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Full-Text Articles in Life Sciences

The Snakeskin-Mesh Complex Of Smooth Septate Junction Restricts Yorkie To Regulate Intestinal Homeostasis In Drosophila, Hsi-Ju Chen, Qi Li, Niraj K. Nirala, Y. Tony Ip May 2020

The Snakeskin-Mesh Complex Of Smooth Septate Junction Restricts Yorkie To Regulate Intestinal Homeostasis In Drosophila, Hsi-Ju Chen, Qi Li, Niraj K. Nirala, Y. Tony Ip

Open Access Articles

Tight junctions in mammals and septate junctions in insects are essential for epithelial integrity. We show here that, in the Drosophila intestine, smooth septate junction proteins provide barrier and signaling functions. During an RNAi screen for genes that regulate adult midgut tissue growth, we found that loss of two smooth septate junction components, Snakeskin and Mesh, caused a hyperproliferation phenotype. By examining epitope-tagged endogenous Snakeskin and Mesh, we demonstrate that the two proteins are present in the cytoplasm of differentiating enteroblasts and in cytoplasm and septate junctions of mature enterocytes. In both enteroblasts and enterocytes, loss of Snakeskin and Mesh ...


Mathematic Modeling Of Covid-19 In The United States, Yuanji Tang, Shixia Wang Apr 2020

Mathematic Modeling Of Covid-19 In The United States, Yuanji Tang, Shixia Wang

Coronavirus COVID-19 Publications by UMMS Authors

Since the early reports of COVID-19 cases in China in late January 2020 (1-2), the worst pandemic in 100 years has spread to the entire globe with approximately 2.4 million diagnosed cases and over 165,000 deaths up to April 20, 2020.

While scientists from various public and private groups use math and computer to simulate the course of this pandemic to try to predict how this outbreak might evolve (3), most of such analyses are either quite complicated or not publicly available.

Here a simple mathematic modeling approach is taken to track the outbreaks of COVID-19 in the ...


The Coordinate Actions Of Calcineurin And Hog1 Mediate The Stress Response Through Multiple Nodes Of The Cell Cycle Network, Cassandra M. Leech, Mackenzie J. Flynn, Heather E. Arsenault, Jianhong Ou, Haibo Liu, Lihua Julie Zhu, Jennifer A. Benanti Apr 2020

The Coordinate Actions Of Calcineurin And Hog1 Mediate The Stress Response Through Multiple Nodes Of The Cell Cycle Network, Cassandra M. Leech, Mackenzie J. Flynn, Heather E. Arsenault, Jianhong Ou, Haibo Liu, Lihua Julie Zhu, Jennifer A. Benanti

Open Access Articles

Upon exposure to environmental stressors, cells transiently arrest the cell cycle while they adapt and restore homeostasis. A challenge for all cells is to distinguish between stress signals and coordinate the appropriate adaptive response with cell cycle arrest. Here we investigate the role of the phosphatase calcineurin (CN) in the stress response and demonstrate that CN activates the Hog1/p38 pathway in both yeast and human cells. In yeast, the MAPK Hog1 is transiently activated in response to several well-studied osmostressors. We show that when a stressor simultaneously activates CN and Hog1, CN disrupts Hog1-stimulated negative feedback to prolong Hog1 ...


Sars-Cov-2 Receptor Ace2 Is An Interferon-Stimulated Gene In Human Airway Epithelial Cells And Is Detected In Specific Cell Subsets Across Tissues, Carly G. K. Ziegler, Yuming Cao, Zhiru Guo, Jennifer P. Wang, Robert W. Finberg, Manuel Garber, Alex K. Shalek, Jose Ordovas-Montanes, Hca Lung Biological Network Apr 2020

Sars-Cov-2 Receptor Ace2 Is An Interferon-Stimulated Gene In Human Airway Epithelial Cells And Is Detected In Specific Cell Subsets Across Tissues, Carly G. K. Ziegler, Yuming Cao, Zhiru Guo, Jennifer P. Wang, Robert W. Finberg, Manuel Garber, Alex K. Shalek, Jose Ordovas-Montanes, Hca Lung Biological Network

Coronavirus COVID-19 Publications by UMMS Authors

There is pressing urgency to understand the pathogenesis of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2), which causes the disease COVID-19. SARS-CoV-2 spike (S) protein binds angiotensin-converting enzyme 2 (ACE2), and in concert with host proteases, principally transmembrane serine protease 2 (TMPRSS2), promotes cellular entry. The cell subsets targeted by SARS-CoV-2 in host tissues and the factors that regulate ACE2 expression remain unknown. Here, we leverage human, non-human primate, and mouse single-cell RNA-sequencing (scRNA-seq) datasets across health and disease to uncover putative targets of SARS-CoV-2 among tissue-resident cell subsets. We identify ACE2 and TMPRSS2 co-expressing cells within lung ...


