Search bioRxiv⌕ Search

Biology subjects

Ghosh, S.

Publications and source records attributed to Ghosh, S..

At least 181 records · Page 10Linked to original sources

Large Language Models for Pathway Curation: A Preliminary Investigation

The pathway curation task involves analyzing scientific literature to identify and represent cellular processes as pathways. This process, often time-consuming and labor-intensive, requires significant curation efforts amidst the rapidly growing biomedical literature. Natural Language Processing (NLP) offers a promising method to automatically extract these interactions from scientific texts. Despite immense progress, there remains room for improvement in these systems. The emergence of Large Language Models (LLMs) provides a promising solution for this challenge. Our study conducts a preliminary investigation into leveraging LLMs for the pathway curation task. This paper first presents a review of the current state-of-the-art algorithms for the pathway curation task. Our objective is to check the feasibility and formulate strategies of using these LLMs to improve the accuracy of pathway curation task. Our experiments demonstrate that our GPT-3.5 based fine-tuned models outperforms existing state-of-the-art methods. Specifically, our model achieved a 10 basis point improvement in over-all recall and F1 score compared to the best existing algorithms. These findings highlight the potential of LLMs in pathway curation tasks, warranting further research and substantial efforts in this direction. Keypoints/ObjectivesO_LIStudy evaluates the feasibility of using Large Language Models (LLMs) for pathway curation in scientific literature. C_LIO_LIUsing GPT-3.5 based fine tuned models for pathway curation, we compare its performance with existing methods, focusing on precision, recall and F1 score metrics. C_LIO_LIEmphasize the promise and need for further research on using LLMs for pathway curation. C_LI

systems biology↗

Infection of Alfalfa Cotyledons by an Incompatible but Not a Compatible Species of Colletotrichum Induces Formation of Paramural Bodies and Secretion of EVs

Hemibiotrophic fungi in the genus Colletotrichum employ a biotrophic phase invading host epidermal cells followed by a necrotrophic phase spreading through neighboring mesophyll and epidermal cells. We used serial block face scanning electron microscopy (SBF-SEM) to compare subcellular changes that occur in Medicago sativa (alfalfa) cotyledons during infection by Colletotrichum destructivum (compatible on M. sativa) and C. higginsianum (incompatible on M. sativa). Three-dimensional reconstruction of serial images revealed that alfalfa epidermal cells infected with C. destructivum undergo massive cytological changes during the first 60 hours following inoculation to accommodate extensive intracellular hyphal growth. Conversely, inoculation with the incompatible species C. higginsianum resulted in no successful penetration events and frequent formation of papilla-like structures and cytoplasmic aggregates beneath attempted fungal penetration sites. Further analysis of the incompatible interaction using focused ion beam-scanning electron microcopy (FIB-SEM) revealed formation of large multivesicular body-like structures that appeared spherical and were not visible in compatible interactions. These structures often fused with the host plasma membrane, giving rise to paramural bodies that appeared to be releasing extracellular vesicles (EVs). Isolation of EVs from the apoplastic space of alfalfa leaves at 60h post inoculation showed significantly more vesicles secreted from alfalfa infected with incompatible fungus compared to compatible fungus, which in turn was more than produced by non-infected plants. Thus, the increased frequency of paramural bodies during incompatible interactions correlated with an increase in EV quantity in apoplastic wash fluids. Together, these results suggest that EVs and paramural bodies contribute to immunity during pathogen attack in alfalfa.

plant biology↗

Time-resolved function of cell polarity kinases PRKCZ and PRKCI in CNS myelination

The atypical Protein Kinase C (aPKC) is a critical component of the PAR polarity complex, as well as of cell polarity in general. There are two paralogs of aPKC in the mammalian genome. Their expression pattern and functional role in oligodendrocyte lineage differentiation and development remains heretofore uncharacterized. Here we show that both paralogs of aPKC - PRKCI, the primary transcript of Prkci and PKMz, an alternate transcript of Prkcz - are expressed during oligodendrocyte differentiation, yet are functionally non-redundant. Asymmetric cell division and early specification of the oligodendrocyte fate stage required both paralogs. By contrast, the stage of oligodendrocyte maturation involving membrane polarization and myelination of axons continued to require PKMz, but no longer needed PRKCI. Taken together, our results indicate to a two-stage role of aPKCs and cell polarity in oligodendrocyte differentiation and development.

