Atherogenic potential of microgravity hemodynamics in the carotid bifurcation: a numerical investigation

Long-duration spaceflight poses multiple hazards to human health, including physiological changes associated with microgravity. The hemodynamic adaptations occurring upon entry into weightlessness have been associated with retrograde stagnant flow conditions and thromboembolic events in the venous vasculature but the impact of microgravity on cerebral arterial hemodynamics and function remains poorly understood. The objective of this study was to quantify the effects of microgravity on hemodynamics and wall shear stress (WSS) characteristics in 16 carotid bifurcation geometries reconstructed from ultrasonography images using computational fluid dynamics modeling. Microgravity resulted in a significant 21% increase in flow stasis index, a 22–23% decrease in WSS magnitude and a 16–26% increase in relative residence time in all bifurcation branches, while preserving WSS unidirectionality. In two anatomies, however, microgravity not only promoted flow stasis but also subjected the convex region of the external carotid arterial wall to a moderate increase in WSS bidirectionality, which contrasted with the population average trend. This study suggests that long-term exposure to microgravity has the potential to subject the vasculature to atheroprone hemodynamics and this effect is modulated by subject-specific anatomical features. The exploration of the biological impact of those microgravity-induced WSS aberrations is needed to better define the risk posed by long spaceflights on cardiovascular health

Comparative genomic analysis reveals habitat-specific genes and regulatory hubs within the genus Novosphingobium

© The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in mSystems 2 (2017): e00020-17, doi:10.1128/mSystems.00020-17.Species belonging to the genus Novosphingobium are found in many different habitats and have been identified as metabolically versatile. Through comparative genomic analysis, we identified habitat-specific genes and regulatory hubs that could determine habitat selection for Novosphingobium spp. Genomes from 27 Novosphingobium strains isolated from diverse habitats such as rhizosphere soil, plant surfaces, heavily contaminated soils, and marine and freshwater environments were analyzed. Genome size and coding potential were widely variable, differing significantly between habitats. Phylogenetic relationships between strains were less likely to describe functional genotype similarity than the habitat from which they were isolated. In this study, strains (19 out of 27) with a recorded habitat of isolation, and at least 3 representative strains per habitat, comprised four ecological groups—rhizosphere, contaminated soil, marine, and freshwater. Sulfur acquisition and metabolism were the only core genomic traits to differ significantly in proportion between these ecological groups; for example, alkane sulfonate (ssuABCD) assimilation was found exclusively in all of the rhizospheric isolates. When we examined osmolytic regulation in Novosphingobium spp. through ectoine biosynthesis, which was assumed to be marine habitat specific, we found that it was also present in isolates from contaminated soil, suggesting its relevance beyond the marine system. Novosphingobium strains were also found to harbor a wide variety of mono- and dioxygenases, responsible for the metabolism of several aromatic compounds, suggesting their potential to act as degraders of a variety of xenobiotic compounds. Protein-protein interaction analysis revealed β-barrel outer membrane proteins as habitat-specific hubs in each of the four habitats—freshwater (Saro_1868), marine water (PP1Y_AT17644), rhizosphere (PMI02_00367), and soil (V474_17210). These outer membrane proteins could play a key role in habitat demarcation and extend our understanding of the metabolic versatility of the Novosphingobium species.This work was supported by grants from the Department of Biotechnology (DBT), R.K., S.H., K.P., A.B., and U.S. gratefully acknowledge the National Bureau of Agriculturally Important Microorganisms (NBAIM), Science and Engineering Research Board (SERB), N-PDF (PDF/2015/000062), (PDF/2015, 000319), University Grant Commission (UGC) for the Dr. D. S. Kothari Postdoctoral Fellowship and UGC for providing fellowships, respectively

Botany, chemistry, and pharmaceutical significance of Sida cordifolia: a traditional medicinal plant

Sida cordifolia Linn. belonging to the family, Malvaceae has been widely employed in traditional medications in many parts of the world including India, Brazil, and other Asian and African countries. The plant is extensively used in the Ayurvedic medicine preparation. There are more than 200 plant species within the genus Sida, which are distributed predominantly in the tropical regions. The correct taxonomic identification is a major concern due to the fact that S. cordifolia looks morphologically similar with its related species. It possesses activity against various human ailments, including cancer, asthma, cough, diarrhea, malaria, gonorrhea, tuberculosis, obesity, ulcer, Parkinson’s disease, urinary infections, and many others. The medical importance of this plant is mainly correlated to the occurrence of diverse biologically active phytochemical compounds such as alkaloids, flavonoids, and steroids. The major compounds include β-phenylamines, 2-carboxylated tryptamines, quinazoline, quinoline, indole, ephedrine, vasicinone, 5-3-isoprenyl flavone, 5,7-dihydroxy-3-isoprenyl flavone, and 6-(isoprenyl)- 3-methoxy- 8-C-β-D-glucosyl-kaempferol 3-O-β-D-glucosyl[1–4]-α-D-glucoside. The literature survey reveals that most of the pharmacological investigations on S. cordifolia are limited to crude plant extracts and few isolated pure compounds. Therefore, there is a need to evaluate many other unexplored bioactive phytoconstituents with evidences so as to justify the traditional usages of S. cordifolia. Furthermore, detailed studies on the action of mechanisms of these isolated compounds supported by clinical research are necessary for validating their application in contemporary medicines. The aim of the present chapter is to provide a detailed information on the ethnobotanical, phytochemical, and pharmacological aspects of S. cordifolia

