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2015

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Articles 1 - 21 of 21

Full-Text Articles in Molecular Biology

Homozygous Knockout Of The Piezo1 Gene In The Zebrafish Is Not Associated With Anemia, Boris E. Shmukler, Nicholas C. Huston, Jonathan N. Thon, Chih-Wen Ni, George Kourkoulis, Nathan D. Lawson, Barry H. Paw, Seth L. Alper Dec 2015

Homozygous Knockout Of The Piezo1 Gene In The Zebrafish Is Not Associated With Anemia, Boris E. Shmukler, Nicholas C. Huston, Jonathan N. Thon, Chih-Wen Ni, George Kourkoulis, Nathan D. Lawson, Barry H. Paw, Seth L. Alper

Molecular, Cell and Cancer Biology Publications

We have now examined the erythroid phenotype in this zebrafish strain carrying a ZFN genomic knockout of piezo1. Genotyping was performed as previously described. In contrast to the anemic phenotype observed in zebrafish subjected to morpholino knockdown of piezo, the genomic ZFN knockout of piezo1 did not segregate either with anemia in the 3-dpf embryo or with dysmorphic erythrocyte morphology in the adult fish.


Psychiatric Gene Discoveries Shape Evidence On Adhd's Biology, Anita Thapar, J. Martin, Eric Mick, A. Arias Vasquez, Kate Langley, Stephen W. Scherer, Russell Schachar, Jennifer Crosbie, N. Williams, Barbara Franke, J. Elia, J. Glessner, H. Hakonarson, M. J. Owen, S. V. Faraone, Michael C. O'Donovan, Peter Holmans Nov 2015

Psychiatric Gene Discoveries Shape Evidence On Adhd's Biology, Anita Thapar, J. Martin, Eric Mick, A. Arias Vasquez, Kate Langley, Stephen W. Scherer, Russell Schachar, Jennifer Crosbie, N. Williams, Barbara Franke, J. Elia, J. Glessner, H. Hakonarson, M. J. Owen, S. V. Faraone, Michael C. O'Donovan, Peter Holmans

UMass Center for Clinical and Translational Science Supported Publications

A strong motivation for undertaking psychiatric gene discovery studies is to provide novel insights into unknown biology. Although attention-deficit hyperactivity disorder (ADHD) is highly heritable, and large, rare copy number variants (CNVs) contribute to risk, little is known about its pathogenesis and it remains commonly misunderstood. We assembled and pooled five ADHD and control CNV data sets from the United Kingdom, Ireland, United States of America, Northern Europe and Canada. Our aim was to test for enrichment of neurodevelopmental gene sets, implicated by recent exome-sequencing studies of (a) schizophrenia and (b) autism as a means of testing the hypothesis that ...


Cladribine Analogues Via O6-(Benzotriazolyl) Derivatives Of Guanine Nucleosides, Sakilam Satishkumar, Prasanna K. Vuram, Siva Subrahmanyam Relangi, Venkateshwarlu Gurram, Hong Zhou, Robert J. Kreitman, Michelle M. Martínez Montemayor, Lijia Yang, Muralidharan Kaliyaperumal, Somesh Sharma, Narender Pottabathini, Mahesh K. Lakshman Oct 2015

Cladribine Analogues Via O6-(Benzotriazolyl) Derivatives Of Guanine Nucleosides, Sakilam Satishkumar, Prasanna K. Vuram, Siva Subrahmanyam Relangi, Venkateshwarlu Gurram, Hong Zhou, Robert J. Kreitman, Michelle M. Martínez Montemayor, Lijia Yang, Muralidharan Kaliyaperumal, Somesh Sharma, Narender Pottabathini, Mahesh K. Lakshman

Publications and Research

Cladribine, 2-chloro-2′-deoxyadenosine, is a highly efficacious, clinically used nucleoside for the treatment of hairy cell leukemia. It is also being evaluated against other lymphoid malignancies and has been a molecule of interest for well over half a century. In continuation of our interest in the amide bond-activation in purine nucleosides via the use of (benzotriazol-1yl-oxy)tris(dimethylamino)phosphonium hexafluorophosphate, we have evaluated the use of O6-(benzotriazol-1-yl)-2′-deoxyguanosine as a potential precursor to cladribine and its analogues. These compounds, after appropriate deprotection, were assessed for their biological activities, and the data are presented herein. Against hairy cell leukemia ...


