Biology subjects

Yadav, P.

Publications and source records attributed to Yadav, P..

At least 55 records · Page 3Linked to original sources

bioRxiv2023

Zea mays genotype influences microbial and viral rhizobiome community structure

Plant genotype is recognized to contribute to variations in microbial community structure in the rhizosphere, soil adherent to roots. However, the extent to which the viral community varies has remained poorly understood and has the potential to contribute to variation in soil microbial communities. Here we cultivated replicates of two different genotypes of Zea mays parviglumis and Z. mays genotype B73 in a greenhouse and harvested the rhizobiome (rhizoplane and rhizosphere) to identify the abundance of cells and viruses as well as apply 16S rRNA gene amplicon sequencing and genome resolved metagenomics to identify the rhizobiome microbial and viral community. Our results demonstrate that viruses exceeded microbial abundance in the rhizobiome of parviglumis and B73 with a significant variation in both, the microbial and viral community between the two genotypes. Of the viral contigs identified only 4.5% (n =7) of total viral contigs were shared between the two genotypes, demonstrating that plants even at the level of genotype can significantly alter the surrounding soil viral community. An auxiliary metabolic gene associated with glycoside hydrolase (GH5) degradation was identified in one viral metagenome-assembled genome (vMAG) identified in the B73 rhizobiome infecting Propionibacteriaceae (Actinobacteriota) further demonstrating the viral contribution in metabolic potential for carbohydrate degradation and carbon cycling in the rhizosphere. This variation demonstrates the potential of plant genotype to contribute to microbial and viral heterogeneity in soil systems and harbor genes capable of contributing to carbon cycling in the rhizosphere.

microbiology↗

bioRxiv2023

In silico characterization of five novel disease-resistance proteins in Oryza sativa sp. japonica against bacterial leaf blight and rice blast diseases

Oryza sativa sp. japonica is the most widely cultivated variety of rice. It has evolved several defense mechanisms, including PAMP-triggered immunity (PTI) and effector-triggered immunity (ETI), which provide resistance against different pathogens to overcome biotic stresses. Several disease-resistance genes and proteins, such as R genes and PRR proteins, have been reported in the scientific literature which shows resistance against Xanthomonas oryzae pv. oryzae (Xoo), a causative agent for bacterial leaf blight disease (BB), and Magnaporthe oryzae (M. oryzae), causing rice blast disease (RB). Although some of these resistance proteins have been studied, the functional characterization of resistance proteins in rice is not exhaustive. In the current study, we identified five novel resistance proteins against BB and RB diseases through gene network analysis. Structure and function prediction, disease-resistance domain identification, protein-protein interaction (PPI), and pathway analysis revealed that the five new proteins played a role in the disease resistance against BB and RB. In silico modeling, refinement, and model quality assessment were performed to predict the best structures of these five proteins, and submitted to ModelArchive for future use. The functional annotation of the proteins revealed their involvement in the bacterial disease resistance of rice. We predicted that the new resistance proteins could be localized to the nucleus and plasma membrane. This study provides insight into developing disease-resistant rice varieties by predicting novel candidate resistance proteins, which will pave the way for their future characterization and assist rice breeders in improving crop yield and addressing future food security.

bioinformatics↗

bioRxiv2023

Red Fluorescent Carbon Nanoparticles Derived from Spinacia oleracea L.: A Versatile Tool for Bioimaging & Biomedical Applications

Carbon-based fluorescent quantum dots are an emerging class of nanoparticles for targeted bioimaging and biomedical applications. We present a facile microwave-assisted approach for synthesizing carbon nanoparticles with bright red fluorescence using ethanolic extracts of Spinacia oleracea leaves, with a quantum yield of 94.67%. These nanoparticles, called CNPs, ranging from 15-50 nm, demonstrated fluorescence emission in the near-infrared (NIR) region between 650 and 700 nm, independent of excitation wavelength. Upon excitation at a wavelength of 410 nm, they exhibit an emission maxima peak at 672 nm. The significant uptake of CNPs in mammalian cells and zebrafish larvae highlights their potential as bioimaging agents in diverse biomedical applications in vivo. Further, these quantum dots enhance cellular proliferation and migration as observed by wound healing assay in mammalian cells, indicating their possible application in tissue engineering and regenerative medicine. These findings suggest that biosynthesized carbon nanoparticles possess significant potential for biomedical activities, which can serve as a robust benchmark for researchers towards promoting sustainability.

