Medical Physiology Commons^™

Evidence That Bdnf Regulates Heart Rate By A Mechanism Involving Increased Brainstem Parasympathetic Neuron Excitability, Ruqian Wan, Letitia A. Weigand, Ryan Bateman, Kathleen Griffioen, David Mendelowitz, Mark P. Mattson

Pharmacology and Physiology Faculty Publications

Autonomic control of heart rate is mediated by cardioinhibitory parasympathetic cholinergic neurons located in the brainstem and stimulatory sympathetic noradrenergic neurons. During embryonic development the survival and cholinergic phenotype of brainstem autonomic neurons is promoted by brain-derived neurotrophic factor (BDNF). We now provide evidence that BDNF regulates heart rate by a mechanism involving increased brainstem cardioinhibitory parasympathetic activity. Mice with a BDNF haploinsufficiency exhibit elevated resting heart rate, and infusion of BDNF intracerebroventricularly reduces heart rate in both wild-type and BDNF+/− mice. The atropine-induced elevation of heart rate is diminished in BDNF+/− mice and is restored by BDNF infusion, whereas …

Cyclic Nucleotide-Dependent Phosphorylation Regulates Bk-Ca Channel Activity In Human Coronary Artery Smooth Muscle Cells, Raeonda Williams

PCOM Biomedical Studies Student Scholarship

Cardiovascular diseases (CVD) can induce dysfunction in organ systems by attenuating normal blood flow. Gonadal steroids are vasoactive hormones, but their role in contributing to cardiovascular function remains controversial. We have demonstrated that gonadal steroids can relax coronary arteries by opening the large-conductance, calcium- and voltage-activated potassium (BKca) channel in smooth muscle cells by increasing cyclic nucleotide levels; however, the signaling pathways involved remain to be elucidated. The purpose of this study was to identify how phosphorylation (via cAMP- and cGMP-dependent protein kinases) I dephosphorylation (via phosphoprotein phosphatase 2A, PP2A) regulates BKca channel activity in human coronary artery smooth muscle …

Life History Tradeoffs And The Costs Of Reproduction In Arizona Bark Scorpions (Centruroides Sculpturatus), Michael Marie Webber

UNLV Theses, Dissertations, Professional Papers, and Capstones

Tradeoffs in life history evolution result from conflicts in the time and energy that can be simultaneously invested in activities such as growth, reproduction, and survival. Reproduction is an energetically costly activity for organisms, and is known to elicit alterations in the daily activity patterns of individuals. I investigated reproductive tradeoffs in the Arizona Bark Scorpion,Centruroides sculpturatus. To better understand the nature of tradeoffs in this species, I examined the influence of reproductive state on the predatory efficiency and thermal preference of reproductive females. Further, I examined the influence of reproductive activities (i.e. gestation) on the ability of reproductive females …

The Grass Shrimp, Palaemonetes, Pugio: Hypoxic Influences On Embryonic Development, Christensen C. Javier

UNLV Theses, Dissertations, Professional Papers, and Capstones

Grass shrimp,Palaemonetes pugio, can survive in brackish waters and estuarine ecosystems despite the frequent oscillations and fluctuations in salinity, temperature and oxygen. AdultP. pugiohave the ability to osmoregulate (Romney and Reiber 2011), change cardiac parameters to tolerate temperatures (not yet published, Mika and Reiber) and oxyregulate (Guadagnoli and Reiber 2013). Manipulation of cardiac parameters allows for these methods of regulation. However, cardiac contraction and internal convection of oxygen do not occur until later stages of embryonic development. Studies focused on these morphological and physiological advantages may provide further understanding of the regulatory mechanisms within grass shrimp embryos, larvae and adults. …

Extracellular Ubiquitin: Role In Cardiac Myocyte Apoptosis And Myocardial Remodeling, Christopher Ray Daniels