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

Abstract: The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era

Determination of Factors Affecting Extraction of Rebaudioside A & Stevioside from Stevia Leaves

Solid-liquid extraction is a recovery process in which the extracting solvent will recover certain components from a solid material. In this study, three extracting solvents were used which are absolute ethanol, acetone and distilled water. These solvents extracted two sweet components, Rebaudioside A and stevioside from Stevia rebaudiana. These two components can be converted into natural sweetener with zero calorie which does not affect blood glucose level. The objective of this study was to determine the optimum value of parameters to extract the highest amount of steviol glycosides. The extraction was done in 3 phases. First phase was to determine the best ratio between stevia and extracting solvent, second phase determined the best extracting time and third phase was to obtain the optimum temperature. From this study, ethanol proved to be the best extracting solvent. Ethanol extraction of Rebaudioside A and stevioside in the most suitable condition (ratio 1:25, 1 hour and 40℃) produced 12.48% of stevioside and 0.57% of Rebaudioside A

Optimization of Rebaudioside A extraction from stevia leaves using response surface methodology

Rebaudioside A or Reb A is an extractable component from stevia leaves or scientifically known as Stevia rebaudiana. Reb A is famous for its exceptional sweetness and widely used as a non-caloric sweetener. Its potential widespread use requires an easy and effective extraction method. In this study, extraction of Reb A from stevia leaves with parameters such as temperature, material ratio and extraction time were investigated. Time of extraction were 1, 1.5, 2, 2.5 and 3 hours. Temperature was varied at 400C, 450C, 500C, 550C and 600C. Material ratio was 1:5, 1:10, 1:15, 1:20 and 1:25. Then, using Design Expert software, the ranges of the parameters were entered in the Central Composite Design (CCD) to create 20 different combinations of parameters for extraction. After executing the experiments, the yield of Reb A obtained was keyed in Response Surface Methodology (RSM) for optimization. Finally, the optimum condition was tested and validated by calculating the percentage error. Since the percentage error was less than 10%, the optimum condition, which is, 350C, 1:6 material ratio and 5 hours of extraction was accepte

Pollutant concentrations and exposure variability in four urban microenvironments of London

We compared various pollutant concentrations (PM1, PM2.5, PM10, PNC, BC) at four different urban microenvironments (MEs) in London (Indoor, IN; Traffic Intersection, TI; Park, PK; and Street Canyon, SC). The physico-chemical characteristics of particles were analysed, and the respiratory deposition doses (RDD) were estimated. Field measurements were conducted over a period of 121 days. The mean PM2.5 (PNC) concentrations were found to be 9.47 ± 7.05 (16366 ± 11815), 8.09 ± 4.57 (10951 ± 6445), 5.11 ± 2.96 (7717 ± 4576), 3.88 ± 3.06 (5672 ± 2934) μg m−3 (# cm−3) at TI, SC, PK and IN, respectively. PM2.5, PM10 and PNC exhibited a trend of TI \u3e SC \u3e PK \u3e IN; higher concentrations for PM1 and BC were observed at IN than PK due to the emissions from printers, producing a trend of TI \u3e SC \u3e IN \u3e PK. We observed 12%–30% higher fine PM concentrations at TI and SC sites during morning peak (07:00–09:30) than the evening peak hours (16:00–19:00); while IN showed a smaller variation in fine PM concentrations compared with outdoor TI, PK and SC sites owing to their prevalence in the IN for a longer time. Fine and ultrafine PM containing potentially toxic trace transition metals including Fe, Ti, Cr, Mn, Al and Mg were detected by high resolution electron microscopy at all sites. There was a similar relative abundance of different elements at the TI, IN and PK sites, which suggests a transport of PM between MEs. RDD for PM1 was highest (2.45 ± 2.27 μg h−1) at TI for females during running; PM2.5 and PM10 were highest at SC (11.23 ± 6.34 and 37.17 ± 20.82 μg h−1, respectively). The results show that the RDD variation between MEs does not follow the PM concentration trend. RDD at PK was found to be 39%–53% lower than TI and SC during running for all the PM fractions. Overall, the study findings show the air quality variation at different MEs and reveals the exposure inequalities around the city, which enable the management of personal exposure by selecting appropriate MEs for different activities

Insight into the effect of inhibitor resistant S130G mutant on physico-chemical properties of SHV type beta-lactamase: a molecular dynamics study.

Bacterial resistance is a serious threat to human health. The production of β-lactamase, which inactivates β-lactams is most common cause of resistance to the β-lactam antibiotics. The Class A enzymes are most frequently encountered among the four β-lactamases in the clinic isolates. Mutations in class A β-lactamases play a crucial role in substrate and inhibitor specificity. SHV and TEM type are known to be most common class A β-lactamases. In the present study, we have analyzed the effect of inhibitor resistant S130G point mutation of SHV type Class-A β-lactamase using molecular dynamics and other in silico approaches. Our study involved the use of different in silico methods to investigate the affect of S130G point mutation on the major physico-chemical properties of SHV type class A β-lactamase. We have used molecular dynamics approach to compare the dynamic behaviour of native and S130G mutant form of SHV β-lactamase by analyzing different properties like root mean square deviation (RMSD), H-bond, Radius of gyration (Rg) and RMS fluctuation of mutation. The results clearly suggest notable loss in the stability of S130G mutant that may further lead to decrease in substrate specificity of SHV. Molecular docking further indicates that S130G mutation decreases the binding affinity of all the three inhibitors in clinical practice