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Ray, S.

Publications and source records attributed to Ray, S..

At least 37 records · Page 2Linked to original sources

RareCapsNet: An explainable capsule networks enable robust discovery of rare cell populations from large-scale single-cell transcriptomics

In-silico analysis of single cell data (downstream analysis) seeks considerable attention to the machine learning researchers in the last few years. Recent technological advances and increases in throughput capabilities open up great new chances to discover rare cell types. We develop RareCapsNet, a rare cell identification technique through capsule network in large single cell RNA-seq data. RareCapsNet aiming to leverage the landmark advantages of capsule networks in single cell domain, by identifying novel rare cell population through markers genes explained from human-mind-friendly interpretation of lower-level (primary) capsules. We demonstrate the explainability of capsule network for identifying novel markers that are act as signature of certain cell population of rare type. A comprehensive evaluation in simulated and real life single cell data demonstrate the efficacy of RareCapsNet for finding out rare population in large scRNA-seq data. RareCapsNet outperforms the other state-of-the-art not only in specificity and selectivity for identifying rare cell types, it can also successfully extract transcriptomic signature of the cell population. We demonstrate RareCapsNet to the dataset of multiple batch, where the model can store the knowledge of one batch which can be transferred to find out rare cells of other batch without training the model. Availability and ImplementationRareCapsNet is available at: https://github.com/sumantaray/RareCapsNet.

bioinformatics↗

Structural and functional basis of proton-independent transition metal import by a canonical bacterial Nramp transporter

Natural resistance-associated macrophage proteins (Nramps) are divalent transition metal transporters found in most organisms, typically coupling metal uptake to proton co-transport. How this coupling evolved, however, remains unclear. We present structural, functional, and evolutionary analyses of a clade B Nramp from the gut bacterium Bacteroides fragilis (BfraNramp). Phylogenetic reconstruction positions clade B as the most basal group of canonical Nramps, retaining conserved metal-binding motifs while lacking most residues that form the canonical proton pathway. We show that BfraNramp efficiently transports Mn{superscript 2} and Cd{superscript 2} with high apparent affinity but without proton co-transport or dependence on membrane potential or pH. Structures of metal-free and Mn{superscript 2}-bound BfraNramp reveal an inward-open conformation and a distinct metal coordination geometry involving a conserved glutamate on transmembrane helix 3. Together, these results identify clade B Nramps as proton-independent transition metal uniporters and suggest that proton coupling emerged later in Nramp evolution, following establishment of the metal-binding site.

biochemistry↗

Transcriptomic Analysis Reveals Inflammatory and Metabolic Dysregulation in Unexplained Female Infertility

Infertility is a complex condition affecting both the male and female population. Influenced by multiple factors, it remains a constant challenge due to limited understanding of endometrial abnormalities. With this study we aim to investigate the molecular basis of infertility using transcriptomic analysis of endometrial tissue from the NCBI GEO dataset GSE92324. We performed exploratory data analysis using Principal Component Analysis (PCA) to find samples variance followed by differential gene expression (DGE) analysis using DESeq2 package where we identified 168 significant genes with adjusted p-value < 0.05 and |log2FC| > 2. Upregulated genes included GPX3, CXCL14, and PPARGC1A and downregulated genes included WNK4, GJB2, and TRPM6. Functional enrichment using KEGG and GO showed that differentially expressed genes (DEGs) are involved in immune-inflammatory pathways, lipid metabolism and steroid biosynthesis pathways. Through Ingenuity Pathway Analysis (IPA) we identified affected canonical pathways such as increased innate immune responses, altered lipid metabolism and inhibition of mitochondrial dysfunction. Upstream regulator analysis highlighted PTEN, PRKAA1, HDAC4, IL10RA, and RAD51, which were impacting metabolic pathways and anti-inflammatory signalling. Further, through Weighted Gene Co-expression Network Analysis (WGCNA) we found a Turquoise module that had very strong and highly significant negative correlation (cor = - 0.84, respectively and P < 0.0001) with traits of interest. This led to the discovery of C7orf50 as a novel insight involved in cholesterol metabolism linked to infertility. This integrative approach reveals crucial genes, co-expression modules, and underlying pathways involved in female infertility. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/701467v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@4418a6org.highwire.dtl.DTLVardef@ae7900org.highwire.dtl.DTLVardef@89f581org.highwire.dtl.DTLVardef@154f1a9_HPS_FORMAT_FIGEXP M_FIG C_FIG HIGHLIGHTSO_LIFrom the dataset GSE92324 total of 168 significant DEGs associated with unexplained infertility were identified using adjusted p-value < 0.05 and |log2FC| > and < 2. C_LIO_LIIn comparison with the CTD list we identified five genes C1orf106, C15orf59, LINC00461, C15orf48, and C10orf99 previously unknown as having direct evidence of involvement in infertility. C_LIO_LIWGCNA analysis highlighted the turquoise module as highly associated and gave the novel gene C7orf50 associated with cholesterol metabolism. C_LIO_LIIPA revealed PTEN, PRKAA1, IL10RA, and RAD51 as potential upstream regulators and inflammatory pathways, mitochondrial dysfunction as canonical pathways. C_LIO_LIThe study highlights a novel link between GI inflammation and endometrial receptivity. C_LI

