Uric Acid-Induced Adipocyte Dysfunction Is Attenuated by HO-1 Upregulation: Potential Role of Antioxidant Therapy to Target Obesity

Increased uric acid levels have been implicated in the pathogenesis of metabolic syndrome. To examine the mechanisms by which this occurs, we hypothesized that an increase in heme oxygenase 1, a potent antioxidant gene, will decrease uric acid levels and adipocyte dysfunction via suppression of ROS and xanthine oxidase (XO) levels. We examined the effect of uric acid on adipogenesis in human mesenchymal stem cells (MSCs) in the presence and absence of cobalt protoporphyrin (CoPP), an HO-1 inducer, and tin mesoporphyrin (SnMP), an HO activity inhibitor. Uric acid increased adipogenesis by increasing NADPH oxidase expression and elevation in the adipogenesis markers C/EBPα, PPARγ, and Mest, while decreasing small lipid droplets and Wnt10b levels. We treated MSCs with fructose, a fuel source that increases uric acid levels. Our results showed that fructose increased XO expression as compared to the control and concomitant treatment with CoPP significantly decreased XO expression and uric acid levels. These beneficial effects of CoPP were reversed by SnMP, supporting a role for HO activity in mediating these effects. These findings demonstrate that increased levels of HO-1 appear crucial in modulating the phenotype of adipocytes exposed to uric acid and in downregulating XO and NADPH oxidase levels

Challenging assumptions of the enlargement literature : the impact of the EU on human and minority rights in Macedonia

This article argues that from the very start of the transition process in Macedonia, a fusion of concerns about security and democratisation locked local nationalist elites and international organisations intoa political dynamic that prioritised security over democratisation. This dynamic resulted in little progress in the implementation of human and minority rights until 2009, despite heavy EU involvement in Macedonia after the internal warfare of 2001. The effects of this informally institutionalised relationship have been overlooked by scholarship on EU enlargement towards Eastern Europe, which has made generalisations based on assumptions relevant to the democratisation of countries in Eastern Europe, but not the Western Balkans

A conditional mutation in a wheat (Triticum aestivum L.) gene regulating root morphology

Key message: Characterisation and genetic mapping of a key gene defining root morphology in bread wheat. Abstract: Root morphology is central to plants for the efficient uptake up of soil water and mineral nutrients. Here we describe a conditional mutant of hexaploid wheat (Triticum aestivum L.) that when grown in soil with high Ca 2+ develops a larger rhizosheath accompanied with shorter roots than the wild type. In wheat, rhizosheath size is a reliable surrogate for root hair length and this was verified in the mutant which possessed longer root hairs than the wild type when grown in high Ca 2+ soil. We named the mutant Stumpy and showed it to be due to a single semi-dominant mutation. The short root phenotype at high Ca 2+ was due to reduced cellular elongation which might also explain the long root hair phenotype. Analysis of root cell walls showed that the polysaccharide composition of Stumpy roots is remodelled when grown at non-permissive (high) Ca 2+ concentrations. The mutation mapped to chromosome 7B and sequencing of the 7B chromosomes in both wild type and Stumpy identified a candidate gene underlying the Stumpy mutation. As part of the process to determine whether the candidate gene was causative, we identified wheat lines in a Cadenza TILLING population with large rhizosheaths but accompanied with normal root length. This finding illustrates the potential of manipulating the gene to disconnect root length from root hair length as a means of developing wheat lines with improved efficiency of nutrient and water uptake. The Stumpy mutant will be valuable for understanding the mechanisms that regulate root morphology in wheat.</p

A conditional mutation in a wheat (Triticum aestivum L.) gene regulating root morphology

