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Abstract The agronomic stability and nutritional importance of 30 (Test genotypes: 29 + Check: 1 = 30) promising horse gram mutants were evaluated in this multi-environment-based experiment (MEE). Attempts were made to (i) identify stable mutants for agronomic traits through AMMI and GGE biplot models, (ii) quantify nutritional traits, (iii) understand the linkage between yield and nutritional traits, and (iv) estimate physical (PP) and cooking properties (CP) of selected genotypes to fix their food-chain usability. The ANOVA of the pooled data exhibited significant differences among environments (E), genotypes (G), and GxE interaction. The combined AMMI and GGE results helped to identify a few good-yielding and stable genotypes (GYSM) (G1, G25, G3, and G27). The yield advantages of these GYSMs over the parent PAIYUR 2 are 42.99%, 34.63%, 28.68%, and 30.59% respectively. The nutrient profiling of mutants revealed (i) a significant coefficient of variation for macronutrients (fat: 29.98%; fibre: 20.72%, and protein: 5.01%), (ii) a good range of variation for micronutrients, and (iii) helped to identify macro (MaNSM) and micro nutrient-specific mutants (MiNSM). The relationship analysis between yield and nutrient traits ascertained that yield had (i) positivity with protein (r2 = 0.69) and negativity for micronutrients except for Mn (r2 = 0.63), Cu (r2 = 0.46), and B (r2 = 0.01) in GYSM, (ii) positivity with protein and fibre in MaNSM, and (iii) negativity with micronutrients in MiNSM. Of the GYSM, G1 and G25 offer scope for commercial exploitation, and their PP and CP analyses revealed that G1 can be used for pastry and baked product preparation while G25 for weaning foods. Cooking time exhibited positivity with seed size parameters and negativity with water absorption capacity (r2 = − 0.53). An LC–MS–MS-based amino acid (AA) fractionation study showed the effect of induced mutagenesis on the contents of amino acids and also revealed the significance of horse gram for its lysine and methionine contents.

Abstract Most high-risk neuroblastomas that initially respond to therapy will ultimately relapse. Currently, no curative treatment is available. Acquired genetic/molecular rearrangement in therapy-resistant cells contributes to tumor relapse. Recently, we identified significant RD3 loss in progressive disease (PD) and defined its association with advanced disease-stage and poor clinical outcomes. Here, we investigated whether RD3 loss is an acquired process in cells that survive intensive multi-modal clinical therapy (IMCT) and its significance in disease evolution. RD3 status (mRNA, protein) during diagnosis (Dx) and PD after IMCT was investigated in NB patient cohort (n = 106), stage-4 NB cell lines (n = 15) with known treatment status and validated with independent data from another set of 15 cell-lines. Loss of RD3 in metastatic disease was examined using a mouse model of PD and metastatic-site-derived aggressive cells (MSDACs) ex vivo. RD3 silencing/expression assessed changes in metastatic state. Influence of RD3 loss in therapy resistance was examined through independent in vitro and in vivo studies. A significant loss of RD3 mRNA and protein was observed in resistant cells derived from patients with PD after IMCT. This is true to the effect within and between patients. Results from the mouse model identified significant transcriptional/translational loss of RD3 in metastatic tumors and MSDACs. RD3 re-expression in MSDACs and silencing RD3 in parental cells defined the functional relevance of RD3-loss in PD pathogenesis. Analysis of independent studies with salvage therapeutic agents affirmed RD3 loss in surviving resistant cells and residual tumors. The profound reductions in RD3 transcription indicate the de novo regulation of RD3 synthesis in resistant cells after IMCT. Defining RD3 loss in PD and the benefit of targeted reinforcement could improve salvage therapy for progressive neuroblastoma.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

During the COVID-19 pandemic, wastewater surveillance of the SARS CoV-2 virus has been demonstrated to be effective for population surveillance at the county level down to the building level. At the University of California, San Diego, daily high-resolution wastewater surveillance conducted at the building level is being used to identify potential undiagnosed infections and trigger notification of residents and responsive testing, but the optimal determinants for notifications are unknown. To fill this gap, we propose a pipeline for data processing and identifying features of a series of wastewater test results that can predict the presence of COVID-19 in residences associated with the test sites. Using time series of wastewater results and individual testing results during periods of routine asymptomatic testing among UCSD students from 11/2020 to 11/2021, we develop hierarchical classification/decision tree models to select the most informative wastewater features (patterns of results) which predict individual infections. We find that the best predictor of positive individual level tests in residence buildings is whether or not the wastewater samples were positive in at least 3 of the past 7 days. We also demonstrate that the tree models outperform a wide range of other statistical and machine models in predicting the individual COVID-19 infections while preserving interpretability. Results of this study have been used to refine campus-wide guidelines and email notification systems to alert residents of potential infections., (© 2023. The Author(s).)

Research on heterosexual mating has demonstrated that acoustic parameters (e.g., pitch) of men's voices influence their attractiveness to women and appearance of status and formidability to other men. However, little is known about how men's tendency to clearly articulate their speech influences these important social perceptions. In the current study, we used a repeated-measures design to investigate how men's articulatory clarity or conformity influenced women's (N = 45) evaluations of men's attractiveness for both short- and long-term relationships, and men's (N = 46) evaluations of physical formidability and prestige. Results largely supported our hypotheses: men who enunciated phonemes more distinctly were more attractive to women for long-term relationships than short-term relationships and were perceived by other men to have higher prestige than physical dominance. These findings suggest that aspects of articulatory behavior that influence perceptions of prestige and long-term mating attractiveness may indicate an early social history characterized by high socioeconomic status, likely owing to crystallization of articulatory patterns during the critical period of language development. These articulatory patterns may also be honest signals of condition or disposition owing to the nature of complex, multicomponent traits, which deserve further empirical attention., (© 2023. The Author(s).)

