Medicine and Health Sciences Commons^™

Syndecan 4 Is Required For Endothelial Alignment In Flow And Atheroprotective Signaling, Nicolas Baeyens, Mary Jo Mulligan-Kehoe, Federico Corti, David D. Simon, Tyler D. Ross, John M. Rhodes, Thomas Z. Wang

Dartmouth Scholarship

Atherosclerotic plaque localization correlates with regions of disturbed flow in which endothelial cells (ECs) align poorly, whereas sustained laminar flow correlates with cell alignment in the direction of flow and resistance to atherosclerosis. We now report that in hypercholesterolemic mice, deletion of syndecan 4 (S4−/−) drastically increased atherosclerotic plaque burden with the appearance of plaque in normally resistant locations. Strikingly, ECs from the thoracic aortas of S4−/− mice were poorly aligned in the direction of the flow. Depletion of S4 in human umbilical vein endothelial cells (HUVECs) using shRNA also inhibited flow-induced alignment in vitro, which was rescued by re-expression …

Site-Specific Mutation Of The Sensor Kinase Gras In Staphylococcus Aureus Alters The Adaptive Response To Distinct Cationic Antimicrobial Peptides, Ambrose L. Cheung, Arnold S. Bayer, Michael R. Yeaman, Yan Q. Xiong, Alan J. Waring, Guido Memmi, Niles Donegan

Dartmouth Scholarship

The Staphylococcus aureus two-component regulatory system, GraRS, is involved in resistance to killing by distinct host defense cationic antimicrobial peptides (HD-CAPs). It is believed to regulate downstream target genes such as mprF and dltABCD to modify the S. aureus surface charge. However, the detailed mechanism(s) by which the histidine kinase, GraS, senses specific HD-CAPs is not well defined. Here, we studied a well-characterized clinical methicillin-resistant S. aureus (MRSA) strain (MW2), its isogenic graS deletion mutant (ΔgraS strain), a nonameric extracellular loop mutant (ΔEL strain), and four residue-specific ΔEL mutants (D37A, P39A, P39S, and D35G D37G D41G strains). The ΔgraS and …

Simplified Post Processing Of Cine Dense Cardiovascular Magnetic Resonance For Quantification Of Cardiac Mechanics, Jonathan D. Suever, Gregory J. Wehner, Christopher M. Haggerty, Linyuan Jing, Sean M. Hamlet, Cassi M. Binkley, Sage P. Kramer, Andrea C. Mattingly, David K. Powell, Kenneth C. Bilchick, Frederick H. Epstein, Brandon K. Fornwalt

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Cardiovascular magnetic resonance using displacement encoding with stimulated echoes (DENSE) is capable of assessing advanced measures of cardiac mechanics such as strain and torsion. A potential hurdle to widespread clinical adoption of DENSE is the time required to manually segment the myocardium during post-processing of the images. To overcome this hurdle, we proposed a radical approach in which only three contours per image slice are required for post-processing (instead of the typical 30-40 contours per image slice). We hypothesized that peak left ventricular circumferential, longitudinal and radial strains and torsion could be accurately quantified using this simplified analysis.

METHODS …

Latexin Sensitizes Leukemogenic Cells To Gamma-Irradiation-Induced Cell-Cycle Arrest And Cell Death Through Rps3 Pathway, Y. You, R. Wen, R. Pathak, A. Li, W. Li, D. St. Clair, M. Hauer-Jensen, D. Zhou, Ying Liang

Toxicology and Cancer Biology Faculty Publications

Leukemia is a leading cause of cancer death. Recently, the latexin (Lxn) gene was identified as a potential tumor suppressor in several types of solid tumors and lymphoma, and Lxn expression was found to be absent or downregulated in leukemic cells. Whether Lxn functions as a tumor suppressor in leukemia and what molecular and cellular mechanisms are involved are unknown. In this study, the myeloid leukemogenic FDC-P1 cell line was used as a model system and Lxn was ectopically expressed in these cells. Using the protein pull-down assay and mass spectrometry, ribosomal protein subunit 3 (Rps3) was identified as a …

Developmental Stress, Condition, And Birdsong: A Case Study In Song Sparrows., Kim L Schmidt, Elizabeth A Macdougall-Shackleton, Shawn P Kubli, Scott A Macdougall-Shackleton

