Discovering Fragile Clades and Causal Sequences in Phylogenomics by Evolutionary Sparse Learning.

Phylogenomic analyses of long sequences, consisting of many genes and genomic segments, reconstruct organismal relationships with high statistical confidence. But, inferred relationships can be sensitive to excluding just a few sequences. Currently, there is no direct way to identify fragile relationships and the associated individual gene sequences in species. Here, we introduce novel metrics for gene-species sequence concordance and clade probability derived from evolutionary sparse learning models. We validated these metrics using fungi, plant, and animal phylogenomic datasets, highlighting the ability of the new metrics to pinpoint fragile clades and the sequences responsible. The new approach does not necessitate the investigation of alternative phylogenetic hypotheses, substitution models, or repeated data subset analyses. Our methodology offers a streamlined approach to evaluating major inferred clades and identifying sequences that may distort reconstructed phylogenies using large datasets.

Methods for Estimating Personal Disease Risk and Phylogenetic Diversity of Hematopoietic Stem Cells.

An individual's chronological age does not always correspond to the health of different tissues in their body, especially in cases of disease. Therefore, estimating and contrasting the physiological age of tissues with an individual's chronological age may be a useful tool to diagnose disease and its progression. In this study, we present novel metrics to quantify the loss of phylogenetic diversity in hematopoietic stem cells (HSCs), which are precursors to most blood cell types and are associated with many blood-related diseases. These metrics showed an excellent correspondence with an age-related increase in blood cancer incidence, enabling a model to estimate the phylogeny-derived age (phyloAge) of HSCs present in an individual. The HSC phyloAge was generally older than the chronological age of patients suffering from myeloproliferative neoplasms (MPNs). We present a model that relates excess HSC aging with increased MPN risk. It predicted an over 200 times greater risk based on the HSC phylogenies of the youngest MPN patients analyzed. Our new metrics are designed to be robust to sampling biases and do not rely on prior knowledge of driver mutations or physiological assessments. Consequently, they complement conventional biomarker-based methods to estimate physiological age and disease risk.

Omics-driven utilization of wild relatives for empowering pre-breeding in pearl millet.

MAIN CONCLUSION: Pearl millet wild relatives harbour novel alleles which could be utilized to broaden genetic base of cultivated species. Genomics-informed pre-breeding is needed to speed up introgression from wild to cultivated gene pool in pearl millet. Rising episodes of intense biotic and abiotic stresses challenge pearl millet production globally. Wild relatives provide a wide spectrum of novel alleles which could address challenges posed by climate change. Pre-breeding holds potential to introgress novel diversity in genetically narrow cultivated Pennisetum glaucum from diverse gene pool. Practical utilization of gene pool diversity remained elusive due to genetic intricacies. Harnessing promising traits from wild pennisetum is limited by lack of information on underlying candidate genes/QTLs. Next-Generation Omics provide vast scope to speed up pre-breeding in pearl millet. Genomic resources generated out of draft genome sequence and improved genome assemblies can be employed to utilize gene bank accessions effectively. The article highlights genetic richness in pearl millet and its utilization with a focus on harnessing next-generation Omics to empower pre-breeding.

Acid mine drainage from coal mines in the eastern Himalayan sub-region: Hydrogeochemical processes, seasonal variations and insights from hydrogen and oxygen stable isotopes.

