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Ray, S.

Publications and source records attributed to Ray, S..

At least 55 records · Page 3Linked to original sources

A Graph-Attentive GAN for Rare-Cell-Aware Single-Cell RNA-Seq Data Generation

A central challenge in downstream single-cell RNA sequencing (scRNA-seq) analysis is the high-dimensional, small-sample (HDSS) regime, often compounded by class imbalance from rare cell types. These factors hinder robust feature (gene) selection and cell clustering and limit the realism of samples generated by existing simulators. We introduce GARAGE, a Graph-Attentive RAre-cell aware single-cell data GEneration that augments the generators input with a small, attention-weighted leakage of real cells in addition to prior noise. Specifically, we build a k-nearest-neighbour cell graph and use a graph attention network (GAT) to prioritize nodes that likely represent under-sampled (rare) subpopulations; these high-attention cell embeddings are injected into the generator input to steer synthesis toward biologically plausible regions of the data manifold while respecting cell-type proportions. This attention-guided leakage accelerates training, reduces mode dropping, and yields realistic synthetic cells that preserve rare-cell structure. Across real scRNA-seq benchmarks, GARAGE improves downstream feature selection and clustering compared with state-of-the-art baselines. In summary, GARAGE directly addresses HDSS and rarity in scRNA-seq by coupling graph attention with adversarial generation to produce high-fidelity synthetic cells that enhance downstream analyses.

bioinformatics↗

L2 loop engineering enhances the enzymatic activity and synergism property of the AA16 family Lytic polysaccharide monooxygenase enzyme from Aspergillus fumigatus.

Lytic polysaccharide monooxygenase (LPMO) is an enzyme that has enormous potential for industrial applications. It has a synergistic effect with the cellulase enzyme complex. The LPMO enzymes typically adopt a compact {beta}-sandwich fold that consists of a 7 to 9 {beta}-strand with a flat active site containing copper in its active site. There are a few loops in LPMO, among them the L2 loop is reported to take a key role in shaping the active site and substrate binding. Now, in this work, we want to investigate the role of the L2 loop in enzymatic activity and synergistic effect. In achieving our goal, we have replaced the L2 loop of our concerning AfLPMO16 with other L2 loops from different LPMOs: HiLPMO9B (PDB: 5NNS), McLPMO9 (PDB: 7NTL) and CsLPMO9 (PDB: 7EXK). Interestingly, L2 loop replacement from CsLPMO9 (PDB: 7EXK) showed enhanced activity and synergism compared to others. The secondary structural analysis by circular dichroism also suggested that it changed the structure significantly. Moreover, this is the first report of complete L2 loop engineering in LPMO.

biochemistry↗

Slow-varying normalization explains auditory steady-state masking interactions in human EEG

The inherent ability of sensory neurons to entrain to modulations in the temporal structure of an auditory stimulus gives rise to the auditory steady-state response (ASSR). Simultaneous presentation of multiple acoustic stimuli by frequency tagging them to generate ASSRs at different frequencies is routinely employed for hearing threshold determination and cognitive studies. However, the nature of ASSR interactions as a function of competing modulation frequencies in the absence of overt behaviour and the underlying neural mechanisms have not been well studied. Such interactions have previously been studied with visual stimuli that generate steady-state visually evoked potentials (SSVEPs) and explained using a normalization model. Here, we tested whether similar interactions are observed in the auditory domain, and if so, can be explained using a similar model. We played sinusoidally amplitude-modulated stimuli simultaneously modulated at two frequencies while we recorded a 64-channel EEG from subjects who passively listened to these sounds with closed eyes. We used multiple modulation frequencies and depths to characterize the ASSR modulation masking response profile. We observed that modulation frequencies closer to each other suppress the ASSR strongly than frequencies that are farther apart, similar to the interaction observed in the visual domain using SSVEPs. The observed suppression was captured by a slow-varying normalization model, which was initially used to explain SSVEP interactions. We obtained a band-pass shaped suppression profile with a low-pass cutoff that matched to that observed for SSVEP interactions. Our findings highlight the universality of the normalization model in accounting for masking interactions across modalities.

