Digital Commons Network^™

Associations Between Caregiver-Provider Communication Quality And Unmet Care Needs Among Older Adults, Jiaming Liang, Rafael Samper-Ternent, Brian Downer, Zhigang Xie

Faculty, Staff and Student Publications

BACKGROUND: Unmet care needs (lack of assistance with daily activities) among older adults are common and linked to adverse health outcomes, greater healthcare utilization, and caregiver burden. While effective patient-provider communication is known to improve care quality, less is understood about the role of caregiver-provider communication, particularly across sociodemographic, health, and caregiving contexts. METHODS: We conducted a cross-sectional secondary analysis of pooled 2021–2023 National Health and Aging Trends Study (NHATS) and National Study of Caregiving (NSOC) data, restricted to community-dwelling older adults (65 + years) who received assistance from caregivers due to difficulty with daily activities, and had at least …

Mouse White Matter Matters: Cortical Origins And Spatial Organization Of Mouse White Matter Tracts, Sofia D Gordeev, Melissa Franch, Sarah R Heilbronner

Faculty, Staff and Students Publications

White matter—the fundamental structure underlying network connectivity—lies at the heart of the brain’s computational power. White matter is organized into fiber tracts, or bundles, in both human and nonhuman primate brains. These bundles consist of long-range axonal projections with a set of shared origin and termination points and exhibit a predictable organization. However, the organization of white matter in the mouse brain remains relatively unknown. This knowledge gap is surprising given the central role of mice in neuroscience, with mouse brains serving as the dominant model for transgenics, in vivo calcium imaging, and circuit manipulation. To address this gap, we …

Molecular Characterization Of Humanized Apoe Mouse Models Reveals Source And Genotype Dependent Differences, Na Wang, Gefei Yu, Zhen Wang, Alla Alnobani, Suren Jeevaratnam, Xue Zhang, Meghan Mcreynolds, Yuzhou Chang, Fangfang Qi, William Tauer, Cassandra Rosenberg, Melissa Wren, Tadafumi C Ikezu, Yuka A Martens, Minghui Wang, Bin Zhang, Gregory W Carter, Michael Sasner, David M Holtzman, Junmin Peng, Long-Jun Wu, Takahisa Kanekiyo, Chia-Chen Liu, Guojun Bu

The Brown Foundation: Institute of Molecular Medicine

Background

Humanized APOE targeted-replacement (TR) mice are essential tools for studying apoE isoform effects in Alzheimer’s disease (AD) and other apoE-related disorders. Despite their widespread use, existing APOE mouse models, generated with different gene targeting strategies, have not been directly compared in terms of apoE isoform expression, lipid profiles, and transcriptomic signatures. Such differences could impact how we interpret APOE genotype-related outcomes, as well as related underlying molecular mechanisms.

Methods

We conducted a comprehensive molecular comparison of humanized APOE mouse models from three sources: Taconic Biosciences (TAC), the Cure Alzheimer’s Fund (CAF), and The Jackson Laboratory (JAX). We assessed apoE …

Molecular Characterization Of Humanized Apoe Mouse Models Reveals Source And Genotype Dependent Differences, Na Wang, David M Holtzman, Et Al.

2020-Current year OA Pubs

BACKGROUND: Humanized APOE targeted-replacement (TR) mice are essential tools for studying apoE isoform effects in Alzheimer’s disease (AD) and other apoE-related disorders. Despite their widespread use, existing APOE mouse models, generated with different gene targeting strategies, have not been directly compared in terms of apoE isoform expression, lipid profiles, and transcriptomic signatures. Such differences could impact how we interpret APOE genotype-related outcomes, as well as related underlying molecular mechanisms. METHODS: We conducted a comprehensive molecular comparison of humanized APOE mouse models from three sources: Taconic Biosciences (TAC), the Cure Alzheimer’s Fund (CAF), and The Jackson Laboratory (JAX). We assessed apoE …

Synthetic Lethality Between Rb-Loss And E2f3 Inhibition In Small Cell Cancers Targeted By Pyrimidine Synthesis Blockade, Evan R. Abt, Liang Wang, Grigor Varuzhanyan, Jack Freeland, Tian He, Guadalupe M. Peña-Garcia, Lauryn Ruegg, Jami Mclaughlin, Donghui Cheng, Nikolas G. Balanis, Chia-Chun Chen, Yang Xu, Yi Xing, Sanaz Memarzadeh, Caius G. Radu, Thomas G. Graeber, Owen N. Witte