developmental biology↗

Multi-omic Analysis Identifies Glioblastoma Dependency on H3K9me3 Methyltransferase Activity

Histone H3 Lysine 9 dimethylation or trimethylation (H3K9me2 or H3K9me3) marks more than half of the human genome, particularly in heterochromatin regions and specific genes within euchromatic regions. Enzymes catalyzing the methylation of H3K9 have individually been associated with the modulation of gene expression patterns involved in cancer progression, including suppressor of variegation 3-9 homologue 1 (SUV39H1), SUV39H2, SET domain bifurcated 1 (SETDB1), SETDB2, euchromatic histone-lysine N-methyltransferase 1 and 2 (EHMT1/2). However, a comprehensive comparison and understanding of the characteristics and mechanisms of these chromatin-modifying enzymes in cancers remains incompletely understood. In this study, we demonstrated that these six H3K9 methyltransferases differentially expressed in tumors and correlated expression with somatic copy number variations (CNVs) and DNA methylation patterns. Through integrative multi-omics analyses, we identified SUV39H1, SUV39H2, and SETDB1 as the key players among the six H3K9 methyltransferases that exhibited the most significant associations with cancer phenotypes. By incorporating SUV39H1, SUV39H2, and SETDB1, we developed a novel signature termed "H3K9me3 MtSig" (H3K9me3 methyltransferases signature). H3K9me3 MtSig was unique for various tumor types, had prognostic implications and was linked to significant signaling pathways, particularly in glioblastoma (GBM). Furthermore, elevated H3K9me3 MtSig was confirmed in GBM patient-derived cells and tissues. In addition, single-cell expression analysis of H3K9me3 MtSig in GBM tissues demonstrated a pattern related to the G2/M cell cycle and was negatively correlated with immune responses. H3K9me3-mediated repetitive sequence silencing by H3K9me3 MtSig, determined using ChIP-sequencing, contributed to these phenotypes, and inhibiting H3K9me3 MtSig in patient-derived GBM cells suppressed proliferation and increased immune responses. Translationally, H3K9me3 MtSig performed as an independent prognostic factor in a clinical prediction model, and drug susceptibility screening integrating H3K9me3 MtSig identified potential biomarkers and therapeutics for GBM. In summary, H3K9me3 MtSig has the potential to elucidate novel prognostic markers, therapeutic targets, and predictors of treatment response in GBM and other cancer types for clinical intervention. SignificanceDifferential expressions of H3K9 methyltransferases across cancers correlates with clinical outcomes; in GBM, an H3K9me3 methyltransferase signature links to G2/M cell cycle, immune response pathways, and prognosis, aiding biomarker and treatment development.

cancer biology↗

TAM receptors control actomyosin dynamics in osteoclasts via RHOA-COFILIN-MYOSIN II signaling

The TAM family of receptor tyrosine kinases were recently identified to regulate bone homeostasis by controlling osteoblasts and bone formation. Despite extensive knowledge of TAM receptor function in the mononuclear phagocyte system, the role of TAM receptors in osteoclasts remains largely unknown. Here, we identify a physiological regulatory system including MERTK and TYRO3 in osteoclasts controlling RHOA-ROCK-COFILIN/Myosin II signaling, thereby antagonistically regulating osteoclast-mediated bone remodeling to maintain bone homeostasis. Myeloid-specific lysozyme M-mediated deletion of Mertk led to increased bone mass in mice. In early stages of RANKL-induced osteoclast differentiation MERTK promotes amoeboid migration mode in osteoclast precursor cells by inducing RHOA-COFILIN-MLC2 pathway leading to increased osteoclast formation. In contrast, TYRO3 inhibits RHOA-ROCK signaling in osteoclast precursor cells thereby inhibiting these processes. Furthermore, we unraveled an inhibitory role of MERTK as well as TYRO3 in osteoclast differentiation and function. In line with this, mice with cathepsin K-mediated deletion of Mertk and Tyro3 exhibited an osteoporotic bone phenotype. We found that osteoclast precursor cell morphology dictates its fusion capacity and identified MERTK as a negative regulator of osteoclast fusion. In multinucleated cells, deletion of Mertk inhibits actin ring formation by mediating central actomyosin contraction and inactivation of COFILIN. In contrast, spatially well-ordered RHOA activation at adhesion structures, induced by loss of Tyro3, improves osteoclast biomechanotransduction to ameliorate podosome belt formation and enhance osteoclast function. By using a syngeneic breast cancer bone metastasis osteolysis models we identified TYRO3 as a bone protective receptor for osteolytic bone diseases, whereas MERTK represents a pharmacologic accessible target to inhibit osteoclast formation because its stimulatory effects of osteoclast precursors prevail the inhibitory effects on mature osteoclasts. Next to the recently uncovered role of MERTK as a target for osteoanabolic therapy MERTK may represent a one-drug two-target treatment strategy to increase osteoblast function and reduce osteoclast formation for treatments of bone diseases.

