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Abstract The study presented here aims at assessing the effects of hypobaric hypoxia on RAAS pathway and its components along with mitigation of anomalies with quercetin prophylaxis. One hour prior to hypobaric hypoxia exposure, male SD rats were orally supplemented with quercetin (50 mg/kg BW) and acetazolamide (50 mg/kg BW) and exposed them to 25,000 ft. (7,620 m) in a simulated environmental chamber for 12 h at 25 ± 2 °C. Different biochemical parameters like renin activity, aldosterone, angiotensin I, ACE 2 were determined in plasma. As a conventional response to low oxygen conditions, oxidative stress parameters (ROS and MDA) were elevated along with suppressed antioxidant system (GPx and catalase) in plasma of rats. Quercetin prophylaxis significantly down regulated the hypoxia induced oxidative stress by reducing plasma ROS & MDA levels with efficient enhancement of antioxidants (GPx and Catalase). Further, hypoxia mediated regulation of renin and ACE 2 proves the outstanding efficacy of quercetin in repudiating altercations in RAAS cascade due to hypobaric hypoxia. Furthermore, differential protein expression of HIF-1α, NFκB, IL-18 and endothelin-1 analyzed by western blotting approves the biochemical outcomes and showed that quercetin significantly aids in the reduction of inflammation under hypoxia. Studies conducted with Surface Plasmon Resonance demonstrated a binding among quercetin and ACE 2 that indicates that this flavonoid might regulate RAAS pathway via ACE 2. Henceforth, the study promotes the prophylaxis of quercetin for the better adaptability under hypobaric hypoxic conditions via modulating the RAAS pathway.

Abstract Millions of people worldwide visit, live or work in the hypoxic environment encountered at high altitudes and it is important to understand the biomolecular responses to this stress. This would help design mitigation strategies for high altitude illnesses. In spite of a number of studies spanning over 100 years, still the complex mechanisms controlling acclimatization to hypoxia remain largely unknown. To identify potential diagnostic, therapeutic and predictive markers for HA stress, it is important to comprehensively compare and analyse these studies. Towards this goal, HighAltitudeOmicsDB is a unique resource that provides a comprehensive, curated, user-friendly and detailed compilation of various genes/proteins which have been experimentally validated to be associated with various HA conditions, their protein–protein interactions (PPIs) and gene ontology (GO) semantic similarities. For each database entry, HighAltitudeOmicsDB additionally stores the level of regulation (up/down-regulation), fold change, study control group, duration and altitude of exposure, tissue of expression, source organism, level of hypoxia, method of experimental validation, place/country of study, ethnicity, geographical location etc. The database also collates information on disease and drug association, tissue-specific expression level, GO and KEGG pathway associations. The web resource is a unique server platform that offers interactive PPI networks and GO semantic similarity matrices among the interactors.These unique features help to offer mechanistic insights into the disease pathology. Hence, HighAltitudeOmicsDBis a unique platform for researchers working in this area to explore, fetch, compare and analyse HA-associated genes/proteins, their PPI networks, and GO semantic similarities. The database is available at http://www.altitudeomicsdb.in .

Abstract The oral cavity of human contains bacteria that are critical for maintaining the homeostasis of the body. External stressors such as high altitude (HA) and low oxygen affect the human gut, skin and oral microbiome. However, compared to the human gut and skin microbiome, studies demonstrating the impact of altitude on human oral microbiota are currently scarce. Alterations in the oral microbiome have been reported to be associated with various periodontal diseases. In light of the increased occurrence of HA oral health related problems, the effect of HA on the oral salivary microbiome was investigated. We conducted a pilot study in 16 male subjects at two different heights i.e., H1 (210 m) and H2 (4420 m). Total of 31 saliva samples,16 at H1 and 15 at H2 were analyzed by utilizing the 16S rRNA high-throughput sequencing, to explore the relationship between the HA environment and salivary microbiota. The preliminary results suggesting that, the most abundant microbiome at the phylum level are: Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. Interestingly, 11 genera were identified at the both heights with different relative abundances. In addition, the salivary microbiome was more diverse at H1 compared to H2 as demonstrated by decreased alpha diversity. Further, predicted functional results indicate that microbial metabolic profiles significantly decreased at H2 as compared to H1, including two major metabolic pathways involving carbohydrates, and amino acids. Our findings show that HA induces shifts in the composition and structure of human oral microbiota which can affect host health homeostasis.

