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Sen, R.

Publications and source records attributed to Sen, R..

At least 19 recordsLinked to original sources

A new neural code for position: generalizable spatial maps in mouse medial frontal cortex

Navigation requires the brain to encode spatial relationships that support extrapolation from explored to unexplored regions of space. We identified a novel neural code for space in the mouse medial frontal cortex (mFC) that is well suited for this form of spatial generalization. Using calcium imaging of excitatory neurons in mFC, hippocampus (dorsal CA1), and lateroventral orbitofrontal cortex (lvOFC) as mice explored a square arena with landmarks, we found that mFC activity supports extrapolation. Linear regression of the animal's x or y coordinates trained in one region of the arena generalized to a completely different region. This property was observed in mFC but not in dCA1 or lvOFC. A model in which neurons encode the squared distance from the animal to multiple landmarks explains several properties of the geometry of the mFC representation, including extrapolation. The neural map that we observed in the frontal cortex may provide a basis for vector computation in navigation and complex route planning.

neuroscience↗

Lifestyle intervention is associated with attenuation of ER stress/inflammation and enhancement of naive immune cell identity in older adults with metabolic disease

Chronic inflammation and cellular stress are hallmarks of aging, obesity, and type 2 diabetes (T2D), but whether these programs can be modulated by lifestyle intervention in late life, particularly in the presence of established metabolic disease, remain unknown. We profiled circulating immune cells from older adults with obesity and T2D (ages 66-83 years; n = 9) before and after a 6-month lifestyle intervention combining caloric restriction with exercise training. Participants showed substantial weight loss ([~]7%) alongside improvements in glycemic control, insulin sensitivity, and physical performance. Longitudinal single-cell transcriptomic and epigenomic profiling identified two major changes. First, intervention was associated with downregulation of inflammatory and endoplasmic reticulum (ER) stress transcriptional programs, with the most pronounced effects observed in CD14+ monocytes. DDIT3 (CHOP) was transcriptionally and epigenetically downregulated and its inferred regulatory network encompassed multiple inflammatory mediators. Second, naive CD4+ T, naive Treg, and naive B cells exhibited an upregulation of naive cell identity genes, with naiveness scores increasing after intervention, which declines with age in an independent healthy adult cohort. Together, these findings suggest that lifestyle intervention is associated with coordinated remodeling of both innate and adaptive immune compartments in older adults, revealing substantial plasticity of the aging immune system especially targeting ER stress, inflammation, and naive lymphocyte identity programs.

immunology↗

Bacterial Stress Responses Lower mRNA-Protein Level Correlations

Diverse bacterial pathogens have evolved complex regulatory mechanisms to adapt to various environmental stresses during infection. The uncertainty in mRNA-protein levels in response to environmental stressors complicates our understanding of bacterial physiology and their adaptation to stressful environments. To examine this issue, we have integrated transcriptomics and proteomics data on three human bacterial pathogens Salmonella enterica Typhimurium, Yersinia pseudotuberculosis, and Staphylococcus aureus under ten infection-relevant stress conditions. We observed positive correlations between mRNA and protein levels, which were decreased under different stress conditions. Essential genes exhibited higher expression levels with lower variation across the conditions and stronger mRNA-protein correlations compared to non-essential genes, highlighting their critical role in bacterial adaptability and survival. Moreover, we identified a substantial number of genes with stress-induced non-correlating mRNA-protein levels, especially under conditions triggering strong stress responses. Particularly this level was dramatically lowered for osmotic stress specific genes affected by impaired translational activity under osmotic stress. Our findings highlight the prevalence of non-correlating mRNA-protein levels and the potential role of post-translational modifications in modulating protein levels in response to environmental stressors during infection. This study provides a comprehensive framework for integrating transcriptomics and proteomics data and identifies potential gene products that might significantly impact the ability of diverse bacterial pathogens to adapt to hostile infection environments. Significance StatementUnderstanding how bacteria adapt to host environments is crucial for combating infections. We employed an integrative transcriptomics and proteomics approach to investigate mRNA-protein correlations in three clinically relevant pathogens under ten infection-relevant stress conditions. We identified genes whose mRNA-protein relationships are significantly disrupted by specific stressors. This study provides a deeper understanding of mRNA-protein level uncertainty, coupling it to stress responses known to trigger critical post-transcriptional and post-translational regulations. These findings help reveal novel mechanisms of bacterial adaptation and pathogenesis. By providing a comprehensive, multi-species dataset, this study serves as a foundational resource for infection biology, driving future advancements in understanding complex regulatory networks and identifying potential antimicrobial targets.

