Biology subjects

Beaver, M.

Publications and source records attributed to Beaver, M..

4 recordsLinked to original sources

bioRxiv2025

cNPDB: A comprehensive empirical crustacean neuropeptide database

Neuropeptides, key signaling molecules essential for dynamic regulation of biological processes, have been studied via crustacean model systems for more than 40 years. We present cNPDB, the first centralized resource dedicated to this dynamic area of research, promisingly accelerating crustacean neuropeptidome research and offering a blueprint for cross-species translational studies of neuropeptide signaling. cNPDB is comprised of 1364 published neuropeptides from 29 crustacean species, each annotated with corresponding taxonomic information, computed physicochemical properties, spatial localization, and predicted three-dimensional structure. The intuitive web-interface supports keyword and property-based filtering, sequence alignment, property calculation, and links to available mass spectrometry imaging data, streamlining discovery. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC="FIGDIR/small/667494v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@ec5445org.highwire.dtl.DTLVardef@19084a3org.highwire.dtl.DTLVardef@f4228dorg.highwire.dtl.DTLVardef@89504_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2025

HILIC-Enabled Mass Spectrometric Discovery of Novel Endogenous and Glycosylated Neuropeptides in the American Lobster Nervous System

Neuropeptides are a highly conserved and diverse class of intercellular signaling molecules that regulate a broad range of neural and hormonal processes across animal phyla. The American lobster, Homarus americanus, has long served as a powerful invertebrate model for the discovery and functional investigation of neuropeptides. Among common post-translational modifications (PTMs) found in neuropeptides, glycosylation remains underexplored due to the inherently low in vivo abundance and intrinsically complex structural heterogeneity. In this study, we employed hydrophilic interaction liquid chromatography (HILIC) enrichment coupled with oxonium-ion triggered EThcD fragmentation strategy to simultaneously profile novel endogenous and glycosylated neuropeptides across eight distinct neural tissues and neuroendocrine organs of Homarus americanus. This integrative mass spectrometry-based approach led to the identification of 154 endogenous neuropeptides derived from 25 families, approximately one-third of which are newly reported, and uncovered 24 glycosylated neuropeptides in this species for the first time. These peptides exhibit strong tissue-specific expression, distinct proteolytic cleavage patterns, and confidently localized glycosylation sites. Our results highlight the utility of integrated sampling enrichment and hybrid fragmentation strategies for deep neuropeptidomic profiling and provide a valuable resource for future studies on the functional roles of newly identified neuropeptides and glycosylation in crustacean neuromodulation and peptidergic signaling. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/661634v2_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@9a1745org.highwire.dtl.DTLVardef@6decc4org.highwire.dtl.DTLVardef@d34256org.highwire.dtl.DTLVardef@1a83b4c_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2021

Chromatin and transcriptomic profiling uncover dysregulation of the Tip60 HAT/HDAC2 epigenomic landscape in the neurodegenerative brain

Disruption of histone acetylation mediated gene control is a critical step in Alzheimers Disease (AD), yet chromatin analysis of antagonistic histone acetyltransferases (HATs) and histone deacetylases (HDACs) causing these alterations remains uncharacterized. We report the first Tip60 HAT versus HDAC2 chromatin and transcriptional profiling study in Drosophila brains that model early human AD. We find Tip60 and HDAC2 predominantly recruited to identical neuronal genes. Moreover, AD brains exhibit robust genome-wide early alterations that include enhanced HDAC2 and reduced Tip60 binding and transcriptional dysregulation. Orthologous human genes to co-Tip60/HDAC2 Drosophila neural targets exhibit conserved disruption patterns in AD patient hippocampi. Notably, we discovered distinct transcription factor (TF) binding sites within Tip60/HDAC2 co-peaks in neuronal genes, implicating them in co-enzyme recruitment. Increased Tip60 protects against transcriptional dysregulation and enhanced HDAC2 enrichment genome-wide. We advocate Tip60 HAT/HDAC2 mediated epigenetic neuronal gene disruption as a genome-wide initial causal event in AD.

genomics↗

bioRxiv2020

Transcriptome analysis uncovers distinct modes of epigenetic gene changes in early versus late stages of amyloid-β induced Alzheimer's disease pathology

Alzheimers disease (AD) is an age-related neurodegenerative disorder hallmarked by amyloid-{beta} (A{beta}) plaque accumulation, neuronal cell death, and cognitive deficits that worsen during disease progression. Histone acetylation dysregulation, caused by an imbalance between reduced histone acetyltransferases (HAT) Tip60 and increased histone deacetylase 2 (HDAC2) levels, can directly contribute to AD pathology. However, whether such AD-associated neuroepigenetic alterations occur in response to A{beta} peptide production and can be protected against by increasing Tip60 levels over the course of neurodegenerative progression remains unknown. Here we profile Tip60 HAT/HDAC2 dynamics and transcriptome-wide changes across early and late stage AD pathology in the Drosophila brain produced solely by human amyloid-{beta}42. We show that early A{beta}42 induction leads to disruption of Tip60 HAT/HDAC2 balance during early neurodegenerative stages preceding A{beta} plaque accumulation that persists into late AD stages. Correlative transcriptome-wide studies reveal alterations in biological processes we classified as transient (early-stage only), late-onset (late-stage only), and constant (both). Increasing Tip60 HAT levels in the A{beta}42 fly brain protects against AD functional pathologies that include A{beta} plaque accumulation, neural cell death, cognitive deficits, and shorter life-span. Strikingly, Tip60 protects against A{beta}42-induced transcriptomic alterations via distinct mechanisms during early and late stages of neurodegeneration. Our findings reveal distinct modes of neuroepigenetic gene changes and Tip60 neuroprotection in early versus late stages in AD that can serve as early biomarkers for AD, and support the therapeutic potential of Tip60 over the course of AD progression.

neuroscience↗