Digital Commons Network^™

Week Of November 16, 2015, New York Medical College

InTouch

• Amy S. Kahn Named Vice President for Development and Alumni Affairs
• BioInc@NYMC Welcomes Two New Clients
• Three High School Students Named Siemens Competition Semi-Finalists

Emerging Immunopharmacological Targets In Multiple Sclerosis., Mojtaba Farjam, Guang-Xian Zhang, Bogoljub Ciric, Abdolmohamad Rostami

Department of Neurology Faculty Papers

Inflammatory demyelination of the central nervous system (CNS) is the hallmark of multiple sclerosis (MS), a chronic debilitating disease that affects more than 2.5 million individuals worldwide. It has been widely accepted, although not proven, that the major pathogenic mechanism of MS involves myelin-reactive T cell activation in the periphery and migration into the CNS, which subsequently triggers an inflammatory cascade that leads to demyelination and axonal damage. Virtually all MS medications now in use target the immune system and prevent tissue damage by modulating neuroinflammatory processes. Although current therapies such as commonly prescribed disease-modifying medications decrease the relapse rate …

Mice Deficient In Endothelial Α5 Integrin Are Profoundly Resistant To Experimental Ischemic Stroke, Jill Roberts, Leon De Hoog, Gregory J. Bix

Sanders-Brown Center on Aging Faculty Publications

Stroke is a disease in dire need of better therapies. We have previously shown that a fragment of the extracellular matrix proteoglycan, perlecan, has beneficial effects following cerebral ischemia via the α5β1 integrin receptor. We now report that endothelial cell selective α5 integrin deficient mice (α5 KO) are profoundly resistant to ischemic infarct after transient middle cerebral artery occlusion. Specifically, α5 KOs had little to no infarct 2–3 days post-stroke, whereas controls had an increase in mean infarct volume over the same time period as expected. Functional outcome is also improved in the α5 KOs compared with controls. Importantly, no …

Science Associated With Producing Gmos, Darren Stoub

Faculty Work Comprehensive List

"Are our understandings of GMOs based in reality? Are GMOs bad? Are they good? Should we make them? These are challenging questions. We, as a society, must discuss the issues."

Posting about the science associated with GMOs from In All Things - an online hub committed to the claim that the life, death, and resurrection of Jesus Christ has implications for the entire world.

http://inallthings.org/the-science-associated-with-producing-gmos/

Murine Cmv Infection Induces The Continuous Production Of Mucosal Resident T Cells., Corinne J Smith, Sofia Caldeira-Dantas, Holly Turula, Christopher M. Snyder

Department of Microbiology and Immunology Faculty Papers

Cytomegalovirus (CMV) is a herpesvirus that persists for life and maintains extremely large numbers of T cells with select specificities in circulation. However, it is unknown how viral persistence impacts T cell populations in mucosal sites. We found that many murine (M)CMV-specific CD8s in mucosal tissues became resident memory T cells (TRM). These cells adopted an intraepithelial localization in the salivary gland that correlated with, but did not depend on, expression of the integrin CD103. MCMV-specific TRM cells formed early after infection, and spleen-localized cells had reduced capacities to become TRM at late times. Surprisingly, however, small numbers of new …

Sh2 Ligand-Like Effects Of Second Cytosolic Domain Of Na/K-Atpase Α1 Subunit On Src Kinase, Moumita Banerjee, Qiming Duan, Zijian Xie

Pharmaceutical Science and Research

Our previous studies have suggested that the α1 Na/K-ATPase interacts with Src to form a receptor complex. In vitro binding assays indicate an interaction between second cytosolic domain (CD2) of Na/K-ATPase α1 subunit and Src SH2 domain. Since SH2 domain targets Src to specific signaling complexes, we expressed CD2 as a cytosolic protein and studied whether it could act as a Src SH2 ligand in LLC-PK1 cells. Co-immunoprecipitation analyses indicated a direct binding of CD2 to Src, consistent with the in vitro binding data. Functionally, CD2 expression increased basal Src activity, suggesting a Src SH2 ligand-like property of CD2. Consistently, …