Uncontrolled coal mining using non-scientific methods has presented a major threat to the quality of environment, particularly the water resources in eastern himalayan sub-region of India. Water bodies in the vicinity of mining areas are contaminated by acid mine drainage (AMD) that is released into streams and rivers. This study attempted to assess the impact of AMD, deciphering hydrogeochemical processes, seasonal fluctuations, and stable isotope features of water bodies flowing through and around coal mining areas. Self-organizing maps (SOMs) used to separate and categorize AMD, AMD-impacted and non-AMD impacted water from the different study locations for two sampling seasons revealed four clusters (C), with C1 and C2 impacted by AMD, C3 and C4 showing negligible to no impact of AMD. AMD impacted water was SO42- - Mg2+- Ca2+ hydrochemical type with sulphide oxidation and evaporation dominating water chemistry, followed by silicate weathering during both the sampling seasons. Water with negligible-to-no AMD-impact was Mg2+- Ca2+- SO42- to Ca2+ - HCO3- to mixed hydrochemical type with rock weathering and dissolution, followed by ion exchange as major factors controlling water chemistry during both the sampling seasons. Most of physicochemical parameters of C1 and C2 exceeded the prescribed limits, whereas in C3 and C4 water samples, parameters were found within the prescribed limits. Stable isotopes of hydrogen (δ2H) and oxygen (δ18O) during post-monsoon (PoM) varied between -41.04 ‰ and -29.98 ‰, and -6.60 ‰ to -3.94 ‰; and during pre-monsoon (PrM) varied between -58.18 ‰ and - 33.76 ‰ and -8.60 ‰ to -5.46 ‰. Deuterium excess (d-excess) ranged between 1.57 ‰ and 12.47 ‰ during PoM and 5.70 ‰ to 15.17 ‰ during PrM season. The stable isotopes analysis revealed that evaporation, mineral dissolution and mixing with rainwater are the key factors in study area.

Effect of tropospheric ozone and its protectants on gas exchange parameters, antioxidant enzymes and quality of Garlic (Allium sativum. L).

An experimental study was conducted to assess the detrimental effect of ground-level ozone (O3) on garlic physiology and to find out appropriate control measures against ground-level O3, at TNAU-Horticultural Research farm, Udhagamandalam. Elevated ground ozone levels significantly decreased garlic leaf chlorophyll, photosynthetic rate, stomatal conductance, total soluble solids and pungency. The garlic chlorophyll content was highest in ambient ozone level and lowest in elevated ozone@200 ppb, highest stomatal conductance was recorded in ambient ozone with foliar spray of 3%Panchagavya, and the lowest was observed in elevated ozone@200 ppb. Since the elevated O3 had reduced in garlic photosynthetic rate significantly the lowest was observed in elevated O3@200 ppb and the highest photosynthetic rate was observed in ambient Ozone with foliar spray 3% of panchagavya after a week. The antioxidant enzymes of garlic were increased with increased concentration of tropospheric ozone. The highest catalase (60.97 µg of H2O2/g of leaf) and peroxidase (9.13 ΔA/min/g of leaf) concentration was observed at 200 ppb elevated ozone level. Garlic pungency content was highest in ambient ozone with foliar spray of 0.1% ascorbic acid and the lowest was observed under elevated O3@200 ppb. Highest total soluble solids were observed in ambient ozone with foliar spray of 3%Panchagavya and the lowest observed in elevated ozone@200 ppb. Thus, tropospheric ozone has a detrimental impact on the physiology of crops, which reduced crop growth and yield. Under elevated O3 levels, ascorbic acid performed well followed by panchagavya and neem oil. The antioxidant such as catalase and peroxidase had positive correlation among themselves and had negative correlation with chlorophyll content, stomatal conductance, photosynthetic rate, pungency and TSS. The photosynthetic rate has high positive correlation with chlorophyll content, pungency and TSS. Correlation analysis confirmed the negative effects of tropospheric ozone and garlic gas exchange parameters and clove quality. The ozone protectants will reduce stomatal opening by which the entry of O3 in to the cell will be restricted and other hand they also will alleviate ROS and allied stresses.

Advancements in unravelling the fundamental function of the ATAD3 protein in multicellular organisms.

ATPase family AAA domain containing protein 3, commonly known as ATAD3 is a versatile mitochondrial protein that is involved in a large number of pathways. ATAD3 is a transmembrane protein that spans both the inner mitochondrial membrane and outer mitochondrial membrane. It, therefore, functions as a connecting link between the mitochondrial lumen and endoplasmic reticulum facilitating their cross-talk. ATAD3 contains an N-terminal domain which is amphipathic in nature and is inserted into the membranous space of the mitochondria, while the C-terminal domain is present towards the lumen of the mitochondria and contains the ATPase domain. ATAD3 is known to be involved in mitochondrial biogenesis, cholesterol transport, hormone synthesis, apoptosis and several other pathways. It has also been implicated to be involved in cancer and many neurological disorders making it an interesting target for extensive studies. This review aims to provide an updated comprehensive account of the role of ATAD3 in the mitochondria especially in lipid transport, mitochondrial-endoplasmic reticulum interactions, cancer and inhibition of mitophagy.