microbiology↗

In Utero CFTR Modulation Alleviates Disease in G551D Cystic Fibrosis Pigs

Previous studies indicate that pigs with CFTR-null and CFTR-{Delta}F508 mutations develop multiorgan disease similar to that in people with cystic fibrosis (CF). At birth, their airways exhibit host defense defects that predispose to airway infection, inflammation, and mucus accumulation. The CFTR-G551D mutation causes CF by producing CFTR channels that localize correctly but have reduced channel activity. Ivacaftor (VX-770) is a small molecule drug developed to potentiate CFTR activity. To test the phenotype of the CFTR-G551D mutation in pigs and determine whether ivacaftor can rescue CF abnormalities, we developed CFTRG551D/G551D (CF-G551D) pigs through homologous recombination in fetal fibroblasts and somatic cell nuclear transfer. Newborn CF-G551D piglets exhibited phenotypes similar to CF-null piglets, including meconium ileus, exocrine pancreatic destruction, micro-gallbladder, vas deferens destruction, and airway structural abnormalities. Compared to wild-type pigs, CF-G551D pigs had reduced forskolin-stimulated short-circuit current in airway and intestinal tissues. Ivacaftor increased the single-channel open state probability of CFTR-G551D and increased short-circuit current to near wild-type levels. Similar to our other CF pig models, we found that 100% of CF-G551D pigs were born with meconium ileus. To test whether in utero ivacaftor treatment could prevent or alleviate meconium ileus, pregnant sows were treated with ivacaftor beginning at day 35 of gestation and continuing until delivery. This treatment rescued the pancreas, gallbladder, and vas deferens phenotype in the majority of CF-G551D pigs. Animals that were spared from meconium ileus were able to survive without ivacaftor treatment. Airway disease developed similar to other CF pig models. These findings indicate that this model may be useful for studies in which CFTR function can be reversed, for investigating in utero CFTR correction strategies, and for longitudinal studies in CF pigs.

physiology↗

The blood proteome predicts the impact of circulating factors on age-related mitochondrial health

Circulating non-cellular factors, such as plasma proteins, contribute to various features of aging. To determine the impacts of endogenous circulating factors on human age-related bioenergetic decline, we treated primary human fibroblasts with serum samples representing the adult life-course. Our results demonstrate that the maximal mitochondrial bioenergetic capacity of fibroblasts treated with serum is negatively correlated with the chronological and epigenetic age of the serum donor. Using targeted proteomics, we identified plasma proteins associated with the bioenergetic effects of serum. We then utilized elastic net, a linear regression modeling technique, to derive a novel proteomic signature of age-related mitochondrial differences. MitoAge is a 25-protein signature of age-related mitochondrial health that predicts the systemic bioenergetic effects of circulating factors and is related to differences in physical function across human aging. Signatures that report on cellular hallmarks of aging, such as mitochondrial function, represent a new generation of mechanistically-informed biomarkers of biological aging. GRAPHICAL ABSTRACTIn this study, we describe the development of a novel proteomic signature, MitoAge. This signature was developed by utilizing human primary fibroblasts treated with serum samples representing the adult human life-course and analyzing how resulting respirometry correlated with chronological age, epigenetic age, and abundance of serum proteins. Utilizing machine learning techniques, we derived a 25-protein signature which can predict bioenergetics and physical features related to aging. Application and utility of this signature may be used to identify novel drivers of health and longevity. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=103 SRC="FIGDIR/small/687483v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@905c12org.highwire.dtl.DTLVardef@18ca82forg.highwire.dtl.DTLVardef@175d397org.highwire.dtl.DTLVardef@966faa_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

Morphological variations in external genitalia do not explain the interspecific reproductive isolation in Nasonia species complex (Hymenoptera: Pteromalidae)

External genitalia play a crucial role in the successful copulation of conspecific partners in insects. Due to their structural specificity, external genitalia have often been used for distinguishing closely related species in different insects. However, in the young Pteromalid species complex Nasonia, these structures have not received much attention. Nasonia is a genus of parasitoid wasps, that lays eggs and completes its life cycle in dipteran pupae. All behavioral studies (including this study) conducted on this genus indicate that varied prezygotic isolation operates among these recently diverged ([~]1 million years) species. Whether such prezygotic isolation is caused by the incompatibility in their reproductive organs is not known. Here, we studied the internal male reproductive system of the four species and show that all four species have a similar organisation and thus ruling it out as a potential barrier. Furthermore, to investigate the role of male external genitalia as a prezygotic barrier, we also examined the ultrastructural details, including aedeagal length, aedeagal aperture length, and digital spines. We show that all these parameters and sperm length show variations across the four species. However, these variations do not correlate with the female acceptance of the heterospecific males. Therefore, we conclude that there must be other olfactory or behavioral isolating mechanisms and spatial or temporal factors that maintain the reproductive isolation of these four species.

zoology↗

Nasonia vitripennis males exhibit greater effort and competency in detecting hosts with conspecific females than other Nasonia males.

