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Full-Text Articles in Life Sciences

In Vivo Clonal Expansion And Phenotypes Of Hypocretin-Specific Cd4(+) T Cells In Narcolepsy Patients And Controls, Wei Jiang, James R. Birtley, Grant C. Weaver, Liying Lu, Lawrence J. Stern, Elizabeth D. Mellins Nov 2019

In Vivo Clonal Expansion And Phenotypes Of Hypocretin-Specific Cd4(+) T Cells In Narcolepsy Patients And Controls, Wei Jiang, James R. Birtley, Grant C. Weaver, Liying Lu, Lawrence J. Stern, Elizabeth D. Mellins

Open Access Articles

Individuals with narcolepsy suffer from abnormal sleep patterns due to loss of neurons that uniquely supply hypocretin (HCRT). Previous studies found associations of narcolepsy with the human leukocyte antigen (HLA)-DQ6 allele and T-cell receptor alpha (TRA) J24 gene segment and also suggested that in vitro-stimulated T cells can target HCRT. Here, we present evidence of in vivo expansion of DQ6-HCRT tetramer(+)/TRAJ24(+)/CD4(+) T cells in DQ6(+) individuals with and without narcolepsy. We identify related TRAJ24(+) TCRalphabeta clonotypes encoded by identical alpha/beta gene regions from two patients and two controls. TRAJ24-G allele(+) clonotypes only expand in the two ...


A Big-Data Approach To Understanding Metabolic Rate And Response To Obesity In Laboratory Mice, June K. Corrigan, Deepti Ramachandran, Yuchen He, Colin Palmer, Michael J. Jurczak, Bingshan Li, Randall H. Friedline, Jason K. Kim, Jon J. Ramsey, Louise Lantier, Owen P. Mcguinness, Alexander S. Banks, Mouse Metabolic Phenotyping Center Energy Balance Working Group Nov 2019

A Big-Data Approach To Understanding Metabolic Rate And Response To Obesity In Laboratory Mice, June K. Corrigan, Deepti Ramachandran, Yuchen He, Colin Palmer, Michael J. Jurczak, Bingshan Li, Randall H. Friedline, Jason K. Kim, Jon J. Ramsey, Louise Lantier, Owen P. Mcguinness, Alexander S. Banks, Mouse Metabolic Phenotyping Center Energy Balance Working Group

University of Massachusetts Medical School Faculty Publications

Maintaining a healthy body weight requires an exquisite balance between energy intake and energy expenditure. In humans and in laboratory mice these factors are experimentally measured by powerful and sensitive indirect calorimetry devices. To understand the genetic and environmental factors that contribute to the regulation of body weight, an important first step is to establish the normal range of metabolic values and primary sources contributing to variability in results. Here we examine indirect calorimetry results from two experimental mouse projects, the Mouse Metabolic Phenotyping Centers and International Mouse Phenotyping Consortium to develop insights into large-scale trends in mammalian metabolism. Analysis ...


Coronary Disease Is Not Associated With Robust Alterations In Inflammatory Gene Expression In Human Epicardial Fat, Timothy P. Fitzgibbons, Nancy Lee, Khanh-Van T. Tran, Sarah M. Nicoloro, Mark Kelly, Stanley Kc Tam, Michael P. Czech Oct 2019

Coronary Disease Is Not Associated With Robust Alterations In Inflammatory Gene Expression In Human Epicardial Fat, Timothy P. Fitzgibbons, Nancy Lee, Khanh-Van T. Tran, Sarah M. Nicoloro, Mark Kelly, Stanley Kc Tam, Michael P. Czech