Circulating Cell And Plasma Microrna Profiles Differ Between Non-St-Segment And St-Segment-Elevation Myocardial Infarction, Jeanine Ward, Nada Esa, Rahul Pidikiti, Jane E. Freedman, John F. Keaney, Kahraman Tanriverdi, Olga Vitseva, Victor R. Ambros, Rosalind Lee, David D. Mcmanus Oct 2015

Circulating Cell And Plasma Microrna Profiles Differ Between Non-St-Segment And St-Segment-Elevation Myocardial Infarction, Jeanine Ward, Nada Esa, Rahul Pidikiti, Jane E. Freedman, John F. Keaney, Kahraman Tanriverdi, Olga Vitseva, Victor R. Ambros, Rosalind Lee, David D. Mcmanus

Victor R. Ambros

BACKGROUND: Differences in plasma and whole blood expression microRNAs (miRNAs) in patients with an acute coronary syndrome (ACS) have been determined in both in vitro and in vivo studies. Although most circulating miRNAs are located in the cellular components of whole blood, little is known about the miRNA profiles of whole blood subcomponents, including plasma, platelets and leukocytes in patients with myocardial ischemia. METHODS: Thirteen patients with a ST-segment-elevation (STEMI) or non-ST-segment elevation (NSTEMI) myocardial infarction were identified in the University of Massachusetts Medical Center Emergency Department (ED) or cardiac catheterization laboratory between February and June of 2012. Whole blood ...


Homozygous Aloxe3 Nonsense Variant Identified In A Patient With Non-Bullous Congenital Ichthyosiform Erythroderma Complicated By Superimposed Bullous Majocchi's Granuloma: The Consequences Of Skin Barrier Dysfunction, Tao Wang, Chenchen Xu, Xiping Zhou, Chunjia Li, Hongbing Zhang, Bill Q. Lian, Jonathan J. Lee, Jun Shen, Yuehua Liu, Christine Guo Lian Sep 2015

Homozygous Aloxe3 Nonsense Variant Identified In A Patient With Non-Bullous Congenital Ichthyosiform Erythroderma Complicated By Superimposed Bullous Majocchi's Granuloma: The Consequences Of Skin Barrier Dysfunction, Tao Wang, Chenchen Xu, Xiping Zhou, Chunjia Li, Hongbing Zhang, Bill Q. Lian, Jonathan J. Lee, Jun Shen, Yuehua Liu, Christine Guo Lian

Open Access Articles

Non-bullous congenital ichthyosiform erythroderma (NBCIE) is a hereditary disorder of keratinization caused by pathogenic variants in genes encoding enzymes important to lipid processing and terminal keratinocyte differentiation. Impaired function of these enzymes can cause pathologic epidermal scaling, significantly reduced skin barrier function. In this study, we have performed a focused, genetic analysis of a probrand affected by NBCIE and extended this to his consanguineous parents. Targeted capture and next-generation sequencing was performed on NBCIE associated genes in the proband and his unaffected consanguineous parents. We identified a homozygous nonsense variant c.814C > T (p.Arg272*) in ALOXE3 (NM_001165960.1) in ...


Weekly Treatment Of 2-Hydroxypropyl-Beta-Cyclodextrin Improves Intracellular Cholesterol Levels In Ldl Receptor Knockout Mice, Sofie M.A. Walenbergh, Tom Houben, Tim Hendrikx, Mike L.J. Jeurissen, Patrick J. Van Gorp, Nathalie Vaes, Steven W.M. Olde Damink, Fons Verheyen, Ger H. Koek, Dieter Lutjohann, Alena Grebe, Eicke Latz, Ronit Shiri-Sverdlov Sep 2015

Weekly Treatment Of 2-Hydroxypropyl-Beta-Cyclodextrin Improves Intracellular Cholesterol Levels In Ldl Receptor Knockout Mice, Sofie M.A. Walenbergh, Tom Houben, Tim Hendrikx, Mike L.J. Jeurissen, Patrick J. Van Gorp, Nathalie Vaes, Steven W.M. Olde Damink, Fons Verheyen, Ger H. Koek, Dieter Lutjohann, Alena Grebe, Eicke Latz, Ronit Shiri-Sverdlov