Week Of November 9, 2015, New York Medical College

InTouch

• Penghua Wang, Ph.D., Identifies Protein that Fights Intestinal Bugs
• Changes are Coming to NYMC's Open Enrollment and Payroll
• The Flu Vaccine is Now Available in Health Services

A Phase I Study Of Ad5-Gucy2c-Padre In Stage I And Ii Colon Cancer Patients, Adam E. Snook, Trevor R. Baybutt, Michael J. Mastrangelo, Nancy L. Lewis, Scott D. Goldstein, Walter K. Kraft, Yaa D. Oppong, Terry Hyslop, Ronald E. Myers, Vitali Alexeev, Laurence C. Eisenlohr, Takami Sato, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Posters

Background

Ad5-GUCY2C-PADRE is a replication-deficient human type 5 recombinant adenovirus (Ad5) vaccine encoding guanylyl cyclase C (GUCY2C) fused to the PAn DR Epitope (PADRE). GUCY2C, a paracrine hormone receptor producing the second messenger cyclic GMP (cGMP), is selectively expressed by intestinal epithelial cells and a subset of hypothalamic neurons, but not other tissues. Importantly, GUCY2C is over-expressed in nearly all primary and metastatic human colorectal tumors. Preclinical studies in mice demonstrated selective tolerance of GUCY2C-specific CD4+ T cells, but not CD8+ T or B cells, necessitating inclusion of the exogenous CD4+ T helper cell epitope PADRE to maximize GUCY2C-specific CD8+ …

Identification And Characterization Of The Interaction Site Between Cflipl And Calmodulin, Gabriel Gaidos, Alexandra E. Panaitiu, Bingqian Guo, Maria Pellegrini, Dale F. Mierke

Dartmouth Scholarship

Overexpression of the cellular FLICE-like inhibitory protein (cFLIP) has been reported in a number of tumor types. As an inactive procaspase-8 homologue, cFLIP is recruited to the intracellular assembly known as the Death Inducing Signaling Complex (DISC) where it inhibits apoptosis, leading to cancer cell proliferation. Here we characterize the molecular details of the interaction between cFLIP_L and calmodulin, a ubiquitous calcium sensing protein. By expressing the individual domains of cFLIP_L, we demonstrate that the interaction with calmodulin is mediated by the N-terminal death effector domain (DED1) of cFLIP_L. Additionally, we mapped the interaction to …

Hiv-1-Tat Protein Inhibits Sc35-Mediated Tau Exon 10 Inclusion Through Up-Regulation Of Dyrk1a Kinase, Ferdous Kadri, Marco Pacifici, Anna Wilk, Amanda Parker-Struckhoff, Luis Del Valle, Kurt F. Hauser, Pamela E. Knapp, Christopher Parsons, Duane Jeansonne, Adam Lassak, Francesca Peruzzi

School of Medicine Faculty Publications

The HIV-1 transactivator protein Tat is implicated in the neuronal damage that contributes to neurocognitive impairment affecting people living with HIV/AIDS. Aberrant splicing of TAU exon 10 results in tauopathies characterized by alterations in the proportion of TAU isoforms containing three (3R) or four (4R) microtubule-binding repeats. The splicing factor SC35/SRSF2 binds to nuclear RNA and facilitates the incorporation of exon 10 in the TAU molecule. Here, we utilized clinical samples, an animal model, and neuronal cell cultures and found that Tat promotes TAU 3R up-regulation through increased levels of phosphorylated SC35, which is retained in nuclear speckles. This mechanism …

Week Of November 2, 2015, New York Medical College

InTouch

• NYMC Supporters Gather at Founder's Dinner
• School of Medicine Hosts Cardiovascular Translational Research Workshop
• Medical Student, Adrian Romero, is the Recipient of 2015 AMA Foundation
• SHSP Hosts Two-Day Asthma Institute
• NYMC Hosts Second Annual Pre-Medical and Pre-Health Mentoring Program
• More NYMC History Adorns Walls of BSB
• Speech-Language Pathology Students Lead Disabilities Awareness Challenge at Local Boy Scout Event
• Peer to Peer Committee Recognizes Role Models at NYMC