bioinformatics↗

A Systems-Level Transcriptomic Analysis of Polycystic Ovary Syndrome as a Mitochondrial-Immunometabolic Disorder

Polycystic Ovary Syndrome (PCOS) is known as an endocrine and metabolic disorder; however, emerging molecular evidence suggests a far more complex systems-level pathology. In this study, we performed an integrative transcriptomic and pathway-level analysis of endometrial tissue from women with PCOS to gain a deeper understanding of the underlying mechanism facilitating the disorder. The findings of the study highlighted mitochondrial dysfunction, chronic oxidative stress, and multi-layered immune dysregulation, adding some new insight apart from classical hyperandrogenism and insulin resistance. We identified some novel gene disease associations which involve C15orf48, ODF3B PRR15-DT, LINC01176, and LOC105379193. The upstream regulators such as (NFE2L2, TWNK, ALKBH1, BCOR, SMARCA4) involved in processes including mitochondrial genome, redox balance, and chromatin remodeling provided new insights into regulatory mechanisms. The IPA pathway analysis validated the compromised immune recovery with low grade inflammations and mitochondrial dysfunctionality. The observations emphasize on complex associations discarding its PCOS pure endocrine nature through immunometabolic-mitochondrial dysfunctionalities.

bioinformatics↗

Gamma oscillations across recording scales show a preference for saturated long-wavelength (reddish) hues in the primate visual cortex

Stimulus-induced narrowband gamma oscillations (30-70 Hz) arise due to excitatory-inhibitory interactions and have been proposed to carry feedforward prediction errors during visual processing. However, the dependence of gamma on stimulus color is not well characterized, with some studies showing a preference for saturated long-wavelength (reddish) hues in invasive recordings from the primary visual cortex (V1), while others showing no preference for red in luminance and cone-contrast balanced colors spanning the Derrington-Krauskopf-Lennie (DKL) isoluminant plane in non-invasive magnetoencephalography (MEG) recordings. To address these discrepancies, we simultaneously recorded local field potentials (LFPs) from V1 (n=2 monkeys) along with scalp electroencephalography (EEG), while presenting luminance-matched hues spanning the entire permissible range of colors. We found that saturated reddish hues produced the strongest gamma in both LFP and EEG in both monkeys. However, gamma was reduced when the colors were desaturated, so that selectivity for reddish hues was diminished or absent on the DKL space, as shown previously. Interestingly, selectivity was further reduced in EEG compared to LFP. Simultaneous recordings from an intermediate visual area (V4, n=1) revealed weak color-induced gamma, partially explaining the weakening of hue selectivity in macro-signals. Gamma power increased with increasing activation along the red-green (L-M) cardinal axis but was virtually absent along the blue-yellow (S-(L+M)) axis, suggesting that gamma could be a reflection of the L-M cone-contrast mechanism. These results comprehensively resolve the earlier discrepancy and shed light about the neural mechanisms underlying gamma generation in primate V1. Significance StatementGamma-band brain rhythms are markers of cortical computation and disease, yet their dependence on color has remained controversial because studies using different recording methods and stimulus color spaces yielded conflicting results. By densely sampling colors across the entire monitor gamut in an isoluminant space and mapping brain rhythms across multiple neural scales in primates, we show that primary visual cortex generates exceptionally strong gamma for saturated reddish hues. Crucially, this effect is driven by contrast in specific cone pathways (specifically, L-M cone contrast), and the selectivity diminishes in desaturated color spaces, downstream visual areas and scalp recordings. This explains why the "red bias" observed invasively often vanishes in non-invasive recordings and demonstrates that color-induced gamma reflects pathway-specific circuit engagement.