cell biology↗

Plant Development Drives Dynamic Shifts in the Root Compartment Microbiomes of Wild and Domesticated Finger Millet Cultivars

BackgroundPlant-microbe interactions in two root compartments - the rhizosphere and endosphere - play vital roles in maintaining plant health and ecosystem dynamics. The microbial communities in these niches are shaped in complex ways by factors including the plants developmental stage and cultivar, and the compartment where the interactions occur. Different plant cultivars provide distinct nutritional and ecological niches and may selectively enrich specific microbial populations through the secretion of root exudates. This gives rise to complex and dynamic plant-microbe interactions; some cultivars promote the recruitment of beneficial symbionts while others may deter pathogens. To clarify these processes, this work investigated the structure of the endosphere and rhizosphere microbial communities of wild type finger millet and five domesticated cultivars across two plant developmental stages. ResultsOur results showed that the plant developmental stage, compartment, and cultivar have varying degrees of impact on root-associated microbiomes. The dominant bacterial phyla in all samples were Proteobacteria, Actinobacteria, and Bacteroidetes, while the dominant fungal phyla were Ascomycota and Basidiomycota. All of these phyla exhibited pronounced variations in abundance. In general, an increased abundance of Actinobacteria in the endosphere was accompanied by a reduced abundance of Proteobacteria. The most pronounced changes in microbial community structure were observed in the rhizosphere during the flowering stage. Changes in the microbiome patterns of the rhizosphere were driven predominantly by the genus Pseudomonas. Moreover, the host plants developmental stage strongly influenced the microbial communities, suggesting that plants can recruit specific taxa based on their need for particular soil consortia. ConclusionsOur results show that both host developmental stage and domestication strongly affect the assembly and structure of the plant microbiome. Moreover, plant root compartments can selectively recruit specific taxa from associated core microbial communities to fulfill their needs in a manner that depends on both the plants developmental stage and the specific root compartment that is involved. These findings show that deterministic selection pressures exerted by plants during their growth and development can significantly affect their microbial communities and have important implications for efforts to create tools for manipulating the microbiome to sustainably improve primary productivity.

microbiology↗

Crude extract of Ruellia tuberosa L. flower induces intracellular ROS, promotes DNA damage and apoptosis in Triple Negative Breast Cancer Cells

