Digital Commons Network^™

Targeting Cathepsin C Ameliorates Murine Acetaminophen-Induced Liver Injury, Jessica Raith, Malte Bachmann, Sina Gonther, Hendrik Stülb, Ali A Aghdassi, Christine T N Pham, Heiko Mühl

2020-Current year OA Pubs

Acetaminophen (APAP) overdosing is a major cause of acute liver failure worldwide and an established model for drug-induced acute liver injury (ALI). While studying gene expression during murine APAP-induced ALI by 3'mRNA sequencing (massive analysis of cDNA ends, MACE), we observed splenic mRNA accumulation encoding for the neutrophil serine proteases cathepsin G, neutrophil elastase, and proteinase-3 - all are hierarchically activated by cathepsin C (CtsC). This, along with increased serum levels of these proteases in diseased mice, concurs with the established phenomenon of myeloid cell mobilization during APAP intoxication.

Reverse Genetics Of Murine Rotavirus: A Comparative Analysis Of The Wild-Type And Cell-Culture-Adapted Murine Rotavirus Vp4 In Replication And Virulence In Neonatal Mice, Takahiro Kawagishi, Liliana Sánchez-Tacuba, Ningguo Feng, Harry B Greenberg, Siyuan Ding

2020-Current year OA Pubs

Small-animal models and reverse genetics systems are powerful tools for investigating the molecular mechanisms underlying viral replication, virulence, and interaction with the host immune response in vivo. Rotavirus (RV) causes acute gastroenteritis in many young animals and infants worldwide. Murine RV replicates efficiently in the intestines of inoculated suckling pups, causing diarrhea, and spreads efficiently to uninoculated littermates. Because RVs derived from human and other non-mouse animal species do not replicate efficiently in mice, murine RVs are uniquely useful in probing the viral and host determinants of efficient replication and pathogenesis in a species-matched mouse model. Previously, we established an …

Optimization Of The Antifungal Properties Of The Bacterial Peptide Entv By Variant Analysis, Shantanu Guha, Shane A Cristy, Giuseppe Buda De Cesare, Melissa R Cruz, Michael C Lorenz, Danielle A Garsin

Journal Articles

Fungal resistance to commonly used medicines is a growing public health threat, and there is a dire need to develop new classes of antifungals. We previously described a peptide produced by Enterococcus faecalis, EntV, that restricts Candida albicans to a benign form rather than having direct fungicidal activity. Moreover, we showed that one 12-amino acid (aa) alpha helix of this peptide retained full activity, with partial activity down to the 10aa alpha helix. Using these peptides as a starting point, the current investigation sought to identify the critical features necessary for antifungal activity and to screen for new variants …

A Rat-Based Preclinical Platform Facilitating Transcatheter Hepatic Arterial Infusion In Immunodeficient Rats With Liver Xenografts Of Patient-Derived Pancreatic Ductal Adenocarcinoma, Masanori Ozaki, Ken Kageyama, Kenjiro Kimura, Shinpei Eguchi, Akira Yamamoto, Ryota Tanaka, Takehito Nota, Hiroki Yonezawa, Hideyuki Nishiofuku, Yuki Sakai, Naoki Tani, Atsushi Jogo, Mizue Terai, Takami Sato, Takeaki Ishizawa, Yukio Miki

Department of Medical Oncology Faculty Papers

Liver metastases from pancreatic ductal adenocarcinoma (PDAC) are highly fatal. A rat-based patient-derived tumor xenograft (PDX) model is available for transcatheter therapy. This study aimed to create an immunodeficient rat model with liver xenografts of patient-derived primary PDAC and evaluate efficacy of hepatic arterial infusion chemotherapy with cisplatin in this model. Three patient-derived PDACs were transplanted into the livers of 21 rats each (totally, 63 rats), randomly assigned into hepatic arterial infusion, systemic venous infusion, and control groups (n = 7 each) four weeks post-implantation. Computed tomography evaluated tumor volumes before and four weeks after treatment. Post-euthanasia, resected tumor specimens …

Chronic Stress-Induced Neuroinflammation: Relevance Of Rodent Models To Human Disease., Abigail G White, Elias Elias, Andrea Orozco, Shivon A Robinson, Melissa T Manners

