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Full-Text Articles in Medicine and Health Sciences

Oral Chemotherapy: Safe Handling In The Home, Cynthia Huff Dec 2020

Oral Chemotherapy: Safe Handling In The Home, Cynthia Huff

DNP Qualifying Manuscripts

Background: According to the National Institute for Occupational Safety and Health (2016), oral anticancer agents (OAC) are hazardous drugs (HD) and require the same safe handling interventions in the home setting as in controlled health care environments. The use of a safe handling checklist for OAC administration is a way nurses can provide safe handling education to patients and caregivers and assess for understanding and competency for critical tasks. Effective home management strategies outlining caregiver protections, proper storage, administration of OACs, spill clean-up, and waste disposal could reduce exposure risks to toxic agents.

Objective: To present a safe-handling checklist and ...


Click-Free Synthesis Of A Multivalent Tricyclic Peptide As A Molecular Transporter, Sumit Kumar, Dindyal Mandal, Shaima Ahmed El-Mowafi, Saghar Mozaffari, Rakesh Kumar Tiwari, Keykavous Parang Sep 2020

Click-Free Synthesis Of A Multivalent Tricyclic Peptide As A Molecular Transporter, Sumit Kumar, Dindyal Mandal, Shaima Ahmed El-Mowafi, Saghar Mozaffari, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

The cellular delivery of cell-impermeable and water-insoluble molecules remains an ongoing challenge to overcome. Previously, we reported amphipathic cyclic peptides c[WR]4 and c[WR]5 consisting of alternate arginine and tryptophan residues as nuclear-targeting molecular transporters. These peptides contain an optimal balance of positive charge and hydrophobicity, which is required for interactions with the phospholipid bilayer to facilitate their application as a drug delivery system. To further optimize them, we synthesized and evaluated a multivalent tricyclic peptide as an efficient molecular transporter. The monomeric cyclic peptide building blocks were synthesized using Fmoc/tBu solid-phase chemistry and cyclization in ...


Effect Of High Glucose On Ocular Surface Epithelial Cell Barrier And Tight Junction Proteins, Saleh M. Alfuraih, Ashley Barbarino, Christopher Ross, Kiumars Shamloo, Vishal Jhanji, Miao Zhang, Ajay Sharma Sep 2020

Effect Of High Glucose On Ocular Surface Epithelial Cell Barrier And Tight Junction Proteins, Saleh M. Alfuraih, Ashley Barbarino, Christopher Ross, Kiumars Shamloo, Vishal Jhanji, Miao Zhang, Ajay Sharma

Pharmacy Faculty Articles and Research

PURPOSE. Patients with diabetes mellitus are reported to have ocular surface defects, impaired ocular surface barrier function, and a higher incidence of corneal and conjunctival infections. Tight junctions are critical for ocular surface barrier function. The present study was designed to investigate the effect of high glucose exposure on human corneal and conjunctival epithelial cell barrier function and tight junction proteins.

METHODS. Human corneal and conjunctival epithelial cells were exposed to 15 mM and 30 mM glucose for 24 and 72 hours. The barrier function was measured using transepithelial electrical resistance (TEER). The cell migration was quantified using scratch assay ...


The Bromodomains Of The Mammalian Swi/Snf (Mswi/Snf) Atpases Brahma (Brm) And Brahma Related Gene 1 (Brg1) Promote Chromatin Interaction And Are Critical For Skeletal Muscle Differentiation, Anthony N. Imbalzano, Hanna Witwicka, Tapan Sharma Sep 2020

The Bromodomains Of The Mammalian Swi/Snf (Mswi/Snf) Atpases Brahma (Brm) And Brahma Related Gene 1 (Brg1) Promote Chromatin Interaction And Are Critical For Skeletal Muscle Differentiation, Anthony N. Imbalzano, Hanna Witwicka, Tapan Sharma

University of Massachusetts Medical School Faculty Publications

Skeletal muscle differentiation induces changes in the epigenome of myoblasts as they proceed towards a myogenic phenotype. mSWI/SNF chromatin remodeling enzymes coordinate with lineage-determining transcription factors and are key regulators of differentiation. Three mSWI/SNF proteins, the mutually exclusive ATPases, BRG1 and BRM, and the BAF180 protein (Polybromo1, PBRM1) contain bromodomains belonging to the same structural subfamily. Bromodomains bind to acetylated lysines on histone N-terminal tails and on other proteins. Pharmacological inhibition of mSWI/SNF bromodomain function using the selective inhibitor PFI-3 reduced differentiation, decreased expression of myogenic genes, and increased the expression of cell cycle-related genes and the ...


