Antagonistic potential and biological control mechanisms of Pseudomonas strains against banded leaf and sheath blight disease of maize.

Rhizoctonia solani, the causal agent of banded leaf and sheath blight (BL&SB), poses a significant threat to maize and various crops globally. The increasing concerns surrounding the environmental and health impacts of chemical fungicides have encouraged intensified concern in the development of biological control agents (BCAs) as eco-friendly alternatives. In this study, we explored the potential of 22 rhizobacteria strains (AS1-AS22) isolates, recovered from the grasslands of the Pithoragarh region in the Central Himalayas, as effective BCAs against BL&SB disease. Among these strains, two Pseudomonas isolates, AS19 and AS21, exhibited pronounced inhibition of fungal mycelium growth in vitro, with respective inhibition rates of 57.04% and 54.15% in cell cultures and 66.56% and 65.60% in cell-free culture filtrates. Additionally, both strains demonstrated effective suppression of sclerotium growth. The strains AS19 and AS21 were identified as Pseudomonas sp. by 16S rDNA phylogeny and deposited under accession numbers NAIMCC-B-02303 and NAIMCC-B-02304, respectively. Further investigations revealed the mechanisms of action of AS19 and AS21, demonstrating their ability to induce systemic resistance (ISR) and exhibit broad-spectrum antifungal activity against Alternaria triticina, Bipolaris sorokiniana, Rhizoctonia maydis, and Fusarium oxysporum f. sp. lentis. Pot trials demonstrated significant reductions in BL&SB disease incidence (DI) following foliar applications of AS19 and AS21, with reductions ranging from 25 to 38.33% compared to control treatments. Scanning electron microscopy revealed substantial degradation of fungal mycelium by the strains, accompanied by the production of hydrolytic enzymes. These findings suggest the potential of Pseudomonas strains AS19 and AS21 as promising BCAs against BL&SB and other fungal pathogens. However, further field trials are warranted to validate their efficacy under natural conditions and elucidate the specific bacterial metabolites responsible for inducing systemic resistance. This study contributes to the advancement of sustainable disease management strategies and emphasizes the potential of Pseudomonas strains AS19 and AS21 in combating BL&SB and other fungal diseases affecting agricultural crops.

Comprehensive Genetic Study of a Monozygotic Triplet Discordant for Autism Spectrum Disorder.

There are a few comprehensive genetic studies on autism spectrum disorders (ASD) in India. Children of multiple births are valuable for genomics studies of complex disorders such as ASD. We report whole-exome sequencing (WES) in a triplet family in which only one among the triplet has ASD. The objective of this study was to identify potential candidate genes for ASD. Exome DNA was enriched using a twist human customized core exome kit, and paired-end sequencing was performed. Proband-specific de novo variants included 150 single nucleotide polymorphisms (SNPs) and 74 indels. Thirteen SNPs were in exonic regions, 7 of them being missense variations. Seventeen variants were previously reported in ASD. Genes harboring variants have functions in the development and maintenance of the central nervous system and are enriched in biological processes involving cell adhesion. This is the first comprehensive genetic study of a monozygotic triplet in ASD.

Mass Production of Arbuscular Mycorrhizal Fungi on the Sorghum Plants Inoculated with Burkholderia arboris Using Soybean Mill Waste and Vermicompost-Amended Soil-Sand Substrate.

Arbuscular mycorrhizal (AM) fungi are being used as a new generation of biofertilizers to increase plant growth by improving plant nutrition and bio-protection. However, because of the obligatory nature of the plant host, large-scale multiplication of AM propagules is challenging, which limits its applicability. This study evaluates the ability of Burkholderia arboris to increase AM production in soybean mill waste and vermicompost amended by soil-sand mixture planted with sorghum as a host plant. The experiment was conducted in a nursery using a completely randomized design with four inoculation treatments (B. arboris, AM fungi, B. arboris + AM fungi, and control) under sterilized and unsterilized conditions. AM production was investigated microscopically (spore density and root colonization), and biochemically (AM-specific lipid biomarker, 16:1ω5cis derived from neutral lipid fatty acid (NLFA), and phospholipid fatty acid (PLFA) fractions from both soil and roots). Integrating B. arboris with AM fungi in organically amended pots was found to increase AM fungal production by 62.16 spores g-1 soil and root colonization by 80.85%. Biochemical parameters also increased with B. arboris inoculation: 5.49 nmol PLFA g-1 soil and 692.68 nmol PLFA g-1 root and 36.72 nmol NLFA g-1 soil and 3147.57 nmol NLFA g-1 root. Co-inoculation also increased glomalin-related soil protein and root biomass. Principal component analysis (PCA) further supported the higher contribution of B. arboris to AM fungi production under unsterilized conditions. In conclusion, inoculation of AM plant host seeds with B. arboris prior to sowing into organic potting mix could be a promising and cost-effective approach for increasing AM inoculum density for commercial production. Furthermore, efforts need to be made for up-scaling the AM production with different plant hosts and soil-substrate types.

