Biology subjects

Mohanty, A.

Publications and source records attributed to Mohanty, A..

At least 19 recordsLinked to original sources

bioRxiv2026

A Low-Cost, Modular Hardware and Software Platform for Head-Fixed Mouse Decision-Making Tasks

Head-fixed behavior in rodents is a foundational technique in systems neuroscience which enables use of sophisticated imaging techniques in combination with animal behavior. However, accessibility of head-fixed behavior techniques is limited. Animal training consumes a large amount of experimenter labor and commercial setups, when available, are largely inflexible and financially burdensome. Here, we present a low-cost, modular, and open-source hardware and software implementation for head-fixed rodent decision-making tasks. Our design lowers experimenter labor and enables large teams of researchers to participate in animal training with minimal experimenter error using a simple touchscreen GUI and automated training progression. We demonstrate the efficacy of the platform by training a cohort of animals in a two-choice probabilistic rapid-reversal task in which mice continuously update action choices based on recent reward history. The presented design lowers the barrier to entry for laboratories seeking to conduct head-fixed rodent behavior and provides modular solutions for developing custom rigs based on experimental demands. Significance StatementHead-fixation in behaving rodents is a common neuroscience procedure that enables the use of electrical or optical techniques for neural circuit interrogation. While commercial head-fixed behavior platforms are available, their high cost and inflexibility make them unsuitable for modification or high-throughput training. This study presents a novel open-source hardware and software system for mouse head-fixed behavior. The modular design and use of low-cost components enable broad adaptability across behavioral tasks, compatibility with practical research demands, and significantly lowers the barrier to entry to head-fixed behavioral research.

neuroscience↗

bioRxiv2026

In vitro and in silico characterization of competitive inhibition and repression of DUX4 target gene activation as a therapeutic approach for facioscapulohumeral muscular dystrophy (FSHD)

Facioscapulohumeral muscular dystrophy (FSHD) is a rare neuromuscular disease caused by aberrant re-expression of the embryonic transcription factor DUX4 in skeletal muscle, which activates a toxic transcriptional program that drives progressive muscle wasting. No disease-modifying therapies currently exist. Prior work in mammalian and zebrafish models has shown that a truncated form of DUX4 retaining only its DNA-binding domain (DBD) lacks transactivation capacity and can suppress DUX4-FL-driven pathology; separately, dCas9/KRAB-based epigenetic repressors have demonstrated efficacy in silencing DUX4 expression, though CRISPR-based strategies face challenges from the repetitive nature of the D4Z4 locus, the immunogenicity associated with bacterial Cas proteins, and the payload limitations of gene delivery vehicles. Building on these findings, we corroborate that the DUX4 DBD, comprising both homeodomains, acts as a non-toxic competitive inhibitor of full-length DUX4 (DUX4-FL) at its genomic target sites, and extend this strategy by fusing the DBD to a human KRAB(ZNF10) domain, converting DUX4 from a transcriptional activator into a fully humanized epigenetic silencer of its own targets. Using a fluorescent DUX4-responsive reporter, we show that DBD alone produces dose-dependent repression of DUX4-FL transcriptional activity in HEK293T cells (200-fold at the highest inducible dose tested), while a constitutively expressed DBD-KRAB fusion produces significantly greater repression than DBD alone (949-fold versus 17-fold at a 25x molar ratio), with a similar trend observed in C2C12 myoblasts (47-fold versus 3.3-fold knockdown). To contextualize these findings and explore dosing considerations, we developed three complementary computational models - a transcription factor competitive binding model, a myotube diffusion model, and an ordinary differential equation (ODE) compartmental model - that illustrate how DBD concentration, intracellular diffusion, and population-level cell state transitions may relate to therapeutic efficacy. Together, these results corroborate and extend existing approaches into a single, fully humanized construct that may help circumvent the immunogenicity and delivery limitations of Cas-based systems.

bioengineering↗

bioRxiv2026

CDK1 facilitates RAD51-mediated DNA repair to protect dictyate stage arrested oocytes from genotoxic stress

