Digital Commons Network^™

Enhancement Of The Endocannabinoid System Through Monoacylglycerol Lipase Inhibition Relieves Migraine-Associated Pain In Mice, Elizaveta Mangutov, Yaseen Awad-Igbaria, Kendra Siegersma, Francois Gastambide, Ayodeji A Asuni, Amynah A A Pradhan

2020-Current year OA Pubs

BACKGROUND: Migraine affects over 1 billion people worldwide and is a leading cause of disability. Targeting the cannabinoid system offers a promising approach for pain and migraine relief. This study evaluated a novel monoacylglycerol lipase (MAGL) inhibitor to prolong endocannabinoid action in acute and chronic mouse models of migraine. It also examined MAGL and cannabinoid receptor 1 (CB

METHODS: C57BL6/J male and female mice received the human migraine trigger nitroglycerin (NTG) acutely or every other day for 9 days. Allodynia was assessed by von Frey hair stimulation of the periorbital area. A single dose of MAGL inhibitor (ABD-1970) was tested …

Age-Related Meningeal Extracellular Matrix Remodeling Compromises Cns Lymphatic Function, Kate Hitpass Romero, Taylor J Stevenson, Leon C D Smyth, Ben Watkin, Samuel J C Mccullough, Luca Vinnell, Amy M Smith, Patrick Schweder, Jason A Correia, Jonathan Kipnis, Mike Dragunow, Justin Rustenhoven

2020-Current year OA Pubs

Efficient clearance of central nervous system (CNS) waste proteins and appropriate immune surveillance is essential for brain health. These processes are facilitated by lymphatic networks present in the meninges that drain cerebrospinal fluid (CSF). Age-related impairments to meningeal lymphatic drainage contribute to CNS waste accumulation and immune dysfunction, yet the underlying mechanisms remain poorly understood. Here, we identify extracellular matrix (ECM) remodeling in the aged dura as a key driver of CSF clearance deficits, demonstrating that peri-lymphatic collagen accumulation disrupts lymphatic function. Exploring immune-derived factors contributing to this ECM remodeling, we identify transforming growth factor beta 1 (TGFβ1) as a …

Asynchronous Development Of The Mouse Auditory Cortex Is Driven By Hemispheric Identity And Sex, Ashlan P Reid, Demetrios Neophytou, Robert Levy, Cody Pham, Hysell V Oviedo

2020-Current year OA Pubs

Lateralized auditory processing is essential for specialized functions such as speech processing, typically dominated by the Left Auditory Cortex (ACx) in humans. Hemispheric specializations also occur in the adult mouse ACx, but their developmental origins are unclear. Our study finds that the Left and Right ACx in mice reach developmental milestones at different ages. Thalamocortical responses and maturation of synaptic dynamics develop earlier in the Right ACx than the Left. We show that this timing offset predicts hemisphere-dependent differences in sensory-driven plasticity. Juvenile tone exposure at specific times results in imbalanced adult tone frequency representations in the Right and Left …

The Essential Calcium Channel Of Sperm Catsper Is Temperature-Gated, Dilip K Swain, Citlalli Vergara, Júlia Castro-Arnau, Polina V Lishko

2020-Current year OA Pubs

The flagellar calcium channel CatSper is essential for male fertility, as it regulates calcium influx to trigger the hyperactive motility required for sperm to fertilize the egg. Precise activation of CatSper is critical, as premature activation can impair sperm function. While optimal temperature is known to influence fertilization, its effect on CatSper remains unknown. By directly recording from mouse spermatozoa, we reveal that CatSper functions as a temperature-gated ion channel, with a thermal threshold of 33.5 °C and a temperature coefficient Q

Imaging Peripheral Nerves In Vivo With Ct Neurogram Using Novel 2,4,6-Tri-Iodinated Lidocaine Contrast Agent, Rui Tang, Ron Perez, David M Brogan, Mikhail Y Berezin, James E Mccarthy