Molecular surveillance of dengue virus in field-collected Aedes mosquitoes from Bhopal, central India: evidence of circulation of a new lineage of serotype 2.

Introduction: Dengue fever is hyperendemic in several Southeast and South Asian countries, including India, with all four serotypes (DENV 1-4) circulating at different periods and in different locations. Sustainable and improved virological and entomological surveillance is the only tool to prevent dengue and other vector-borne diseases. Objectives: The present study has been carried out to detect and characterize the circulating dengue virus (DENV) in field-collected Aedes mosquitoes in Bhopal, Central India. Methods: Aedes mosquitoes were collected from 29 localities within Bhopal city during October 2020 to September 2022. DENV infection was assessed in the individual head and thorax regions of Aedes mosquitoes using reverse transcriptase PCR. Positive samples were sequenced, and the circulating serotypes and genotypes were determined using phylogenetic analysis. Results: DENV RNA was detected in 7 Aedes aegypti and 1 Aedes albopictus, with infection rates of 0.59 and 0.14%, respectively. Phylogenetic analysis revealed all the isolates belonged to DENV serotype 2 and distinctly clustered with the non-Indian lineage (cosmopolitan genotype 4a), which was not recorded from the study area earlier. The time to most common recent ancestor (TMRCA) of these sequences was 7.4 years old, with the highest posterior density (HPD) of 3.5-12.2 years, indicating that this new lineage emerged during the year 2014. This is the first report on the DENV incrimination in both Ae. aegypti and Ae. albopictus mosquitoes collected from Bhopal, Central India. Conclusion: The observed emergence of the non-Indian lineage of DENV-2 in Bhopal, which again is a first report from the area, coincides with the gradual increase in DENV cases in Bhopal since 2014. This study emphasizes the importance of DENV surveillance and risk assessment in this strategically important part of the country to decipher its outbreak and severe disease-causing potential.

Prevalence of chronic kidney disease among severely gas-exposed survivors in Bhopal, India.

Background The survivors of the 1984 Bhopal gas disaster frequently express concern of them being at higher risk of developing chronic kidney disease (CKD) as a consequence of the long-term health effects of gas exposure. We aimed to estimate the prevalence of CKD among the survivors of severely gas-exposed cohort assembled in 1985 after the Bhopal gas disaster to study the long-term health consequences of gas exposure. Methods We did this cross-sectional study with a sample size of 215 systematically selected participants among the severely gas-exposed survivors in Bhopal to estimate the prevalence of CKD. Sociodemographic and relevant past medical history of the participants was obtained using a semi-structured questionnaire and their blood and urine samples were collected. The estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease equation. Those found with reduced e-GFR and proteinuria, suggestive of CKD, were further surveyed after 3 months to differentiate CKD from acute renal damage. Results The prevalence of CKD among the severely gas-exposed cohort survivors in Bhopal was 16.7%. Multiple logistic regression analysis revealed that body mass index and level of education were significant predictors of CKD. Conclusion The prevalence of CKD among the severely exposed survivors of Bhopal was at par with the national prevalence, putting at rest the apprehension of gas-exposed survivors of being at higher risk of developing CKD.

Enhancing Biotic Stress Tolerance in Soybean Affected by Rhizoctonia solani Root Rot Through an Integrated Approach of Biocontrol Agent and Fungicide.