Open Access Articles

Epicardial adipose tissue (EAT) is the visceral fat depot of the heart. Inflammation of EAT is thought to contribute to coronary artery disease (CAD). Therefore, we hypothesized that the EAT of patients with CAD would have increased inflammatory gene expression compared with controls without CAD. Cardiac surgery patients with (n = 13) or without CAD (n = 13) were consented, and samples of EAT and subcutaneous adipose tissue (SAT) were obtained. Transcriptomic analysis was performed using Affymetrix Human Gene 1.0 ST arrays. Differential expression was defined as a 1.5-fold change (ANOVA P < 0.05). Six hundred ninety-three genes were differentially expressed between SAT and EAT in controls and 805 in cases. Expression of 326 genes was different between EAT of cases and controls; expression of 14 genes was increased in cases, while 312 were increased in controls. Quantitative reverse transcription PCR confirmed that there was no difference in expression of CCL2, CCR2, TNF-alpha, IL-6, IL-8, and PAI1 between groups. Immunohistochemistry showed more macrophages in EAT than SAT, but there was no difference in their number or activation state between groups. In contrast to prior studies, we did not find increased inflammatory gene expression in the EAT of patients with CAD. We conclude that the specific adipose tissue depot, rather than CAD status, is responsible for the majority of differential gene expression.


Memory Cd4 T Cell-Derived Il-2 Synergizes With Viral Infection To Exacerbate Lung Inflammation, K. Kai Mckinstry, Fahmida Alam, Valeria Flores-Malavet, Mate Z. Nagy, Stewart Sell, Andrea M. Cooper, Susan L. Swain, Tara M. Strutt Aug 2019

Memory Cd4 T Cell-Derived Il-2 Synergizes With Viral Infection To Exacerbate Lung Inflammation, K. Kai Mckinstry, Fahmida Alam, Valeria Flores-Malavet, Mate Z. Nagy, Stewart Sell, Andrea M. Cooper, Susan L. Swain, Tara M. Strutt

Open Access Articles

Defining the most penetrating correlates of protective memory T cells is key for designing improved vaccines and T cell therapies. Here, we evaluate how interleukin (IL-2) production by memory CD4 T cells, a widely held indicator of their protective potential, impacts immune responses against murine influenza A virus (IAV). Unexpectedly, we show that IL-2-deficient memory CD4 T cells are more effective on a per cell basis at combating IAV than wild-type memory cells that produce IL-2. Improved outcomes orchestrated by IL-2-deficient cells include reduced weight loss and improved respiratory function that correlate with reduced levels of a broad array of ...


Reducing Sugary Drink Intake Through Youth Empowerment: Results From A Pilot-Site Randomized Study, Monica L. Wang, Marisa Otis, Milagros C. Rosal, Christina F. Griecci, Stephenie C. Lemon Jul 2019

Reducing Sugary Drink Intake Through Youth Empowerment: Results From A Pilot-Site Randomized Study, Monica L. Wang, Marisa Otis, Milagros C. Rosal, Christina F. Griecci, Stephenie C. Lemon

Open Access Articles

BACKGROUND: Efficacious strategies to reduce sugar-sweetened beverage (SSB) consumption among youth are needed. This pilot study assessed the feasibility and preliminary efficacy of a community-based youth empowerment intervention to reduce SSB consumption and obesity risk among a low-income, ethnically diverse sample of youth.

METHODS: The H2GO! intervention was pilot-tested in an afterschool setting (Boys and Girls Clubs (BGC)) in Massachusetts, USA. One site was randomized to receive the intervention; the other site received standard programming. Youth ages 9-12 years and their parents/caregivers were eligible to participate. A total of N = 110 parent-child pairs (N = 55 parent-child pairs per site ...


A Permethrin Metabolite Is Associated With Adaptive Immune Responses In Gulf War Illness, Utsav Joshi, Lawrence J. Stern, Laila Abdullah Jul 2019

A Permethrin Metabolite Is Associated With Adaptive Immune Responses In Gulf War Illness, Utsav Joshi, Lawrence J. Stern, Laila Abdullah

Open Access Articles

Gulf War Illness (GWI), affecting 30% of veterans from the 1991 Gulf War (GW), is a multi-symptom illness with features similar to those of patients with autoimmune diseases. The objective of the current work is to determine if exposure to GW-related pesticides, such as permethrin (PER), activates peripheral and central nervous system (CNS) adaptive immune responses. In the current study, we focused on a PER metabolite, 3-phenoxybenzoic acid (3-PBA), as this is a common metabolite previously shown to form adducts with endogenous proteins. We observed the presence of 3-PBA and 3-PBA modified lysine of protein peptides in the brain, blood ...