Electronic Theses and Dissertations

Activation of sympathetic nervous system is a key component of myocardial remodeling that generally occurs following ischemia/reperfusion (I/R) injury and myocardial infarction. It induces cardiac myocyte apoptosis and myocardial fibrosis, leading to myocardial dysfunction. Intracellular ubiquitin (UB) regulates protein turnover by the UB-proteosome pathway. The biological functions of extracellular UB in the heart remain largely unexplored. Previously, our lab has shown that β-adrenergic receptor (β-AR) stimulation increases extracellular UB levels, and extracellular UB inhibits β-AR-stimulated apoptosis in adult rat ventricular myocytes (ARVMs). This study explores the role of extracellular UB in myocyte apoptosis, fibroblast phenotype and function, and myocardial remodeling …

Novel Therapeutic Approaches For Ischemic Heart And Brain Injury: Modulation Of Toll-Like Receptor-Mediated Signaling Pathways And Pi3k/Akt Signaling, Chen Lu

Electronic Theses and Dissertations

Innate immune and inflammatory responses contribute to myocardial and cerebral ischemia/reperfusion (I/R) injury. Toll-like receptors (TLRs) play a critical role in the induction of innate immune and inflammatory responses via activation of nuclear factor kappa B (NF-κB). We have shown that activation of NF-κB contributes to myocardial and cerebral I/R injury. Indeed, inhibition of TLR4-mediated NF-κB activation significantly decreased myocardial and cerebral I/R injury via activation of PI3K/Akt signaling. PI3K/Akt signaling is an important pathway in regulating cellular survival and inflammatory responses. Therefore, an important question is how to differentially modulate PI3K/Akt signaling and TLR/NF-κB-mediated signaling pathway during I/R injury? …

9-Phenanthrol And Flufenamic Acid Inhibit Calcium Oscillations In Hl-1 Mouse Cardiomyocytes, Rees A. Burt

Undergraduate Honors Theses

Electrical potentials exist across the membranes of nearly every cell type in the body. In addition, excitable cells, such as neurons, myocytes and even some endocrine cells elicit electrochemical fluctuations, action potentials (AP), in the cell membrane to initiate cell-to-cell communication or intracellular processes. The basis for the electrical potential is rooted within an array of complex interactions between monovalent ions and their associated membrane channels and transporters that regulate the flux of these charged species across the hydrophobic bilayer. Here, an expansion of our recently published work [1] will serve to explore the modern concepts regarding the …

Bisphenol A Exposure And Cardiac Electrical Conduction In Excised Rat Hearts, Nikki G. Posnack, Rafael Jaimes Iii, Huda Asfour, Luther Swift, Anastasia M. Wengrowski, Narine Sarvazyan, Matthew Kay

Pharmacology and Physiology Faculty Publications

BACKGROUND:

Bisphenol A (BPA) is used to produce polycarbonate plastics and epoxy resins that are widely used in everyday products, such as food and beverage containers, toys and medical devices. Human biomonitoring studies have suggested that a large proportion of the population may be exposed to BPA. Recent epidemiological studies have reported correlations between increased BPA urinary concentrations and cardiovascular disease; yet the direct effects of BPA on the heart are unknown.

OBJECTIVES:

The goal of our studies was to measure BPA's effect (0.1-100 μM) on cardiac impulse propagation ex vivo, using excised whole hearts from adult rats.

METHODS: …

Adult Spinal Motoneurones Are Not Hyperexcitable In A Mouse Model Of Inherited Amyotrophic Lateral Sclerosis, Nicolas Delestrée, Marin Manuel, Caroline Iglesias, Sherif M. Elbasiouny, C. J. Heckman, Daniel Zytnicki

Neuroscience, Cell Biology & Physiology Faculty Publications

In amyotrophic lateral sclerosis (ALS), an adult onset disease in which there is progressive degeneration of motoneurones, it has been suggested that an intrinsic hyperexcitability of motoneurones (i.e. an increase in their firing rates), contributes to excitotoxicity and to disease onset. Here we show that there is no such intrinsic hyperexcitability in spinal motoneurones. Our studies were carried out in an adult mouse model of ALS with a mutated form of superoxide dismutase 1 around the time of the first muscle fibre denervations. We showed that the recruitment current, the voltage threshold for spiking and the frequency–intensity gain in the …