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Small cell carcinoma is a highly lethal cancer variant often found with neuroendocrine (NE) features, as exemplified by small cell lung cancer and small cell NE prostate cancer (SCPC). A genome-wide CRISPR dependency screen using SCPC models generated through human prostate cell transformation identifies a requirement for the transcription factor E2F3. E2F3 dependency is linked to RB inactivation, a near universal occurrence across small cell cancers. The requirement for E2F3 is shared by RB-deficient cells originating from the prostate, lung, and adnexa. In RB-deficient cancer cells, E2F3 inhibition restrains cell cycle progression, proliferation, and tumor growth in vivo. Inhibition of …

Photobiomodulation In Treatment Of Head And Neck Cancer-Related Chronic Lymphedema: A Pilot Randomized Controlled Trial, Jie Deng, John N. Lukens, Barbara A. Murphy, Erin Mcmenamin, Karthik Rajasekaran, Ryan J. Quinn, Joy C. Cohn, Wendy Schlessinger, Lucy P. Andersen, Bryan A. Spinelli, Alexander Lin

Department of Physical Therapy Faculty Papers

BACKGROUND: Chronic lymphedema is a common late effect after completion of head and neck cancer (HNC) treatment, contributing to substantial symptom burden and negatively impacting quality of life. No effective approaches are available to treat this progressive condition. This study aimed to evaluate the preliminary efficacy of photobiomodulation (PBM) therapy for chronic lymphedema in HNC survivors.

METHODS: This was a pilot, randomized, wait-list controlled trial. Eligible HNC survivors included those with chronic lymphedema after completion of complete decongestive therapy. Participants were randomized (1:1) to 1 of 2 arms: intervention group (active) or wait-list control group (control). The active group received …

Targeting Cardiomyocyte-Derived Extracellular Vesicle Mir-574-5p Protects Against Cognitive Impairment Induced By Ischemia-Reperfusion, Erya Chen, Xiaoyu Zhu, Haiqing Chang, Qi Li, Zhenkun Zhao, Changteng Zhang, Yu Cao, Yajing Wang, Xinliang Ma, Tao Zhu, Shu Zhang, Lu Gan, Jin Liu, Chan Chen

Department of Emergency Medicine Faculty Papers

BACKGROUND:  Acute myocardial ischemia/reperfusion (MI/R) increases risk for cognitive decline, yet the underlying mechanisms mediating heart-brain communication remain poorly understood. Small extracellular vesicles (sEVs) have emerged as novel long-range signaling mediators and may play a critical role.

METHODS: MI/R was induced by transient ligation of the left anterior descending artery. Cognitive performance was assessed using multiple behavioral tests. sEVs derived from cardiomyocytes were labeled to track their distribution and cellular uptake in the brain. Heart and brain tissues were analyzed for microRNAs (miRNAs) expression using bioinformatics, qPCR, and RNAScope. The role of specific miRNAs was investigated through genetic inhibition of …

Fibrinogen-Bmal1 Signaling As A Therapeutic Target To Limit Aortic Dissection By Preserving Vsmc Contractility, Xiaohan Zhong, Dongjie Li, Yuanfei Zhao, Lu Dai, Jinzhang Li, Zhiqi Ji, Bojing Zuo, Hongshan Liu, Haixia Huang, Wei Wang, Haiyang Li, Yuyong Liu, Ming Gong, Xin-Liang Ma, Wenjian Jiang, Meili Wang, Hongjia Zhang

Department of Emergency Medicine Faculty Papers

Aortic dissection (AD) is a life-threatening vascular disease with a high mortality rate. Surgery is essential in the acute phase but carries significant risks, whereas elective surgery during the chronic phase yields better outcomes. However, no pharmacological therapy has been proven effective in slowing AD progression. In our recent pilot clinical study, an association between higher plasma fibrinogen levels and improved clinical outcomes was observed in AD patients, suggesting a potential protective role of fibrinogen. However, direct evidence supporting this hypothesis is lacking. In this study, a population-based analysis of nonsurgically managed patients with acute AD revealed a distinct association: …