Faculty Scholarship for the College of Science & Mathematics

The brain is the central organ of adaptation to stress because it perceives and determines threats that induce behavioral, physiological, and molecular responses. In humans, chronic stress manifests as an enduring consistent feeling of pressure and being overwhelmed for an extended duration. This can result in a persistent proinflammatory response in the peripheral and central nervous system (CNS), resulting in cellular, physiological, and behavioral effects. Compounding stressors may increase the risk of chronic-stress-induced inflammation, which can yield serious health consequences, including mental health disorders. This review summarizes the current knowledge surrounding the neuroinflammatory response in rodent models of chronic stress-a …

Deficiency Of Il-22-Binding Protein Enhances The Ability Of The Gut Microbiota To Protect Against Enteric Pathogens, José L Fachi, Blanda Di Luccia, Susan Gilfillan, Hao-Wei Chang, Christina Song, Jiye Cheng, Marina Cella, Marco Aurelio Vinolo, Jeffrey I Gordon, Marco Colonna

2020-Current year OA Pubs

Interleukin 22 (IL-22) promotes intestinal barrier integrity, stimulating epithelial cells to enact defense mechanisms against enteric infections, including the production of antimicrobial peptides. IL-22 binding protein (IL-22BP) is a soluble decoy encoded by the

Wormbase 2024: Status And Transitioning To Alliance Infrastructure, Paul W Sternberg, Tim Schedl, Et Al.

2020-Current year OA Pubs

WormBase has been the major repository and knowledgebase of information about the genome and genetics of Caenorhabditis elegans and other nematodes of experimental interest for over 2 decades. We have 3 goals: to keep current with the fast-paced C. elegans research, to provide better integration with other resources, and to be sustainable. Here, we discuss the current state of WormBase as well as progress and plans for moving core WormBase infrastructure to the Alliance of Genome Resources (the Alliance). As an Alliance member, WormBase will continue to interact with the C. elegans community, develop new features as needed, and curate …

Biallelic Borcs8 Variants Cause An Infantile-Onset Neurodegenerative Disorder With Altered Lysosome Dynamics., Raffaella De Pace, Reza Maroofian, Adeline Paimboeuf, Mina Zamani, Maha S. Zaki, Saeid Sadeghian, Reza Azizimalamiri, Hamid Galehdari, Jawaher Zeighami, Chad D. Williamson, Emily Fleming, Dihong Zhou, Jennifer L. Gannon, Isabelle Thiffault, Emmanuel Roze, Mohnish Suri, Giovanni Zifarelli, Peter Bauer, Henry Houlden, Mariasavina Severino, Shunmoogum A. Patten, Emily G. Farrow, Juan S. Bonifacino

Manuscripts, Articles, Book Chapters and Other Papers

BLOC-one-related complex (BORC) is a multiprotein complex composed of eight subunits named BORCS1-8. BORC associates with the cytosolic face of lysosomes, where it sequentially recruits the small GTPase ARL8 and kinesin-1 and -3 microtubule motors to promote anterograde transport of lysosomes toward the peripheral cytoplasm in non-neuronal cells and the distal axon in neurons. The physiological and pathological importance of BORC in humans, however, remains to be determined. Here, we report the identification of compound heterozygous variants [missense c.85T>C (p.Ser29Pro) and frameshift c.71-75dupTGGCC (p.Asn26Trpfs*51)] and homozygous variants [missense c.196A>C (p.Thr66Pro) and c.124T>C (p.Ser42Pro)] in BORCS8 in five …

Novel Loss-Of-Function Variants Expand Abcc9-Related Intellectual Disability And Myopathy Syndrome, Stephanie Efthymiou, Robert C Tryon, Colin G Nichols, Et Al.