21 In The 21st—An Evaluation Of The Tobacco Regulation Trend, Casey Kellum Sep 2020

21 In The 21st—An Evaluation Of The Tobacco Regulation Trend, Casey Kellum

St. Mary's Law Journal

Tobacco regulation persists as a controversial issue both legally and politically in the United States. Throughout American history, states rely on local legislation to provide adequate protection to consumers of tobacco products, as “Big Tobacco” targets consumers for its addictive product. One of the most recent amendments in this arena is the state by state decision to raise the minimum legal sales age for tobacco to twenty-one.

Despite rigorous regulation of tobacco products in the United States, however, tobacco remains the leading cause of preventable deaths in the country. These “Tobacco 21” ordinances come at a critical time when the ...


Antibacterial Properties Of Common Gap Plants From Monteverde, Costa Rica, Hannah Pletcher Aug 2020

Antibacterial Properties Of Common Gap Plants From Monteverde, Costa Rica, Hannah Pletcher

The Journal of Purdue Undergraduate Research

No abstract provided.


Nano-Vesicle (Mis)Communication In Senescence-Related Pathologies, Sherin Saheera, Ajay Godwin Potnuri, Prasanna Krishnamurthy Aug 2020

Nano-Vesicle (Mis)Communication In Senescence-Related Pathologies, Sherin Saheera, Ajay Godwin Potnuri, Prasanna Krishnamurthy

COVID-19 Publications by UMMS Authors

Extracellular vesicles are a heterogeneous group of cell-derived membranous structures comprising of exosomes, apoptotic bodies, and microvesicles. Of the extracellular vesicles, exosomes are the most widely sorted and extensively explored for their contents and function. The size of the nanovesicular structures (exosomes) range from 30 to 140 nm and are present in various biological fluids such as saliva, plasma, urine etc. These cargo-laden extracellular vesicles arise from endosome-derived multivesicular bodies and are known to carry proteins and nucleic acids. Exosomes are involved in multiple physiological and pathological processes, including cellular senescence. Exosomes mediate signaling crosstalk and play a critical role ...


Pfred: A Computational Platform For Sirna And Antisense Oligonucleotides Design, Simone Sciabola, Hualin Xi, Dario Cruz, Qing Cao, Christine Lawrence, Tianhong Zhang, Sergio Rotstein, Jason D. Hughes, Daniel R. Caffrey, Robert Stanton Aug 2020

Pfred: A Computational Platform For Sirna And Antisense Oligonucleotides Design, Simone Sciabola, Hualin Xi, Dario Cruz, Qing Cao, Christine Lawrence, Tianhong Zhang, Sergio Rotstein, Jason D. Hughes, Daniel R. Caffrey, Robert Stanton

University of Massachusetts Medical School Faculty Publications

PFRED a software application for the design, analysis, and visualization of antisense oligonucleotides and siRNA is described. The software provides an intuitive user-interface for scientists to design a library of siRNA or antisense oligonucleotides that target a specific gene of interest. Moreover, the tool facilitates the incorporation of various design criteria that have been shown to be important for stability and potency. PFRED has been made available as an open-source project so the code can be easily modified to address the future needs of the oligonucleotide research community. A compiled version is available for downloading at https://github.com/pfred ...


Opioid Dependency And Its Effects On Alcohol Consumption, Emily V. Flores Aug 2020

Opioid Dependency And Its Effects On Alcohol Consumption, Emily V. Flores

Psychology and Counseling Theses

Previous research has found dualistic effects on alcohol consumption with low doses of buprenorphine increasing alcohol and higher doses of buprenorphine reducing alcohol consumption in rats (Ciccocioppo et al., 2006). Other existing research on naloxone treatment and alcohol consumption in opioid use has demonstrated that alcohol consumption decreases after naloxone treatment in rats (Hyytia & Sinclair, 1993). Yet, no research has been conducted on either rats or humans on the effects of buprenorphine and naloxone medication combined. The effects of opioid maintenance therapy are controversial and the relationship between alcohol consumption and opioid dependency treatment is mainly based on literature review ...


