Medicine and Health Sciences Commons^™

Rapamycin Rescues Vascular, Metabolic And Learning Deficits In Apolipoprotein E4 Transgenic Mice With Pre-Symptomatic Alzheimer’S Disease, Ai-Ling Lin, Jordan B. Jahrling, Wei Zhang, Nicholas Derosa, Vikas Bakshi, Peter Romero, Veronica Galvan, Arlan Richardson

Sanders-Brown Center on Aging Faculty Publications

Apolipoprotein E ɛ4 allele is a common susceptibility gene for late-onset Alzheimer's disease. Brain vascular and metabolic deficits can occur in cognitively normal apolipoprotein E ɛ4 carriers decades before the onset of Alzheimer's disease. The goal of this study was to determine whether early intervention using rapamycin could restore neurovascular and neurometabolic functions, and thus impede pathological progression of Alzheimer's disease-like symptoms in pre-symptomatic Apolipoprotein E ɛ4 transgenic mice. Using in vivo, multimodal neuroimaging, we found that apolipoprotein E ɛ4 mice treated with rapamycin had restored cerebral blood flow, blood–brain barrier integrity and glucose metabolism, compared …

Suppression Of F1 Male-Specific Lethality In Caenorhabditis Hybrids By Cbr-Him-8, Vaishnavi Ragavapuram, Emily Elaine King, Scott Everet Baird

Biological Sciences Faculty Publications

Haldane's Rule and Darwin's Corollary to Haldane's Rule are the observations that heterogametic F1 hybrids frequently are less fit than their homogametic siblings and that asymmetric results often are obtained from reciprocal hybrid crosses. In Caenorhabditis, Haldane's Rule and Darwin's Corollary have been observed in several hybrid crosses, including crosses of Caenorhabditis briggsae and Caenorhabditis nigoni. Fertile F1 females are obtained from reciprocal crosses. However, F1 males obtained from C. nigoni mothers are sterile and F1 males obtained from C. briggsae die during embryogenesis. We have identified cbr-him-8 as a recessive maternal-effect suppressor of F1 hybrid male-specific lethality …

Perbedaan Perubahan Tekanan Darah Dan Denyut Jantung Pada Berbagai Intensitas Latihan Atlet Balap Sepeda, Mirza Hapsari Sakti Titis Penggalih, Marina Hardiyanti, Fadhila Ika Sani

Jurnal Keolahragaan

Latihan pada cabang bersepeda memperhatikan intensitas dengan salah satu parameternya denyut jantung. Penelitian ini bertujuan mengetahui perbedaan perubahan tekanan darah dan denyut jantung pada berbagai intensitas latihan atlet balap sepeda. Populasi dalam penelitian ini adalah 11 atlet balap sepeda Pegasus Continental Cycling Team selama periode pengamatan April-Juni 2015. Teknik sampling menggunakan total sampling. Analisis data menggunakan uji One Way Anova. F hitung denyut jantung dengan intensitas latihan 3,695 ‰¥ F tabel 3,316 dengan probabilitas 0,037 < 0,05 menunjukkan ada perbedaan signifikan antara perubahan denyut jantung dengan berbagai intensitas latihan. F hitung tekanan sistol dengan intensitas latihan 2,372 ‰¤ F tabel 3,316 dengan probabilitas 0,111 > 0,05 menunjukkan tidak ada perbedaan signifikan antara perubahan tekanan sistol pada berbagai intensitas latihan. F hitung tekanan diastol dengan intensitas latihan 0,852 ‰¤ F …

Cellular Responses And Tissue Depots For Nanoformulated Antiretroviral Therapy., Andrea L. Martinez-Skinner, Mariluz Araínga, Pavan Puligujja, Diana L. Palandri, Hannah M. Baldridge, Benson J. Edagwa, Joellyn Mcmillan, R. Lee Mosley, Howard Gendelman

