Digital Commons Network^™

Week Of March 25, 2019, New York Medical College

InTouch

• Graduate Student Research Forum Displays a Broad Field of Research
• NYMC Hosts Fourth Annual HeLa Diversity and Inclusion Conference
• Center for Disaster Medicine Conducts Inaugural Tactical Emergency Casualty Course
• NYMC Welcomes AMSNY to Campus
• NYMC AMWA Chapter Hosts Annual Mentorship Dinner
• Alpha Omega Alpha Lecture Set for April 2

H3k27m Induces Defective Chromatin Spread Of Prc2-Mediated Repressive H3k27me2/Me3 And Is Essential For Glioma Tumorigenesis., Ashot S. Harutyunyan, Brian Krug, Haifen Chen, Simon Papillon-Cavanagh, Michele Zeinieh, Nicolas De Jay, Shriya Deshmukh, Carol C L Chen, Jad Belle, Leonie G. Mikael, Dylan M. Marchione, Rui Li, Hamid Nikbakht, Bo Hu, Gael Cagnone, Warren A. Cheung, Abdulshakour Mohammadnia, Denise Bechet, Damien Faury, Melissa K. Mcconechy, Manav Pathania, Siddhant U. Jain, Benjamin Ellezam, Alexander G. Weil, Alexandre Montpetit, Paolo Salomoni, Tomi Pastinen, Chao Lu, Peter W. Lewis, Benjamin A. Garcia, Claudia L. Kleinman, Nada Jabado, Jacek Majewski

Manuscripts, Articles, Book Chapters and Other Papers

Lys-27-Met mutations in histone 3 genes (H3K27M) characterize a subgroup of deadly gliomas and decrease genome-wide H3K27 trimethylation. Here we use primary H3K27M tumor lines and isogenic CRISPR-edited controls to assess H3K27M effects in vitro and in vivo. We find that whereas H3K27me3 and H3K27me2 are normally deposited by PRC2 across broad regions, their deposition is severely reduced in H3.3K27M cells. H3K27me3 is unable to spread from large unmethylated CpG islands, while H3K27me2 can be deposited outside these PRC2 high-affinity sites but to levels corresponding to H3K27me3 deposition in wild-type cells. Our findings indicate that PRC2 recruitment and propagation on …

Week Of March 18, 2019, New York Medical College

InTouch

• It's A Match for School of Medicine Class 2019
• Renowned Neuroscientist to Address 31st Annual Graduate Student Research Forum
• SHSP Hosts Special Dean's Lecture

The Myth Of "It's All In Your Head"

DePaul Magazine

Researchers at DePaul's Center for Community Research are mapping the brain to uncover the causes of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). Psychologist Leonard Jason has been carrying out community-based epidemiology prevalence studies that show that about one million Americans, many of them from ethnic minorities, are afflicted with the condition.

Can Assisted Reproductive Technologies Help Conserve 300 Million Years Of Evolution? A First Attempt At Developing These Technologies For Male Reptiles, Sean M. Perry

LSU Doctoral Dissertations

Biodiversity loss is the most critical environmental problem threatening ecosystem, animal, and human health today. Increases in extinction rates have been observed over the past 50 years, with reptile losses occurring twelve times faster than traditional extinction rates. This demonstrated biodiversity loss is secondary to climate change, habitat destruction, infectious disease, invasive species, poaching, and unsustainable trade. Approximately 20% of all reptiles are threatened with extinction and population declines are approaching rates similar to the current amphibian extinction crisis. Preventing the extinction of reptiles will require humans to acknowledge these losses and develop plans to preserve these evolutionary sentinel species. …

Week Of March 11, 2019, New York Medical College

InTouch

• NYMC Days of Giving Set for March 26 and 27
• School of Medicine Class of 2019 Gets Ready for Match Day

A Human Papillomavirus-Independent Cervical Cancer Animal Model Reveals Unconventional Mechanisms Of Cervical Carcinogenesis, Chunbo He, Xiangmin Lv, Cong Huang, Peter C. Angeletti, Guohua Hua, Jixin Dong, Jin Zhou, Zhengfeng Wang, Bowen Ma, Xingcheng Chen, Paul F. Lambert, Bo R. Rueda, John S. Davis, Cheng Wang