Oocytes arrested at the dictyate stage of meiosis I must maintain genomic integrity for prolonged periods to preserve female fertility. During this extended arrest, DNA lesions arising from endogenous and exogenous sources threaten oocyte survival, yet the molecular mechanisms coordinating DNA repair in dormant oocytes remain poorly understood. Here, we identify cyclin-dependent kinase 1 (CDK1) as a critical regulator of the oocyte DNA damage response and homologous recombination (HR) repair under genotoxic stress. Using cisplatin-induced DNA damage models in fetal goat ovaries and neonatal mouse ovaries, we investigated repair mechanisms operating within the ovarian reserve. Label-free proteomic profiling revealed significant enrichment of DNA damage response pathways following cisplatin exposure, with CDK1 emerging as one of the most prominently upregulated kinases. Pharmacological inhibition of CDK1 had little effect on follicle survival under physiological conditions but aggravated oocyte and follicle loss following DNA damage, indicating a stress-dependent role for CDK1 in preserving ovarian follicle pool integrity. Mechanistically, DNA damage activated a Chk2-dependent signaling pathway that promoted p63 phosphorylation and altered the WEE1-CDK1 regulatory axis, resulting in reduced inhibitory CDK1 phosphorylation (Thr14/Tyr15) and increased activating phosphorylation (Thr161). Activated CDK1 was associated with enhanced RAD51 phosphorylation and accumulation at DNA damage foci, supporting homologous recombination (HR)-mediated repair in dictyate-arrested oocytes. In contrast, CDK1 inhibition reduced phospho-RAD51 levels, impaired RAD51 localization, increased persistent {gamma}H2AX accumulation, and elevated oocyte apoptosis. Notably, suppression of CDK1 was accompanied by increased expression of the non-homologous end joining (NHEJ) marker Ku80 and the nucleotide excision repair (NER) factor XPA, suggesting increased engagement of alternative DNA repair pathways. Furthermore, inhibition of Chk2 abolished the DNA damage-associated CDK1 activation signature and restored WEE1 expression, supporting a model in which CDK1 functions downstream of Chk2 signaling during the oocyte DNA damage response. Collectively, our findings identify a previously unrecognized Chk2-CDK1-RAD51 signaling axis that coordinates homologous recombination repair in dormant oocytes and safeguards ovarian follicular pool integrity under genotoxic stress. These findings provide new mechanistic insight into how dictyate-arrested oocytes maintain genome stability during prolonged meiotic arrest.

Cell Biology↗

bioRxiv2026

Monitoring Sphingomyelin Biosynthesis at Nanoscale Resolution by Expansion Microscopy

Sphingomyelin is the most abundant sphingolipid in mammalian cells and is synthesized by two isoenzymes, sphingomyelin synthase 1 and 2, located in the Golgi and in the plasma membrane. Abnormal sphingomyelin synthesis is associated with infections and diseases such as diabetes and cancer. Measuring cellular sphingomyelin synthase activity fosters our understanding of how these enzymes are involved in pathological processes and can be crucial for the identification of therapeutic compounds modifying sphingomyelin biosynthesis. We have developed a novel fluorometric assay that enables microscopic detection of cellular sphingomyelin synthase activity. We show that sphingomyelin synthases use propargyl choline and -NH2-{omega}-N3-C6-ceramide to generate trifunctional sphingomyelin, a lipid derivative detectable with spatial resolution via Forster resonance energy transfer. By combining this assay with expansion microscopy, a super-resolution imaging technique, we measured the distribution of de novo synthesized trifunctional sphingomyelin in cells at nanoscale resolution, thereby directly demonstrating sphingomyelin biosynthesis at the Golgi and the plasma membrane. By monitoring sphingomyelin biosynthesis and degradation in cells infected with the obligate intracellular pathogen Chlamydia trachomatis, we dissected the complex sphingolipid metabolization of these bacteria with unprecedented resolution. By correlating spatial metabolic information with lipidomics, we provide a powerful tool for investigating cellular sphingomyelin metabolism. TeaserCombining functional lipids, expansion microscopy and FRET helps visualise sphingolipid metabolism at unprecedented resolution.

biochemistry↗

bioRxiv2026

HIPK2-and IKKβ-dependent phosphorylation stabilizes TAp63α during the oocyte DNA damage response