neuroscience↗

A Phosphoinositide Interacting Protein Coordinates Stress Precursor Activities

Samd14 is crucial for cell signaling and survival in mouse models of acute anemia. Samd14 has an N-terminal actin capping protein (CP) and a C-terminal sterile alpha motif (SAM) to coordinate stem cell factor/Kit and erythropoietin receptor signaling pathways during terminal differentiation of red blood cell precursors. Here we present new findings that Samd14 expression is needed to maintain balanced autophagy in red blood cell precursors following acute anemia. Autophagy gene signatures and protein levels are markedly altered within the context of acute anemia when red blood cell precursors accelerate the process of erythropoiesis. Samd14 interacted via its SAM domain with phosphatidylinositol 3-phosphate (PI3P) which is an integral component of endosomal and autophagic membranes. We tested PI3Ps role in red blood cell differentiation using a small molecule inhibitor of the Class III PI 3-kinase VPS34, which is the sole kinase responsible for PI3P genesis. SAR405 treatment blocked red blood cell formation. In the absence of Samd14, higher doses of VPS34 inhibition were required to block erythroid differentiation. Given the critical roles of autophagy in normal differentiation, Samd14s stress-dependent activation and roles in autophagy suggest that this mechanism is needed to maintain progenitor levels and balance the production of healthy, mature red blood cells. Key Points- Autophagy genes/proteins are deregulated in red blood cell progenitors after hemolysis-induced acute anemia. - The anemia-activated Samd14 protein interacts with the PI3P lipid moiety which is integral to endosomal and autophagic membrane functions. - VPS34 inhibition blocks terminal erythroid maturation in a Samd14-dependent manner.

molecular biology↗

Isolation and Quantification of mRNAs from Subcellular Phase-Separated Structures from Detergent Permeabilized Brain Cells

Post-transcriptional regulation by RNA processing bodies, also known as P-bodies (PBs), is crucial for mRNA translation, localization, and stability in various animal cells, including neurons and glial cells. PBs facilitate spatial regulation of protein synthesis, influencing differentiation and synaptic function. Understanding mRNA dynamics in PBs is vital and is suspected to be impaired in neurodegenerative disorders. We developed a detergent-based method to isolate phase-separated P-bodies (PBs) free from cytosolic factors and RNAs, which allows us to examine their mRNA content under altered conditions. Using neuronal and glial cell models, we investigated the impact of A{beta}-oligomers on PB-associated mRNAs. In neurons, exposure to amyloid proteins disrupted the release of neuronal differentiation-related mRNAs, hindering their translation. Glial cells exhibited increased levels of cytoplasmic pro-inflammatory cytokine mRNAs after amyloid treatment, as they escaped from RNA processing bodies (PBs), ensuring enhanced translation. These findings underscore the dual role of PBs in controlling mRNA dynamics across cell types and illustrate how amyloid-induced stress may differently affect PB-mediated post-transcriptional control in neurons and astroglia. This method provides a platform for studying the mechanism and quantifying sub-organellar mRNA localization, as well as its effects on altered gene expression caused by amyloid proteins. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=195 HEIGHT=200 SRC="FIGDIR/small/669016v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@335e76org.highwire.dtl.DTLVardef@7ecf8dorg.highwire.dtl.DTLVardef@16c375dorg.highwire.dtl.DTLVardef@1a6c086_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIA detergent-based differential solubilization of RNAs from PBs in brain cells. C_LIO_LIIn neuronal cells, {beta}-Amyloid oligomers target specific neuronal differentiation-related mRNAs to PBs. C_LIO_LIIn astroglia, {beta}-amyloid triggers the escape of inflammatory cytokine mRNAs from PBs. C_LIO_LIAltered mRNAs -protein phase separation connects PBs to neuroinflammation. C_LI

cell biology↗

Change of Guards: ELAVL Proteins Switch miRNA Export Responsibility to Regulate Neuronal Differentiation