Carcinogenic Liver Fluke Secretes Extracellular Vesicles That Promote Cholangiocytes To Adopt A Tumorigenic Phenotype, Sujittra Chaidayet, Javier Sotillo, Michael Smout, Cinzia Cantacessi, Malcolm Jones, Paul J. Brindley, Jeffrey M. Bethony, +9 Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background. Throughout Asia there is an unprecedented link between cholangiocarcinoma and infection with the liver fluke Opisthorchis viverrini. Multiple processes including chronic inflammation and secretion of parasite proteins into the biliary epithelium drive infection towards cancer. Until now, the mechanism and effects of parasite protein entry into cholangiocytes was unknown.

Methods. Various microscopy techniques were used to identify O. viverrini extracellular vesicles (EVs) and their internalization by human cholangiocytes. Using mass spectrometry we characterised the EV proteome and associated changes in cholangiocytes after EV uptake, and detected EV proteins in bile of infected hamsters and humans. Cholangiocyte proliferation and …

Evaluation Of Cytosine Dna Methylation Of The Biomphalaria Glabratahe At Shock Protein 70 Locus After Biological And Physiological Stresses, Wannaporn Ittiprasert, Andre Miller, Matty Knight, Matt Tucker, Michael H. Hsieh

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Deoxyribonucleic (DNA) methylation is one of the widespread epigenetic modifications of genomic DNA, and has been postulated to be a predisposing influence on disease onset and infections. The ability to quantify differences in DNA methylation between the genomes of normal vs.stressed Biomphalaria glabrata would help to profile changes potentially linked to resistance to Schistosoma mansoni infection. Thus, this study sought to measure differences in cytosine DNA methylation of various B. glabrata tissues responding over time to either biological or physiological stresses (S. mansoni exposure vs. heat shock). Here, this study measured DNA methylation at the B. glabrataheat …

Abcc9/Sur2 In The Brain: Implications For Hippocampal Sclerosis Of Aging And A Potential Therapeutic Target, Peter T. Nelson, Gregory A. Jicha, Wang-Xia Wang, Eseosa T. Ighodaro, Sergey C. Artiushin, Colin G. Nichols, David W. Fardo

Sanders-Brown Center on Aging Faculty Publications

The ABCC9 gene and its polypeptide product, SUR2, are increasingly implicated in human neurologic disease, including prevalent diseases of the aged brain. SUR2 proteins are a component of the ATP-sensitive potassium (“K _ATP ”) channel, a metabolic sensor for stress and/or hypoxia that has been shown to change in aging. The K _ATP channel also helps regulate the neurovascular unit. Most brain cell types express SUR2, including neurons, astrocytes, oligodendrocytes, microglia, vascular smooth muscle, pericytes, and endothelial cells. Thus it is not surprising that ABCC9 gene variants are associated with risk for human brain diseases. For example, Cantu syndrome is …

The Effects Of Thujone On The Function Of Nicotinic Acetylcholine Receptors, Ahmed Salaheldin Mustafa Ali Sultan

Theses

Thujone is a natural compound found in plants such as “wormwood” and “sage” and it’s also found in the alcoholic drink “Absinthe”. Thujone has been suggested as a neurotoxic compound and reported to modulate GABAA receptors. In this study, we investigated the pharmacology of Thujone on nicotinic receptors expressed in Xenopus oocytes using the two electrode voltage clamp method. Thujone (100μM) caused an 80% inhibition of Acetylcholine (ACh) induced currents in human α7-nAChRs expressed in frog oocytes while only 30% inhibition currents in α4β2 expressed oocytes and no effect on α3β4, α3β2 and α4β4 nAChRs. The mechanisms of Thujone effect …