Ethnophamacological relevanceIn the traditional folklore medicine system, the primary uses of Ruellia tuberosa L. include as a diuretic, anti-hypertensive, antipyretic, anti-diabetic, analgesic, and gastroprotective agent. Some reports also demonstrated that it has been used to treat gonorrhea-like diseases. PurposeExploring the anti-cancer potential of the methanolic extract of Ruellia tuberosa L. flower (RTME) with special emphasis on human triple-negative breast cancer (TNBC) and investigating the possible signaling networks and regulatory pathways underlying it. MethodsPreparation of RTME and identifying the possible phytochemicals through GC-MS analysis. The anti-cancer potential of RTME was executed through in-vitro cytotoxicity assay, clonogenic assay, wound healing assay, ROS generation assay, cell cycle arrest, apoptotic nuclear morphology study, cellular apoptosis study, mitochondrial membrane potential (MMP) alteration study, protein and gene expressions alteration study. Apart from this, toxicological status and in-silico molecular docking studies were also conducted. ResultsFrom this study, it was obvious that several phytochemicals within RTME have the potential to act as anti-cancerous agents. RTME was found to exhibit significant in-vitro cytotoxicity along with a reduction in colony formation and inhibition of cell migratory potential in MDA-MB-231 cells. RTME also induced intracellular ROS, promoted G0/G1 cell cycle arrest, caused mitochondrial membrane potential (MMP) alteration, and promoted cell death. From the pro- and anti-apoptotic marker study through the western blot and the qRT-PCR analysis, it was revealed that RTME promoted the intrinsic pathway of apoptosis. Furthermore, blood parameters and histological analysis revealed that RTME doesnt exhibit any toxic effect on female Balb/C mice. Finally, an in-silico molecular docking study revealed that the three identified lead phytochemicals in RTME show strong receptor-ligand interactions with the anti-apoptotic Bcl-2 and give a clue to the possible molecular mechanism of the RTME extract. ConclusionFrom the findings, it was concluded that RTME has a significant therapeutic potential against TNBC which could be an alternative option for anti-cancer drug development. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=188 SRC="FIGDIR/small/586749v1_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@72780corg.highwire.dtl.DTLVardef@1276029org.highwire.dtl.DTLVardef@1a2d91org.highwire.dtl.DTLVardef@a5cb44_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIPreparation of methanolic extract of Ruellia tuberosa L. flower, C_LIO_LIIdentification of phytochemicals from the methanolic extract of Ruellia tuberosa L. flower, C_LIO_LIMethanolic extract of Ruellia tuberosa L. (RTME) flower exhibited significant anti-cancer potential in triple-negative breast cancer (TNBC) cells, MDA-MB-231 through induction of intracellular ROS, G0/G1 cell cycle arrest, and apoptosis, C_LIO_LIToxicological assessments of RTME on female Balb/C mice, C_LIO_LIIn-silico assessments of lead phytochemicals with the target anti-apoptotic protein, bcl-2 C_LI

cancer biology↗

MelAnalyze: Fact-Checking Melatonin claims using Large Language Models and Natural Language Inference

With the explosion of health related information in mainstream discourse, distinguishing accurate health-related claims from misinformation is important. Using computational tools and algorithms to help is key. Our focus in this paper is on the hormone Melatonin which is claimed to have broad health benefits and largely sold as a supplement. This paper introduces MelAnalyze, a framework for using generative and transformer-based deep learning models adapted as a natural language inference (NLI) task, to semi-automate the fact-checking of general melatonin claims. MelAnalyze is built upon a comprehensive collection of melatonin-related scientific abstracts from PubMed for validation. The framework incorporates components for precise extraction of information from scientific literature, semantic similarity and NLI. At its core, MelAnalyze leverages pre trained NLI models that are fine-tuned on melatonin-specific claims along with semantic search based on vectorized representation of the articles. The best models, fine-tuned on LLaMA1 and RoBERTa, attain good precision, recall, and F1-scores of approximately 0.92. We also introduce a user-friendly web-based tool for fact-checking algorithm evaluation and use. In summary, we show MelAnalyzes role in empowering users and researchers to assess melatonin-related claims using evidence-based decision-making.

bioinformatics↗

Enhanced extracellular matrix remodeling due to embedded spheroid fluidization

Tumor spheroids are in vitro three-dimensional, cellular collectives consisting of cancerous cells. Embedding these spheroids in an in vitro fibrous environment, such as a collagen network, to mimic the extracellular matrix (ECM) provides an essential platform to quantitatively investigate the biophysical mechanisms leading to tumor invasion of the ECM. To understand the mechanical interplay between tumor spheroids and the ECM, we computationally construct and study a three-dimensional vertex model for a tumor spheroid that is mechanically coupled to a cross-linked network of fibers. In such a vertex model, cells are represented as deformable polyhedrons that share faces. Some fraction of the boundary faces of the tumor spheroid contain linker springs connecting the center of the boundary face to the nearest node in the fiber network. As these linker springs actively contract, the fiber network remodels. By toggling between fluid-like and solid-like spheroids via changing the dimensionless cell shape index, we find that the spheroid rheology affects the remodeling of the fiber network. More precisely, fluid-like spheroids displace the fiber network more on average near the vicinity of the spheroid than solid-like spheroids. We also find more densification of the fiber network near the spheroid for the fluid-like spheroids. These spheroid rheology-dependent effects are the result of cellular motility due to active cellular rearrangements that emerge over time in the fluid-like spheroids to generate spheroid shape fluctuations. These shape fluctuations lead to emergent feedback between the spheroid and the fiber network to further remodel the fiber network with, for example, lower radial alignment of the higher-tensioned fibers given the breaking of spheroidal radial symmetry, which can then further remodel the spheroid. Our results uncover intricate morphological-mechanical interplay between an embedded spheroid and its surrounding fiber network with both spheroid contractile strength and spheroid shape fluctuations playing important roles in the pre-invasion stages of tumor invasion.