Transcriptomic Profiling Reveals Extraordinary Diversity Of Venom Peptides In Unexplored Predatory Gastropods Of The Genus Clavus, Aiping Lu, Maren Watkins, Qing Li, Samuel D. Robinson, Gisela P. Concepcion, Mark Yandell, Zhiping Weng, Baldomero M. Olivera, Helena Safavi-Hemami, Alexander E. Fedosov Apr 2020

Transcriptomic Profiling Reveals Extraordinary Diversity Of Venom Peptides In Unexplored Predatory Gastropods Of The Genus Clavus, Aiping Lu, Maren Watkins, Qing Li, Samuel D. Robinson, Gisela P. Concepcion, Mark Yandell, Zhiping Weng, Baldomero M. Olivera, Helena Safavi-Hemami, Alexander E. Fedosov

Open Access Articles

Predatory gastropods of the superfamily Conoidea number over 12,000 living species. The evolutionary success of this lineage can be explained by the ability of conoideans to produce complex venoms for hunting, defense and competitive interactions. Whereas venoms of cone snails (family Conidae) have become increasingly well studied, the venoms of most other conoidean lineages remain largely uncharacterized. In the present study we present the venom gland transcriptomes of two species of the genus Clavus that belong to the family Drilliidae. Venom gland transcriptomes of two specimens of Clavus canalicularis, and two specimens of Cv. davidgilmouri were analyzed, leading to ...


The Covid-19 Pandemic: A Comprehensive Review Of Taxonomy, Genetics, Epidemiology, Diagnosis, Treatment, And Control, Yosra A. Helmy, Mohamed Fawzy, Ahmed Elaswad, Ahmed Sobieh, Scott P. Kenney, Awad A. Shehata Apr 2020

The Covid-19 Pandemic: A Comprehensive Review Of Taxonomy, Genetics, Epidemiology, Diagnosis, Treatment, And Control, Yosra A. Helmy, Mohamed Fawzy, Ahmed Elaswad, Ahmed Sobieh, Scott P. Kenney, Awad A. Shehata

Coronavirus COVID-19 Publications by UMMS Authors

A pneumonia outbreak with unknown etiology was reported in Wuhan, Hubei province, China, in December 2019, associated with the Huanan Seafood Wholesale Market. The causative agent of the outbreak was identified by the WHO as the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), producing the disease named coronavirus disease-2019 (COVID-19). The virus is closely related (96.3%) to bat coronavirus RaTG13, based on phylogenetic analysis. Human-to-human transmission has been confirmed even from asymptomatic carriers. The virus has spread to at least 200 countries, and more than 1,700,000 confirmed cases and 111,600 deaths have been recorded, with massive global ...


Chemical Modifications Of Adenine Base Editor Mrna And Guide Rna Expand Its Application Scope, Tingting Jiang, Xiao-Ou Zhang, Yueying Cao, Zhiping Weng, Wen Xue Apr 2020

Chemical Modifications Of Adenine Base Editor Mrna And Guide Rna Expand Its Application Scope, Tingting Jiang, Xiao-Ou Zhang, Yueying Cao, Zhiping Weng, Wen Xue

Open Access Articles

CRISPR-Cas9-associated base editing is a promising tool to correct pathogenic single nucleotide mutations in research or therapeutic settings. Efficient base editing requires cellular exposure to levels of base editors that can be difficult to attain in hard-to-transfect cells or in vivo. Here we engineer a chemically modified mRNA-encoded adenine base editor that mediates robust editing at various cellular genomic sites together with moderately modified guide RNA, and show its therapeutic potential in correcting pathogenic single nucleotide mutations in cell and animal models of diseases. The optimized chemical modifications of adenine base editor mRNA and guide RNA expand the applicability of ...


