Biology subjects

Katz, D.

Publications and source records attributed to Katz, D..

9 recordsLinked to original sources

bioRxiv2026

Molecular Transducers of Physical Activity Consortium (MoTrPAC): Initial Insights into the Dynamic Human Responses to Exercise

The goal of the Molecular Transducers of Physical Activity Consortium (MoTrPAC) is to examine the physiological and molecular basis for health benefits in response to acute and chronic exercise. Prior to COVID-19 suspension, healthy, sedentary participants (N=206, 18-74y) were randomized to endurance exercise (N=80), resistance exercise (N=81), or non-exercise control (N=45) interventions. The prescribed vigorous acute endurance and resistance exercise bouts induced physiological and metabolic perturbations relative to resting homeostasis. The supervised chronic (3d/wk, 12wk) endurance or resistance training programs robustly improved several physiological parameters (i.e., VO2peak, muscular strength). Temporal biospecimen (blood, muscle, and adipose) collections and processing coupled to the acute exercise bouts were highly successful. In most cases, over 90% success was achieved for blood, muscle, and adipose samples. Endurance and resistance exercise induced distinct acute and chronic physiological responses, which provide a framework to interrogate the molecular basis for health adaptations to these two popular exercise modalities. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/705347v1_ufig1.gif" ALT="Figure 1"> View larger version (65K): org.highwire.dtl.DTLVardef@554ee9org.highwire.dtl.DTLVardef@afb28dorg.highwire.dtl.DTLVardef@f381cdorg.highwire.dtl.DTLVardef@cef19c_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗

bioRxiv2025

Similar processing of novelty in rat dorsal and intermediate CA1 despite differences in spatial tuning

Elucidating the fundamental neural mechanisms of hippocampal information processing is necessary for understanding memory formation and related brain disorders. Differences in hippocampal genetics, anatomy, and connectivity across the longitudinal axis suggest functional heterogeneity in this structure. The dorsal pole is suggested to be primarily involved in spatial processing, whereas the ventral pole is implicated in emotional processing. Connectivity and genetic studies show this functional segregation is more prominent near their respective poles and weaker toward the intermediate region. The current study compares the firing properties of CA1 cells in the dorsal and intermediate regions of the hippocampus during spatial or social/odor novelty. We measured basic spatial properties, firing rate response, and remapping to the spatial re-configuration of a linear track or the social/odor presentation of a novel male conspecific, female bedding, or coyote urine. Behaviorally, the average rat exhibited slower maze running latencies during the novel spatial manipulation and spent more time adjacent to the chamber containing the novel social/odor stimulus. As previously shown, dorsal cells had fewer, smaller place fields, and higher spatial information content than intermediate cells in the hippocampus. Despite the differences in place field characteristics, cells in both regions responded similarly to spatial and social/odor manipulations. Taken together, these data support the differentiation of some functions, together with an overlap of other functions progressing along the longitudinal axis, which may facilitate the integration of information throughout the hippocampus.

neuroscience↗

bioRxiv2024

FinaleMe: Predicting DNA methylation by the fragmentation patterns of plasma cell-free DNA

Analysis of DNA methylation in cell-free DNA (cfDNA) reveals clinically relevant biomarkers but requires specialized protocols and sufficient input material that limits its applicability. Millions of cfDNA samples have been profiled by genomic sequencing. To maximize the gene regulation information from the existing dataset, we developed FinaleMe, a non-homogeneous Hidden Markov Model (HMM), to predict DNA methylation of cfDNA and, therefore, tissues-of-origin directly from plasma whole-genome sequencing (WGS). We validated the performance with 80 pairs of deep and shallow-coverage WGS and whole-genome bisulfite sequencing (WGBS) data.

bioinformatics↗

bioRxiv2023

Characterization of the RBM15 protein binding with XCI-escaping long noncoding RNAs