Abstract Many genome annotations include false‐positive gene models, leading to errors in phylogenetic and comparative studies. Here, we propose a method to support gene model prediction based on evolutionary conservation and use it to identify potentially erroneous annotations. Using this method, we developed a set of 15,345 representative gene models from 12 legume assemblies that can be used to support genome annotations for other legumes.

Abstract Both genomics- and proteomics-based investigations have identified several essential genes, proteins, and pathways that may facilitate human adaptive genotype/phenotype in a population-specific manner. This comprehensive review provides an up-to-date list of genes and proteins identified for human adaptive responses to high altitudes. Genomics studies for indigenous high-altitude populations like Tibetans, Andeans, Ethiopians, and Sherpas have identified 169 genes under positive natural selection. Similarly, global proteomics studies have identified 258 proteins (± 1.2-fold or more) for Tibetan, Sherpa, and Ladakhi highlanders. The primary biological processes identified for genetic signatures include hypoxia-inducible factor (HIF)-mediated oxygen sensing, angiogenesis, and erythropoiesis. In contrast, major biological processes identified for proteomics signatures include 14–3-3 mediated sirtuin signaling, integrin-linked kinase (ILK), phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT), and integrin signaling. Comparing genetic and protein signatures, we identified 7 common genes/proteins (HBB/hemoglobin subunit beta, TF/serotransferrin, ANGPTL4/angiopoietin-related protein 4, CDC42/cell division control protein 42 homolog, GC/vitamin D-binding protein, IGFBP1/insulin-like growth factor-binding protein 1, and IGFBP2/insulin-like growth factor-binding protein 2) involved in crucial molecular functions like IGF-1 signaling, LXR/RXR activation, ferroptosis signaling, iron homeostasis signaling and regulation of cell cycle. Our combined multi-omics analysis identifies common molecular targets and pathways for human adaptation to high altitude. These observations further corroborate convergent positive selection of hypoxia-responsive molecular pathways in humans and advocate using multi-omics techniques for deciphering human adaptive responses to high altitude.

Abstract Background Aflatoxin contamination caused by Aspergillus fungi has been a serious factor affecting food safety of peanut (Arachis hypogaea L.) because aflatoxins are highly harmful for human and animal health. As three mechanisms of resistance to aflatoxin in peanut including shell infection resistance, seed infection resistance and aflatoxin production resistance exist among naturally evolved germplasm stocks, it is highly crucial to pyramid these three resistances for promoting peanut industry development and protecting consumers’ health. However, less research effort has been made yet to investigate the differentiation and genetic relationship among the three resistances in diversified peanut germplasm collections. Results In this study, the Chinese peanut mini-mini core collection selected from a large basic collection was systematically evaluated for the three resistances against A. flavus for the first time. The research revealed a wide variation among the diversified peanut accessions for all the three resistances. Totally, 14 resistant accessions were identified, including three with shell infection resistance, seven with seed infection resistance and five with aflatoxin production resistance. A special accession, Zh.h1312, was identified with both seed infection and aflatoxin production resistance. Among the five botanic types of A. hypogaea, the var. vulgaris (Spanish type) belonging to subspecies fastigiata is the only one which possessed all the three resistances. There was no close correlation between shell infection resistance and other two resistances, while there was a significant positive correlation between seed infection and toxin production resistance. All the three resistances had a significant negative correlation with pod or seed size. A total of 16 SNPs/InDels associated with the three resistances were identified through genome-wide association study (GWAS). Through comparative analysis, Zh.h1312 with seed infection resistance and aflatoxin production resistance was also revealed to possess all the resistance alleles of associated loci for seed infection index and aflatoxin content. Conclusions This study provided the first comprehensive understanding of differentiation of aflatoxin resistance in diversified peanut germplasm collection, and would further contribute to the genetic enhancement for resistance to aflatoxin contamination.