2020-Current year OA Pubs

Peripheral nerve injuries are a significant concern in surgical procedures, often leading to chronic pain and functional impairment. Despite advancements in imaging, preoperative and intraoperative visualization of peripheral nerves remains a challenge. This study introduces and evaluates a novel tri-iodinated lidocaine-based contrast agent for computed tomography neurography, aiming to enhance the intraoperative visibility of peripheral nerves in vivo. A tri-iodinated lidocaine analogue was synthesized and characterized for its radiodensity, sodium channel binding and nerve affinity. Sodium channel affinity was performed using molecular docking. In vitro contrast enhancement was assessed by comparing the agent's Hounsfield unit (HU) values with those of …

Elevated Mitochondrial Membrane Potential Is A Therapeutic Vulnerability In Dnmt3a-Mutant Clonal Hematopoiesis, Kira A Young, Grant A Challen, Et Al.

2020-Current year OA Pubs

The competitive advantage of mutant hematopoietic stem and progenitor cells (HSPCs) underlies clonal hematopoiesis (CH). Drivers of CH include aging and inflammation; however, how CH-mutant cells gain a selective advantage in these contexts is an unresolved question. Using a murine model of CH (Dnmt3a

Synapsin Condensation Is Governed By Sequence-Encoded Molecular Grammars, Christian Hoffmann, Kiersten M Ruff, Irina A Edu, Min Kyung Shinn, Johannes V Tromm, Matthew R King, Avnika Pant, Hannes Ausserwöger, Jennifer R Morgan, Tuomas P J Knowles, Rohit V Pappu, Dragomir Milovanovic

2020-Current year OA Pubs

Multiple biomolecular condensates coexist at the pre- and post- synapse to enable vesicle dynamics and controlled neurotransmitter release in the brain. In pre-synapses, intrinsically disordered regions (IDRs) of synaptic proteins are drivers of condensation that enable clustering of synaptic vesicles (SVs). Using computational analysis, we show that the IDRs of SV proteins feature evolutionarily conserved non-random compositional biases and sequence patterns. Synapsin-1 is essential for condensation of SVs, and its C-terminal IDR has been shown to be a key driver of condensation. Focusing on this IDR, we dissected the contributions of two conserved features namely the segregation of polar and …

Immunotherapeutic Strategies In Head And Neck Cancer: Challenges And Opportunities, Xia Liu, R. Alex Harbison, Mark A. Varvares, Sidharth V. Puram, Guangyong Peng

2020-Current year OA Pubs

HNSCC remains a substantial health issue, with treatment options including surgery, radiation, and platinum-based chemotherapy. Unfortunately, despite progress in research, only modest gains have been made in disease control, with existing treatments resulting in significant functional and quality-of-life issues. The introduction of immunotherapy in the treatment of HNSCC has resulted in some improvements in outlook for patients and is now standard of care for populations with both recurrent and metastatic disease. However, despite the early successes, responses to immune checkpoint inhibition (ICI) remain modest to low, approaching 14%-22% objective response rates. Challenges to the effectiveness of ICI and other immunotherapies …

Label-Free Evaluation Of Mouse Embryo Quality Using Time-Lapse Bright Field And Optical Coherence Microscopy, Fei Wang, Senyue Hao, Kibeom Park, Ali Ahmady, Chao Zhou

2020-Current year OA Pubs

The selection of high-quality embryos is essential to enhance the implantation rate for in vitro fertilization (IVF). Optical coherence microscopy (OCM) can noninvasively provide three-dimensional (3D) high-resolution imaging of developing embryos. The revealed microstructures can be used for accurate embryo evaluation. Here, we acquire time-lapse 3D OCM images with co-registered bright-field imaging on mouse embryo development from the one-cell stage to the fully hatched blastocyst inside an incubator. Our results demonstrate the capability of OCM to detect structural features of the developing embryos. The second and third embryonic cell cycles are indicated to be associated with blastocyst formation and the …