bioengineering↗

bioRxiv2023

Metabolic alterations unravel the materno fetal immune responses with disease severity in pregnant women infected with SARS-CoV-2

BackgroundPregnancy being immune compromised state, COVID-19 disease poses high risk of premature delivery and threat to fetus. Plasma metabolome regulates immune cellular responses and we aimed to analyze the plasma secretome, metabolome and immune cells in COVID-19 positive pregnant mother and cord blood. MethodsCOVID-19 RT-PCR positive pregnant females (n=112) asymptomatic (n=82), or with mild (n=21) or moderate (n=9) disease and control healthy pregnant (n=10) females were included. Mothers blood and cord blood (n=80) was analysed for untargeted metabolome profiling and plasma cytokines by high-resolution mass spectrometry (MS) and multiplex cytokine bead array. Immune scan in mothers was done using flow cytometry. ResultsIn asymptomatic SARS-CoV-2 infection, --the amino acid metabolic pathways such as glycine, serine, L-lactate and threonine metabolism was upregulated, riboflavin and tyrosine metabolism, downregulated. In mild to moderate disease, the pyruvate and NAD+ metabolism (energy metabolic pathways) were mostly altered. In addition to raised TNF-, IFN-, IFN-{gamma}, IL-6 cytokine storm, IL-9 was increased in both mothers and neonates. Pyruvate and NAD+ metabolic pathways along with IL-9 and IFN-{gamma} had impact on non-classical monocytes, increased CD4 T cells and B cells but depleted CD8+ T cells. Cord blood mimicked the mothers metabolomic profiles by showing altered valine, leucine, isoleucine, glycine, serine, threonine in asymptomatic and NAD+ and riboflavin metabolism in mild and moderate disease subjects. ConclusionsOur results demonstrate a graduated immune-metabolomic interplay in mother and fetus in pregnant females with different degrees of severity of COVID-19 disease. IL-9 and IFN- {gamma} regulated pyruvate, lactate TCA metabolism and riboflavin metabolism with context to disease severity are hall marks of this materno-fetal metabolome. HighlightsO_LISARS-CoV-2 infection alters energy consumption metabolic pathways during pregnancy. C_LIO_LIPregnant women with mild to moderate COVID-19 show increased energy demands, and consume stored glucose by upregulating pyruvate and NAD+ metabolism. C_LIO_LIIncreased TNF- and IL-9 in mild COVID-19 disease involve TCA cycle to produce lactate and consume stored glucose by up regulating pyruvate and nicotinamide and nicotinate metabolism. C_LIO_LIWith mild to moderate disease, raised IL-9 and TNF-, decreased riboflavin pathway, exhaustion of T and B cells cause pathogenesis. C_LIO_LICord blood mimics the metabolic profile of mothers peripheral blood, SARS- CoV-2 infection reshapes immune-metabolic profiles of mother-infant dyad. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=141 HEIGHT=200 SRC="FIGDIR/small/540101v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@657cc3org.highwire.dtl.DTLVardef@e1e76forg.highwire.dtl.DTLVardef@12153f2org.highwire.dtl.DTLVardef@10e5332_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2023

Lipid modification of DNA nanocages enhances cellular uptake, migration, and in vivo uptake

The extraordinary self-assembling nature of DNA nanostructures and high functionality enables the formulation of DNA nanostructures with multiple chemical and biological molecules. How the whole organisms in native as well as modified; and how stable they are inside take up exactly these modified DNA nanostructures the organisms still remains to be explored. Here we report the fabrication and evaluation of a new conjugate of a cationic lipid, N-[one-(two, 3-dioleyloxy) propyl]-N, N, N-trimethylammonium chloride (DOTMA) and DNA tetrahedron nanostructure (TdN) for the enhanced uptake, stability, bioimaging, and biotherapeutics in cells and zebrafish (Danio rerio) eleuthero embryos as a model organism. We summarise the enhanced uptake potential of TdN-DOTMA conjugate for futuristic biomedical applications such as drug delivery, bioimaging, biosensing, and therapeutics.

