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Rfx Transcription Factors Are Essential For Hearing In Mice, Ran Elkon, Beatrice Milon, Laura Morrison, Manan Shah, Sarath Vijayakumar, Manoj Racherla, Carmen C. Leitch, Lorna Silipino, Shadan Hadi, Michèle Weiss-Gayte, Emmanuèle Barras, Christoph D. Schmid, Aouatef Ait-Lounis, Ashley Barnes, Yang Song, David J. Eisenman, Efrat Eliyahu, Gregory I. Frolenkov, Scott E. Strome, Bénédicte Durand, Norann A. Zaghloul, Sherri M. Jones, Walter Reith, Ronna Hertzano Oct 2015

Rfx Transcription Factors Are Essential For Hearing In Mice, Ran Elkon, Beatrice Milon, Laura Morrison, Manan Shah, Sarath Vijayakumar, Manoj Racherla, Carmen C. Leitch, Lorna Silipino, Shadan Hadi, Michèle Weiss-Gayte, Emmanuèle Barras, Christoph D. Schmid, Aouatef Ait-Lounis, Ashley Barnes, Yang Song, David J. Eisenman, Efrat Eliyahu, Gregory I. Frolenkov, Scott E. Strome, Bénédicte Durand, Norann A. Zaghloul, Sherri M. Jones, Walter Reith, Ronna Hertzano

Department of Special Education and Communication Disorders: Faculty Publications

Sensorineural hearing loss is a common and currently irreversible disorder, because mammalian hair cells (HCs) do not regenerate and current stem cell and gene delivery protocols result only in immature HC-like cells. Importantly, although the transcriptional regulators of embryonic HC development have been described, little is known about the postnatal regulators of maturating HCs. Here we apply a cell type-specific functional genomic analysis to the transcriptomes of auditory and vestibular sensory epithelia from early postnatal mice. We identify RFX transcription factors as essential and evolutionarily conserved regulators of the HC-specific transcriptomes, and detect Rfx1,2,3,5 and 7 in the developing HCs. …


Association Of Adipokines With Insulin Resistance, Microvascular Dysfunction, And Endothelial Dysfunction In Healthy Young Adults., Cindy Cheng, Md, Phd, Constantine Daskalakis Oct 2015

Association Of Adipokines With Insulin Resistance, Microvascular Dysfunction, And Endothelial Dysfunction In Healthy Young Adults., Cindy Cheng, Md, Phd, Constantine Daskalakis

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Proinflammatory adipokines (inflammation markers) from visceral adipose tissue may initiate the development of insulin resistance (IR) and endothelial dysfunction (ED). This study's objective was to investigate the association of five inflammation markers (CRP and four adipokines: IL-6, TNFα, PAI-1, and adiponectin) with IR (quantitative insulin resistance check index (QUICKI)), microvascular measures (capillary density and albumin-to-creatinine ratio (ACR)), and endothelial measures (forearm blood flow (FBF) increases from resting baseline to maximal vasodilation). Analyses were conducted via multiple linear regression. The 295 study participants were between 18 and 45 years of age, without diabetes or hypertension. They included 24% African Americans and …


Dynamic Ubiquitination Drives Herpesvirus Neuroinvasion, Nicholas J. Huffmaster, Patricia J. Sollars, Alexsia L. Richards, Gary E. Pickard, Gregory A. Smith Oct 2015

Dynamic Ubiquitination Drives Herpesvirus Neuroinvasion, Nicholas J. Huffmaster, Patricia J. Sollars, Alexsia L. Richards, Gary E. Pickard, Gregory A. Smith

School of Veterinary and Biomedical Sciences: Faculty Publications

Neuroinvasive herpesviruses display a remarkable propensity to enter the nervous system of healthy individuals in the absence of obvious trauma at the site of inoculation. We document a repurposing of cellular ubiquitin during infection to switch the virus between two invasive states. The states act sequentially to defeat consecutive host barriers of the peripheral nervous system and together promote the potent neuroinvasive phenotype. The first state directs virus access to nerve endings in peripheral tissue, whereas the second delivers virus particles within nerve fibers to the neural ganglia. Mutant viruses locked in either state remain competent to overcome the corresponding …


