Digital Commons Network^™

Cloning, Sequencing, Expression And Characterization Of An Alzheimer’S-Specific Monoclonal Antibody, Anna K. Jones, Thao Pham

Undergraduate Research Symposium

Alzheimer’s disease (AD) is characterized by chronic inflammation and neurodegeneration, which leads to loss of cognitive functions. Dr. Nichols’ research laboratory is studying the neurological effects associated with AD. Amyloid precursor protein (APP) is a membrane spanning protein whose primary function is unknown, but it is associated with many tissue types and found clustered at the synapse of neurons. APP can be cleaved by secretases into 40 or 42 amino acid fragments called amyloid beta protein (Aβ). These cleaved amyloid-β proteins can accumulate (aggregate) and form extracellular plaques in AD brains. Antibodies are normally produced in an adaptive immune response …

Trna Methylation Is A Global Determinant Of Bacterial Multi-Drug Resistance., Isao Masuda, Ryuma Matsubara, Thomas Christian, Enrique R. Rojas, Srujana S. Yadavalli, Lisheng Zhang, Mark Goulian, Leonard J. Foster, Kerwyn Casey Huang, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

Gram-negative bacteria are intrinsically resistant to drugs because of their double-membrane envelope structure that acts as a permeability barrier and as an anchor for efflux pumps. Antibiotics are blocked and expelled from cells and cannot reach high-enough intracellular concentrations to exert a therapeutic effect. Efforts to target one membrane protein at a time have been ineffective. Here, we show that m ¹ G37-tRNA methylation determines the synthesis of a multitude of membrane proteins via its control of translation at proline codons near the start of open reading frames. Decreases in m ¹ G37 levels in Escherichia coli and Salmonella impair …

Empathy, Religious Affiliation, And The Growth Of Osteopathic Medicine, Brianna Cunningham

Senior Honors Theses

A key distinction of Doctors of Osteopathic Medicine (D.O.s) is their recognition of each patient as a whole person rather than just addressing his ailment. This focus previously highlighted physical manipulation over medications; however, the osteopathic profession has evolved significantly over the years. As this field is no longer identified by its original rejection of pharmaceuticals, other original principles of osteopathic medicine have impacted the growth of the field. The data collected from surveyed patients indicated that many osteopathic patients and physicians have religious backgrounds, and there is a widespread emphasis on psychological integration. The increased number of patients is …

Initial Evaluation Of Computer-Assisted Radiologic Assessment For Renal Mass Edge Detection As An Indication Of Tumor Roughness To Predict Renal Cancer Subtypes, Rahul Rajendran, Kevan Iffrig, Deepak K. Pruthi, Allison Wheeler, Brian Neuman, Dharam Kaushik, Ahmed M. Mansour, Karen Panetta, Sos Agaian, Michael A. Liss

Publications and Research

Objective. To develop software to assess the potential aggressiveness of an incidentally detected renal mass using images. Methods. Thirty randomly selected patients who underwent nephrectomy for renal cell carcinoma (RCC) had their images independently reviewed by engineers. Tumor “Roughness” was based on image algorithm of tumor topographic features visualized on computed tomography (CT) scans. Univariant and multivariant statistical analyses are utilized for analysis. Results. We investigated 30 subjects that underwent partial or radical nephrectomy. After excluding poor image-rendered images, 27 patients remained (benign cyst = 1, oncocytoma = 2, clear cell RCC = 15, papillary RCC = …

A Background Of The Opioid Epidemic And Its Relationship To The Medicaid Expansion, Er Yearn Jang

Senior Honors Theses

Despite the recent increase in public awareness of the opioid epidemic, the background of this epidemic is still disappointingly unknown to the public. The opioid epidemic is a national crisis which impacts, not only individuals’ wellbeing but the economy of the United States. The federal government sought to mitigate it through the enactment of the Patient Protection and Affordable Care Act. The Medicaid expansion, which was built into this law, sparked controversy; controversy which has yet to be solved to this day. Going forward, the knowledge we gather from examining the connection between this epidemic and the Medicaid expansion will …

Week Of April 22, 2019, New York Medical College

InTouch

• NYMed Talks Highlights Success Through Diversity
• Lectureship Honors the Late Gabor Kaley, Ph.D.