Nebraska Center for Virology: Faculty Publications

HPV infections are common in healthy women and only rarely cause cervical cancer, suggesting that individual genetic susceptibility may play a critical role in the establishment of persistent HPV infection and the development of cervical cancer. Here, we provide convincing in vitro and in vivo evidence showing that differential expression and activation of YAP1 oncogene determine individual susceptibility to HPV infection and cervical carcinogenesis. We found that hyperactivation of YAP1 in mouse cervical epithelium was sufficient to induce invasive cervical cancer. Cervical epithelial cell-specific HPV16 E6/E7 and YAP1 double-knockin mouse model demonstrated that high-risk HPV synergized with hyperactivated YAP1 to …

Week Of March 4, 2019, New York Medical College

InTouch

• NYMC Welcomes Jerry L. Nadler, M.D., MACP, FAHA, FACE, Dean of the School of Medicine
• NYMC Honors the Legacy of Clarence Sumner Janifer Sr., M.D., Class of 1915
• Advanced Infant Patient Simulators Improve Access to Hands-On Pediatric Care Training

Best Practices For Long-Term Monitoring And Follow-Up Of Alemtuzumab-Treated Ms Patients In Real-World Clinical Settings., Krista Barclay, Robert Carruthers, Anthony Traboulsee, Ann D Bass, Christopher Laganke, Antonio Bertolotto, Aaron Boster, Elisabeth G Celius, Jérôme De Seze, Dionisio Dela Cruz, Mario Habek, Jong-Mi Lee, Volker Limmroth, Sven G Meuth, Celia Oreja-Guevara, Patricia Pagnotta, Cindy Vos, Tjalf Ziemssen, Darren P Baker, Bart Van Wijmeersch

Neuroscience Articles

Multiple sclerosis (MS) is a chronic autoimmune neurological disease that typically affects young adults, causing irreversible physical disability and cognitive impairment. Alemtuzumab, administered intravenously as 2 initial courses of 12 mg/day (5 consecutive days at baseline, and 3 consecutive days 12 months later), resulted in significantly greater improvements in clinical and MRI outcomes vs. subcutaneous interferon beta-1a over 2 years in patients with active relapsing-remitting MS (RRMS) who were either treatment-naive (CARE-MS I; NCT00530348) or had an inadequate response to prior therapy (CARE-MS II; NCT00548405). Efficacy with alemtuzumab was maintained over 7 years in subsequent extension studies (NCT00930553; NCT02255656), in …

Transcranial Doppler Assessment Of Patients With Cerebral Small Vessel Disease, Alaa Ebrahim Ata Ata Shaaban, Mahmoud H. Ebrahim, Mohamed M. T. Elbaghdady, Salma H. M. Khalil

Journal of Medicine in Scientific Research

Background Cerebral small vessel disease (SVD) refers to any pathology in all vascular structures (small arteries, arterioles, capillaries, venules, and small veins). Transcranial Doppler is a bedside, inexpensive, noninvasive technique that can assess intracerebral circulation in real time and can be used for continuous monitoring. Aim of the work Our study tried to detect the pathogenesis of cerebral SVD, especially the implication of the cerebral large artery disease. Moreover, it assessed the ability of transcranial Doppler in evaluating the severity of cerebral SVD and people who are at risk. Patients with cardioembolic risk were excluded. Patients and methods A cross-sectional …

Osteoblasts Are "Educated" By Crosstalk With Metastatic Breast Cancer Cells In The Bone Tumor Microenvironment., Alexus D. Kolb, Alison B. Shupp, Dimpi Mukhopadhyay, Frank C. Marini, Karen M. Bussard

Department of Cancer Biology Faculty Papers

INTRODUCTION: In a cancer-free environment in the adult, the skeleton continuously undergoes remodeling. Bone-resorbing osteoclasts excavate erosion cavities, and bone-depositing osteoblasts synthesize osteoid matrix that forms new bone, with no net bone gain or loss. When metastatic breast cancer cells invade the bone, this balance is disrupted. Patients with bone metastatic breast cancer frequently suffer from osteolytic bone lesions that elicit severe bone pain and fractures. Bisphosphonate treatments are not curative. Under ideal circumstances, osteoblasts would synthesize new matrix to fill in erosion cavities caused by osteoclasts, but this is not what occurs. Our prior evidence demonstrated that osteoblasts are …

Saturated Fatty Acid Activates T Cell Inflammation Through A Nicotinamide Nucleotide Transhydrogenase (Nnt)-Dependent Mechanism, Grace Mccambridge, Madhur Agrawal, Alanna Keady, Philip A. Kern, Hatice Hasturk, Barbara S. Nikolajczyk, Leena P. Bharath