Gsk-3Β Regulates Tumor Growth And Angiogenesis In Human Glioma Cells., Peng Zhao, Qi Li, Zhumei Shi, Charlie Li, Lin Wang, Xue Liu, Chengfei Jiang, Xu Qian, Yongping You, Ning Liu, Ling-Zhi Liu, Lianshu Ding, Bing-Hua Jiang Oct 2015

Gsk-3Β Regulates Tumor Growth And Angiogenesis In Human Glioma Cells., Peng Zhao, Qi Li, Zhumei Shi, Charlie Li, Lin Wang, Xue Liu, Chengfei Jiang, Xu Qian, Yongping You, Ning Liu, Ling-Zhi Liu, Lianshu Ding, Bing-Hua Jiang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Glioma accounts for the majority of primary malignant brain tumors in adults.

METHODS: Glioma specimens and normal brain tissues were analyzed for the expression levels of GSK-3β and p-GSK-3β (Ser9) by tissue microarray analysis (TMA) and Western blotting. Glioma cells over-expressing GSK-3β were used to analyze biological functions both in vitro and in vivo.

RESULTS: The levels of p-GSK-3β (Ser9), but not total GSK-3β, are significantly up-regulated in glioma tissues compared to normal tissues, and are significantly correlated with the glioma grades. Ectopic expression of GSK-3β decreased the phosphorylation levels of mTOR and p70S6K1; and inhibited β-catenin, HIF-1α and …


Role Of The Slingshot-Cofilin And Ranbp9 Pathways In Alzheimer's Disease Pathogenesis, Jung A Woo Oct 2015

Role Of The Slingshot-Cofilin And Ranbp9 Pathways In Alzheimer's Disease Pathogenesis, Jung A Woo

USF Tampa Graduate Theses and Dissertations

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by two major pathological hallmarks, amyloid plaques and neurofibrillary tangles. The accumulation of amyloid-β protein (Aβ) is an early event associated with synaptic and mitochondrial damage in AD. Therefore, molecular pathways underlying the neurotoxicity and generation of Aβ represent promising therapeutic targets for AD. Recent studies have shown that actin severing protein, Cofilin plays an important role in synaptic remodeling, mitochondrial dysfunction, and AD pathogenesis. However, whether Cofilin is an essential component of AD pathogenesis and how Aβ induced neurotoxicity impinges its signals to Cofilin are unclear.

In my dissertation studies, we …


A Tail Of Two Phages: Genomic And Functional Analysis Of Listeria Monocytogenes Phages Vb_Lmos_188 And Vb_Lmos_293 Reveal The Receptor-Binding Proteins Involved In Host Specificity, Aidan Casey, Kieran Jordan, Horst Neve, Aidan Coffey, Olivia Mcauliffe Oct 2015

A Tail Of Two Phages: Genomic And Functional Analysis Of Listeria Monocytogenes Phages Vb_Lmos_188 And Vb_Lmos_293 Reveal The Receptor-Binding Proteins Involved In Host Specificity, Aidan Casey, Kieran Jordan, Horst Neve, Aidan Coffey, Olivia Mcauliffe

Department of Biological Sciences Publications

The physical characteristics of bacteriophages establish them as viable candidates for downstream development of pathogen detection assays and biocontrol measures. To utilize phages for such purposes, a detailed knowledge of their host interaction mechanisms is a prerequisite. There is currently a wealth of knowledge available concerning Gram-negative phage-host interaction, but little by comparison for Gram-positive phages and Listeria phages in particular. In this research, the lytic spectrum of two recently isolated Listeria monocytogenes phages (vB_LmoS_188 and vB_LmoS_293) was determined, and the genomic basis for their observed serotype 4b/4e host-specificity was investigated using comparative genomics. The late tail genes of these …


Cd151-Α3Β1 Integrin Complexes Are Prognostic Markers Of Glioblastoma And Cooperate With Egfr To Drive Tumor Cell Motility And Invasion, Pengcheng Zhou, Sonia Erfani, Zeyi Liu, Changhe Jia, Yecang Chen, Bingwei Xu, Xinyu Deng, Jose E. Alfáro, Li Chen, Dana L. Napier, Michael Lu, Jian-An Huang, Chunming Liu, Olivier Thibault, Rosalind Segal, Binhua P. Zhou, Natasha Kyprianou, Craig Horbinski, Xiuwei H. Yang Oct 2015