Journal Articles: Pharmacology & Experimental Neuroscience

Long-acting nanoformulated antiretroviral therapy (nanoART) induces a range of innate immune migratory, phagocytic and secretory cell functions that perpetuate drug depots. While recycling endosomes serve as the macrophage subcellular depots, little is known of the dynamics of nanoART-cell interactions. To this end, we assessed temporal leukocyte responses, drug uptake and distribution following both intraperitoneal and intramuscular injection of nanoformulated atazanavir (nanoATV). Local inflammatory responses heralded drug distribution to peritoneal cell populations, regional lymph nodes, spleen and liver. This proceeded for three days in male Balb/c mice. NanoATV-induced changes in myeloid populations were assessed by fluorescence-activated cell sorting (FACS) with CD45, …

Cellular Responses And Tissue Depots For Nanoformulated Antiretroviral Therapy., Andrea L. Martinez-Skinner, Mariluz Araínga, Pavan Puligujja, Diana L. Palandri, Hannah M. Baldridge, Benson J. Edagwa, Joellyn Mcmillan, R. Lee Mosley, Howard Gendelman

Journal Articles: Pharmacology & Experimental Neuroscience

Long-acting nanoformulated antiretroviral therapy (nanoART) induces a range of innate immune migratory, phagocytic and secretory cell functions that perpetuate drug depots. While recycling endosomes serve as the macrophage subcellular depots, little is known of the dynamics of nanoART-cell interactions. To this end, we assessed temporal leukocyte responses, drug uptake and distribution following both intraperitoneal and intramuscular injection of nanoformulated atazanavir (nanoATV). Local inflammatory responses heralded drug distribution to peritoneal cell populations, regional lymph nodes, spleen and liver. This proceeded for three days in male Balb/c mice. NanoATV-induced changes in myeloid populations were assessed by fluorescence-activated cell sorting (FACS) with CD45, …

What Does Recent Neuroscience Tell Us About Criminal Responsibility?, Uri Maoz, Gideon Yaffe

Psychology Faculty Articles and Research

A defendant is criminally responsible for his action only if he is shown to have engaged in a guilty act—actus reus (eg for larceny, voluntarily taking someone else’s property without permission)—while possessing a guilty mind—mens rea (eg knowing that he had taken someone else’s property without permission, intending not to return it)—and lacking affirmative defenses (eg the insanity defense or self-defense). We therefore first review neuroscientific studies that bear on the nature of voluntary action, and so could, potentially, tell us something of importance about the actus reus of crimes.Then we look at studies of intention, perception of …

Surface Display Of Glycosylated Tyrosinase Related Protein-2 (Trp-2) Tumour Antigen On Lactococcus Lactis, Jeevanathan Kalyanasundram, Suet Lin Chia, Adelene Ai Lian Song, Abdul Rahim Raha, Howard A. Young, Khatijah Yusoff

Public Health Resources

Background: The exploitation of the surface display system of food and commensal lactic acid bacteria (LAB) for bacterial, viral, or protozoan antigen delivery has received strong interest recently. The Generally Regarded as Safe (GRAS) status of the Lactococcus lactis coupled with a non-recombinant strategy of in-trans surface display, provide a safe platform for therapeutic drug and vaccine development. However, production of therapeutic proteins fused with cell-wall anchoring motifs is predominantly limited to prokaryotic expression systems. This presents a major disadvantage in the surface display system particularly when glycosylation has been recently identified to significantly enhance epitope presentation. In this study, …

Thermophilic Phosphatases And Methods For Processing Starch Using The Same, Matthew S. Gentry, Craig W. Vander Kooi

Molecular and Cellular Biochemistry Faculty Patents

The presently-disclosed subject matter includes thermophilic glucan phosphatase polypeptides. In some embodiments the polypeptide includes non-native laforin polypeptides, or fragments and/or variants thereof, and in some instances the polypeptide can alter the biophysical properties of starch in vitro or in planta. The presently-disclosed subject matter also includes isolated polynucleotides encoding the present polypeptides, methods for processing starch by exposing starch to the present polypeptides, and methods for making the present polypeptides.