Nasonia is a species complex of four parasitoid wasps. N. vitripennis is cosmopolitan, while the other three species are micro-sympatric with it. This distribution can select for distinct species-specific mate recognition capabilities. However, whether Nasonia males can identify hosts with conspecific females against hosts with heterospecific females is not known. Therefore, we tested this hypothesis in a cafeteria-based choice assay and show that N. vitripennis males can distinguish hosts with conspecific wasps against those parasitised by N. giraulti and N. oneida, exhibiting longer search time and distance traversed with faster search speed. We also found that N. longicornis males can distinguish hosts with conspecific wasps, but only against the hosts parasitised by N. oneida. We further investigated the pairwise differences in the cuticular hydrocarbon (CHC) profiles of the parasitised hosts and adult female wasps. The results reveal that the males show this ability only when the compounds responsible for differences in adult female CHC profiles were also the key differentiators of the host CHC profiles. The comparative mate searching behaviour of males of all reported species within a genus has rarely been studied. Therefore, this study makes a significant contribution to our understanding of interspecific variation of conspecific-mate searching behaviour.

zoology↗

Genomic data confirms phenotypic predictions of hybridization between cryptic Hawaiian cricket species

Hybridization is increasingly recognized as an important driver of species radiations, yet its detection in morphologically cryptic taxa remains challenging. The Hawaiian crickets of the genus Laupala represent a rapid non-adaptive radiation in which species are morphologically indistinguishable but differ in acoustic mating signals. Here we report the first discovery of natural hybridization in the Laupala radiation. During field surveys on Maui, we observed crickets with intermediate pulse rates and unusually high acoustic variation at sites where the ranges of Laupala makaio (slow singer) and Laupala orientalis (fast singer) converge. We hypothesized these represented natural hybrids and tested this prediction using genomic data from genotyping-by-sequencing (GBS). Maximum likelihood phylogenetic analysis showed that fast-singing putative hybrids clustered with L. orientalis and the slow-singing ones with L. makaio, yet all putative hybrids formed a cohesive geographic group. Using 9,345 ancestry-informative markers, we calculated hybrid indices and heterozygosity values for triangle plot analysis. All hybrids showed excess L. makaio ancestry (predicted from analysis of pulse rate patterns) and were classified as later-generation hybrids or backcrosses to L. makaio, with no F1 hybrids detected. Critically, we found a strong positive correlation (R = +0.74, p = 4.1x10-) between pulse rate and hybrid index at the site with highest pulse rate variation, showing that genomic ancestry predicts pulse rate phenotype. Morphological comparisons confirmed that hybrids were cryptic, reinforcing the difficulty of detecting hybridization without genomic data. Together, our results provide the first demonstration of natural hybridization in Laupala, showing that phenotypic predictions based on acoustic intermediacy can be confirmed with genomic evidence. The discovery of natural hybridization in Laupala opens new avenues for investigating how hybridization contributes to rapid diversification in non-adaptive radiations, paralleling patterns observed in some adaptive radiations.

evolutionary biology↗

Sexual isolation maintains species boundaries between Hawaiian crickets in sympatry despite weak habitat isolation