A Receptor Of The Immunoglobulin Superfamily Regulates Adaptive Thermogenesis, Carmen Hurtado Del Pozo, Randall H. Friedline, Hye Lim Noh, Jason K. Kim, Ann Marie. Schmidt Jul 2019

A Receptor Of The Immunoglobulin Superfamily Regulates Adaptive Thermogenesis, Carmen Hurtado Del Pozo, Randall H. Friedline, Hye Lim Noh, Jason K. Kim, Ann Marie. Schmidt

Open Access Articles

Exquisite regulation of energy homeostasis protects from nutrient deprivation but causes metabolic dysfunction upon nutrient excess. In human and murine adipose tissue, the accumulation of ligands of the receptor for advanced glycation end products (RAGE) accompanies obesity, implicating this receptor in energy metabolism. Here, we demonstrate that mice bearing global- or adipocyte-specific deletion of Ager, the gene encoding RAGE, display superior metabolic recovery after fasting, a cold challenge, or high-fat feeding. The RAGE-dependent mechanisms were traced to suppression of protein kinase A (PKA)-mediated phosphorylation of its key targets, hormone-sensitive lipase and p38 mitogen-activated protein kinase, upon beta-adrenergic receptor stimulation-processes ...


Persistent Inflammation During Anti-Tuberculosis Treatment With Diabetes Comorbidity, Nathella Pavan Kumar, Kiyoshi F. Fukutani, Basavaradhya S. Shruthi, Thabata Alves, Paulo S. Silveira-Mattos, Michael S. Rocha, Kim West, Mohan Natarajan, Vijay Viswanathan, Subash Babu, Bruno B. Andrade, Hardy Kornfeld Jul 2019

Persistent Inflammation During Anti-Tuberculosis Treatment With Diabetes Comorbidity, Nathella Pavan Kumar, Kiyoshi F. Fukutani, Basavaradhya S. Shruthi, Thabata Alves, Paulo S. Silveira-Mattos, Michael S. Rocha, Kim West, Mohan Natarajan, Vijay Viswanathan, Subash Babu, Bruno B. Andrade, Hardy Kornfeld

Open Access Articles

Diabetes mellitus (DM) increases risk for pulmonary tuberculosis (TB) and adverse treatment outcomes. Systemic hyper-inflammation is characteristic in people with TB and concurrent DM (TBDM) at baseline, but the impact of TB treatment on this pattern has not been determined. We measured 17 plasma cytokines and growth factors in longitudinal cohorts of Indian and Brazilian pulmonary TB patients with or without DM. Principal component analysis revealed virtually complete separation of TBDM from TB individuals in both cohorts at baseline, with hyper-inflammation in TBDM that continued through treatment completion at six months. By one year after treatment completion, there was substantial ...


Mtorc2/Akt Activation In Adipocytes Is Required For Adipose Tissue Inflammation In Tuberculosis, Nuria Martinez, Catherine Y. Cheng, Natkunam Ketheesan, Aidan Cullen, Yuefeng Tang, Josephine Lum, Kim West, Michael Poidinger, David A. Guertin, Amit Singhal, Hardy Kornfeld Jul 2019

Mtorc2/Akt Activation In Adipocytes Is Required For Adipose Tissue Inflammation In Tuberculosis, Nuria Martinez, Catherine Y. Cheng, Natkunam Ketheesan, Aidan Cullen, Yuefeng Tang, Josephine Lum, Kim West, Michael Poidinger, David A. Guertin, Amit Singhal, Hardy Kornfeld

Open Access Articles

BACKGROUND: Mycobacterium tuberculosis has co-evolved with the human host, adapting to exploit the immune system for persistence and transmission. While immunity to tuberculosis (TB) has been intensively studied in the lung and lymphoid system, little is known about the participation of adipose tissues and non-immune cells in the host-pathogen interaction during this systemic disease.