Ensuring international benefit-sharing from sequence data without jeopardising open sharing is a major obstacle for the Convention on Biological Diversity and other UN negotiations. Here, the authors propose a solution to address the concerns of both developing countries and life scientists.

Outbreak of COVID-19 pandemic in December 2019 affected millions of people globally. After substantial research, several biomarkers for COVID-19 have been validated however no specific and reliable biomarker for the prognosis of patients with COVID-19 infection exists. Present study was designed to identify specific biomarkers to predict COVID-19 severity and tool for formulating treatment. A small cohort of subjects (n = 43) were enrolled and categorized in four study groups; Dead (n = 16), Severe (n = 10) and Moderate (n = 7) patients and healthy controls (n = 10). Small RNA sequencing was done on Illumina platform after isolation of microRNA from peripheral blood. Differential expression (DE) of miRNA (patients groups compared to control) revealed 118 down-regulated and 103 up-regulated known miRNAs with fold change (FC) expression ≥2 folds and p ≤ 0.05. DE miRNAs were then subjected to functional enrichment and network analysis. Bioinformatic analysis resulted in 31 miRNAs (24 Down-regulated; 7 up-regulated) significantly associated with COVID-19 having AUC>0.8 obtained from ROC curve. Seventeen out of 31 DE miRNAs have been linked to COVID-19 in previous studies. Three miRNAs, hsa-miR-147b-5p and hsa-miR-107 (down-regulated) and hsa-miR-1299 (up-regulated) showed significant unique DE in Dead patients. Another set of 4 miRNAs, hsa-miR-224-5p (down-regulated) and hsa-miR-4659b-3p, hsa-miR-495-3p and hsa-miR-335-3p were differentially up-regulated uniquely in Severe patients. Members of three miRNA families, hsa-miR-20, hsa-miR-32 and hsa-miR-548 were significantly down-regulated in all patients group in comparison to healthy controls. Thus a distinct miRNA expression profile was observed in Dead, Severe and Moderate COVID-19 patients. Present study suggests a panel of miRNAs which identified in COVID-19 patients and could be utilized as potential diagnostic biomarkers for predicting COVID-19 severity.

Abstract Background Seed systems are considered as a vehicle through which the sustainable agricultural intensification can be achieved. However, most sub-Saharan African countries have been ineffective to provide sufficient incentives for stakeholders to consistently invest in the seed systems specifically for crops like sorghum. This study was therefore conducted to uncover investment opportunities for stakeholders in the sorghum seed systems to attain an impact-oriented seed production and delivery systems. Results The study applied descriptive statistics, Logit regression model, and Gross margin to analyze possible areas for investments. Descriptive statistics analyzed the percentage of farmers using sorghum improved varieties and sources used to obtained improved variety seeds. Logit regression model was applied to analyze factors correlating with planting of improved seeds. Gross margin was applied to show profitability of growing improved sorghum seeds and grain. Findings revealed that 39.2% of the sampled farmers were growing improved sorghum variety seeds. Farmers obtained improved variety seeds from both informal (57.8%) and formal (42.2%) sources. Logit estimates indicate that variety preference, unavailability of seeds, resistance to diseases, and drought had significant correlation with planting of improved variety seeds. Seed companies and quality declared seed (QDS) producers earned high margin of 53,08,900 Tanzanian Shillings per hectare (TZS/ha, 1 USD = 2315 TZS during the period of data collection) and 33,94,709 TZS/ha, respectively. Farmers using improved variety seed earned higher margin (8,19,805 TZS/ha) than farmers who did not use improved variety seeds (3,17,373 TZS/ha) Conclusions The identified investment opportunities were increasing number of farmers using improved variety seeds that would drive increased production, distribution, and marketing of quality seed. The large number of farmers still sourcing seed from the informal channel provides avenue to reach out to these farmers through demand creation and wide variety popularization meeting farmer preferences. The huge margin seed producers make provides good incentive to drive private seed companies and individual seed entrepreneurs to make sustainable business out of sorghum seed. The policy implications for reviving sorghum production and productivity are further discussed.