Understanding the relative importance of different reproductive isolating barriers in maintaining species boundaries is fundamental to understanding how closely related species coexist without hybridizing. Habitat isolation and sexual isolation are often the first barriers between closely related species, yet they are rarely studied together, making their relative contributions to reproductive isolation unclear. We conducted the first comprehensive study of both barriers in Hawaiian swordtail crickets (Laupala), focusing on the recently diverged, sympatric species pair Laupala kona and Laupala hualalai. Using genomic data, we confirmed that the two species are genetically distinct, which can only be achieved by strong reproductive isolation through a prolonged time period. Through field surveys, we quantified microhabitat use, spatial distribution, and diets, and found extensive ecological overlap. Both species occupied similar substrates, elevations, and microclimates, and occurred in mixed-species aggregations. They only differ in their diets (inferred from stable isotopes), which might have some implications in reducing encounter rates. Despite this weak habitat isolation, they have divergent sexual traits and exhibit strong sexual isolation in lab assays. The species differ significantly in male pulse rate and cuticular hydrocarbon profiles, and females consistently preferred conspecific song stimuli. Mating trials showed almost complete sexual incompatibility between heterospecific pairs, with very rare interspecies copulations. Together, these results demonstrate that sexual isolation, rather than habitat partitioning, maintains species boundaries between L. hualalai and L. kona in sympatry. Our findings highlight the sufficiency of sexual isolation to prevent hybridization even in the absence of strong ecological divergence, providing rare empirical evidence that sexual barriers alone can maintain reproductive isolation in natural populations.

evolutionary biology↗

Early postpartum development of pup urine preference in mothers

The transition to motherhood involves profound physiological and neural changes, including adaptations in the sensory systems that support infant care.1,2 While the olfactory system plays a critical role in guiding maternal behaviors such as pup retrieval and nesting,3,4 how olfactory processing itself is reshaped during motherhood remains poorly understood. Here, we show that first-time mothers develop a selective preference for pup urine following parturition and early postpartum care, a preference not observed for other social or neutral odors. Using odor preference assays combined with liquid and gas chromatography-mass spectrometry, we identify specific volatile compounds in pup urine that may contribute to this maternal attraction. Disruption of olfactory input or restriction of contact chemosensation abolished the preference, indicating that both volatile and non-volatile sensory modalities contribute, likely through combined input from the main olfactory epithelium (MOE) and vomeronasal organ (VNO).5,6 Notably, this preference is absent in late-pregnant females, in mothers separated from pups at birth, and in virgins cohoused with pups or exposed to pup urine-highlighting that pup urine preference depends on the convergence of internal hormonal signals and external chemosensory cues.7,8 These findings reveal a previously unrecognized specificity in maternal olfactory behavior and provide insight into how motherhood modulates the sense of smell to support offspring recognition and care. In BriefMaternal pup urine preference depends on both hormonal changes and chemosensory cues associated with motherhood. HighlightsO_LIPup urine specifically attracts postpartum mothers but not virgin females C_LIO_LIPup urine contains distinct volatile and non-volatile metabolites C_LIO_LIPup urine preference requires both pup experience and the hormonal priming of motherhood C_LI

neuroscience↗

Human genetic variation shapes the antibody repertoire across B cell development

The peripheral antibody repertoire is shaped by inherited genetic variation and selection during B cell development. However, how the repertoire changes across developmental stages--and the relative impact of genetics and selection in establishing the antibody repertoire--remain largely unknown. To dissect the individual and combined effects of these factors, we integrated antibody repertoire transcriptomics across pro-B, pre-B, immature, and naive B cells with single-molecule real-time long-read DNA sequencing of the immunoglobulin heavy (IGH), kappa (IGK), and lambda (IGL) chain loci. We find that IGH genetic variants establish gene usage biases at the pro-B stage that persist throughout development. In contrast, IGK and IGL repertoires are extensively remodeled during maturation, consistent with receptor editing. Surprisingly, IGH variants also exert trans effects on light chain gene usage, suggesting coordinated constraints on heavy-light chain pairing. Principal component and allele-specific analyses reveal that genetics primarily shapes the heavy chain repertoire, while selection more strongly influences light chain diversity. These findings define distinct dynamics of antibody repertoire development and underscore the importance of personal immunogenomics in understanding individual immune responses.

genomics↗

Closed-loop sonothermogenetic control of CAR T cells for metronomic brain cancer therapy

Achieving durable CAR T cell responses against primary brain tumors and metastases requires strategies that enable intracranial control of therapy to overcome the barriers of solid tumor treatment without compromising safety. Here, we show that closed-loop sonothermogenetics enables remote regulation of CAR T cell therapeutic activity through the intact skull. Using MR-guided focused ultrasound with closed-loop temperature feedback, we modulate CAR T cells engineered with a genetically encoded thermal bioswitch to achieve metronomic activation in the brain without lasting adverse effects on healthy brain tissue. In murine models of brain cancer, metronomic production of NKG2D T cell engagers by intratumoral CAR T cells overcomes antigen heterogeneity in breast cancer brain metastasis and myeloid-derived immunosuppression in glioblastoma to drive antitumor responses. Our findings support the use of closed-loop sonothermogenetics for spatial and temporal control of CAR T cell therapies targeting solid brain tumors.