Dolphinnext: A Distributed Data Processing Platform For High Throughput Genomics, Onur Yukselen, Osman Turkyilmaz, Ahmet R. Ozturk, Manuel Garber, Alper Kucukural Apr 2020

Dolphinnext: A Distributed Data Processing Platform For High Throughput Genomics, Onur Yukselen, Osman Turkyilmaz, Ahmet R. Ozturk, Manuel Garber, Alper Kucukural

Open Access Articles

BACKGROUND: The emergence of high throughput technologies that produce vast amounts of genomic data, such as next-generation sequencing (NGS) is transforming biological research. The dramatic increase in the volume of data, the variety and continuous change of data processing tools, algorithms and databases make analysis the main bottleneck for scientific discovery. The processing of high throughput datasets typically involves many different computational programs, each of which performs a specific step in a pipeline. Given the wide range of applications and organizational infrastructures, there is a great need for highly parallel, flexible, portable, and reproducible data processing frameworks. Several platforms currently ...


Broad Host Range Of Sars-Cov-2 Predicted By Comparative And Structural Analysis Of Ace2 In Vertebrates, Joana Damas, Elinor K. Karlsson, Harris A. Lewin Apr 2020

Broad Host Range Of Sars-Cov-2 Predicted By Comparative And Structural Analysis Of Ace2 In Vertebrates, Joana Damas, Elinor K. Karlsson, Harris A. Lewin

University of Massachusetts Medical School Faculty Publications

The novel coronavirus SARS-CoV-2 is the cause of Coronavirus Disease-2019 (COVID-19). The main receptor of SARS-CoV-2, angiotensin I converting enzyme 2 (ACE2), is now undergoing extensive scrutiny to understand the routes of transmission and sensitivity in different species. Here, we utilized a unique dataset of 410 vertebrates, including 252 mammals, to study cross-species conservation of ACE2 and its likelihood to function as a SARS-CoV-2 receptor. We designed a five-category ranking score based on the conservation properties of 25 amino acids important for the binding between receptor and virus, classifying all species from very high to very low. Only mammals fell ...


Single-Cell Analysis Of Upper Airway Cells Reveals Host-Viral Dynamics In Influenza Infected Adults, Yuming Cao, Zhiru Guo, Pranitha Vangala, Elisa Donnard, Ping Liu, Patrick Mcdonel, Jose Ordovas Montanes, Alex K. Shalek, Robert W. Finberg, Jennifer P. Wang, Manuel Garber Apr 2020

Single-Cell Analysis Of Upper Airway Cells Reveals Host-Viral Dynamics In Influenza Infected Adults, Yuming Cao, Zhiru Guo, Pranitha Vangala, Elisa Donnard, Ping Liu, Patrick Mcdonel, Jose Ordovas Montanes, Alex K. Shalek, Robert W. Finberg, Jennifer P. Wang, Manuel Garber

University of Massachusetts Medical School Faculty Publications

Influenza virus infections are major causes of morbidity and mortality. Research using cultured cells, bulk tissue, and animal models cannot fully capture human disease dynamics. Many aspects of virus-host interactions in a natural setting remain unclear, including the specific cell types that are infected and how they and neighboring bystander cells contribute to the overall antiviral response. To address these questions, we performed single-cell RNA sequencing (scRNA-Seq) on cells from freshly collected nasal washes from healthy human donors and donors diagnosed with acute influenza during the 2017-18 season. We describe a previously uncharacterized goblet cell population, specific to infected individuals ...


Covid-19 Travel Restrictions And The International Health Regulations - Call For An Open Debate On Easing Of Travel Restrictions, Eskild Petersen, Brian Mccloskey, David S. Hui, Richard Kock, Francine Ntoumi, Ziad A. Memish, Nathan Kapata, Esam I. Azhar, Marjorie Pollack, Lawrence C. Madoff, Davidson H. Hamer, Jean B. Nachega, N. Pshenichnaya, Alimuddin Zumla Apr 2020

Covid-19 Travel Restrictions And The International Health Regulations - Call For An Open Debate On Easing Of Travel Restrictions, Eskild Petersen, Brian Mccloskey, David S. Hui, Richard Kock, Francine Ntoumi, Ziad A. Memish, Nathan Kapata, Esam I. Azhar, Marjorie Pollack, Lawrence C. Madoff, Davidson H. Hamer, Jean B. Nachega, N. Pshenichnaya, Alimuddin Zumla

Coronavirus COVID-19 Publications by UMMS Authors

The COVID-19 pandemic caused by the novel coronavirus (SARS-CoV-2) has made national governments worldwide to mandate several generic infection control measures such as physical distancing, self-isolation, and closure of non-essential shops, restaurants schools, among others. Some models suggest physical distancing would have to persist for 3 months to mitigate the peak effects on health systems and could be required on an intermittent basis for 12 to 18 months (Flaxman et al., 2020).