Open Access Articles

Recently, the importance of lysosomes in the context of the metabolic syndrome has received increased attention. Increased lysosomal cholesterol storage and cholesterol crystallization inside macrophages have been linked to several metabolic diseases, such as atherosclerosis and non-alcoholic fatty liver disease (NAFLD). Two-hydroxypropyl-beta-cyclodextrin (HP-B-CD) is able to redirect lysosomal cholesterol to the cytoplasm in Niemann-Pick type C1 disease, a lysosomal storage disorder. We hypothesize that HP-B-CD ameliorates liver cholesterol and intracellular cholesterol levels inside Kupffer cells (KCs). Hyperlipidemic low-density lipoprotein receptor knockout (Ldlr(-/-)) mice were given weekly, subcutaneous injections with HP-B-CD or control PBS. In contrast to control injections, hyperlipidemic mice ...


Positive Selection Drives Preferred Segment Combinations During Influenza Virus Reassortment, Konstantin Zeldovich, Ping Liu, Nicholas Renzette, Matthieu Foll, Serena Pham, Sergey Venev, Glen Gallagher, Daniel Bolon, Evelyn Kurt-Jones, Jeffrey Jensen, Daniel Caffrey, Celia Schiffer, Timothy Kowalik, Jennifer Wang, Robert Finberg Jun 2015

Positive Selection Drives Preferred Segment Combinations During Influenza Virus Reassortment, Konstantin Zeldovich, Ping Liu, Nicholas Renzette, Matthieu Foll, Serena Pham, Sergey Venev, Glen Gallagher, Daniel Bolon, Evelyn Kurt-Jones, Jeffrey Jensen, Daniel Caffrey, Celia Schiffer, Timothy Kowalik, Jennifer Wang, Robert Finberg

Celia A. Schiffer

Influenza A virus (IAV) has a segmented genome that allows for the exchange of genome segments between different strains. This reassortment accelerates evolution by breaking linkage, helping IAV cross species barriers to potentially create highly virulent strains. Challenges associated with monitoring the process of reassortment in molecular detail have limited our understanding of its evolutionary implications. We applied a novel deep sequencing approach with quantitative analysis to assess the in vitro temporal evolution of genomic reassortment in IAV. The combination of H1N1 and H3N2 strains reproducibly generated a new H1N2 strain with the hemagglutinin and nucleoprotein segments originating from H1N1 ...


Local Modulation And Measurement Of Macrophage-Derived Bioactive Proteins From Implanted Biomaterials In Rat, Geetika Bajpai May 2015

Local Modulation And Measurement Of Macrophage-Derived Bioactive Proteins From Implanted Biomaterials In Rat, Geetika Bajpai

Theses and Dissertations

Fibrosis around the implanted medical devices is a severe problem that can plague long-term device reliability. Activation of macrophage phenotype (macrophage polarization) has emerged as a new and possible means for reducing fibrosis in the fields of biomaterials and regenerative medicine. Macrophages are phagocytic cells that respond to microenvironmental cues that direct their phenotype. Macrophage activation has been widely studied in mouse and human in the context of tumor biology, yet little information is available regarding how macrophage activation could be used in a biomaterials context. Further, rats rather than mice are the common subjects in biomaterials experiments. A significant ...


Circulating Cell And Plasma Microrna Profiles Differ Between Non-St-Segment And St-Segment-Elevation Myocardial Infarction, Jeanine Ward, Nada Esa, Rahul Pidikiti, Jane E. Freedman, John F. Keaney, Kahraman Tanriverdi, Olga Vitseva, Victor R. Ambros, Rosalind Lee, David D. Mcmanus Feb 2015

Circulating Cell And Plasma Microrna Profiles Differ Between Non-St-Segment And St-Segment-Elevation Myocardial Infarction, Jeanine Ward, Nada Esa, Rahul Pidikiti, Jane E. Freedman, John F. Keaney, Kahraman Tanriverdi, Olga Vitseva, Victor R. Ambros, Rosalind Lee, David D. Mcmanus

David D. McManus

BACKGROUND: Differences in plasma and whole blood expression microRNAs (miRNAs) in patients with an acute coronary syndrome (ACS) have been determined in both in vitro and in vivo studies. Although most circulating miRNAs are located in the cellular components of whole blood, little is known about the miRNA profiles of whole blood subcomponents, including plasma, platelets and leukocytes in patients with myocardial ischemia.