Rethinking Ratio-Based Normalization Towards Model-Based Approaches In Heart Weight Analysis., Manuela A Oestereicher, Patricia Da Silva-Buttkus, Valérie Gailus-Durner, Susan Marschall, Helmut Fuchs, Impc Consortium, Martin Hrabě De Angelis, Elida Schneltzer, Nadine Spielmann

Faculty Research 2026

Heart weight (HW) is a critical parameter in cardiology and mouse research, commonly normalized to body weight (BW) or tibia length (TL) to account for size differences. Ratio-based normalization, however, assumes strict proportionality between variables, an assumption that is rarely tested and may bias group comparisons. We analysed HW, BW, and TL measurements from over 25,000 C57BL/6N wildtype mice generated by the International Mouse Phenotyping Consortium. Sex- and age-stratified analyses were combined with simulation-based modelling to evaluate empirical scaling relationships and the statistical behaviour of ratio-based normalization. Across all age and sex groups, correlations between HW, BW, and TL were …

Avian Influenza Preparedness In Ghana: A Cross-Sectional Assessment Of Knowledge, Attitudes, And Practices Among Residents Of Nsawam-Adoagyiri Municipality, Eastern Region, Christopher Yaw Dumevi, George Boateng Kyei, Et Al.

2020-Current year OA Pubs

BACKGROUND: Avian influenza (AI) represents a persistent threat to public health, food security, and livelihoods in Ghana, where outbreaks of H5N1 and H9N2 have occurred. This cross-sectional study evaluated the knowledge, attitudes, and practices (KAP) related to avian influenza among residents of the Nsawam-Adoagyiri Municipality; an area characterized by intensive poultry production with the aim of delineating deficits in community-level preparedness and guiding evidence-based public health interventions. METHODS: A community-based cross-sectional study was conducted from May to July 2025 using a four-stage sampling technique. We surveyed 321 adults via structured questionnaires, evaluating socio-demographics and KAP related to AI. Scale reliability …

Fungal Meningitis In Us Patients Who Received Epidural Anesthesia In Matamoros, Mexico, Dallas J Smith, Elizabeth Misas, Jeremy A W Gold, Nicole Evert, Thi Dang, Emilie Prot, Simone Godwin, Julieanna Rivas, Jessica Pearson, Lori Koenecke, Nirma D Bustamante, Maria Julia Marinissen, Gabriel Garcia Rodriquez, Irma López-Martínez, Caitlyn Lutfy, Samantha Williams, Axel A Vazquez Deida, Katrina M Byrd, Julian A Villalba, Sarah Reagan-Steiner, Lindsay Parnell, Lalitha Gade, Romney M Humphries, Nathan P Wiederhold, Charles Y Chiu, Joshua A Lieberman, Anastasia P Litvintseva, Tom Chiller, Luis Ostrosky-Zeichner, Fungal Meningitis Response Team

Faculty, Staff and Student Publications

Background: Fungal meningitis outbreaks are rare and entail high mortality rates. Beginning May 2023, we investigated fungal meningitis caused by Fusarium solani species complex occurring in US patients who received epidural anesthesia in Matamoros, Mexico.

Methods: Early epidemiological information suggested US patients with suspected fungal meningitis had undergone mostly cosmetic procedures under epidural anesthesia performed in 2 Matamoros clinics. US patients known to have received surgery at these clinics during 1 January-13 May 2023 (clinic closures date) were identified and notified by public health officials. Epidemiological and clinical data were used to update diagnostic and clinical guidance for outbreak response, …

Short-Term Sleep Restriction In Humans Alters Diurnal Circulating Metabolite Profiles, Including Those Of Microbial Origin., Vanessa A Leone, Katya Frazier, Manpreet Kaur, Evan A Chrisler, Ashley M Sidebottom, Ethan Tai, Vilinh Tran, Shuzhao Li, Eugene B Chang, Dean P Jones, Eve Van Cauter, Erin C Hanlon

Faculty Research 2026

BACKGROUND. Gut microbes and their metabolites contribute to the host circulating metabolome and exhibit diurnal variation influenced by sleep-wake cycles and meal timing. Sleep deprivation alters the rhythmic circulating metabolome, but its impact on microbial metabolites remains unclear. We tested whether 24-hour circulating metabolite profiles, including those of microbial origin, differ under normal (habitual) versus short-term restricted sleep.