Signal Intensity Analysis And Optimization For In Vivo Imaging Of Cherenkov And Excited Luminescence., Ethan P. M. Larochelle, Jennifer R. Shell, Jason R. Gunn, Scott C. Davis, Brian W. Pogue

Dartmouth Scholarship

During external beam radiotherapy (EBRT), in vivo Cherenkov optical emissions can be used as a dosimetry tool or to excite luminescence, termed Cherenkov-excited luminescence (CEL) with microsecond-level time-gated cameras. The goal of this work was to develop a complete theoretical foundation for the detectable signal strength, in order to provide guidance on optimization of the limits of detection and how to optimize near real time imaging. The key parameters affecting photon production, propagation and detection were considered and experimental validation with both tissue phantoms and a murine model are shown. Both the theoretical analysis and experimental data indicate that the …

Ucp1 Expression-Associated Gene Signatures Of Human Epicardial Adipose Tissue., Kanta Chechi, Jinchu Vijay, Pierre Voisine, Patrick Mathieu, Yohan Bossé, Andre Tchernof, Elin Grundberg, Denis Richard

Manuscripts, Articles, Book Chapters and Other Papers

Multiple reports of uncoupling protein 1 (UCP1) expression have established its presence in human epicardial adipose tissue (eAT). Its functional relevance to eAT, however, remains largely unknown. In a recent study, we reported that adrenergic stimulation of eAT was associated with downregulation of secreted proteins involved in oxidative stress-related and immune-related pathways. Here, we explored the UCP1-associated features of human eAT using next-generation deep sequencing. Paired biopsies of eAT, mediastinal adipose tissue (mAT), and subcutaneous adipose tissue (sAT) obtained from cardiac surgery patients, with specific criteria of high and low expression of UCP1 in eAT, were subjected to RNA sequencing. …

Single-Cell Gene Expression Analysis Identifies Chronic Alcohol-Mediated Shift In Hepatocyte Molecular States After Partial Hepatectomy., Sirisha Achanta, Aalap Verma, Ankita Srivastava, Harshavardhan Nilakantan, Jan B. Hoek, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The analysis of molecular states of individual cells, as defined by their mRNA expression profiles and protein composition, has gained widespread interest in studying biological phenomena ranging from embryonic development to homeostatic tissue function and genesis and evolution of cancers. Although the molecular content of individual cells in a tissue can vary widely, their molecular states tend to be constrained within a transcriptional landscape partly described by the canonical archetypes of a population of cells. In this study, we sought to characterize the effects of an acute (partial hepatectomy) and chronic (alcohol consumption) perturbation on the molecular states of individual …

Week Of April 15, 2019, New York Medical College

InTouch

• D.P.T. Class of 202 1 Marks Milestone at White Coat Ceremony
• NYMC Kicks Off Its Strategic Planning Process
• NYMC Stands out at Resident Research Day
• NYMC Shows Support for Autism Awareness
• SOM Seeks MMI Interviewers

The Promise Of Anti-Idiotype Revisited, Heinz Köhler, Anastas Pashov, Thomas Kieber-Emmons

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The promise of idiotype-based therapeutics has been disappointing forcing a new look at the concept and its potential to generate an effective approach for immunotherapy. Here, the idiotype network theory is revisited with regard to the development of efficacious anti-idiotype vaccines. The experience of polyclonal anti-Idiotype reagents in animal models as well as an understanding of the immune response in humans lends to the proposition that polyclonal anti-Idiotype vaccines will be more effective compared to monoclonal-based anti-Idiotype vaccines. This novel strategy can be adapted in Biotech-standard production of therapeutic antibodies.

Gasdermin Pores Permeabilize Mitochondria To Augment Caspase-3 Activation During Apoptosis And Inflammasome Activation., Corey Rogers, Dan A. Erkes, Alexandria Nardone, Andrew E. Aplin, Teresa Fernandes-Alnemri, Emad S. Alnemri

Department of Biochemistry and Molecular Biology Faculty Papers

Gasdermin E (GSDME/DFNA5) cleavage by caspase-3 liberates the GSDME-N domain, which mediates pyroptosis by forming pores in the plasma membrane. Here we show that GSDME-N also permeabilizes the mitochondrial membrane, releasing cytochrome c and activating the apoptosome. Cytochrome c release and caspase-3 activation in response to intrinsic and extrinsic apoptotic stimuli are significantly reduced in GSDME-deficient cells comparing with wild type cells. GSDME deficiency also accelerates cell growth in culture and in a mouse model of melanoma. Phosphomimetic mutation of the highly conserved phosphorylatable Thr6 residue of GSDME, inhibits its pore-forming activity, thus uncovering a potential mechanism by which GSDME …