Pilot First-In-Human Ccr2 Pet/Ct To Detect Abdominal Aortic Aneurysm Wall Instability, Santiago Elizondo-Benedetto, Deborah Sultan, Ryan Wahidi, Mahdjoub Hamdi, Mohamed S Zaghloul, Shahab Hafezi, Batool Arif, Laura K Mcdonald, Kitty Harrison, Dakkota Thies, Gyu Seong Heo, Hannah Luehmann, Lisa Detering, J Westley Ohman, Zachary J Wanken, Luis A Sanchez, Joseph E Ippolito, Jie Zheng, Robert J Gropler, Richard Laforest, Yongjian Liu, Mohamed A Zayed

2020-Current year OA Pubs

No abstract provided.

The Antimicrobial Resistance-Water-Corporate Interface: Exploring The Connections Between Antimicrobials, Water, And Pollution, Jason P Burnham

2020-Current year OA Pubs

Antibiotic resistance is a public health emergency, with ten million deaths estimated annually by the year 2050. Water systems are an important medium for the development and dissemination of antibiotic resistance from a variety of sources, explored in this perspective review. Hospital wastewater and wastewater systems more broadly are breeding grounds for antibiotic resistance because of the nature of their waste and how it is processed. Corporations from various sectors contribute to antibiotic resistance in many direct and indirect ways. Pharmaceutical factory runoff, agricultural antibiotic use, agricultural use of nitrogen fertilizers, heavy metal pollution, air pollution (atmospheric deposition, burning of …

The Human Brainstem's Red Nucleus Was Upgraded To Support Goal-Directed Action, Samuel R Krimmel, Timothy O Laumann, Roselyne J Chauvin, Tamara Hershey, Jarod L Roland, Joshua S Shimony, Jon T Willie, Scott A Norris, Scott Marek, Andrew N Van, Anxu Wang, Julia Monk, Kristen M Scheidter, Forrest I Whiting, Nadeshka Ramirez-Perez, Athanasia Metoki, Noah J Baden, Benjamin P Kay, Hadas Nahman-Averbuch, Abraham Z Snyder, Marcus E Raichle, Evan M Gordon, Nico U F Dosenbach, Et Al.

2020-Current year OA Pubs

The red nucleus, a large brainstem structure, coordinates limb movement for locomotion in quadrupedal animals. In humans, its pattern of anatomical connectivity differs from that of quadrupeds, suggesting a different purpose. Here, we apply our most advanced resting-state functional connectivity based precision functional mapping in highly sampled individuals (n = 5), resting-state functional connectivity in large group-averaged datasets (combined n ~ 45,000), and task based analysis of reward, motor, and action related contrasts from group-averaged datasets (n > 1000) and meta-analyses (n > 14,000 studies) to precisely examine red nucleus function. Notably, red nucleus functional connectivity with motor-effector networks (somatomotor hand, foot, …

Gramd1b Is A Regulator Of Lipid Homeostasis, Autophagic Flux And Phosphorylated Tau, Diana Acosta Ingram, Jacob Marsh, Celeste M Karch, Et Al.

2020-Current year OA Pubs

Lipid dyshomeostasis and tau pathology are present in frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD). However, the relationship between lipid dyshomeostasis and tau pathology remains unclear. We report that GRAM Domain Containing 1B (GRAMD1B), a nonvesicular cholesterol transporter, is increased in excitatory neurons of human neural organoids (HNOs) with the MAPT R406W mutation. Human FTLD, AD cases, and PS19 tau mice also have increased GRAMD1B expression. We show that overexpression of GRAMD1B increases levels of free cholesterol, lipid droplets, and impairs autophagy flux. Modulating GRAMD1B in iPSC-derived neurons also alters key autophagy-related components such as PI3K, phospho-AKT, and p62, …

