Biology subjects

Tiwari, N.

Publications and source records attributed to Tiwari, N..

16 recordsLinked to original sources

bioRxiv2026

Colon-to-hind paw cross-organ sensitization is partially mediated by TrkB.T1-facilitated spinal neuroinflammation to activate lumbar DRG neurons

Patients with bowel disease can develop referred somatic pain at a later time with unknown molecular mechanisms. Using experimental mice with colitis induced by intracolonic installation of 2,4,6-Trinitrobenzenesulfonic acid (TNBS), we find an increase in the percentage of hind paw primary afferent neurons expressing Piezo2 or calcitonin gene-related peptide (CGRP), which are attenuated by TrkB.T1 knockout (KO). Concomitantly, TrkB.T1 KO also attenuates colitis-induced hind paw mechanical hypersensitivity and pain. Next, we find that TrkB.T1 is expressed in spinal cord astrocytes and its expression level is increased by colitis. TrkB.T1 KO reduces colitis-induced upregulation of Tumor necrosis factor-alpha (TNF-) mRNA but not upregulation of interleukin (IL)-6 mRNA in the spinal cord. Using calcium (Ca2+) imaging and ex vivo approaches, we find that TNF- elicits Ca2+ transients in capsaicin-sensitive as well as capsaicin-insensitive DRG neurons, and increases Piezo2 and CGRP expression in DRG neurons via distinct signaling pathways. Notably, TNF-or colitis-induced Piezo2 upregulation in L4 DRG neurons is mediated by or associated with the PI3K/Akt pathway that does not participate in CGRP upregulation. In contrast, CGRP upregulation in hind paw primary afferent neurons is associated with an upregulation of phosphorylated cAMP response element binding protein (p-CREB). Finally, we find that TrkB.T1 KO does not change the expression level of transient receptor potential cation channel subfamily V member 1 (TrpV1) in L4 DRG in colitis, explaining the ineffectiveness of TrkB.T1 KO on colitis-induced hind paw thermal hyperalgesia. These results suggest complex and distinct molecular pathways in colitis-induced somatic pain modalities and provide information for specific pain modality management.

neuroscience↗

bioRxiv2026

Alzheimer's Disease Selectively Perturbs Age-Sensitive Brain Radiomic Features Across the Disease Continuum

Normal brain aging and Alzheimers disease both involve progressive structural brain alterations, making it challenging to distinguish pathological neurodegeneration from normative aging-related atrophy. This study investigated whether Alzheimers disease exhibits radiomic patterns that mimic, diverge from, or selectively perturb age-associated structural brain changes. T1-weighted magnetic resonance imaging scans from the Alzheimers Disease Neuroimaging Initiative were analyzed using a region-wise radiomics framework across 10 anatomically defined brain regions. Radiomic features were extracted following automated segmentation, bias field correction, and intensity normalization. Age-associated radiomic patterns were first identified in cognitively normal subjects using Spearman correlation analysis. Features demonstrating significant age sensitivity were subsequently compared between cognitively normal and Alzheimers disease cohorts across age bins using Welchs two-sample t-tests with permutation-based significance estimation and false discovery rate correction. Medial temporal and limbic regions, particularly the hippocampus, entorhinal cortex, and cingulum, demonstrated consistent age-aligned radiomic trajectories with systematic, statistically significant disease-related shifts across all age bins, supported by large effect sizes and bootstrap-validated confidence intervals. In contrast, several other regions demonstrated more heterogeneous and less stable patterns of group separation across age bins. Secondary analysis using late mild cognitive impairment subjects demonstrated that these radiomic divergences are detectable at the transition from normal cognition to mild cognitive impairment, with statistically significant CN-LMCI separation but no significant LMCI-AD separation, positioning the identified markers as early-stage rather than late-stage indicators of neurodegeneration. These findings indicate that Alzheimers disease does not uniformly mimic normal aging across the brain but instead selectively perturbs radiomic features associated with normative aging trajectories. The identified markers represent promising candidates for age-adjusted radiomic biomarkers, warranting validation in independent cohorts to establish their generalisability. The fully automated nature of the analytical pipeline -- spanning segmentation, feature extraction, and statistical comparison without manual annotation -- may facilitate scalable validation of these biomarkers in larger neuroimaging cohorts.

neuroscience↗

bioRxiv2026

Pleiotropic antimalarial activities and immunomodulation exhibited by Himalayan Buransh (Rhododendron arboreum) in human and rodent malaria models