Exploration Of Prostate Cancer Cells: The Significance Of Active Herv, Dakota Shepherd

Student Scholar Showcase

The second most common cancer in men is prostate cancer. Prostate cancer is traditionally diagnosed by a digital rectal exam. Blood tests can also be used to test for PSA (prostate-specific antigen). These two methods can be used together but can sometimes provide both false negative and false positive results. A new method of testing for prostate cancer could prove to be beneficial. Previous studies have shown that active HERV sequences have been identified in some cancers, including prostate cancer. We hypothesize that the presence of active HERV in prostate cancer lines is significant. In this study, rabbit polyclonal antibodies …

Synthesis And Antiproliferative Activities Of Conjugates Of Paclitaxel And Camptothecin With A Cyclic Cell-Penetrating Peptide, Naglaa Salem El-Sayed, Amir Nasrolahi Shirazi, Muhammad Imran Sajid, Shang Eun Park, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

Cell-penetrating peptide [WR]5 has been previously shown to be an efficient molecular transporter for various hydrophilic and hydrophobic molecules. The peptide was synthesized using Fmoc/tBu solid-phase chemistry, and one arginine was replaced with one lysine to enable the conjugation with the anticancer drugs. Paclitaxel (PTX) was functionalized with an esterification reaction at the C20 hydroxyl group of PTX with glutaric anhydride and conjugated with the cyclic peptide [W(WR)4K(bAla)] in DMF to obtain the peptide-drug conjugate PTX1. Furthermore, camptothecin (CPT) was modified at the C(20)-hydroxyl group through the reaction with triphosgene. Then, it was conjugated with two functionalized cyclic peptides through …

Fluorometholone Modulates Gene Expression Of Ocular Surface Mucins, Jonathan Taniguchi, Ajay Sharma

Pharmacy Faculty Articles and Research

Purpose

Mucins are vital to keep the ocular surface hydrated. Genes encoding for mucins contain a glucocorticoid response element. The purpose of this study was to evaluate the effect of fluorometholone, a glucocorticoid receptor agonist used in the management of dry eye, on the gene expression of conjunctival and corneal epithelial cell mucins.

Methods

Stratified cultures of human conjunctival and corneal epithelial cells were exposed to 25, 50 and 100 nM of fluorometholone alone or in presence of mifepristone, a glucocorticoid receptor antagonist. The mRNA was isolated from the cells and reverse transcribed to cDNA. The cDNA was used for …

Role Of Ribosome Recycling Factor As A Ribosome Releasing Factor, Yoshio Inokuchi, Fabio Quaglia, Akikazu Hirashima, Yoshihiro Yamamoto, Hideko Kaji, A. Kaji

Department of Biochemistry and Molecular Biology Posters

The objective of this presentation is to study the in vivo actions of ribosome recycling factor (RRF) and compare them with those found in vitro. RRF is known to catalyze three separate reactions: release of tRNA and mRNA from the post-termination complex (PoTC), and splitting of the ribosome of the PoTC. To study the mechanism of RRF reaction in vivo, we used E. coli harboring temperature sensitive (ts) RRF and assayed by following downstream reading of translationally coupled ORF. At the non-permissive temperature, ribosomes remain on the termination codon of the junction sequence of coupled ORFs and translate downstream ORF …

Effects Of Vitamin D3 And Its Chemical Analogs On The Growth Of Hodgkin’S Lymphoma, In Vitro, Rajendra Ghardbaran, Bo Zhang, Luis Valerio, Onyekwere Onwumere, Madeline Wong, Jason Mighty, Stephen Redenti

Publications and Research

Objective: Vitamin D receptor (VDR) activities have been noted for a number of B cell malignancies which showed varying sensitivities to vitamin D3 (1,25-dihydroxyvitamin D3, VD3, calcitriol) and its synthetic analogs. The objective of this study was to address the potential effects of VD3 and vitamin D3 analogs (VDAs) on the growth of Hodgkin’s lymphoma (HL), a malignant pathology of B cell origin, in vitro.