METHODS: C57BL/6J mice were aerosol infected with M. tuberculosis Erdman and presence of the bacteria and the fitness of the white and brown adipose tissues, liver and skeletal muscle were studied compared to uninfected mice.

FINDINGS: M. tuberculosis infection in mice stimulated immune cell infiltration ...


Gene Expression Signature Of Atypical Breast Hyperplasia And Regulation By Sfrp1, Kelly J. Gregory, Giovanna M. Crisi, Brooke A. Bentley, Grace Makari-Judson, Holly S. Mason, Jun Yu, Lihua Julie Zhu, Karl J. Simin, Jacob P. S. Johnson, Ashraf Khan, Sallie S. Schneider, D. Joseph Jerry Jun 2019

Gene Expression Signature Of Atypical Breast Hyperplasia And Regulation By Sfrp1, Kelly J. Gregory, Giovanna M. Crisi, Brooke A. Bentley, Grace Makari-Judson, Holly S. Mason, Jun Yu, Lihua Julie Zhu, Karl J. Simin, Jacob P. S. Johnson, Ashraf Khan, Sallie S. Schneider, D. Joseph Jerry

Open Access Articles

BACKGROUND: Atypical breast hyperplasias (AH) have a 10-year risk of progression to invasive cancer estimated at 4-7%, with the overall risk of developing breast cancer increased by ~ 4-fold. AH lesions are estrogen receptor alpha positive (ERalpha+) and represent risk indicators and/or precursor lesions to low grade ERalpha+ tumors. Therefore, molecular profiles of AH lesions offer insights into the earliest changes in the breast epithelium, rendering it susceptible to oncogenic transformation.

METHODS: In this study, women were selected who were diagnosed with ductal or lobular AH, but no breast cancer prior to or within the 2-year follow-up. Paired AH and ...


The Influence Of Different Fat Sources On Steatohepatitis And Fibrosis Development In The Western Diet Mouse Model Of Non-Alcoholic Steatohepatitis (Nash), Hannah K. Drescher, Ralf Weiskirchen, Annabelle Fulop, Carsten Hopf, Estibaliz Gonzalez De San Roman, Pitter F. Huesgen, Alain De Bruin, Laura Bongiovanni, Anette Christ, Rene Tolba, Christian Trautwein, Daniela C. Kroy Jun 2019

The Influence Of Different Fat Sources On Steatohepatitis And Fibrosis Development In The Western Diet Mouse Model Of Non-Alcoholic Steatohepatitis (Nash), Hannah K. Drescher, Ralf Weiskirchen, Annabelle Fulop, Carsten Hopf, Estibaliz Gonzalez De San Roman, Pitter F. Huesgen, Alain De Bruin, Laura Bongiovanni, Anette Christ, Rene Tolba, Christian Trautwein, Daniela C. Kroy

Open Access Articles

Non-alcoholic steatohepatitis (NASH) is the leading cause of chronic liver injury and the third most common reason for liver transplantations in Western countries. It is unclear so far how different fat sources in Western diets (WD) influence the development of NASH. Our study investigates the impact of non-trans fat (NTF) and corn oil (Corn) as fat source in a WD mouse model of steatohepatitis on disease development and progression. C57BL/6J wildtype (WT) mice were fed "standard" WD (WD-Std), WD-NTF or WD-Corn for 24 weeks. WT animals treated with WD-NTF exhibit distinct features of the metabolic syndrome compared to WD-Std ...