Rhizoctonia solani causes root rot in soybean, a worldwide severe concern for soybean cultivation. The fungus grows and clogs the xylem tissue of the host plant by producing numerous sclerotia, which results in disease symptoms, such as yellowing of leaves, wilt, and plant death. Overuse of chemical fungicides increases the threat of developing resistance to pathogens, reduces soil productivity, and negatively impacts the health of the soil, the environment, and humans. An integrated pest management strategy improves crop yield, profit, and safety. The present study focused on a fungicide (carbendazim) compatibility test with a biocontrol agent (Pseudomonas fluorescence). It evaluated the effect of this combined approach on photosynthetic reactions and growth in soybean in the presence of the fungal pathogen R. solani. The study showed that P. fluorescence significantly inhibited the mycelial growth of R. solani (43%) and tolerated 0.05-0.15% concentration of carbendazim. This confirms the suitability compatibility of P. fluorescence with chemical fungicides for IPM. These novel blending significantly reduced the disease incidence by about 75%, and a 72% decrease in disease severity was observed compared to pathogen control. Moreover, this combined approach has also improved plant growth, yield parameters, and photosynthetic efficiency in the presence of R. solani treated with an integrated system showed better overall growth despite being infected by the pathogen.

An interpretable block-attention network for identifying regulatory feature interactions.

The importance of regulatory features in health and disease is increasing, making it crucial to identify the hallmarks of these features. Self-attention networks (SAN) have given rise to numerous models for the prediction of complex phenomena. But the potential of SANs in biological models was limited because of high memory requirement proportional to input token length and lack of interpretability of self-attention scores. To overcome these constraints, we propose a deep learning model named Interpretable Self-Attention Network for REGulatory interactions (ISANREG) that combines both block self-attention and attention-attribution mechanisms. This model predicts transcription factor-bound motif instances and DNA-mediated TF-TF interactions using self-attention attribution scores derived from the network, overcoming the limitations of previous deep learning models. ISANREG will serve as a framework for other biological models in interpreting the contribution of the input with single-nucleotide resolution.

Exploring potential soybean bradyrhizobia from high trehalose-accumulating soybean genotypes for improved symbiotic effectiveness in soybean.

Drought is the most important factor limiting the activity of rhizobia during N-fixation and plant growth. In the present study, we isolated Bradyrhizobium spp. from root nodules of higher trehalose-accumulating soybean genotypes and examined for moisture stress tolerance on a gradient of polyethylene glycol (PEG 6000) amended in yeast extract mannitol (YEM) broth. In addition, the bradyrhizobial strains were also evaluated for symbiotic effectiveness on soybean. Based on 16S rDNA gene sequences, four bradyrhizobial species were recovered from high trehalose-accumulating genotypes, i.e., two Bradyrhizobium liaoningense strains (accession number KX230053, KX230054) from EC 538828 and PK-472, respectively, one Bradyrhizobium daqingense (accession number KX230052) from PK-472, and one Bradyrhizobium kavangense (accession number MN197775) from Valder genotype having low trehalose. These strains, along with two native strains, viz., Bradyrhizobium japonicum (JF792425), Bradyrhizobium liaoningense (JF792426), and one commercial rhizobium, were studied for nodulation, leghaemoglobin, and N-fixation abilities on soybean under sterilized sand microcosm conditions in a completely randomized design. Among all the strains, D-4A (B. daqingense) followed by D-4B (B. liaoningense) was found to have significantly higher nodulation traits and acetylene reduction assay (ARA) activity when compared to other strains and commercial rhizobia. The bradyrhizobia isolates showed plant growth promotion traits such as indole acetic acid (IAA), exopolysaccharide (EPS), and siderophore production, phosphate-solubilizing potential, and proline accumulation. The novel species B. daqingense was reported for the first time from Indian soil and observed to be a potential candidate strain and should be evaluated for conferring drought tolerance in soybean under simulated stress conditions.

An assessment of remotely sensed environmental variables on Dengue epidemiology in Central India.

In recent decades, dengue has been expanding rapidly in the tropical cities. Even though environmental factors and landscape features profoundly impact dengue vector abundance and disease epidemiology, significant gaps exist in understanding the role of local environmental heterogeneity on dengue epidemiology in India. In this study, we assessed the role of remotely sensed climatic factors (rainfall, temperature and humidity) and landscape variables (land use pattern, vegetation and built up density) on dengue incidence (2012-2019) in Bhopal city, Central India. Dengue hotspots in the city were assessed through geographical information system based spatial statistics. Dengue incidence increased from 0.59 cases in 2012 to 9.11 cases in 2019 per 10,000 inhabitants, and wards located in Southern Bhopal were found to be dengue hotspots. Distributed lag non-linear model combined with quasi Poisson regression was used to assess the exposure-response association, relative risk (RR), and delayed effects of environmental factors on dengue incidence. The analysis revealed a non-linear relationship between meteorological variables and dengue cases. The model shows that the risk of dengue cases increases with increasing mean temperature, rainfall and absolute humidity. The highest RR of dengue cases (~2.0) was observed for absolute humidity ≥60 g/m3 with a 5-15 week lag. Rapid urbanization assessed by an increase in the built-up area (a 9.1% increase in 2020 compared to 2014) could also be a key factor driving dengue incidence in Bhopal city. The study sheds important insight into the synergistic effects of both the landscape and climatic factors on the transmission dynamics of dengue. Furthermore, the study provides key baseline information on the climatic variables that can be used in the micro-level dengue prediction models in Bhopal and other cities with similar climatic conditions.