TAp63, a member of the p53 family, serves as a central quality control factor in oocytes, safeguarding genomic integrity during the prolonged dictyate arrest of meiosis. In healthy oocytes, TAp63 is maintained in an inactive dimeric state; upon DNA damage, it undergoes phosphorylation-dependent tetramerization, enabling transcriptional activation of pathways that determine oocyte fate. While the upstream activation cascade of TAp63 has been well characterized, the mechanisms that regulate its stability during the DNA damage response remain incompletely understood. Here, we identify the kinases HIPK2 and IKK{beta} as key regulators of TAp63 stability. We show that TAp63 interacts with both kinases and is phosphorylated at distinct residues, T452 by HIPK2 and S4/S12 by IKK{beta} in vitro and in vivo, in addition to previously described CHK2 and CK1-mediated phosphorylation. Functionally, these phosphorylation events do not primarily contribute to activation, but instead stabilize TAp63 by limiting MDM4-dependent ubiquitination and subsequent proteasomal degradation. Mechanistically, our data support a model in which CHK2 and CK1 initiate TAp63 phosphorylation, while HIPK2 and IKK{beta} act in a complementary manner to maintain protein stability during genotoxic stress. Disruption of HIPK2 or IKK{beta} activity reduces TAp63 stability, whereas their inhibition in vivo attenuates oocyte loss following DNA damage, resulting in increased preservation of the follicle pool. Importantly, these effects are observed across multiple systems, including mouse models and ex vivo goat ovary cultures, supporting an evolutionarily conserved role for this regulatory axis. Together, our findings uncover a previously unidentified layer of TAp63 regulation, in which phosphorylation not only contributes to its activation but also enhances protein stability, thereby fine-tuning oocyte responses to DNA damage. Our results further indicate that HIPK2 and IKK{beta}-mediated phosphorylation modulates oocyte survival under genotoxic stress, highlighting this pathway as a potential target for strategies aimed at limiting oocyte loss.

cell biology↗

bioRxiv2026

Humidity shapes the thermal niche of Anopheles stephensi,an invasive malaria vector

Vector-borne pathogens cause 17% of all human infectious diseases, and rising global temperatures are shifting the distribution and abundance of mosquito vectors. Because mosquitoes are ectotherms, temperature strongly governs biological rates and physiology; however, mosquitoes also experience other environmental factors that may interact with temperature to shape the thermal performance of traits driving population dynamics. Here, we use a factorial life-table experiment spanning five relative humidities (30-90%) and seven temperatures (16-38{whitebullet}C) to show that humidity modifies the thermal performance of key fitness traits in adult Anopheles stephensi, an invasive urban malaria vector. When integrated into a demographic model, humidity markedly reshapes projections of population fitness relative to temperatureonly models, suppressing growth and contracting year-round suitability in hot, arid regions while enhancing fitness in more humid or high-elevation climates characteristic of South Asia and Africa. Together, these results highlight the need to integrate multiple environmental drivers into projections of climatic suitability, as temperature-only approaches may mischaracterize both the magnitude and spatial structure of mosquito population fitness. More broadly, our findings demonstrate how moisture availability reshapes thermal niches, population fitness, and climate-driven projections of vector distributions.

ecology↗

bioRxiv2026

SUMO modulates meiotic crossover rates between and within vertebrate species

Crossing over during meiosis drives genetic diversity and ensures the accurate segregation of homologous chromosomes. Variation in the rate of crossing over has been linked to evolutionary divergence and environmental adaptability, shaping fitness and responses to selective pressures. Despite its significance, the molecular mechanisms underlying this variation remain poorly understood. Crossover sites are selected from a large pool of potential sites initiated by programmed DNA double-strand breaks. Post-translational modification by SUMO (Small Ubiquitin-like Modifier) has been implicated in this process. Here, we show that crossover rate, chromosome length, and abundance of chromosome-associated SUMO are positively correlated across a range of vertebrate species, including mouse, chicken, pig, cattle, sheep, and goat. Crossover variation between goat breeds across the Indian subcontinent was also positively correlated with chromosomal SUMO level. Furthermore, modulating SUMO levels in cultured goat spermatocytes altered crossover frequency. Cumulatively, these observations point to a central role for SUMO in mediating crossover variation both between and within vertebrate species.

cell biology↗

bioRxiv2025

Lipid Droplet Remodeling Safeguards Redox Balance through the DGAT1-PANK2-NRF2 Axis in Mammalian Oocytes and Drives Age-Associated Decline