2020-Current year OA Pubs

Loss-of-function mutation of ABCC9, the gene encoding the SUR2 subunit of ATP sensitive-potassium (KATP) channels, was recently associated with autosomal recessive ABCC9-related intellectual disability and myopathy syndrome (AIMS). Here we identify nine additional subjects, from seven unrelated families, harbouring different homozygous loss-of-function variants in ABCC9 and presenting with a conserved range of clinical features. All variants are predicted to result in severe truncations or in-frame deletions within SUR2, leading to the generation of non-functional SUR2-dependent KATP channels. Affected individuals show psychomotor delay and intellectual disability of variable severity, microcephaly, corpus callosum and white matter abnormalities, seizures, spasticity, short stature, muscle …

Delta Like 4 Regulates Cerebrovascular Development And Endothelial Integrity Via Dll4-Notch-Cldn5 Pathway And Is Vulnerable To Neonatal Hyperoxia., Xingrao Ke, Sheng Xia, Wei Yu, Sherry M. Mabry, Qi Fu, Heather Menden, Venkatesh Sampath, Robert H. Lane

Manuscripts, Articles, Book Chapters and Other Papers

The mechanisms governing brain vascularization during development remain poorly understood. A key regulator of developmental vascularization is delta like 4 (DLL4), a Notch ligand prominently expressed in endothelial cells (EC). Exposure to hyperoxia in premature infants can disrupt the development and functions of cerebral blood vessels and lead to long-term cognitive impairment. However, its role in cerebral vascular development and the impact of postnatal hyperoxia on DLL4 expression in mouse brain EC have not been explored. We determined the DLL4 expression pattern and its downstream signalling gene expression in brain EC using Dll4^+/+ and Dll4^+/LacZ mice. We also …

Head-To-Head Comparison Of Relevant Cell Sources Of Small Extracellular Vesicles For Cardiac Repair: Superiority Of Embryonic Stem Cells, Hernán González-King, Patricia G Rodrigues, Tamsin Albery, Benyapa Tangruksa, Ramya Gurrapu, Andreia M Silva, Gentian Musa, Dominika Kardasz, Kai Liu, Bengt Kull, Karin Åvall, Katarina Rydén-Markinhuhta, Tania Incitti, Nitin Sharma, Cecilia Graneli, Hadi Valadi, Kasparas Petkevicius, Miguel Carracedo, Sandra Tejedor, Alena Ivanova, Sepideh Heydarkhan-Hagvall, Phillipe Menasché, Jane Synnergren, Niek Dekker, Qing-Dong Wang, Karin Jennbacken

Journal Articles

Small extracellular vesicles (sEV) derived from various cell sources have been demonstrated to enhance cardiac function in preclinical models of myocardial infarction (MI). The aim of this study was to compare different sources of sEV for cardiac repair and determine the most effective one, which nowadays remains limited. We comprehensively assessed the efficacy of sEV obtained from human primary bone marrow mesenchymal stromal cells (BM-MSC), human immortalized MSC (hTERT-MSC), human embryonic stem cells (ESC), ESC-derived cardiac progenitor cells (CPC), human ESC-derived cardiomyocytes (CM), and human primary ventricular cardiac fibroblasts (VCF), in in vitro models of cardiac repair. ESC-derived sEV (ESC-sEV) …

Complement Regulation In The Eye: Implications For Age-Related Macular Degeneration, Georgia A. Wilke, Rajendra S. Apte

2020-Current year OA Pubs

Careful regulation of the complement system is critical for enabling complement proteins to titrate immune defense while also preventing collateral tissue damage from poorly controlled inflammation. In the eye, this balance between complement activity and inhibition is crucial, as a low level of basal complement activity is necessary to support ocular immune privilege, a prerequisite for maintaining vision. Dysregulated complement activation contributes to parainflammation, a low level of inflammation triggered by cellular damage that functions to reestablish homeostasis, or outright inflammation that disrupts the visual axis. Complement dysregulation has been implicated in many ocular diseases, including glaucoma, diabetic retinopathy, and …

Interferons And Tuft Cell Numbers Are Bottlenecks For Persistent Murine Norovirus Infection, Somya Aggarwal, Forrest C. Walker, James S. Weagley, Broc T. Mccune, Xiaofen Wu, Lawrence A. Schriefer, Heyde Makimaa, Dylan Lawrence, Pratyush Sridhar, Megan T. Baldridge

2020-Current year OA Pubs

Noroviruses (NoVs) are a leading cause of viral gastroenteritis. Despite global clinical relevance, our understanding of how host factors, such as antiviral cytokines interferons (IFNs), modulate NoV population dynamics is limited. Murine NoV (MNoV) is a tractable in vivo model for the study of host regulation of NoV. A persistent strain of MNoV, CR6, establishes a reservoir in intestinal tuft cells for chronic viral shedding in stool. However, the influence of host innate immunity and permissive cell numbers on viral population dynamics is an open question. We generated a pool of 20 different barcoded viruses (CR6BC) by inserting 6-nucleotide barcodes …