Substance P Differentially Modulates Firing Rate Of Solitary Complex (Sc) Neurons From Control And Chronic Hypoxia-Adapted Adult Rats, Nicole L. Nichols, Frank L. Powell, Jay B. Dean, Robert W. Putnam

Neuroscience, Cell Biology & Physiology Faculty Publications

NK1 receptors, which bind substance P, are present in the majority of brainstem regions that contain CO₂/H⁺-sensitive neurons that play a role in central chemosensitivity. However, the effect of substance P on the chemosensitive response of neurons from these regions has not been studied. Hypoxia increases substance P release from peripheral afferents that terminate in the caudal nucleus tractus solitarius (NTS). Here we studied the effect of substance P on the chemosensitive responses of solitary complex (SC: NTS and dorsal motor nucleus) neurons from control and chronic hypoxia-adapted (CHx) adult rats. We simultaneously measured intracellular pH …

Complexity Of Interferon-Γ Interactions With Hsv-1, Nancy J. Bigley

Neuroscience, Cell Biology & Physiology Faculty Publications

The intricacies involving the role of interferon-gamma (IFN-γ) in herpesvirus infection and persistence are complex. Herpes simplex virus type 1 (HSV-1) uses a variety of receptors to enter cells and is transported to and from the host cell nucleus over the microtubule railroad via retrograde and anterograde transport. IFN-γ exerts dual but conflicting effects on microtubule organization. IFN-γ stimulates production of suppressors of cytokine signaling 1 and 3 (SOCS1 and SOCS3), which are involved in microtubule stability and are negative regulators of IFN-γ signaling when overexpressed. IFN-γ also interferes with the correct assembly of microtubules causing them to undergo severe …

Medial Septal Cholinergic Neurons Modulate Isoflurane Anesthesia., Siew Kian Tai, Jingyi Ma, L Stan Leung

Physiology and Pharmacology Publications

BACKGROUND: Cholinergic drugs are known to modulate the response of general anesthesia. However, the sensitivity of isoflurane or other volatile anesthetics after selective lesion of septal cholinergic neurons that project to the hippocampus is not known.

METHODS: Male Long Evans rats had 192 immunoglobulin G-saporin infused into the medial septum (n = 10), in order to selectively lesion cholinergic neurons, whereas control, sham-lesioned rats were infused with saline (n = 12). Two weeks after septal infusion, the hypnotic properties of isoflurane and ketamine were measured using a behavioral endpoint of loss of righting reflex (LORR). Septal lesion was assessed by …

Maternal Biomarkers Of Endothelial Dysfunction And Preterm Delivery, Xinhua Chen, Theresa O Scholl

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Endothelial dysfunction is key to the development of atherosclerosis. Preterm delivery foreshadows later maternal cardiovascular disease (CVD), but it is not known if endothelial dysfunction also occurs. We prospectively measured circulating biomarkers of endothelial dysfunction in pregnant women with preterm or term delivery.

METHODS: We conducted a case-control study nested within a large prospective epidemiological study of young, generally healthy pregnant women. Women who delivered preterm (gestation, n = 240) and controls who delivered at term (n = 439) were included. Pregnancies complicated by preeclampsia were analyzed separately. Circulating endothelial dysfunction biomarkers included soluble intercellular adhesion molecule-1 (sICAM-1), vascular …

Concordant Integrative Gene Set Enrichment Analysis Of Multiple Large-Scale Two-Sample Expression Data Sets, Yinglei Lai, Fanni Zhang, Tapan K. Nayak, Reza Modarres, Norman H. Lee, Timothy A. Mccaffrey

Pharmacology and Physiology Faculty Publications

Background

Gene set enrichment analysis (GSEA) is an important approach to the analysis of coordinate expression changes at a pathway level. Although many statistical and computational methods have been proposed for GSEA, the issue of a concordant integrative GSEA of multiple expression data sets has not been well addressed. Among different related data sets collected for the same or similar study purposes, it is important to identify pathways or gene sets with concordant enrichment.