biophysics↗

Assessment of Antibiotic Resistance Profiles in Cultivable Coliform Organisms Isolated from Ganga River Waters Across the Upper, Middle, and Lower Ganga Stretch

Antibiotic resistance in coliform organisms isolated from the Ganga River waters across its Upper, Middle, and Lower stretches was assessed. The study revealed varying levels of antibiotic resistance among the coliform isolates, with differences observed across the different stretches of the river. In the Upper stretch, sites like Devprayag and Gangotri exhibited high levels of E. coli contamination, with corresponding moderate antibiotic resistance (MAR) values. In the Middle stretch, sites like Farrukhabad and Bithoor showed lower E. coli contamination compared to the Upper stretch but had higher MAR values. The Lower stretch, particularly sites like Revelganj and Bahachoki in Bihar, displayed significantly elevated E. coli contamination levels and MAR values. These findings underscore the presence of antibiotic-resistant coliform organisms in different segments of the Ganga River, emphasizing the need for targeted interventions to mitigate antibiotic resistance spread in this vital water resource. Understanding the antibiotic resistance profiles at specific sites along the Ganga River can inform strategies to preserve water quality and protect public health in regions dependent on this iconic river.

microbiology↗

Nuclear compression-mediated DNA damage drives ATR-dependent Lamin expression and mouse ESC differentiation

Embryonic stem cells (ESCs) which are susceptible to DNA damage depend on a robust and highly efficient DNA damage response (DDR) mechanism for their survival. However, the implications of physical force-mediated DNA damage on ESC fate remains unclear. We show that stiffness-dependent spreading of mouse ESCs (mESCs) induces DNA damage through nuclear compression, with DNA damage causing differentiation through early induction of Lamin A/C expression. Interestingly, differentiation is associated with rescue of DNA damage and activation of the DDR factor ATR. While ATR is typically known to play roles in DDR pathway, its role during stiffness-mediated nuclear compression and mESC differentiation is unknown. Nuclear enrichment of activated ATR on stiff substrates and reduction of Lamin A/C expression upon ATR inhibition suggests that mESC differentiation is driven by nuclear compression-mediated DNA damage and involves ATR-dependent modulation of Lamin A/C.

cell biology↗

Abnormal global longitudinal strain and reduced serum inflammatory markers in cardiac AL amyloidosis patients without significant amyloid fibril deposition

BackgroundCardiac dysfunction in AL amyloidosis is thought to be partly related to the direct impact of AL LCs on cardiomyocyte function, with the degree of dysfunction at diagnosis as a major determinant of clinical outcomes. Nonetheless, mechanisms underlying LC-induced myocardial toxicity are not well understood. MethodsWe identified gene expression changes correlating with human cardiac cells exposed to a cardiomyopathy-associated {kappa}AL LC. We then sought to confirm these findings in a clinical dataset by focusing on clinical parameters associated with the pathways dysregulated at the gene expression level. ResultsUpon exposure to a cardiomyopathy-associated {kappa}AL LC, cardiac cells exhibited gene expression changes related to myocardial contractile function and inflammation, leading us to hypothesize that there could be clinically detectable changes in GLS on echocardiogram and serum inflammatory markers in patients. Thus, we identified 29 patients with normal IVSd but abnormal cardiac biomarkers suggestive of LC-induced cardiac dysfunction. These patients display early cardiac biomarker staging, abnormal GLS, and significantly reduced serum inflammatory markers compared to patients with clinically evident amyloid fibril deposition. ConclusionCollectively, our findings highlight early molecular and functional signatures of cardiac AL amyloidosis, with potential impact for developing improved patient biomarkers and novel therapeutics.