bioengineering↗

Performance Evaluation of Ciprofloxacin loaded Micellar Bioconjugate Carrier for Eradication of Bacterial Biofilms

This study reports the utilization of a Curcumin-Exopolysaccharide (Cur-EPS) micellar bioconjugate comprising acid-labile ester bond as a carrier for ciprofloxacin (Cip) to improve its ability to eradicate mature bacterial biofilms. The most significant attributes of Cip-loaded Cur-EPS micelles, including hydrodynamic particle size, polydispersity index (PDI), and encapsulation efficiency (EE), were statistically optimized to be 305.43 {+/-} 1.47 nm, 0.38 {+/-} 1.23, and 84.50 {+/-} 2.01 %, respectively. At an acidic pH of 5.6, the pH-responsive release of Cip from Cur-EPS micelles was 82.51 {+/-} 2.95 % over a duration of 100 h, but it was reduced to 39.10 {+/-} 1.55 % at a pH of 7.4 over the same period. This pH-dependent Cip release may be attributed to the destabilisation of Cur-EPS micelles due to hydrolysis of the succinic acid linker in the acidic pH range. Thus, the acidic pH microenvironment of biofilms formed by pathogenic bacterial strains, such as methicillin resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, enhances the pH-responsive release of Cip from Cur-EPS micelles, thereby leading to the eradication of mature biofilms. This enhanced antibiofilm effect of Cip-Cur-EPS, in contrast to the free form of Cip, was evident from the significant decrease in the biofilm biomass. Furthermore, mature biofilms that formed on the surface of the urinary catheter were almost eradicated when treated in vitro with Cip-Cur-EPS for 72 h in the presence of artificial urine media (AUM). Moreover, Cip-Cur-EPS could also eradicate the biofilms formed by P. aeruginosa and MRSA in a catheterized bladder model employing recirculated artificial urine. Overall, this study demonstrated the antibiofilm potential of Cip-Cur-EPS micelles, rendering them suitable therapeutic agents for addressing biofilm-associated infections in clinical settings. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=125 SRC="FIGDIR/small/630303v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@135f68org.highwire.dtl.DTLVardef@1dcd61forg.highwire.dtl.DTLVardef@16d9976org.highwire.dtl.DTLVardef@762425_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

Parasite-induced replacement of host microbiota- Impact of Xenos gadagkari parasitization on the microbiota of Polistes wattii

AbstractO_ST_ABSBackgroundC_ST_ABSThe study of microbiota of social insects under different ecological conditions can provide important insights into the role of microbes in their biology and behaviour. Polistes is one of the most widely distributed and extensively studied genera of social wasps, yet the microbiota of any species of Polistes or any primitively eusocial wasp is still unknown. Polistes wattii is an abundantly distributed Asian wasp which hibernates in winter and exhibits a unique biannual nest founding strategy. It is often parasitized by the strepsipteran endoparasite Xenos gadagkari, which changes the morpho-physiology and behaviour of their hosts. In this study we employ 16S rRNA amplicon sequencing, using the Oxford Nanopore platform, to study the microbial community associated with P. wattii and compared the microbiota of the unparasitized male and female P. wattii with their parasitized counterparts. ResultsThe microbiota of females from preemergence solitary foundress nests differs from the females from the late colony phase of multiple foundress nests. The males and females also differ in their microbiota. To estimate the effect of strepsipteran parasitism on the microbiota of P. wattii, we compared the unparasitized wasps with that of the female and male X. gadagkari parasitoids and parasitized wasps. We show that the microbiota of the parasitoids and the parasitized wasps are dominated by Wolbachia and Providencia. {beta}-diversity differences indicated that the parasitoid replaces and homogenizes the microbiota of P. wattii. Although the normal microbiota of P. wattii resembles that of highly eusocial vespid wasps, we show X. gadagkari parasitization replaces the microbiota of P. wattii and it becomes more like the microbiota of strepsipterans. Therefore, it appears that X. gadagkari and other such strepsipteran parasitoids may have a bigger impact on the biology of their hosts, than previously thought. ConclusionThis is the first study of microbiota of any primitively eusocial Polistine wasp and any strepsipteran parasitoid associated with a hymenopteran species. Although strepsipteran parasitoids are commonly found in hymenopteran insects, the change on the microbiota of the host due to the parasitism was not known before. This study shows the drastic impact of the parasitoid on the microbiota of the host.