Methods

We categorize the underlying true states of differential expression into three representative categories: no change, positive change and negative change. Due to data noise, what …

Heat Shock Factor 2 Is A Stress‐Responsive Mediator Of Neuronal Migration Defects In Models Of Fetal Alcohol Syndrome, Rachid El Fatimy, Federico Miozzo, Anne Le Mouël, Ryma Abane, Leslie Schwendimann, Délara Sabéran‐Djoneidi, Aurélie De Thonel, Illiasse Massaoudi, Liliana Paslaru, Kazue Hashimoto-Torii, Elisabeth Christians, Pasko Rakic, Pierre Gressens, Valérie Mezger

Pharmacology and Physiology Faculty Publications

Fetal alcohol spectrum disorder (FASD) is a frequent cause of mental retardation. However, the molecular mechanisms underlying brain development defects induced by maternal alcohol consumption during pregnancy are unclear. We used normal andHsf2‐deficient mice and cell systems to uncover a pivotal role for heat shock factor 2 (HSF2) in radial neuronal migration defects in the cortex, a hallmark of fetal alcohol exposure. Upon fetal alcohol exposure, HSF2 is essential for the triggering of HSF1 activation, which is accompanied by distinctive post‐translational modifications, and HSF2 steers the formation of atypical alcohol‐specific HSF1–HSF2 heterocomplexes. This perturbs the in vivo binding …

Complement Expression In The Retina Is Not Influenced By Short-Term Pressure Elevation, Konstantin Astafurov, Cecilia Q. Dong, Lampros Panagis, Gautam Kamtham, Lizhen Ren, Anna Rozenboym, Tarique D. Perera, Jeremy D. Coplan, John Danias

Publications and Research

Purpose: To determine whether short-term pressure elevation affects complement gene expression in the retina in vitro and in vivo.

Methods: Muller cell (TR-MUL5) cultures and organotypic retinal cultures from adult mice and monkeys were sub- jected to either 24-h or 72-h of pressure at 0, 15, 30, and 45 mmHg above ambient. C57BL/6 mice were subjected to microbead-induced intraocular pressure (IOP) elevation for 7 days. RNA and protein were extracted and used for analysis of expression levels of complement component genes and complement component 1, q subcomponent (C1q) and comple- ment factor H (CFH) immunoblotting. …

Waveguide Evanescent Field Scattering Microscopy: Bacterial Biofilms And Their Sterilization Response Via Uv Irradiation, Qamrun Nahar, Frederik Fleiβner, Jeremiah Shuster, Michael Morawitz, Christopher Halfpap, Mihaela Stefan, Uwe Langbein, Gordon Southam, Silvia Mittler

Physiology and Pharmacology Publications

Waveguide Evanescent Field Scattering (WEFS) microscopy is introduced as a new and simple tool for label-free, high contrast imaging of bacteria and bacteria sensors. Bacterial microcolonies and single bacteria were discriminated both by their bright field images and by their evanescent scattering intensity. By comparing bright field images with WEFS images, the proportion of planktonic: sessile (i.e., ‘floating’: attached) bacteria were measured. Bacteria were irradiated with UV light, which limited their biofilm forming capability. A quantitative decrease in attachment of individual, sessile bacteria and in attached, microcolony occupied areas was easily determined within the apparent biofilms with increasing UV dose. …

Absence Of Manganese Superoxide Dismutase Delays P53-Induced Tumor Formation., Adam J. Case, Frederick E. Domann