Characterization Of Viral Insulins Reveals White Adipose Tissue Specific Effects In Mice, Martina Chrudinová, Francois Moreau, Hye Lim Noh, Terezie Páníková, Lenka Žáková, Randall H. Friedline, Francisco A. Valenzuela, Jason K. Kim, Czech Academy Of Sciences, Harvard Medical School, Boston College Aug 2020

Characterization Of Viral Insulins Reveals White Adipose Tissue Specific Effects In Mice, Martina Chrudinová, Francois Moreau, Hye Lim Noh, Terezie Páníková, Lenka Žáková, Randall H. Friedline, Francisco A. Valenzuela, Jason K. Kim, Czech Academy Of Sciences, Harvard Medical School, Boston College

University of Massachusetts Medical School Faculty Publications

Members of the insulin/IGF superfamily are well conserved across the evolutionary tree. We recently showed that four viruses in the Iridoviridae family possess genes that encode proteins highly homologous to human insulin/IGF-1. Using chemically synthesized single chain (sc), i.e. IGF-1-like, forms of the viral insulin/IGF-1 like peptides (VILPs), we previously showed that they can stimulate human receptors. Because these peptides possess potential cleavage sites to form double chain (dc), i.e. more insulin-like, VILPs, in this study, we have characterized dc forms of VILPs for Grouper iridovirus (GIV), Singapore grouper iridovirus (SGIV) and Lymphocystis disease virus-1 ...


Cyclic Peptide-Gadolinium Nanoparticles For Enhanced Intracellular Delivery, Amir Nasrolahi Shirazi, Shang Eun Park, Shirin Rad, Luiza Baloyan, Dindyal Mandal, Muhammad Imran Sajid, Ryley Hall, Sandeep Lohan, Khalid Zoghebi, Keykavous Parang, Rakesh Tiwari Aug 2020

Cyclic Peptide-Gadolinium Nanoparticles For Enhanced Intracellular Delivery, Amir Nasrolahi Shirazi, Shang Eun Park, Shirin Rad, Luiza Baloyan, Dindyal Mandal, Muhammad Imran Sajid, Ryley Hall, Sandeep Lohan, Khalid Zoghebi, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

A cyclic peptide containing one cysteine and five alternating tryptophan and arginine amino acids [(WR)5C] was synthesized using Fmoc/tBu solid-phase methodology. The ability of the synthesized cyclic peptide to produce gadolinium nanoparticles through an in situ one-pot mixing of an aqueous solution of GdCl3 with [(WR)5C] peptide solution was evaluated. Transmission electron microscopy showed the formed peptide-Gd nanoparticles in star-shape morphology with a size of ~250 nm. Flow cytometry investigation showed that the cellular uptake of a cell-impermeable fluorescence-labeled phosphopeptide (F′-GpYEEI, where F′ = fluorescein) was approximately six times higher in the presence of ...


Host Immunity Increases Mycobacterium Tuberculosis Reliance On Cytochrome Bd Oxidase, Yi Cai, Eleni Jaecklein, Jared Mackenzie, Kadamba Papavinasasundaram, Michigan State University, Xinchun Chen, Africa Health Research Institute, Christopher M. Sassetti Aug 2020

Host Immunity Increases Mycobacterium Tuberculosis Reliance On Cytochrome Bd Oxidase, Yi Cai, Eleni Jaecklein, Jared Mackenzie, Kadamba Papavinasasundaram, Michigan State University, Xinchun Chen, Africa Health Research Institute, Christopher M. Sassetti

University of Massachusetts Medical School Faculty Publications

In order to sustain a persistent infection, Mycobacterium tuberculosis (Mtb) must adapt to a changing environment that is shaped by the developing immune response. This necessity to adapt is evident in the flexibility of many aspects of Mtb metabolism, including a respiratory chain that consists of two distinct terminal cytochrome oxidase complexes. Under the conditions tested thus far, the bc1/aa3 complex appears to play a dominant role, while the alternative bd oxidase is largely redundant. However, presence of two terminal oxidases in this obligate pathogen implies that respiratory requirements might change during infection. We report that the ...