Emerging drug resistance against the malaria parasite is worrisome and necessitates the development of novel antimalarials. Himalayan Buransh (Rhododendron arboreum) is a well-known medicinal plant found in the northern states of India. In this study, we observed the pleiotropic antimalarial activities and immunomodulation exhibited by the aqueous extract of Buransh flower (AEBF). AEBF demonstrated significant IC50 values (16-29 {micro}g/ml) against the asexual stages of various P. falciparum strains (3D7, Dd2-chloroquine-resistant and C580Y-artemisinin resistant). The oral administration of AEBF (200 mg/kg) in mice, suppressed [~]80% P. berghei parasitemia, improved mean survival time (MST-23.5 days) and prevented splenomegaly. Notably, the combination of AEBF and artesunate not only cleared primary infection, but also conferred sustained immunity. This immunomodulatory effect, driven by protective IFN-{gamma} resulted in reduced parasitemia during a homologous challenge without the need for further treatment. It is important to highlight the malaria transmission blocking activity of AEBF, resulting in reduced sexual stage male gametocyte exflagellation. Furthermore, the virtual drug screening of selected bioactive constituents from Buransh flower demonstrated potent binding against multiple P. falciparum proteins, suggested a pleiotropic mode of action. Altogether, our results corroborated the first ever evidence of the multistage antimalarial potential of Buransh flower, supported by in vitro cell studies, in vivo rodent malaria model and in silico docking analyses. Based on our studys findings and the traditional use of Buransh juice as a medicinal beverage in Uttarakhand, India, we propose exploring it as an adjunct therapy for drug-resistant malaria, subject to further clinical validation.

pathology↗

bioRxiv2026

Tau regulates epithelial morphogenesis through vesicle trafficking dependent Notch activation

Tau is a conserved microtubule-associated protein best known for its roles in neuronal cytoskeletal stability and axonal transport. However, its functions in non-neuronal tissues remain poorly understood. Here we demonstrate that Drosophila Tau (dTau) regulates epithelial growth and tissue architecture in the Drosophila Malpighian tubules by controlling vesicular trafficking and Notch signaling. Loss of dTau results in pronounced epithelial hyperplasia, increased tubule diameter, and ectopic branching. Despite elevated Notch transcript levels, dTau-deficient tubules exhibit significantly reduced Notch intracellular domain (NICD), indicating impaired pathway activation. Proteomic and cellular analyses reveal widespread disruption of endocytic regulators and vesicle trafficking components, including reduced levels of the endocytic adaptor Liquid facets (Epsin) and altered distribution of Rab5, Rab7, and Rab11 endosomes. dTau loss also disrupts autophagic-lysosomal homeostasis and reduces endosome-lysosome fusion. These trafficking defects correlate with abnormal Delta localization and diminished Notch signaling. Together, our findings uncover a previously unrecognized role for dTau in maintaining epithelial signaling homeostasis by coordinating vesicular trafficking and receptor activation. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/713835v1_ufig1.gif" ALT="Figure 1"> View larger version (67K): org.highwire.dtl.DTLVardef@d8e3b6org.highwire.dtl.DTLVardef@14de1f6org.highwire.dtl.DTLVardef@2de65aorg.highwire.dtl.DTLVardef@16e2702_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2025

Early disruption of neurogenesis and neural architecture by amyloid β and Tau during Drosophila development

Alzheimers disease is recognized as a late-onset neurodegenerative disorder; however, accumulating evidence suggests that disease-associated proteins may exert deleterious effects much earlier during neural development. Using a Drosophila model expressing human amyloid-{beta} and Tau, we investigated the impact of these proteins on embryonic neurodevelopment and neural stem cell dynamics. Embryos expressing amyloid-{beta} and Tau exhibited pronounced defects in axonal patterning and compromised neuronal cytoskeletal integrity, indicating early disruption of neural architecture. We observed aberrant elevation and mislocalization of the cell fate determinant Prospero, leading to premature neuronal differentiation and disruption of progenitor lineage progression. Consequently, larval brains displayed a reduced number of Prospero-positive ganglion mother cells, reflecting impaired neuroblast lineage maintenance. Cell-cycle analysis using the FUCCI system revealed altered neuroblast cell-cycle dynamics, characterized by depletion of proliferative populations and enrichment of G1-phase cells, indicative of stem cell exhaustion. In addition, increased apoptotic signaling was detected in larval neural tissues expressing amyloid-{beta} and Tau. Together, our findings demonstrate that amyloid-{beta} and Tau disrupt asymmetric division, differentiation, and self-renewal of neural stem cells during development, resulting in reduced neuronal output and defective brain organization. This study highlights that amyloid-{beta} and Tau exert neurotoxic effects early in development, providing mechanistic insight into how neurodevelopmental perturbations may contribute to later neurodegeneration.