Journal Articles: Cellular & Integrative Physiology

BACKGROUND: Manganese superoxide dismutase (MnSOD) is a mitochondrial antioxidant enzyme that is down-regulated in a majority of cancers. Due to this observation, as well as MnSOD's potent antioxidant enzymatic activity, MnSOD has been suggested as a tumor suppressor for over 30 years. However, testing this postulate has proven difficult due to the early post-natal lethality of the MnSOD constitutive knock-out mouse. We have previously used a conditional tissue-specific MnSOD knock-out mouse to study the effects of MnSOD loss on the development of various cell types, but long-term cancer development studies have not been performed. We hypothesized the complete loss of …

Over-Expressed Copper/Zinc Superoxide Dismutase Localizes To Mitochondria In Neurons Inhibiting The Angiotensin Ii-Mediated Increase In Mitochondrial Superoxide, Shumin Li, Adam J. Case, Rui-Fang Yang, Harold D. Schultz, Matthew C. Zimmerman

Journal Articles: Cellular & Integrative Physiology

Angiotensin II (AngII) is the main effector peptide of the renin-angiotensin system (RAS), and contributes to the pathogenesis of cardiovascular disease by exerting its effects on an array of different cell types, including central neurons. AngII intra-neuronal signaling is mediated, at least in part, by reactive oxygen species, particularly superoxide (O2 (•-)). Recently, it has been discovered that mitochondria are a major subcellular source of AngII-induced O2 (•-). We have previously reported that over-expression of manganese superoxide dismutase (MnSOD), a mitochondrial matrix-localized O2 (•-) scavenging enzyme, inhibits AngII intra-neuronal signaling. Interestingly, over-expression of copper/zinc superoxide dismutase (CuZnSOD), which is believed …

Expression And Splicing Of Alzheimer’S Disease Risk Gene Phosphatidylinositol-Binding Clathrin Assembly Protein, Ishita Parikh

Theses and Dissertations--Physiology

Recent Genome Wide Association Studies (GWAS) have identified a series of single nucleotide polymorphism (SNP)s that are associated with Alzheimer’s disease (AD). One of the SNPs, rs3851179 (G/A), is near the gene phosphatidylinositol-binding clathrin assembly protein (PICALM). To evaluate whether this SNP is associated with PICALM expression, we quantified PICALM mRNA in 56 brain cDNA samples. Using linear regression analysis, we analyzed PICALM expression relative to rs3851179, AD status, and cell type specific markers. An association was detected between rs3851179 and PICALM, microvessel mRNA, glial fibrillary acidic protein (GFAP) mRNA, and synaptophysin (SYN) mRNA. To gain clarity …

Serotonin Receptor 2-Induced Mitochondrial Biogenesis As A Therapeutic Strategy For The Treatment Of Multiple Pathologies, Jennifer Linton Harmon

MUSC Theses and Dissertations

Mitochondrial dysfunction is a common pathophysiological feature in many acute and chronic organ injury states. Often, this mitochondrial dysfunction is sub-lethal and persistent and is a major contributor to loss of cellular function in the absence of cell death. Mitochondrial biogenesis (MB) is the process by which new mitochondria are created, and studies have demonstrated that pharmacological induction of MB can reverse loss of mitochondrial content, improve mitochondrial function and reduce measures of acute organ injury. Several classes of pharmacological agents that induce MB through divergent mechanisms have been identified. Previous studies demonstrated that 2,5-Dimethoxy-4-iodoamphetamine (DOI), a potent but non-specific …

Comparison Of Two Different Sprint Interval Training Work-To-Rest Ratios On Acute Metabolic And Inflammatory Responses, Christopher R. Harnish

Theses and Dissertations

High intensity exercise is believed to yield greater results on health and human performance than moderate intensity exercise. Extensive research indicates that not only do high-intensity interval training (HIT) and sprint interval training (SIT) produce significant improvements in cardiovascular fitness and disease, they may be more effective at improving long-term metabolic function, including insulin sensitivity (Si), by producing more mitochondria. Moreover, compliance rates for HIT and SIT participation are reported to be the same or better than traditional moderate intensity exercise. Because lack of time is often cited as major hindrance to exercise participation, SIT is also seen as a …