Cd151-Α3Β1 Integrin Complexes Are Prognostic Markers Of Glioblastoma And Cooperate With Egfr To Drive Tumor Cell Motility And Invasion, Pengcheng Zhou, Sonia Erfani, Zeyi Liu, Changhe Jia, Yecang Chen, Bingwei Xu, Xinyu Deng, Jose E. Alfáro, Li Chen, Dana L. Napier, Michael Lu, Jian-An Huang, Chunming Liu, Olivier Thibault, Rosalind Segal, Binhua P. Zhou, Natasha Kyprianou, Craig Horbinski, Xiuwei H. Yang

Pharmacology and Nutritional Sciences Faculty Publications

Glioblastoma, one of the most aggressive forms of brain cancer, is featured by high tumor cell motility and invasiveness, which not only fuel tumor infiltration, but also enable escape from surgical or other clinical interventions. Thus, better understanding of how these malignant traits are controlled will be key to the discovery of novel biomarkers and therapies against this deadly disease. Tetraspanin CD151 and its associated α3β1 integrin have been implicated in facilitating tumor progression across multiple cancer types. How these adhesion molecules are involved in the progression of glioblastoma, however, remains largely unclear. Here, we examined an in-house tissue microarray-based …


Cerium Oxide Nanoparticle Treatment Ameliorates Peritonitis-Induced Diaphragm Dysfunction, Shinichi Asano, Ravikumar Arvapalli, Nandini D. Manne, Mani Maheshwari, Bing Ma, Kevin M. Rice, Vellaisamy Selvaraj, Eric Blough Oct 2015

Cerium Oxide Nanoparticle Treatment Ameliorates Peritonitis-Induced Diaphragm Dysfunction, Shinichi Asano, Ravikumar Arvapalli, Nandini D. Manne, Mani Maheshwari, Bing Ma, Kevin M. Rice, Vellaisamy Selvaraj, Eric Blough

MIIR Faculty Research

The severe inflammation observed during sepsis is thought to cause diaphragm dysfunction, which is associated with poor patient prognosis. Cerium oxide (CeO2) nanoparticles have been posited to exhibit anti-inflammatory and antioxidative activities suggesting that these particles may be of potential use for the treatment of inflammatory disorders. To investigate this possibility, Sprague Dawley rats were randomly assigned to the following groups: sham control, CeO2 nanoparticle treatment only (0.5 mg/kg iv), sepsis, and sepsis+CeO2 nanoparticles. Sepsis was induced by the introduction of cecal material (600 mg/kg) directly into the peritoneal cavity. Nanoparticle treatment decreased sepsis-associated impairments in …


Week Of October 5, 2015, New York Medical College Oct 2015

Real-Time Detection Of Breast Cancer Cells Using Peptidefunctionalized Microcantilever Arrays, Hashem Etayash, Keren Jiang, Sarfuddin Azmi, Thomas Thundat, Kamaljit Kaur Oct 2015

Real-Time Detection Of Breast Cancer Cells Using Peptidefunctionalized Microcantilever Arrays, Hashem Etayash, Keren Jiang, Sarfuddin Azmi, Thomas Thundat, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Ligand-directed targeting and capturing of cancer cells is a new approach for detecting circulating tumor cells (CTCs). Ligands such as antibodies have been successfully used for capturing cancer cells and an antibody based system (CellSearch®) is currently used clinically to enumerate CTCs. Here we report the use of a peptide moiety in conjunction with a microcantilever array system to selectively detect CTCs resulting from cancer, specifically breast cancer. A sensing microcantilever, functionalized with a breast cancer specific peptide 18-4 (WxEAAYQrFL), showed significant deflection on cancer cell (MCF7 and MDA-MB-231) binding compared to when exposed to noncancerous (MCF10A and HUVEC) cells. …