bioengineering↗

bioRxiv2023

Identification of Mirror Repeats in Viral Genomes using FPCB Analysis

The majority of living domains consist of DNA as genetic material with the minor exception of viruses. The unique nature of every species determines by its unique pattern of genome or gene products. The genomic features become an evident example of evolutionary study also. Different types of repeat patterns are observed in genomes of living domains including human beings whose two third portion of the genome is repetitive. Among the varied type of repeat sequences Mirror Repeats (MR) play crucial roles at the genetic level in every species. The major focus of our research is on identification & to check the distribution of mirror repeat. For this, we employed a bioinformatics-based approach refer as FASTA PARALLEL COMPLEMENT BLAST (FPCB) to identify unique mirror repeat (MR) sequences in some selected viral genomes from three different categories (Animal, Plant & Human). The identified repeats vary in their length as well as found to be distributed throughout the selected viral genomes. The maximum no of MR were reported in the case of Dengue virus (229) & minimum is in the case of TMV (97). In the remaining selected viruses - HCV, HPV, HTLV-1, PVY, Rabies virus 178, 156, 175, 203 & 204 MR sequences were reported. These sequences can be utilized in many ways like in molecular diagnosis, drug delivery target as well as evolutionary study, etc. The present research also helps in the development of novel tools of bioinformatics to study mirror repeats and their functional perspective in the context of their occurrence in all domains.

bioinformatics↗

bioRxiv2022

Comparison of Dimensionality Reduction and Clustering Methods for Single-Cell Transcriptomics Data

Dimensionality reduction (DR) methods are applied to extract relevant features from inherently high dimensional and noisy single-cell RNA sequencing (scRNA-seq) data. Choice of DR method could influence the performance of clustering algorithm and subsequent analysis outcomes. We performed a benchmarking study of seven popular DR methods and four clustering algorithms widely used for scRNA-seq datasets. For this purpose, we used three publicly available real scRNA-seq datasets. The performance was evaluated using two clustering metrics viz. adjusted random index (ARI) and normalized mutual index (NMI). We also compared our results with a similar study published by Xiang and colleagues. Overall, we observed higher ARI and NMI scores for DR methods when compared with Xiangs study. We also noticed several differences between our and Xiangs study. Noteworthy, three methods, namely, Independent Component Analysis (ICA), t-Distributed Stochastic Neighbor Embedding (t-SNE) and Uniform Manifold Approximation and Projection (UMAP) performed consistently well across three datasets. Linear method ICA was best performer on Segerstolpe dataset, while nonlinear methods UMAP and t-SNE best performed on Deng and Chu datasets, respectively. Neural network-based methods Variational Autoencoder (VAE) and Deep Count Autoencoder (DCA) could not perform well probably due to their sensitivity to hyperparameters and overfitting. Among clustering methods, Gaussian Mixture Models (GMMs) performed consistently well across datasets. This might be because GMMs are the universal approximators of posterior probability densities. We conclude that performance of different DR methods is more dataset dependent and for various scRNA-seq datasets different algorithms are more suited and there is no one-fit-all method.

bioinformatics↗

bioRxiv2022

Gene expression profiling and protein-protein network analysis revealed prognostic hub biomarkers linking cancer risk in type 2 diabetic patients

Type 2 diabetes mellitus (T2DM) and cancer are highly prevalent diseases imposing major health burden globally. Several epidemiological studies indicate increased susceptibility to cancer in T2DM patients. However, genetic factors linking T2DM with cancer are poorly studied so far. We used computational approach on the raw gene expression data of peripheral blood mononuclear cells of Homo sapiens available at the gene expression omnibus (GEO) database, to identify shared differentially expressed genes (DEGs) in T2DM and three common cancer types namely, pancreatic (PC), liver (LC) and breast cancer (BC). Additional functional and pathway enrichment analysis of identified common DEGs highlighted involvement of important biological pathways including cell cycle events, immune system process, cell morphogenesis, gene expression and metabolism. Furthermore, we retrieved the PPI network for crucial DEGs obtained from above analysis to deduce molecular level interactions. Based on the result of network analysis, we found 8, 5 and 9 common hub genes in T2DM vs PC, T2DM vs LC and T2DM vs BC, respectively. Overall, our analysis identified important genetic markers potentially able to predict the chances of pancreatic, liver and breast cancer onset in T2DM patients.