Comparison Of Semi-Automated And Manual Measurements Of Carotid Intima-Media Thickening, Oscar Mac Ananey, G Mellotte, V Maher

Articles

Carotid intima-media thickening (CIMT) is a marker of both arteriosclerotic and atherosclerotic risks. Technological advances have semiautomated CIMT image acquisition and quantification. Studies comparing manual and automated methods have yielded conflicting results possibly due to plaque inclusion in measurements. Low atherosclerotic risk subjects (n = 126) were recruited to minimise the effect of focal atherosclerotic lesions on CIMT variability. CIMT was assessed by high-resolution B-mode ultrasound (Philips HDX7E, Phillips, UK) images of the common carotid artery using both manual and semiautomated methods (QLAB, Phillips, UK). Intraclass correlation coefficient (ICC) and the mean differences of paired measurements (Bland-Altman method) were used …

Factors Influencing Peripheral Skin Temperature Circadian Rhythm In Young Adult Males, Hannah Tranel

Theses and Dissertations--Kinesiology and Health Promotion

Periodic cues, including scheduled exercise, social interactions, sleep habits, and feeding time, have been shown to alter the circadian system. A disruption in circadian rhythms has been shown to have negative effects on health. Frequent skin temperature measures have been shown to be a valid method of assessing circadian rhythm parameters. The purpose of this study was to determine group mean differences in temperature amplitude, stability and lag measures among groups of young men of varying (optimal, fair and poor) adiposities. The strength of the association among the temperatures parameters and measures of body composition, physical fitness and activity, nutritional …

A Mechanism Linking Id2-Tgfβ Crosstalk To Reversible Adaptive Plasticity In Neuroblastoma, Lina Chakrabarti, Bi-Dar Wang, Norman H. Lee, Anthony D. Sandler

Pharmacology and Physiology Faculty Publications

The ability of high-risk neuroblastoma to survive unfavorable growth conditions and multimodal therapy has produced an elusive childhood cancer with remarkably poor prognosis. A novel phenomenon enabling neuroblastoma to survive selection pressure is its capacity for reversible adaptive plasticity. This plasticity allows cells to transition between highly proliferative anchorage dependent (AD) and slow growing, anoikis-resistant anchorage independent (AI) phenotypes. Both phenotypes are present in established mouse and human tumors. The differential gene expression profile of the two cellular phenotypes in the mouse Neuro2a cell line delineated pathways of proliferation in AD cells or tyrosine kinase activation/ apoptosis inhibition in AI …

Caveolins And Njks Influence Brain Endothelial Permeability After Juvenile Tbi, David Olufemi Ajao

Loma Linda University Electronic Theses, Dissertations & Projects

Disruption of blood-brain barrier (BBB) is a key secondary event that exacerbates brain damage following traumatic brain injury (TBI). BBB disruption is particularly damaging to the developing brain – which is highly vulnerable to various stress stimuli, resulting in increased brain swelling, disrupted cerebral blood flow (CBF) autoregulation, long-term disabilities and death following TBI in young demographic. Unsurprisingly, BBB disruption and the resultant cerebral edema have emerged as therapeutic targets in juvenile TBI. It is therefore important to understand the molecular players and mechanisms involved in TBI-induced BBB disruption in the juvenile brain. To this end, the endothelial caveolins and …

Auditory Stimuli Mimicking Ambient Sounds Drive Temporal "Delta Brushes" In Premature Infants, Mathilde Chipaux, Matthew Colonnese, Audrey Mauguen, Laure Fellous, Mostafa Mokhtari, Oscar Lezcano, Mathieu Milh, Olivier Dulac, Catherine Chiron, Rustem Khazipov, Anna Kaminska