neuroscience↗

Generative Reconstruction of Unobserved Cellular Dynamics using Single-Cell Transcriptomic Trajectories

The primary challenge in cellular dynamics is to capture the intermediate states between two distinct biological stages. This is because of the technical constraints in capturing transient states or the nature of single-cell sequencing protocols. To address this challenge, we introduce a new computational framework, GRAIL (Generative Reconstruction of Artificial Intermediate Lineages), which aims to bridge these missing transitions. GRAIL reconstructs biologically plausible intermediate cell states between two distinct developmental stages (A and B) through a Locality Sensitive Hashing (LSH) based cell selection strategy followed by a smooth interpolation in learned latent space. The interpolated latent representations are subsequently decoded into gene expression profiles using a trained generator from a Generative Adversarial Network (GAN). The framework consists of three components: (a) a pretrained autoencoder that learns latent representations of stage specific transcriptomes, (b) an LSH-guided interpolation procedure that identifies anchor cells and performed interpolation in latent space, and (c) a GAN generator that extrapolates realistic intermediate expression from the interpolated samples consistent with the underlying trajectory. We benchmarked GRAIL with different state-of-the-arts (SOTA) in diverse setup of simulated dataets as well as in real life scRNA-seq datasets. Generated samples from GRAIL preserve expected marker gene expression patterns and also improve downstream analyses, including differential expression and cell clustering. Our method addresses the critical gap in studying cellular transitions when experimental intermediate samples are unavailable.

bioinformatics↗

Systems Level Analysis of Gene, Pathway and Phytochemical Associations with Psoriasis

Psoriasis is an inflammatory skin disorder driven by abnormal immune activation that promotes excessive proliferation and accelerated turnover of epidermal keratinocytes. IL-17 and TNF pathways are well established in psoriasis, but the other mechanisms that keep the disease active and link it to systemic comorbidities are not yet fully understood. A combined transcriptomic and systems biology framework was applied to map regulatory circuits in psoriatic lesions and to identify phytochemical candidates capable of multi-target modulation for topical intervention. Differential gene expression between lesional and healthy skin was analyzed, followed by functional characterization, employing Qiagens Ingenuity Pathway Analysis (IPA) for pathway and upstream regulator inference, protein-protein interaction network, and chemical-gene interaction mapping. This integrative strategy revealed a transcriptional landscape dominated by type I/III interferon signaling, antiviral and antimicrobial responses, immunometabolic dysregulation, and transcriptional hubs centered on AP-1 and CREB1. Several previously unreported genes and upstream regulators without prior documented association with psoriasis were identified within inflammatory and cell migration-related modules, indicating unexplored regulatory layers in disease control. Network-guided chemical prioritization and direction-of-effect filtering highlighted seven phytochemicals (mahanine, atractylon, protopine, annomontine, taraxasterol, tricin, and tamarixetin) with multi-target activity across key disease axes. ADMET-based screening suggested protopine and atractylon as favorable candidates for topical delivery, while synergy modeling identified compatible phytochemical combinations, with flavonoid-alkaloid pairings among the top candidates. This multi-layered approach provides mechanistically informed phytochemicals targeting the IL-17/TNF-interferon-AP-1/CREB1-COX-2/MMP9 axis in psoriasis. Experimental validation in keratinocyte and organotypic skin models will be required to determine whether these compounds, individually or in combination, can effectively modulate psoriatic signaling in vivo.

bioinformatics↗

POLQ variants with aberrant DNA polymerase activity protect against UV-induced cell death.