Discovering Fragile Clades And Causal Sequences In Phylogenomics By Evolutionary Sparse Learning.

Phylogenomic analyses of long sequences, consisting of many genes and genomic segments, infer organismal relationships with high statistical confidence. But, these relationships can be sensitive to excluding just a few sequences. Currently, there is no direct way to identify fragile relationships and the associated individual gene sequences in species. Here, we introduce novel metrics for gene-species sequence concordance and clade probability derived from evolutionary sparse learning models. We validated these metrics using fungi, plant, and animal phylogenomic datasets, highlighting the ability of the new metrics to pinpoint fragile clades and the sequences responsible. The new approach does not necessitate the investigation of alternative phylogenetic hypotheses, substitution models, or repeated data subset analyses. Our methodology offers a streamlined approach to evaluating major inferred clades and identifying sequences that may distort reconstructed phylogenies using large datasets.

Hydrochemical systematics and isotope (δ18O, δD and 3H) variations of aquifer system of southern Bengal Basin: implications for groundwater pollution.

Hydrogeological, hydrochemical and isotopic traits of the groundwater in the Quaternary aquifer system in an urban-periurban locality within and encircling the Kolkata-Howrah twin city in the south Bengal Basin have been synthesised to explain the present- and paleo-hydrological processes, surface and groundwater interaction and mixing dynamics of contamination of groundwater. Rock-weathering, evaporation, ion-exchange and active mineral dissolution are the key processes commanding the groundwater chemistry. Freshwater flushing from the recharge zones had thinned the entrapped sea water which has generated the present-day brackish water by a non-uniform fusion. The best-fit line of the plots of δD and δ18O of groundwater samples displays a slope lower than that of local meteoric water line (LMWL) and global meteoric water line (GMWL) which hints that isotopic constitution of the groundwater of the present area is primarily formed by evaporation before or in the recharging process. A wide range of δ18O values in groundwater suggests that these waters are not blended enough to remove dissimilarities in isotope configuration of recharge water. This also suggests that many groundwaters are a result of mixing of present-day recharge and an older integrant recharged under previously cooler climatic conditions. The groundwater samples are more depleted of oxygen at the shallower level. The depleted samples cluster around the Tolly's nala (canal) where upper aquitard is missing or < 10-m thick. The tritium values range between 0.70 and 15.02 which indicate the occurrence of 'sub-modern', 'a mix of modern and sub-modern water' and 'modern water'. It indicates mingling of isotope-depleted water from the Hugli River by means of Tolly's canal with relatively less-depleted groundwater of Kolkata's late Pleistocene aquifer. The tritium values and Cl/Br ratio of groundwater samples adjoining Tolly's canal and elsewhere refer the direct infiltration of 'modern wastewater and freshwater' which mixes with the 'sub-modern water' in the aquifer system.

Integrating Phylogenies with Chronology to Assemble the Tree of Life.

Reconstructing the global Tree of Life necessitates computational approaches to integrate numerous molecular phylogenies with limited species overlap into a comprehensive supertree. Our survey of published literature shows that individual phylogenies are frequently restricted to specific taxonomic groups due to the expertise of investigators and molecular evolutionary considerations, resulting in any given species present in a minuscule fraction of phylogenies. We present a novel approach, called the chronological supertree algorithm (Chrono-STA), that can build a supertree of species from such data by using node ages in published molecular phylogenies scaled to time. Chrono-STA builds a supertree of organisms by integrating chronological data from molecular timetrees. It fundamentally differs from existing approaches that generate consensus phylogenies from gene trees with missing taxa, as Chrono-STA does not impute nodal distances, use a guide tree as a backbone, or reduce phylogenies to quartets. Analyses of simulated and empirical datasets show that Chrono-STA can combine taxonomically restricted timetrees with extremely limited species overlap. For such data, approaches that impute missing distances or assemble phylogenetic quartets did not perform well. We conclude that integrating phylogenies via temporal dimension enhances the accuracy of reconstructed supertrees that are also scaled to time.

Impact of Microplastics on Pregnancy and Fetal Development: A Systematic Review.