How lipid droplets (LDs) buffer metabolic stress and redox imbalance in aging oocytes remains poorly understood. Here, we identify de novo LD remodeling as a metabolic capacitor that couples lipid storage to mitochondrial fitness and oxidative resilience in mammalian oocytes. Live imaging revealed pronounced LD dynamics, with LD number peaking at metaphase I and declining by metaphase II, while LD area shifted inversely. Despite stable triacylglyceride and free fatty acid pools, {beta}-oxidation increased sharply, indicating elevated lipid turnover during meiotic progression. Spatial mapping and fatty-acid tracing demonstrated that newly synthesized lipids are actively incorporated into LDs, which arise primarily from the endoplasmic reticulum and engage with lysosomes and mitochondria. Acute inhibition of DGAT1, the rate-limiting enzyme of LD biogenesis, disrupted meiotic maturation and triggered oxidative stress, mitochondrial aggregation, and ultrastructural damage. Proteomic profiling revealed robust PANK2 upregulation and suppression of NRF2-linked antioxidant pathways. Mechanistic analyses showed that {beta}-oxidation blockade, PANK2 inhibition, antioxidant supplementation, or NRF2 activation each partially rescued DGAT1-dependent defects, and genetic validation in NRF2-null oocytes confirmed pathway dependence. Notably, aged oocytes exhibited reduced de novo LD biogenesis and impaired DGAT1-ER organization despite increased LD accumulation, resulting in smaller, metabolically inert droplets and a mismatch between lipid formation and utilization. Inhibiting PANK2 alleviated oxidative stress in aged oocytes, further implicating the DGAT1-PANK2-NRF2 axis in redox control and oocyte quality. Together, these findings establish LD biogenesis as a core metabolic capacitor safeguarding mitochondrial and organelle integrity during meiosis and reveal dysfunction of the DGAT1-PANK2-NRF2 axis as a mechanistic driver of reproductive aging.

cell biology↗

bioRxiv2025

Discrete interneuron subsets participate in GluN1/GluN3A excitatory glycine receptor (eGlyR)-mediated regulation of hippocampal network activity throughout development and evolution.

Decades of studies implicating GluN3A N-methyl-D-aspartate receptor (NMDAR) subunits in physiological and pathological function have largely been interpreted through direct regulation of conventional glutamatergic NMDARs. However, emerging evidence indicates that GluN3A frequently assembles with GluN1 forming unconventional glutamate-insensitive NMDARs that operate as native excitatory glycine receptors (eGlyRs). Here we demonstrate that hippocampal somatostatin and neurogliaform interneurons (Sst-INs and NGFCs) express functional eGlyRs from early postnatal through adult ages. In the developing hippocampus eGlyR-mediated excitation of NGFCs with ambient glycine dramatically increases GABAergic tone, with consequences for the generation of giant depolarizing potentials (GDPs). In the mature hippocampus, eGlyR- mediated excitation of Sst-INs regulates sharp wave ripples (SWRs). Finally, we reveal evolutionary conservation of hippocampal Sst-IN eGlyRs and eGlyR- mediated SWR regulation in non-human primates confirming functional eGlyR availability for therapeutic potential in higher species. Our findings underscore that eGlyR mediated regulation of cell and circuit excitability through both cell autonomous and cell non-autonomous mechanisms must be considered to understand GluN3A roles in brain development, plasticity, and disease.

neuroscience↗

bioRxiv2025

A novel, evolutionarily conserved inhibitory circuit selectively regulates dentate gyrus mossy cell function.

The mammalian dentate gyrus contributes to mnemonic function by parsing similar events and places. The disparate activity patterns of mossy cells and granule cells is believed to enable this function yet the mechanisms that drive this circuit dynamic remain elusive. We identified a novel inhibitory interneuron subtype, characterized by VGluT3 expression, with overwhelming target selectivity for mossy cells while also revealing that CCK, PV, SOM and VIP interneurons preferentially innervate granule cells. Leveraging pharmacology and novel enhancer viruses, we find that this target-specific inhibitory innervation pattern is evolutionarily conserved in non-human primates and humans. In addition, in vivo chemogenetic manipulation of VGluT3+ interneurons selectively alters the activity and functional properties of mossy cells. These findings establish that mossy cells and granule cells have unique, evolutionarily conserved inhibitory innervation patterns and suggest selective inhibitory circuits may be necessary to maintain DG circuit dynamics and enable pattern separation across species.

neuroscience↗

bioRxiv2025

Conformational dynamics and multi-modal interaction of Paxillin with the Focal Adhesion Targeting Domain