A Cross-Reactive Human Iga Monoclonal Antibody Blocks Sars-Cov-2 Spike-Ace2 Interaction, Ejemel Monir, Qi Li, Shurong Hou, Zachary Schiller, Aaron Wallace, Alla Amcheslavsky, Nese Kurt Yilmaz, Jacqueline R. Toomey, Ryan Schneider, Anudeep S. Ramchetty, Chandrashekar Ganesa, Lisa Cavacini, Mark S. Klempner, Celia A. Schiffer, Yan Wang Aug 2020

A Cross-Reactive Human Iga Monoclonal Antibody Blocks Sars-Cov-2 Spike-Ace2 Interaction, Ejemel Monir, Qi Li, Shurong Hou, Zachary Schiller, Aaron Wallace, Alla Amcheslavsky, Nese Kurt Yilmaz, Jacqueline R. Toomey, Ryan Schneider, Anudeep S. Ramchetty, Chandrashekar Ganesa, Lisa Cavacini, Mark S. Klempner, Celia A. Schiffer, Yan Wang

COVID-19 Publications by UMMS Authors

COVID-19 caused by SARS-CoV-2 has become a global pandemic requiring the development of interventions for the prevention or treatment to curtail mortality and morbidity. No vaccine to boost mucosal immunity, or as a therapeutic, has yet been developed to SARS-CoV-2. In this study, we discover and characterize a cross-reactive human IgA monoclonal antibody, MAb362. MAb362 binds to both SARS-CoV and SARS-CoV-2 spike proteins and competitively blocks ACE2 receptor binding, by overlapping the ACE2 structural binding epitope. Furthermore, MAb362 IgA neutralizes both pseudotyped SARS-CoV and SARS-CoV-2 in 293 cells expressing ACE2. When converted to secretory IgA, MAb326 also neutralizes authentic SARS-CoV-2 ...


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 Aug 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

COVID-19 Publications by UMMS Authors

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of 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 ACE2 sequences from 410 vertebrate species, including 252 mammals, to study the conservation of ACE2 and its potential to be used as a receptor by SARS-CoV-2. We designed a five-category binding score based on the conservation properties of 25 amino acids important for the binding between ACE2 and the SARS-CoV-2 spike ...


Reduced Neurog3 Gene Dosage Shifts Enteroendocrine Progenitor Toward Goblet Cell Lineage In The Mouse Intestine, Joyce H. Li, Subir Ray, Alper Kucukural, Gerard Gradwohl, Andrew B. Leiter Aug 2020

Reduced Neurog3 Gene Dosage Shifts Enteroendocrine Progenitor Toward Goblet Cell Lineage In The Mouse Intestine, Joyce H. Li, Subir Ray, Alper Kucukural, Gerard Gradwohl, Andrew B. Leiter

University of Massachusetts Medical School Faculty Publications

BACKGROUND and AIMS: Transient expression of Neurog3 commits intestinal secretory progenitors to become enteroendocrine-biased progenitors and hence drive enteroendocrine differentiation. Loss of Neurog3 in mouse resulted in the depletion of intestinal enteroendocrine cells (EECs) and an increase in goblet cells. Earlier studies in developing mouse pancreas showed Neurog3 gene dosage in endocrine and exocrine cell fate allocation. We aimed to determine whether Neurog3 gene dosage controls fate choice of enteroendocrine progenitors.

METHODS: We acquired mutant Neurog3 reporter mice carrying 2, 1, or null Neurog3 alleles to study Neurog3 gene dosage effect by lineage tracing. Cell types arising from Neurog3+ progenitors ...


Cancer-Targeting Immunostimulatory Peptides As An Immunotherapeutic Approach To Cancer, Rachel Montel Aug 2020

Cancer-Targeting Immunostimulatory Peptides As An Immunotherapeutic Approach To Cancer, Rachel Montel

Seton Hall University Dissertations and Theses (ETDs)

This dissertation reports the synthesis and biological applications of bifunctional trimeric peptides with B7H6-derived NKp30 binding motifs that serve to activate an immunocytotoxic response in natural killer cells and a GRP78-binding motif that can target tumors that express surface GRP78. In this manner the cancer-targeting immunostimulatory peptides are anticipated to directly bind and activate effector NK92-MI cells while also recognizing and binding to target A549 tumor cells to facilitate NK cell-dependent immunocytotoxicity of the targeted tumors. The NKp30 binding peptide motifs are derived from the tumor associated B7H6 antigen that is often downregulated or shed from the surface of tumors ...