microbiology↗

Thioether-functionalized cellulose for the fabrication of oxidation-responsive biomaterial coatings and films

Biomaterial coatings and films can prevent premature failure and enhance performance of chronically implanted medical devices. However, current hydrophilic polymer coatings and films have significant drawbacks, including swelling and delamination. To address these issues, we modified hydroxyethyl cellulose with thioether groups to generate an oxidation-responsive polymer, HECMTP. HECMTP readily dissolves in green solvents and can be fabricated as coatings or films with tunable thicknesses. HECMTP coatings effectively scavenge hydrogen peroxide, resulting in conversion of thioether groups to sulfoxide groups on the polymer chain. Oxidation-driven, hydrophobic-to-hydrophilic transitions that are isolated to the surface of HECMTP coating under physiologically relevant conditions increase wettability, decrease stiffness, and reduce protein adsorption to generate a non-fouling interface with minimal coating delamination or swelling. HECMTP can be used in diverse optical applications and permits oxidation-responsive, controlled drug release. HECMTP films are non-resorbable in vivo and evoke minimal foreign body responses. These results highlight the versatility of HECMTP and support its incorporation into chronically implanted medical devices.

bioengineering↗

Comparison of microbial and sono-assisted alkaline pre-treatment of sugarcane bagasse, followed by one-pot synthesis of microbial extracellular polymeric substance through simultaneous delignification, saccharification, and fermentation

Lignocellulosic biomass (LCB) captures a major fraction of agro-industrial wastes that are mostly valorised for the production of second-generation biofuels. The extensive pre-treatment followed by saccharification of LCB restricts its usability for the production of a wide array of bioproducts. This study highlights the performance comparison of sono-assisted alkaline pre-treatment versus microbial pre-treatment of sugarcane bagasse by a no. of analytical techniques such as FTIR, XRD, CHNS, and SEM. Moreover, simultaneous delignification, saccharification and fermentation (SDSF) in one pot is highly desirable for the cost effective and environment friendly production of microbial products. In the present study SDSF was carried out by a cellulolytic bacterium Cellulomonas flavigena, for the production of extracellular polymeric substance (EPS), which is, by chemical nature a biopolymer made up of carbohydrate and protein subunits. The biopolymer was found to have an overall positive charge as analysed by ion exchange chromatography. Two major fractions of molecular weight 237 KDa and 29 KDa were obtained from gel filtration chromatography, in addition to that, the EPS was found to be composed of monosaccharides, D (+) mannosamine and D (+) xylose as identified from high pressure liquid chromatography (HPLC).

bioengineering↗

Morphology, biology and phylogeny of Xenos gadagkari sp.nov. (Strepsiptera: Xenidae): an endoparasite of Polistes wattii (Hymenoptera: Vespidae).

We report the morphology, biology and phylogeny of a new strepsipteran endoparasitic species: Xenos gadagkari, from the primitively eusocial wasp Polistes wattii from Punjab, India. We report a high abundance of the endoparasite in P. wattii population of our study area and provide the morphological description of adult males, male puparium and neotenic females. This species is sufficiently different from other Xenos sp reported from various social wasps and therefore, constitutes a new species, X. gadagkari Sen and Nain, sp. nov. Although there are a few reports of Strepsipteran parasites from India, this is the first confirmational report with a thorough description of a Xenos species from the Indian population of P. wattii and underscores the need for further investigation of the diversity and distribution of this group in India. Our findings contribute to the growing body of knowledge on Xenos and provide a foundation for future behavioural, microbial and molecular studies on this enigmatic group of insects.

zoology↗

E-proteins set the threshold for optimal TCF1 expression during αβ T cell development.

Expression of T Cell Factor-1 (TCF1), encoded by Tcf7, regulates lineage fate decisions during T cell development. Here we demonstrate that E-proteins control the threshold of TCF1 expression required for development of T cells. E-proteins bind to five elements (EPEs) in the Tcf7 locus. The third element, EPE3, interacts directly with Tcf7 promoter in Hi-ChIP analyses, suggesting it is an active enhancer. CRISPR-ablation of EPE3 reduces TCF1 protein expression in precursor thymocytes by 2-fold and dramatically impairs development of {beta} and {gamma}{delta} T cells. Single cell gene expression analysis identified differentiation blocks at multiple CD4-CD8- stages and subsequent transition to CD4+CD8+ stage. These data identify E-proteins and EPE3 as critical for the optimal TCF1 expression required for T cell development.

immunology↗