Methodology Of An Exercise Intervention Program Using Social Incentives And Gamification For Obese Children, Yue Fang, Yunsheng Ma, Dandan Mo, Shunxing Zhang, Mi Xiang, Zhiruo Zhang Jun 2019

Methodology Of An Exercise Intervention Program Using Social Incentives And Gamification For Obese Children, Yue Fang, Yunsheng Ma, Dandan Mo, Shunxing Zhang, Mi Xiang, Zhiruo Zhang

Open Access Articles

BACKGROUND: Traditional exercise [supervised exercise (SE)] intervention has been proved to be one of the most effective ways to improve metabolic health. However, most exercise interventions were on a high-cost and small scale, moreover lacking of the long-term effect due to low engagement. On the other hand, it was noteworthy that gamification and social incentives were promising strategies to increase engagement and sustain exercise interventions effects; as well as mobile technologies such as WeChat also can provide an appropriate platform to deploy interventions on a broader, low-cost scale. Thus, we aim to develop a novel exercise intervention ('SandG exercise intervention ...


Dysfunction In Serotonergic And Noradrenergic Systems And Somatic Symptoms In Psychiatric Disorders, Yi Liu, Jingping Zhao, Xiaoduo Fan, Wenbin Guo May 2019

Dysfunction In Serotonergic And Noradrenergic Systems And Somatic Symptoms In Psychiatric Disorders, Yi Liu, Jingping Zhao, Xiaoduo Fan, Wenbin Guo

Open Access Articles

Somatic symptoms include a range of physical experiences, such as pain, muscle tension, body shaking, difficulty in breathing, heart palpitation, blushing, fatigue, and sweating. Somatic symptoms are common in major depressive disorder (MDD), anxiety disorders, and some other psychiatric disorders. However, the etiology of somatic symptoms remains unclear. Somatic symptoms could be a response to emotional distress in patients with those psychiatric conditions. Increasing evidence supports the role of aberrant serotoninergic and noradrenergic neurotransmission in somatic symptoms. The physiological alterations underlying diminished serotonin (5-HT) and norepinephrine (NE) signaling may contribute to impaired signal transduction, reduced 5-HT, or NE release from ...


Exercise Rescues Gene Pathways Involved In Vascular Expansion And Promotes Functional Angiogenesis In Subcutaneous White Adipose Tissue, So Yun Min, Heather Learnard, Shashi Kant, Olga Gaelikman, Raziel Rojas-Rodriguez, Tiffany Desouza, Anand Desai, John F. Keaney Jr., Silvia Corvera, Siobhan M. Craige Apr 2019

Exercise Rescues Gene Pathways Involved In Vascular Expansion And Promotes Functional Angiogenesis In Subcutaneous White Adipose Tissue, So Yun Min, Heather Learnard, Shashi Kant, Olga Gaelikman, Raziel Rojas-Rodriguez, Tiffany Desouza, Anand Desai, John F. Keaney Jr., Silvia Corvera, Siobhan M. Craige

Open Access Articles

Exercise mitigates chronic diseases such as diabetes, cardiovascular diseases, and obesity; however, the molecular mechanisms governing protection from these diseases are not completely understood. Here we demonstrate that exercise rescues metabolically compromised high fat diet (HFD) fed mice, and reprograms subcutaneous white adipose tissue (scWAT). Using transcriptomic profiling, scWAT was analyzed for HFD gene expression changes that were rescued by exercise. Gene networks involved in vascularization were identified as prominent targets of exercise, which led us to investigate the vasculature architecture and endothelial phenotype. Vascular density in scWAT was found to be compromised in HFD, and exercise rescued this defect ...


Gait Mechanics Contribute To Exercise Induced Pain Flares In Knee Osteoarthritis, Katherine A. Boyer, Jocelyn F. Hafer Mar 2019

Gait Mechanics Contribute To Exercise Induced Pain Flares In Knee Osteoarthritis, Katherine A. Boyer, Jocelyn F. Hafer

Open Access Articles

BACKGROUND: Exercise-induced pain flares represent a significant barrier for individuals with knee osteoarthritis to meet physical activity recommendations. There is a need to understand factors that contribute to pain flares and the potential for the motor system to adapt and reduce joint loading should a flare occur. The study aim was to examine the impact of a bout of exercise on self-reported pain, walking mechanics and muscle co-contraction for participants with knee osteoarthritis.