Pharmacology and Nutritional Sciences Faculty Publications

Circulating fatty acids (FAs) increase with obesity and can drive mitochondrial damage and inflammation. Nicotinamide nucleotide transhydrogenase (NNT) is a mitochondrial protein that positively regulates nicotinamide adenine dinucleotide phosphate (NADPH), a key mediator of energy transduction and redox homeostasis. The role that NNT-regulated bioenergetics play in the inflammatory response of immune cells in obesity is untested. Our objective was to determine how free fatty acids (FFAs) regulate inflammation through impacts on mitochondria and redox homeostasis of peripheral blood mononuclear cells (PBMCs). PBMCs from lean subjects were activated with a T cell-specific stimulus in the presence or absence of generally pro-inflammatory …

Student-Faculty Collaborative Research Grant Report, Megan Bestwick

Post-Grant Reports

Mitochondria are essential organelles in most eukaryotic cells because of their role in metabolism and the production of ATP by the oxidative phosphorylation (OXPHOS) pathway, as well as other key cellular processes. Metal cofactors, such as copper (Cu) and iron (Fe), are incorporated into OXPHOS protein complexes of yeast located within the inner membrane of the mitochondria. Misincorporation or modulation of these available metals in mitochondrial enzymes leads to the production of reactive oxygen species (ROS). ROS are reactive molecules containing oxygen such as peroxides, superoxide, and hydroxyl radicals. Yeast are a good model for studying aging and the effect …

Yap1-Lats2 Feedback Loop Dictates Senescent Or Malignant Cell Fate To Maintain Tissue Homeostasis, Chunbo He, Xiangmin Lv, Cong Huang, Guohua Hua, Bowen Ma, Xingcheng Chen, Peter C. Angeletti, Jixin Dong, Jin Zhou, Zhengfeng Wang, Bo R. Rueda, John S. Davis, Cheng Wang

Nebraska Center for Virology: Faculty Publications

Dysfunction of the homeostasis-maintaining systems in specific cell types or tissues renders the organism susceptible to a range of diseases, including cancers. One of the emerging mechanisms for maintaining tissue homeostasis is cellular senescence. Here, we report that the Hippo pathway plays a critical role in controlling the fate of ovarian cells. Hyperactivation of Yes-associated protein 1 (YAP1), the major effector of the Hippo pathway, induces senescence in cultured primary human ovarian surface epithelial cells (hOSEs). Large tumor suppressor 2 (LATS2), the primary upstream negative regulator of YAP1, is elevated in both YAP1-induced and natural replicative-triggered senescence. Deletion of LATS2 …

Week Of February 11, 2019, New York Medical College

InTouch

• George D. Yancopoulos, M.D., Ph.D., Will Deliver the 160th Commencement Address
• Medical Student Research is Flourishing at NYMC
• NYMC Kicks Off Black History Month With Movie Screening
• Trumada Initiative Hosts Investor Club Presentation

Tradd Regulates Perinatal Development And Adulthood Survival In Mice Lacking Ripk1 And Ripk3., John P. Dowling, Mohamed Alsabbagh, Christina Del Casale, Zheng-Gang Liu, Jianke Zhang

Department of Microbiology and Immunology Faculty Papers

TRADD is an adaptor for TNFR1-induced apoptosis and NFκB activation. However, TRADD-deficient mice undergo normal development and contain normal lymphoid populations, which contrasts with an embryonic defect in mice lacking FADD, the shared adaptor mediating apoptosis. Recent studies indicate FADD suppresses embryonic necroptosis mediated by RIPK1. TRADD was suggested to also mediate necroptosis. Here we report that targeting TRADD fails to rescue Fadd ^−/− embryos from necroptosis, and ablation of TRADD rescues Ripk1 ^−/− mice from perinatal lethality when RIPK3-mediated necroptosis is disabled. The resulting Ripk1 ^−/− Ripk3 ^−/− Tradd ^−/− mice survive until early adulthood, but die thereafter. A …

Identification Of Novel Regulatory Genes In Apap Induced Hepatocyte Toxicity By A Genome-Wide Crispr-Cas9 Screen., Katherine Shortt, Daniel P. Heruth, Nini Zhang, Weibin Wu, Shipra Singh, Ding-You Li, Li Qin Zhang, Gerald J. Wyckoff, Lei S Qi, Craig A. Friesen, Shui Qing Ye