cell biology↗

Application of Quantum Tensor Networks for Protein Classification

Computational methods in drug discovery significantly reduce both time and experimental costs. Nonetheless, certain computational tasks in drug discovery can be daunting with classical computing techniques which can be potentially overcome using quantum computing. A crucial task within this domain involves the functional classification of proteins. However, a challenge lies in adequately representing lengthy protein sequences given the limited number of qubits available in existing noisy quantum computers. We show that protein sequences can be thought of as sentences in natural language processing and can be parsed using the existing Quantum Natural Language framework into parameterized quantum circuits of reasonable qubits, which can be trained to solve various proteinrelated machine-learning problems. We classify proteins based on their sub-cellular locations--a pivotal task in bioinformatics that is key to understanding biological processes and disease mechanisms. Leveraging the quantum-enhanced processing capabilities, we demonstrate that Quantum Tensor Networks (QTN) can effectively handle the complexity and diversity of protein sequences. We present a detailed methodology that adapts QTN architectures to the nuanced requirements of protein data, supported by comprehensive experimental results. We demonstrate two distinct QTNs, inspired by classical recurrent neural networks (RNN) and convolutional neural networks (CNN), to solve the binary classification task mentioned above. Our top-performing quantum model has achieved a 94% accuracy rate, which is comparable to the performance of a classical model that uses the ESM2 protein language model embeddings. Its noteworthy that the ESM2 model is extremely large, containing 8 million parameters in its smallest configuration, whereas our best quantum model requires only around 800 parameters. We demonstrate that these hybrid models exhibit promising performance, showcasing their potential to compete with classical models of similar complexity.

bioinformatics↗

The transition from a non-westernized to westernized gut microbiome in Indian-Immigrants and Indo-Canadians is associated with dietary acculturation

Indian immigration to westernized countries has recently surged, increasing their risk of Inflammatory Bowel Disease (IBD) post-migration. While crucial for understanding IBD risk, the gut microbiome remains understudied in Indians. This cross-sectional study examines the gut microbiomes of Indians residing in India, Indo-Immigrants, and Indo-Canadians in comparison to Euro-Canadian and Euro-Immigrant controls to understand the impact of westernization on their gut. Stool samples for 16S rRNA and shotgun sequencing assessed microbial taxa and functional profiles, complemented by dietary and demographic data to evaluate lifestyle patterns. Results revealed distinct microbiotas in Indians and Indo-Immigrants compared to control groups, with high abundances of Prevotella spp. and CAZymes reflecting their high complex carbohydrate diet. Indo-Canadians exhibited a transitional microbiome towards westernization, mirroring increasing dietary acculturation. Considering 44% of Canadians are first- and second-generation immigrants and the global adoption of westernized practices, future research should investigate the health implications of such microbiome transitions in immigrant populations and newly industrialized nations.

microbiology↗

Evaluation Of Suitability Analysis of Gangetic Water from Upper, Middle, And Lower Ganga Rivers

This study assesses the suitability of water from distinct segments of the Ganga River in India for drinking, irrigation, and industrial purposes, utilizing various indices. Conducted in MAR-MAY 2023, water samples were collected from multiple sites along the river, and categorized into upper, middle, and lower stretches. The findings revealed differing levels of suitability for various purposes among the sampled sites within each stretch. Parameters for drinking water quality generally adhered to specified limits across all stretches, except for E. coli, emphasizing the importance of disinfection measures. Moreover, the study evaluated irrigation suitability, with most sites falling within the good to excellent range, albeit some exhibiting elevated sodium levels, particularly in the lower stretch. Analysis of major ion abundance revealed an alkaline nature dominated by sodium and potassium ions over calcium and magnesium ions across all stretches. Heavy metal concentrations were either within specified limits or absent, indicating minimal industrial pollution. However, caution is warranted regarding industrial applications due to water aggressiveness, as suggested by indices such as the Langelier saturation index and Ryznar stability index, which hint at potential corrosion issues. Water quality in the Ganga River in India exhibited variability across the upper, middle, and lower stretches, with each segment presenting unique characteristics and suitability levels. Continuous monitoring and control measures, especially concerning the most probable number (MPN) of contaminants, are imperative to ensure the sustainability of water quality and meet the diverse usage needs along the river. The evaluation of Gangetic water from the Upper, Middle, and Lower Ganga Rivers is crucial for understanding water quality in one of Indias vital river basins. This study assesses physical, chemical, and biological parameters to determine suitability for drinking, irrigation, and aquatic life. Factors like pH, dissolved oxygen, turbidity, nutrients, heavy metals, and microbial load are analyzed to reveal water quality and potential risks. Temporal and spatial variations, influenced by natural processes and human activities, are explored. The findings aid in sustainable water management and conservation in the Gangetic basin, addressing the urgent need to safeguard this critical resource.