ELAVL1 protein HuR controls the stability and activity of miRNAs by disconnecting miRNPs from their target mRNAs and exporting Ago2-uncoupled miRNAs to help hepatic and macrophage cells manage stress. In mammalian neurons, the homolog of HuR, ELAVL4 or HuD, is expressed; however, its role in miRNA regulation remains unknown. PC12, a rat pheochromocytoma cell line, is a well-established model for studying neuronal differentiation that resembles sympathetic neurons. In PC12 cells, HuD levels increase during differentiation, which suppresses HuR expression. Thus, HuD overrides HuRs control of miRNA activity in differentiating cells, promoting differentiation by regulating the activity and levels of specific miRNAs, such as let-7a and miR-125b. When HuD is present, it decreases the activity of these miRNAs by binding to them, thereby facilitating their export and ensuring neuronal differentiation. Overall, there is a shift in miRNA regulation, with HuR being replaced by HuD in controlling miRNA export during neuronal differentiation. This switch in ELAVL-mediated miRNA regulation is essential for the differentiation process.

molecular biology↗

A mathematical framework for human neutrophil state transitions inferred from single-cell RNA sequence data

Neutrophils, the most abundant immune cells in the human circulation, play a central role in the innate immune system. While neutrophil heterogeneity is a topic of increasing research interest, few efforts have been made to model the dynamics of neutrophil population subsets. We develop a mathematical model to describe the dynamics that characterizes the states and transitions involved in the maturation of human neutrophils. We use single-cell gene expression data to identify five clusters of healthy human neutrophils, and pseudo-time analysis to inform model structure. We find that precursor neutrophils transition into immature neutrophils, which then either transition to an interferon-responsive state or continue to mature through two further states. The key model parameters are the transition rates (the inverse of a transition rate is the mean waiting time in one state before transitioning to another). In this framework, the transition from the precursor to immature state (mean time less than an hour) is more rapid than subsequent transitions (mean times more than 12 hours). Approximately a quarter of neutrophils are estimated to follow the interferon-responsive path; the remainder continue along the standard maturation pathway. We use Bayesian inference to describe the variation, between individuals, in the fraction of cells within each cluster.

cell biology↗

Ethanolic leaf extract of Cleome spinosa induces apoptosis in Ehrlich ascites carcinoma cells through upregulation of p53 and down-regulation of Bcl-xL in vitro and in vivo

Cleome genus is commonly known as spider flower plant or cats whiskers, and is the largest genus of the family Cleomaceae, with around 200 species containing a range of remedial applications. Several species of Cleome genus show anti-cancer properties, however, nothing has been reported with genus spinosa, an anti-inflammatory and immunomodulatory plant. Thus, the present study examined the likely anti-cancer property of ethanolic leaf extract of Cleome spinosa (CSE) in Ehrlich ascites carcinoma (EAC) cells in vitro and in vivo. CSE treatment in vitro significantly caused higher percentage of death in EAC in a dose dependent manner compared to control groups (untreated and ethanol treated). Bright field, fluorescence and electron microscopies revealed apoptotic changes such as surface blebbings, nuclear fragmentation, chromatin condensation and apoptotic body formation, which probably could be the cause of death in EAC cells with CSE treatment. Apoptosis of CSE-treated EAC cells appeared to be mediated through upregulation of pro-apoptotic protein p53 and downregulation of anti-apoptotic protein, Bcl-xL expression, as ascertained through western blot both in vitro and in vivo. CSE was protective toward murine splenocytes by scavenging free radicals; it also reduced the ascitic tumor burden and increased the survival of the tumor-bearing mice compared to the control. Gas Chromatography-Mass Spectrometry (GCMS) analysis identified 43 phytocompounds in CSE. In silico molecular docking analysis indicated that a number of bioactive compounds, such as cycloartenol, stigmasterol, clionasterol, beta-sitosterol, lupenone, and sitostenone that were abundant in the CSE extract, exhibited strong binding affinities for the key apoptosis-regulating proteins, p53 and Bcl-xL. Thus, CSE derived-compounds appear to act as natural antioxidants, and have anti-cancer properties via induction of apoptosis in EAC possibly through upregulation of p53 and downregulation of Bcl-xL proteins in murine model. Hence, CSE could be considered as a promising natural compound for future cancer therapies.