DNA polymerases are important for maintaining genomic stability by protecting against mutagenic lesions caused by external and internal factors. If left unrepaired, DNA damage can lead to replication errors resulting in changes in DNA sequences that could impact peptide sequences and gene expression, as well as lead to chromosomal breaks. Highlighting the importance of DNA polymerase repair function, variant DNA polymerases and cofactors of DNA repair pathways have been identified in many different cancer types. Recently, variant forms of DNA polymerase Q (POLQ) have been identified in patient isolated melanoma tumors. Previous work identifying biochemical characteristics of these variants has shown that they display aberrant DNA polymerase activity compared to wild-type (WT). To better understand the role these variants have in DNA repair, genomic stability and cell survival, we tested their ability to bypass and extend DNA past cyclobutane pyrimidine dimers (CPD) as well as prevent cell death when exposed to ultra-violet (UV) radiation. Biochemically we show that the patient derived variants of POLQ tested here display decreased efficiency during DNA bypass and extension of CPD lesions and prefer to incorporate purines. In addition, two of the three variants protect against UV induced cell death. Together these data suggest that POLQ variants can support cell survival and further supports that POLQ variants can act as both protectors of cell viability as well as drivers of genomic instability, characteristics important in cancer cells. HIGHLIGHTS[vrecto] POLQ variants have decreased efficiency during bypass and extension of CPD damaged DNA compared to WT POLQ [vrecto]POLQ is able to bypass and extend cyclobutane pyrimidine dimers, but prefers purine over pyrimidine incorporation [vrecto]POLQ variants can protect against UV induced cell death.

biochemistry↗

BoltzGen: Toward Universal Binder Design

We introduce BoltzGen, an all-atom generative model for designing proteins and peptides across all modalities to bind a wide range of biomolecular targets. BoltzGen builds strong structural reasoning capabilities about target-binder interactions into its generative design process. This is achieved by unifying design and structure prediction, resulting in a single model that also reaches state-of-the-art folding performance. BoltzGens generation process can be controlled with a flexible design specification language over covalent bonds, structure constraints, binding sites, and more. We experimentally validate these capabilities in eight diverse design campaigns with functional and affinity readouts across 26 targets. In our experiments, binder modalities span from nanobodies to disulfide-bonded peptides, and targets from disordered proteins to small molecules. In particular, we identify nanobody binders for novel targets with low similarity to proteins with already known bound structures. We release model weights, data, and both inference and training code at: https://github.com/HannesStark/boltzgen.

bioengineering↗

Persistent Activation of Monocytes/Macrophages and Cell Senescence in SIV-Infected Macaques on ART

Despite effective viral suppression with antiretroviral therapy (ART), people living with HIV (PLWH) experience persistent inflammation, immune dysfunction, and premature onset of cardiovascular and aging-related comorbidities. To define the underlying mechanisms, we performed longitudinal transcriptomic profiling in peripheral blood mononuclear cells (PBMCs) from a cohort of simian immunodeficiency virus (SIV)-infected rhesus macaques spanning four key stages: pre-infection, acute infection, short-term ART, and long-term ART. Bulk RNA sequencing revealed dynamic immune remodeling across infection and treatment. Acute SIV infection induced robust antiviral and inflammatory programs, with upregulation of interferon-stimulated genes (ISGs), IL-27, JAK/STAT, and NF-{kappa}B signaling, coupled with suppression of T- and B-cell activation pathways. Short-term ART effectively reversed these transcriptional perturbations, restoring adaptive immune gene expression and reducing innate antiviral responses to near-baseline levels. In contrast, chronic SIV infection on long-term ART maintained viral suppression but was characterized by reactivation of innate immune pathways, including TLR2/TLR4/MYD88, NF-{kappa}B, and inflammasome (NLRP3/or NLRP12, caspase-1) signaling, along with sustained macrophage activation, platelet/coagulation signaling, and senescence-associated secretory phenotype. Protein analyses confirmed persistent CASPASE-1 and NF-{kappa}B activation in spleen tissue. Pathologic evaluation of a carotid artery from an SIV-infected, long-term ART- treated macaque revealed macrophage-rich plaques with p21 senescent cells with intraluminal thrombus formation, recapitulating key features of HIV-associated atherogenesis. Together, these findings demonstrate that while ART normalizes acute infection-induced immune dysregulation, chronic SIV infection sustains a chronic, macrophage- and TLR-driven inflammatory state linked to vascular injury and aging process regardless of long-term suppression of viremia. Targeting inflammasome, NF-{kappa}B, and senescence pathways may mitigate non-AIDS comorbidities in PLWH.

immunology↗

Naturally occurring CodY variants alter ligand binding, DNA target affinity, and virulence in Clostridioides difficile