METHODS: Thirty-six adults (17 healthy older and 19 knee osteoarthritis) participated in this study. Self-reported pain, joint mechanics and muscle co-activation during gait at two self-selected speeds ...


The Neutrophil-To-Lymphocyte And Monocyte-To-Lymphocyte Ratios Are Independently Associated With Neurological Disability And Brain Atrophy In Multiple Sclerosis, Christopher C. Hemond, Bonnie I. Glanz, Rohit Bakshi, Tanuja Chitnis, Brian C. Healy Feb 2019

The Neutrophil-To-Lymphocyte And Monocyte-To-Lymphocyte Ratios Are Independently Associated With Neurological Disability And Brain Atrophy In Multiple Sclerosis, Christopher C. Hemond, Bonnie I. Glanz, Rohit Bakshi, Tanuja Chitnis, Brian C. Healy

Open Access Articles

BACKGROUND: Serum hematological indices such as the neutrophil-lymphocyte ratio (NLR) or monocyte-lymphocyte ratio (MLR) have been used as biomarkers of pathogenic inflammation and prognostication in multiple areas of medicine; recent evidence shows correlation with psychological parameters as well.

OBJECTIVES/AIMS: To characterize clinical, neuroimaging, and psycho-neuro-immunological associations with NLR and MLR in persons with multiple sclerosis (MS).

METHODS: We identified a large cohort of clinically well-defined patients from our longitudinal database that included MS-related outcomes, disease-modifying therapy, patient-reported outcome (PRO) measures, and quantified cerebral MRI at 1.5 T. We queried hospital records for complete blood counts within 2 months ...


Compartmentalization Of Immune Response And Microbial Translocation In Decompensated Cirrhosis, Camila Alvarez-Silva, Robert Schierwagen, Alessandra Pohlmann, Fernando Magdaleno, Frank E. Uschner, Patrick Ryan, Maria J.G.T. Vehreschild, Joan Claria, Eicke Latz, Benjamin Lelouvier, Manimozhiyan Arumugam, Jonel Trebicka Feb 2019

Compartmentalization Of Immune Response And Microbial Translocation In Decompensated Cirrhosis, Camila Alvarez-Silva, Robert Schierwagen, Alessandra Pohlmann, Fernando Magdaleno, Frank E. Uschner, Patrick Ryan, Maria J.G.T. Vehreschild, Joan Claria, Eicke Latz, Benjamin Lelouvier, Manimozhiyan Arumugam, Jonel Trebicka

Open Access Articles

Background: Acquired dysfunctional immunity in cirrhosis predisposes patients to frequent bacterial infections, especially spontaneous bacterial peritonitis (SBP), leading to systemic inflammation that is associated with poor outcome. But systemic inflammation can also be found in the absence of a confirmed infection. Detection of bacterial DNA has been investigated as a marker of SBP and as a predictor of prognosis. Data is, however, contradictory. Here we investigated whether levels of IL-6 and IL-8 putatively produced by myeloid cells in ascites are associated with systemic inflammation and whether inflammation depends on the presence of specific bacterial DNA.

Methods and Materials: We enrolled ...


Necroptosis In Anti-Viral Inflammation, Himani Nailwal, Francis Ka-Ming Chan Jan 2019

Necroptosis In Anti-Viral Inflammation, Himani Nailwal, Francis Ka-Ming Chan

Open Access Articles

The primary function of the immune system is to protect the host from invading pathogens. In response, microbial pathogens have developed various strategies to evade detection and destruction by the immune system. This tug-of-war between the host and the pathogen is a powerful force that shapes organismal evolution. Regulated cell death (RCD) is a host response that limits the reservoir for intracellular pathogens such as viruses. Since pathogen-specific T cell and B cell responses typically take several days and is therefore slow-developing, RCD of infected cells during the first few days of the infection is critical for organismal survival. This ...