Activation Of Endoplasmic Reticulum-Localized Metabotropic Glutamate Receptor 5 (Mglu5) Triggers Calcium Release Distinct From Cell Surface Counterparts In Striatal Neurons, Yuh-Jiin I Jong, Steven K Harmon, Karen L O'Malley

2020-Current year OA Pubs

Metabotropic glutamate receptor 5 (mGlu

Nbeal2 Knockout Mice Are Not Protected Against Hypoxia-Induced Pulmonary Vascular Remodeling And Pulmonary Hypertension, Janelle N Posey, Mariah Jordan, Caitlin V Lewis, Christina Sul, Evgenia Dobrinskikh, Delaney Swindle, Frederik Denorme, David Irwin, Jorge Di Paola, Kurt Stenmark, Eva S Nozik, Cassidy Delaney

2020-Current year OA Pubs

Inflammation drives the initiation and progression of pulmonary hypertension (PH). Platelets, increasingly recognized as immune cells, are activated and increased in the lungs of patients with PH. Platelet activation leads to the release of α-granule chemokines, many of which are implicated in PH. We hypothesized that hypoxia-induced secretion of platelet α-granule-stored proteins and PH would be prevented in Neurobeachin-like 2 knockout (Nbeal2-/-) α-granule-deficient mice. Wild-type (WT) and Nbeal2-/- mice were maintained in normoxia or exposed to 10% hypobaric hypoxia for 3, 14, 21, or 35 days. We observed macrothrombocytopenia, increased circulating neutrophils and monocytes, and increased lung interstitial macrophages (IMs) …

Shared Pathway Of Wdfy4-Dependent Cross-Presentation Of Immune Complexes By Cdc1 And Cdc2, Suin Jo, Ray A Ohara, Derek J Theisen, Sunkyung Kim, Tiantian Liu, Christopher B Bullock, Michelle He, Feiya Ou, Jing Chen, Sytse J Piersma, J Luke Postoak, Wayne M Yokoyama, Michael S Diamond, Theresa L Murphy, Kenneth M Murphy

2020-Current year OA Pubs

Priming CD8+ T cells against tumors or viral pathogens results largely from cross-presentation of exogenous antigens by type 1 conventional dendritic cells (cDC1s). Although monocyte-derived DCs and cDC2s can cross-present in vitro, their physiological relevance remains unclear. Here, we used genetic models to evaluate the role of cDC subsets in presentation of cell-associated and immune complex antigens to CD4+ and CD8+ T cells in vivo. For cell-associated antigens, cDC1s were necessary and sufficient to prime both CD4+ and CD8+ T cells. In contrast, for immune complex antigens, either cDC1 or cDC2, but not monocyte-derived DCs, could carry out cross-presentation to …

Loss Of Atg7 In Microglia Impairs Upr, Triggers Ferroptosis, And Weakens Amyloid Pathology Control, Zhangying Cai, Shoutang Wang, Siyan Cao, Yun Chen, Silvia Penati, Vincent Peng, Carla M Yuede, Wandy L Beatty, Kent Lin, Yiyang Zhu, Yingyue Zhou, Marco Colonna

2020-Current year OA Pubs

Microglia impact brain development, homeostasis, and pathology. One important microglial function in Alzheimer's disease (AD) is to contain proteotoxic amyloid-β (Aβ) plaques. Recent studies reported the involvement of autophagy-related (ATG) proteins in this process. Here, we found that microglia-specific deletion of Atg7 in an AD mouse model impaired microglia coverage of Aβ plaques, increasing plaque diffusion and neurotoxicity. Single-cell RNA sequencing, biochemical, and immunofluorescence analyses revealed that Atg7 deficiency reduces unfolded protein response (UPR) while increasing oxidative stress. Cellular assays demonstrated that these changes lead to lipoperoxidation and ferroptosis of microglia. In aged mice without Aβ buildup, UPR reduction and …