Advances In The Diagnosis Of Human Opisthorchiasis: Development Of Opisthorchis Viverrini Antigen Detection In Urine, Chanika Worasith, Christine Kamamia, Anna Yakovleva, Kunyarat Duenngai, Chompunoot Wangboon, Jeffrey M. Bethony, +8 Additional Authors Oct 2015

Advances In The Diagnosis Of Human Opisthorchiasis: Development Of Opisthorchis Viverrini Antigen Detection In Urine, Chanika Worasith, Christine Kamamia, Anna Yakovleva, Kunyarat Duenngai, Chompunoot Wangboon, Jeffrey M. Bethony, +8 Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Many strategies to control opisthorchiasis have been employed in Thailand, but not in the other neighbouring countries. Specific control methods include mass drug administration (MDA) and health education to reduce raw fish consumption. These control efforts have greatly shifted the epidemiology of Opisthorchis viverrini (OV) infection over the last decade from presenting as densely concentrated "heavy" infections in single villages to widespread "light" OV infections distributed over wide geographical areas. Currently, the "gold standard" detection method for OV infection is formalin ethyl-acetate concentration technique (FECT), which has limited diagnostic sensitivity and diagnostic specificity for light OV infections, with OV …


Tracing The Human Healthcare Roots Of Antibiotic Resistance In India: Causes, Challenges, And Promising Solutions, Kelsey Matteson Oct 2015

Tracing The Human Healthcare Roots Of Antibiotic Resistance In India: Causes, Challenges, And Promising Solutions, Kelsey Matteson

Independent Study Project (ISP) Collection

The rapid development of biological defense mechanisms by bacteria, or antibiotic resistance, is a dangerously progressing public health concern worldwide. The spread of antibiotic resistant pathogens are not only a threat to the security of healthcare facilities and the stability of modern medicine across the globe, but this phenomenon also creates a particular burden on countries with a high prevalence of infectious disease such as India. This study attempts to explore India’s unique human healthcare causes of the emergence and spread of antibiotic resistance, comprehend the obstacles that have created roadblocks to change, and outline possible solutions to overcome these …


Myricetin Inhibits Proliferation Of Cisplatin-Resistant Cancer Cells Through A P53-Dependent Apoptotic Pathway, Haizhi Huang, Allen Y. Chen, Xingqian Ye, Bingyun Li, Yon Rojanasakul, Gary O. Rankin, Yi Charlie Chen Oct 2015

Myricetin Inhibits Proliferation Of Cisplatin-Resistant Cancer Cells Through A P53-Dependent Apoptotic Pathway, Haizhi Huang, Allen Y. Chen, Xingqian Ye, Bingyun Li, Yon Rojanasakul, Gary O. Rankin, Yi Charlie Chen

Pharmacology, Physiology and Toxicology

Cisplatin is a commonly used drug for cancer treatment by crosslinking DNA, leading to apoptosis of cancer cells, resistance to cisplatin treatment often occurs, leading to relapse. Therefore, there is a need for the development of more effective treatment strategies that can overcome chemoresistance. Myricetin is a flavonoid from fruits and vegetables, showing anticancer activity in various cancer cells. In this study, we found myricetin exhibited greater cytotoxicity than cisplatin in two cisplatin-resistant ovarian cancer cell lines, OVCAR-3 and A2780/CP70, and it was less cytotoxic to the normal ovarian cell line IOSE-364. Myricetin selectively induced apoptosis in both cisplatinresistant cancer …


We Are… Bridging Medicine And Science, Vol. 1, Issue 4, Fall 2015, Marshall University Biomedical Sciences Oct 2015

We Are… Bridging Medicine And Science, Vol. 1, Issue 4, Fall 2015, Marshall University Biomedical Sciences

We Are... Bridging Medicine Science

No abstract provided.