Dbf4-Dependent Kinase (Ddk)-Mediated Proteolysis Of Cenp-A Prevents Mislocalization Of Cenp-A In Saccharomyces Cerevisiae, Jessica R. Eisenstatt, Lars Boeckmann, Wei-Chun Au, Valerie Garcia, Levi Bursch, Josefina Ocampo, Michael Costanzo, Michael Weinreich, Robert A. Sclafani, Anastasia Baryshnikova, Chad L. Myers, Charles Boone, David J. Clark, Richard E. Baker, Munira A. Basrai Apr 2020

Dbf4-Dependent Kinase (Ddk)-Mediated Proteolysis Of Cenp-A Prevents Mislocalization Of Cenp-A In Saccharomyces Cerevisiae, Jessica R. Eisenstatt, Lars Boeckmann, Wei-Chun Au, Valerie Garcia, Levi Bursch, Josefina Ocampo, Michael Costanzo, Michael Weinreich, Robert A. Sclafani, Anastasia Baryshnikova, Chad L. Myers, Charles Boone, David J. Clark, Richard E. Baker, Munira A. Basrai

Open Access Articles

The evolutionarily conserved centromeric histone H3 variant (Cse4 in budding yeast, CENP-A in humans) is essential for faithful chromosome segregation. Mislocalization of CENP-A to non-centromeric chromatin contributes to chromosomal instability (CIN) in yeast, fly, and human cells and CENP-A is highly expressed and mislocalized in cancers. Defining mechanisms that prevent mislocalization of CENP-A is an area of active investigation. Ubiquitin-mediated proteolysis of overexpressed Cse4 (GALCSE4) by E3 ubiquitin ligases such as Psh1 prevents mislocalization of Cse4, and psh1Delta strains display synthetic dosage lethality (SDL) with GALCSE4. We previously performed a genome-wide screen and identified five alleles of CDC7 and DBF4 ...


Trim34 Restricts Hiv-1 And Siv Capsids In A Trim5alpha-Dependent Manner, Molly Ohainle, Kyusik Kim, Sevnur Komurlu Keceli, Abby Felton, Ed Campbell, Jeremy Luban, Michael Emerman Apr 2020

Trim34 Restricts Hiv-1 And Siv Capsids In A Trim5alpha-Dependent Manner, Molly Ohainle, Kyusik Kim, Sevnur Komurlu Keceli, Abby Felton, Ed Campbell, Jeremy Luban, Michael Emerman

Open Access Articles

The HIV-1 capsid protein makes up the core of the virion and plays a critical role in early steps of HIV replication. Due to its exposure in the cytoplasm after entry, HIV capsid is a target for host cell factors that act directly to block infection such as TRIM5alpha and MxB. Several host proteins also play a role in facilitating infection, including in the protection of HIV-1 capsid from recognition by host cell restriction factors. Through an unbiased screening approach, called HIV-CRISPR, we show that the CPSF6-binding deficient, N74D HIV-1 capsid mutant is sensitive to restriction mediated by human TRIM34 ...


Interpretation Of The Epigenetic Signature Of Facioscapulohumeral Muscular Dystrophy In Light Of Genotype-Phenotype Studies, Ana Nikolic, Louise Maranda, Rossella Ginevra Tupler Apr 2020

Interpretation Of The Epigenetic Signature Of Facioscapulohumeral Muscular Dystrophy In Light Of Genotype-Phenotype Studies, Ana Nikolic, Louise Maranda, Rossella Ginevra Tupler

Open Access Articles

Facioscapulohumeral muscular dystrophy (FSHD) is characterized by incomplete penetrance and intra-familial clinical variability. The disease has been associated with the genetic and epigenetic features of the D4Z4 repetitive elements at 4q35. Recently, D4Z4 hypomethylation has been proposed as a reliable marker in the FSHD diagnosis. We exploited the Italian Registry for FSHD, in which FSHD families are classified using the Clinical Comprehensive Evaluation Form (CCEF). A total of 122 index cases showing a classical FSHD phenotype (CCEF, category A) and 110 relatives were selected to test with the receiver operating characteristic (ROC) curve, the diagnostic and predictive value of D4Z4 ...