Nitrous Oxide Activates Layer 5 Prefrontal Neurons Via Sk2 Channel Inhibition For Antidepressant Effect, Joseph Cichon, Thomas T Joseph, Xinguo Lu, Andrzej Z Wasilczuk, Max B Kelz, Steven J Mennerick, Charles F Zorumski, Peter Nagele

2020-Current year OA Pubs

Nitrous oxide (N

Unraveling The Complexities Of Myeloid-Derived Suppressor Cells In Inflammatory Bowel Disease, Yangzhuangzhuang Zhu, Siyan Cao

2020-Current year OA Pubs

Myeloid-derived suppressor cells (MDSCs) regulate immune responses in many pathological conditions, one of which is inflammatory bowel disease (IBD), an incurable chronic disorder of the digestive tract and beyond. The pathophysiology of IBD remains unclear, likely involving aberrant innate and adaptive immunity. Studies have reported altered population of MDSCs in patients with IBD. However, their distribution varies among patients and different preclinical models of IBD. The expansion and activation of MDSCs are likely driven by various stimuli during intestinal inflammation, but the in-depth mechanisms remain poorly understood. The role of MDSCs in the pathogenesis of IBD appears to be paradoxical. …

Neuroimmune Mechanisms Of Type 2 Inflammation In The Skin And Lung, Masato Tamari, Aaron M Ver Heul

2020-Current year OA Pubs

Type 2 inflammation has a major role in barrier tissues such as the skin and airways and underlies common conditions including atopic dermatitis (AD) and asthma. Cytokines including interleukin 4 (IL-4), IL-5, and IL-13 are key immune signatures of type 2 inflammation and are the targets of multiple specific therapeutics for allergic diseases. Despite shared core immune mechanisms, the distinct structures and functions of the skin and airways lead to unique therapeutic responses. It is increasingly recognized that the nervous system has a major role in sensing and directing inflammatory processes. Indeed, crosstalk between type 2 immune activation and somatosensory …

Enhancing Human Nk Cell Antitumor Function By Knocking Out Smad4 To Counteract Tgfβ And Activin A Suppression, Anna Rea, Bishan Bhattarai, Marco Colonna, Et Al.

2020-Current year OA Pubs

Transforming growth factor beta (TGFβ) and activin A suppress natural killer (NK) cell function and proliferation, limiting the efficacy of adoptive NK cell therapies. Inspired by the partial resistance to TGFβ of NK cells with SMAD4 haploinsufficiency, we used CRISPR-Cas9 for knockout of SMAD4 in human NK cells. Here we show that SMAD4

Associations Of Cerebrospinal Fluid Orexin-A, Alzheimer Disease Biomarkers, And Cognitive Performance, Ruijin Lu, Krish Shah, Cristina D Toedebusch, Ashley Hess, Rachel Richardson, Emmanuel Mignot, Suzanne E Schindler, Tammie L S Benzinger, Shaney Flores, Jason Hassenstab, Chengjie Xiong, John C Morris, David M Holtzman, Brendan P Lucey

2020-Current year OA Pubs

OBJECTIVE: Cerebrospinal fluid (CSF) orexin-A has been suggested to be a biomarker of Alzheimer disease (AD). In both cognitively unimpaired healthy older adults and individuals with symptomatic AD, CSF orexin-A is positively associated with CSF Aβ42, p-tau181, and total tau (t-tau) concentrations. However, a recent systematic review and meta-analysis did not support differences in orexin-A between AD and controls. In this study, we tested the association between CSF orexin-A concentrations, AD biomarkers, and cognitive performance in older adults with and without symptomatic AD.