Abstract Ship voyage to Antarctica is a stressful journey for expedition members. The response of human gut microbiota to ship voyage and a feasible approach to maintain gut health, is still unexplored. The present findings describe a 24-day long longitudinal study involving 19 members from 38th Indian Antarctic Expedition, to investigate the impact of ship voyage and effect of probiotic intervention on gut microbiota. Fecal samples collected on day 0 as baseline and at the end of ship voyage (day 24), were analyzed using whole genome shotgun sequencing. Probiotic intervention reduced the sea sickness by 10% compared to 44% in placebo group. The gut microbiome in placebo group members on day 0 and day 24, indicated significant alteration compared to a marginal change in the microbial composition in probiotic group. Functional analysis revealed significant alterations in carbohydrate and amino acid metabolism. Carbohydrate-active enzymes analysis represented functional genes involved in glycoside hydrolases, glycosyltransferases and carbohydrate binding modules, for maintaining gut microbiome homeostasis. Suggesting thereby the possible mechanism of probiotic in stabilizing and restoring gut microflora during stressful ship journey. The present study is first of its kind, providing a feasible approach for protecting gut health during Antarctic expedition involving ship voyage.

Background: Present study aimed to identify DNA polymorphisms (variants) which can modulate the risk of COVID-19 infection progression to severe condition. TaqMan based SNP genotyping assay was performed for 11 single nucleotide polymorphisms (SNPs) in pro-coagulant and anti-coagulant genes. Methodology: A total of 33 COVID-19 patients, including dead, severe and moderately infected individuals were compared to 35 healthy controls. Both alleles in the SNP were labelled with two different fluorescent dyes (FAM and VIC) during assay formulation. DNA of study subjects were mixed with SNP assay and TaqMan master mix on 96 well PCR plate according to manufacturer’s protocol and RT-PCR was performed. Allelic discrimination assay gave clear results for presence of specific allele in each sample. Three SNPs were located in the pro-coagulant genes, another three involved in blood clot dissolution while rest five were in the genes encoding natural anti-coagulants. COVID-19 infected patients were further sub-divided into three groups, deceased (n = 16), severe (n = 10) and moderately infected (n = 7). Results: SNP genotyping showed significant differences between COVID-19 patients and controls in two SNPs, rs6133 in Selectin-P (SELP) and rs5361 in Selectin-E (SELE) gene. Also, rs2020921 and rs8176592, in clot dissolution genes, tissue Plasminogen activator (tPA) and tissue factor pathway inhibitor (TFPI) respectively showed significant genotypic and allelic difference in patients of COVID-19 compared to healthy controls. Further three SNPs rs2227589, rs757583846, and rs121918476 in natural anti-coagulant genes anti-thrombin III (ATIII), protein C (PROC), and protein S (PROS) respectively showed statistically significant difference between the study groups. Conclusion: Our findings indicate that gene variants, those involved in coagulation and anti-coagulation may play a major role in determining individual susceptibility to COVID-19.

The alarming pandemic situation of novel Severe Acute Respiratory Syndrome Coronavirus 2 (nSARS-CoV-2) infection, high drug development cost and slow process of drug discovery have made repositioning of existing drugs for therapeutics a popular alternative. It involves the repurposing of existing safe compounds which results in low overall development costs and shorter development timeline. In the present study, a computational network-biology approach has been used for comparing three candidate drugs i.e. quercetin, N-acetyl cysteine (NAC), and 2-deoxy-glucose (2-DG) to be effectively repurposed against COVID-19. For this, the associations between these drugs and genes of Severe Acute Respiratory Syndrome (SARS) and the Middle East Respiratory Syndrome (MERS) diseases were retrieved and a directed drug-gene-gene-disease interaction network was constructed. Further, to quantify the associations between a target gene and a disease gene, the shortest paths from the target gene to the disease genes were identified. A vector DV was calculated to represent the extent to which a disease gene was influenced by these drugs. Quercetin was quantified as the best among the three drugs, suited for repurposing with DV of -70.19, followed by NAC with DV of -39.99 and 2-DG with DV of -13.71. The drugs were also assessed for their safety and efficacy balance (in terms of therapeutic index) using network properties. It was found that quercetin was a forerunner than other two drugs.