METHODS: Thirteen patients with a ST-segment-elevation (STEMI) or non-ST-segment elevation (NSTEMI) myocardial infarction were identified in the University of Massachusetts Medical Center Emergency Department (ED) or cardiac catheterization laboratory between February and June of 2012. Whole blood ...


The Therapeutic Targeting Of Folate Receptor Alpha Positive Tumors Via Folate Receptor Selective Novel 5- And 6- Substituted Pyrrolo [2,3-D]Pyrimidine Antifolates", Shermaine Kimberly Mitchell-Ryan Jan 2015

The Therapeutic Targeting Of Folate Receptor Alpha Positive Tumors Via Folate Receptor Selective Novel 5- And 6- Substituted Pyrrolo [2,3-D]Pyrimidine Antifolates", Shermaine Kimberly Mitchell-Ryan

Wayne State University Dissertations

Ovarian Cancer is the fifth leading cause of cancer-related death of women in the United States. Epithelial Ovarian Cancer (EOC) constitutes 85-90% of malignancies within the ovary, with an alarming majority of these cases diagnosed at advanced stage. While most patients are initially highly responsive to the current treatment standard, there is a very high probability that they will recur with a drug resistant fatal disease. Currently there is no validated comprehensive model of disease progression for ovarian cancer, although tremendous progress has been made in understanding the origin of this disease and a putative precursor lesion has been identified ...


Extraordinary Diversity Of Immune Response Proteins Among Sea Urchins: Nickel-Isolated Sp185/333 Proteins Show Broad Variations In Size And Charge., Lauren S. Sherman, Catherine S. Schrankel, Kristy J. Brown, L. Courtney Smith Jan 2015

Extraordinary Diversity Of Immune Response Proteins Among Sea Urchins: Nickel-Isolated Sp185/333 Proteins Show Broad Variations In Size And Charge., Lauren S. Sherman, Catherine S. Schrankel, Kristy J. Brown, L. Courtney Smith

Pediatrics Faculty Publications

Effective protection against pathogens requires the host to produce a wide range of immune effector proteins. The Sp185/333 gene family, which is expressed by the California purple sea urchin Strongylocentrotus purpuratus in response to bacterial infection, encodes a highly diverse repertoire of anti-pathogen proteins. A subset of these proteins can be isolated by affinity to metal ions based on multiple histidines, resulting in one to four bands of unique molecular weight on standard Western blots, which vary depending on the individual sea urchin. Two dimensional gel electrophoresis (2DE) of nickel-isolated protein samples followed by Western blot was employed to ...


Nitric Oxide Generating/Releasing Materials, Honying Liang, Parimala Nacharaju, Adam J. Friedman, Joel Friedman Jan 2015

Nitric Oxide Generating/Releasing Materials, Honying Liang, Parimala Nacharaju, Adam J. Friedman, Joel Friedman

Dermatology Faculty Publications

Harnessing the impressive therapeutic potential of nitric oxide (NO) remains an ongoing challenge. This paper describes several of the current strategies both with respect to the underlying chemistry and physics and to the applications where they have shown promise. Included in this overview are molecular systems such as NONOates that release NO through chemical reactions and delivery vehicles such as nanoparticles that can generate, store, transport and deliver NO and related bioactive forms of NO such as nitrosothiols. Although there has been much positive movement, it is clear that we are only at the early stages of knowing how to ...


Mach: A Model For Explaining Molecular And Cellular Mechanisms, Caleb M. Trujillo Jan 2015

Mach: A Model For Explaining Molecular And Cellular Mechanisms, Caleb M. Trujillo

Open Access Dissertations

Biologists use mechanistic explanations to understand behaviors of the immense complexity of molecular and cellular systems. In undergraduate biology courses, students are expected to explain molecular and cellular mechanisms, but teaching this skill presents many challenges due to the highly abstract, intangible nature of the cellular world, the influence of everyday language, and the tendency of students to overestimate how much they can explain. Therefore, across three studies this dissertation addresses these obstacles to teach undergraduate biology students to explain molecular and cellular mechanisms. ^ The first step was to model how biology experts explain molecular and cellular mechanisms, and to ...