METHODS: Two hundred and seventy community-dwelling older adults underwent standardized cognitive assessments, sleep monitoring with a single-channel …

Multi-Omic Analysis Of Biological Aging Biomarkers In Long-Term Calorie Restriction And Endurance Exercise Practitioners: A Cross-Sectional Study, Giovanni Fiorito, Valeria Tosti, Silvia Polidoro, Beatrice Bertozzi, Nicola Veronese, Edda Cava, Francesco Spelta, Laura Piccio, Dayna S Early, Daniel Raftery, Paolo Vineis, Luigi Fontana

2020-Current year OA Pubs

Calorie restriction (CR) and physical exercise (EX) are well-established interventions known to extend health span and lifespan in animal models. However, their impact on human biological aging remains unclear. With recent advances in omics technologies and biological age (BioAge) metrics, it is now possible to assess the impact of these lifestyle interventions without the need for long-term follow-up. This study compared BioAge biomarkers in 41 middle-aged and older adult long-term CR practitioners, 41 age- and sex-matched endurance athletes (EX), and 35 sedentary controls consuming Western diets (WD), through PhenoAge: a composite score derived from nine blood-biomarkers. Additionally, a subset of …

Dynein Light Chains 1 And 2 Are Auxiliary Proteins Of Ph-Sensitive Kir4.1 Channels, Sun-Joo Lee, Jian Gao, Ellen Thompson, Jonathan Mount, Colin G Nichols

2020-Current year OA Pubs

Inward rectifier Kir4.1 potassium channels are abundantly expressed in cells that are important for electrolyte homeostasis. Dysregulation of Kir4.1 underlies various neurological disorders. Here, through biochemical and structural studies of full-length Kir4.1, we show that dynein light chain 1 and 2 proteins, also as known as LC8, copurify with Kir4.1 at stoichiometric levels. Direct interaction between Kir4.1 and LC8 is supported by in vitro binding assays and reiterated with native Kir4.1 proteins from mouse brain. Notably, we identify a LC8 binding motif in the unstructured N terminus of Kir4.1. Among Kir subtypes, the motif is unique to Kir4.1 and is …

Engineering Adhesive Hydrogels For Hemostasis And Vascular Repair, Juya Jeon, Shri Venkatesh Subramani, Kok Zhi Lee, Santiago Elizondo-Benedetto, Mohamed Adel Zayed, Fuzhong Zhang

2020-Current year OA Pubs

Adhesive hydrogels with tunable mechanical properties and strong adhesion to wet, dynamic tissues have emerged as promising materials for tissue repair, with potential applications in wound closure, hemorrhage control, and surgical adhesives. This review highlights the key design principles, material classifications, and recent advances in adhesive hydrogels designed for vascular repair. The limitations of existing adhesive hydrogels, including insufficient mechanical durability, suboptimal biocompatibility, and challenges in targeted delivery, are critically evaluated. Furthermore, innovative strategies-such as incorporating self-healing capabilities, developing stimuli-responsive systems, integrating functional nanocomposites, and employing advanced fabrication techniques like 3D bioprinting-are discussed to enhance adhesion, mechanical stability, and vascular …

Transcriptome Meta-Analysis Uncovers Cell-Specific Regulatory Relationships In Embryonic, Juvenile, Adult, And Aged Mouse Lens Epithelium And Fibers, Matthieu Duot, Sarah Y Coomson, Sanjaya K Shrestha, M V Murali Krishna Nagulla, Yann Audic, Ruteja A Barve, Hongzhan Huang, Carole Gautier-Courteille, Luc Paillard, Salil A Lachke

2020-Current year OA Pubs

PURPOSE: The lens transcriptome has been examined using microarrays and RNA-sequencing (RNA-seq). These omics data are the basis of the bioinformatics web-resource iSyTE that has identified new genes involved in lens development and cataract. The lens predominantly contains epithelial and fiber cells, and yet, presently, iSyTE is based on whole lens data. To gain cell-specific regulatory insights, we meta-analyzed isolated epithelium and fiber transcriptomes from embryonic/postnatal, adult and aged lenses.