Results: Immunofluorescence staining showed the expression of VDR by primary Hodgkin’s (H) and Reed–Sternberg (RS)—HRS-tumor cells in HL histological sections. Western blot analyses revealed expression of VDR in the HL cell lines Hs445, HDLM2, KMH2, …

Week Of April 8, 2019, New York Medical College

InTouch

• Members of the School of Medicine Class of 2020 Inducted into GHHS
• AOA Iota Chapter Hosts Annual Visiting Professor Lecture and Induction Ceremony
• NYMC Celebrates National Public Health Week
• Katharine Yamulla, M.A., Is Named Senior Director of Competency Based Assessment and Clinical Skills Education

The One Health Approach To Toxoplasmosis: Epidemiology, Control, And Prevention Strategies, A. Alonso Aguirre, Travis Longcore, Michelle Barbieri, Haydee Dabritz, Dolores Hill, Patrice N. Klein, Christopher Lepczyk, Emily L. Lilly, Rima Mcleod, Judith Milcarsky, Caroline E. Murphy, Chunlei Su, Elizabeth Vanwormer, Robert Yolken, Grant C. Sizemore

School of Veterinary and Biomedical Sciences: Faculty Publications

One Health is a collaborative, interdisciplinary effort that seeks optimal health for people, animals, plants, and the environment. Toxoplasmosis, caused by Toxoplasma gondii, is an intracellular protozoan infection distributed worldwide, with a heteroxenous life cycle that practically affects all homeotherms and in which felines act as definitive reservoirs. Herein, we review the natural history of T. gondii, its transmission and impacts in humans, domestic animals, wildlife both terrestrial and aquatic, and ecosystems. The epidemiology, prevention, and control strategies are reviewed, with the objective of facilitating awareness of this disease and promoting transdisciplinary collaborations, integrative research, and capacity building among universities, …

Induction Of Lipid Bodies In Leishmania Infantum-Infected C57bl/6 Macrophages Of Male Versus Female Origin, Victor A. Soupene, Ryan D. Lockard, Mary E. Wilson, Nilda E. Rodriguez

Research in the Capitol

Worldwide, 12 million people are infected with Leishmania spp. parasites. Leishmania are transmitted by the bite of sand flies. The parasite is internalized by immune cells where they develop, reproduce, and spread to new immune cells causing disease. Epidemiological studies have shown that males are more likely to develop disease. We recently demonstrated that Leishmania infantum survive better in immune cells of male origin than in cells derived from females. We also showed that L. infantum infection is characterized by fat accumulation. Additional experiments have shown that infected immune cells from males accumulate more fat than cells from females. We …

Parameter Estimation And Optimal Design Techniques To Analyze A Mathematical Model In Wound Healing, Nigar Karimli

Masters Theses & Specialist Projects

For this project, we use a modified version of a previously developed mathematical model, which describes the relationships among matrix metalloproteinases (MMPs), their tissue inhibitors (TIMPs), and extracellular matrix (ECM). Our ultimate goal is to quantify and understand differences in parameter estimates between patients in order to predict future responses and individualize treatment for each patient. By analyzing parameter confidence intervals and confidence and prediction intervals for the state variables, we develop a parameter space reduction algorithm that results in better future response predictions for each individual patient. Moreover, use of another subset selection method, namely Structured Covariance Analysis, that …

Reproducibility Of Neurite Orientation Dispersion And Density Imaging (Noddi) In Rats At 9.4 Tesla, Patrick Mccunn, Kyle M. Gilbert, Peter Zeman, Alex X. Li, Michael J. Strong, Ali R. Khan, Robert Bartha

Medical Biophysics Publications

© 2019 McCunn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Purpose Neurite Orientation Dispersion and Density Imaging (NODDI) is a diffusion MRI (dMRI) technique used to characterize tissue microstructure by compartmental modelling of neural water fractions. Intra-neurite, extra-neurite, and cerebral spinal fluid volume fractions are measured. The purpose of this study was to determine the reproducibility of NODDI in the rat brain at 9.4 Tesla. Methods Eight data sets were successfully …

Annual Research Review: Educational Neuroscience: Progress And Prospects, Michael S.C. Thomas, Daniel Ansari, Victoria C.P. Knowland

Brain and Mind Institute Researchers' Publications

© 2018 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health. Educational neuroscience is an interdisciplinary research field that seeks to translate research findings on neural mechanisms of learning to educational practice and policy and to understand the effects of education on the brain. Neuroscience and education can interact directly, by virtue of considering the brain as a biological organ that needs to be in the optimal condition to learn (‘brain health’); or indirectly, as neuroscience shapes psychological theory and psychology influences education. In …