bioinformatics↗

bioRxiv2022

Visual processing and collective motion-related decision-making in desert locusts

Collectively moving groups of animals rely on the decision-making of locally interacting individuals in order to maintain swarm cohesion. However, the complex and noisy visual environment poses a major challenge to the extraction and processing of relevant information. We addressed this challenge by studying swarming-related decision-making in desert locust last-instar nymphs. Controlled visual stimuli, in the form of random dot kinematograms, were presented to tethered locust nymphs in a trackball setup, while monitoring movement trajectory and walking parameters. In a complementary set of experiments, the neurophysiological basis of the observed behavioral responses was explored. Our results suggest that locusts utilize filtering and discrimination upon encountering multiple stimuli simultaneously. Specifically, we show that locusts are sensitive to differences in speed at the individual conspecific level, and to movement coherence at the group level, and may use these to filter out non-relevant stimuli. The locusts also discriminate and assign different weights to different stimuli, with an observed interactive effect of stimulus size, relative abundance, and motion direction. Our findings provide insights into the cognitive abilities of locusts in the domain of decision-making and visual-based collective motion, and support locusts as a model for investigating sensory-motor integration and motion-related decision-making in the intricate swarm environment.

animal behavior and cognition↗

bioRxiv2022

Effects of Face Repetition on Ventral Visual Stream Connectivity using Dynamic Causal Modelling of fMRI data

Stimulus repetition normally causes reduced neural activity in brain regions that process that stimulus. Some theories claim that this "repetition suppression" reflects local mechanisms such as neuronal fatigue or sharpening within a region, whereas other theories claim that it results from changed connectivity between regions, following changes in synchrony or top-down predictions. In this study, we applied dynamic causal modelling (DCM) on a public fMRI dataset involving repeated presentations of faces and scrambled faces to test whether repetition affected local (self-connections) and/or between-region connectivity in left and right early visual cortex (EVC), occipital face area (OFA) and fusiform face area (FFA). Face "perception" (faces versus scrambled faces) modulated nearly all connections, within and between regions, including direct connections from EVC to FFA, supporting a non-hierarchical view of face processing. Face "recognition" (familiar versus unfamiliar faces) modulated connections between EVC and OFA/FFA, particularly in the left hemisphere. Most importantly, immediate and delayed repetition of stimuli were also best captured by modulations of connections between EVC and OFA/FFA, but not self-connections of OFA/FFA, consistent with synchronization or predictive coding theories.

neuroscience↗

bioRxiv2022

Protective efficacy of COVAXIN(R) against Delta and Omicron variants in hamster model

The immunity acquired after natural infection or vaccinations against SARS-CoV-2 tend to wane with time. Vaccine effectiveness also varies with the variant of infection. Here, we compared the protective efficacy of COVAXIN(R) following 2 and 3 dose immunizations against the Delta variant and also studied the efficacy of COVAXIN(R) against Omicron variants in a Syrian hamster model. The antibody response, clinical observations, viral load reduction and lung disease severity after virus challenge were studied. Protective response in terms of the reduction in lung viral load and lung lesions were observed in both the 2 dose as well as 3 doses COVAXIN(R) immunized group when compared to placebo group following the Delta variant challenge. In spite of the comparable neutralizing antibody response against the homologous vaccine strain in both the 2 dose and 3 dose immunized groups, considerable reduction in the lung disease severity was observed in the 3 dose immunized group post Delta variant challenge indicating the involvement of cell mediated immune response also in protection. In the vaccine efficacy study against the Omicron variants i.e., BA.1 and BA.2, lesser virus shedding, lung viral load and lung disease severity were observed in the immunized groups in comparison to the placebo groups. The present study shows that administration of COVAXIN(R) booster dose will enhance the vaccine effectiveness against the Delta variant infection and give protection against the Omicron variants BA.1.1 and BA.2.

immunology↗

bioRxiv2022

Low immune response after 1.5 years of primary SARS-CoV-2 infection and Covishield vaccination lead to SARS-CoV-2 reinfection