METHODS: Mouse lens epithelium and fiber transcriptome public datasets at embryonic (E) and postnatal (P) stages E12.5, E14.5, E16.5, E18.5, P0.5, P0, P5, P13, and age one month, three months, …

Sexually Dimorphic Cardiovascular Impacts Of Prenatal Exposure To A Real-Life Environmental Chemical Mixture In Adult Offspring, Noor Muhammad Khan, Victoria Scott, Mohammad Ghasemzadeh-Hasankolaei, Vasantha Padmanabhan, Arpita Vyas, Neil P Evans, Michelle Bellingham

2020-Current year OA Pubs

Cardiovascular disease (CVD) is a leading cause of death that is sexually dimorphic. This study used an ovine model to investigate whether maternal exposure to an environmental chemical (EC) mixture (biosolids) prior to and throughout pregnancy, affected offspring cardiovascular (CV) structure and function in adulthood. CV function of male and female offspring from ewes grazed on either conventionally fertilised (control, C) or biosolids-treated pasture (B) was assessed. Males exhibited higher blood pressure compared to females with no significant effect of EC exposure. Heart rate variability in females suggested reduced autonomic regulation in the B group. EC-exposed males, but not females, …

In Vivo Manipulation Of Human Gut Bacteroides Fitness By Abiotic Oligosaccharides, Darryl A Wesener, Zachary W Beller, Megan F Hill, Han Yuan, David B Belanger, Cheryl Frankfater, Nicolas Terrapon, Bernard Henrissat, Dmitry A Rodionov, Semen A Leyn, Andrei Osterman, Johan E T Van Hylckama Vlieg, Jeffrey I Gordon

2020-Current year OA Pubs

Synthetic glycans (SGs) containing glycosidic linkages and structures not identified in nature offer a means for deliberately altering microbial community properties. Here pools of SG oligosaccharides were generated via polymerization of monosaccharides and screened for their ability to increase saccharolytic Bacteroides in ex vivo cultures of human fecal samples. A lead SG preparation was orally administered to gnotobiotic mice harboring a consortium of 56 cultured, phylogenetically diverse human gut bacteria and fed a Western diet. The abundances of 3 of 15 Bacteroides strains increased, most prominently B. intestinalis. Underlying mechanisms were characterized by analyzing in vivo expression of the carbohydrate …

Single-Cell Transcriptomic Analysis Of Kaposi Sarcoma, Daniel A. Rauch, Paula Valiño Ramos, Mariam Khanfar, John Harding, Ancy Joseph, Anam Fahad, Paul Simonson, Isabel Risch, Obi Griffith, Malachi Griffith, Lee Ratner

2020-Current year OA Pubs

Kaposi Sarcoma (KS) is a complex tumor caused by KS-associated herpesvirus 8 (KSHV). Histological analysis reveals a mixture of "spindle cells", vascular-like spaces, extravasated erythrocytes, and immune cells. In order to elucidate the infected and uninfected cell types in KS tumors, we examined twenty-five skin and blood samples from sixteen subjects by single cell RNA sequence analyses. Two populations of KSHV-infected cells were identified, one of which represented a CD34-negative proliferative fraction of endothelial cells, and the second representing CD34-positive cells expressing endothelial genes found in a variety of cell types including high endothelial venules, fenestrated capillaries, and endothelial tip …

The Role Of Androgens On Experimental Pain Sensitivity: A Systemic Review And Meta-Analysis, Elizabeth Wu-Chen, Gourav Banerjee, Elise Requadt, Benjamin Hunter, Thomas J. Baranski, Whitney Trotter Ross, Hadas Nahman-Averbuch

2020-Current year OA Pubs

Animal studies have shown androgens, especially testosterone, may have an analgesic effect on nociceptive behavior. However, it is unclear if this effect is present in humans. This review and meta-analysis aim to summarize and synthesize the role of androgens on experimental pain sensitivity in humans. Studies were included if they examined the (1) relationships between androgens and experimental pain sensitivity, (2) group differences in androgen or pain levels, and (3) the effect of androgen interventions on experimental pain sensitivity. After a comprehensive search, 31 papers were identified. When possible, meta-analyses were performed. Most studies examined the impact of testosterone on …