cancer biology↗

Hydrolysis-dependent severing tunes internal monomeric heterogeneity to shape actin length distributions

The coordination of actin-binding proteins (ABPs) is essential for forming a wide range of actin structures that drive vital cellular processes. Many of the ABPs, like the severing protein cofilins, exhibit affinities dependent on the nucleotide state of actin monomers. Experiments have shown that cofilins interact with actin filaments cooperatively in a concentration-dependent manner, where it severs less at both low and high concentrations. However, how this nucleotide state-dependent severing influences actin filament distributions is poorly understood. Here, we propose a computational model of actin filament dynamics that combines stochastic polymerization, phosphate release, hydrolysis-dependent cooperative binding of cofilins, and severing of actin monomers. This model simultaneously reproduces key experimentally observed features: The non-monotonic change of the filament length and the monotonic decay in actin cap size with the increasing cofilin concentration, as well as the linear increase of the cap size with the actin concentration. We elucidate how both these emerge from the tuning of the heterogeneity in the arrangement of cofilin decorated and undecorated monomers within a filament. We also predict that, with varying cofilin concentrations, steady-state length distributions can change from symmetric bell-shaped to long-tailed skewe d shapes. We show that, in some regimes, our model simplifies to a coarse-grained model enabling us to mathematically predict that the distribution of undecorated monomers is exponential with a decay exponent that depends on cofilin and actin concentration. This study highlights the importance of non equilibrium processes that can modulate structural heterogeneity within a filament to shape actin length variation.

biophysics↗

A unifying model for microRNA-guided silencing of messenger RNAs

Silencing by the miRNA-guided RNA induced silencing complex (miRISC) is dependent on Ago2-chaperoned base pairing between the miRNA 5' seed (5'S) and a complementary sequence in the 3' untranslated region of an mRNA. Prevailing mechanistic understanding posits that initial 5'S pairing can further allow functional base pair expansion into the 3' non-seed (3'NS), while functionally distinct non-canonical pairing was reported between only the 3'NS and the mRNA coding sequence. We developed single-molecule kinetics through equilibrium Poisson sampling (SiMKEPS) to measure highly precise binding and dissociation rate constants of varying-length target sequences to 5'S and 3'NS in a paradigmatic miRISC isolated from human cells, revealing distinct stable states of miRISC with mutually exclusive 5'S and 3'NS pairing. Our data suggest conformational rearrangements of the Ago2-bound miRNA that regulate alternative 5'S-and 3'NS-driven target recognition. The resulting model reconciles previously disparate observations and deepens our acumen for successfully marshaling RNA silencing therapies. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=166 SRC="FIGDIR/small/643529v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@1e92bb5org.highwire.dtl.DTLVardef@1348249org.highwire.dtl.DTLVardef@559fdborg.highwire.dtl.DTLVardef@1721b74_HPS_FORMAT_FIGEXP M_FIG C_FIG In brief: In this study, Chatterjee et al. developed a technique to characterize and identify multiple conformations of the RNA-induced silencing complex (RISC) present in human cells. Two distinct pathways of target recognition through different RISC conformations reconcile previously observed divergent findings on the microRNA (miRNA) binding mechanism to messenger RNA (mRNA). HighlightsO_LISiMKEPS is developed to precisely measure binding and dissociation of miRISC:mRNA C_LIO_LISingle human miRISC molecules exhibit mutually exclusive seed and non-seed pairing C_LIO_LISiMKEPS unveils conformational changes of single miRNAs bound to Ago2 C_LIO_LIResulting model reconciles previously divergent findings, supporting RNAi therapies C_LI

biophysics↗

Slow-varying normalization explains diverse temporal frequency masking interactions in the macaque primary visual cortex