A Comparative Study of Functional Outcome Following Dynamic Hip Screw and Proximal Femoral Nailing for Intertrochanteric Fractures of the Femur.

Introduction Intertrochanteric fractures are common in the old age group. The goal/aim of the treatment for intertrochanteric fractures will be to nearly restore pre-injury condition as early as it is possible. Dynamic hip screw (DHS) and proximal femoral nailing (PFN) have been the two standard treatment methods used for treating these kinds of fractures. The main goal of this proposed study was to compare functional outcomes of two available fixation devices for inter-trochanteric fracture using Harris hip scoring. The aim of this study is to compare the functional outcome of the DHS and PFN for the treatment of Intertrochanteric hip fractures achieved by the patient based on Harris hip score. Methods and materials The clinical methodology for the study consists of 46 cases of Inter-trochanteric fractures of femur that meet the inclusion criteria of patients aged above 45 years diagnosed with closed intertrochanteric fractures that are less than three weeks duration who were able to walk prior to fracture and exclusion criteria, admitted to R L Jalappa Hospital, Tamaka, Kolar between November 2019 and November 2021. The patients were divided into two groups, group A treated with DHS and group B treated with PFN and followed up at six weeks, 12 weeks, and 24 weeks based on the functional outcome on the 24th week using Harris hip score. Results A total of 46 patients were included in the study. The mean age in Group DHS was 61.09 ± 11.69 and in Group PFN was 65 ± 14.98. In the group of DHS, nine out of 23 patients were male and 14 out of 23 patients were female patients. In a group of PFN, 12 out of 23 patients were male and 11 out of 23 patients were female. The mean six weeks score in Group DHS was 34.43 ± 3.23 out of 100 and in Group PFN was 34.35 ± 2.5 out of 100. The mean Harris hip score in Group DHS was 84.3 ± 7.68 out of 100. The mean Harris hip score in Group PFN was 89.26 ± 6.53 out of 100. In Group DHS, 52.17% had injuries on the left side and 47.83% had on the right side. In Group PFN, 39.13% had Injury on the left side and 60.87% had on the right side. In Group DHS, results were excellent in 34.78% (eight patients), good in 43.48% (10 patients), fair in 17.39% (four patients out of 23 patients), and poor in 4.35% (one patient). In Group PFN, results were excellent in 56.52% (13 patients), good in 34.78% (eight patients), and fair in 8.70% (two patients). Conclusion From the study, it can be concluded that PFN had a better outcome in intertrochanteric fractures compared to DHS. The highest percentage of subjects in the PFN group had excellent to a good outcome and none of them had poor outcomes when compared to the DHS group. PFN group had higher scores of Harris hip score at 12 weeks, 24 weeks, and at the end of follow-up.

Biosurfactant from Bacillus sp. A5F Reduces Disease Incidence of Sclerotinia sclerotiorum in Soybean Crop.

The present study was conducted to assess the biocontrol activity of biosurfactants obtained from Bacillus species A5F. The variables significantly influencing the production of biosurfactants under in vitro conditions were further optimized using response surface methodology. Optimal values of selected culture variables, i.e., glucose, soybean oil, and incubation time were 3.5 g l-1, 3.5 ml l-1, and 78 h, respectively, resulting in 2.14-fold enhancement in biosurfactant levels in 5 l fermentor. Identified biosurfactants had a significant effect on chlorophyll content, shoot biomass, number of pods, and seed weight. Biosurfactants also reduced the disease incidence in S. sclerotiorum infected soybean plants and showed antagonistic action against major phytopathogens by disrupting the hyphal cell wall. 16% reduction in ITS gene copy number was observed as compared to control with less non-target effect upon biosurfactant spray on foliar parts of soybean. Thus, the study confirms that biosurfactants from strain A5F can be used as a potent biocontrol agent to control sclerotium wilt on soybean plants.