T(3;8)(Q26;Q24) With Myc Rearrangement In Acute Myeloid Leukemia: A Case Report, Vandi Ly, Md, Renu Bajaj, Phd, Jerald Z. Gong, Md, Zi-Xuan Wang, Phd, Stephen C Peiper, Md, Guldeep Uppal, Md

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Rearrangements of 3q26 have been described in 5% of de novo or therapy related acute myeloid leukemia, myelodysplastic syndrome (MDS), and blast phase of chronic myeloid leukemia. The most common translocations involving 3q26 are t(3;12)(q26;p13), t(3;21)(q26;q22), t(3;3)(q21;q26), t(2;3)(p15∼23;q26∼27) and rarely t(3;7)(q26;q21). However, t(3;8)(q26;q24) with or without monosomy 7 is a rare phenomenon and has been reported in only 10 patients so far. Hereby, we describe a 58 year old patient who was diagnosed with refractory anemia with multilineage dysplasia. Cytogenetic studies revealed monosomy 7. He was then lost to follow-up. A year later he was found to have worsening cytopenias …

Cross-Sectional Survey Of Relevant Literatures As To The Current Proposed Disease Mechanisms And Treatments Of Amyotrophic Lateral Sclerosis (Als), Zachary Sanford

Marshall Journal of Medicine

Amyotrophic Lateral Sclerosis (ALS), more commonly referred to as Lou Gehrig’s disease, is a progressively degenerative neuromuscular disorder affecting both the upper and lower motor neurons and preferentially affecting males in their forties to seventies. Although the pathology of ALS has been clearly elucidated elsewhere, the precise mechanisms by which the disease progresses and the means by which it is acquired are still poorly understood areas of medicine. Current genomic and proteomic studies in human and animal models have yielded exciting and promising new findings that may help elucidate this pathology. It is the purpose of this review article to …

Dendritic Cell Autophagy Contributes To Herpes Simplex Virus-Driven Stromal Keratitis And Immunopathology, Yike Jiang, Xiaotang Yin, Patrick M. Stuart, David A. Leib

Dartmouth Scholarship

Herpetic stromal keratitis (HSK) is a blinding ocular disease that is initiated by HSV-1 and characterized by chronic inflammation in the cornea. Although HSK immunopathology of the cornea is well documented in animal models, events preceding this abnormal inflammatory cascade are poorly understood. In this study, we have examined the activation of pathological CD4T cells in the development of HSK. Dendritic cell autophagy (DC-autophagy) is an important pathway regulating ma- jor histocompatibility complex class II (MHCII)-dependent antigen presentation and proper CD4T cell activation during infectious diseases. Using DC-autophagy-deficient mice, we found that DC-autophagy significantly and specifically contributes to HSK disease …

Detection And Characterization Of Mineralo-Organic Nanoparticles In Human Kidneys, Tsui-Yin Wong, Cheng-Yeu Wu, Jan Martel, Cheng-Wei Lin, Fu-Yung Hsu, David M. Ojcius, Paul Y. Lin, John Ding-E. Young

All Dugoni School of Dentistry Faculty Articles

Ectopic calcification is associated with various human diseases, including atherosclerosis, cancer, chronic kidney disease, and diabetes mellitus. Although mineral nanoparticles have been detected in calcified blood vessels, the nature and role of these particles in the human body remain unclear. Here we show for the first time that human kidney tissues obtained from end-stage chronic kidney disease or renal cancer patients contain round, multilamellar mineral particles of 50 to 1,500 nm, whereas no particles are observed in healthy controls. The mineral particles are found mainly in the extracellular matrix surrounding the convoluted tubules, collecting ducts and loops of Henle as …

Hirsutella Sinensis Mycelium Attenuates Bleomycin-Induced Pulmonary Inflammation And Fibrosis In Vivo, Tsung-Teng Huang, Hsin-Chih Lai, Yun-Fei Ko, David M. Ojcius, Ying-Wei Lan, Jan Martel, John Ding-E. Young, Kowit-Yu Chong