Dual Therapy Treatment Of Pediatric Acute Lymphoblastic Leukemia With Blinotumomab And A Standard Chemotherapy Regimen, Tori I. Scheffler

Selected Honors Theses

Leukemia is the number one cancer affecting children in the nation, with acute lymphoblastic leukemia being the most prevalent classification.1 While new and innovative treatment protocols have greatly increased the success rate of primary cancer patients, those who face relapse receive a much more dismal prognosis. Recent studies have shown that patients who relapse quite frequently have developed drug-resistant clones of the original cancer cells, leading to a need for various secondary treatment options. The drug-resistance is due to clonal mutations that take place within the cancer cell, most often because of an outside pressure or stress within the environment …

Dean's Report - Spring 2019, Marina K. Holz

GSBMS Dean’s Report

No abstract provided.

Transposon Mutagenesis In Mycobacterium Avium Subspecies Paratuberculosis, John P. Bannantine, Denise K. Zinniel, Raul G. Barletta

School of Veterinary and Biomedical Sciences: Faculty Publications

While transposon mutagenesis has been developed for Mycobacterium avium subspecies paratuberculosis (Map), relatively few laboratories have adopted this important genetic tool to examine gene function and essentiality. Here we describe the construction of a Map transposon library using the Himar1 mariner transposon, but concepts can also be applied to the Tn5367 transposon, which has also been used by our group. Delivery of the transposon is by a temperature-sensitive phagemid, ϕMycoMarT7, and plating transductants requires patience and specialized media due to length of incubation required to observe colonies. Several transposon mutants obtained from these libraries have been tested in vaccine and …

What To Expect When You Are Not Expecting: The Biological, Psychological, And Cultural Setbacks Following Infertility, Lauren Butler 19

Honor Scholar Theses

No abstract provided.

Neuroprotective Activity Of Leukemia Inhibitory Factor Is Relayed Through Myeloid Zinc Finger-1 In A Rat Model Of Stroke, Stephanie M. Davis, Lisa A. Collier, Elspeth A. Foran, Christopher C. Leonardo, Craig T. Ajmo Jr., Keith R. Pennypacker

Neurology Faculty Publications

The aim of this study was to determine whether leukemia inhibitory factor (LIF) exerts its neuroprotective effects through signal transduction of the transcription factor myeloid zinc finger-1 (MZF-1). According to the hypothesis of this study, MZF-1 mediates LIF-induced neuroprotective signaling during ELVO through increased expression and transcriptional activity. To determine the in vivo role of MZF-1 in LIF-induced neuroprotection, we used Genomatix software was used to MZF-1 sites in the promoter region of the rat superoxide dismutase 3 (SOD3) gene. Stroke was induced via middle cerebral artery occlusion, and animals were administered PBS or 125 μg/kg LIF at …

The Pharmabiotic For Phenylketonuria: Development Of A Novel Therapeutic, Chloé Elizabeth Lebegue

Senior Theses

Phenylketonuria, now known as phenylalanine hydroxylase (PAH) deficiency, is a genetic disorder of metabolism affecting approximately one in every 15,000 infants born in the United States. Patients have nonfunctional PAH enzyme secondary to one or more genetic mutations. The enzyme deficit results in destructive supraphysiologic blood phenylalanine levels upon consumption of the essential dietary amino acid phenylalanine. Current standards of care mitigate signs and symptoms of the disorder, but do not approach a cure. The methods for creating a prototype pharmabiotic as an innovative treatment strategy for PAH deficiency are described herein.

DNA molecular cloning techniques were utilized to engineer …

Redefining Burnout: Exploring Common Conceptualizations And The Neurophysiology Of Chronic Stress To Establish An Integrated Allostatic Model, Danny A. Guzzi

Dissertations

Burnout is a widely researched stress-related phenomenon associated with numerous adverse outcomes for employees and organizations. Unfortunately, burnout is not well understood and research to this point has been flawed due to a lack of consensus on the definition, dimensionality, and context of the construct. Prevalent conceptualizations of burnout have been criticized for being arbitrarily developed without solid theoretical foundation and for failing to clearly distinguish burnout from depression or other work-related conditions such as compassion fatigue, secondary traumatization, and vicarious traumatization. The current project first examines relevant literature to identify commonalities among prevalent burnout conceptualizations. Then relevant stress research …