Manuscripts, Articles, Book Chapters and Other Papers

Acetaminophen (APAP) is a commonly used analgesic responsible for more than half of acute liver failure cases. Identification of previously unknown genetic risk factors would provide mechanistic insights and novel therapeutic targets for APAP-induced liver injury. This study used a genome-wide CRISPR-Cas9 screen to evaluate genes that are protective against, or cause susceptibility to, APAP-induced liver injury. HuH7 human hepatocellular carcinoma cells containing CRISPR-Cas9 gene knockouts were treated with 15 mM APAP for 30 minutes to 4 days. A gene expression profile was developed based on the 1) top screening hits, 2) overlap of expression data from APAP overdose studies, …

Week Of February 4, 2019, New York Medical College

InTouch

• Mary M. Petzke, Ph.D., is Appointed Assistant Dean for Medical Student Research
• SHSP Hosts Seminar on "HRTP: A Public Health Internship Program"

The Tenets Of Teneurin: Conserved Mechanisms Regulate Diverse Developmental Processes In The Drosophila Nervous System, Alison T. Depew, Michael A. Aimino, Timothy J. Mosca

Department of Neuroscience Faculty Papers

To successfully integrate a neuron into a circuit, a myriad of developmental events must occur correctly and in the correct order. Neurons must be born and grow out toward a destination, responding to guidance cues to direct their path. Once arrived, each neuron must segregate to the correct sub-region before sorting through a milieu of incorrect partners to identify the correct partner with which they can connect. Finally, the neuron must make a synaptic connection with their correct partner; a connection that needs to be broadly maintained throughout the life of the animal while remaining responsive to modes of plasticity …

Week Of January 28, 2019, New York Medical College

InTouch

• Heart Transplant Specialist to Address 23rd Annual Medical Student Research Forum
• HSL Pilots Critical Appraisal Institute for Librarians

Patient Perceptions Of Planned Organ Removal During Hysterectomy, Zeinab Kassem, Chad M. Coleman, Andrew S. Bossick, Wan-Ting Su, Roopina Sangha, Ganesa Wegienka

Journal of Patient-Centered Research and Reviews

Purpose: Previous reports indicate many women may not have a firm grasp on likely outcomes of different hysterectomy procedures. This study aimed to assess women’s self-reported expectations of how they think their anatomy will change after hysterectomy.

Methods: Women scheduled for hysterectomy at a tertiary care hospital, for non-oncological reasons, reported their planned procedure type and the organs they understood would be removed 2 weeks prior to surgery. Patient reports and electronic medical records were reviewed, and kappa statistics (κ) were calculated to assess agreement for all women and within subgroups.

Results: Most of the 456 study participants (mean age: …

Itch Nuclear Translocation And H1.2 Polyubiquitination Negatively Regulate The Dna Damage Response, Lufen Chang, Lei Shen, Hu Zhou, Jing Gao, Hangyi Pan, Li Zheng, Brian Armstrong, Yang Peng, Guang Peng, Binhua P. Zhou, Steven T. Rosen, Binghui Shen

Molecular and Cellular Biochemistry Faculty Publications

The downregulation of the DNA damage response (DDR) enables aggressive tumors to achieve uncontrolled proliferation against replication stress, but the mechanisms underlying this process in tumors are relatively complex. Here, we demonstrate a mechanism through which a distinct E3 ubiquitin ligase, ITCH, modulates DDR machinery in triple-negative breast cancer (TNBC). We found that expression of a nuclear form of ITCH was significantly increased in human TNBC cell lines and tumor specimens. Phosphorylation of ITCH at Ser257 by AKT led to the nuclear localization of ITCH and ubiquitination of H1.2. The ITCH-mediated polyubiquitination of H1.2 suppressed RNF8/RNF168-dependent formation of 53BP1 foci, …

Absence Of Endothelial Α5Β1 Integrin Triggers Early Onset Of Experimental Autoimmune Encephalomyelitis Due To Reduced Vascular Remodeling And Compromised Vascular Integrity, Ravi Kant, Sebok K. Halder, Gregory J. Bix, Richard Milner

Sanders-Brown Center on Aging Faculty Publications

Early in the development of multiple sclerosis (MS) and its mouse model experimental autoimmune encephalomyelitis (EAE), vascular integrity is compromised. This is accompanied by a marked vascular remodeling response, though it is currently unclear whether this is an adaptive vascular repair mechanism or is part of the pathogenic process. In light of the well-described angiogenic role for the α5β1 integrin, the goal of this study was to evaluate how genetic deletion of endothelial α5 integrin (α5-EC-KO mice) impacts vascular remodeling and repair following vascular disruption during EAE pathogenesis, and how this subsequently influences clinical progression and inflammatory demyelination. Immunofluorescence staining …

Histology For Cytotechnologists I, Joanna Burkhardt

Library Impact Statements

No abstract provided.