Acute exposure to high altitude perturbs physiological parameters and induces an array of molecular changes in healthy lowlanders. However, activation of compensatory mechanisms and biological processes facilitates high altitude acclimatization. A large number of lowlanders stay at high altitude regions from weeks to months for work and professional commitments, and thus are vulnerable to altitude-associated disorders. Despite this, there is a scarcity of information for molecular changes associated with long-term stay at high altitudes. In the present study, we evaluated oxygen saturation (SpO2), heart rate (HR), and systolic and diastolic blood pressure (SBP and DBP) of lowlanders after short- (7 days, HA-D7) and long-term (3 months, HA-D150) stay at high altitudes, and used TMT-based proteomics studies to decipher plasma proteome alterations. We observed improvements in SpO2 levels after prolonged stay, while HR, SBP, and DBP remained elevated as compared with short-term stay. Plasma proteomics studies revealed higher levels of apolipoproteins APOB, APOCI, APOCIII, APOE, and APOL, and carbonic anhydrases (CA1 and CA2) during hypoxia exposure. Biological network analysis also identified profound alterations in lipoprotein-associated pathways like plasma lipoprotein assembly, VLDL clearance, chylomicron assembly, chylomicron remodeling, plasma lipoprotein clearance, and chylomicron clearance. In corroboration, lipid profiling revealed higher levels of total cholesterol (TC), triglycerides (TGs), low-density lipoprotein (LDL) for HA-D150 whereas high density lipoproteins (HDL) levels were lower as compared with HA-D7 and sea-level indicating dyslipidemia. We also observed higher levels of proinflammatory cytokines IL-6, TNFα, and CRP for HA-D150 along with oxidized LDL (oxLDL), suggesting vascular inflammation and proartherogenic propensity. These results demonstrate that long-term stay at high altitudes exacerbates dyslipidemia and associated disorders.

Chickpea has a profound nutritional and economic value in vegetarian society. Continuous decline in chickpea productivity is attributed to insufficient genetic variability and different environmental stresses. Chickpea like several other legumes is highly susceptible to terminal drought stress. Multiple genes control drought tolerance and ASR gene plays a key role in regulating different plant stresses. The present study describes the molecular characterization and functional role of Abscissic acid and stress ripening (ASR) gene from chickpea (Cicer arietinum) and the gene sequence identified was submitted to NCBI Genbank (MK937569). Molecular analysis using MUSCLE software proved that the ASR nucleotide sequences in different legumes show variations at various positions though ASR genes are conserved in chickpea with only few variations. Sequence similarity of ASR gene to chickpea putative ABA/WDS induced protein mRNA clearly indicated its potential involvement in drought tolerance. Physiological screening and qRT-PCR results demonstrated increased ASR gene expression under drought stress possibly enabled genotypes to perform better under stress. Conserved domain search, protein structure analysis, prediction and validation, network analysis using Phyre2, Swiss-PDB viewer, ProSA and STRING analysis established the role of hypothetical ASR protein NP_001351739.1 in mediating drought responses. NP_001351739.1 might have enhanced the ASR gene activity as a transcription factor regulating drought stress tolerance in chickpea. This study could be useful in identification of new ASR genes that play a major role in drought tolerance and also develop functional markers for chickpea improvement.

Genetic diversity among 40 chickpea (Cicer arietinum L.) genotypes was investigated using 125 microsatellite (SSR, simple sequence repeat) markers. Twenty five polymorphic markers with average genetic diversity and PIC (Polymorphic Information Content) value of 0.489 and 0.437, respectively, generated a total of 90 alleles. High PIC and gene diversity (HE) values indicated good variability amongst the chickpea genotypes. Sequential Agglomerative Hierarchical Non-overlapping (SAHN) grouping revealed two main clusters with 29 genotypes in cluster I and 11 genotypes in cluster II. The Cluster analysis did not follow geographical diversity rather it was in agreement for genetic diversity with respect to seed type and parentage/pedigree. Grouping clearly delineated the diverse kabuli and desi genotypes. Molecular variance analysis also indicated 97% variation within the populations and 3% variation among the populations. Principal coordinate analysis (PCoA) divided all the 40 genotypes into three populations based on their seed type and pedigree. The 2D plot largely supported the dendrogram with similar pattern of clustering. It also indicated that the material used was diverse. Thus, the study proved that SSR markers are informative tools for assessing genetic diversity and can be recommended for characterization studies in chickpea.