developmental biology↗

bioRxiv2025

MicroRNA-mRNA Gene Regulatory Circuitry Orchestrates the Epigenetic and Transcriptional Reprogramming from Pluripotency to Murine Mammary Epithelial stem-like-Cells lactogenic differentiation

MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression via mRNA degradation or translational repression. While miRNAs are established regulators of development and differentiation, their role in the dynamic mRNA transitions during lactogenic differentiation of mammary epithelial cells remains incompletely characterized. In this study, we profiled miRNA expression across four distinct developmental states: embryonic stem cells (ESCs), and three progressive stages of HC11 murine mammary epithelial differentiation, including undifferentiated growth factor-maintained cells (HC11-N), glucocorticoid-primed cells (HC11-P), and prolactin-induced lactogenic cells (HC11-PRL). By integrating these signatures with parallel mRNA expression profiles, we identified stage-specific miRNA-mRNA regulatory axes. Our analysis revealed miRNAs coordinate networks of transcription factors and epigenetic regulators to shape the lactogenic transcriptome. While ESCs and undifferentiated HC11 cells were characterized by pathways associated with pluripotency and oncogenic signalling, the pregnancy-like priming stage showed enrichment in, neurotrophin signalling. Crucially, the lactation-like state was dominated by PI3K-Akt and mTOR signalling-- critical drivers of epithelial proliferation and milk synthesis. Furthermore, the integration of miRNAs with transcriptional and epigenetic regulators highlighted the modulation of prolactin signalling and extracellular matrix-receptor interactions during lactation. This study provides a comprehensive map of the miRNA-associated post-transcriptional landscape of lactogenesis, offering a mechanistic framework for understanding mammary gland development and associated pathologies.

genomics↗

bioRxiv2025

Autism-like behavior induced by conditional ablation of the Bassoon gene in GABAergic interneurons

Synaptic dysfunction and resulting imbalance of excitatory vs. inhibitory transmission are fundamental aspects of autism spectrum disorders (ASD). Here we addressed the role of inhibitory synapse disturbances in ASD employing mice with a conditional ablation in inhibitory forebrain interneurons of the presynaptic active zone scaffolding protein Bassoon (Bsn), a key factor in synaptic development, activity and maintenance. The conditional Bsn gene knock out resulted in a reduction of synaptic vesicles and reduced synaptic efficacy of affected inhibitory synapses as well as diminished GABAergic inhibition in hippocampal pyramidal neurons. Bsn mutants further displayed a reconfiguration of the hippocampal synaptic network in vivo, as seen in subfield-specific changes of inhibitory synaptic markers and reduced numbers of parvalbumin interneurons, culminating in disturbance of hippocampal network activity patterns and profound mitochondrial and metabolic dysregulation. Importantly, the mutant mice developed behavioral abnormalities reminiscent of ASD including widespread social behavioral deficits and novelty-induced hyperarousal with altered motor behavior, increased anxiety and epileptiform activity. Bsn conditional knock out mice thus provide strong evidence for a causal involvement of GABAergic synapses in the emergence of ASD-related behavioral and physiological phenotypes.

neuroscience↗

bioRxiv2025

In-situ diversification and regional attributes shape asymmetric diversity of Miliusa (Annonaceae) in tropical Asia.