Identification And Characterization Of The Lactating Mouse Mammary Gland Citrullinome, Guangyuan Li, Coleman H. Young, Bryce Snow, Amanda O. Christensen, M. Kristen Demoruelle, Venkatesh V. Nemmara, Paul R. Thompson, Heather M. Rothfuss, Brian D. Cherrington Apr 2020

Identification And Characterization Of The Lactating Mouse Mammary Gland Citrullinome, Guangyuan Li, Coleman H. Young, Bryce Snow, Amanda O. Christensen, M. Kristen Demoruelle, Venkatesh V. Nemmara, Paul R. Thompson, Heather M. Rothfuss, Brian D. Cherrington

Open Access Articles

Citrullination is a post-translational modification (PTM) in which positively charged peptidyl-arginine is converted into neutral peptidyl-citrulline by peptidylarginine deiminase (PAD or PADI) enzymes. The full protein citrullinome in many tissues is unknown. Herein, we used mass spectrometry and identified 107 citrullinated proteins in the lactation day 9 (L9) mouse mammary gland including histone H2A, alpha-tubulin, and beta-casein. Given the importance of prolactin to lactation, we next tested if it stimulates PAD-catalyzed citrullination using mouse mammary epithelial CID-9 cells. Stimulation of CID-9 cells with 5 microg/mL prolactin for 10 min induced a 2-fold increase in histone H2A citrullination and a ...


Histone Deacetylases 1 And 2 Silence Cryptic Transcription To Promote Mitochondrial Function During Cardiogenesis, Zachary J. Milstone, Sherin Saheera, Lauren Bourke, Tomer Shpilka, Cole M. Haynes, Chinmay M. Trivedi Apr 2020

Histone Deacetylases 1 And 2 Silence Cryptic Transcription To Promote Mitochondrial Function During Cardiogenesis, Zachary J. Milstone, Sherin Saheera, Lauren Bourke, Tomer Shpilka, Cole M. Haynes, Chinmay M. Trivedi

Open Access Articles

Cryptic transcription occurs widely across the eukaryotic genome; however, its regulation during vertebrate development is not understood. Here, we show that two class I histone deacetylases, Hdac1 and Hdac2, silence cryptic transcription to promote mitochondrial function in developing murine hearts. Mice lacking Hdac1 and Hdac2 in heart exhibit defective developmental switch from anaerobic to mitochondrial oxidative phosphorylation (OXPHOS), severe defects in mitochondrial mass, mitochondrial function, and complete embryonic lethality. Hdac1/Hdac2 promotes the transition to OXPHOS by enforcing transcriptional fidelity of metabolic gene programs. Mechanistically, Hdac1/Hdac2 deacetylates histone residues including H3K23, H3K14, and H4K16 to suppress cryptic transcriptional initiation ...


Cryoem Structure Of Ctbp2 Confirms Tetrameric Architecture, Anne M. Jecrois, M. Michael Dcona, Xiaovan Deng, Dipankar Bandyopadhyay, Steven R. Grossman, Celia A. Schiffer, William E. Royer Apr 2020

Cryoem Structure Of Ctbp2 Confirms Tetrameric Architecture, Anne M. Jecrois, M. Michael Dcona, Xiaovan Deng, Dipankar Bandyopadhyay, Steven R. Grossman, Celia A. Schiffer, William E. Royer

University of Massachusetts Medical School Faculty Publications

C-terminal binding proteins 1 and 2 (CtBP1 and CtBP2) are transcriptional regulators that activate or repress many genes involved in cellular development, apoptosis and metastasis. CtBP proteins are activated under hypoxic conditions where NAD(H) levels tend to be higher. NADH-dependent activation of CtBP2 has direct implication in multiple types of cancers and poor patient prognosis. Previous studies have proposed dimeric CtBP as the relevant oligomeric state, however our studies with multi-angle light scattering have shown that the primary effect of NADH binding is to promote the assembly of two CtBP dimers into tetramers. Here, we present the cryoEM structures ...


Sars-Cov-2, Jeremy Luban Apr 2020

Sars-Cov-2, Jeremy Luban

Coronavirus COVID-19 Publications by UMMS Authors

This presentation about the biology of Coronaviruses was presented virtually to the RNA Biology Journal Club at the University of Massachusetts Medical School on April 7, 2020.


Innate Immunity In The C. Elegans Intestine Is Programmed By A Neuronal Regulator Of Awc Olfactory Neuron Development, Kyle J. Foster, Hilary K. Cheesman, Pengpeng Liu, Nicholas D. Peterson, Sarah M. Anderson, Read Pukkila-Worley Apr 2020

Innate Immunity In The C. Elegans Intestine Is Programmed By A Neuronal Regulator Of Awc Olfactory Neuron Development, Kyle J. Foster, Hilary K. Cheesman, Pengpeng Liu, Nicholas D. Peterson, Sarah M. Anderson, Read Pukkila-Worley

Open Access Articles

Olfactory neurons allow animals to discriminate nutritious food sources from potential pathogens. From a forward genetic screen, we uncovered a surprising requirement for the olfactory neuron gene olrn-1 in the regulation of intestinal epithelial immunity in Caenorhabditis elegans. During nematode development, olrn-1 is required to program the expression of odorant receptors in the AWC olfactory neuron pair. Here, we show that olrn-1 also functions in AWC neurons in the cell non-autonomous suppression of the canonical p38 MAPK PMK-1 immune pathway in the intestine. Low activity of OLRN-1, which activates the p38 MAPK signaling cassette in AWC neurons during larval development ...