Paxillin (PXN) and focal adhesion kinase (FAK) are two major components of the focal adhesion complex, a multiprotein structure linking the intracellular cytoskeleton to the cell exterior. The interaction between the disordered N-terminal domain of PXN and the C-terminal targeting domain of FAK (FAT) is necessary and sufficient for localizing FAK to focal adhesions. Furthermore, PXN serves as a platform for recruiting other proteins that together control the dynamic changes needed for cell migration and survival. Here, we show that the PXN N-domain undergoes significant compaction upon FAT binding, forming a 48-kDa multi-modal complex with four major interconverting states. Although the complex is flexible, each state has unique sets of contacts involving disordered regions that are both highly represented in ensembles and conserved. PXN being a hub protein, the results provide a structural basis for understanding how shifts in the multi-state equilibrium (e.g. through ligand binding and phosphorylation) may rewire cellular networks leading to phenotypic changes. TeaserThe fuzzy complex between Paxillin and Focal adhesion targeting domain is resolved, with functional and translational implications.

biophysics↗

bioRxiv2024

An enhancer-AAV toolbox to target and manipulate distinct interneuron subtypes

In recent years, we and others have identified a number of enhancers that, when incorporated into rAAV vectors, can restrict the transgene expression to particular neuronal populations. Yet, viral tools to access and manipulate specific neuronal subtypes are still limited. Here, we performed systematic analysis of single cell genomic data to identify enhancer candidates for each of the telencephalic interneuron subtypes. We established a set of enhancer-AAV tools that are highly specific for distinct cortical interneuron populations and striatal cholinergic interneurons. These enhancers, when used in the context of different effectors, can target (fluorescent proteins), observe activity (GCaMP) and manipulate (opto-genetics) specific neuronal subtypes. We also validated our enhancer-AAV tools across species. Thus, we provide the field with a powerful set of tools to study neural circuits and functions and to develop precise and targeted therapy.

neuroscience↗

bioRxiv2024

Cathepsin B regulates ovarian reserve quality and quantity via mitophagy by modulating IGF1R turnover.

The quality and quantity of the ovarian reserve are meticulously regulated through various cell death pathways to guarantee the availability of high-quality oocytes for fertilization. While apoptosis is recognized for contributing to maintaining ovarian reserve, the involvement of other cell death pathways remains unclear. Employing chemical genetics and proteomics, this study reveals the crucial involvement of Cathepsin B in maintaining the ovarian reserve. Results indicate that apoptosis and autophagy play pivotal roles, and inhibiting these pathways significantly increases follicle numbers. Proteomics reveals a dynamic shift from apoptosis to autophagy during follicular development, with Cathepsin B emerging as a key player in this transition. Inhibiting Cathepsin B not only mimics the augmented oocyte reserve observed with autophagy inhibition but also upregulated IGF1R and AKT-mTOR pathways without compromising fertility. Further, IGF1R inhibition partially compromised the protective effects of Cathepsin B inhibition on oocyte reserves, suggesting their interdependence. This association is further supported by the finding that Cathepsin B can degrade IGF1R in vitro. Moreover, the increased IGF1R levels enhance the oocyte mitochondrial membrane potential via transcriptional regulation of mitochondrial biogenesis and mitophagy genes. Remarkably, this Cathepsin B-dependent ovarian reserve maintenance mechanism is conserved in higher-order vertebrates. Cumulatively, our study sheds valuable light on the intricate interplay of autophagy, Cathepsin B, and growth factors in ovarian reserve maintenance, offering potential implications for fertility research.

cell biology↗

bioRxiv2024

Divergent opioid-mediated suppression of inhibition between hippocampus and neocortex across species and development

Within the adult rodent hippocampus, opioids suppress inhibitory parvalbumin-expressing interneurons (PV-INs), thus disinhibiting local micro-circuits. However, it is unknown if this disinhibitory motif is conserved in other cortical regions, species, or across development. We observed that PV-IN mediated inhibition is robustly suppressed by opioids in hippocampus proper but not primary neocortex in mice and nonhuman primates, with spontaneous inhibitory tone in resected human tissue also following a consistent dichotomy. This hippocampal disinhibitory motif was established in early development when PV-INs and opioids were found to regulate early population activity. Acute opioid-mediated modulation was partially occluded with morphine pretreatment, with implications for the effects of opioids on hippocampal network activity important for learning and memory. Together, these findings demonstrate that PV-INs exhibit a divergence in opioid sensitivity across brain regions that is remarkably conserved across evolution and highlights the underappreciated role of opioids acting through immature PV-INs in shaping hippocampal development.