Neurons in the primary visual cortex (V1) respond non-linearly with the presentation of multiple stimuli, which has been explained by a normalization model where the excitatory drive is divided by the summed activity of a large neuronal population. While recent studies have suggested that normalization could be time and frequency-dependent, neural mechanisms underlying this dependence remain unknown. Steady-state visually evoked potentials (SSVEPs), which are produced by presenting flickering or counterphasing visual stimuli, serve as a robust tool to probe these underlying mechanisms by leveraging frequency-specific tagging of concurrently presented stimuli. We presented two overlapping counterphasing grating stimuli (plaids), either parallelly or orthogonally, at multiple contrasts and temporal frequencies and recorded spikes, local field potential, and electrocorticogram from V1 of bonnet macaques while they passively fixated. We also recorded electroencephalogram (EEG) activity. The resulting SSVEPs exhibited complicated dynamics - with "low-pass" and "band-pass" suppression profiles for orthogonal and parallel plaids, respectively. Importantly, these dynamics were conserved across scales - from spiking activity to EEG. Surprisingly, adding a simple low-pass filter in the normalization signal sufficiently explained these diverse effects. Our results present a simple mechanism to explain the spectro-temporal dynamics of normalization. These insights may also aid in designing and interpreting SSVEP-based cognitive and EEG-based brain-computer interfacing (EEG-BCI) studies.

neuroscience↗

Chromato-kinetic fingerprinting enables multiomic digital counting of single disease biomarker molecules

Early and personalized intervention in complex diseases requires robust molecular diagnostics, yet the simultaneous detection of diverse biomarkers--microRNAs (miRNAs), mutant DNAs, and proteins--remains challenging due to low abundance and preprocessing incompatibilities. We present Biomarker Single-molecule Chromato-kinetic multi-Omics Profiling and Enumeration (Bio-SCOPE), a next-generation, triple-modality, multiplexed detection platform that integrates both chromatic and kinetic fingerprinting for molecular profiling through digital encoding. Bio-SCOPE achieves femtomolar sensitivity, single-base mismatch specificity, and minimal matrix interference, enabling precise, parallel quantification of up to six biomarkers in a single sample with single-molecule resolution. We demonstrate its versatility in accurately detecting low-abundance miRNA signatures from human tissues, identifying upregulated miRNAs in the plasma of prostate cancer patients, and measuring elevated interleukin-6 (IL-6) and hsa-miR-21 levels in cytokine release syndrome patients. By seamlessly integrating multiomic biomarker panels on a unified, high-precision platform, Bio-SCOPE provides a transformative tool for molecular diagnostics and precision medicine.

biophysics↗

A generalizable Hi-C foundation model for chromatin architecture, single-cell and multi-omics analysis across species