Deconstructing Circadian Disruption: Assessing The Contribution Of Reduced Peripheral Oscillator Amplitude On Obesity And Glucose Intolerance In Mice, Vincent Van Der Vinne, Blanca Martin Burgos, Mary E. Harrington, David R. Weaver Apr 2020

Deconstructing Circadian Disruption: Assessing The Contribution Of Reduced Peripheral Oscillator Amplitude On Obesity And Glucose Intolerance In Mice, Vincent Van Der Vinne, Blanca Martin Burgos, Mary E. Harrington, David R. Weaver

Neurobiology Publications

Disturbing the circadian regulation of physiology by disruption of the rhythmic environment is associated with adverse health outcomes but the underlying mechanisms are unknown. Here, the response of central and peripheral circadian clocks to an advance or delay of the light-dark cycle was determined in mice. This identified transient damping of peripheral clocks as a consequence of an advanced light-dark cycle. Similar depression of peripheral rhythm amplitude was observed in mice exposed to repeated phase shifts. To assess the metabolic consequences of such peripheral amplitude depression in isolation, temporally chimeric mice lacking a functional central clock (Vgat-Cre(+) Bmal1(fl/fl ...


Epidemic To Endemic Or Pandemic Infectious Diseases: Commonalities And Distinctions Between Malaria, Ebola And Covid19, Ann M. Moormann Apr 2020

Epidemic To Endemic Or Pandemic Infectious Diseases: Commonalities And Distinctions Between Malaria, Ebola And Covid19, Ann M. Moormann

PEER Liberia Project

This presentation provides an overview of epidemics by discussing malaria, Ebola and COVID-19: definition of terms; examples of diseases, transmission and health impact; diagnostics versus presumptive diagnosis –how to make strategic decisions with limited resources and specific context; how strategies are modified by what we learn -- how fast can we adapt; control, elimination, eradication -- modeling the end game.


Biomarker Exploration In Human Peripheral Blood Mononuclear Cells For Monitoring Sulforaphane Treatment Responses In Autism Spectrum Disorder, Hua Liu, Andrew W. Zimmerman, Kanwaljit Singh, Susan Connors, Eileen Diggins, Katherine K. Stephenson, Albena T. Dinkova-Kostova, Jed W. Fahey Apr 2020

Biomarker Exploration In Human Peripheral Blood Mononuclear Cells For Monitoring Sulforaphane Treatment Responses In Autism Spectrum Disorder, Hua Liu, Andrew W. Zimmerman, Kanwaljit Singh, Susan Connors, Eileen Diggins, Katherine K. Stephenson, Albena T. Dinkova-Kostova, Jed W. Fahey

Open Access Articles

Autism Spectrum Disorder (ASD) is one of the most common neurodevelopmental disorders with no drugs treating the core symptoms and no validated biomarkers for clinical use. The multi-functional phytochemical sulforaphane affects many of the biochemical abnormalities associated with ASD. We investigated potential molecular markers from three ASD-associated physiological pathways that can be affected by sulforaphane: redox metabolism/oxidative stress; heat shock response; and immune dysregulation/inflammation, in peripheral blood mononuclear cells (PBMCs) from healthy donors and patients with ASD. We first analyzed the mRNA levels of selected molecular markers in response to sulforaphane ex vivo treatment in PBMCs from healthy ...


Are Dietary Fish Oil Supplements Appropriate For Dyslipidemia Management? A Review Of The Evidence, Samuel C. R. Sherratt, Michael Lero, R. Preston Mason Apr 2020

Are Dietary Fish Oil Supplements Appropriate For Dyslipidemia Management? A Review Of The Evidence, Samuel C. R. Sherratt, Michael Lero, R. Preston Mason

Open Access Articles

PURPOSE OF REVIEW: The purpose of this review is to assess whether dietary fish oil supplements can be appropriate for patients with elevated triglycerides and cardiovascular risk based on a comprehensive analysis of their composition, and level of regulatory oversight.