Targeting Dendritic Cell Dysfunction To Circumvent Anti-Pd1 Resistance In Head And Neck Cancer, Shin Saito, Michihisa Kono, Hoang C B Nguyen, Ann Marie Egloff, Cameron Messier, Patrick Lizotte, Cloud Paweletz, Douglas Adkins, Ravindra Uppaluri

2020-Current year OA Pubs

PURPOSE: Neoadjuvant anti-PD1 (aPD1) therapies are being explored in surgically resectable head and neck squamous cell carcinoma (HNSCC). Encouraging responses have been observed, but further insights into the mechanisms underlying resistance and approaches to improve responses are needed.

EXPERIMENTAL DESIGN: We integrated data from syngeneic mouse oral carcinoma (MOC) models and neoadjuvant pembrolizumab HNSCC patient tumor RNA-sequencing data to explore the mechanism of aPD1 resistance. Tumors and tumor-draining lymph nodes (DLN) from MOC models were analyzed for antigen-specific priming. CCL5 expression was enforced in an aPD1-resistant model.

RESULTS: An aPD1-resistant mouse model showed poor priming in the tumor DLN due …

Loss Of Katnal2 Leads To Ependymal Ciliary Hyperfunction And Autism-Related Phenotypes In Mice, Ryeonghwa Kang, Zachary Papadopoulos, Jonathan Kipnis, Et Al.

2020-Current year OA Pubs

Autism spectrum disorders (ASD) frequently accompany macrocephaly, which often involves hydrocephalic enlargement of brain ventricles. Katnal2 is a microtubule-regulatory protein strongly linked to ASD, but it remains unclear whether Katnal2 knockout (KO) in mice leads to microtubule- and ASD-related molecular, synaptic, brain, and behavioral phenotypes. We found that Katnal2-KO mice display ASD-like social communication deficits and age-dependent progressive ventricular enlargements. The latter involves increased length and beating frequency of motile cilia on ependymal cells lining ventricles. Katnal2-KO hippocampal neurons surrounded by enlarged lateral ventricles show progressive synaptic deficits that correlate with ASD-like transcriptomic changes involving synaptic gene down-regulation. Importantly, early …

Decorin Suppresses Tumor Lymphangiogenesis: A Mechanism To Curtail Cancer Progression, Dipon K. Mondal, Christopher Xie, Gabriel J. Pascal, Simone Buraschi, Renato V. Iozzo

Kimmel Cancer Center Faculty Papers

The complex interplay between malignant cells and the cellular and molecular components of the tumor stroma is a key aspect of cancer growth and development. These tumor-host interactions are often affected by soluble bioactive molecules such as proteoglycans. Decorin, an archetypical small leucine-rich proteoglycan primarily expressed by stromal cells, affects cancer growth in its soluble form by interacting with several receptor tyrosine kinases (RTK). Overall, decorin leads to a context-dependent and protracted cessation of oncogenic RTK activity by attenuating their ability to drive a prosurvival program and to sustain a proangiogenic network. Through an unbiased transcriptomic analysis using deep RNAseq, …

Quorum-Sensing, Magdalena Podkowik, Andrew I Perault, Gregory Putzel, Andrew Pountain, Jisun Kim, Ashley L Dumont, Erin E Zwack, Robert J Ulrich, Theodora K Karagounis, Chunyi Zhou, Andreas F Haag, Julia Shenderovich, Gregory A Wasserman, Junbeom Kwon, John Chen, Anthony R Richardson, Jeffrey N Weiser, Carla R Nowosad, Desmond S Lun, Dane Parker, Alejandro Pironti, Xilin Zhao, Karl Drlica, Itai Yanai, Victor J Torres, Bo Shopsin

Journal Articles

The agr quorum-sensing system links Staphylococcus aureus metabolism to virulence, in part by increasing bacterial survival during exposure to lethal concentrations of H2O2, a crucial host defense against S. aureus. We now report that protection by agr surprisingly extends beyond post-exponential growth to the exit from stationary phase when the agr system is no longer turned on. Thus, agr can be considered a constitutive protective factor. Deletion of agr resulted in decreased ATP levels and growth, despite increased rates of respiration or fermentation at appropriate oxygen tensions, suggesting that Δagr cells undergo a shift towards a hyperactive metabolic …