Amelioration in traditional farming system by exploring the different plant growth-promoting attributes of endophytes for sustainable agriculture.

Agriculture demands environmentally friendly, economic and stable agro-practices for achievement of global food security challenges. Exploration of beneficial plant-microbe interactions and input of microbial inoculants has been getting great attention for improvement of traditional agriculture system. Endophytes are beneficial partners of plants; they live inside the host with mutual association. The advantageous role of endophytes is gaining great importance from last century in agricultural research due to their valuable role in enhancement of crop yield and disease management. Endophytes exhibit various plant growth-promoting attributes by production of many bioactive metabolites and by different mechanisms. Development of modern biotechnological approaches to explore the hidden interaction of plants and microbes can be useful tools for establishment of novel bioinoculants for particular crop. In this review, we provide the knowledge about the endophytes, mode of action and their role in the development of sustainable agriculture system for human welfare.

Glycoproteins of arbuscular mycorrhiza for soil carbon sequestration: Review of mechanisms and controls.

Glycoproteins, e.g., glomalin related soil proteins (GRSP), are sticky organic substances produced by arbuscular mycorrhizal fungi (AMF). This review summarizes the information on i) the biochemical nature, physical state and origin of GRSP, ii) GRSP decomposition and residence time in soil, iii) GRSP functions, in particular the physical, chemical, and biochemical roles for soil aggregation and carbon (C) sequestration, and finally iv) how land use and agricultural management affect GRSP production and subsequently, organic C sequestration. GRSP augment soil quality by increasing water holding capacity, nutrient storage and availability, microbial and enzymatic activities, and microbial production of extracellular polysaccharides. After release into the soil, GRSP become prone to microbial decomposition due to stabilization with organic matter and sesquioxides, and thereby increasing the residence time between 6 and 42 years. Temperate soils contain 2-15 mg GRSP g-1, whereas arid and semiarid grasslands amount for 0.87-1.7 mg g-1, and GRSP are lower in desert soils. GRSP content is highest in acidic soils as compared to neutral and calcareous soils. Conservation tillage, organic fertilizers and AMF inhabiting crops (e.g. maize, sorghum, soybean, and wheat) increase GRSP production and transform C into stable forms, thereby sustaining soil health and reducing CO2 emissions. Crop rotations with non-mycorrhizal species (e.g. rapeseed) and fallow soils reduce AMF growth and consequently, the GRSP production. The GRSP production increases under nutrient and water deficiency, soil warming and elevated CO2. In the context of global climate change, increased C sequestration through GRSP induced aggregate formation and organic matter stabilization prolong the mean residence time of soil C. Protecting soils against degradation under intensive land use, stable aggregate formation, and prolonging the residence time of C calls for strategies that maximize GRSP production and functions based on reduced tillage, AMF-relevant crop rotations and organic farming.

Genomic selection signatures in autism spectrum disorder identifies cognitive genomic tradeoff and its relevance in paradoxical phenotypes of deficits versus potentialities.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by paradoxical phenotypes of deficits as well as gain in brain function. To address this a genomic tradeoff hypothesis was tested and followed up with the biological interaction and evolutionary significance of positively selected ASD risk genes. SFARI database was used to retrieve the ASD risk genes while for population datasets 1000 genome data was used. Common risk SNPs were subjected to machine learning as well as independent tests for selection, followed by Bayesian analysis to identify the cumulative effect of selection on risk SNPs. Functional implication of these positively selected risk SNPs was assessed and subjected to ontology analysis, pertaining to their interaction and enrichment of biological and cellular functions. This was followed by comparative analysis with the ancient genomes to identify their evolutionary patterns. Our results identified significant positive selection signals in 18 ASD risk SNPs. Functional and ontology analysis indicate the role of biological and cellular processes associated with various brain functions. The core of the biological interaction network constitutes genes for cognition and learning while genes in the periphery of the network had direct or indirect impact on brain function. Ancient genome analysis identified de novo and conserved evolutionary selection clusters. The de-novo evolutionary cluster represented genes involved in cognitive function. Relative enrichment of the ASD risk SNPs from the respective evolutionary cluster or biological interaction networks may help in addressing the phenotypic diversity in ASD. This cognitive genomic tradeoff signatures impacting the biological networks can explain the paradoxical phenotypes in ASD.