RECENT FINDINGS: Approximately 19 million people in the United States take fish oil supplements, many for the purpose of treating or preventing heart disease. Unlike prescription products, fish oil supplements are classified as food by the Food and Drug Administration (FDA) and are not required to undergo manufacturing oversight or clinical testing. Analysis of widely used dietary fish oil supplements ...


Mechanisms Of Insulin Resistance Related To White, Beige, And Brown Adipocytes, Michael P. Czech Apr 2020

Mechanisms Of Insulin Resistance Related To White, Beige, And Brown Adipocytes, Michael P. Czech

Open Access Articles

BACKGROUND: The diminished glucose lowering effect of insulin in obesity, called "insulin resistance," is associated with glucose intolerance, type 2 diabetes, and other serious maladies. Many publications on this topic have suggested numerous hypotheses on the molecular and cellular disruptions that contribute to the syndrome. However, significant uncertainty remains on the mechanisms of its initiation and long-term maintenance.

SCOPE OF REVIEW: To simplify insulin resistance analysis, this review focuses on the unifying concept that adipose tissue is a central regulator of systemic glucose homeostasis by controlling liver and skeletal muscle metabolism. Key aspects of adipose function related to insulin resistance ...


Avoiding Drug Resistance By Substrate Envelope-Guided Design: Toward Potent And Robust Hcv Ns3/4a Protease Inhibitors, Ashley N. Matthew, Jacqueto Zephyr, Nageswara Rao Desaboini, Mina Henes, Wasih Kamran, Klajdi Kosovrasti, Adam Hedger, Gordon J. Lockbaum, Jennifer Timm, Akbar Ali, Nese Kurt Yilmaz, Celia A. Schiffer Mar 2020

Avoiding Drug Resistance By Substrate Envelope-Guided Design: Toward Potent And Robust Hcv Ns3/4a Protease Inhibitors, Ashley N. Matthew, Jacqueto Zephyr, Nageswara Rao Desaboini, Mina Henes, Wasih Kamran, Klajdi Kosovrasti, Adam Hedger, Gordon J. Lockbaum, Jennifer Timm, Akbar Ali, Nese Kurt Yilmaz, Celia A. Schiffer

University of Massachusetts Medical School Faculty Publications

Hepatitis C virus (HCV) infects millions of people worldwide, causing chronic liver disease that can lead to cirrhosis, hepatocellular carcinoma, and liver transplant. In the last several years, the advent of direct-acting antivirals, including NS3/4A protease inhibitors (PIs), has remarkably improved treatment outcomes of HCV-infected patients. However, selection of resistance-associated substitutions and polymorphisms among genotypes can lead to drug resistance and in some cases treatment failure. A proactive strategy to combat resistance is to constrain PIs within evolutionarily conserved regions in the protease active site. Designing PIs using the substrate envelope is a rational strategy to decrease the susceptibility ...


Investigating The Impact Of Asymptomatic Carriers On Covid-19 Transmission, Jacob B. Aguilar, Jeremy Samuel Faust, Lauren M. Westafer, Juan B. Gutierrez Mar 2020

Investigating The Impact Of Asymptomatic Carriers On Covid-19 Transmission, Jacob B. Aguilar, Jeremy Samuel Faust, Lauren M. Westafer, Juan B. Gutierrez

Coronavirus COVID-19 Publications by UMMS Authors

Coronavirus disease 2019 (COVID-19) is a novel human respiratory disease caused by the SARS-CoV-2 virus. Asymptomatic carriers of the virus display no clinical symptoms but are known to be contagious. Recent evidence reveals that this sub-population, as well as persons with mild, represent a major contributor in the propagation of COVID-19. The asymptomatic sub-population frequently escapes detection by public health surveillance systems. Because of this, the currently accepted estimates of the basic reproduction number (Ro) of the virus are inaccurate. It is unlikely that a pathogen can blanket the planet in three months with an Ro in the vicinity of ...


