Biology subjects

Dave, S.

Publications and source records attributed to Dave, S..

8 recordsLinked to original sources

bioRxiv2026

Olfactory neuroepithelium biomarker platform: a proof from Alzheimer's disease

Unlike other diseases where target organs for biopsy are accessible, surrogate platforms are warranted for biomarkers of neuropsychiatric disorders due to the inaccessibility of the brain. We demonstrate a non-invasive platform combining a nasal soft-brush swab with single-cell Western blotting for neuron-specific protein analysis. Applied to Alzheimer's disease targeting phosphorylated tau, this demonstrated superior diagnostic capacity compared with blood-based approaches, indicating that the olfactory neuroepithelium is a sensitive biomarker platform.

biochemistry↗

bioRxiv2026

When feeling is better than seeing: Adult Zebrafish Ignore Wide-Field Optic-Flow in Laminar, but not Turbulent Hydrodynamic Environments.

Many animals navigate their world largely by seeing and feeling it. To disentangle these visual and mechanosensory contributions, we developed a virtual reality assay targeting the optomotor response in adult wild-type zebrafish swimming against flow. By projecting dynamic visual patterns onto the walls of a variable-speed flow tank, we decoupled wide-field optic flow from hydrodynamic velocity. We then tested fish responses to abrupt visual perturbations while they held station in the unsteady wake behind a bluff body. These perturbations reliably elicited compensatory optomotor responses, with fish aligning to the direction of the moving stimulus. Notably, this behavior was absent in uniform flows, suggesting that fish prioritize visual input when predictive lateral line signaling is compromised. We propose that this sensory shift serves to optimize swimming energetics in turbulent wakes. Extending this framework, we further show that zebrafish swimming against flow, whether alone or in groups, exhibit heightened escape responses to looming visual stimuli. Together, our findings reveal that fish sensory strategies are not fixed but dynamically tuned to hydrodynamic context: favoring visual cues in turbulent environments and lateral line input in uniform flows. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=84 SRC="FIGDIR/small/715425v1_ufig1.gif" ALT="Figure 1"> View larger version (18K): org.highwire.dtl.DTLVardef@1d7ba00org.highwire.dtl.DTLVardef@1f456f1org.highwire.dtl.DTLVardef@7826c4org.highwire.dtl.DTLVardef@391a68_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2025

Clustering within a single-component biomolecular condensate

Biomolecular condensates (BMCs) are assemblies of hundreds to many thousands of macromolecules within cells that are organized without physical barriers. Condensate function is dictated not only by its molecular composition, but also by substructural organization and molecular mobility. One hypothesis for the onset of multiple protein aggregation diseases is that the increased densities of specific proteins within BMCs promotes the formation of solid inclusions. However, deciphering the internal structural and functional properties of BMCs at the nanoscale and identifying the initiating events of inclusion formation requires tools with high spatiotemporal precision. Here we show using single molecule and other microscopy approaches that single component Fused in Sarcoma (FUS) condensates exhibit confinement and contain clusters with higher FUS density even at early timepoints. Upon aging, condensates displayed altered physical properties and reduced monomer mobility, and yet most FUS monomers diffused throughout the condensate within seconds. While an increase in connectivity over time explains reduced mobility, the large fraction of molecules retaining high mobility suggests a sponge-like structure rather than a system-spanning network. These findings indicate that a pseudo-equilibrium between distinct structural connectivities can exist within simple condensates, suggesting the potential for substantial structural and functional complexity of BMCs at the nanoscale.

biophysics↗

bioRxiv2024

A series of spontaneously blinking dyes for super-resolution microscopy

Spontaneously blinking fluorophores permit the detection and localization of individual molecules without reducing buffers or caging groups, thus simplifying single-molecule localization microscopy (SMLM). The intrinsic blinking properties of such dyes are dictated by molecular structure and modulated by environment, which can limit utility. We report a series of tuned spontaneously blinking dyes with duty cycles that span two orders of magnitude, allowing facile SMLM in cells and dense biomolecular structures.

cell biology↗

bioRxiv2023

An inimitable proprotein convertase subtilisin kexin-9 (PCSK9) cleavage site VFAQ on Spike protein along with furin cleavage site makes SARS-CoV-2 unique

A novel coronavirus (2019-nCoV) or Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) that affects humans has been discovered in Wuhan, China, in 2019. Its genome has been sequenced, and the genetic data was quickly made public. We discovered a novel proprotein convertase subtilisin kexin-9 (PCSK9) cleavage site in the Spike protein of the 2019-nCoV. The recent research also demonstrates that the previously found proprotein convertase 3 (PC3) or furin cleavage site, which was assumed to be unique, is already present in animal corona viruses. In this article, we suggest that the combination of the both proprotein convertase PC3 cleavage site and the PCSK9 site renders SARS-CoV-2 unique in terms of the pathogenicity, potential functional effects, and implications for the development of antiviral drugs.