METHODS. In a randomized crossover design, 9 healthy adults completed 2 in-lab 24-hour blood sampling sessions (q120): one following 3 nights of normal sleep (8.5 hours/night), the other following 3 nights of sleep restriction (4.5 hours/night). Meal timing and caloric intake were …

Short-Term Sleep Restriction In Humans Alters Diurnal Circulating Metabolite Profiles, Including Those Of Microbial Origin., Vanessa A Leone, Katya Frazier, Manpreet Kaur, Evan A Chrisler, Ashley M Sidebottom, Ethan Tai, Vilinh Tran, Shuzhao Li, Eugene B Chang, Dean P Jones, Eve Van Cauter, Erin C Hanlon

Faculty Research 2026

BACKGROUNDGut microbes and their metabolites contribute to the host circulating metabolome and exhibit diurnal variation influenced by sleep-wake cycles and meal timing. Sleep deprivation alters the rhythmic circulating metabolome, but its impact on microbial metabolites remains unclear. We tested whether 24-hour circulating metabolite profiles, including those of microbial origin, differ under normal (habitual) versus short-term restricted sleep.METHODSIn a randomized crossover design, 9 healthy adults completed 2 in-lab 24-hour blood sampling sessions (q120): one following 3 nights of normal sleep (8.5 hours/night), the other following 3 nights of sleep restriction (4.5 hours/night). Meal timing and caloric intake were held constant. Serum …

Glycative Stress Disrupts The Mitochondrial-Lysosome Axis And Promotes Geroconversion In Aging Cardiomyocytes, Diana Bou-Teen, Simonas Valiuska, Elisabet Miro-Casas, Chiara Rubeo, Elena Bonzon-Kulichenko, Zuzana Nichtova, Celia Fernandez-Sanz, Javier Inserte, Antonio Rodriguez-Sinovas, Begoña Benito, Eduard Ródenas-Alesina, Jesús Vázquez, Ignacio Ferreira-González, Marisol Ruiz-Meana

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Aging is a major risk factor for heart failure, yet the molecular mechanisms linking cardiac aging to the inflammatory pathophysiology of heart failure remain elusive. Mitochondrial dysfunction and defective organelle quality control are emerging hallmarks of the aging heart, but their biochemical underpinnings are poorly defined. Using comprehensive glycomics, we found that cardiac mitochondria from physiologically aged mice (≥ 20 months) are the major intracellular reservoirs of advanced glycation end products (AGEs), derived primarily from the chemical attack of some α-oxoaldehydes on proteins. This was associated with mild mitochondrial dysfunction and structural remodeling. Lysosomes in aged hearts were enlarged, more …

Megakaryocyte And Platelet Thrombospondin-1 Regulates Matrix Remodeling By Stabilizing Basement Membrane Col6a1 In Lung Injury, Hernán F Peñaloza, Atish Gheware, Ananya Gupta, Donovan Watza, Anupam Kumari, Zeyu Xiong, Pooja Bhojraj, Jae-Sung Kim, Bo-Ram Jin, Kyunghee Choi, Matthew R Rosengart, Jaehyung Cho, Janet S Lee, Et Al.

2020-Current year OA Pubs

An early event after lung injury is extracellular matrix (ECM) remodeling and the formation of a provisional matrix. While megakaryocytes and platelets (Mgk/plt) play important roles in hemostasis, their impact on the matrix in lung injury is not fully understood. Using lung intravital microscopy, 3D large area scanning with multiphoton confocal hybrid imaging, and label-free quantitative proteomics, the matricellular protein thrombospondin-1 (TSP1) arising from Mgk/plt protects the lung from alveolar injury. Mgk/plt cell-specific Thbs1 knockout (cKO) mice show increased alveolar barrier disruption with exaggerated neutrophil-mediated injury. The cKO mice exhibit striking extracellular matrix re-organization with reduction in basement membrane matrix …

Genetic Architecture Of The Murine Red Blood Cell Proteome Reveals Central Role Of Hemoglobin Beta Cysteine 93 In Maintaining Redox Balance., Gregory R Keele, Monika Dzieciatkowska, Ariel M Hay, Matthew Vincent, Callan O'Connor, Daniel Stephenson, Julie A Reisz, Travis Nemkov, Kirk C Hansen, Grier P Page, James C Zimring, Gary Churchill, Angelo D'Alessandro

