Abstract 224: Sub-cytotoxic Levels of Heavy Metals Induce Pro-inflammatory Signaling in the Aortic Endothelium without Impairing Flow-Mediated Dilation in Rats

Introduction: Acute exposure to tobacco or marijuana secondhand smoke (SHS) causes endothelial dysfunction. The identity of specific SHS constituents that cause vascular toxicity is unclear. Heavy metals are present in SHS and at elevated levels in the blood of smokers, and may mediate acute endothelial dysfunction through reactive oxygen species formation and decreasing NO bioavailability. We assessed the effects of exposure to cadmium, lead, mercury, and arsenic at levels present in the blood of human smokers on flow-mediated dilation (FMD) as a measure of endothelial function in rats. We also evaluated the effects of heavy metal exposure on intimal structure, protein localization pattern, and inflammatory gene expression in the aortic endothelium. Hypothesis: Sub-cytotoxic levels of heavy metals impair FMD, alter intimal structure, and induce pro-inflammatory signaling in endothelium. Methods: We injected rats (n=8/group) with heavy metal cocktail or vehicle intravenously and quantitated pre- and post-exposure FMDs measures defined as percent vasodilation of femoral artery after transient ischemia. We performed en face aorta immunostaining and assessed endothelial cell axis alignment, cell length ratio, and localization pattern of PECAM-1, VE-cadherin, and vimentin. We also quantified gene expression of key endothelial proteins in aorta homogenates. Results: FMD was not impaired in the heavy metal group (8.8±3.6(SD)% vs. 12.9±8.0%, p=.31 or controls (7.5±2.7% vs. 8.8±5.8%, p=.63). No significant difference in cell length ratio and endothelial x and y axes of alignment were detected between groups (p>.8) and localization of PECAM-1, VE-cadherin, and vimentin in the aorta endothelium remained unaltered following heavy metal injection. However, expression of PECAM-1 and VE-cadherin was significantly lower in the heavy metal-treated rats, while VCAM-1 gene expression was significantly higher (p<.05). Conclusion: Acute exposure to sub-cytotoxic levels of heavy metals can induce pro-inflammatory signaling in endothelium, which could potentially lead to vascular injury. However, FMD and endothelial structure remain unchanged by heavy metal exposure

Current and Nascent SETI Instruments

Here we describe our ongoing efforts to develop high-performance and sensitive instrumentation for use in the search for extra-terrestrial intelligence (SETI). These efforts include our recently deployed Search for Extraterrestrial Emissions from Nearby Developed Intelligent Populations Spectrometer (SERENDIP V.v) and two instruments currently under development; the Heterogeneous Radio SETI Spectrometer (HRSS) for SETI observations in the radio spectrum and the Optical SETI Fast Photometer (OSFP) for SETI observations in the optical band. We will discuss the basic SERENDIP V.v instrument design and initial analysis methodology, along with instrument architectures and observation strategies for OSFP and HRSS. In addition, we will demonstrate how these instruments may be built using low-cost, modular components and programmed and operated by students using common languages, e.g. ANSI C.Comment: 12 pages, 5 figures, Original version appears as Chapter 2 in "The Proceedings of SETI Sessions at the 2010 Astrobiology Science Conference: Communication with Extraterrestrial Intelligence (CETI)," Douglas A. Vakoch, Edito

Radio Interferometric Planet Search II: Constraints on sub-Jupiter-Mass Companions to GJ 896A

We present results from the Radio Interferometric Planet (RIPL) search for compan- ions to the nearby star GJ 896A. We present 11 observations over 4.9 years. Fitting astrometric parameters to the data reveals a residual with peak-to-peak amplitude of ~ 3 mas in right ascension. This residual is well-fit by an acceleration term of 0.458 \pm 0.032 mas/y^2. The parallax is fit to an accuracy of 0.2 mas and the proper motion terms are fit to accuracies of 0.01 mas/y. After fitting astrometric and acceleration terms residuals are 0.26 mas in each coordinate, demonstrating that stellar jitter does not limit the ability to carry out radio astrometric planet detection and characterization. The acceleration term originates in part from the companion GJ 896B but the amplitude of the acceleration in declination is not accurately predicted by the orbital model. The acceleration sets a mass upper limit of 0.15 MJ at a semi-major axis of 2 AU for a planetary companion to GJ 896A. For semi-major axes between 0.3 and 2 AU upper limits are determined by the maximum angular separation; the upper limits scale from the minimum value in proportion to the inverse of the radius. Upper limits at larger radii are set by the acceleration and scale as the radius squared. An improved solution for the stellar binary system could improve the exoplanet mass sensitivity by an order of magnitude.Comment: Accepted for publication in Ap