Environmental Endocrine-Disrupting Chemical Exposure: Role in Non-Communicable Diseases.

The exponential growth of pollutant discharges into the environment due to increasing industrial and agricultural activities is a rising threat for human health and a biggest concern for environmental health globally. Several synthetic chemicals, categorized as potential environmental endocrine-disrupting chemicals (EDCs), are evident to affect the health of not only livestock and wildlife but also humankind. In recent years, human exposure to environmental EDCs has received increased awareness due to their association with altered human health as documented by several epidemiological and experimental studies. EDCs are associated with deleterious effects on male and female reproductive health; causes diabetes, obesity, metabolic disorders, thyroid homeostasis and increase the risk of hormone-sensitive cancers. Sewage effluents are a major source of several EDCs, which eventually reach large water bodies and potentially contaminate the drinking water supply. Similarly, water storage material such as different types of plastics also leaches out EDCs in drinking Water. Domestic wastewater containing pharmaceutical ingredients, metals, pesticides and personal care product additives also influences endocrine activity. These EDCs act via various receptors through a variety of known and unknown mechanisms including epigenetic modification. They differ from classic toxins in several ways such as low-dose effect, non-monotonic dose and trans-generational effects. This review aims to highlight the hidden burden of EDCs on human health and discusses the non-classical toxic properties of EDCs in an attempt to understand the magnitude of the exposome on human health. Present data on the environmental EDCs advocate that there may be associations between human exposure to EDCs and several undesirable health outcomes that warrants further human bio-monitoring of EDCs.

Techniques for improving formulations of bioinoculants.

Bioinoculants are eco-friendly microorganisms having a variety of products commonly utilized for improving the potential of soil and providing the nutrient requirements to the host plant. The usage of chemical fertilizers is not beneficial because it affects the soil microbial communities on large scale. The toxicity of chemical fertilizer decreases the fertility of soil and causes microbial disruption. Bioinoculants that are used as PGPR play an important role in the enhancement of crop production and beneficial for both producers and consumers economically by protecting the soil during unfavourable conditions. The utilization of PGPR in the bioinoculant form imparts successfully sustain agricultural yield production and such formulated products contain living microbial cells of bioinoculants that also helps in seed treatment and enhances the mobilization process of nutrients by the low-cost process. This review mainly focuses on different bioinoculant formulations related to its recent approaches such as metabolite formulations, liquid formulations, solid carrier-based formulations and synthetic polymer-based formulations. This review also gives an overview of some aspects of the bioinoculant efficiency and their appropriate formulation, production and storage condition of microbial cells.

In silico analysis and molecular characterization of Influenza A (H1N1) pdm09 virus circulating and causing major outbreaks in central India, 2009-2019.

BACKGROUND AND OBJECTIVES: Influenza A/H1N1pdm09 causes respiratory illness and remains a concern for public health. Since its first emergence in 2009, the virus has been continuously circulating in the form of its genetic variants. Influenza A/H1N1pdm09 surveillance is essential for uncovering emerging variants of epidemiologic and vaccine efficacy. The present study attempts in silico analysis and molecular characterization of Influenza A (H1N1) pdm09 virus circulating and causing major outbreaks in central India during 2009-2019. MATERIALS AND METHODS: We have investigated the antigenic drift analysis of 96 isolates' hemagglutinin (HA) gene sequences (59 central Indian and 37 local Indian and 28 global reference HA gene sequences) of Influenza A/H1N1pdm09 viruses from 2009 to 2019. The study includes mutational (Multiple sequence Alignment), phylogenetic (Maximum Likelihood Method), and statistical analysis (Covariance and correlation) of HA sequences submitted in NCBI, IRD and GISAID from central India. RESULTS: Phylogenetic analysis indicated maximum clustering of central Indian HA gene sequences in genogroup 6B. Analysis of amino acid sequence alignment revealed changes in receptor binding site (RBS). The frequency of S220T amino acid substitution was found to be high followed by S202T, K300E A273T, K180Q. The Karl Pearson correlation coefficient (r) and covariance between the number of mutations and the death toll was found +0.246 and +100.3 respectively. CONCLUSION: The study identifies the continuous genetic variations in the HA gene sequences of circulating Influenza A/H1N1pdm09 in central India from the year 2009 to 2019. Further suggesting importance of monitoring the gradual evolution of the virus with regards to an increase in virulence, pathogenicity and vaccine efficacy timely.