Microplastic (MP) pollution is a growing global concern because of its potential to impair human health, particularly with regard to fetal development. However, the origins of prenatal MP exposure and its effects on fetal development have not been well studied. This study aimed to provide a systematic review of the literature regarding the impact of microplastics on pregnancy and fetal development. PubMed, Embase, ScienceDirect, Web of Science, Scopus, and Google Scholar were searched from 2010 until March 2024. Original publications exploring the impact of microplastics on pregnancy and fetal development were included in the study. After selecting papers, two independent reviewers extracted data regarding study characteristics, microplastics identified, and reproductive impacts. The quality of studies was assessed using the Critical Appraisal Checklists for Studies created by the Joanna Briggs Institute (JBI). Twelve studies, including 234 subjects, were selected from a total of 2,809 citations for the final qualitative analysis. Articles were published between 2021 and 2024, and most were conducted in China. The results of the included studies confirmed the existence of microplastics with varying sizes (2.1 to 100 micrometers) in the placenta and the fetal body. Studies revealed correlations between lifestyle choices and the presence of microplastics in the placenta. They also reported correlations between the level of microplastics and diminished microbiome diversity, reduced birthweights, affected gestational age, and fetal growth and development. Microplastics may be detrimental to a developing fetus during pregnancy. Nonetheless, more thorough research is required to comprehend the impact of microplastic exposure on pregnancy and fetal development.

Collection efficiencies of cylindrical and plane parallel ionization chambers: analytical and numerical results and implications for experimentally determined correction factors.

Objectives.To derive a collection efficiency formula,fGauss, for cylindrical ionization chambers in pulsed radiation beams from a volume recombination model of Boaget al(1996Phys. Med. Biol.41885-97) including free electrons. To validatefGaussand a parallel plate chamber formulafexpusing an ion transport code and calculate changes in collection efficiencies caused by electric field charge screening at 0.1-100 mGy doses-per-pulse. And to determine collection efficienciesCE∞predicted at infinite voltage in the absence of avalanche effects by fitting scaled formulae to efficiencies computed for 100-400 V chamber voltages and 10 and 100 mGy doses-per-pulse.Approach.Calculations were performed for an idealized parallel plate chamber with 2 mm electrode separationd, and for an idealized cylindrical chamber with 0.5 and 2.333 mm inner and electrode radiirinandrout.Main results.fGaussandfexppredict the same collection efficiencies for cylindrical and parallel plate chambers satisfyingd2=(rout2-rin2)ln(rout/rin)/2, an equivalence condition met by the chambers studied. Without charge screening, efficiencies computed using the code equalledfGaussandfexp. With screening, efficiencies changed by ⩽0.03%, ⩽1.1% and ⩽21.3% at 1, 10 and 100 mGy doses-per-pulse, and differed between the chambers by ⩽0.9% and ⩽19.6% at ⩽10 and 100 mGy dose-per-pulse. For fits offexpandfGauss,CE∞values were ⩽1.2% and ⩽17.6% from unity at 10 and 100 mGy per pulse respectively, closer than for other formulae tested.Significance.Allowing for screening,fGaussandfexpdescribed computed collection efficiencies to within 0.03%, 1.1% and 21.3% at doses-per-pulse ⩽1, 10 and 100 mGy. Equivalence of the two chambers broke down at 100 mGy per pulse. Departures ofCE∞values from unity suggest that collection efficiencies determined experimentally by fittingfGaussorfexpto readings made at multiple voltages will be accurate to within 1.2% and 17.6% at 10 and 100 mGy per pulse respectively.

Assessment of Potentially Malignant Disorders among Men and Women in South Bihar Population.

Oral cancer is detected in 270,000 people per annum or around 3% of all malignancies. It ranks sixth among males and twelve among females in terms of prevalence. Mostly, all oral squamous cell carcinomas (OSCC) are responsible for 92-95% of cases. Oral carcinoma starts five years before the average age of PMD patients, who range in age from 5th to 6th decade of life. Thus, the goal of this study is to identify any relevant risk factors and assess the incidence of oral possibly malignant disorders in both men and women living in rural Bhojpur District, Bihar. A cross-sectional study has been carried out at the Sadar Hospital in Bhojpur by surveying volunteers at various oral health screening and treatment camps held from January 2022 to July 2022. A pre-validated questionnaire adapted and modified from Kumar S et al. was utilized to collect data in a qualitative interview. It was discovered that (17%) of all people had an oral possibly malignant disease. OSMF was the lesion with the greatest prevalence (7%) and lichen planus having the smallest prevalence (1%). Malignancy frequently develops from oral potential malignant diseases. Diabetes and BMI were inversely related, which is expected provided the socioeconomic position.

miRNAs and genes as molecular regulators of rice grain morphology and yield.