The RNA binding motif 15 protein (RBM15) plays a critical role in post-transcriptional regulation. Its role in facilitating N6-methyladenosine (m6A) modification, specifically through guiding the writer complex (WTAP METTL13 METTL14) to DRACH sequence motifs, has been demonstrated for several classes of RNA, including long noncoding RNAs (lncRNAs). The structural mechanism that underlies how RBM15 interacts with RNA has yet to be elucidated. In this study, we mined and bioinformatically assessed publicly available genome-wide RNA 2D structural probing and RBP cross-linking and immunoprecipitation data to investigate how RBM15 interacts with RNA, with a focus on lncRNA transcripts. RBM15, which possesses three RNA recognition motifs (RRMs), primarily interacts with stem-loop structured RNA motifs. Structural modeling reveals RRMs 2 and 3 are coaxially stacked in solution; these two RRMs are responsible for driving RBM15s interaction with RNA. We further demonstrate this experimentally with two RNA hairpins, revealing low micromolar binding affinities. Altogether, this work provides insight into the structural mechanism by which RBM15 interacts with RNAs to govern biological function.

biochemistry↗

bioRxiv2022

LiCl-induced sickness modulates spontaneous activity and response dynamics in rat gustatory cortex.

Gustatory Cortex (GC), a structure deeply involved in the making of consumption decisions, presumably performs this function by integrating information about taste, experiences, and internal states related to the animals health, such as illness. Here, we investigated this assertion, examining whether illness is represented in GC activity, and how this representation impacts taste responses and behavior. We recorded GC single-neuron activity and local field potentials (LFP) from healthy rats and (the same) rats made ill (via LiCl injection). We show (consistent with the extant literature) that the onset of illness-related behaviors arises contemporaneously with alterations in spontaneous 7-12Hz LFP power at [~]11 min following injection. This process was accompanied by reductions in single-neuron taste response magnitudes and discriminability, and with enhancements in palatability-relatedness - a result reflecting the collapse of responses toward a simple "good-bad" code arising in a specific subset of GC neurons. Overall, our data show that a state (illness) that profoundly reduces consumption changes basic properties of the sensory cortical response to tastes, in a manner that can easily explain illness impact on consumption. Significance StatementNeural responses in primary sensory cortex are often thought to faithfully represent physical stimuli, and while recent studies (including ours) have challenged this view by documenting enhancements and decrements in stimulus-induced firing related to animals internal states, there has been little work setting these changes in any sort of functional, mechanistic context. Here we show that a state (illness) that profoundly reduces consumption changes basic properties of the sensory cortical response to tastes, and then go beyond this to precisely characterize this response plasticity, connecting it to the specific perceptual changes that drive illness impact on consumption.

neuroscience↗

bioRxiv2020

Polymer-assisted intratumoral delivery of ethanol: Preclinical investigation of safety and efficacy in a murine breast cancer model

Focal tumor ablation with ethanol could provide benefits in low-resource settings because of its low overall cost, minimal imaging technology requirements, and acceptable clinical outcomes. Unfortunately, ethanol ablation is not commonly utilized because of a lack of predictability of the ablation zone, caused by inefficient retention of ethanol at the injection site. To create a predictable zone of ablation, we have developed a polymer-assisted ablation method using ethyl cellulose (EC) mixed with ethanol. EC is ethanol-soluble and water-insoluble, allowing for EC-ethanol to be injected as a liquid and precipitate into a solid, occluding the leakage of ethanol upon contact with tissue. The aims of this study were to compare the 1) safety, 2) release kinetics, 3) spatial distribution, 4) necrotic volume, and 5) overall survival of EC-ethanol to conventional ethanol ablation in a murine breast tumor model. Non-target tissue damage was monitored through localized adverse events recording, ethanol release kinetics with Raman spectroscopy, injectate distribution with in vivo imaging, target-tissue necrosis with NADH-diaphorase staining, and overall survival by proxy of tumor growth. EC-ethanol exhibited decreased localized adverse events, a slowing of the release rate of ethanol, more compact injection zones, 5-fold increase in target-tissue necrosis, and longer overall survival rates compared to the same volume of pure ethanol. A single 150 {micro}L dose of 6% EC-ethanol achieved a similar survival probability rates to six daily 50 {micro}L doses of pure ethanol used to simulate a slow-release of ethanol over 6 days. Taken together, these results demonstrate that EC-ethanol is safer and more effective than ethanol alone for ablating tumors. Graphical AbstractThe inclusion of ethylcellulose limits extra-tumoral leakage of ethanol and increases the target-tissue ablation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=102 SRC="FIGDIR/small/123125v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@172afb5org.highwire.dtl.DTLVardef@6d96deorg.highwire.dtl.DTLVardef@cbdf9borg.highwire.dtl.DTLVardef@c56187_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2020