All Dugoni School of Dentistry Faculty Articles

Hirsutella sinensis mycelium (HSM), the anamorph of Cordyceps sinensis, is a traditional Chinese medicine that has been shown to possess various pharmacological properties. We previously reported that this fungus suppresses interleukin-1β and IL-18 secretion by inhibiting both canonical and non-canonical inflammasomes in human macrophages. However, whether HSM may be used to prevent lung fibrosis and the mechanism underlying this activity remain unclear. Our results show that pretreatment with HSM inhibits TGF-β1–induced expression of fibronectin and α-SMA in lung fibroblasts. HSM also restores superoxide dismutase expression in TGF-β1–treated lung fibroblasts and inhibits reactive oxygen species production in lung epithelial cells. Furthermore, …

Meta-Gsa: Combining Findings From Gene-Set Analyses Across Several Genome-Wide Association Studies, Albert Rosenberger, Stefanie Friedrichs, Christopher I. Amos, Paul Brennan, Gordon Fehringer, Joachim Heinrich, Rayjean J. Hung, Thomas Muley, Martina Müller-Nurasyid, Angela Risch, Heike Bickeböller

Dartmouth Scholarship

Gene-set analysis (GSA) methods are used as complementary approaches to genome-wide association studies (GWASs). The single marker association estimates of a predefined set of genes are either contrasted with those of all remaining genes or with a null non-associated background. To pool the p-values from several GSAs, it is important to take into account the concordance of the observed patterns resulting from single marker association point estimates across any given gene set. Here we propose an enhanced version of Fisher’s inverse χ²-method META-GSA, however weighting each study to account for imperfect correlation between association patterns.

Week Of October 26, 2015, New York Medical College

InTouch

• William Campbell, Ph.D., Longtime, Celebrated NYMC Adjunct Professor, Wins Nobel
• Steven A. Wartman, M.D., Ph.D., M.A.C.P., Announced as 2016 NYMC Commencement Speaker
• Dean Miller Reports on LCME Mock Site Visit
• School of Medicine Launches Personal Accolades and Incidents Reporting (PAIR)
• Medical Student Brian Yum Selected Semi-Finalist in Essay Program
• D.P.T. Students Host Successful Race for Rehab
• NYMC Welcomes BOCES New Visions Health Students
• NYMC Sends Support to Liberia
• SHSP Welcomes New Cohort of Dr.P.H. Candidates

Phytochemicals In Cancer Prevention And Therapy, Poyil Pratheeshkumar, Young-Ok Son, Preethi Korangath, Kanjoormana Aryan Manu, Kodappully Sivaraman Siveen

Toxicology and Cancer Biology Faculty Publications

Despite advances in modern medicine, cancer is still the major cause of mortality in both developing and developed countries. Search for safer and more effective chemoprevention and treatment strategy is a need for the improvement of patient care in the field. Prevention may be more effective and less costly because cancer is largely a preventable disease which could be attributed to a greater extent to lifestyle. Dietary phytochemicals have been used for the treatment of cancer throughout history due to their safety, low toxicity, and general availability. Population based studies suggest that a reduced risk of cancer is associated with …

Steroid Receptor Isoform Expression In Drosophila Nociceptor Neurons Is Required For Normal Dendritic Arbor And Sensitivity, Aidan L. Mcparland, Taylor L. Follansbee, Gwendolyn D. Vesenka, Alexandra E. Panaitiu, Geoffrey K. Ganter

Biology Student Publications

Steroid hormones organize many aspects of development, including that of the nervous system. Steroids also play neuromodulatory and other activational roles, including regulation of sensitivity to painful stimuli in mammals. In Drosophila, ecdysteroids are the only steroid hormones, and therefore the fly represents a simplified model system in which to explore mechanisms of steroid neuromodulation of nociception. In this report, we present evidence that ecdysteroids, acting through two isoforms of their nuclear ecdysone receptor (EcR), modulate sensitivity to noxious thermal and mechanical stimuli in the fly larva. We show that EcRA and EcRB1 are expressed by third instar larvae in …