Rice is one of the most consumed crops worldwide and the genetic and molecular basis of its grain yield attributes are well understood. Various studies have identified different yield-related parameters in rice that are regulated by the microRNAs (miRNAs). MiRNAs are endogenous small non-coding RNAs that silence gene expression during or after transcription. They control a variety of biological or genetic activities in plants including growth, development and response to stress. In this review, we have summarized the available information on the genetic control of panicle architecture and grain yield (number and morphology) in rice. The miRNA nodes that are associated with their regulation are also described while focussing on the central role of miR156-SPL node to highlight the co-regulation of two master regulators that determine the fate of panicle development. Since abiotic stresses are known to negatively affect yield, the impact of abiotic stress induced alterations on the levels of these miRNAs are also discussed to highlight the potential of miRNAs for regulating crop yields.

Renal resistive index measurements by ultrasound in patients with liver cirrhosis: Magnitude and associations with renal dysfunction.

BACKGROUND: The hemodynamic alterations seen in liver cirrhosis lead to renal vasoconstriction, ultimately causing acute kidney injury (AKI). The renal resistive index (RRI) is the most common Doppler ultrasound variable for measuring intrarenal vascular resistance. AIM: To evaluate the association of the RRI with AKI in patients with liver cirrhosis and to identify risk factors for high RRI. METHODS: This was a prospective observational study, where RRI was measured using Doppler ultrasound in 200 consecutive hospitalized patients with cirrhosis. The association of RRI with AKI was studied. The receiver operating characteristic (ROC) curve analysis was utilized to determine discriminatory cut-offs of RRI for various AKI phenotypes. Multivariate analysis was conducted to determine the predictors of high RRI. RESULTS: The mean patient age was 49.08 ± 11.68 years, with the majority (79.5%) being male; the predominant etiology of cirrhosis was alcohol (39%). The mean RRI for the study cohort was 0.68 ± 0.09, showing a progressive increase with higher Child-Pugh class of cirrhosis. Overall, AKI was present in 129 (64.5%) patients. The mean RRI was significantly higher in patients with AKI compared to those without it (0.72 ± 0.06 vs 0.60 ± 0.08; P < 0.001). A total of 82 patients (41%) had hepatorenal syndrome (HRS)-AKI, 29 (22.4%) had prerenal AKI (PRA), and 18 (13.9%) had acute tubular necrosis (ATN)-AKI. The mean RRI was significantly higher in the ATN-AKI (0.80 ± 0.02) and HRS-AKI (0.73 ± 0.03) groups than in the PRA (0.63 ± 0.07) and non-AKI (0.60 ± 0.07) groups. RRI demonstrated excellent discriminatory ability in distinguishing ATN-AKI from non-ATN-AKI (area under ROC curve: 93.9%). AKI emerged as an independent predictor of high RRI (adjusted odds ratio [OR]: 11.52), and high RRI independently predicted mortality among AKI patients (adjusted OR: 3.18). CONCLUSION: In cirrhosis patients, RRI exhibited a significant association with AKI, effectively differentiated between AKI phenotypes, and predicted AKI mortality.

Hepatogenous Diabetes as Compared to Type-2 Diabetes Mellitus and Non-diabetes in Patients With Liver Cirrhosis: Magnitude, Characteristics, and Implications.

