtained from this type of network analysis (i.e., signaling pathways, key residues for signal transmission, etc.) are profoundly affected by the topology of the network, with normally used determination of network edges by geometrical cutoff schemes giving rise to substantial statistical errors. We propose a method of determining protein structure networks by calculating inter-residue interaction energies and show that it gives an accurate and reliable description of the signal-propagation properties of a known allosteric enzyme. We also show that including covalent interactions in the network topology is essential for accurate results to be obtained.
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