Is There An Ideal Level Of Platelet P2y12-Receptor Inhibition In Patients Undergoing Percutaneous Coronary Intervention?: "Window" Analysis From The Adapt-Des Study (Assessment Of Dual Antiplatelet Therapy With Drug-Eluting Stents)., Ajay J. Kirtane Md, Puja B. Parikh Md, Thomas D. Stuckey Md, Ke Xu Phd, Bernhard Witzenbichler Md, Giora Weisz Md, Michael J. Rinaldi Md, Franz-Josef Neumann Md, D Christopher Metzger Md, Timothy D. Henry Md, David A. Cox Md, Peter L. Duffy Md, Bruce R. Brodie Md, Ernest L. Mazzaferri Md, Rupa Parvataneni Ms, Akiko Maehara Md, Philippe Généreux Md, Roxana Mehran Md, Gregg W. Stone Md

Department of Medicine

OBJECTIVES: This study sought to determine whether there is an ideal level of platelet reactivity (PR) to optimize safety and efficacy within the large multicenter ADAPT-DES (Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents) study of 8,582 patients receiving successful drug-eluting stent implantation.

BACKGROUND: Patients with high PR on clopidogrel have a greater incidence of adverse ischemic events after stent implantation, whereas low PR may increase bleeding. Due to limited sample size, previous studies have not been able to adjust for differences in baseline characteristics that may confound the relationship of PR and outcomes.

METHODS: In the ADAPT-DES study, routine …

Gliopathy Of Demyelinating And Non-Demyelinating Strains Of Mouse Hepatitis Virus., Lawrence C. Kenyon, Kaushiki Biswas, Kenneth S Shindler, Manasi Nabar, Marjorie Stout, Susan T Hingley, Judith B Grinspan, Jayasri Das Sarma

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Demyelination in the central nervous system induced by neurovirulent strains of Mouse Hepatitis Virus (MHV) is mediated by the viral spike glycoprotein, but it is not clear whether the mechanism of this disease pathology involves direct viral infection of oligodendrocytes. Detailed studies of glial cell tropism of MHV are presented, demonstrating that direct MHV infection of oligodendrocytes differs between demyelinating (RSA59) and non-demyelinating (RSMHV2) viral strains both in vitro and in vivo. Our results indicate that direct injury of mature oligodendrocytes is an important mechanism of virus-induced demyelination. In vivo, RSA59 infection was identified in spinal cord gray and white …

Architecture Of High-Affinity Unnatural-Base Dna Aptamers Toward Pharmaceutical Applications, Ken Ichiro Matsunaga, Michiko Kimoto, Charlotte Hanson, Michael Sanford, Howard A. Young, Ichiro Hirao

Public Health Resources

We present a remodeling method for high-affinity unnatural-base DNA aptamers to augment their thermal stability and nuclease resistance, for use as drug candidates targeting specific proteins. Introducing a unique mini-hairpin DNA provides robust stability to unnatural-base DNA aptamers generated by SELEX using genetic alphabet expansion, without reducing their high affinity. By this method, >80% of the remodeled DNA aptamer targeting interferon-γ (KD of 33 pM) survived in human serum at 37 °C after 3 days under our experimental conditions, and sustainably inhibited the biological activity of interferon-γ.

Ethnic Differences In Maternal Adipokines During Normal Pregnancy, Xinhua Chen, Theresa O Scholl

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Two adipokines (adiponectin and resistin) have opposite relations with insulin resistance and inflammation. Our major focus was to determine whether there were detectable ethnic differences in maternal adipokines during pregnancy. We also explored the correlation of the adipokines with maternal glucose homeostasis, blood pressure and anthropometric parameters. Pregnant women (n = 1634) were from a large prospective cohort study in Camden NJ (African-American 36.8%; Hispanic 47.6%; Caucasian 15.6%). Serum adiponectin and resistin were measured at entry (week 16.8) and the 3rd trimester (week 30.7) using the Luminex xMapTechnology. Significant differences were observed among ethnic groups, controlling for confounding variables. African …

How The Manipulation Of The Ras Homolog Enriched In Striatum Alters The Behavioral And Molecular Progression Of Huntington’S Disease, Franklin A. Lee

University of New Orleans Theses and Dissertations

Huntington’s disease is an incurable, progressive neurological disorder characterized by loss of motor control, psychiatric dysfunction, and eventual dystonia leading to death. Despite the fact that this disorder is caused by a mutation in one single gene, there is no cure. The mutant Huntingtin (mHtt) protein is expressed ubiquitously throughout the brain but frank cell death is limited to the striatum. Recent work has suggested that Rhes, Ras homolog enriched in striatum, which is selectively expressed in the striatum, may play a role in Huntington’s disease neuropathology. In vitro studies have shown Rhes to be an E3 ligase for the …