Comparisons Of Antibody Populations In Different Pre-Fusion F Vlp-Immunized Cotton Rat Dams And Their Offspring, Lori Mcginnes Cullen, Marina S. Boukhvalova, Jorge C. G. Blanco, Trudy G. Morrison Mar 2020

Comparisons Of Antibody Populations In Different Pre-Fusion F Vlp-Immunized Cotton Rat Dams And Their Offspring, Lori Mcginnes Cullen, Marina S. Boukhvalova, Jorge C. G. Blanco, Trudy G. Morrison

Open Access Articles

Respiratory syncytial virus (RSV) infection poses a significant risk for infants. Since the direct vaccination of infants is problematic, maternal vaccination may provide a safer, more effective approach to their protection. In the cotton rat (CR) model, we have compared the immunization of pregnant CR dams with virus-like particles assembled with the prototype mutation stabilized pre-fusion F protein, DS-Cav1, as well two alternative mutation stabilized pre-fusion proteins (UC-2 F, UC-3 F) and showed that the alternative pre-fusion F VLPs protected the offspring of immunized dams significantly better than DS-Cav1 F VLPs (Blanco, et al. J. Virol. 93: e00914). Here, we ...


Humanity's Best Friend: A Dog-Centric Approach To Addressing Global Challenges, Naomi Sykes, Elinor K. Karlsson, Greger Larson Mar 2020

Humanity's Best Friend: A Dog-Centric Approach To Addressing Global Challenges, Naomi Sykes, Elinor K. Karlsson, Greger Larson

Open Access Articles

No other animal has a closer mutualistic relationship with humans than the dog (Canis familiaris). Domesticated from the Eurasian grey wolf (Canis lupus), dogs have evolved alongside humans over millennia in a relationship that has transformed dogs and the environments in which humans and dogs have co-inhabited. The story of the dog is the story of recent humanity, in all its biological and cultural complexity. By exploring human-dog-environment interactions throughout time and space, it is possible not only to understand vital elements of global history, but also to critically assess our present-day relationship with the natural world, and to begin ...


Beta-Amyloid Clustering Around Asc Fibrils Boosts Its Toxicity In Microglia, Lea L. Friker, Hannah Scheiblich, Inga V. Hochheiser, Rebecca Brinkschulte, Dietmar Riedel, Eicke Latz, Matthias Geyer, Michael T. Heneka Mar 2020

Beta-Amyloid Clustering Around Asc Fibrils Boosts Its Toxicity In Microglia, Lea L. Friker, Hannah Scheiblich, Inga V. Hochheiser, Rebecca Brinkschulte, Dietmar Riedel, Eicke Latz, Matthias Geyer, Michael T. Heneka

Open Access Articles

Alzheimer's disease is the world's most common neurodegenerative disorder. It is associated with neuroinflammation involving activation of microglia by beta-amyloid (Abeta) deposits. Based on previous studies showing apoptosis-associated speck-like protein containing a CARD (ASC) binding and cross-seeding extracellular Abeta, we investigate the propagation of ASC between primary microglia and the effects of ASC-Abeta composites on microglial inflammasomes and function. Indeed, ASC released by a pyroptotic cell can be functionally built into the neighboring microglia NOD-like receptor protein (NLRP3) inflammasome. Compared with protein-only application, exposure to ASC-Abeta composites amplifies the proinflammatory response, resulting in pyroptotic cell death, setting free ...


A Systematic Re-Examination Of Processing Of Mhci-Bound Antigenic Peptide Precursors By Er Aminopeptidase 1, George Mavridis, Richa Arya, Alexander Domnick, Jerome Zoidakis, Manousos Makridakis, Antonia Vlahou, Anastasia Mpakali, Angelos Lelis, Dimitris Georgiadis, Robert Tampe, Athanasios Papakyriakou, Lawrence J. Stern, Efstratios Stratikos Mar 2020

A Systematic Re-Examination Of Processing Of Mhci-Bound Antigenic Peptide Precursors By Er Aminopeptidase 1, George Mavridis, Richa Arya, Alexander Domnick, Jerome Zoidakis, Manousos Makridakis, Antonia Vlahou, Anastasia Mpakali, Angelos Lelis, Dimitris Georgiadis, Robert Tampe, Athanasios Papakyriakou, Lawrence J. Stern, Efstratios Stratikos

Open Access Articles

Endoplasmic reticulum aminopeptidase 1 (ERAP1) trims antigenic peptide precursors to generate mature antigenic peptides for presentation by major histocompatibility complex class I (MHCI) molecules and regulates adaptive immune responses. ERAP1 has been proposed to trim peptide precursors both in solution and in pre-formed MHCI-peptide complexes, but which mode is more relevant to its biological function remains controversial. Here, we compared ERAP1-mediated trimming of antigenic peptide precursors in solution or when bound to three MHCI alleles, HLA-B*58, HLA-B*08 and HLA-A*02. For all MHCI-peptide combinations, peptide binding onto MHCI protected against ERAP1-mediated trimming. In only a single MHCI-peptide combination ...