We have investigated six COVID recovered cases with two doses of Covishield vaccination followed by reinfection. The primary SARS-CoV-2 infection found to occur with B.1 and reinfection with Omicron BA.1 and BA.2 variants. The genomic characterization and duration between two infections confirms these cases as SARS-CoV-2 reinfection. The mutation analysis of the reinfection cases correlated with immune evasion potential of BA.1 and BA.2 sub lineages. The immune response determined at different time intervals demonstrated boost post two dose vaccination, decline in pre-reinfection sera post 7 months and rise post reinfection. Apparently, these cases suffered from SARS-CoV-2 reinfection with the declined hybrid immunity acquired from primary infection and two dose covishield vaccination. This suggests the need for booster dose of vaccination. Besides this, multiple non-pharmaceutical interventions should be used to cope up with SARS-CoV-2 infection.

microbiology↗

bioRxiv2022

Green emitting carbon quantum dots (GCQDs) to probe endocytic pathways in cells; for tissue and in vivo bioimaging

Small sized, carbon-based organic nanoparticles have recently gained attention due their advantage of biocompatibility, photostability and biological non-toxicity as compared to their inorganic counterparts. Herein, a new class of small (5-8 nm), green emitting fluorescent carbon quantum dots (GCQDs) were synthesized using organic substrates like citric acid and ascorbic acid in aqueous solvent containing water and ethanol. The very small size and bright green photoluminescence prompted their use for both in vitro and in vivo bioimaging. GCQDs were uptaken via clathrin mediated pathways in mouse kidney and liver primary cells. Similarly, they showed active uptake and distribution in the zebrafish embryo model system. The optical tunability and surface modification properties of these GCQDs provide a platform to be explored for them to emerge as a new class of targeted bioimaging entities, as well as tools for biomedical applications.

bioengineering↗

bioRxiv2022

Single-Cell Transcriptome Analysis Identifies Novel Biomarkers Involved in Major Liver Cancer Subtypes

Liver cancers including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are leading cause of death worldwide. Single-cell transcriptomics studies have vast potential in advancing our understanding of cancers by defining the cellular composition of different solid tumor types. We peformed an integrated analysis using single-cell RNA sequencing (scRNA-seq) data from cancerous and healthy liver tissues in order to identify the molecular progression and intercellular heterogeneity across cell types in the liver cancer. Moreover, we performed a subtype specific analyses, separately for HCC and ICC, to identify any molecular drivers uniquely associated with these liver cancers. The scRNA-seq dataset comprising 5 healthy controls and 19 liver cancer patients were collected from Human Cell Atlas and Gene Expression Omnibus (GEO), respectively. Our analyses confirmed upregulation of four previously known malignant cell marker genes, namely, EPCAM, KRT19, KRT7 and S100P in the cancerous liver cells. Of these, KRT7 gene has been reported to be associated with ovarian cancer in the past studies. Noteworthy, four marker genes specific to the G1/S (MCM5 and PCNA) and G2/M phases (HMGB2 and CKS2) of the cell cycle were upregulated in the cancerous liver cells. This indicates that these four marker genes are actively dividing in these two phases in cancerous cells as compared to normal liver cells. Our differential expression analysis identified 2 upregulated genes (ATF3 and S100A11) and 2 downregulated genes (FCN3 and FGB) in the liver cancer. Our subtype based differential expression analysis identified 4 genes (HSPA6, LMNA, ATP1B1 and DCXR) specific to HCC and 3 genes (HSPB1, APOC3 and APOA1) specific to ICC. CD4+ T-cell, Hepatocyte, neutrophil, mesenchymal cells and liver bud hepatic cells are the predominant cell-types in liver cells. Our scRNA-seq study revealed the mesenchymal cells as potential malignant cell types in liver cancers. Our work suggests future research on developing liver cancer subtypes therapies could target these cell types and associated molecular markers.

genomics↗

bioRxiv2022

Engineering Rotating Apical-Out Airway Organoid for Assessing Respiratory Cilia Motility