Carcinogenic Parasite Secretes Growth Factor That Accelerates Wound Healing And Potentially Promotes Neoplasia., Michael J. Smout, Javier Sotillo, Thewarach Laha, Atiroch Papatpremsiri, Gabriel Rinaldi, Rafael N. Pimenta, Paul J. Brindley, +11 More Oct 2015

Carcinogenic Parasite Secretes Growth Factor That Accelerates Wound Healing And Potentially Promotes Neoplasia., Michael J. Smout, Javier Sotillo, Thewarach Laha, Atiroch Papatpremsiri, Gabriel Rinaldi, Rafael N. Pimenta, Paul J. Brindley, +11 More

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Infection with the human liver fluke Opisthorchis viverrini induces cancer of the bile ducts, cholangiocarcinoma (CCA). Injury from feeding activities of this parasite within the human biliary tree causes extensive lesions, wounds that undergo protracted cycles of healing, and re-injury over years of chronic infection. We show that O. viverrini secreted proteins accelerated wound resolution in human cholangiocytes, an outcome that was compromised following silencing of expression of the fluke-derived gene encoding the granulin-like growth factor, Ov-GRN-1. Recombinant Ov-GRN-1 induced angiogenesis and accelerated mouse wound healing. Ov-GRN-1 was internalized by human cholangiocytes and induced gene and protein expression changes associated …


Autophosphorylation Of The Smk1 Mapk Is Spatially And Temporally Regulated By Ssp2 During Meiotic Development In Yeast., Chong Wai Tio, Gregory Omerza, Sham Sunder, Edward Winter Oct 2015

Autophosphorylation Of The Smk1 Mapk Is Spatially And Temporally Regulated By Ssp2 During Meiotic Development In Yeast., Chong Wai Tio, Gregory Omerza, Sham Sunder, Edward Winter

Department of Biochemistry and Molecular Biology Faculty Papers

Smk1 is a meiosis-specific MAPK that controls spore wall morphogenesis in Saccharomyces cerevisiae. Although Smk1 is activated by phosphorylation of the threonine (T) and tyrosine (Y) in its activation loop, it is not phosphorylated by a dual-specificity MAPK kinase. Instead, the T is phosphorylated by the cyclin-dependent kinase (CDK)-activating kinase, Cak1. The Y is autophosphorylated in an intramolecular reaction that requires a meiosis-specific protein named Ssp2. The meiosis-specific CDK-like kinase, Ime2, was previously shown to positively regulate Smk1. Here we show that Ime2 activity is required to induce the translation of SSP2 mRNA at anaphase II. Ssp2 protein is then …


Methods Of Reducing Pain During Bone Marrow Biopsy: A Narrative Review, Mohammad Faizan Zahid Oct 2015

Methods Of Reducing Pain During Bone Marrow Biopsy: A Narrative Review, Mohammad Faizan Zahid

Medical College Documents

Bone marrow examination plays a crucial role in the diagnosis and management of various hematological and systemic diseases. Even though the procedure has been carried out for decades, it remains an extremely painful and uncomfortable experience for a majority of patients. This paper reviews the different strategies used to provide analgesia and summarizes the advantages and drawbacks of one strategy over the other. A literature review was carried out addressing the different approaches to providing pain relief during bone marrow aspiration and biopsy. Several different methods, procedure modifications and protocols are employed at various centers but pain control and analgesia …


Parasite Manipulation Of The Invariant Chain And The Peptide Editor H2-Dm Affects Major Histocompatibility Complex Class Ii Antigen Presentation During Toxoplasma Gondii Infection, Louis-Philippe Leroux, Manami Nishi, Sandy El-Hage, Barbara A. Fox, David I Bzik, Florence Dzierszinsk Oct 2015

Parasite Manipulation Of The Invariant Chain And The Peptide Editor H2-Dm Affects Major Histocompatibility Complex Class Ii Antigen Presentation During Toxoplasma Gondii Infection, Louis-Philippe Leroux, Manami Nishi, Sandy El-Hage, Barbara A. Fox, David I Bzik, Florence Dzierszinsk

Dartmouth Scholarship

Toxoplasma gondii is an obligate intracellular protozoan parasite. This apicomplexan is the causative agent of toxoplasmosis, a leading cause of central nervous system disease in AIDS. It has long been known that T. gondii interferes with major histocompatibility complex class II (MHC-II) antigen presentation to attenuate CD4(+) T cell responses and establish persisting infections. Transcriptional downregulation of MHC-II genes by T. gondii was previously established, but the precise mechanisms inhibiting MHC-II function are currently unknown. Here, we show that, in addition to transcriptional regulation of MHC-II, the parasite modulates the expression of key components of the MHC-II antigen presentation pathway, …