microbiology↗

Addressing anemia severity in antimony-resistant Leishmania donovani infection at the nexus of oxidative outburst and iron transit

Despite the withdrawal of pentavalent-antimonials in treating Visceral leishmaniasis for more than a decade, recent clinical isolates of Leishmania donovani (LD) exhibit unresponsiveness towards pentavalent-antimony (LD-R). This antimony-unresponsiveness points towards a genetic adaptation that underpins LD-Rs evolutionary persistence and superiority over sensitive counterparts. This study highlights LDs response to antimony exposure in terms of increased potential of scavenging host-derived iron within its parasitophorous vacuoles (PV). LD-R employs a strategy to both produce and rapidly scavenge host-iron in a ROS-dependant manner, and selectively reshuffle iron exporter, Ferroportin, around its PV. Higher iron utilization leads to subsequent iron-insufficiency, compensated by increased erythrophagocytosis facilitated by the breakdown of SIRP, orchestrated by a complex interplay of two proteases, Furin and ADAM10. Understanding these mechanisms is crucial for managing LD-R infections and their associated complications, like anemia, and may also provide valuable insights into understanding resistance developed in other pathogens that rely on host iron.

microbiology↗

Unraveling the Interplay between Phytochemicals and Rhizosphere Bacteria in Ficus racemosa

Plant-microbe interactions in the rhizosphere play crucial roles in plant health and ecosystem functioning. Despite extensive research, gaps persist in understanding the relationship between phytochemicals and rhizosphere bacteria, particularly in species like Ficus racemosa. This study aims to investigate this interplay by characterizing the diversity and abundance of rhizosphere bacteria in Ficus racemosa and assessing the influence of phytochemical composition on microbial community structure and function. Through a multidisciplinary approach integrating microbiology and phytochemistry, our findings contribute to a holistic understanding of rhizosphere ecology and inform strategies for optimizing plant-microbe interactions in agricultural and environmental contexts.

microbiology↗

A proteome-wide quantitative guide for nanoscale spatially resolved extraction of membrane proteins into native nanodiscs

The intricate molecular environment of the native membrane profoundly influences every aspect of membrane protein (MP) biology. Despite this, the most prevalent method of studying MPs uses detergent-like molecules that disrupt and remove this vital local membrane context. This severely impedes our ability to quantitatively decipher the local molecular context and comprehend its regulatory role in the structure, function, and biogenesis of MPs. Using a library of membrane-active polymers we have developed a platform for the high-throughput analysis of the membrane proteome. The platform enables near-complete spatially resolved extraction of target MPs directly from their endogenous membranes into native nanodiscs that maintain the local membrane context. We accompany this advancement with an open-access database that quantifies the polymer-specific extraction variability for 2065 unique mammalian MPs and provides the most optimized condition for each of them. Our method enables rapid and near-complete extraction and purification of target MPs directly from their endogenous organellar membranes at physiological expression levels while maintaining the nanoscale local membrane environment. Going beyond the plasma membrane proteome, our platform enables extraction from any target organellar membrane including the endoplasmic reticulum, mitochondria, lysosome, Golgi, and even transient organelles such as the autophagosome. To further validate this platform, we took several independent MPs and demonstrated how our resource can enable rapid extraction and purification of target MPs from different organellar membranes with high efficiency and purity. Further, taking two synaptic vesicle MPs, we show how the database can be extended to capture multiprotein complexes between overexpressed MPs. We expect these publicly available resources to empower researchers across disciplines to efficiently capture membrane nano-scoops containing a target MP and interface with structural, functional, and other bioanalytical approaches. We demonstrate an example of this by combining our extraction platform with single-molecule TIRF imaging to demonstrate how it can enable rapid determination of homo-oligomeric states of target MPs in native cell membranes.

biophysics↗