Biology subjects

Crosby, T.

Publications and source records attributed to Crosby, T..

4 recordsLinked to original sources

bioRxiv2025

Chromosomal instability shapes the tumor microenvironment of esophageal adenocarcinoma via a cGAS-chemokine-myeloid axis

Chromosomal instability (CIN), a characteristic feature of esophageal adenocarcinoma (EAC), drives tumor aggressiveness and therapy resistance, presenting an intractable problem in cancer treatment. CIN leads to constitutive stimulation of the innate immune cGAS-STING pathway, which has been typically linked to anti-tumor immunity. However, despite the high CIN burden in EAC, the cGAS- STING pathway remains largely intact. To address this paradox, we developed novel esophageal cancer models, including a CIN-isogenic model, discovering myeloid-attracting chemokines - with the chemokine CXCL8 (IL-8) as a prominent hit - as conserved CIN-driven targets in EAC. Using high-resolution multiplexed immunofluorescence microscopy, we quantified the extent of ongoing cGAS-activating CIN in human EAC tumors by measuring cGAS-positive micronuclei in tumor cells, validated by orthogonal whole-genome sequencing-based CIN metrics. By coupling in situ CIN assessment with single-nucleus RNA sequencing and multiplex immunophenotypic profiling, we found tumor cell-intrinsic innate immune activation and intratumoral myeloid cell inflammation as phenotypic consequences of CIN in EAC. Additionally, we identified increased tumor cell-intrinsic CXCL8 expression in CINhigh EAC, accounting for the inflammatory tumor microenvironment. Using a novel signature of CIN, termed CINMN, which captures ongoing CIN-associated gene expression, we confirm poor patient outcomes in CINhigh tumors with signs of aberrantly rewired cGAS-STING pathway signaling. Together, our findings help explain the counterintuitive maintenance and expression of cGAS-STING pathway components in aggressive, CINhigh tumors and emphasize the need to understand the contribution of CIN to the shaping of a pro-tumor immune landscape. Therapeutic strategies aimed at disrupting the cGAS-driven inflammation axis may be instrumental in improving patient outcomes in this aggressive cancer.

cancer biology↗

bioRxiv2023

Microbiota of laboratory channel catfish skin mucosa and aquaria water exposed to chloramine-T trihydrate

Here, we describe the skin mucosa microbiome of channel catfish (Ictalurus punctatus) before and after exposure to chloramine-T. We also describe the aquaria water microbiome after the post-treatment period. These data provide a unique baseline description of skin mucosa and aquaria water microbiome from catfish reared in research aquaria. DisclaimerThe views expressed in this announcement are those of the authors and do not necessarily reflect the official policy of the Department of Health and Human Services, the U.S. Food and Drug Administration, or the U.S. Government. Reference to any commercial materials, equipment, or process does not in any way constitute approval, endorsement, or recommendation by the Food and Drug Administration

microbiology↗

bioRxiv2023

Perilaryngeal Functional Muscle Network in Patients with Vocal Hyperfunction - A Case Study

Patients with both phonotraumatic and non-phonotraumatic dysphonia commonly present with vocal hyperfunction, defined as excessive perilaryngeal muscle activity and characterized by muscular pain and strain in the neck, increased vocal effort, and vocal fatigue. The inability to reliably measure vocal hyperfunction is a barrier to adequate evaluation and treatment of hyperfunctional voice disorders. We have recently demonstrated that the perilaryngeal functional muscle network can be a novel sensitive neurophysiological window to vocal performance in vocally healthy subjects. In this paper, for the first time, we evaluate the performance and symmetry of functional perilaryngeal muscle networks in three patients with voice disorders. Surface electromyography signals were recorded from twelve sensors (six on each side of the neck) using the wireless Trigno sEMG system (Delsys Inc., Natick, MA). Patient 1 was diagnosed with primary muscle tension dysphonia, Patient 2 was diagnosed with unilateral vocal fold paresis, and Patient 3 was diagnosed with age-related glottal insufficiency. This paper reports altered functional connectivity and asymmetric muscle network scan behavior in all three patients when compared with a cohort of eight healthy subjects. Our approach quantifies synergistic network activity to interrogate coordination of perilaryngeal and surrounding muscles during voicing and potential discoordination of the muscle network for dysphonic conditions. Asymmetry in muscle networks is proposed here as a biomarker for monitoring vocal hyperfunction.

bioengineering↗

bioRxiv2021

Characterization of Cervical-Cranial Muscle Network in Correlation with Vocal Features

Objective evaluation of physiological responses using non-invasive methods has attracted great interest regarding the assessment of vocal performance and disorders. This paper, for the first time, demonstrates that the topographical features of the cervical-cranial intermuscular coherence network generated using surface electromyography (sEMG) have a strong potential for detecting subtle changes in vocal performance. For this purpose, in this paper, 12 sEMG signals were collected from six cervical and cranial muscles bilaterally. Data were collected from four subjects without a history of a voice disorder performing a series of vocal tasks. The vocal tasks were varied phonation (an /a/ sustained for the maximal duration with combinations of two levels of loudness and two levels of pitch), a pitch glide from low to high, singing a familiar song, spontaneous speech, and reading with different loudness levels. The varied phonation tasks showed the median degree, and weighted clustering coefficient of the coherence-based intermuscular network ascends monotonically, with a high effect size (|rrb| = 0.52). The set of tasks, including pitch glide, singing, and speech, was significantly distinguishable using the network features as both degree and weighted clustering coefficient had a very high effect size (|rrb| > 0.83) across these tasks. Also, pitch glide has the highest degree and weighted clustering coefficient among all tasks (degree > 0.6, weighted clustering coefficient > 0.6). Spectrotemporal features performed far less effective than the proposed functional muscle network metrics to differentiate the vocal tasks. The highest effect size for spectrotemporal features was only |rrb| = 0.19. In this paper, for the first time, the power of a cervical-cranial muscle network has been demonstrated as a neurophysiological window to vocal performance. The results also shed light on the tasks with the highest network involvement, which may be potentially used in monitoring vocal disorders and tracking rehabilitation progress.

neuroscience↗