AimWe examine biogeography and speciation patterns in Miliusa Lesch. ex A. DC. ([~]65 species) distributed in tropical Asia to understand the uneven distribution of its extant diversity. LocationTropical Asia TaxonMiliusa (Annonaceae) MethodsPhylogenetic reconstruction was performed using six plastid markers across 52 species using both ML and BI approaches. Divergence times were estimated using two fossil calibrations and an optimised relaxed clock, and ancestral areas were inferred with BioGeoBEARS. Speciation rates were examined using ClaDS and the DR statistic, and community structure was assessed using phylogenetic diversity metrics. ResultsMiliusa likely originated in the mid-Miocene, with Indo-Burma and peninsular India (PI) as its ancestral range. Its extant diversity is primarily attributed to in-situ speciation, with dispersal or vicariance playing limited but important roles in PI, and Wallacea and Sahul. Lineages in Indo-Burma began accumulating in the mid-Miocene, preceding those in PI ([~]10 Myr) and Wallacea and Sahul ([~]5 Myr). PI showed signs of lineage saturation and had lower speciation rates compared to Wallacea and Sahul and Indo-Burma, both of which had similar rates. All regions exhibited phylogenetic clustering, but Indo-Burma and PI differed in their sensitivity to phylogenetic depths. Main conclusionsThe uneven diversity of Miliusa is shaped by time for speciation, age, and dispersal, although their relative influence varies across regions. In Indo-Burma, long-term geo-climatic stability and greater niche availability likely facilitated the persistence of lineages, rapid speciation, and dispersal, making it an evolutionary hotspot for Miliusa. In contrast, PI exhibited lower richness and speciation rates despite being old, likely due to the contraction of wet habitats in the Miocene that limited available niches for speciation. Lineages in Wallacea and Sahul show typical island-like radiations, with speciation rates comparable to the larger and more geo-climatically stable Indo-Burma, despite their more recent origin. Overall, our results highlight the role of Miocene-driven climatic vicariance and Pliocene-Pleistocene climatic fluctuations in shaping the diversification dynamics and regional diversity patterns across tropical Asia.

evolutionary biology↗

bioRxiv2025

PNPLA3 I148M Reduces Hepatic Triacylglycerol Secretion and Mitigates Left Ventricular Diastolic Dysfunction in MASH Diet Mice

Cardiovascular disease (CVD) is a leading cause of mortality among individuals with metabolic dysfunction-associated steatotic liver disease (MASLD). Paradoxically, the strongest genetic risk factor for MASLD, PNPLA3-I148M, is associated with a reduced risk of CVD. The mechanisms for how PNPLA3-I148M causes MASLD and preserves cardiac health are not well understood. To further investigate cardioprotective effects of PNPLA3-I148M we expressed human WT-PNPLA3, PNPLA3-I148M or a GFP control in the livers of PNPLA3-/- mice. In agreement with prior investigations, mice expressing PNPLA3-I148M displayed greater hepatic neutral lipid accumulation on chow and a Metabolic Dysfunction-Associated Steatohepatitis (MASH) promoting diet. Changes in hepatosteatosis between the groups was not due to alterations in whole body metabolic parameters, although WT-PNPLA3 promoted greater glucose intolerance on a MASH diet. Echocardiography revealed that hearts from PNPLA3-WT mice had changes in left ventricular mass and thickness following 16-weeks of MASH, but not chow diet, which was not seen in the GFP or PNPLA3-I148M groups. Moreover, PNPLA3-WT and GFP mice had reduced E/A ratios (diastolic function), post MASH diet, which was not detected in PNPLA3-I148M mice. In addition, PNPLA3-I148M reduced hepatic secretion of TAGs under a MASH, but not chow diet. The expression of PNPLA3-I148M modified the liver lipidome, while minimal effects were observed in the heart. No differences in atherosclerotic plaque formation were observed following 24 weeks of MASH diet. These findings indicate that hepatic PNPLA3-I148M promotes hepatosteatosis yet protects against diet induced cardiac remodeling and diastolic dysfunction primarily through reductions in hepatic TAG secretion.

physiology↗

bioRxiv2025

Tau mediated regulation of Rho1- cytoskeletal dynamics in shaping renal tubule development in Drosophila

The present study explored the significance of the microtubule-associated protein Tau in the morphogenesis and physiological processes of Malpighian tubules (MTs) in Drosophila melanogaster. Employing genetic manipulation techniques and microscopy, we established that Tau plays a crucial role in MTs development and function. Genetic ablation and RNAi-mediated suppression of Tau led to pronounced structural abnormalities, including cystic formations, non-uniform tubule diameters, and disorganized epithelial architecture. These aberrations are accompanied by perturbations in the cytoskeletal arrangement, compromised cellular polarity, and ionic imbalances. Functional analyses revealed deficiencies in salt homeostasis and fluid secretion within Tau-deficient tubules. Attenuation of Rho1 expression mitigated the structural defects observed in Tau mutants, highlighting the importance of Tau in modulating Rho1-mediated actin-microtubule dynamics suggesting a genetic interplay between Tau and Rho1 GTPase in orchestrating tubule morphogenesis The phenotypic parallels between Tau-deficient MTs and mammalian models of polycystic kidney disease implies an evolutionarily conserved function of Tau in tubular organ biology. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/634261v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@1f4afc6org.highwire.dtl.DTLVardef@1402eb7org.highwire.dtl.DTLVardef@bb089dorg.highwire.dtl.DTLVardef@1328b2e_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2024