A Neurobiological Pathway That Mediates Stress-Induced Drug Use, Oliver Vranjkovic Oct 2015

A Neurobiological Pathway That Mediates Stress-Induced Drug Use, Oliver Vranjkovic

Dissertations (1934 -)

Cocaine addiction represents a tremendous health and financial burden on our society and the high rate of relapse to cocaine use in abstinent addicts represents a major barrier to effective therapy. Thus, understanding the factors that contribute to relapse and the underlying neurobiological processes is important for guiding the development of treatment for addiction. Stressful life events often trigger drug use in recovering addicts. The contribution of stress to drug use is problematic due to the unpredictable and often uncontrollable nature of stress. A growing literature indicates that norepinephrine and corticotropin releasing factor (CRF) in the brain play key roles …


Human Polyclonal Antibodies Produced Through Dna Vaccination Of Transchromosomal Cattle Provide Mice With Post-Exposure Protection Against Lethal Zaire And Sudan Ebolaviruses., Callie E Bounds, Steven A Kwilas, Ana I Kuehne, Jennifer M Brannan, Russell R Bakken, John M Dye, Jay W Hooper, Lesley C Dupuy, Barry Ellefsen, Drew Hannaman, Hua Wu, Jin-An Jiao, Eddie J Sullivan, Connie S Schmaljohn, Matthias J. Schnell Sep 2015

Human Polyclonal Antibodies Produced Through Dna Vaccination Of Transchromosomal Cattle Provide Mice With Post-Exposure Protection Against Lethal Zaire And Sudan Ebolaviruses., Callie E Bounds, Steven A Kwilas, Ana I Kuehne, Jennifer M Brannan, Russell R Bakken, John M Dye, Jay W Hooper, Lesley C Dupuy, Barry Ellefsen, Drew Hannaman, Hua Wu, Jin-An Jiao, Eddie J Sullivan, Connie S Schmaljohn, Matthias J. Schnell

Department of Medicine Faculty Papers

DNA vaccination of transchromosomal bovines (TcBs) with DNA vaccines expressing the codon-optimized (co) glycoprotein (GP) genes of Ebola virus (EBOV) and Sudan virus (SUDV) produce fully human polyclonal antibodies (pAbs) that recognize both viruses and demonstrate robust neutralizing activity. Each TcB was vaccinated by intramuscular electroporation (IM-EP) a total of four times and at each administration received 10 mg of the EBOV-GPco DNA vaccine and 10 mg of the SUDV-GPco DNA vaccine at two sites on the left and right sides, respectively. After two vaccinations, robust antibody responses (titers > 1000) were detected by ELISA against whole irradiated EBOV or SUDV …


The Dna Structure And Sequence Preferences Of Wrn Underlie Its Function In Telomeric Recombination Events, Deanna N. Edwards, Amrita Machwe, Li Chen, Vilhelm A. Bohr, David K. Orren Sep 2015

The Dna Structure And Sequence Preferences Of Wrn Underlie Its Function In Telomeric Recombination Events, Deanna N. Edwards, Amrita Machwe, Li Chen, Vilhelm A. Bohr, David K. Orren

Toxicology and Cancer Biology Faculty Publications

Telomeric abnormalities caused by loss of function of the RecQ helicase WRN are linked to the multiple premature ageing phenotypes that characterize Werner syndrome. Here we examine WRN's role in telomeric maintenance, by comparing its action on a variety of DNA structures without or with telomeric sequences. Our results show that WRN clearly prefers to act on strand invasion intermediates in a manner that favours strand invasion and exchange. Moreover, WRN unwinding of these recombination structures is further enhanced when the invading strand contains at least three G-rich single-stranded telomeric repeats. These selectivities are most pronounced at NaCl concentrations within …


Distributed Task Related Bold Signal During Auditory Sub-Second Timing, Yuriy Bronshteyn Sep 2015