Seroprevalence Of Sars-Cov-2-Specific Igg Antibodies Among Adults Living In Connecticut Between March 1 And June 1, 2020: Post-Infection Prevalence (Pip) Study, Shiwani Mahajan, Lokinendi V. Rao, Harlan M. Krumholz Aug 2020

Seroprevalence Of Sars-Cov-2-Specific Igg Antibodies Among Adults Living In Connecticut Between March 1 And June 1, 2020: Post-Infection Prevalence (Pip) Study, Shiwani Mahajan, Lokinendi V. Rao, Harlan M. Krumholz

University of Massachusetts Medical School Faculty Publications

Importance: A seroprevalence study can estimate the percentage of people with SARS-CoV-2 antibodies in the general population. Most existing reports have used a convenience sample, which may bias their estimates.

Objective: To estimate the seroprevalence of antibodies against SARS-CoV-2 based on a random sample of adults living in Connecticut between March 1 and June 1, 2020.

Design: Cross-sectional. Setting: We sought a representative sample of Connecticut residents who completed a survey between June 4 and June 23, 2020 and underwent serology testing for SARS-CoV-2-specific IgG antibodies between June 10 and July 6, 2020.

Participants: 505 respondents, aged ≥18 years, residing ...


Upregulating Beta-Hexosaminidase Activity In Rodents Prevents Alpha-Synuclein Lipid Associations And Protects Dopaminergic Neurons From Alpha-Synuclein-Mediated Neurotoxicity, Oeystein R. Brekk, Joanna A. Korecka, Cecile C. Crapart, Mylene Huebecker, Zachary K. Macbain, Sara Ann Rosenthal, Miguel Sena-Esteves, David A. Priestman, Frances M. Platt, Ole Isacson, Penelope J. Hallett Aug 2020

Upregulating Beta-Hexosaminidase Activity In Rodents Prevents Alpha-Synuclein Lipid Associations And Protects Dopaminergic Neurons From Alpha-Synuclein-Mediated Neurotoxicity, Oeystein R. Brekk, Joanna A. Korecka, Cecile C. Crapart, Mylene Huebecker, Zachary K. Macbain, Sara Ann Rosenthal, Miguel Sena-Esteves, David A. Priestman, Frances M. Platt, Ole Isacson, Penelope J. Hallett

Open Access Articles

Sandhoff disease (SD) is a lysosomal storage disease, caused by loss of beta-hexosaminidase (HEX) activity resulting in the accumulation of ganglioside GM2. There are shared features between SD and Parkinson's disease (PD). alpha-synuclein (aSYN) inclusions, the diagnostic hallmark sign of PD, are frequently found in the brain in SD patients and HEX knockout mice, and HEX activity is reduced in the substantia nigra in PD. In this study, we biochemically demonstrate that HEX deficiency in mice causes formation of high-molecular weight (HMW) aSYN and ubiquitin in the brain. As expected from HEX enzymatic function requirements, overexpression in vivo of ...


The Rna Phosphatase Pir-1 Regulates Endogenous Small Rna Pathways In C. Elegans, Daniel A. Chaves, Hui Dai, Lichao Li, James J. Moresco, Myung Eun Oh, Darryl Conte Jr., John R. Yates Iii, Craig C. Mello, Weifeng Gu Aug 2020

The Rna Phosphatase Pir-1 Regulates Endogenous Small Rna Pathways In C. Elegans, Daniel A. Chaves, Hui Dai, Lichao Li, James J. Moresco, Myung Eun Oh, Darryl Conte Jr., John R. Yates Iii, Craig C. Mello, Weifeng Gu

University of Massachusetts Medical School Faculty Publications

Eukaryotic cells regulate 5' triphosphorylated (ppp-) RNAs to promote cellular functions and prevent recognition by antiviral RNA sensors. For example, RNA capping enzymes possess triphosphatase domains that remove the γ phosphates of ppp-RNAs during RNA capping. Members of the closely related PIR1 family of RNA polyphosphatases remove both the β and γ phosphates from ppp-RNAs. Here we show that C. elegans PIR-1 dephosphorylates ppp-RNAs made by cellular RdRPs and is required for the maturation of 26G-RNAs, Dicer-dependent small RNAs that regulate thousands of genes during spermatogenesis and embryogenesis. PIR-1 also regulates the CSR-1 22G-RNA pathway and has critical functions in ...