Alarming Immunity: A Wake Up Call For Cd8 T Cells Using Genetic Adjuvants (Il-33 And Isg15), Daniel Villarreal Jan 2015

Alarming Immunity: A Wake Up Call For Cd8 T Cells Using Genetic Adjuvants (Il-33 And Isg15), Daniel Villarreal

Publicly Accessible Penn Dissertations

There exists a paramount need for effective vaccines against cancer, TB, malaria, HIV, HCV, and other chronic infections. The hope for long-term control of these important diseases ultimately may depend upon development of potent T cell-based therapeutic vaccines. However, current, licensed vaccines or capable vaccine platforms have not made a substantial impact on treatment of these conditions, likely due in part to poor CD8 T cell immune induction. Thus, identification of novel adjuvants to be deployed to induce effective T responses is an important area of research in T cell based vaccines. While multiple adjuvants have been readily identified which ...


Context- Dependent Gene Expression Programs Promote Lymphocyte Development And Function And Suppress Transformation, Amy Demicco Jan 2015

Context- Dependent Gene Expression Programs Promote Lymphocyte Development And Function And Suppress Transformation, Amy Demicco

Publicly Accessible Penn Dissertations

Coordinated orchestration of gene expression programs at the transcriptional, post-transcriptional, and post-translational levels is essential for development and function of all cells, including lymphocytes. Normal tissue function also demands that the genome be faithfully passed from mother to daughter cell during the many rounds of cell division required to generate a mammalian organism. Genome integrity is maintained in part by integration of DNA damage signaling with cell cycle control. These mechanisms are especially critical for lymphocytes following V(D)J recombination, since V(D)J recombination involves genetic cutting and pasting of germline gene segments to form antigen receptors (AgRs ...


Adeno-Associated Viral Vector-Driven Expression Of Coagulation Proteins For Treatment Of Hemophilias And Cancer, Julie Marie Crudele Jan 2015

Adeno-Associated Viral Vector-Driven Expression Of Coagulation Proteins For Treatment Of Hemophilias And Cancer, Julie Marie Crudele

Publicly Accessible Penn Dissertations

Treatment of hemophilia, which involves infusion of the missing clotting factor, is often hindered by the development of neutralizing antibodies to the replaced clotting factor. We utilized liver-directed AAV gene therapy to tolerize outbred hemophiliac dogs with pre-existing anti-factor VIII and IX antibodies and to treat their underlying hemophilia. Additionally, we sought to shed light on the immunologic mechanisms responsible for this tolerization. Staining for CD4+CD25+FoxP3+ T cells and cytokine profiles of treated dogs suggest that induced Tregs are at least partially responsible for inducing and maintaining tolerance.

The second part of the dissertation attempts to determine the ...


Liver Perilipin 5 Expression Worsens Hepatosteatosis But Not Insulin Resistance In High Fat-Fed Mice, Michelle B. Trevino, David Mazur-Hart, Yui Machida, Timothy King, Joseph Nadler, Elena V. Galkina, Arjun Poddar, Sucharita Dutta, Yumi Imai Jan 2015

Liver Perilipin 5 Expression Worsens Hepatosteatosis But Not Insulin Resistance In High Fat-Fed Mice, Michelle B. Trevino, David Mazur-Hart, Yui Machida, Timothy King, Joseph Nadler, Elena V. Galkina, Arjun Poddar, Sucharita Dutta, Yumi Imai

Mathematics & Statistics Faculty Publications

Perilipin 5 (PLIN5) is a lipid droplet (LD) protein highly expressed in oxidative tissues, including the fasted liver. However, its expression also increases in nonalcoholic fatty liver. To determine whether PLIN5 regulates metabolic phenotypes of hepatosteatosis under nutritional excess, liver targeted overexpression of PLIN5 was achieved using adenoviral vector (Ad-PLIN5) in male C57BL/6J mice fed high-fat diet. Mice treated with adenovirus expressing green fluorescent protein (GFP) (Ad-GFP) served as control. Ad-PLIN5 livers increased LD in the liver section, and liquid chromatography with tandem mass spectrometry revealed increases in lipid classes associated with LD, including triacylglycerol, cholesterol ester, and phospholipid ...