A novel antibacterial immunostimulant using Platinum nanoparticles (PtNPs) and lectin from Metapenaeus dobsoni (Md-Lec) was developed. The Md-Lec and PtNPs (Pt-lec) hybrid formed through non-covalent interaction exhibits antimicrobial activity against fish specific pathogens by affecting membrane integrity and producing excess reactive oxygen species. The therapeutic efficacy of Pt-lec was demonstrated through rescuing Aeromonas hydrophila infected Nile Tilapia. Pt-lec prevents the infection spreading and reduces the bacterial bioburden in less than 12 h, and as a result of this the fish were restored to normalcy. To assess immunostimulation, we studied the expression of three different immune related genes, namely LEC, Myd88 and COX-2 in the gills, liver, spleen and kidney of fish under various experimental conditions. Our results showed that Pt-lec treatment appeared to be better when compared to lectin alone in enhancing the expression of Myd88 and COX-2, but LEC was not as expected. These results suggest that Pt-lec has the ability to protect Nile Tilapia against bacterial infection by restricting bacterial bioburden through their direct effects on the bacterial membrane and indirectly through their effects on host immune-related gene expression. This hybrid could have potential "green" application in fish farming in rescuing infected animals when compared to widely and unregulated antibiotics., (© 2023. The Author(s).)

This study aims to systematically review the diagnostic accuracy of a digital blood pressure measurement device compared to the gold standard mercury sphygmomanometer in published studies. Searches were conducted in PubMed, Cochrane, EBSCO, EMBASE and Google Scholar host databases using the specific search strategy and filters from 1st January 2000 to 3rd April 2021. We included studies reporting data on the sensitivity or specificity of blood pressure measured by digital devices and mercury sphygmomanometer used as the reference standard. Studies conducted among children, special populations, and specific disease groups were excluded. We considered published manuscripts in the English language only. The risk of bias and applicability concerns were assessed based on the author's judgment using the QUADAS2 manual measurement evaluation tool. Based on the screening, four studies were included in the final analysis. Sensitivity, specificity, diagnostic odds ratio (DOR), and 95% confidence interval were estimated. The digital blood pressure monitoring has a moderate level of accuracy and the device can correctly distinguish hypertension with a pooled estimate sensitivity of 65.7% and specificity of 95.9%. After removing one study, which had very low sensitivity and very high specificity, the pooled sensitivity estimate was 79%, and the specificity was 91%. The meta-analysis of DOR suggests that the digital blood pressure monitor had moderate accuracy with a mercury sphygmomanometer. This will provide the clinician and patients with accurate information on blood pressure with which diagnostic and treatment decisions could be made., (© 2022. The Author(s).)

3,4-dihydroxy-2-butanone-4-phosphate synthase (DHBPS) catalyzes the conversion of D-ribulose 5-phosphate (Ru5P) to L-3,4-dihydroxy-2-butanone-4-phosphate in the presence of Mg 2+ . Although crystal structures of DHBPS in complex with Ru5P and non-catalytic metal ions have been reported, structure with Ru5P along with Mg 2+ is still elusive. Therefore, mechanistic role played by Mg 2+ in the structure of DHBPS is poorly understood. In this study, molecular dynamics simulations of DHBPS-Ru5P complex along with Mg 2+ have shown entry of Mg 2+ from bulk solvent into active site. Presence of Mg 2+ in active site has constrained conformations of Ru5P and has reduced flexibility of loop-2. Formation of hydrogen bonds among Thr-108 and residues - Gly-109, Val-110, Ser-111, and Asp-114 are found to be critical for entry of Mg 2+ into active site. Subsequent in silico mutations of residues, Thr-108 and Asp-114 have substantiated the importance of these interactions. Loop-4 of one monomer is being proposed to act as a "lid" covering the active site of other monomer. Further, the conserved nature of residues taking part in the transfer of Mg 2+ suggests the same mechanism being present in DHBPS of other microorganisms. Thus, this study provides insights into the functioning of DHBPS that can be used for the designing of inhibitors.

Cellulase catalyzes the hydrolysis of β-1,4-linkages of cellulose to produce industrially relevant monomeric subunits. Cellulases find their applications in pulp and paper, laundry, food and feed, textile, brewing industry and in biofuel production. These industries always have great demand for cellulases that can work efficiently even in harsh conditions such as high salt, heat, and acidic environments. While, cellulases with high thermal and acidic stability are already in use, existence of a high halotolerant cellulase is still elusive. Here, we report a novel cellulase Cel5R, obtained from soil metagenome that shows high halotolerance and thermal stability. The biochemical and functional characterization of Cel5R revealed its endoglucanase activity and high halostability. In addition, the crystal structure of Cel5R determined at 2.2 Å resolution reveals a large number of acidic residues on the surface of the protein that contribute to the halophilic nature of this enzyme. Moreover, we demonstrate that the four free and non-conserved cysteine residues (C65, C90, C231 and C273) contributes to the thermal stability of Cel5R by alanine scanning experiments. Thus, the newly identified endoglucanase Cel5R is a promising candidate for various industrial applications.

Lack of an in vitro model of metastasis has been a major impediment in understanding the molecular regulation of metastatic processes, and identification of specific therapeutic targets. We have established an in vitro model which displayed the signatures of metastatic phenotype such as migration, invasiveness, chemoresistance and expression of cancer stem-cell markers. This in vitro model was developed by the induction of reversal of multicellular spheroids that were generated by anchorage-independent growth. In vivo data further validated the metastatic phenotype of the in vitro model. Besides delineating the molecular events of metastasis, this model could also improve the screening efficiency of antimetastatic agents.