Lipid Droplet Targeting of ABHD5 and PNPLA3 I148M is required to promote liver steatosis

The storage and release of triacylglycerol (TAG) in lipid droplets (LDs) is regulated by dynamic protein interactions. /{beta} hydrolase domain-containing protein 5 (ABHD5; also known as CGI-58) is a membrane/LD bound protein that functions as a co-activator of Patatin Like Phospholipase Domain Containing 2 (PNPLA2; also known as Adipose triglyceride lipase, ATGL) the rate-limiting enzyme for TAG hydrolysis. The dysregulation of TAG hydrolysis is involved in various metabolic diseases such as metabolic dysfunction-associated steatotic liver disease (MASLD). We previously demonstrated that ABHD5 interacted with PNPLA3, a closely related family member to PNPLA2. Importantly, a common missense variant in PNPLA3 (I148M) is the greatest genetic risk factor for MASLD. PNPLA3 148M functions to sequester ABHD5 and prevent co-activation of PNPLA2, which has implications for initiating MASLD; however, the exact mechanisms involved are not understood. Here we demonstrate that LD targeting of both ABHD5 and PNPLA3 I148M is required for the interaction. Molecular modeling demonstrates important resides in the C-terminus of PNPLA3 for LD binding and fluorescence cross-correlation spectroscopy demonstrates that PNPLA3 I148M greater associates with ABHD5 than WT PNPLA3. Moreover, the C-terminus of PNPLA3 is sufficient for functional targeting of PNPLAs to LD and the interaction with ABHD5. In addition, ABHD5 is a general binding partner of LD-bound PNPLAs. Finally, PNPLA3 I148M targeting to LD is required to promote steatosis in vitro and in the liver. Overall results suggest that PNPLA3 I148M is a gain of function mutation and that the interaction with ABHD5 on LD is required to promote liver steatosis.

cell biology↗

bioRxiv2023

Klebsiella Pneumoniae turns more virulent under flow stresses in capillary like microchannels

Fluidic habitats are very common to bacterial life, however, very little is known about the effect of the flow stresses on the virulence of the bacteria. In the present work, we conduct microfluidic experiments to understand the consequence of stresses generated by flowing fluid on the bacterial morphology and virulence. We consider Klebsiella pneumoniae (KP), an ESKAPE pathogen as the model bacteria that are responsible for blood stream infections like bacteremia apart from pneumonia, urinary tract infections and more. We generate four different stress conditions by changing the flow rate and channel geometry subsequently altering the shear rate and stressing time ({tau}). We observe significant changes in the structural aspects of the stressed bacteria. With an increase in stressing parameters, the viability of the bacterial sample deteriorated. Most importantly, these stressed samples proliferate much more than unstressed samples inside the RAW264.7 murine macrophages. The results shed light on the complex relationship between flow stresses and bacterial virulence. Furthermore, we challenge the bacterial samples with ciprofloxacin to see how they behave under different stress conditions. The present study can be extended to model deadly diseases like bacteremia using organ-on-a-chip technology and help understand bacterial pathogenicity under realistic environments. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/558194v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@1111ea1org.highwire.dtl.DTLVardef@f20494org.highwire.dtl.DTLVardef@10ac86dorg.highwire.dtl.DTLVardef@ec6eb1_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure:C_FLOATNO A schematic representation of the present work. Figure created with BioRender (www.biorender.com) C_FIG

biophysics↗

bioRxiv2023

Intermittent Fasting induced ketogenesis inhibits mouse epithelial ovarian tumors by promoting anti-tumor T cell response.

Epithelial Ovarian Cancer (EOC) is the most lethal gynecologic cancer with limited genetic alterations identified that can be therapeutically targeted. In tumor bearing mice, short-term fasting, fasting mimicking diet and calorie restriction enhance the activity of antineoplastic treatment by modulating systemic metabolism and boosting anti-tumor immunity. We tested the outcome of sixteen-hour intermittent fasting (IF) on mouse EOC progression with focus on fasting driven antitumor immune responses. IF resulted in consistent decrease of tumor promoting metabolic growth factors and cytokines, recapitulating changes that creates a tumor antagonizing environment. Immune profiling revealed that IF profoundly reshapes anti-cancer immunity by inducing increase in CD4+ and CD8+ cells, paralleled by enhanced antitumor Th1 and cytotoxic responses, by enhancing their metabolic fitness. Metabolic studies revealed that IF generated bioactive metabolite BHB which can be a potential substitute for simulating the antitumor benefits of IF. However, in a direct comparison, IF surpassed exogenous BHB therapy in improving survival and activating anti-tumor immune response. Thus, our data provides strong evidence for IF and its metabolic mediator BHB for ameliorating EOC progression and as a viable approach in maintaining and sustaining an effective anti-tumor T cell response.

cancer biology↗

bioRxiv2020

Molecular phylogenetics and character evolution in Haplanthodes (Acanthaceae), an endemic genus from peninsular India.