Pml::Rara And Gata2 Proteins Interact Via Dna Templates To Induce Aberrant Self-Renewal In Mouse And Human Hematopoietic Cells, Casey D S Katerndahl, Olivia R S Rogers, Ryan B Day, Ziheng Xu, Nichole M Helton, Sai Mukund Ramakrishnan, Christopher A Miller, Timothy J Ley

2020-Current year OA Pubs

The underlying mechanism(s) by which the PML::RARA fusion protein initiates acute promyelocytic leukemia is not yet clear. We defined the genomic binding sites of PML::RARA in primary mouse and human hematopoietic progenitor cells with V5-tagged PML::RARA, using anti-V5-PML::RARA chromatin immunoprecipitation sequencing and CUT&RUN approaches. Most genomic PML::RARA binding sites were found in regions that were already chromatin-accessible (defined by ATAC-seq) in unmanipulated, wild-type promyelocytes, suggesting that these regions are "open" prior to PML::RARA expression. We found that GATA binding motifs, and the direct binding of the chromatin "pioneering factor" GATA2, were significantly enriched near PML::RARA binding sites. Proximity labeling studies …

Interaction Of High-Fat Diet And Brain Trauma Alters Adipose Tissue Macrophages And Brain Microglia Associated With Exacerbated Cognitive Dysfunction, Rebecca J Henry, James P Barrett, Maria Vaida, Niaz Z Khan, Oleg Makarevich, Rodney M Ritzel, Alan I Faden, Bogdan A Stoica

Journal Articles

Obesity increases the morbidity and mortality of traumatic brain injury (TBI). Detailed analyses of transcriptomic changes in the brain and adipose tissue were performed to elucidate the interactive effects between high-fat diet-induced obesity (DIO) and TBI. Adult male mice were fed a high-fat diet (HFD) for 12 weeks prior to experimental TBI and continuing after injury. High-throughput transcriptomic analysis using Nanostring panels of the total visceral adipose tissue (VAT) and cellular components in the brain, followed by unsupervised clustering, principal component analysis, and IPA pathway analysis were used to determine shifts in gene expression patterns and molecular pathway activity. Cellular …

Tailoring Fxr Modulators For Intestinal Specificity: Recent Progress And Insights, Amanda Morrison, Bahaa Elgendy

2020-Current year OA Pubs

While FXR has shown promise in regulating bile acid synthesis and maintaining glucose and lipid homeostasis, undesired side effects have been observed in clinical trials. To address this issue, the development of intestinally restricted FXR modulators has gained attention as a new avenue for drug design with the potential for safer systematic effects. Our review examines all currently known intestinally restricted FXR ligands and provides insights into the steps taken to enhance intestinal selectivity.

Imputation Of 3d Genome Structure By Genetic-Epigenetic Interaction Modeling In Mice., Lauren Kuffler, Daniel A Skelly, Anne M Czechanski, Haley J Fortin, Steven C. Munger, Christopher L. Baker, Laura G Reinholdt, Gregory W. Carter

Faculty Research 2024

Gene expression is known to be affected by interactions between local genetic variation and DNA accessibility, with the latter organized into three-dimensional chromatin structures. Analyses of these interactions have previously been limited, obscuring their regulatory context, and the extent to which they occur throughout the genome. Here, we undertake a genome-scale analysis of these interactions in a genetically diverse population to systematically identify global genetic-epigenetic interaction, and reveal constraints imposed by chromatin structure. We establish the extent and structure of genotype-by-epigenotype interaction using embryonic stem cells derived from Diversity Outbred mice. This mouse population segregates millions of variants from eight …

An Update On Implant-Associated Malignancies And Their Biocompatibility, Grace C Keane Tahmaseb, Alexandra M Keane, Jose A Foppiani, Terence M Myckatyn