Biotransformed Metabolites Of The Hop Prenylflavanone Isoxanthohumol, Hyun Jung Kim, Soon-Ho Yim, Fubo Han, Bok Yun Kang, Hyun Jin Choi, Da-Woon Jung, Darren R. Williams, Kirk R. Gustafson, Edward J. Kennelly, Ik-Soo Lee

Publications and Research

A metabolic conversion study on microbes is known as one of the most useful tools to predict the xenobiotic metabolism of organic compounds in mammalian systems. The microbial biotransformation of isoxanthohumol (1), a major hop prenylflavanone in beer, has resulted in the production of three diastereomeric pairs of oxygenated metabolites (2–7). The microbial metabolites of 1 were formed by epoxidation or hydroxylation of the prenyl group, and HPLC, NMR, and CD analyses revealed that all of the products were diastereomeric pairs composed of (2S)- and (2R)- isomers. The structures of these metabolic compounds were elucidated to be (2S,200S)- and (2R,200S)-40 …

Week Of January 22, 2019, New York Medical College

InTouch

• Celia S. Freeman, M.B.A., Is Named Assistant Dean for Continuous Quality Improvement and Strategic Planning
• Center for Disaster Medicine Symposium Addresses Current State and Future Direction of Disaster Medicine and Preparedness
• NYMC Welcomes Senator Peter Harckham to Campus
• NYMC and TouroCOM Forge New Agreement for Admissions Interviews

Impaired Nuclear Export Of Polyglutamine-Expanded Androgen Receptor In Spinal And Bulbar Muscular Atrophy., Frederick J. Arnold, Anna Pluciennik, Diane E. Merry

Department of Biochemistry and Molecular Biology Faculty Papers

Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease caused by polyglutamine (polyQ) expansion in the androgen receptor (AR). Prior studies have highlighted the importance of AR nuclear localization in SBMA pathogenesis; therefore, in this study, we sought to determine the role of AR nuclear export in the pathological manifestations of SBMA. We demonstrate here that the nuclear export of polyQ-expanded AR is impaired, even prior to the formation of intranuclear inclusions of aggregated AR. Additionally, we find that promoting AR export with an exogenous nuclear export signal substantially reduces its aggregation and blocks hormone-induced toxicity. Moreover, we show …

The Effect Of Flavonoid Galangin On The Cell Viability And Toxicity Of Mcf-7 Human Breast Cancer Cells Exposed To Polycyclic Aromatic Hydrocarbons (Pahs), Abhimanyu Sailesh

Journal of the South Carolina Academy of Science

Polycyclic aromatic hydrocarbons (PAHs) are chemical compounds ubiquitous in the environment; many of which are known human and animal carcinogen. The purpose of this study was to investigate MCF-7 epithelial breast cancer cells’ viability and toxicity following a short-term in vitro exposure to a cocktail of PAHs and benzo[a]pyrene (B[a]P) separately in the presence and absence of varying concentrations of flavonoid galangin. It was predicted that presence of galangin will completely or partially block the damaging effects of PAHs. It was hypothesized that exposing the cells to 7 µM cocktail of PAHs or 10 µM B[a]P in the presence of …

The Effects Of Oxidative Stress On Inducing Senescence In Human Fibroblasts, Shivani Chowdhary

Journal of the South Carolina Academy of Science

Oxidative stress, specifically from hydrogen peroxide exposure, was performed to determine if it induced senescence in cell lines such as Hela cells and primary human fibroblasts. The purpose of this experiment was to find the optimal stage, concentration, and time of exposure to induce the greatest number of senescent cells. After dividing cultures of both the Hela and human fibroblasts cells in order to reduce confluency, the cells were placed in a six well plate and exposed to hydrogen peroxide for two hours at various concentrations. The plates were checked at twenty-four-hour intervals, and then fixed with senescence associated beta-galactosidase …

Week Of January 14, 2019, New York Medical College

InTouch

• Salomon Amar, D.D.S., Ph.D., Is Appointed Vice President for Research
• Movie Highlights the Importance of Open Access