Malaria in North-East India: Importance and Implications in the Era of Elimination.

Worldwide and in India, malaria elimination efforts are being ramped up to eradicate the disease by 2030. Malaria elimination efforts in North-East (NE) India will have a great bearing on the overall efforts to eradicate malaria in the rest of India. The first cases of chloroquine and sulfadoxine-pyrimethamine resistance were reported in NE India, and the source of these drug resistant parasites are most likely from South East Asia (SEA). NE India is the only land route through which the parasites from SEA can enter the Indian mainland. India's malaria drug policy had to be constantly updated due to the emergence of drug resistant parasites in NE India. Malaria is highly endemic in many parts of NE India, and Plasmodium falciparum is responsible for the majority of the cases. Highly efficient primary vectors and emerging secondary vectors complicate malaria elimination efforts in NE India. Many of the high transmission zones in NE India are tribal belts, and are difficult to access. The review details the malaria epidemiology in seven NE Indian states from 2008 to 2018. In addition, the origin and evolution of resistance to major anti-malarials are discussed. Furthermore, the bionomics of primary vectors and emergence of secondary malaria vectors, and possible strategies to prevent and control malaria in NE are outlined.

Anti-proliferative role of recombinant lethal toxin of Bacillus anthracis on primary mammary ductal carcinoma cells revealing its therapeutic potential.

Bacillus anthracis secretes three secretary proteins; lethal factor (LF), protective antigen (PA) and edema factor (EF). The LF has ability to check proliferation of mammary tumors, chiefly depending on mitogen activated protein kinase (MAPK) signaling pathway. Evaluation of therapeutic potential of recombinant LF (rLF), recombinant PA (rPA) and lethal toxin (rLF + rPA = LeTx) on the primary mammary ductal carcinoma cells revealed significant (p < 0.01) reduction in proliferation of tumor cells with mean inhibition indices of 28.0 ± 1.37% and 19.6 ± 1.47% respectively. However, treatment with rPA alone had no significant anti-proliferative effect as evident by low mean inhibition index of 3.4 ± 3.87%. The higher inhibition index observed for rLF alone as compared to LeTx is contrary to the existing knowledge on LF, which explains the requirement of PA dependent endocytosis for its enzymatic activity. Therefore, the plausible existence of PA independent mode of action of LF including direct receptor mediated endocytosis or modulation of signal transduction cascade via unknown means is hypothesized. In silico protein docking analysis of other cellular receptors for any plausibility to play the role of receptor for LF revealed c-Met receptor showing strongest affinity for LF (H bond = 19; Free energy = -773.96), followed by nerve growth factor receptor (NGFR) and human epidermal growth factor receptor (HER)-1. The study summarizes the use of rLF or LeTx as therapeutic molecule against primary mammary ductal carcinoma cells and also the c-Met as potential alternative receptor for LF to mediate and modulate PA independent signal transduction.

Historical environmental change in Africa drives divergence and admixture of Aedes aegypti mosquitoes: a precursor to successful worldwide colonization?

Increasing globalization has promoted the spread of exotic species, including disease vectors. Understanding the evolutionary processes involved in such colonizations is both of intrinsic biological interest and important to predict and mitigate future disease risks. The Aedes aegypti mosquito is a major vector of dengue, chikungunya and Zika, the worldwide spread of which has been facilitated by Ae. aegypti's adaption to human-modified environments. Understanding the evolutionary processes involved in this invasion requires characterization of the genetic make-up of the source population(s). The application of approximate Bayesian computation (ABC) to sequence data from four nuclear and one mitochondrial marker revealed that African populations of Ae. aegypti best fit a demographic model of lineage diversification, historical admixture and recent population structuring. As ancestral Ae. aegypti were dependent on forests, this population history is consistent with the effects of forest fragmentation and expansion driven by Pleistocene climatic change. Alternatively, or additionally, historical human movement across the continent may have facilitated their recent spread and mixing. ABC analysis and haplotype networks support earlier inferences of a single out-of-Africa colonization event, while a cline of decreasing genetic diversity indicates that Ae. aegypti moved first from Africa to the Americas and then to Asia. ABC analysis was unable to verify this colonization route, possibly because the genetic signal of admixture obscures the true colonization pathway. By increasing genetic diversity and forming novel allelic combinations, divergence and historical admixture within Africa could have provided the adaptive potential needed for the successful worldwide spread of Ae. aegypti.