Biology subjects

Dar, N.

Publications and source records attributed to Dar, N..

4 recordsLinked to original sources

bioRxiv2025

Mef2c Controls Postnatal Callosal Axon Targeting by Regulating Sensitivity to Ephrin Repulsion

Cortical connectivity is contingent on ordered emergence of neuron subtypes followed by the formation of subtype-specific axon projections. Intracortical circuits, including long-range callosal projections, are crucial for information processing, but mechanisms of intracortical axon targeting are still unclear. We find that the transcription factor Myocyte enhancer factor 2-c (Mef2c) directs the development of somatosensory cortical (S1) layer 4 and 5 pyramidal neurons during embryogenesis. During early postnatal development, Mef2c expression shifts to layer 2/3 callosal projection neurons (L2/3 CPNs), and we find a novel function for Mef2c in targeting homotopic contralateral cortical regions by S1-L2/3 CPNs. We demonstrate, using functional manipulation of EphA-EphrinA signaling in Mef2c-mutant CPNs, that Mef2c downregulates EphA6 to desensitize S1-L2/3 CPN axons to EphrinA5-repulsion at their contralateral targets. Our work uncovers dual roles for Mef2c in cortical development: regulation of laminar subtype specification during embryogenesis, and axon targeting in postnatal callosal neurons. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=163 SRC="FIGDIR/small/634300v1_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@108c788org.highwire.dtl.DTLVardef@163c6c3org.highwire.dtl.DTLVardef@18e6d8borg.highwire.dtl.DTLVardef@1b9f9e4_HPS_FORMAT_FIGEXP M_FIG C_FIG HIGHLIGHTSO_LIMef2c is required for the development of L4 and L5 neurons in the embryonic neocortex C_LIO_LIPostnatally, Mef2c is enriched in L2/3 neurons and is required for axon targeting C_LIO_LIL2/3-specific Mef2c deletion leads to EphA6 upregulation C_LIO_LIMef2c deletion in L2/3 neurons sensitizes them to EfnA5 repulsion in the contralateral cortex C_LI

neuroscience↗

bioRxiv2021

Killed whole genome-reduced bacteria surface-expressed coronavirus fusion peptide vaccines protect against disease in a porcine model

As the coronavirus disease 2019 (COVID-19) pandemic rages on, it is important to explore new evolution-resistant vaccine antigens and new vaccine platforms that can produce readily scalable, inexpensive vaccines with easier storage and transport. We report here a synthetic biology-based vaccine platform that employs an expression vector with an inducible Gram-negative autotransporter to express vaccine antigens on surface of genome-reduced bacteria to enhance interaction of vaccine antigen with immune system. As a proof of principle, we utilized genome-reduced E. coli to express SARS-CoV-2 and porcine epidemic diarrhea virus (PEDV) fusion peptide (FP) on the cell surface, and evaluated their use as a killed whole cell vaccine. The FP sequence is highly conserved across coronaviruses; the 6 FP core amino acid residues along with the 4 adjacent residues upstream and the 3 residues downstream the core are identical between SARS-CoV-2 and PEDV. We tested the efficacy of PEDV FP and SARS-CoV-2 FP vaccines in a PEDV challenge pig model. We demonstrated that both vaccines induced potent anamnestic responses upon virus challenge, potentiated IFN-{gamma} responses, reduced viral RNA loads in jejunum tissue, and provided significant protection against clinical disease. However, neither vaccines elicited sterilizing immunity. Since SARS-CoV-2 FP and PEDV FP vaccines provided similar clinical protection, the coronavirus FP could be a target for a broadly-protective vaccine using any platform. Importantly, the genome-reduced bacterial surface-expressed vaccine platform, when using a vaccine appropriate bacterial vector, has potential utility as an inexpensive, readily manufactured, and rapid vaccine platform for other pathogens. Significance StatementWe report a new vaccine platform to express vaccine antigens on surface of genome-reduced bacteria to enhance vaccine immunogenicity. We demonstrated the utility of this vaccine platform by expressing the highly conserved fusion peptide (FP) of SARS-CoV-2 and porcine epidemic diarrhea virus on the surface of E.coli to produce killed whole cell bacterial vaccines. The vaccine primes a potent anamnestic response, potentiates IFN-{gamma} responses, and provides significant protection in pigs against disease following virus challenge. The FP could be a target for a broadly-protective coronavirus vaccine since a Betacoronavirus SARS-CoV-2 FP vaccine provided cross-protection against Alphacoronavirus PEDV. When using a vaccine appropriate bacteria vector, this inexpensive new vaccine platform offers the potential for use in developing countries.

microbiology↗

bioRxiv2021

In situ single-cell activities of microbial populations revealed by spatial transcriptomics

Microbial populations and communities are heterogeneous, yet capturing their diverse activities has proven challenging at the relevant spatiotemporal scales. Here we present par-seqFISH, a targeted transcriptome-imaging approach that records both gene-expression and spatial context within microscale assemblies at a single-cell and molecule resolution. We apply this approach to the opportunistic bacterial pathogen, Pseudomonas aeruginosa, analyzing [~]600,000 individuals across dozens of physiological conditions in planktonic and biofilm cultures. We explore the phenotypic landscape of this bacterium and identify metabolic and virulence related cell-states that emerge dynamically during growth. We chart the spatial context of biofilm-related processes including motility and kin-exclusion mechanisms and identify extensive and highly spatially-resolved metabolic heterogeneity. We find that distinct physiological states can co-exist within the same biofilm, just a few microns away, underscoring the importance of the microenvironment. Together, our results illustrate the complexity of microbial populations and present a new way of studying them at high-resolution.

microbiology↗

bioRxiv2018

Strenuous occupational physical activity - potential association with esophageal squamous cell carcinoma risk

The impact of leisure time or recreational physical activity (RPA) on cancer risk has been extensively studied. However, the association of the occupational physical activity (OPA), which differs in dose and intensity from RPA, with different cancers including esophageal squamous cell carcinoma (ESCC), has received less attention. Here, we present data from a case-control study which was conducted for assessing the risk factors for ESCC. Histopathologically confirmed 703 ESCC cases and 1664 controls, individually matched to the respective cases for age, sex and district of residence were recruited. Information on type, duration and intensity of physical activity was obtained in face-to-face interviews with participants using a structured questionnaire. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). A high level of occupational physical activity was associated with increased ESCC risk (OR = 2.17, 95% CI; 1.41 - 3.32), compared to subjects with moderate occupational physical activity. The association with ESCC risk was stronger in strenuous workers (OR = 3.64, 95% CI; 2.13 - 6.20). The association of strenuous OPA with ESCC risk persisted only in subjects that were involved in strenuous activities for equal to or greater than 5days/week. Our study suggests a possible association of strenuous occupational physical activity with ESCC risk. Although, our results were adjusted for multiple factors including indicators of socioeconomic status, more replicative occupational epidemiological studies are needed to rule out any residual confounding.

epidemiology↗