Aim: Hepatogenous diabetes (HD) is frequently underestimated among cirrhosis patients. The current study assessed the magnitude, clinical characteristics, and implications of HD in cirrhosis patients as compared to the patients with type-2 diabetes mellitus (T2DM) and non-diabetes (ND) cirrhosis. Methods: In a prospective observational study, 338 consecutive eligible cirrhosis patients were screened for diabetes mellitus. A 2-hour oral glucose tolerance test (OGTT) was used to detect HD. The clinical characteristics, complications, and outcomes were ascertained and compared amongst HD, T2DM, and ND patients. Results: In the final study cohort of 316 patients, the proportion of HD, T2DM, and ND was 22.5% (n = 71), 26.3% (n = 83), and 51.3% (n = 162), respectively. HD was the predominant form of diabetes (68.9%) in Child-Pugh class-C cirrhosis. The majority (73%) of HD patients had abnormal OGTT without fasting hyperglycaemia. A lower cut-off of 98.5 mg/dl for fasting blood glucose had a modest sensitivity (72%) and specificity (75%) for predicting HD. In comparison to T2DM patients, HD patients were younger, leaner, and had more advanced cirrhosis. In comparison to ND patients, HD patients were leaner but had higher glycemic indices, serum cholesterol, and arterial ammonia levels. During a median follow-up period of 12 (03-21) months, the frequency of hepatic encephalopathy and variceal haemorrhage were higher in HD and T2DM patients compared to that in the ND group. Conclusions: HD is prevalent in about one fifth of cirrhosis patients. It differs from T2DM and ND in a number of ways, and has association with complications of cirrhosis.

Protocol for the isolation of tumor cell-derived extracellular vesicles followed by in vivo metastasis assessment in a murine ovarian cancer model.

Extracellular vesicles (EVs) play a crucial role in facilitating communication between cancer cells and their immediate or remote microenvironments, thereby promoting the extensive spread of cancer throughout the body. In this context, we present a protocol for the isolation of tumor cell-derived EVs followed by in vivo metastasis assessment in a murine ovarian cancer model. We describe steps for the isolation and characterization of EVs from ID8 cells, development of a metastatic mouse model, and sample preparation for flow cytometry. For complete details on the use and execution of this protocol, please refer to Gupta et al.1.

Uncovering sources, distribution, and seasonal patterns of trace element deposition: the elemental puzzle of the western Himalayas.

The transport and deposition of atmospheric pollutants in the Himalayas have a adverse impact on the climate, cryosphere, ecosystem, and monsoon patterns. Unfortunately, there is a insufficiency of data on trace element concentrations and behaviors in the high-altitude Himalayan region, leading to limited research in this area. This study presents a comprehensive and detailed comprehension of trace element deposition, its spatial distribution, seasonal variations, and anthropogenic signals in the high-altitude Kashmir region of the Western Himalayas. Our investigation involved the analysis of 10 trace elements (Al, Cr, Mn, Fe, Co, Ni, Cu, Zn, Cd, and Pb) in glacier ice, snow pits, surface snow, and rainwater collected at various sites including Kolahoi, Thajwas, Pahalgam (Greater Himalayan ranges), and Kongdori and Shopian (Pir Panjal Ranges) during 2021. The study reveals distinct ranges of concentrations for the trace elements at different sampling sites. Our analysis of trace element concentration depth profiles in snow pits reveals seasonal fluctuations during the deposition year. The highest concentrations were found in the autumn (below 20 cm) and summer (top layer), compared to the winter concentration (10-20 cm). The high enrichment factors (EFs) suggest the severity of human-induced trace metal deposition in the western Himalayan region, relative to surrounding regions. Surprisingly, the concentrations and EFs of trace elements showed seasonal contradictions, with lower concentration values and higher EFs during the non-monsoon season and vice versa. A source apportionment analysis using the positive matrix factorization (PMF) technique identified five sources of trace element deposition in the region, including crustal sources (32.33%), coal combustion (15.62%), biomass burning (17.63%), traffic emission (18.8%), and industrial sources (15.6%). Additionally, the study incorporated backward trajectories coupled with δ18O using the NOAA HYSPLIT model to estimate moisture sources in the region, which suggests atmospheric pollutants predominately deposited from the large-scale atmospheric circulation from westerlies (75%) during non-monsoon season. These findings underscore the urgent need for enhanced monitoring and research efforts in the future.

Some mechanistic underpinnings of molecular adaptations of SARS-COV-2 spike protein by integrating candidate adaptive polymorphisms with protein dynamics.