Faculty Research 2026

Red blood cells (RBCs) transport oxygen but accumulate oxidative damage over time, reducing function in vivo and during storage, critical for transfusions. To explore the genetics of RBC resilience, we profiled proteins, metabolites, and lipids from fresh and stored RBCs from 350 genetically diverse mice. Our analysis identified over 6,000 quantitative trait loci (QTLs). Compared to other tissues, the prevalence of trans genetic effects over cis ones reflects the absence of de novo protein synthesis in anucleated RBCs. QTL hotspots at Hbb, Hba, Mon1a, and (storage-specific) Steap3 linked ferroptosis to hemolysis. Proteasome QTLs clustered at multiple loci, underscoring the importance …

Genetic Architecture Of The Murine Red Blood Cell Proteome Reveals Central Role Of Hemoglobin Beta Cysteine 93 In Maintaining Redox Balance., Gregory R Keele, Monika Dzieciatkowska, Ariel M Hay, Matthew Vincent, Callan O'Connor, Daniel Stephenson, Julie A Reisz, Travis Nemkov, Kirk C Hansen, Grier P Page, James C Zimring, Gary Churchill, Angelo D'Alessandro

Faculty Research 2026

Red blood cells (RBCs) transport oxygen but accumulate oxidative damage over time, reducing function in vivo and during storage, critical for transfusions. To explore the genetics of RBC resilience, we profiled proteins, metabolites, and lipids from fresh and stored RBCs from 350 genetically diverse mice. Our analysis identified over 6,000 quantitative trait loci (QTLs). Compared to other tissues, the prevalence of trans genetic effects over cis ones reflects the absence of de novo protein synthesis in anucleated RBCs. QTL hotspots at Hbb, Hba, Mon1a, and (storage-specific) Steap3 linked ferroptosis to hemolysis. Proteasome QTLs clustered at multiple loci, underscoring the importance …

Bi-Allelic Variants In Nrdc Cause A Neurodevelopmental Disorder Characterized By Neonatal Lethality, Microcephaly, And Brain Abnormalities, Davut Pehlivan, Abigail Sandoval, Reza Maroofian, François Lecoquierre, Aisha M Al Shamsi, Gyu S Lee, Osman Yesilbas, Preston Taylor, Matthew B Mcdougal, Vahid Bahrambeigi, Omid Aryani, Juan Felipe Ramirez, Khalid Hama Salih, Chadi Al Alam, Heba Morsy, Haytham Hussien, Tarek Omar, Ibrahim M Abdelrazek, Anne Claire Brehin, Dana Marafi, Tugba Kalayci, Jubran Abu Rahma, Jawabreh Kassem Talbeya, Husein Dabbah, Eric Verspyck, Toktam Moosavian, Jawid M Fatih, Tadahiro Mitani, Gulsen Akay, Daniel G Calame, Anne-Marie Guerrot, Wendy K Chung, Henry Houlden, James R Lupski, Adel Shalata, Wan Hee Yoon

Faculty, Staff and Students Publications

Nardilysin (NRDC) plays a role in multiple cellular functions in diverse cellular compartments, including ectodomain shedding in the plasma membrane, as well as chaperoning a key Krebs cycle enzyme in mitochondria. We had previously reported limited clinical information from two individuals with homozygous frameshift variants in NRDC. With inclusion of previously published individuals, here we report 14 individuals (10 females, four males) from nine unrelated families carrying homozygous NRDC pathogenic variants. Common clinical features include severe to profound developmental delay/intellectual disability (12/12), microcephaly (13/13), prematurity (5/13), lethality in the first 3 years of life (9/14), seizures (7/11), joint contractures (4/8), …

Glucagon-Like Peptide-1 Receptor Agonists And Risk Of Substance Use Disorders Among Us Veterans With Type 2 Diabetes: Cohort Study, Miao Cai, Taeyoung Choi, Yan Xie, Ziyad Al-Aly

2020-Current year OA Pubs

OBJECTIVES: To investigate whether initiation of glucagon-like peptide-1 (GLP-1) receptor agonists is associated with both reduced risks of incident alcohol, cannabis, cocaine, nicotine, opioid, and other substance use disorders (SUDs) in people with no history of SUDs (protocol 1) and with reduced risk of SUD related adverse clinical outcomes among people with a pre-existing SUD (protocol 2).