Pharmacology and Physiology Faculty Publications

In the premature infant, somatosensory and visual stimuli trigger an immature electroencephalographic (EEG) pattern, “delta-brushes,” in the corresponding sensory cortical areas. Whether auditory stimuli evoke delta-brushes in the premature auditory cortex has not been reported. Here, responses to auditory stimuli were studied in 46 premature infants without neurologic risk aged 31 to 38 postmenstrual weeks (PMW) during routine EEG recording. Stimuli consisted of either low-volume technogenic “clicks” near the background noise level of the neonatal care unit, or a human voice at conversational sound level. Stimuli were administrated pseudo-randomly during quiet and active sleep. In another protocol, the cortical response …

Comparison Of Electrogustometrically Determined Taste Threshold And Phenylthiocarbamide Sensitivity Between Non-Diabetic Subjects With First Degree Relatives With Type 2 Diabetes And Non-Diabetic Subjects Without Type 2 Diabetic First Degree Relatives, Matthew E. Joseph Do

PCOM Biomedical Studies Student Scholarship

Diabetes is a systemic degenerative disease, having adverse effects on many different organ systems. Nerve conduction specifically related to taste is one of the affected functions and can lead to altered taste perceptions and taste thresholds. Electrogustometry was used in this study to evaluate taste thresholds, and taste sensitivity was tested using phenylthiocarbamide-impregnated testing strips. Healthy non-diabetic subjects were divided into two experimental groups: One with a first degree relative with Type 2 diabetes and the other matched controls having no family history of Type 2 diabetes. The hypotheses: 1). There is a significant difference in taste threshold values and …

Aspirin And Low-Molecular Weight Heparin Combination Therapy Effectively Prevents Recurrent Miscarriage In Hyperhomocysteinemic Women., Pratip Chakraborty, Sayani Banerjee, Piyali Saha, Shyam Sundar Nandi, Sunita Sharma, Sourendra K. Goswami, Baidyanath Chakravarty, Syed N. Kabir

Journal Articles: Cellular & Integrative Physiology

The management of recurrent pregnancy loss (RPL) still remains a great challenge, and women with polycystic ovarian syndrome (PCOS) are at a greater risk for spontaneous abortion. Treatment with low-molecular-weight heparin (LMWH) has become an accepted treatment option for women with RPL; however, the subgroup of women, who are likely to respond to LMWH, has not been precisely identified. The present study evaluated the efficacy of LMWH with reference to PCOS and associated metabolic phenotypes including hyperhomocysteinemia (HHcy), insulin resistance (IR) and obesity. This prospective observational study was conducted at Institute of Reproductive Medicine, Kolkata, India. A total of 967 …

Nf1 Loss And Ras Hyperactivation In Oligodendrocytes Induce Nos-Driven Defects In Myelin And Vasculature, Debra A. Mayes, Tilat A. Rizvi, Haley E. Titus-Mitchell, Rachel Oberst, Georgianne M. Ciraolo, Charles V. Vorhees, Andrew P. Robinson, Stephen D. Miller, Jose A. Cancelas, Anat O. Stemmer-Rachamimov, Nancy Ratner

Neuroscience, Cell Biology & Physiology Faculty Publications

Patients with neurofibromatosis type 1 (NF1) and Costello syndrome Rasopathy have behavioral deficits. In NF1 patients, these may correlate with white matter enlargement and aberrant myelin. To model these features, we induced Nf1 loss or HRas hyperactivation in mouse oligodendrocytes. Enlarged brain white matter tracts correlated with myelin decompaction, downregulation of claudin-11, and mislocalization of connexin-32. Surprisingly, non-cell-autonomous defects in perivascular astrocytes and the blood-brain barrier (BBB) developed, implicating a soluble mediator. Nitric oxide (NO) can disrupt tight junctions and gap junctions, and NO and NO synthases (NOS1-NOS3) were upregulated in mutant white matter. Treating mice with the NOS inhibitor …