The Dhodh Inhibitor Ptc299 Arrests Sars-Cov-2 Replication And Suppresses Induction Of Inflammatory Cytokines, Jeremy Luban, Caterina Strambio De Castilla, Yetao Wang, Allan Jacobson, Stuart Peltz Aug 2020

The Dhodh Inhibitor Ptc299 Arrests Sars-Cov-2 Replication And Suppresses Induction Of Inflammatory Cytokines, Jeremy Luban, Caterina Strambio De Castilla, Yetao Wang, Allan Jacobson, Stuart Peltz

University of Massachusetts Medical School Faculty Publications

The coronavirus disease 2019 (COVID-19) pandemic has created an urgent need for therapeutics that inhibit the SARS-CoV-2 virus and suppress the fulminant inflammation characteristic of advanced illness. Here, we describe the anti-COVID-19 potential of PTC299, an orally available compound that is a potent inhibitor of dihydroorotate dehydrogenase (DHODH), the rate-limiting enzyme of the de novo pyrimidine biosynthesis pathway. In tissue culture, PTC299 manifests robust, dose-dependent, and DHODH-dependent inhibition of SARS CoV-2 replication (EC50 range, 2.0 to 31.6 nM) with a selectivity index >3,800. PTC299 also blocked replication of other RNA viruses, including Ebola virus. Consistent with known ...


Separation And Identification Of Permethylated Glycan Isomers By Reversed Phase Nanolc-Nsi-Msn, Simone Kurz, M. Osman Sheikh, Shan Lu, Lance Wells, Michael Tiemeyer Aug 2020

Separation And Identification Of Permethylated Glycan Isomers By Reversed Phase Nanolc-Nsi-Msn, Simone Kurz, M. Osman Sheikh, Shan Lu, Lance Wells, Michael Tiemeyer

University of Massachusetts Medical School Faculty Publications

High performance liquid chromatography has been employed for decades to enhance detection sensitivity and quantification of complex analytes within biological mixtures. Among these analytes, glycans released from glycoproteins and glycolipids have been characterized as underivatized or fluorescently tagged derivatives by HPLC coupled to various detection methods. These approaches have proven extremely useful for profiling the structural diversity of glycoprotein and glycolipid glycosylation but require the availability of glycan standards and secondary orthogonal degradation strategies to validate structural assignments. A robust method for HPLC separation of glycans as their permethylated derivatives, coupled with in-line MSn fragmentation to assign structural features independent ...


Single-Cell Rna Profiling Reveals Adipocyte To Macrophage Signaling Sufficient To Enhance Thermogenesis, Felipe Henriques, Alexander H. Bedard, Adilson L. Guilherme, Mark Kelly, Lawrence M. Lifshitz, Karl D. Bellve, Leslie A. Rowland, Batuhan Yenilmez, Shreya Kumar, Yetao Wang, Jeremy Luban, Michael P. Czech Aug 2020

Single-Cell Rna Profiling Reveals Adipocyte To Macrophage Signaling Sufficient To Enhance Thermogenesis, Felipe Henriques, Alexander H. Bedard, Adilson L. Guilherme, Mark Kelly, Lawrence M. Lifshitz, Karl D. Bellve, Leslie A. Rowland, Batuhan Yenilmez, Shreya Kumar, Yetao Wang, Jeremy Luban, Michael P. Czech

Open Access Articles

Adipocytes deficient in fatty acid synthase (iAdFASNKO) emit signals that mimic cold exposure to enhance the appearance of thermogenic beige adipocytes in mouse inguinal white adipose tissues (iWATs). Both cold exposure and iAdFASNKO upregulate the sympathetic nerve fiber (SNF) modulator Neuregulin 4 (Nrg4), activate SNFs, and require adipocyte cyclic AMP/protein kinase A (cAMP/PKA) signaling for beige adipocyte appearance, as it is blocked by adipocyte Gsalpha deficiency. Surprisingly, however, in contrast to cold-exposed mice, neither iWAT denervation nor Nrg4 loss attenuated adipocyte browning in iAdFASNKO mice. Single-cell transcriptomic analysis of iWAT stromal cells revealed increased macrophages displaying gene expression ...