neuroscience↗

bioRxiv2023

Fractal Dimension and Lacunarity Measures of Glioma Subcomponents Provide a Quantitative Platform Discriminative of IDH Status: A Radiogenomics Approach in Gliomas

BackgroundThe presence of structural and geometric variations within gliomas, even among those with similar histologic grades, reflects the phenotypic heterogeneity unique to a genetic and epigenetic landscape. Whole glioma mass comprises of various subcomponents identified on MR imaging: enhancing, nonenhancing, necrosis, and edema fractions in varied fractions across patients. The geometry of whole tumor mass and the glioma subcomponents is highly irregular. Thereby, traditional Euclidean geometry is not suitable for quantifying the geometric dimensions. Here, we employ non-Euclidean geometric measurements: Fractal Dimension and lacunarity of the glioma subcomponents as a discriminator of IDH and MGMT status of gliomas. MethodsFractality and Lacunarity measurements were obtained using the tumor masks generated for enhancing, nonenhancing, and edema subcomponents from the preoperative T1, T1c, and T2-Flair MRI. Fractality and lacunarity measures of each subcomponent were evaluated between IDH mutant and wildtype gliomas. The fractality and lacunarity measures in IDH mutant and wildtype gliomas were further stratified for MGMT methylated and unmethylated gliomas. The fractality and lacunarities were trained and tested using supervised ML modeling as discriminators of IDH and MGMT status. Further, Cox Hazard estimations and the Kaplan-Meir investigations were performed to evaluate the impact of fractality and lacunarity measures of glioma subcomponents on the overall survival of the patients. ResultsIDH wildtype gliomas had [~]2-fold higher fractality for the enhancing subcomponent compared to IDH mutant enhancing subcomponent, while IDH mutant gliomas showed higher fractality for the nonenhancing subcomponent. Furthermore, the edema subcomponent did not differ for fractality or lacunarity measures between IDH mutant and wildtype gliomas. Fractal or lacunarity measures for either of the three subcomponents do not vary across MGMT methylated and unmethylated status with a given IDH mutant or wildtype gliomas. A combination of fractal measures of the enhancing and nonenhancing subcomponents together provided highly accurate and sensitive discrimination of IDH status using the supervised ML models. Moreover, fractality measure [≥] 0.69 for the enhancing subcomponent was associated with shortened patient survival: a fractal dimension value corresponding to that of IDH wild type gliomas. However, fractality and lacunarity estimates were not sensitive for discrimination of MGMT status. ConclusionGlioma structural heterogeneity measured as fractality and lacunarity using routine structural MRI measurements provide a noninvasive quantitative platform definitive of the molecular subtype of gliomas: IDH mutant vs. wildtype. Establishing fractality and/or lacunarity quantities as signatures of prognostic molecular events provides an avenue to bypass the need of biopsy/surgical interventions for decision-making, determining the molecular subtypes and overall clinical management of gliomas. Importance of the StudyThe non-Euclidean geometric measurements such as fractal dimension and lacunarity of enhancing, nonenhancing, and edema subcomponents are potentially unique quantitative metrics, discriminative of IDH status and patient survival. Fractality and Lacunarity estimates using the conventional structural MRI (T1w, T1C, T2, and T2F) provide an easy-to-use quantitative radiogenomics platform for improved clinical decisions, bypassing the need for immediate surgical interventions to ascertain prognostic molecular markers in gliomas, which is likely to improve overall clinical management and outcomes. Key PointsO_LIIncreased fractal dimensions of the enhancing subcomponents in IDH wildtype tumors, suggestive of highly irregular geometry, may potentially serve as a quantitative noninvasive determinant of IDH wildtype tumors. C_LIO_LIA combined fractal estimation of enhancing and nonenhancing subcomponents is the optimal and accurate discriminator of IDH mutant vs. wildtype. C_LIO_LIHigh fractal dimension of enhancing subcomponent and reduced fractality of nonenhancing subcomponent is predictive of shortened patient survival. C_LI

cancer biology↗

bioRxiv2023

Phase Separation of a Novel form of Euchromatic Histone Methyltransferase1 (EHMT1N/C) into cytoplasmic RNA viral Inclusion bodies facilitates their coalescence, thereby enhancing viral replication