2020-Current year OA Pubs

Implanted medical devices are widely used across various medical specialties for numerous applications, ranging from cardiovascular supports to orthopedic prostheses and cosmetic enhancements. However, recent observations have raised concerns about the potential of these implants to induce malignancies in the tissues surrounding them. There have been several case reports documenting the occurrence of cancers adjacent to these devices, prompting a closer examination of their safety. This review delves into the epidemiology, clinical presentations, pathological findings, and hypothesized mechanisms of carcinogenesis related to implanted devices. It also explores how the surgical domain and the intrinsic properties and biocompatibility of the implants …

Xpo1 Blockade With Kpt-330 Promotes Apoptosis In Cutaneous T-Cell Lymphoma By Activating The P53-P21 And P27 Pathways, Nitin Chakravarti, Amy Boles, Rachel Burzinski, Paola Sindaco, Colleen Isabelle, Kathleen Mcconnell, Anjali Mishra, Pierluigi Porcu

Kimmel Cancer Center Faculty Papers

Dysregulated nuclear-cytoplasmic trafficking has been shown to play a role in oncogenesis in several types of solid tumors and hematological malignancies. Exportin 1 (XPO1) is responsible for the nuclear export of several proteins and RNA species, mainly tumor suppressors. KPT-330, a small molecule inhibitor of XPO1, is approved for treating relapsed multiple myeloma and diffuse large B-cell lymphoma. Cutaneous T-cell lymphoma (CTCL) is an extranodal non-Hodgkin lymphoma with an adverse prognosis and limited treatment options in advanced stages. The effect of therapeutically targeting XPO1 with KPT-330 in CTCL has not been established. We report that XPO1 expression is upregulated in …

Large-Scale Annotated Dataset For Cochlear Hair Cell Detection And Classification., Christopher J Buswinka, David B Rosenberg, Rubina G Simikyan, Richard T Osgood, Katharine Fernandez, Hidetomi Nitta, Yushi Hayashi, Leslie W Liberman, Emily Nguyen, Erdem Yildiz, Jinkyung Kim, Amandine Jarysta, Justine Renauld, Ella Wesson, Haobing Wang, Punam Thapa, Pierrick Bordiga, Noah Mcmurtry, Juan Llamas, Siân R Kitcher, Ana I López-Porras, Runjia Cui, Ghazaleh Behnammanesh, Jonathan E Bird, Angela Ballesteros, A Catalina Vélez-Ortega, Albert S B Edge, Michael R Deans, Ksenia Gnedeva, Brikha R Shrestha, Uri Manor, Bo Zhao, Anthony J Ricci, Basile Tarchini, Martín L Basch, Ruben Stepanyan, Lukas D Landegger, Mark A Rutherford, M Charles Liberman, Bradley J Walters, Corné J Kros, Guy P Richardson, Lisa L Cunningham, Artur A Indzhykulian

Faculty Research 2024

Our sense of hearing is mediated by cochlear hair cells, of which there are two types organized in one row of inner hair cells and three rows of outer hair cells. Each cochlea contains 5-15 thousand terminally differentiated hair cells, and their survival is essential for hearing as they do not regenerate after insult. It is often desirable in hearing research to quantify the number of hair cells within cochlear samples, in both pathological conditions, and in response to treatment. Machine learning can be used to automate the quantification process but requires a vast and diverse dataset for effective training. …

Dopamine Release Neuroenergetics In Mouse Striatal Slices, Msema Msackyi, Yuanxin Chen, Wangchen Tsering, Ninghan Wang, Hui Zhang

Department of Neuroscience Faculty Papers

Parkinson's disease (PD) is the second most common neurodegenerative disorder. Dopamine (DA) neurons in the substantia nigra pars compacta, which have axonal projections to the dorsal striatum (dSTR), degenerate in PD. In contrast, DA neurons in the ventral tegmental area, with axonal projections to the ventral striatum, including the nucleus accumbens (NAcc) shell, are largely spared. This study aims to uncover the relative contributions of glycolysis and oxidative phosphorylation (OxPhos) to DA release in the striatum. We measured evoked DA release in mouse striatal brain slices using fast-scan cyclic voltammetry applied every two minutes. Blocking OxPhos resulted in a greater …

Topographical And Cell Type-Specific Connectivity Of Rostral And Caudal Forelimb Corticospinal Neuron Populations, Lina Marcela Carmona, Eric D Thomas, Kimberly Smith, Bosiljka Tasic, Rui M Costa, Anders Nelson