Atomistic Mechanism Of Force Generation, Translocation, And Coordination In A Viral Genome Packaging Motor, Joshua Pajak, Erik Dill, Mark A. White, Brian A. Kelch, Paul Jardine, Gaurav Arya, Marc C. Morais Aug 2020

Atomistic Mechanism Of Force Generation, Translocation, And Coordination In A Viral Genome Packaging Motor, Joshua Pajak, Erik Dill, Mark A. White, Brian A. Kelch, Paul Jardine, Gaurav Arya, Marc C. Morais

University of Massachusetts Medical School Faculty Publications

Double-stranded DNA viruses package their genomes into pre-assembled protein capsids using virally-encoded ATPase ring motors. While several structures of isolated monomers (subunits) from these motors have been determined, they provide little insight into how subunits within a functional ring coordinate their activities to efficiently generate force and translocate DNA. Here we describe the first atomic-resolution structure of a functional ring form of a viral DNA packaging motor and characterize its atomic-level dynamics via long timescale molecular dynamics simulations. Crystal structures of the pentameric ATPase ring from bacteriophage asccφ28 show that each subunit consists of a canonical N-terminal ASCE ATPase domain ...


July - August 2020, Southwestern Oklahoma State University Aug 2020

July - August 2020, Southwestern Oklahoma State University

RURAL ROCKS

Rural Rocks, the Rural Health Network newsletter by the SWOSU College of Pharmacy.


Loss Of Supervillin Causes Myopathy With Myofibrillar Disorganization And Autophagic Vacuoles, Carola Hedberg-Oldfors, Elizabeth J. Luna, Anders Oldfors, Cordula Knopp Aug 2020

Loss Of Supervillin Causes Myopathy With Myofibrillar Disorganization And Autophagic Vacuoles, Carola Hedberg-Oldfors, Elizabeth J. Luna, Anders Oldfors, Cordula Knopp

Open Access Articles

The muscle specific isoform of the supervillin protein (SV2), encoded by the SVIL gene, is a large sarcolemmal myosin II- and F-actin-binding protein. Supervillin (SV2) binds and co-localizes with costameric dystrophin and binds nebulin, potentially attaching the sarcolemma to myofibrillar Z-lines. Despite its important role in muscle cell physiology suggested by various in vitro studies, there are so far no reports of any human disease caused by SVIL mutations. We here report four patients from two unrelated, consanguineous families with a childhood/adolescence onset of a myopathy associated with homozygous loss-of-function mutations in SVIL. Wide neck, anteverted shoulders and prominent ...


Drug Delivery In Catheterized Arterial Blood Flow With Atherosclerosis, Saulo Orizaga, Daniel N. Riahi, Jose R. Soto Aug 2020

Drug Delivery In Catheterized Arterial Blood Flow With Atherosclerosis, Saulo Orizaga, Daniel N. Riahi, Jose R. Soto

Mathematical and Statistical Sciences Faculty Publications and Presentations

We study the problem of drug delivery in a catheterized artery in the presence of atherosclerosis. The problem is modeled in the context of a two-phase flow system which consists of red blood cells and blood plasma. The coupled differential equations for fluid (plasma) and particles (red cells) are solved for the relevant quantities in the reasonable limits. The drug delivery problem is modeled with a partial differential equation that is developed in terms of the drug concentration, blood plasma velocity, hematocrit value and the diffusion coefficient of the drug/fluid. A conservative-implicit finite difference scheme is develop in order ...


Performance Of Abbott Architect, Ortho Vitros, And Euroimmun Assays In Detecting Prior Sars-Cov-2 Infection, Shiwani Mahajan, Carrie A. Redlich, Adam V. Wisnewski, Louis E. Fazen, Lokinendi V. Rao, Karthik Kuppusamy, Albert I. Ko, Harlan M. Krumholz Jul 2020

Performance Of Abbott Architect, Ortho Vitros, And Euroimmun Assays In Detecting Prior Sars-Cov-2 Infection, Shiwani Mahajan, Carrie A. Redlich, Adam V. Wisnewski, Louis E. Fazen, Lokinendi V. Rao, Karthik Kuppusamy, Albert I. Ko, Harlan M. Krumholz

University of Massachusetts Medical School Faculty Publications

Background: Several serological assays have been developed to detect anti-SARS-CoV-2 IgG antibodies, but evidence about their comparative performance is limited. We sought to assess the sensitivity of four anti-SARS-CoV-2 IgG enzyme-linked immunosorbent assays (ELISA) in individuals with evidence of prior SARS-CoV-2 infection.