Heterogeneity in Multiple Sclerosis: Scratching the Surface of a Complex Disease

Multiple Sclerosis (MS) is the most common demyelinating disease of the central nervous system. Although the etiology and the pathogenesis of MS has been extensively investigated, no single pathway, reliable biomarker, diagnostic test, or specific treatment have yet been identified for all MS patients. One of the reasons behind this failure is likely to be the wide heterogeneity observed within the MS population. The clinical course of MS is highly variable and includes several subcategories and variants. Moreover, apart from the well-established association with the HLA-class II DRB1*15:01 allele, other genetic variants have been shown to vary significantly across different populations and individuals. Finally both pathological and immunological studies suggest that different pathways may be active in different MS patients. We conclude that these “MS subtypes” should still be considered as part of the same disease but hypothesize that spatiotemporal effects of genetic and environmental agents differentially influence MS course. These considerations are extremely relevant, as outcome prediction and personalised medicine represent the central aim of modern research

Novel public-private partnerships to address the double burden of malnutrition

Public–private partnerships are an effective way to address the global double burden of malnutrition. While public–private partnerships operate in multiple forms, their leadership usually falls to governments, public health agencies, or nongovernmental organizations, with the private sector taking a subordinate role. The rapid ascent of social media and mass communications worldwide has provided a disruptive technology for new nutrition intervention programs. A new model, provisionally called private–public engagement, takes advantage of social media, mass media, and integrated social marketing to reach parents, families, and communities directly. These new private–public engagement initiatives need to be managed in ways suggested for public–private partnerships by the World Health Organization, especially if the private sector is in the lead. Once the rationale for engagement is defined, there is a need to mobilize resources, establish in-country partnerships and codes of conduct, and provide a plan for monitoring, evaluation, and accountability. Provided here is an example consistent with the private–public engagement approach, ie, the United for Healthier Kids program, which has been aimed at families with children aged less than 12 years. Materials to inspire behavioral change and promote healthier diets and lifestyle were disseminated in a number of countries through both digital and physical channels, often in partnership with local or regional governments. A description of this program, along with strategies to promote transparency and communication among stakeholders, serves to provide guidance for the development of future effective private–public engagements

Mining the Mind Research Network: A Novel Framework for Exploring Large Scale, Heterogeneous Translational Neuroscience Research Data Sources

A neuroinformatics (NI) system is critical to brain imaging research in order to shorten the time between study conception and results. Such a NI system is required to scale well when large numbers of subjects are studied. Further, when multiple sites participate in research projects organizational issues become increasingly difficult. Optimized NI applications mitigate these problems. Additionally, NI software enables coordination across multiple studies, leveraging advantages potentially leading to exponential research discoveries. The web-based, Mind Research Network (MRN), database system has been designed and improved through our experience with 200 research studies and 250 researchers from seven different institutions. The MRN tools permit the collection, management, reporting and efficient use of large scale, heterogeneous data sources, e.g., multiple institutions, multiple principal investigators, multiple research programs and studies, and multimodal acquisitions. We have collected and analyzed data sets on thousands of research participants and have set up a framework to automatically analyze the data, thereby making efficient, practical data mining of this vast resource possible. This paper presents a comprehensive framework for capturing and analyzing heterogeneous neuroscience research data sources that has been fully optimized for end-users to perform novel data mining

Daily life stress and the cortisol awakening response : testing the anticipation hypothesis

Acknowledgments We thank Paul Stewart for his contribution to data collection and Dr Matthew Jones for programming the handheld computers. Author Contributions Conceived and designed the experiments: WS DJP. Performed the experiments: DJP. Analyzed the data: WS. Wrote the paper: WS DJP.Peer reviewedPublisher PD

Unstimulated cortisol secretory activity in everyday life and its relationship with fatigue and chronic fatigue syndrome : a systematic review and subset meta-analysis

Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.Peer reviewedPublisher PD