Distributed Task Related Bold Signal During Auditory Sub-Second Timing, Yuriy Bronshteyn

Kaleidoscope

The brain's input/output functions depend heavily on temporal processing. We sought to identify regions of the brain active in task performance during temporal discrimination of a sub-second auditory interval. We presented ten subjects with 40 paired tones and asked them to judge whether these comparison intervals were longer or shorter than a 100 ms standard. We then localized correlations between the Blood Oxygenation Level Dependent signal and task performance across subjects using event-related functional magnetic resonance imaging. We saw no task-related frontal cortex activation and significant activation of traditional auditory areas. Auditory regions included the bilateral superior and middle temporal …


Week Of September 28, 2015, New York Medical College Sep 2015

The Controversy Of Vaccinations, Nicholas G. Aboreden Sep 2015

The Controversy Of Vaccinations, Nicholas G. Aboreden

The Kabod

Recently vaccination has become a controversial topic. There is a growing number of people who believe that vaccines carry great health risks to patients and therefore refuse to be vaccinated or to vaccinate their children. This ill-informed view of immunizations is beginning to cause serious problems in the United States as growing numbers of disease cases are being seen. A closer look into the science of vaccines and the benefits they have brought, clearly show that not only do vaccines carry very little risk to patients, but they are responsible for the eradication and reduction of multiple debilitating diseases.


Lipin1 Regulates Skeletal Muscle Differentiation Through Extracellular Signal-Regulated Kinase (Erk) Activation And Cyclin D Complex-Regulated Cell Cycle Withdrawal, Weihua Jiang, Jing Zhu, Xun Zhuang, Xiping Zhang, Tao Luo, Karyn Esser, Hongmei Ren Sep 2015

Lipin1 Regulates Skeletal Muscle Differentiation Through Extracellular Signal-Regulated Kinase (Erk) Activation And Cyclin D Complex-Regulated Cell Cycle Withdrawal, Weihua Jiang, Jing Zhu, Xun Zhuang, Xiping Zhang, Tao Luo, Karyn Esser, Hongmei Ren

Saha Cardiovascular Research Center Faculty Publications

Lipin1, an intracellular protein, plays critical roles in controlling lipid synthesis and energy metabolism through its enzymatic activity and nuclear transcriptional functions. Several mouse models of skeletal muscle wasting are associated with lipin1 mutation or altered expression. Recent human studies have suggested that children with homozygous null mutations in the LPIN1 gene suffer from rhabdomyolysis. However, the underlying pathophysiologic mechanism is still poorly understood. In the present study we examined whether lipin1 contributes to regulating muscle regeneration. We characterized the time course of skeletal muscle regeneration in lipin1-deficient fld mice after injury. We found that fld mice exhibited smaller regenerated …


An Overview Of Leber’S Hereditary Optic Neuropathy, Matthew R. Dalton Sep 2015

An Overview Of Leber’S Hereditary Optic Neuropathy, Matthew R. Dalton

The Kabod

Typically affecting males ranging from 20 to 24 years of age, Leber’s Hereditary Optic Neuropathy (LHON) is a disorder that is characterized by an acute loss of central vision. Although a heritable disease, LHON does not follow the patterns of classical Mendelian genetics. In fact, one of the most striking characteristics of LHON is that the disease is virtually always inherited maternally. Unlike most genetic disorders that result from a mutation in genomic DNA, LHON is caused by a mutation in the genetic information of mitochondria (mtDNA). Currently there is no treatment for LHON. Despite this, pharmaceutical interventions and contemporary …


Isoflurane Inhibits Synaptic Vesicle Exocytosis Through Reduced Ca2+ Influx, Not Ca2+-Exocytosis Coupling, Joel Baumgart, Zhen-Yu Zhou, Masato Hara, Daniel Cook, Michael Hoppa Sep 2015

Isoflurane Inhibits Synaptic Vesicle Exocytosis Through Reduced Ca2+ Influx, Not Ca2+-Exocytosis Coupling, Joel Baumgart, Zhen-Yu Zhou, Masato Hara, Daniel Cook, Michael Hoppa