Protein lysine methyltransferases (PKMTs) methylate histone and non-histone proteins to regulate biological outcomes such as development and disease including viral infection. While PKMTs have been extensively studied for modulating the antiviral responses via host gene regulation, their role in methylation of proteins encoded by viruses and its impact on host-pathogen interactions remain poorly understood. In this study, we discovered a distinct nucleo-cytoplasmic form of Euchromatic Histone Methyltransferase1(EHMT1N/C), a PKMT, that phase separates into viral inclusion bodies (IBs) upon cytoplasmic RNA-virus infection (Sendai Virus). EHMT1N/C interacts with cytoplasmic EHMT2 and methylates SeV-Nucleoprotein upon infection. Elevated nucleoprotein methylation during infection correlated with coalescence of small IBs into large mature platforms for efficient replication. Inhibition of EHMT activity by pharmacological inhibitors or genetic depletion of EHMT1N/C reduced the size of IBs with a concomitant reduction in replication. Since IB formation is conserved among all cytoplasmic RNA-viruses, our study will have strong implications in understanding the mechanisms regulating IB formation, discerning RNA viral pathogenesis and designing therapeutic strategies.

cell biology↗

bioRxiv2023

How is Emotional Evidence from Multiple Sources Used in Perceptual Decision Making?

Judging the emotional nature of a scene requires us to deliberately integrate pieces of evidence with varying intensity of emotion. Our existing knowledge about emotion-related perceptual decision making is largely based on paradigms using single stimulus and, when involving multiple stimuli, rapid decisions. Consequently, it remains unclear how we sample and integrate multiple pieces of emotional evidence deliberately to form an overall judgment. Findings from non-emotion rapid decision-making studies show humans down-sample and downweight extreme evidence. However, deliberate decision making may rely on a different attention mode than in rapid decision making; and extreme emotional stimuli are inherently salient. Given these critical differences, it is imperative to directly examine the deliberate decision-making process about multiple emotional stimuli. In the current study, human participants (N=33) viewed arrays of faces with expressions ranging from extremely fearful to extremely happy freely with their eye movement tracked. They then decided whether the faces were more fearful or happier on average. In contrast to conclusions drawn from non-emotion and rapid decision-making studies, eye movement measures revealed that participants attentionally sampled extreme emotional evidence more than less extreme evidence. Computational modeling results showed that even though participants exhibited biased attention distribution, they weighted various emotional evidence equally. These findings provide novel insights into how people sample and integrate multiple pieces of emotional evidence, contribute to a more comprehensive understanding of emotion-related decision making, and shed light on the mechanisms of pathological affective decisions.

animal behavior and cognition↗

bioRxiv2022

Socio-demographic determinants of monkeypox virus preventive behavior: a cross-sectional study in Pakistan

BackgroundMonkeypox, a re-emerging zoonotic infectious disease, is striking the world with serious public health concerns, especially in non-endemic countries. The publics knowledge and attitude toward the monkeypox virus (MPXV) influence their adherence to preventive strategies. Therefore, we aimed to assess the general publics knowledge, attitudes, and perceptions (KAP) of MPXV in Pakistan. MethodsWe collected data for this cross-sectional study from 1040 participants via an online self-reported questionnaire from 5th July 2022 to 1stAugust 2022. The questionnaire consisted of a total of 29 items in four sections, assessing socio-demographics, knowledge, attitudes, and practices regarding MPXV. The data was analyzed using IBM SPSS V.25, and factors associated with MPXV knowledge, attitude, and practices were identified by using logistic regression analyses ResultsA total of1040participants were included. 61.4% were male and 57.2% had graduation level education. Only 34.4% had good knowledge about MPXV and 30% were aware of effectiveness of smallpox vaccine against MPXV. 41.7% had positive attitude with 48.6% agreed that it is a fatal disease and 44.6% were in favor of banning travelling from endemic to non-endemic regions.57.7% had good practices and 69.9% would use protective measures if MPXV become an epidemic. Binary logistic regression analysis revealed that gender and education significantly impacted knowledge (p<0.05). While monthly income status had a significant impact on attitudes (p<0.05). The practices were correlated positively with gender and education (p<0.05). ConclusionThe majority of study participants had inadequate levels of knowledge, and attitudes regarding MPXV. To prevent the emergence and spread of MPXV in Pakistan, a comprehensive strategic framework for public health education must be established and implemented.

microbiology↗