2,796 Works

Maelstrom Represses Canonical RNA Polymerase II Transcription in Drosophila Dual-Strand piRNA Clusters

Timothy Chang
Transposons constitute much of the animal genome. While many transposons are ancient and inactivated, numerous others are intact and must be actively repressed. Uncontrolled transposons can cause genomic instability through DNA damage or mutations and must be carefully silenced in the germline or risk sterility or mutations that are passed on to offspring. In Drosophila melanogaster, 23–30 nt long piRNAs direct transposon silencing by serving as guides for Aubergine, Argonaute3, and Piwi, the three fly...

Ventricular Arrhythmias Complicating Coronary Artery Disease: Recent Trends, Risk Associated with Serum Glucose Levels, and Psychological Impact

Hoang Tran
Introduction: Ventricular arrhythmias (VAs) are common after an acute coronary syndrome (ACS) and are associated with worse clinical outcomes. However, little is known about recent trends in their occurrence, their association with serum glucose levels, and their psychological impact in ACS setting. Methods: We examined 25-year (1986-2011) trends in the incidence rates (IRs) and hospital case-fatality rates (CFRs) of VAs, and the association between serum glucose levels and VAs in patients with an acute myocardial...

Data from: Tobacco smoke exposure is an independent predictor of vitamin D deficiency in US children

Benjamin Nwosu & Philip Kum-Nji

Understanding Nuage-mitochondrial Coupling in Drosophila piRNA Biogenesis

Tianfang Ge
In the Drosophilaovary, PIWI-interacting RNAs (piRNAs) suppress transposon expression, ensuring female fertility. PIWI proteins Aub and Ago3, loaded with ping-pong piRNAs and reside in perinuclear nuage granules, engage in reciprocal transposon transcript cleavage termed the ping-pong cycle. The other PIWI protein Piwi, loaded with phased piRNAs and resides in the nucleus, silences transposon transcriptionally. Ping-pong piRNAs are made through the ping-pong amplification loop by Aub and Ago3, whereas phased piRNAs are made through consecutive endonucleolytic...

SERINC5: Its Sensitivity to Nef and Restriction of HIV-1

Weiwei Dai
The accessory protein Nef of human immunodeficiency virus type 1 (HIV-1) has long been known to enhance the infectivity of HIV-1 progeny virions. The multipass transmembrane proteins serine incorporator 3 (SERINC3) and SERINC5 were recently identified as novel antiviral proteins that restrict HIV-1 infectivity. Nef enhances HIV-1 infectivity by removing SERINCs from the plasma membrane, which prevents their incorporation into progeny HIV-1 virions. To exploit this potent intrinsic antiretroviral factor for potential therapy development, it...

Integrated Analysis of miRNA/mRNA Expression in the Neurocircuitry Underlying Nicotine Dependence

Alison Casserly
Nicotine dependence is responsible for perpetuating the adverse health effects due to tobacco use, the leading cause of preventable death worldwide. Nicotine is an agonist for nicotinic acetylcholine receptors, which are enriched in the mesocorticolimbic and habenulo-interpeduncular circuitries, underlying nicotine reward and withdrawal, respectively. Drugs of abuse, including nicotine, induce stable neuroadaptations, requiring protein synthesis through regulation of transcription factors, epigenetic mechanisms, and non-coding RNAs. It also been shown that miRNAs in brain are regulated...

PIE-1, SUMOylation, and Epigenetic Regulation of Germline Specification in Caenorhabditis elegans

In many organisms, the most fundamental event during embryogenesis is differentiating between germline cells and specialized somatic cells. In C. elegans, PIE-1 functions to protect the germline from somatic differentiation and appears to do so by blocking transcription and by preventing chromatin remodeling in the germline during early embryogenesis. Yet the molecular mechanisms by which PIE-1 specifies germline remain poorly understood. Our work shows that SUMOylation facilitates PIE-1-dependent germline maintenance and specification. In vivo SUMO...

An Examination of MHC, Peptide, and TCR Interactions

Peter Trenh
T cell receptors (TCR) bind to peptides from various sources on MHC (Major Histocompatibility Complex) molecules. A long-standing goal in the field is to understand the mechanisms of MHC-peptide exchange and MHC-TCR interactions. Here, I present work from three uniquely different systems that address the following: HLA-DR1 conformational stability, self-tolerant mechanisms of TCRs isolated from self-reactive TCR transgenic mice, and TCR cross-reactivity mechanisms between LCMV and VV. First, I present a crystal structure of HLA-DR1...

FUS and Excitotoxicity Cross Paths in ALS: New Insights into Cellular Stress and Disease

Maeve Tischbein
Amyotrophic lateral sclerosis (ALS) is an incurable and fatal neurodegenerative disease characterized by motor neuron loss. Although pathological mutations exist in >15 genes, the mechanism(s) underlying ALS are unknown. FUS is one such gene and encodes the nuclear RNA-binding protein (RBP), fused in sarcoma (FUS), which actively shuttles between the nucleus and cytoplasm. Intriguingly, nearly half of the ALS mutations identified in FUS cause this protein to mislocalize, suggesting that FUS localization is relevant to...

Posttargeting Events in Cotranslational Translocation Through the Sec61 Complex: a Thesis

Zhiliang Cheng

RIPPLiT and ChimeraTie: High throughput tools for understanding higher order RNP structures

Mihir Metkar
Even after their discovery more than 60 years ago, little is known about how messenger RNAs (mRNAs) are packaged inside the cells. To ensure efficient and accurate delivery of the intended message to its proper destination, it is important to package the informational molecule in a way that protects it from premature degradation but also proper decoding at the destination. However, very little is known about the this fundamentally important step of mRNA packaging inside...