Regulatory Roles Of Mical-L1 And Ehd1 In Cell Signaling And Mitosis, James B. Reinecke

Theses & Dissertations

Membrane trafficking is a basic cell biological process that controls the distribution of proteins and lipids. Our lab is particularly interested in delineating the cellular functions as well as the molecular mechanisms that regulate the C-terminal Eps15 Homology Domain (EHD) protein family of adenosine-5’-triphosphatases in mammalian cells. EHD1-4 are ubiquitously expressed in mammalian tissues and serve partially overlapping but also distinct functions in regulating membrane shaping and fission along the endocytic pathway. Specifically, EHD1 is recruited to tubular recycling endosomes (TREs) by Molecule Interacting with CasL Like-1 (MICAL-L1) and facilitates TRE fission and release of cargo from the perinuclear endocytic …

Epacs: Epigenetic Regulators That Affect Cell Survival In Cancer., Catherine Murari

Theses & Dissertations

Cyclic adenosine monophosphate (cAMP) is a second messenger responsive to many external stimuli, playing an important role in cellular gene expression, metabolism, migration, differentiation, hypertrophy, apoptosis and secretion. All of these cellular functions are important in many diseases including cancer. Most of its effects were initially attributed to the classical protein kinase A (PKA) protein, but cellular functions such as proliferation and migration were found to be PKA independent and dependent on the newly discovered exchange proteins directly activated by cAMP (EPACs). EPACs are single polypeptides that primarily function as guanine exchange factors (GEFs) for Rap proteins that allow the …

The Effect Of Body Mass Index On Graft Function And Kidney Transplant Outcomes, Morgan Galle

Theses & Dissertations

Background: When determining eligibility for kidney transplantation, body mass index (BMI) is often a debatable criterion for transplant due to the clinical indication, an elevated BMI has adverse effects on kidney transplant outcomes. There is a current gap in research on the effect BMI has on kidney transplant outcomes.

Purpose: The purpose of this study was to determine the role BMI plays in post-kidney transplant clinical outcomes including delayed graft function, new onset diabetes after transplant, wound complications, hospital length of stay, albumin, and readmissions to the hospital from initial hospitalization and at six months following kidney transplantation. The primary …

The Feedforward And Feedback Controls On Gait In Adults With Diabetes, Chun-Kai Huang

Theses & Dissertations

There are nearly 26 million people with diabetes mellitus (DM) in the US, and half of chronic DMs develop somatosensory deficits due to diabetic polyneuropathy or diabetic peripheral neuropathy (DPN). The absence or impaired somatosensory feedback (e.g. touch sensation or joint proprioception) resulted from the damage of large nerve fiber, and motor deficits such as attenuated muscle strength and abnormal plantar pressure of lower extremity have been identified in DPN, and these sensorimotor impairments lead to an increased number of falls. To reduce the risk of falling, a well-coordinated and adapted limb movement driven by the feedforward (anticipatory) and feedback …

Association Between Recipient’S Preexisting Antibodies And Allograft Vasculopathy And Mortality In Heart Transplant Patients, Hoang Tran, Lorena Baccaglini, Jane L. Meza, Brian D. Lowes

Theses & Dissertations

Objectives: To evaluate the role of preexisting Angiotensin II receptor type I antibodies (AT1RAb) and anti-HLA antibodies in predicting mortality and cardiac allograft vasculopathy (CAV) among heart transplant patients.

Methods: In this retrospective cohort study, we included 114 adults who received heart transplant from January 1^st, 2007 to December 31, 2014 and were followed up at Nebraska Medicine. 48 hours pre-transplant sera sample were used to detect antibodies. A cutoff of 10UL/ml was used for AT1RAb positive and mean fluorescence intensity of 3,000 and 1,500 were used for anti HLA class I and class II, respectively. Patients were …

Interaction Between Angiotensin Ii And Bdnf In Modulating Sympathetic Nerve Activity, Bryan K. Becker