DESIGN: Emulation of eight parallel, new user, active comparator target trials using electronic health records: seven trials for each incident SUD outcome (protocol 1) and one trial for adverse outcomes in people with pre-existing SUD (protocol 2).

SETTING: US Department of Veterans Affairs. …

Sickle Cell Visualization In Vivo In Humans: Microvascular Occlusion Formation And Hemorheological Indices, Marisa M Morakis, Luojie Huang, Gregory N. Mckay, Sophie Lanzkron, Lydia H. Pecker, Nicholas J. Durr

Cardeza Foundation for Hematologic Research

Vaso-occlusion is a signature pathology of sickle cell disease (SCD). However, the lack of in vivo methods to observe individual blood cell dynamics in humans limits our understanding of occlusion formation mechanisms. We present a novel in vivo, noninvasive, label-free, and high-resolution imaging technique to study blood flow and sickled cell behavior in affected individuals. We used oblique back-illumination microscopy (OBM) to capture videos of 91.0 ± 42.3 sublingual capillaries in each of 10 participants with SCD before and after red cell transfusions and compared the measurements to 10 unaffected controls. With direct observation of blood cell activity, we identified …

Circulating Ketone Bodies And Incident Cardiovascular Outcomes And Mortality: Insights From The Uk Biobank, Parag Anilkumar Chevli, Saeid Mirzai, Richard Kazibwe, Jeff Kingsley, Alexis C Wood, Joseph Yeboah, Leandro Slipczuk, Anurag Mehta, Harpreet S Bhatia, Ambarish Pandey, Michael D Shapiro

Children’s Nutrition Research Center Staff Publications

Background: Ketone bodies (KB) are endogenous energy sources synthesized by the liver in response to metabolic stress. Their associations with atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and mortality and their potential beneficial or harmful effects have yet to be determined. This study aimed to examine the association between KB and incident cardiovascular outcomes and mortality in a large general population cohort free from ASCVD and HF at baseline.

Methods: This analysis included 90 987 participants (mean age 56.4 ± 8.1 years; 54.7% women) from the UK Biobank without prevalent ASCVD or HF. KB were measured by nuclear magnetic resonance …

Ifn Signaling Is Associated With Radiotherapy Response In Malignant Peripheral Nerve Sheath Tumors., Iowis Zhu, Julian Chien, Gabriel E Rech, Kanish Mirchia, Sixuan Pan, Kaeli Miller, Joanna Pak, Rosanna Wustrack, Varun Monga, Steve E Braunstein, Mark D Adams, Line Jacques, Melike Pekmezci, S John Liu, Harish N Vasudevan

Faculty Research 2026

Patients with malignant peripheral nerve sheath tumors (MPNSTs) have poor outcomes despite multimodal treatment with surgery, radiation, and systemic therapy. The responses to radiotherapy (RT) are mixed, and the biologic mechanisms underlying this heterogeneity in the radiation response of MPNSTs are not understood. Here, we combined bulk and single-cell transcriptomics, genome-wide CRISPR interference screens, and multiplatform molecular analysis across MPNST cells, mouse allograft models, and patients' samples to understand the mediators of the radiation response. Our data revealed that MPNSTs, but not benign plexiform neurofibromas, induced a type I IFN signature that functionally mediated the radiation response. Moreover, irradiation of …

Ectopic B Lymphocyte Follicles Exacerbate Ischemic Brain Damage Via Mif-Cd74/Cxcr4 And Interferon Signaling, Sheng Yang, Hang Zhang, Lu-Lu Xu, Luo-Qi Zhou, Yun-Hui Chu, Lian Chen, Xiao-Wei Pang, Lu-Yang Zhang, Li-Fang Zhu, Ming-Hao Dong, Ke Shang, Jun Xiao, Long-Jun Wu, Wei Wang, Dai-Shi Tian, Chuan Qin

Faculty, Staff and Student Publications

Neuroinflammation, encompassing both innate and adaptive immune responses, plays a crucial role in ischemic stroke. Although B lymphocytes are central to adaptive immunity, their contributions to ischemic stroke remain poorly understood. Here, we demonstrated that B lymphocytes accumulate in ischemic lesions, forming germinal center-like structures at the later stage after stroke, which mainly depended on in situ proliferation. This accumulation correlated with worsened neuroinflammation and ischemic injury, whereas B cell depletion reduced chronic brain damage during stroke. Mechanistically, microglia recruited B cells into ischemic lesions through MIF-CD74/CXCR4 signaling during the early phase of stroke, while IFN-related pathways in B cells …