Motile cilia project from the airway apical surface and directly interface with inhaled external environment. Due to cilias nanoscale dimension and high beating frequency, quantitative assessment of their motility remains a sophisticated task. Here we described a robust approach for reproducible engineering of apical-out airway organoid (AOAO) of defined size. Propelled by exterior-facing cilia beating, the mature AOAO exhibited stable rotational motion when surrounded by Matrigel. We developed a computational framework leveraging computer vision algorithms to quantify AOAO rotation and validated its correlation with direct measurement of cilia motility. We further established the feasibility of using AOAO rotation to recapitulate and measure defective cilia motility caused by chemotherapy-induced toxicity and by CCDC39 mutations in cells from primary ciliary dyskinesia patient. We expect our rotating AOAO model and the associated computational pipeline to offer a generalizable framework to expediate modeling of and therapeutic development for genetic and environmental ciliopathies.

bioengineering↗

bioRxiv2022

Histone deacetylase inhibitor overrides the effect of soft hydrogel on the mechanoresponse of human mesenchymal stem cells

Human Mesenchymal stem cells (hMSCs) are promising in regenerative medicine for their multi-lineage differentiation capability. It has been demonstrated that lineage specification is governed by both chemical and mechanical cues. Among all the different mechanical cues known to control hMSCs fate, substrate stiffness is the most well-studied. It has been shown that the naive mesenchymal stem cells when cultured on soft gel, they commit towards adipogenic lineage while on stiff gel they become osteogenic. Soft substrates also cause less cell spreading, less traction, less focal adhesion assembly and stress fibre formation. Furthermore, chromatin condensation increases when cells are cultured on soft substrates. As the nucleus has been postulated to be mechanosensor and mechanotransducer, in this paper we asked the question how mechanosensing and mechanoresponse process will be influenced if we reduce the chromatin condensation in hMSCs cultured on soft substrates by using an external reagent. To address this question, we treated hMSCs cultured on soft polyacrylamide (PA) gels with a histone deacetylase inhibitor (HDACi) called Valproic Acid (VA) which decondense the chromatin by hyperacetylation of histone proteins. We found that the treatment with VA overrides the effect of soft substrates on hMSCs morphology, cellular traction, nuclear localization of mechnosensory protein YAP (yes-associated protein), and differentiation. VA treated cells behaved as if they are on stiff substrates in all aspects tested here. In contrast, when we increase chromatin condensation using histone acetyl transferase inhibitor (HATi), adipogenic differentiation on soft gel increases. Furthermore, we have shown that VA controls hMSCs differentiation via activation of ERK/MAPK pathway by increasing the p-ERK expression. Collectively, these findings demonstrate for the first time that inhibiting histone deacetylase can override the mechanoresponse of hMSCs. This work will help us to fundamentally understand the mechanosignalling process and to control the hMSCs differentiation in tissue engineering and regenerative medicine. SignificanceTo harness the clinical potential of Human mesenchymal stem cells (hMSCs), it is important to understand the working mechanism of various signals in deciding cell fate. It has been shown in the recent past that the substrate rigidity influence hMSCs differentiation. Though the mechanism is not fully understood, the mechanosignals are known to alter the cell fate via reorganizing the chromatin packing. In this work, we ask if altering chromatin packing can change the cell fate as dictated by the mechanical properties of the substrates. We have shown that almost all the known effector of mechanosignals get modified when we tweak the chromatin packing via histone deacetylase inhibitor (HDACi). This study is helpful for developing a better understanding of the mechano-signalling process. It gives us a tool to override the effect of the substrates, particularly when the mechanical properties of biomaterials are not conducive for the desired differentiation outcome. Additionally, as HDACi are being used in the therapy of cancer and different neurodegenerative diseases, our understanding of their crosstalk with tissue stiffness in controlling cell fate will help to understand any unknown and undesirable side effects of using HDACi as therapeutic agent.

cell biology↗

bioRxiv2021

Kismet/CHD7/CHD8 affects gut biomechanics, the gut microbiome, and gut-brain axis in Drosophila melanogaster