Theses & Dissertations

Over activation of the sympathetic nervous system is prevalent in many forms of cardiovascular disease such as chronic heart failure (CHF) and hypertension. Although increased neuronal renin-angiotensin system activity in presympathetic neurons has been well implicated in mediating this sympatho-excitation, many of the neuronal effects of angiotensin II (Ang II) signaling remain poorly understood. One particular mechanism of Ang II-mediated increases in presympathetic neuronal activity is through reductions in voltage-gated K⁺ currents. Another pathway that has profound effects on neuronal K⁺ currents and that has been previously implicated in Ang II-signaling is brain-derived neurotrophic factor (BDNF) activity through …

Selective Vip Receptor Agonists Facilitate Immune Transformation For Dopaminergic Neuroprotection In Mptp-Intoxicated Mice., Katherine E. Olson, Lisa M. Kosloski-Bilek, Kristi M. Anderson, Breha J. Diggs, Barbara E. Clark, John M. Gledhill, Scott J. Shandler, R. Lee Mosley, Howard Gendelman

Journal Articles: Pharmacology & Experimental Neuroscience

UNLABELLED: Vasoactive intestinal peptide (VIP) mediates a broad range of biological responses by activating two related receptors, VIP receptor 1 and 2 (VIPR1 and VIPR2). Although the use of native VIP facilitates neuroprotection, clinical application of the hormone is limited due to VIP's rapid metabolism and inability to distinguish between VIPR1 and VIPR2 receptors. In addition, activation of both receptors by therapeutics may increase adverse secondary toxicities. Therefore, we developed metabolically stable and receptor-selective agonists for VIPR1 and VIPR2 to improve pharmacokinetic and pharmacodynamic therapeutic end points. Selective agonists were investigated for their abilities to protect mice against MPTP-induced neurodegeneration …

Iron-Dependent Gene Expression In Actinomyces Oris, Matthew P. Mulé, David Giacalone, Kayla Lawlor, Alexa Golden, Caroline Cook, Thomas Lott, Elizabeth Aksten, George A. O'Toole, Lori J. Bergeron

Dartmouth Scholarship

Actinomyces oris is a Gram-positive bacterium that has been associated with healthy and diseased sites in the human oral cavity. Most pathogenic bacteria require iron to survive, and in order to acquire iron in the relatively iron-scarce oral cavity A. oris has been shown to produce iron-binding molecules known as siderophores. The genes encoding these siderophores and transporters are thought to be regulated by the amount of iron in the growth medium and by the metal-dependent repressor, AmdR, which we showed previously binds to the promoter of proposed iron-regulated genes.

Serotonergic System And Gait: Dorsal Raphe Nucleus As A Control System For Gait, Nahal Farhani

Electronic Thesis and Dissertation Repository

In advanced stages of Parkinson Disease (PD), gait and postural abnormalities emerge. These symptoms are not prominent at early stages of PD despite significant dopaminergic neuronal loss. Gait abnormalities are largely not responsive to levodopa. Therefore, other types of neurons might be responsible for gait abnormalities of the PD.

Since the reticulospinal tract (RET) is mainly implicated in the control of axial muscles, the degeneration of this pathway or populations of neurons controlling this pathway might be responsible for axial symptoms. However, there is limited data about the neurons controlling the RET. Our aim in this study is to delineate …

Finding Optimal Brain Mappings Using Integer Linear Programming Solvers And Other Methods, Heriberto Flores

Honors Theses

No abstract provided.

Intracellular Acidification In Brain Tumors Induced By Topiramate : In-Vivo Detection Using Chemical Exchange Saturation Transfer Magnetic Resonance Imaging, Kamini Y. Marathe

Electronic Thesis and Dissertation Repository

Glioblastoma Multiforme (GBM) is the most aggressive and malignant form of primary brain tumor. In many tumors, increased intracellular pH (pH_i) is a hallmark of aggressiveness. This increased pH_i has been shown to be related to cell proliferation and evasion of apoptosis as well as resistance to chemotherapy. As such, monitoring pH_i and the tumor pH_i response to pharmacologic challenge, may aid in treatment planning and patient management for this deadly cancer. A magnetic resonance imaging (MRI) method called Chemical Exchange Saturation Transfer (CEST) has been used to detect changes in pH_i. Our group …