Poly(Adp-Ribose) Glycohydrolase Enforces P21 Degradation Via Deparylation To Promote Gastric Cancer Progression, Yangchan Hu, Qimei Bao, Yixing Huang, Yan Wang, Xin Zhao, Junjun Nan, Yuxin Meng, Mingcong Deng, Yuancong Li, Zirui Zhuang, Hanyi He, Dan Zu, Yuke Zhong, Chunkai Zhang, Bing Wang, Ran Li, Yanhua He, Qihan Wang, Min Liu, John A Tainer, Yin Shi, Xiangdong Cheng, Ji Jing, Zu Ye

Faculty, Staff and Student Publications

Dysregulation of cell cycle checkpoints is a cancer hallmark, with ubiquitination-controlled protein stability playing a pivotal role. Although p21, a key cyclin-dependent kinase inhibitor, is tightly regulated by ubiquitin-mediated degradation, the key upstream modulators of its ubiquitination remain incompletely defined. Here, we identify poly(ADP-ribose) glycohydrolase (PARG) as a regulator of p21 stability in gastric cancer (GC) cells. We show that PARG expression is markedly upregulated in GC tissues and correlates with poor patient prognosis. Functional assays revealed that genetic depletion of PARG triggers G2/M phase arrest and impairs GC cell proliferation. Mechanistically, we demonstrate that PARG loss enhances p21 PARylation, …

Aging Reduces Motivation Through Decreased Bdnf Expression In The Ventral Tegmental Area, Hanyue Cecilia Lei, Kyle E Parker, Chao-Cheng Kuo, Carla M Yuede, Jordan G Mccall, Shin-Ichiro Imai

2020-Current year OA Pubs

Age-associated reduced motivation is a hallmark of neuropsychiatric disorders in the elderly. In our rapidly aging societies, it is critical to keep motivation levels high enough to promote healthspan and lifespan. However, how motivation is reduced during aging remains unknown. Here, we used multiple mouse models to evaluate motivation and related affective states in young and old mice. We also compared the effect of social isolation, a common stressor in aged populations, to those of aging. We found that both social isolation and aging decreased motivation in mice, but that Bdnf expression in the ventral tegmental area (VTA) was selectively …

Pre- And Postnatal Exposure To Pm2.5 And No2 And Blood Pressure In Children: Results From The Echo Cohort, Yu Ni, Andrew Law, Xingyu Gao, Adam A Szpiro, Christine T Loftus, Miranda Jones, Logan C Dearborn, Marnie F Hazlehurst, Allison R Sherris, Sindana Ilango, Kaja Z Lewinn, Nicole R Bush, Qi Zhao, Leonardo Trasande, Joseph T Flynn, Daniel A Enquobahrie, Ruby H N Nguyen, Tom O'Connor, Arpita K Vyas, Mingyu Zhang, Hooman Mirzakhani, Alison Hipwell, Anne Starling, Alicia K Peterson, Akhgar Ghassabian, Assiamira Ferrara, Judy Aschner, Scott Collingwood, Margaret R Karagas, Michelle Katzow, Annemarie Stroustrup, Mehtap Haktnair, Tina V Hartert, Brittney M Snyder, Sophia Jan, Anne Marie Singh, Dana Dabelea, Angela M Malek, Jennifer K Straughen, Carlos A Camargo, Miatta A Buxton, Rosalind Wright, Kecia Carroll, Keia Sanderson, Daphne Koinis Mitchell, Viren D'Sa, Christine Hockett, Anne L Dunlop, Shohreh F Farzen, Sunni L Mumford, Akram N Alshawabkeh, Hudson P Santos, Xueying Zhang, Zhongzheng Niu, Nan Ji, Carrie Breton, Donghai Liang, Catherine J Karr, Echo Cohort Consortium

Children’s Nutrition Research Center Staff Publications

Background: There is growing interest in understanding the link between early life exposures to ambient air pollution and childhood blood pressure; however, existing findings, largely from single site/cohort studies, are inconclusive.