Access and use of seed of improved varieties of groundnut among farmers can improve farmers’ livelihoods and contribute to the potential of crop production in Tanzania. This paper analyzes factors underpinning the adoption of improved groundnut varieties among farmers to pave the way for upscaling quality seed used for increased production and commodity business in farming communities. A four-stage stratified sampling was used to collect data from 300 groundnut farmers in seven agro-ecological zones through individual interviews. Secondary data were collected from the literature and the Tanzania Agricultural Research Institute at Naliendele centre (TARI–Naliendele). Descriptive statistics and Probit regression model were used for data analysis. The empirical results showed that Johari 1985, Pendo 1998, Naliendele 2009, Mnanje 2009, Mangaka 2009 and Nachi 2015, are the main six improved groundnut varieties used by farmers, with Pendo 1998 having the highest adoption rate (17.1%). In the grain market, four varieties, namely Pendo 1998, Mnanje 2009, Nachi 2015 and Johari 1985, were observed to be highly preferred by grain off-takers. Furthermore, among the adopted improved varieties, Nachi 2015, is observed to be the most consistent high yielding variety, ranging from 1100 kg/ha to 1500 kg/ha in all agro-ecological zones. A farmer’s decision to adopt new varieties is affected by age and gender, farmer group membership, availability of improved seed and seed cost. Overall, male farmers are more likely to adopt improved varieties of groundnut than female farmers. The implications of these findings are also discussed, in particular in the area of policy support.

Malawi, in south-eastern Africa, is one of the poorest countries in the world. Food security in the country hinges on rainfed systems in which maize and sorghum are staple cereals and groundnut and pigeonpea are now major grain legume crops. While the country has experienced a considerable reduction in forest lands, population growth and demand for food production have seen an increase in the area dedicated to agricultural crops. From 2010, pigeonpea developed into a major export crop, and is commonly intercropped with cereals or grown in double-up legume systems. Information on the spatial extent of these crops is useful for estimating food supply, understanding export potential, and planning policy changes as examples of various applications. Remote sensing analysis offers a number of efficient approaches to deliver spatial, reproducible data on land use and land cover (LULC) and changes therein. Moderate Resolution Imaging Spectroradiometer (MODIS) products (fortnightly and monthly) and derived phenological parameters assist in mapping cropland areas during the agricultural season, with explicit focus on redistributed farmland. Owing to its low revisit time and the availability of long-term period data, MODIS offers several advantages, e.g., the possibility of obtaining cloud-free Normalized Difference Vegetation Index (NDVI) profile and an analysis using one methodology applied to one sensor at regular acquisition dates, avoiding incomparable results. To assess the expansion of areas used in the production of pigeonpea and groundnut resulting from the release of new varieties, the spatial distribution of cropland areas was mapped using MODIS NDVI 16-day time-series products (MOD13Q1) at a spatial resolution of 250 m for the years 2010−2011 and 2016−2017. The resultant cropland extent map was validated using intensive ground survey data. Pigeonpea is mostly grown in the southern dry districts of Mulanje, Phalombe, Chiradzulu, Blantyre and Mwanza and parts of Balaka and Chikwawa as a groundnut-pigeonpea intercrop, and sorghum-pigeonpea intercrop in Mzimba district. By 2016, groundnut extent had increased in Mwanza, Mulanje, and Phalombe and fallen in Mzimba. The result indicates that the area planted with pigeonpea had increased by 29% (75,000 ha) from 2010−2011 to 2016−2017. Pigeonpea expansion in recent years has resulted from major export opportunities to Asian countries like India, and its consumption by Asian expatriates all over the world. This study provides useful information for policy changes and the prioritization of resources allocated to sustainable food production and to support smallholder farmers.