Photodynamic Therapy As An Effective Therapeutic Approach In Mame Models Of Triple Negative And Inflammatory Breast Cancers, Neha Aggarwal Jan 2015

Photodynamic Therapy As An Effective Therapeutic Approach In Mame Models Of Triple Negative And Inflammatory Breast Cancers, Neha Aggarwal

Wayne State University Dissertations

Introduction: Photodynamic therapy (PDT) is a minimally invasive, FDA approved therapy for

treatment of several indications including endobronchial and esophageal cancers that are

accessible to light. Triple negative breast cancer (TNBC) and inflammatory breast cancer (IBC)

are aggressive and lethal subtypes of breast cancer that spread to chest wall and dermal

lymphatics, respectively, sites that would be accessible to light. Both TNBC and IBC patients

have a relatively poor survival rate due to lack of targeted therapies. Use of PDT is

underexplored for breast cancers but has been proposed for treatment of subtypes for which a

targeted therapy is unavailable ...


Host Target Genes Of The Xanthomonas Oryzae Pv. Oryzae Type Iii Effectors For Bacterial Blight In Rice, Junhui Zhou Jan 2015

Host Target Genes Of The Xanthomonas Oryzae Pv. Oryzae Type Iii Effectors For Bacterial Blight In Rice, Junhui Zhou

Graduate Theses and Dissertations

Xanthomonas oryzae pv. oryzae is the causal agent of the bacterial blight in rice, which invades the host rice plant through injecting a myriad of effector proteins through a structure called type Ⅲ secretion system, thereafter, these effectors are also called type Ⅲ effectors. There are two groups of type Ⅲ effectors: TAL (Transcription Activator-Like) effectors that specifically bind to the promoter region of particular host genes and regulate host gene transcription and Non-TAL effectors that bind to host gene products and manipulate the host immune system.

In this thesis, I present the work of three projects. First, I, and ...


Molecular Characterization Of Human, Bovine, And Dolphin Parainfluenza Viruses: Viral Genome Sequencing And Epithelial Cell Signaling Responses Following In Vitro Infection, Kirsten Charlotte Eberle Jan 2015

Molecular Characterization Of Human, Bovine, And Dolphin Parainfluenza Viruses: Viral Genome Sequencing And Epithelial Cell Signaling Responses Following In Vitro Infection, Kirsten Charlotte Eberle

Graduate Theses and Dissertations

This dissertation aims at examining immunological response(s) to PIV-3 infection using in vitro cell culture systems. Based on previous publications, TtPIV-1 was found to be similar to, but distinct from, both human and bovine PIV-3 isolates. These initial findings were based only upon partial sequences of the F and HN viral genes. In Chapter 2 TtPIV-1 is further characterized on cytokine production, viral growth over time, and full genome sequencing as compared to BPIV-3 and HPIV-3. Chapter 3 is aimed at examining the type III IFN response during TtPIV-1, BPIV-3, and HPIV-3 infection. Because paramyxoviruses are known to affect ...


Design And Evaluation Of Immunogens Based On Gp41 Membrane-Proximal External Region For Development Of A Vaccine Against Human Immunodeficiency Virus Type 1, Saikat Banerjee Jan 2015

Design And Evaluation Of Immunogens Based On Gp41 Membrane-Proximal External Region For Development Of A Vaccine Against Human Immunodeficiency Virus Type 1, Saikat Banerjee

Graduate Theses and Dissertations

Since its discovery in 1981, HIV-1 has infected ~78 million people and killed ~39 million people. Developing an HIV-1 vaccine remains one of the top priorities in the fight against this devastating pandemic. The modest efficacy showed by the recent RV144 trial suggests that achieving this goal might be possible. As the search for an effective vaccine continues, the induction of antibodies that can neutralize a large number of antigenically distinct viruses from different clades remains a major goal. In recent years, a number of broadly neutralizing antibodies (bnAbs) that target the HIV-1 envelope have been isolated from virus-infected patients ...