evolutionary biology↗

bioRxiv2020

Consensus-based somatic variant-calling method correlates FBXW7 mutations with poor prognosis in canine B-cell lymphoma

INTRODUCTIONCanine Lymphoma (CL) is the most commonly diagnosed malignancy in the domestic dog, with estimates reaching 80,000 new cases per year in the United States. Understanding of genetic factors involved in development and progression of canine B-Cell Lymphoma (cBCL), the most common of the two major subtypes of CL, can help guide efforts to prevent, diagnose, and treat disease in dogs. Such findings also have implications for human Non-Hodgkin Lymphoma (NHL), as pet dogs have recently emerged as an important translational model due to the many shared histopathological, biological, and clinical characteristics between cBCL and NHL. OBJECTIVESWe aimed to identify potential driver mutations in cBCL and detect associations between affected genes and differential clinical outcomes. METHODSUsing exome sequencing of paired normal and tumor tissues from 71 dogs of various breeds with cBCL, we identified somatic variants with a consensus approach: keeping variants called by both MuTect2 and with high-confidence by VarScan 2. We predicted effects of these variants using SnpEff then measured associations between mutated genes and survival times from clinical data available for 62 cohort dogs using a multivariate Cox Proportional Hazards Model. RESULTSMutations in FBXW7, a gene commonly mutated in both human and canine cancers including lymphoma, were associated with shorter overall survival (OS; p=0.01, HR 3.3 [1.4-7.6]). The two most frequently mutated codons of FBXW7 in our cohort correspond to the most frequently mutated codons in human cancers. CONCLUSIONSOur findings show that exome sequencing results can be combined with clinical data to identify key mutations associated with prognosis in cBCL. These results may have implications for precision medicine in dogs and also allow subsets of dogs to serve as models for specific subtypes of human lymphoma. Translational RelevanceIdentifying tumor biomarkers associated with clinical outcomes has been a major driver in improved success in treating many types of human cancers, including Non-Hodgkin lymphoma (NHL). Since canine B-cell Lymphoma (cBCL) shares many clinically identifiable characteristics with NHL, our detection of recurring mutations in certain genes in cBCL and their association with clinical outcomes stands to benefit both humans and dogs. If common canine lymphoma subtypes show mutational similarity to certain human subtypes, then therapies found to be effective for a subtype in one species may be more likely to improve treatment response in the analogous subtype in the other.

genomics↗

bioRxiv2020

Cerebellar theta and beta noninvasive stimulation rhythms differentially influence episodic memory versus language

The cerebellum is thought to interact with distributed brain networks to support cognitive abilities such as episodic memory and language. Episodic memory and language networks have been associated with distinct endogenous oscillatory activity frequency bands: theta ([~]3-8 Hz) versus beta ([~]13-30 Hz), respectively. We sought to test whether it is possible to toggle cerebellar participation in episodic memory versus language by noninvasively stimulating with theta versus beta rhythmic transcranial magnetic stimulation. Cerebellar theta stimulation improved episodic memory encoding but did not influence neural signals of language processing, whereas beta stimulation of the same cerebellar location increased neural signals of language processing but did not influence episodic memory encoding. This constitutes evidence for double-dissociation of cerebellar contributions to language versus episodic memory based on stimulation frequency pattern, supporting the hypothesis that the cerebellum can be biased to support these distinct cognitive abilities at the command of network-specific rhythmic activity.

neuroscience↗

bioRxiv2017

1/f Neural Noise and Electrophysiological Indices of Contextual Prediction in Normative Aging

Prediction during language comprehension has increasingly been suggested to play a substantive role in efficient language processing. Emerging models have postulated that predictive mechanisms are enhanced when neural networks fire synchronously, but to date, this relationship has been investigated primarily through oscillatory activity in narrow frequency bands. A recently-developed measure proposed to reflect broadband neural activity - and thereby synchronous neuronal firing - is 1/f neural noise extracted from EEG spectral power. Previous research (Voytek et al., 2015) has indicated that this measure of 1/f neural noise changes across the lifespan, and these neural changes predict age-related behavioral impairments in visual working memory. Using a cross-sectional sample of young and older adults, we examined age-related changes in 1/f neural noise and whether this measure would predict ERP correlates of successful lexical prediction during discourse comprehension. 1/f neural noise across two different language tasks revealed high within-subject correlations, indicating that this measure can provide a reliable index of individualized patterns of neural activation. In addition to age, 1/f noise was a significant predictor of N400 effects of successful lexical prediction, but noise did not mediate age-related declines in other ERP effects. We discuss broader implications of these findings for theories of predictive processing, as well as potential applications of 1/f noise across research populations.

neuroscience↗