Methods: We obtained sera from 36 individuals with PCR-confirmed SARS-CoV-2 infection between March and May 2020. We evaluated samples collected at around 21 days (±14 days) after their initial PCR test using 3 commercially available ELISA assays, two anti-spike (Ortho-Clinical Diagnostics Vitros, and Euroimmun) and one anti-nucleocapsid (Abbott Architect), and a Yale-developed anti-spike ELISA test. We determined the ...


Prospects For Rnai Therapy Of Covid-19, Hasan Uludağ, Kylie Parent, Hamidreza Montazeri Aliabadi, Azita Haddadi Jul 2020

Prospects For Rnai Therapy Of Covid-19, Hasan Uludağ, Kylie Parent, Hamidreza Montazeri Aliabadi, Azita Haddadi

Pharmacy Faculty Articles and Research

COVID-19 caused by the SARS-CoV-2 virus is a fast emerging disease with deadly consequences. The pulmonary system and lungs in particular are most prone to damage caused by the SARS-CoV-2 infection, which leaves a destructive footprint in the lung tissue, making it incapable of conducting its respiratory functions and resulting in severe acute respiratory disease and loss of life. There were no drug treatments or vaccines approved for SARS-CoV-2 at the onset of pandemic, necessitating an urgent need to develop effective therapeutics. To this end, the innate RNA interference (RNAi) mechanism can be employed to develop front line therapies against ...


Mycobacterium Tuberculosis Evasion Of Guanylate Binding Protein-Mediated Host Defense In Mice Requires The Esx1 Secretion System, Andrew J. Olive, Clare M. Smith, Christina E. Baer, Jörn Coers, Christopher M. Sassetti Jul 2020

Mycobacterium Tuberculosis Evasion Of Guanylate Binding Protein-Mediated Host Defense In Mice Requires The Esx1 Secretion System, Andrew J. Olive, Clare M. Smith, Christina E. Baer, Jörn Coers, Christopher M. Sassetti

University of Massachusetts Medical School Faculty Publications

Cell-intrinsic immune mechanisms control intracellular pathogens that infect eukaryotes. The intracellular pathogen Mycobacterium tuberculosis (Mtb) evolved to withstand cell-autonomous immunity to cause persistent infections and disease. A potent inducer of cell-autonomous immunity is the lymphocyte-derived cytokine IFNγ. While the production of IFNγ by T cells is essential to protect against Mtb, it is not capable of fully eradicating Mtb infection. This suggests that Mtb evades a subset of IFNγ-mediated antimicrobial responses, yet what mechanisms Mtb resists remains unclear. The IFNγ-inducible Guanylate binding proteins (GBPs) are key host defense proteins able to control infections with intracellular pathogens. GBPs were previously shown ...


Basement Membrane Damage By Ros- And Jnk-Mediated Mmp2 Activation Drives Macrophage Recruitment To Overgrown Tissue, Neha Diwanji, Andreas Bergmann Jul 2020

Basement Membrane Damage By Ros- And Jnk-Mediated Mmp2 Activation Drives Macrophage Recruitment To Overgrown Tissue, Neha Diwanji, Andreas Bergmann

Open Access Articles

Macrophages are a major immune cell type infiltrating tumors and promoting tumor growth and metastasis. To elucidate the mechanism of macrophage recruitment, we utilize an overgrowth tumor model ("undead" model) in larval Drosophila imaginal discs that are attached by numerous macrophages. Here we report that changes to the microenvironment of the overgrown tissue are important for recruiting macrophages. First, we describe a correlation between generation of reactive oxygen species (ROS) and damage of the basement membrane (BM) in all neoplastic, but not hyperplastic, models examined. ROS and the stress kinase JNK mediate the accumulation of matrix metalloproteinase 2 (Mmp2), damaging ...