Nuclear DNA is organized into a compact three-dimensional (3D) structure that impacts critical cellular processes. High-throughput chromosome conformation capture (Hi-C) is the most widely used method for measuring 3D genome architecture, while linear epigenomic assays, such as ATAC-seq, DNase-seq, and ChIP-seq, are extensively employed to characterize epigenomic regulation. However, the integrative analysis of chromatin interactions and associated epigenomic regulation remains challenging due to the pairwise nature of Hi-C data, mismatched resolution between Hi-C and epigenomic assays, and inconsistencies among analysis tools. Here we propose HiCFoundation, a Hi-C-based foundation model for integrative analysis linking chromatin structure to downstream regulatory function. HiCFoundation is trained from hundreds of Hi-C assays encompassing 118 million contact matrix submatrices. The model achieves state-of-the-art performance on multiple types of 3D genome analysis, including reproducibility analysis, resolution enhancement, and loop detection. We further demonstrate the models generalizability through genome architecture analysis of 316 species. Notably, by enhancing low-coverage experimental Hi-C data, HiCFoundation reveals genome-wide loop loss during differentiation of hematopoietic stem and progenitor cells (HSPCs) to neutrophils. Additionally, HiCFoundation is able to predict multiple types of epigenomic activity from Hi-C input and further interprets the link between Hi-C input and epigenomic output to reveal the relationship between chromatin conformation and genome function. Finally, HiCFoundation can analyze single-cell Hi-C data, shedding light on genome structure at single-cell resolution. HiCFoundation thus provides a unified, e"cient, generalizable, and interpretable foundation for genome architecture, single-cell and multi-omics analysis across species, paving the path for systematically studying genome 3D architecture and its regulatory mechanisms.

bioinformatics↗

The antigenic landscape of N1 neuraminidase in human influenza A virus strains isolated between 2009 and 2020

The clinical burden caused by influenza can be mitigated by the prophylactic use of seasonal influenza vaccines. Their immunogen composition is revised biannually to optimally match the antigenic drift of the hemagglutinin of circulating influenza virus strains. Antibodies directed against the influenza neuraminidase also correlate with protection against influenza, yet the antigenic evolution of influenza neuraminidase remains underexplored. To evaluate the antigenic diversity of N1 neuraminidase, we generated a panel of immune sera directed against 17 N1 neuraminidases derived from human H1N1 strains that were isolated between 2009 and 2020 and determined its neuraminidase inhibition titers against a panel of 15 HxN1 viruses. The resulting neuraminidase inhibition pattern revealed two antigenic groups that circulated in this period. A machine learning method identified K432E and I321V as key determinants of N1 neuraminidase antigenicity.

immunology↗

Slow and fast gamma oscillations show phase-amplitude coupling with distinct high-frequency bands in macaque primary visual cortex

Gamma oscillations (25-70 Hz) can be induced in the visual cortex by presenting stimuli like gratings. Large stimuli produce two distinct gamma oscillations in primate primary visual cortex (V1) - slow (25-40 Hz) and fast (40-70 Hz), possibly due to different interneuronal networks. While fast-gamma has been shown to strongly lock spikes, slow-gamma does not, and hence its role in cortical processing is unclear. Here, we studied potential influence of gamma rhythms on neural activity using phase-amplitude coupling (PAC). We recorded spikes, local field potential and electrocorticogram (ECoG) from V1 of two adult female monkeys while presenting stimuli that simultaneously induced both gamma rhythms, and developed a novel method that reduces the influence of spike-related-transient on PAC. Interestingly, while fast-gamma showed coupling with frequencies above 150 Hz, reflecting spike-locking, slow-gamma showed PAC in a distinct frequency range between 80-150 Hz, which was especially prominent in ECoG. PAC varied with orientation and spatial frequency in the same way as power in the respective frequency bands, confirming dissociation in the coupling of the two gamma rhythms. Thus, fast-gamma could be more involved in spike-locking, while slow-gamma could represent a modulatory signal acting by amplitude modulation between 80-150 Hz at a more global scale. Significance StatementGamma oscillations in the visual cortex can be induced by stimuli like gratings, producing two distinct gamma oscillations: slow (20-40 Hz) and fast (40-70 Hz). While fast-gamma strongly locks spikes, the role of slow gamma is unclear. Oscillations have been proposed to influence processing through phase-amplitude coupling (PAC). We recorded spikes, local field potential (LFP) and electrocorticogram (ECoG) from female monkeys and developed a new method to study PAC. While fast-gamma showed PAC with 150-500 Hz, reflecting spike-locking, we found PAC between slow-gamma and 80-150 Hz, which was especially strong in ECoG. The two PAC signatures varied differently with stimulus, reflecting distinct origins. Thus, while fast-gamma could lock spikes, slow-gamma could modulate amplitudes between 80-150 Hz at a global scale.