Haplanthodes (Acanthaceae) is an Indian endemic genus with four species. It is closely related to Andrographis which is also mainly distributed in India. Haplanthodes differs from Andrographis by the presence of cladodes in the inflorescences, sub actinomorphic flowers, stamens included within the corolla tube, pouched stamens and oblate pollen grains. To understand the phylogenetic relationship of Haplanthodes with Andrographis and Haplanthus, another related genus, we used four plastid markers, matK, rbcL, psbA-trnH and trnGR to construct a molecular phylogeny. Our results established the monophyly of this genus and revealed a sister relationship to Andrographis and Haplanthus. Further, to understand the historical biogeography of the genus, we inferred the divergence time and performed ancestral area reconstruction. Our analyses suggest that Haplanthodes has evolved during Late Miocene 5.85 Ma [95%HPD: 2.18-10.34 Ma] in peninsular India where it might have shared a common ancestor with Andrographis. To understand character evolution, the ancestral states of important morphological characters were inferred based on the equal rate model and discussed. The generic status of Haplanthus is not resolved due to incomplete sampling.

evolutionary biology↗

bioRxiv2020

Ratio of hydrophobic-hydrophilic and positive-negative residues at lipid-water-interface influences surface expression and channel-gating of TRPV1

During evolution, TRPV1 has lost, retained or selected certain residues at Lipid-Water-Interface (LWI) and formed specific patterns there. The ratio of "hydrophobic-hydrophilic" and "positive-negative charged" residues at the inner LWI remains conserved throughout vertebrate evolution and play important role in regulating TRPV1 trafficking, localization and functions. Arg575 is an important residue as Arg575Asp mutant has reduced Capsaicin-sensitivity, surface expression, colocalization with lipid-raft markers, cell area, and increased cell lethality. This lethality is due to the disruption of the ratio between positive-negative charges there. Such lethality can be rescued by either using TRPV1-specfic inhibitor 5-IRTX or by restoring the positive-negative charge ratio at that position, i.e. by introducing Asp576Arg mutation in Arg575Asp backbone. We propose that Arg575Asp mutant confers TRPV1 in a "constitutive-open-like" condition. These findings have broader implication in understanding the molecular basis of thermo-gating and channel-gating and the microenvironments involved in such process that goes erratic in different diseases.

cell biology↗

bioRxiv2020

Eocene origin, Miocene diversification and intercontinental dispersal of the genus Drosera (Droseraceae)

Resolving the evolutionary history of plant carnivory is of great interest to biologists throughout the world. Among the carnivorous plants, Genus Drosera (Droseraceae) is highly diverse with a wide pantropical distribution. Despite being a group of interest for evolutionary biology studies since the time of Charles Darwin, the historical biogeography of this group remains poorly understood. In this study, with an improved species sampling from Genbank, we present a reanalyzed phylogenetic hypothesis of the genus Drosera. We developed a dated molecular phylogeny of Drosera from DNA sequences of nuclear ITS and chloroplast rbcL genes. Divergence times were estimated on the combined dataset using an uncorrelated lognormal relaxed clock model and a known fossil calibration implemented in BEAST. The maximum clade credibility tree was then used for ancestral range estimations using DEC+J model implemented in BioGeoBEARS. Our analysis suggests that Drosera evolved during the Mid Eocene 36 Ma [95% HPD: 49.5-26] and have diversified and dispersed from the late Miocene onwards. Ancestral areas estimated using the DEC+J models suggest an African origin followed major radiation within Australia. Diversification in Drosera is temporally congruent with the prevailing drier conditions during the Miocene. From Miocene, grasslands and open habitats dominated across continents and might have provided ecological opportunities for their dispersal and diversification. Several long-distance dispersals and range extensions and in situ radiations coinciding with the evolution of drier conditions can explain their extant distribution across continents. Overall our data set provides fresh insights into the biogeographic factors that shaped the origin and evolution of the genus Drosera.

evolutionary biology↗