Dartmouth Scholarship

Identifying presynaptic mechanisms of general anesthetics is critical to understanding their effects on synaptic transmission. We show that the volatile anesthetic isoflurane inhibits synaptic vesicle (SV) exocytosis at nerve terminals in dissociated rat hippocampal neurons through inhibition of presynaptic Ca2+ influx without significantly altering the Ca2+ sensitivity of SV exocytosis. A clinically relevant concentration of isoflurane (0.7 mM) inhibited changes in [Ca2+]i driven by single action potentials (APs) by 25 ± 3%, which in turn led to 62 ± 3% inhibition of single AP-triggered exocytosis at 4 mM extracellular Ca2+ ([Ca2+]e). Lowering external Ca2+ to match the isoflurane-induced reduction in …


Mir-497 Decreases Cisplatin Resistance In Ovarian Cancer Cells By Targeting Mtor/P70s6k1., Shaohua Xu, Guang-Bo Fu, Zhen Tao, Jun Ouyang, Fanfei Kong, Bing-Hua Jiang, Xiaoping Wan, Ke Chen Sep 2015

Mir-497 Decreases Cisplatin Resistance In Ovarian Cancer Cells By Targeting Mtor/P70s6k1., Shaohua Xu, Guang-Bo Fu, Zhen Tao, Jun Ouyang, Fanfei Kong, Bing-Hua Jiang, Xiaoping Wan, Ke Chen

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The mechanism of cisplatin resistance in ovarian cancer is not clearly understood. In the present investigation, we found that the expression levels of miR-497 were reduced in chemotherapy-resistant ovarian cancer cells and tumor tissues due to hypermethylation of miR-497 promoter. Low miR-497 expression levels were associated with chemo-resistant phonotype of ovarian cancer. By analyzing the expression levels of miR-497, mTOR and p70S6K1 in a clinical gene-expression array dataset, we found that mTOR and p70S6K1, two proteins correlated to chemotherapy-resistance in multiple types of human cancers, were inversely correlated with miR-497 levels in ovarian cancer tissues. By using an orthotopic ovarian …


Statins Increase Plasminogen Activator Inhibitor Type 1 Gene Transcription Through A Pregnane X Receptor Regulated Element., Frederick M Stanley, Kathryn M Linder, Timothy J Cardozo Sep 2015

Statins Increase Plasminogen Activator Inhibitor Type 1 Gene Transcription Through A Pregnane X Receptor Regulated Element., Frederick M Stanley, Kathryn M Linder, Timothy J Cardozo

Department of Medical Genetics Faculty Papers

Plasminogen activator inhibitor type 1 (PAI-1) is a multifunctional protein that has important roles in inflammation and wound healing. Its aberrant regulation may contribute to many disease processes such as heart disease. The PAI-1 promoter is responsive to multiple inputs including cytokines, growth factors, steroids and oxidative stress. The statin drugs, atorvastatin, mevastatin and rosuvastatin, increased basal and stimulated expression of the PAI-1 promoter 3-fold. A statin-responsive, nuclear hormone response element was previously identified in the PAI-1 promoter, but it was incompletely characterized. We characterized this direct repeat (DR) of AGGTCA with a 3-nucleotide spacer at -269/-255 using deletion and …


Eisosomes Provide Membrane Reservoirs For Rapid Expansion Of The Yeast Plasma Membrane, Ruth Kabeche, Louisa Howard, James B. Moseley Sep 2015

Eisosomes Provide Membrane Reservoirs For Rapid Expansion Of The Yeast Plasma Membrane, Ruth Kabeche, Louisa Howard, James B. Moseley

Dartmouth Scholarship

Cell surface area rapidly increases during mechanical and hypoosmotic stresses. Such expansion of the plasma membrane requires 'membrane reservoirs' that provide surface area and buffer membrane tension, but the sources of this membrane remain poorly understood. In principle, the flattening of invaginations and buds within the plasma membrane could provide this additional surface area, as recently shown for caveolae in animal cells. Here, we used microfluidics to study the rapid expansion of the yeast plasma membrane in protoplasts, which lack the rigid cell wall. To survive hypoosmotic stress, yeast cell protoplasts required eisosomes, protein-based structures that generate long invaginations at …