Clostridioides difficile is an important nosocomial pathogen that has been classified as an "urgent threat" by the CDC. Antibiotic use is the primary risk factor for the development of C. difficile-associated disease because it disrupts healthy protective gut flora and enables C. difficile to colonize the colon. C. difficile damages host tissue by secreting toxins and disseminates by forming spores. Nutrient availability and other environmental factors greatly influence toxin production in C. difficile. CodY is a global transcriptional regulator that coordinates metabolism and virulence in Gram-positive pathogens in response to nutrient availability, primarily through sensing branched-chain amino acids (isoleucine, leucine, valine; ILV) and GTP. In C. difficile, CodY indirectly represses toxin production by inhibiting transcription of the positive regulator tcdR and influences sporulation through unknown mechanisms. Here, we characterized two naturally occurring CodY variants, CodY(Y146N) and CodY(V58A). The Y146N substitution is located near the GTP-binding pocket, while V58A is near the ILV-binding site. Ligand binding assays revealed GTP binding ability of CodY(Y146N) is severely compromised. Electrophoretic mobility shift assays (EMSAs) demonstrated that ligand binding differentially influenced promoter binding; in the presence of GTP, CodY(Y146N) bound to the tcdR promoter less efficiently than CodY(WT). In C. difficile, production of either variant resulted in reduced repression of toxin production compared to CodY(WT). Subsequent in vivo experiments in a hamster infection model showed that strains producing CodY(Y146N) or CodY(V58A) were significantly more virulent than the CodY(WT) producing strain. These findings demonstrate that a single amino acid change in this global regulator can alter its ligand affinity and promoter-binding properties to potentially rewire the gene regulatory networks to enhance the pathogenic potential in C. difficile. ImportanceC. difficile has been recognized as an important nosocomial pathogen that causes diarrheal disease as a consequence of antibiotic exposure. CodY controls the expression of numerous metabolic and virulence genes. In this study, we have characterized two CodY variants and have demonstrated that even a single residue change in important domains can affect its function and have implications on bacterial virulence.

microbiology↗

Divergent roles of DNA methylation, TRIM28, and p53 surveillance in human embryonic and trophoblast stem cells

Transcriptional regulation of transposons and genes by TRIM28 and 5mC is critical for proper mammalian embryonic development, but the specific roles for these mediators in human embryonic and placental lineage remain unclear. We find that loss of TRIM28 has a limited effect on global transposon expression and instead results in upregulation of genes proximal to TRIM28-bound Long Terminal Repeats (LTRs) in both human trophoblast stem cells (hTSCs) and human embryonic stem cells (hESCs). MER11A elements show especially strong regulatory importance in hTSCs: these elements are bound by both TRIM28 and placental transcription factors and show both heterochromatic and euchromatic features. Some genes are positively regulated by MER11A elements in hTSC basal state, while other MER11A-proximal genes show upregulation only upon TRIM28 deletion. By contrast, loss of DNA methylation in hESCs or hTSCs leads to a global increase in transposon expression. While many genic 5mC targets are shared in hESCs and hTSCs, we also observe evidence that a handful of genes important for somatic development are repressed by 5mC in trophoblast, while a small parallel set of placental genes are repressed by methylation in embryonic tissue. Interestingly, loss of DNMT1 causes hESCs to be rapidly lost from culture in a TP53 and mitotic surveillance checkpoint-dependent manner, while hTSCs show little p53 response to DNMT1 loss or DNA damage generally, instead showing gradual mitotic defects and aneuploidy and slow loss from culture. This discrepancy may explain the higher frequency of karyotypic abnormality found in human placental cells. Together, this study charts the role of TRIM28 and DNA methylation in regulating embryonic and placental transcription and demonstrates divergent p53-dependent responses to genomic instability.

molecular biology↗

Modeling collective cell migration in a heterogeneous environment: Drosophila border cell migration as a model paradigm

Collective cell migration underpins development and disease progression, yet the influence of heterogeneous microenvironments on intercellular forces and migration dynamics remains elusive. Focusing on the chemotactic migration of border cell clusters in Drosophila egg chambers, we present a computational framework that integrates intercellular force dynamics and cell shape changes during large-scale migration, validated with live imaging data. Our model replicates in vivo observations, such as rotations of the cell cluster and its tendency to follow a central path in the egg chamber. Using the model, we discover instantaneous acceleration/deceleration phases as the cell cluster migrates through junctions of other cell types. We also predict how environmental tissue topology and perturbations in chemoattractant gradients and adhesion impact cluster speed and rotation. By addressing the limitations of prior models of border cell migration, our approach offers broad applicability to other migration contexts involving interactions among different cell types in complex environments.

biophysics↗

Neutrophil myeloperoxidase as a functional biomarker for RSV severity: implications for in vitro therapeutic screening.

Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract infections in infants, yet effective therapeutics are lacking. The aim of this study is to develop an in vitro model that recapitulates key clinical outcomes in infants with RSV bronchiolitis to help accelerate the discovery of effective therapeutics. Neutrophil activation and influx into the airways are hallmarks of severe RSV infection, but these responses are difficult to quantify in clinical trials. Here we profile peripheral blood-derived neutrophils from infants with RSV admitted to the Paediatric Intensive Care Unit (PICU) and identify myeloperoxidase (MPO) as a key indicator of disease severity when compared to age matched controls. To mechanistically model this response, we established a paediatric airway epithelial air-liquid interface (ALI) system incorporating an endothelial layer and primary neutrophils to recapitulate the tissue microenvironment at the blood-airway barrier. Following RSV infection, neutrophil migration and activation were assessed using flow cytometry. The inclusion of an endothelial layer enhanced physiological relevance and more accurately replicated in vivo MPO responses. We then evaluated two antiviral candidates (remdesivir (RDV) and RSV604) to assess their ability to modulate neutrophil activation. While both compounds reduced viral load at 24 hours post-infection, only RSV604 attenuated MPO expression. These findings establish MPO as both a biomarker of RSV disease severity and a functional readout of therapeutic efficacy and demonstrate that targeting neutrophildriven inflammatory pathways may be critical for reducing pathology in infant RSV infection. Take home messageAntiviral drug discovery should include neutrophil MPO reduction as a readout of therapeutic efficacy. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=147 SRC="FIGDIR/small/682115v2_ufig1.gif" ALT="Figure 1"> View larger version (52K): org.highwire.dtl.DTLVardef@170058corg.highwire.dtl.DTLVardef@17c344corg.highwire.dtl.DTLVardef@14d79baorg.highwire.dtl.DTLVardef@172ac3c_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

Arginine methyltransferase PRMT1 equipoises trophoblast development to prevent early pregnancy loss

Abstract1-2% of all human pregnancies suffer from idiopathic recurrent pregnancy loss (RPL) and underlying molecular causes are poorly understood. Here we show that defective Protein Arginine Methyltransferase 1 (PRMT1) function in trophoblast progenitors is a molecular cause for early pregnancy failure. PRMT1 is conserved in trophoblast progenitors and conditional deletion of PRMT1 in mouse trophoblast progenitors arrests placenta and embryonic development leading to lethality [~]E7.5. Remarkably, a subset of idiopathic RPL is associated with loss of PRMT1 in cytotrophoblast progenitors (CTBs). Experiments with human trophoblast stem cells (hTSCs), derived from these RPL-patients as well as PRMT1-depleted hTSCs revealed that PRMT1 is crucial for trophoblast progenitors self-renewal. Employing RNA-seq and CUT&RUN-sequencing in hTSCs, CTBs and primary mouse trophoblast progenitors we discover that PRMT1 promotes transcription of trophoblast stem-state regulators, like TEAD4 and MYBL2, by directly enriching histone H4 arginine 3 asymmetric di-methylation (H4R3Me2a) at their chromatin loci. PRMT1 is also essential for extravillous trophoblast (EVT) development during human placentation, while loss of PRMT1 in hTSCs spontaneously promotes syncytiotrophoblast (STB) differentiation. Our findings indicate that PRMT1 is an epigenetic governor that orchestrates mammalian trophoblast development and implicate the therapeutic potential of targeting the PRMT1-H4R3Me2a axis to mitigate early pregnancy loss.

developmental biology↗

Differential Burst dynamics of Slow and Fast gamma rhythms in Macaque primary visual cortex