neuroscience↗

Divergent effects of pathological α-synuclein truncations and mutations on phase separation

Phase separated condensates can accelerate -synuclein (-Syn) amyloid fibril formation implicated in Parkinsons disease pathogenesis. The effects of pathological modifications, i.e., truncations and familial mutations on the thermodynamics, material properties, and the extent of amyloid aggregation within -Syn condensates remain elusive. Here, we quantitatively demonstrate that terminal truncations significantly alter -Syn phase separation, while familial mutations impart minimal effects. Spontaneous sol-gel phase transitions of the truncated -Syn variants could give rise to amyloid fibrils almost instantly within condensates, suggesting similarities between molecular interactions driving both processes. Extending our study to model coacervate and condensate systems where -Syn acts as a client, we find -Syn can dissolve coacervates and form Pickering clusters on condensate surfaces--regulating their size. Additionally, the C-terminal region of -Syn modulates nucleic acid sequestration within condensates. Together, our findings reveal diverse effects of -Syn modifications on phase separation, both in pathological and physiological contexts. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=151 SRC="FIGDIR/small/624073v1_ufig1.gif" ALT="Figure 1"> View larger version (52K): org.highwire.dtl.DTLVardef@1760f9dorg.highwire.dtl.DTLVardef@1fb155forg.highwire.dtl.DTLVardef@138402dorg.highwire.dtl.DTLVardef@1fd5229_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

Simultaneously induced slow and fast gamma waves travel independently in primate primary visual cortex

Travelling waves have been reported for multiple neuronal oscillations across the cortex. Within the primary visual cortex (V1), large visual stimuli (gratings) can induce two gamma oscillations - slow (20-35 Hz) and fast (40-60 Hz), potentially due to two different interneuronal classes. However, wave like behaviour of these rhythms and their relationship is unknown. We showed large gratings to monkeys that simultaneously induced slow and fast gamma while recording from V1 using microelectrode arrays. Both slow and fast gamma were organized as travelling waves that were not locked to stimulus onset. Direction of wave propagation was significantly different but showed no correlation, even in concurrent waves. Slow gamma waves lasted for longer durations than fast gamma. Wave direction varied with stimulus orientation and spatial frequency. Thus, slow and fast gamma oscillations in V1 show unique spatial and temporal wave dynamics signifying that these gamma rhythms are generated by distinct neural circuits.

neuroscience↗

Transcriptomic-Based Identification of FCRL6 as a Novel Diagnostic Biomarker in Diabetic Nephropathy

Diabetic nephropathy (DN) is a microvascular complication that arises in a sizable portion of individuals with diabetes mellitus, representing a growing public health issue given its progressive injury of the kidney. DN is primarily driven by the upregulation of pro-inflammatory markers and pathways, which cause hyperfiltration and significant physiological changes to the renal structure. To further understand the molecular mechanisms by which DN progresses, we used bioinformatics and meta-analysis techniques to analyze two datasets from the Gene Expression Omnibus (GEO) database: GSE142025 and GSE142153. Differential gene expressions (DGEs) were identified using the Bioconductor DESeq2 library and further used in functional enrichment analysis. DGEs were also constructed into protein-protein interaction networks and used to find regulatory hub genes. In total, 911 DGEs were found, and enrichment using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) revealed strong correlations with immunoreactive responses and cascades. In our analysis, we discovered 12 protein-coding genes novel with regards to DN; we further identified Fc Receptor-Like 6 - FCRL6 - as a potential biomarker in nephropathy and described its involvement in the suppression of natural killer cell-mediated toxicity as a mechanism of poor immunoregulation in the diabetic kidney. The current study presents comparative analyses of the DN transcriptome and a possible diagnostic marker with applications in immunotherapy treatments of nephropathy.

bioinformatics↗