Journal Articles

Corticospinal neurons (CSNs) synapse directly on spinal neurons, a diverse assortment of cells with unique structural and functional properties necessary for body movements. CSNs modulating forelimb behavior fractionate into caudal forelimb area (CFA) and rostral forelimb area (RFA) motor cortical populations. Despite their prominence, the full diversity of spinal neurons targeted by CFA and RFA CSNs is uncharted. Here, we use anatomical and RNA sequencing methods to show that CSNs synapse onto a remarkably selective group of spinal cell types, favoring inhibitory populations that regulate motoneuron activity and gate sensory feedback. CFA and RFA CSNs target similar spinal neuron types, …

Large-Scale Annotated Dataset For Cochlear Hair Cell Detection And Classification, Christopher J Buswinka, Jinkyung Kim, Anthony J Ricci, Mark A Rutherford, Et Al.

2020-Current year OA Pubs

Our sense of hearing is mediated by cochlear hair cells, of which there are two types organized in one row of inner hair cells and three rows of outer hair cells. Each cochlea contains 5-15 thousand terminally differentiated hair cells, and their survival is essential for hearing as they do not regenerate after insult. It is often desirable in hearing research to quantify the number of hair cells within cochlear samples, in both pathological conditions, and in response to treatment. Machine learning can be used to automate the quantification process but requires a vast and diverse dataset for effective training. …

Single-Cell T-Cell Receptor Repertoire Profiling In Dogs, My H Hoang, Zachary L Skidmore, Hans Rindt, Shirley Chu, Bryan Fisk, Jennifer A Foltz, Catrina Fronick, Robert Fulton, Mingyi Zhou, Nathan J Bivens, Carol N Reinero, Todd A Fehniger, Malachi Griffith, Jeffrey N Bryan, Obi L Griffith

2020-Current year OA Pubs

Spontaneous cancers in companion dogs are robust models of human disease. Tracking tumor-specific immune responses in these models requires reagents to perform species-specific single cell T cell receptor sequencing (scTCRseq). scTCRseq and integration with scRNA data have not been demonstrated on companion dogs with cancer. Here, five healthy dogs, two dogs with T cell lymphoma and four dogs with melanoma are selected to demonstrate applicability of scTCRseq in a cancer immunotherapy setting. Single-cell suspensions of PBMCs or lymph node aspirates are profiled using scRNA and dog-specific scTCRseq primers. In total, 77,809 V(D)J-expressing cells are detected, with an average of 3498 …

Bioresorbable, Wireless, Passive Sensors For Continuous Ph Measurements And Early Detection Of Gastric Leakage, Shuo Li, Yameng Xu, Ying Yan, Jorge Zárate Rodriguez, Mitchell A Pet, Chet W Hammill, Matthew R Macewan, Wilson Z Ray, Et Al.

2020-Current year OA Pubs

Continuous monitoring of biomarkers at locations adjacent to targeted internal organs can provide actionable information about postoperative status beyond conventional diagnostic methods. As an example, changes in pH in the intra-abdominal space after gastric surgeries can serve as direct indicators of potentially life-threatening leakage events, in contrast to symptomatic reactions that may delay treatment. Here, we report a bioresorbable, wireless, passive sensor that addresses this clinical need, designed to locally monitor pH for early detection of gastric leakage. A pH-responsive hydrogel serves as a transducer that couples to a mechanically optimized inductor-capacitor circuit for wireless readout. This platform enables real-time …

Host Response During Unresolved Urinary Tract Infection Alters Female Mammary Tissue Homeostasis Through Collagen Deposition And Timp1, Samantha Henry, Xue-Yan He, Et Al.

2020-Current year OA Pubs

Exposure to pathogens throughout a lifetime influences immunity and organ function. Here, we explore how the systemic host-response to bacterial urinary tract infection (UTI) induces tissue-specific alterations to the mammary gland. Utilizing a combination of histological tissue analysis, single cell transcriptomics, and flow cytometry, we identify that mammary tissue from UTI-bearing mice displays collagen deposition, enlarged ductal structures, ductal hyperplasia with atypical epithelial transcriptomes and altered immune composition. Bacterial cells are absent in the mammary tissue and blood of UTI-bearing mice, therefore, alterations to the distal mammary tissue are mediated by the systemic host response to local infection. Furthermore, broad …