Gamma oscillations have been ubiquitously observed across a wide spectrum of brain areas in multiple species. They tend to occur intermittently in the form of bursts, rather than being produced as sustained and continuous rhythmic activity. Recent studies have shown that large visual sinusoidal gratings elicit two distinct gamma rhythms, namely, slow ({approx} 20-35 Hz) and fast gamma ({approx} 40-65 Hz), in the primary visual cortex (V1) of non-human primates. However, their mechanisms of generation and potential functional role in cortical processing remain unclear. Details of their burst signatures could potentially provide crucial insights about how the two rhythms influence network dynamics. Therefore, we computed burst statistics (durations and latencies) of simultaneously induced slow and fast gamma rhythms in the local field potential (LFP) recorded from area V1 of two adult female bonnet monkeys using several burst estimation methods. We found that slow gamma rhythm exhibited significantly longer burst durations and longer latencies as compared to fast gamma. Slow gamma exhibited higher long-range synchrony compared to fast gamma, as estimated by coherence and weighted phase lag index (WPLI), which could aid in enhanced global coordination in neocortex. Interestingly, longer burst length of slow-gamma could be replicated in a recently-developed noisy Wilson-Cowan network model by simply changing the firing-rate time-constant of the corresponding inhibitory interneuronal population, which leads to both slower and longer bursts. These results are consistent with the hypothesis that the two oscillations are generated by different inter-neuronal classes that operate over different temporal and spatial scales of integration. Significance statementSlow ({approx} 20-35 Hz) and fast gamma ({approx} 40-65 Hz) are two distinct rhythms known to be induced by large visual gratings in the primary visual cortex (V1). Interestingly, gamma oscillations manifest in the form of transient and stochastic epochs, generally termed as "bursts". We estimated the durations of stimulus-induced slow and fast gamma bursts generated in the local field potential (LFP) recorded from V1 of monkeys. Slow gamma bursts had significantly longer durations and increased latency to onset compared to fast gamma, which was replicated in a noisy Wilson-Cowan model by changing the time-constant associated with inhibitory neuronal population. These results suggest that slow and fast gamma are generated by different inter-neuronal networks operating at different spatio-temporal scales.

neuroscience↗

Gravity-Dependent Metabolomic Responses in Starbor Kale Brassica oleracea: Comparisons With Simulated Microgravity Versus Gravity Grown

As science continues to push the frontiers on the length of space flight, we begin to experience an enhanced need for food that is nutritionally dense. Nasa-grants have worked to explore the ability of growing superfoods in space on aircrafts. However, it is paramount to ensure the physiological health of the plants being grown in space flight, perform relatively similar to the plants that grow on earth. An aspect which needs to be further probed is the comparison of microgravity and gravity on the plants seeking to be grown in space flight. Within this NASA-funded research, we grew a superfood vegetable, Kale. The kale was grown in simulated microgravity environments to mimic life in outer space. This simulation was induced by means of a 2-D clinostat. Additionally, kale was grown in gravity conditions as well. We used multivariate statistical tools such as Principal Component Analysis (PCA), together with differential-expression visualizations like volcano plots, to summarize complex data rendered from LC-MS. In this study, we used these approaches to examine how horizontal and vertical orientations both in static and rotating configurations simulate aspects of simulated-microgravity and influence metabolic responses; this combined analysis provided a broad perspective on gravity-related metabolic adaptations and points to potential molecular markers that could guide future research on spaceflight health and countermeasure development.

plant biology↗

A Multi-lensed Comparative Analysis of Select Secondary Metabolites Produced by Kale, Brassica oleracea, in Simulated Microgravity Versus Gravity Conditions

Extended journeys through space are a goal of NASA. Yet, astronauts will face elevated health risks from microgravity and radiation as journeys continue for longer time periods. Approaches to combatting these health risks consist of growing fresh super foods in space for astronaut consumption while in flight. However, while a great deal is known about the effects of microgravity of humans, little is known about its effects on the nutrient profiles of plants. Endeavors towards understanding more about these effects are currently funded by NASA grants. Kale, a metabolite and specifically a flavonoid-rich crop, stands as a promising candidate for growth on space flights. We observed the effects of simulated microgravity broadly on the F1 cultivar, Starbor Kale metabolomics, and further focused on flavonoid content, using a 2-D clinostat. Extracts of kale were analyzed by proton nuclear magnetic resonance (1H NMR), and high-performance thin layer chromatography (HPTLC). 1H NMR spectra of clinostat-grown kale showed that samples from simulated microgravity conditions had an increased number of peaks in the aromatic region (6.5 to 8.5 ppm) when compared with gravity grown kale. HPTLC confirmed greater banding in medium- and high-polarity solvent systems, while low-polarity extracts showed no differences. Overall, we noted that the microgravity grown kale had greater amounts of bands present. These results signal that microgravity stressors may be connected to the increased secondary metabolite production in kale. Our findings underscore kale to be a prospective crop to be grown in space flight to combat effects of microgravity.

plant biology↗