The gut-brain axis may contribute to the pathophysiology of neurodevelopmental disorders, yet it is often unclear how risk genes associated with these disorders affect gut physiology in a manner that could impact microbial colonization. We addressed this question using Drosophila melanogaster with a null mutation in kismet, the ortholog of chromodomain helicase DNA-binding protein (CHD) family members CHD7 and CHD8. In humans, CHD7 and CHD8 are risk genes for neurodevelopmental disorders with co-occurring gastrointestinal symptoms. We found kismet mutant flies have a significant increase in gastrointestinal transit time, indicating functional homology of kismet with CHD7/CHD8 in vertebrates. To measure gut tissue mechanics, we used a high-precision force transducer and length controller, capable of measuring forces to micro-Newton precision, which revealed significant changes in the mechanics of kismet mutant guts, in terms of elasticity, strain stiffening, and tensile strength. Using 16S rRNA metagenomic sequencing, we also found kismet mutants have reduced diversity of gut microbiota at every taxonomic level and an increase in pathogenic taxa. To investigate the connection between the gut microbiome and behavior, we depleted gut microbiota in kismet mutant and control flies and measured courtship behavior. Depletion of gut microbiota rescued courtship defects of kismet mutant flies, indicating a connection between gut microbiota and behavior. In striking contrast, depletion of gut microbiome in the control strain reduced courtship activity. This result demonstrated that antibiotic treatment can have differential impacts on behavior that may depend on the status of microbial dysbiosis in the gut prior to depletion. We propose that Kismet influences multiple gastrointestinal phenotypes that contribute to the gut-brain axis to influence behavior. Based on our results, we also suggest that gut tissue mechanics should be considered as an element in the gut-brain communication loop, both influenced by and potentially influencing the gut microbiome and neuronal development.

developmental biology↗

bioRxiv2021

Protective immunity of the primary SARS-CoV-2 infection reduces disease severity post re-infection with Delta variants in Syrian hamsters

Delta variant has evolved to become dominant SARS-CoV-2 lineage worldwide and there are reports of secondary infections with varying severity in vaccinated and unvaccinated naturally recovered COVID-19 patients. As the protective immunity following the infection wanes within few months, studies of re-infection after prolonged duration is needed. Hence we assessed the potential of re-infection by Delta, Delta AY.1 and B.1 in COVID-19 recovered hamsters after 3 months of infection. Re-infection with Delta and B.1 variants in hamsters showed reduced viral shedding, lung pathology and lung viral load, whereas the upper respiratory tract viral load remained similar to that of first infection. The reduction in viral load and lung pathology after re-infection with Delta AY.1 variant was not marked. Further we assessed the disease characteristics of Delta AY.1 to understand whether it has any replication advantage over Delta variant and B.1 variant, an early isolate in Syrian hamsters. Body weight changes, viral load in respiratory organs, lung pathology, cytokine response and neutralizing antibody response were assessed. Delta AY.1 variant produced milder disease in comparison to Delta variant and the neutralizing response was similar against Delta, B.1 and B.1.351 variant in contrast to Delta or B.1 infected hamsters which showed a significant reduction in neutralization titres against B.1.351. Elevation of IL-6 levels was observed post infection in hamsters after primary infection. The prior infection could not produce sterilizing immunity but the protective effect was evident following reinfection. This indicates the importance of the transmission prevention efforts even after achieving herd immunity. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSSecondary infections with Delta variant are being widely reported and there are reports of increased disease severity. Delta sub lineages with K417N substitution has caused concern worldwide due to the presence of the same substitution in Beta variant, a Variant of Concern known for its immune evasion. The information on the biological characteristics of this sub lineage is also scanty. Added value of this studyThe present study showed that the secondary infection with Delta variant does not show any evidence of increased disease severity in hamster model. Delta AY. 1 variant produces mild disease in Syrian hamsters in contrast to severe disease caused by Delta variant. Delta, B.1 and AY.1 variant infected hamster sera showed comparable cross neutralizing response against each other. In contrast to the lower neutralizing response shown by B.1 and Delta variant infected animals against B.1.351 variant, Delta AY.1 showed comparable response as that with other variants. Implications of the available evidenceSARS-CoV-2 infections do not produce sterilizing immunity but protect from developing severe disease in case of Delta variant re-infection indicating the importance of the transmission prevention efforts even after achieving herd immunity. Delta AY. 1 infection in hamsters did not show any evidence of speculated immune evasion.

molecular biology↗