Week Of December 14, 2015, New York Medical College

InTouch

• Summer Fellowship Pays Off in the Form of Published Research
• Department of Surgery Hosts Twelfth Annual Louis R.M. Del Guercio, M.D., Distinguished Visiting Professorship and Research Day
• D.P.T. Students Share Their Community Service Projects
• Department of Pediatrics Hosts Fifth Annual Assistant Professor Pediatric Research Symposium
• NYMC Serves Up International Food and Handicrafts
• P2P Committee Recognizes Role Models at NYMC

Recommendations For The Development Of New Hospital Guidelines Due To The Effects Of Antibiotics On Clostridium Difficile Colitis, Megan Kohsel

Honors Theses

Clostridium difficile colitis is an infection that causes inflammation of the colon and diarrhea. This can even lead to death in some cases. The incidence of this infection and its overall effects have been on the rise throughout the last twenty years as antibiotics have been prescribed more frequently. Therefore, it is necessary that the rate of C. difficile infection is lowered by improved guidelines for hospitals, so that fewer people are infected and also that fewer antibiotics are prescribed to avoid the infection with C. difficle.

The Incidence Of Early Stage Postoperative Nausea And Vomiting Following The Use Of Nitrous Oxide And Prophylactic Antiemetic Therapy: Implications For Clinical Practice, James Sullivan

Doctoral Projects

Nitrous oxide (N₂O) is a volatile agent currently used during the induction and maintenance of general anesthesia. Since it’s discovery in 1786 by Dr. Priestly, it is the oldest volatile agent to find continued use in current practice (Kossick, 2014). In conjunction with its extensive history is the debate regarding its emetic properties. Numerous studies have investigated the effect of nitrous oxide to produce postoperative nausea and vomiting (PONV) with varying and often conflicting results. Generally speaking, nitrous oxide is theoretically an emetic and is believed to be associated with PONV (Tramer, Moore, & McQuay, 1996). This has …

The Effectiveness Of A Preoperative Multimodal Antiemetic Regimen On Reducing Early Postoperative Nausea And Vomiting In Total Joint Arthroplasty Patients, Jerry Mosley

Doctoral Projects

Postoperative nausea and vomiting (PONV) occurs frequently in all types of surgeries including after total joint orthopedic procedures. The resulting PONV can lead to many unwanted occurrences including immobilization, distress, and many serious adverse health complications. These unwanted occurrences may then lead to increased cost to the patient and healthcare facility. Administration of a preoperative multimodal regimen known to reduce PONV has the potential to reduce such unwanted anesthetic side effects influencing a reduction in overall healthcare cost. The purpose of this study is to determine the effectiveness of the preoperative kit which includes the administration of metoclopramide, famotidine, ondansetron, …

Progtar: A Database Of Prognostically Inversely Correlated Mirnas And Genes (Pics) In Multiple Cancers, Chirayu Pankaj Goswami

Department of Pathology, Anatomy, and Cell Biology Posters

ABSTRACT

PROGTar is a database of Prognostically Inversely Correlated miRNA-mRNA pairs (PIC’s) in 23 cancer types. Partner miRNA and mRNA in a PIC show inverse correlation of expression and opposite hazards. We analyzed miRNA and mRNA expression data downloaded from The Cancer Genome Atlas (TCGA) in a 3 step approach to identify PICs in different cancer types. In first step we performed correlation analysis between miRNAs and mRNAs for each cancer type. This was followed by performing hazard analysis separately for miRNAs and mRNAs using expression data and survival related clinical variables. In the third step we merged the correlation …

Role Of Maternal Dietary Peanut Exposure In Development Of Food Allergy And Oral Tolerance, Magdia De Jesus

Biomedical Sciences Faculty Scholarship

Background The impact of maternal ingestion of peanut during pregnancy and lactation on an offspring’s risk for peanut allergy is under debate. Objective To investigate the influence of maternal dietary peanut exposure and breast milk on an offspring’s allergy risk. Methods Preconceptionally peanut-exposed C3H/HeJ females were either fed or not fed peanut during pregnancy and lactation. The offsprings’ responses to peanut sensitization or oral tolerance induction by feeding antigen prior to immunization were assessed. We also assessed the impact of immune murine milk on tolerance induction pre- or post-weaning. For antigen uptake studies, mice were gavaged with fluorescent peanut in …