Dissecting the Mechanism for the Selective Induction of Apoptosis in Transformed Cells by CAV Apoptin: a Dissertation

Destin W. Heilman

Functions of the Cdc14-Family Phosphatase Clp1p in the Cell Cycle Regulation of Schizosaccharomyces pombe: A Dissertation

Susanne Trautmann

A Biochemical Dissection of the RNA Interference Pathway in Drosophila melanogaster: A Dissertation

Benjamin Haley

Cloning and Cell Cycle Analysis of NuMA, a Phosphoprotein That Oscillates Between the Nucleus and the Mitotic Spindle

Cynthia A. Sparks

Mechanics of Fibroblast Migration: a Dissertation

Steven Munevar

The Power of Play: Increasing Physical Activity and Reducing Cardiometabolic Risk in Inner City Youth Using Novel Interactive Gaming

Laura L. Hayman
Dr. Hayman will present the design, methods and results of a recently completed pilot study, a randomized control trial, designed to increase moderate-to-vigorous-physical activity in 3rd to 5th grade children from an inner-citty public school. Lessons learned from this study that incorporated interactive gaming and was conducted at GoKids Boston, an interdisciplinary research, training and community outreach center located within UMass Boston, will be discussed. Emphasis will be placed on the promise and potential of...

Gene Expression and Profiling of Human Islet Cell Subtypes

David M. Blodgett, Susanne Pechhold & David M. Harlan
The endocrine pancreas contains multiple cell types co-localized into clusters called the islets of Langerhans. The predominant cell types include alpha and beta cells, which produce glucagon and insulin, respectively. The regulated release of these hormones maintains whole body glucose homeostasis, essential to prevent complications from diabetes (e.g. blindness, kidney failure, and cardiovascular disease). In type 1 diabetes, an autoimmune reaction destroys the beta cells and patients must monitor their blood sugar levels and inject...

Understanding the mechanisms of IGF2 gene regulation in hepatocellular carcinoma cells

Amalene Cooper-Morgan, Natalia Naumova, Amartya Sanyal, Bryan R. Lajoie, Job Dekker & Brian C. Lewis
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. HCC has a very well studied etiology, and is associated with chronic hepatic viral infections (hepatitis viruses B and C), alcohol abuse, or other causes of chronic liver damage. Currently, tumor resection and liver transplantation are the only potentially curative treatments available for HCC. However, the presence of extra-hepatic invasion and metastasis makes patients ineligible for these treatments. High IGF2 levels are associated with...

Predictors of Improved Pain, Quality of Life, and Physical Function after Surgical Treatment of Lumbar Spinal Stenosis

Natalie Egge, Anthony Lapinsky, Daniel Mandell, Jason C. Eck, Christian P. DiPaola, Jeffrey Lange, Patrick J. Connolly & Patricia D. Franklin
Introduction: Degenerative lumbar stenosis is common in adults and is frequently managed by surgical intervention after non-operative measures fail to relieve pain. Limited evidence-based information regarding optimal selection of patients for surgery exists. Current reform in healthcare policy has sparked significant interest in comparative effectiveness research with the goal of optimizing treatment strategies for common conditions such as degenerative lumbar stenosis. The purpose of this study is to quantify the effectiveness of surgical treatment of...

Development of an Electrowetting Valve in Capillary-Driven Microfluidic Biosensor for Nucleic Acid Detection

Fei He, Tiphaine Mérian, Julie M. Goddard & Sam R. Nugen
This article presents the development of microfluidic valves to be used in capillary flow microfluidic device as a platform for nucleic acid detection. The valve used the principle of electrowetting and was able to be actuated at low voltage. The valve consisted of two silver electrodes which were encountered in series within a microfluidic channel. The second electrode was modified with a hydrophobic monolayer resulting in a cessation of capillary flow. A potential of 4V...

Importance of clinically-refined medical and musculoskeletal co-morbidities in registries that evaluate patient-reported outcomes following TKR

Patricia D. Franklin, Wenjun Li, Carol Otis, Benjamin Snyder, Milagros C. Rosal & David C. Ayers
BACKGROUND: As national joint registries broaden their focus to include patient-reported outcomes, such as pain relief and functional gain, the role of confounding peri-operative complications and co-morbidities must be considered. We hypothesized that emotional, medical, and musculoskeletal co-morbidities influence post-surgical functional gain following primary total knee (TKR) replacement surgery. METHODS: We performed secondary analyses of comprehensive data from 180 primary TKR patients to evaluate the association of age, sex, body mass index (BMI), pre-operative emotional...

rAAV9 airway delivery results in effective knockdown of mutant alpha 1-antitrypsin in the liver while upregulating wildtype alpha 1-antitrypsin in the lung

Alisha Gruntman, Christian Mueller, Qiushi Tang, Lina Song, James M. Wilson, Terence R. Flotte & Maria P. Limberis
Alpha 1-Antitrypsin (AAT) deficiency is a human genetic disease resulting in the production of mutant AAT, a hepatocyte produced serine protease inhibitor that functions to prevent alveolar epithelial damage by inhibiting neutrophil elastase. Patients with AAT deficiency have increased lung disease, due to decreased proteolytic protection, as well as sporadic severe liver disease secondary to accumulation of mutant AAT, especially a common mutant form termed PiZ, within hepatocytes. We previously showed, in a PiZ mutant...

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