Methods: We examined the association between exposures to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) and blood pressure measured at age 5-12 years in 4863 U.S. children from 20 pregnancy cohorts of the NIH ECHO cohort. Point-based residential exposures were derived from spatiotemporal models with a biweekly resolution and averaged over each trimester, the whole pregnancy, and child age 0-2 years. We converted systolic (SBP) and diastolic blood …

Glutamatergic Dysfunction Of Astrocytes In Paraventricular Nucleus Of Thalamus Contributes To Adult Anxiety Susceptibility In Adolescent Ethanol Exposed Mice, Aubrey Bennett, Hyunjung Kim, David Thomas, Peter Biggs, Roxan Ara, Asamoah Bosomtwi, Seungwoo Kang

The Brown Foundation: Institute of Molecular Medicine

Repeated ethanol exposure during adolescence increases adult anxiety risk, but the underlying mechanisms remain unclear. The paraventricular nucleus of the thalamus (PVT) has been considered a hub for controlling anxiety and is affected by experiences from early life. Thus, this study investigated how adolescent intermittent repeated ethanol exposure (AIE) affects the PVT activities and anxiety-related behaviors in adulthood. We found that AIE triggers anxiety-like behaviors and parallelly exhibited elevated firing rates and increased calcium signaling in the PVT neurons compared to control counterpart mice. Chemogenetic inhibition of PVT neurons reduced anxiety-like behaviors in AIE-treated animals, confirming PVT's role in adolescent …

Unilateral Online Ultrasound Stimulation Of Early Visual Cortex Suppresses Responses To Contralateral Visual Stimuli, Suraya Dunsford, Keith Murphy, Ema Darrieutort, Elsa Fouragnan, Giorgio Ganis

School of Psychology

INTRODUCTION: Transcranial ultrasound stimulation (TUS) shows great promise for inducing neuroplastic changes that persist long after stimulation. Evidence of stimulation-locked (online) neural changes would enable the development of closed-loop application of TUS. However, such responses have been difficult to distinguish from coincident neural activity caused by auditory and somatosensory effects of TUS.

METHODS: To dissociate genuine online neuromodulatory effects from peripheral confounds, we leveraged the contralateral retinotopic organization of the early visual cortex in nineteen subjects. Using a hemifield visual stimulation paradigm combined with high-precision, functional MRI-guided TUS, we applied TUS to the left early visual cortex while participants viewed …

Alpha 7 Nicotinic Acetylcholine Receptor Contributes To Long-Term Cognitive Recovery Following Ischemic Stroke, Dustin T Nguyen, Kate Mendoza, Cassandra Hall, Chunfeng Tan, Anjali Chauhan

Faculty, Staff and Student Publications

Stroke is associated with autonomic dysfunction and reduced acetylcholine (ACh), a neurotransmitter critical for cognition. ACh signals in part through the alpha-7 nicotinic acetylcholine receptor (α7nAChR), a ligand-gated ion channel involved in synaptic plasticity, learning, and memory. Impaired α7nAChR signaling has been linked to heightened neuroinflammation and poor acute stroke recovery. Here, we investigated whether α7nAChR contributes to post-stroke cognitive recovery in young male mice. Wild-type (WT) and α7nAChR knockout (α7n0KO) mice underwent 60-min middle cerebral artery occlusion (MCAO). In a pharmacology cohort, the α7nAChR agonist GTS-21 was administered immediately after reperfusion and then daily for 20 days. Cognitive performance …

Selective Deletion Of Fgfr1 In Agrp Neurons Impairs Energy Homeostasis Under High-Fat Diet In Mice, Daniel Shookster, Shea O'Connell, Patel Darshan, Taylor Landry, Wyatt Bunner, Zhiying Jiang, Qingchun Tong, Hu Huang

Faculty, Staff and Student Publications

Background: The global obesity crisis and the limited success of current treatments underscore the need to identify novel regulatory pathways. While central administration of α-Klotho exerts anti-obesity effects in rodents through AgRP neurons, the intracellular signaling mechanisms that mediate this process remain undefined.

Methods: To define the role of FGFR1 within the α-Klotho signaling pathway in AgRP neurons, we performed a targeted deletion of the receptor in adult mice using an AAV-mediated CRISPR/Cas9 system alongside transgenic models.

Results: Deletion of FGFR1 in AgRP neurons disrupted energy homeostasis, promoting weight gain induced by a high-fat diet. Electrophysiological recordings revealed that FGFR1 …