Failure to maternally reprogram histone methylation causes developmental delay due to germline transcription in somatic tissues

Embryos undergo extensive reprogramming at fertilization to prevent the inappropriate inheritance of histone methylation. In C. elegans, this reprogramming is mediated by the H3K4me2 demethylase, SPR-5, and the H3K9 methyltransferase, MET-2. In contrast to this reprogramming, the H3K36 methyltransferase, MES-4, maintains H3K36me2/3 at germline genes between generations to help re-establish the germline. To determine whether the MES-4 germline inheritance system antagonizes spr-5; met-2 reprogramming, we examined the interaction between these two systems. We find that the developmental delay of spr-5; met-2 mutant progeny is associated with ectopic H3K36me2/3 and the ectopic expression of MES-4 targeted germline genes in somatic tissues. Furthermore, the developmental delay is dependent upon MES-4 and the H3K4 methyltransferase, SET-2. We propose that the MES-4 inheritance system prevents critical germline genes from being repressed by maternal spr-5; met-2 reprogramming. Thus, the balance of inherited histone modifications is necessary to distinguish germline versus soma and prevent developmental delay.

developmental biology↗

bioRxiv2019

Managing genomic variant calling workflows with Swift/T

Genomic variant discovery is frequently performed using the GATK Best Practices variant calling pipeline, a complex workflow with multiple steps, fans/merges, and conditionals. This complexity makes management of the workflow difficult on a computer cluster, especially when running in parallel on large batches of data: hundreds or thousands of samples at a time. Here we describe a wrapper for the GATK-based variant calling workflow using the Swift/T parallel scripting language. Standard built-in features include the flexibility to split by chromosome before variant calling, optionally permitting the analysis to continue when faulty samples are detected, and allowing users to analyze multiple samples in parallel within each cluster node. The use of Swift/T conveys two key advantages: (1) Thanks to the embedded ability of Swift/T to transparently operate in multiple cluster scheduling environments (PBS Torque, SLURM, Cray aprun environment, etc.,) a single workflow is trivially portable across numerous clusters; (2) The leaf functions of Swift/T permit developers to easily swap executables in and out of the workflow, conditional on the analysts choice, which makes the workflow easy to maintain. This modular design permits separation of the workflow into multiple stages and the request of resources optimal for each stage of the pipeline. While Swift/Ts implicit data-level parallelism eliminates the need for the developer to code parallel analysis of multiple samples, it does make debugging of the workflow a bit more difficult, as is the case with any implicitly parallel code. With the above features, users have a powerful and portable way to scale up their variant calling analysis to run in many traditional computer cluster architectures.\n\nhttps://github.com/ncsa/Swift-T-Variant-Calling\n\nhttp://swift-t-variant-calling.readthedocs.io/en/latest/

bioinformatics↗

bioRxiv2017

A Resource For The Allele-Specific Analysis Of DNA Methylation At Multiple Genomically Imprinted Loci In Mice

Genomically imprinted loci are expressed mono-allelically dependent upon the parent of origin. Their regulation not only illuminates how chromatin regulates gene expression but also how chromatin can be reprogrammed every generation. Because of their distinct parent of origin regulation, analysis of imprinted loci can be difficult. Single nucleotide polymorphisms (SNPs) are required to accurately assess these elements allele-specifically. However, publicly available SNP databases lack robust verification, making analysis of imprinting difficult. In addition, the allele-specific imprinting assays that have been developed employ different mouse strains, making it difficult to systemically analyze these loci. Here, we have generated a resource that will allow the allele-specific analysis of many significant imprinted loci in a single hybrid strain of Mus musculus. This resource includes verification of SNPs present within ten of the most widely used imprinting control regions and allele-specific DNA methylation assays for each gene in a C57BL/6J and CAST/EiJ hybrid strain background.

genetics↗