Intracellular Information Processing Through Encoding And Decoding Of Dynamic Signaling Features., Hirenkumar K Makadia, James S. Schwaber, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Cell signaling dynamics and transcriptional regulatory activities are variable within specific cell types responding to an identical stimulus. In addition to studying the network interactions, there is much interest in utilizing single cell scale data to elucidate the non-random aspects of the variability involved in cellular decision making. Previous studies have considered the information transfer between the signaling and transcriptional domains based on an instantaneous relationship between the molecular activities. These studies predict a limited binary on/off encoding mechanism which underestimates the complexity of biological information processing, and hence the utility of single cell resolution data. Here we pursue a …

Diabetic Ketoacidosis: Pathophysiology And Treatment, Laura E. Mumme

The Kabod

The pathophysiology of DKA in patients with T1D is addressed, followed by a discussion of proper emergency treatment for this life-threatening condition.

Loss Of Glycosaminoglycan Receptor Binding After Mosquito Cell Passage Reduces Chikungunya Virus Infectivity, Amber M. Paul, Dhiraj Acharya, John F. Anderson, Faqing Huang, Fengwei Bai

Publications

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that can cause fever and chronic arthritis in humans. CHIKV that is generated in mosquito or mammalian cells differs in glycosylation patterns of viral proteins, which may affect its replication and virulence. Herein, we compare replication, pathogenicity, and receptor binding of CHIKV generated in Vero cells (mammal) or C6/36 cells (mosquito) through a single passage. We demonstrate that mosquito cell derived CHIKV (CHIKVmos) has slower replication than mammalian cell derived CHIKV (CHIKVvero), when tested in both human and murine cell lines. Consistent with this, CHIKVmos infection in both cell lines produce less cytopathic …

Week Of October 19, 2015, New York Medical College

InTouch

• NYMC Set to Honor Three at 2015 Founder's Dinner
• School of Medicine Announces New Administrative Appointments
• School of Medicine Retreat Highlights Quality Improvement, Patient Safety and the Education of Medical Learners
• NYMC Mourns the Death of Former Chancellor Rev. Msgr. James P. Cassidy, Ph.D.
• NYMC Steps Out to Fight Heart Disease
• NYMC Hosts 8th Annual Community Health Fair
• Good Food Farmers Network Deliveries to Campus Begin

Tobramycin-Treated Pseudomonas Aeruginosa Pa14 Enhances Streptococcus Constellatus 7155 Biofilm Formation In A Cystic Fibrosis Model System, Katherine E. E. Price, Amanda A. Naimie, Edward F. Griffin, Charles Bay, George A. O'Toole

Dartmouth Scholarship

Cystic fibrosis (CF) is a human genetic disorder which results in a lung environment that is highly conducive to chronic microbial infection. Over the past decade, deep-sequencing studies have demonstrated that the CF lung can harbor a highly diverse polymicrobial community. We expanded our existing in vitro model of Pseudomonas aeruginosa biofilm formation on CF-derived airway cells to include this broader set of CF airway colonizers to investigate their contributions to CF lung disease, particularly as they relate to the antibiotic response of the population. Using this system, we identified an interspecies interaction between P. aeruginosa, a bacterium associated with …

Autophagy Protects Against Cyp2e1/Chronic Ethanol-Induced Hepatotoxicity, Yongke Lu, Arthur I. Cederbaum

Pharmacology, Physiology and Toxicology

Autophagy is an intracellular pathway by which lysosomes degrade and recycle long-lived proteins and cellular organelles. The effects of ethanol on autophagy are complex but recent studies have shown that autophagy serves a protective function against ethanol-induced liver injury. Autophagy was found to also be protective against CYP2E1-dependent toxicity in vitro in HepG2 cells which express CYP2E1 and in vivo in an acute alcohol/CYPE1-dependent liver injury model. The goal of the current report was to extend the previous in vitro and acute in vivo experiments to a chronic ethanol model to evaluate whether autophagy is also protective against CYP2E1-dependent liver …