We integrate evolutionary predictions based on the neutral theory of molecular evolution with protein dynamics to generate mechanistic insight into the molecular adaptations of the SARS-COV-2 spike (S) protein. With this approach, we first identified candidate adaptive polymorphisms (CAPs) of the SARS-CoV-2 S protein and assessed the impact of these CAPs through dynamics analysis. Not only have we found that CAPs frequently overlap with well-known functional sites, but also, using several different dynamics-based metrics, we reveal the critical allosteric interplay between SARS-CoV-2 CAPs and the S protein binding sites with the human ACE2 (hACE2) protein. CAPs interact far differently with the hACE2 binding site residues in the open conformation of the S protein compared to the closed form. In particular, the CAP sites control the dynamics of binding residues in the open state, suggesting an allosteric control of hACE2 binding. We also explored the characteristic mutations of different SARS-CoV-2 strains to find dynamic hallmarks and potential effects of future mutations. Our analyses reveal that Delta strain-specific variants have non-additive (i.e., epistatic) interactions with CAP sites, whereas the less pathogenic Omicron strains have mostly additive mutations. Finally, our dynamics-based analysis suggests that the novel mutations observed in the Omicron strain epistatically interact with the CAP sites to help escape antibody binding.

Bedside assessment of sarcopenia in hospitalized patients with liver cirrhosis: Magnitude and clinical implications.

BACKGROUND: Sarcopenia is associated with many adverse outcomes in patients with cirrhosis. The tools currently in use for assessing sarcopenia have numerous flaws. We evaluated the utility of portable ultrasonography and a dynamometer for the bedside assessment of sarcopenia and its implications in hospitalized cirrhosis patients. METHODS: A dynamometer was used to test the hand-grip strength (HGS) and ultrasound was used to measure the thickness of the forearm and quadriceps muscles. HGS value < 27 kg for men and < 16 kg for women was taken as significant according to the European Working Group on Sarcopenia in Older People (EWGSOP2) criteria. The lower normal limit of muscle mass (5th percentile) was determined on 100 matched healthy controls. RESULTS: According to the EWGSOP2 criteria and HGS values, the prevalence of sarcopenia and probable sarcopenia among 300 cirrhosis patients were 56% and 62.3%, respectively. HGS alone identified sarcopenia in 88.9% of patients, while overestimated it in 6.3% of cases. The prevalence rate of sarcopenic obesity was 11%. Compared to patients without sarcopenia, sarcopenic patients had more complications of cirrhosis such as ascites, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, sepsis, hepatorenal syndrome and refractory ascites. In-hospital (p = 0.037), three-month (p < 0.001), and six-month (p < 0.001) mortality rates were all higher among sarcopenic patients. On cox regression survival analysis, overall six-month mortality was significantly higher in sarcopenic patients compared to patients without sarcopenia (hazard ratio, 6.37; 95% confidence interval, 3.15-12.8, p < 0.001). CONCLUSION: Bedside assessment of sarcopenia using a portable ultrasound machine and a dynamometer detects liver cirrhosis patients with high risk of complications and mortality.

Metagenomic exploration of Andaman region of the Indian Ocean.

Ocean microbiome is crucial for global biogeochemical cycles and primary productivity. Despite numerous studies investigating the global ocean microbiomes, the microbiome composition of the Andaman region of the Indian Ocean remains largely unexplored. While this region harbors pristine biological diversity, the escalating anthropogenic activities along coastal habitats exert an influence on the microbial ecology and impact the aquatic ecosystems. We investigated the microbiome composition in the coastal waters of the Andaman Islands by 16S rRNA gene amplicon and metagenomic shotgun sequencing approaches and compared it with the Tara Oceans Consortium. In the coastal waters of the Andaman Islands, a significantly higher abundance and diversity of Synechococcus species was observed with a higher abundance of photosynthesis pigment-related genes to adapt to variable light conditions and nutrition. In contrast, Prochlorococcus species showed higher abundance in open ocean water samples of the Indian Ocean region, with a relatively limited functional diversity. A higher abundance of antibiotic-resistance genes was also noted in the coastal waters region. We also updated the ocean microbiome gene catalog with 93,172 unique genes from the Andaman coastal water microbiome. This study provides valuable insights into the Indian Ocean microbiome and supplements the global marine microbial ecosystem studies.