Brain and Mind Institute Researchers' Publications

Sexual-selection theory posits that ornaments and displays can reflect a signaler's condition, which in turn is affected both by recent and developmental conditions. Moreover, developmental conditions can induce correlations between sexually selected and other traits if both types of traits exhibit developmental phenotypic plasticity in response to stressors. Thus, sexually selected traits may reflect recent and/or developmental characteristics of signalers. Here, we review data on the relationships between birdsong, a sexually selected trait, and developmental and current condition of birds from a long-term study of a population of song sparrows (Melospiza melodia). Field studies of free-living birds indicate that the …

Stress-Induced Cocaine Seeking Requires A Beta-2 Adrenergic Receptor-Regulated Pathway From The Ventral Bed Nucleus Of The Stria Terminalis That Regulates Crf Actions In The Ventral Tegmental Area, Oliver Vranjkovic, Paul J. Gasser, Clayton H. Gerndt, David A. Baker, John R. Mantsch

Biomedical Sciences Faculty Research and Publications

The ventral bed nucleus of the stria terminalis (vBNST) has been implicated in stress-induced cocaine use. Here we demonstrate that, in the vBNST, corticotropin releasing factor (CRF) is expressed in neurons that innervate the ventral tegmental area (VTA), a site where the CRF receptor antagonist antalarmin prevents the reinstatement of cocaine seeking by a stressor, intermittent footshock, following intravenous self-administration in rats. The vBNST receives dense noradrenergic innervation and expresses β adrenergic receptors (ARs). Footshock-induced reinstatement was prevented by bilateral intra-vBNST injection of the β-2 AR antagonist, ICI-118,551, but not the β-1 AR antagonist, betaxolol. Moreover, bilateral intra-vBNST injection of …

Links Between White Matter Microstructure And Cortisol Reactivity To Stress In Early Childhood: Evidence For Moderation By Parenting., Haroon I Sheikh, Marc F Joanisse, Sarah M Mackrell, Katie R Kryski, Heather J Smith, Shiva M Singh, Elizabeth P Hayden

Brain and Mind Institute Researchers' Publications

Activity of the hypothalamic-pituitary-adrenal axis (measured via cortisol reactivity) may be a biological marker of risk for depression and anxiety, possibly even early in development. However, the structural neural correlates of early cortisol reactivity are not well known, although these would potentially inform broader models of mechanisms of risk, especially if the early environment further shapes these relationships. Therefore, we examined links between white matter architecture and young girls' cortisol reactivity and whether early caregiving moderated these links. We recruited 45 6-year-old girls based on whether they had previously shown high or low cortisol reactivity to a stress task at …

Neurobiological Mechanisms That Contribute To Stress-Related Cocaine Use, John R. Mantsch, Oliver Vranjkovic, Robert C. Twining, Paul J. Gasser, Jayme R. Mcreynolds, Jordan M. Blacktop

Biomedical Sciences Faculty Research and Publications

The ability of stressful life events to trigger drug use is particularly problematic for the management of cocaine addiction due to the unpredictable and often uncontrollable nature of stress. For this reason, understanding the neurobiological processes that contribute to stress-related drug use is important for the development of new and more effective treatment strategies aimed at minimizing the role of stress in the addiction cycle. In this review we discuss the neurocircuitry that has been implicated in stress-induced drug use with an emphasis on corticotropin releasing factor actions in the ventral tegmental area (VTA) and an important pathway from the …

Behavioural And Neurobiological Consequences Of 2 Different Chronic Stressors In Rats, Refi̇a Aslihan Dönmez, Fatma Duygu Kaya, Okşan Deri̇nöz, Ömer Hakan Emmez, Selçuk Candansayar, Hayrunni̇sa Bolay Belen

Turkish Journal of Medical Sciences

To compare the behavioural and neurobiological consequences of chronic headache and chronic mild stress (CMS) in rats. Materials and methods: Forty-eight male Wistar rats were divided into 4 groups: 1) control group, 2) chronic headache group, 3) CMS group, and 4) sham group. Their behaviour prior to (D0) and after (D14) chronic stress was analysed. Afterwards, they were exposed to the Elevated Plus Maze (EPM) in order to evaluate anxiety-like behaviour and the Forced Swim Test (FST) for observation of depressive-like behaviour. Ultrasonic vocalisations (USVs) were recorded by a USV detector system at D0 and D14 and during the FST. …