Key message: Characterisation and genetic mapping of a key gene defining root morphology in bread wheat. Abstract: Root morphology is central to plants for the efficient uptake up of soil water and mineral nutrients. Here we describe a conditional mutant of hexaploid wheat (Triticum aestivum L.) that when grown in soil with high Ca 2+ develops a larger rhizosheath accompanied with shorter roots than the wild type. In wheat, rhizosheath size is a reliable surrogate for root hair length and this was verified in the mutant which possessed longer root hairs than the wild type when grown in high Ca 2+ soil. We named the mutant Stumpy and showed it to be due to a single semi-dominant mutation. The short root phenotype at high Ca 2+ was due to reduced cellular elongation which might also explain the long root hair phenotype. Analysis of root cell walls showed that the polysaccharide composition of Stumpy roots is remodelled when grown at non-permissive (high) Ca 2+ concentrations. The mutation mapped to chromosome 7B and sequencing of the 7B chromosomes in both wild type and Stumpy identified a candidate gene underlying the Stumpy mutation. As part of the process to determine whether the candidate gene was causative, we identified wheat lines in a Cadenza TILLING population with large rhizosheaths but accompanied with normal root length. This finding illustrates the potential of manipulating the gene to disconnect root length from root hair length as a means of developing wheat lines with improved efficiency of nutrient and water uptake. The Stumpy mutant will be valuable for understanding the mechanisms that regulate root morphology in wheat.</p

Random repeated quantum interactions and random invariant states

We consider a generalized model of repeated quantum interactions, where a system $\mathcal{H}$ is interacting in a random way with a sequence of independent quantum systems $\mathcal{K}_n, n \geq 1$. Two types of randomness are studied in detail. One is provided by considering Haar-distributed unitaries to describe each interaction between $\mathcal{H}$ and $\mathcal{K}_n$. The other involves random quantum states describing each copy $\mathcal{K}_n$. In the limit of a large number of interactions, we present convergence results for the asymptotic state of $\mathcal{H}$. This is achieved by studying spectral properties of (random) quantum channels which guarantee the existence of unique invariant states. Finally this allows to introduce a new physically motivated ensemble of random density matrices called the \emph{asymptotic induced ensemble}

New Particles Working Group Report of the Snowmass 2013 Community Summer Study

This report summarizes the work of the Energy Frontier New Physics working group of the 2013 Community Summer Study (Snowmass)

Organizational factors associated with readiness to implement and translate a primary care based telemedicine behavioral program to improve blood pressure control: the HTN-IMPROVE study

Abstract Background Hypertension is prevalent and often sub-optimally controlled; however, interventions to improve blood pressure control have had limited success. Objectives Through implementation of an evidence-based nurse-delivered self-management phone intervention to facilitate hypertension management within large complex health systems, we sought to answer the following questions: What is the level of organizational readiness to implement the intervention? What are the specific facilitators, barriers, and contextual factors that may affect organizational readiness to change? Study design Each intervention site from three separate Veterans Integrated Service Networks (VISNs), which represent 21 geographic regions across the US, agreed to enroll 500 participants over a year with at least 0.5 full time equivalent employees of nursing time. Our mixed methods approach used a priori semi-structured interviews conducted with stakeholders (n = 27) including nurses, physicians, administrators, and information technology (IT) professionals between 2010 and 2011. Researchers iteratively identified facilitators and barriers of organizational readiness to change (ORC) and implementation. Additionally, an ORC survey was conducted with the stakeholders who were (n = 102) preparing for program implementation. Results Key ORC facilitators included stakeholder buy-in and improving hypertension. Positive organizational characteristics likely to impact ORC included: other similar programs that support buy-in, adequate staff, and alignment with the existing site environment; improved patient outcomes; is positive for the professional nurse role, and is evidence-based; understanding of the intervention; IT infrastructure and support, and utilization of existing equipment and space. The primary ORC barrier was unclear long-term commitment of nursing. Negative organizational characteristics likely to impact ORC included: added workload, competition with existing programs, implementation length, and limited available nurse staff time; buy-in is temporary until evidence shows improved outcomes; contacting patients and the logistics of integration into existing workflow is a challenge; and inadequate staffing is problematic. Findings were complementary across quantitative and qualitative analyses. Conclusions The model of organizational change identified key facilitators and barriers of organizational readiness to change and successful implementation. This study allows us to understand the needs and challenges of intervention implementation. Furthermore, examination of organizational facilitators and barriers to implementation of evidence-based interventions may inform dissemination in other chronic diseases.http://deepblue.lib.umich.edu/bitstream/2027.42/112820/1/13012_2013_Article_683.pd

Nanoscale Effects on Heterojunction Electron Gases in GaN/AlGaN Core/Shell Nanowires

The electronic properties of heterojunction electron gases formed in GaN/AlGaN core/shell nanowires with hexagonal and triangular cross-sections are studied theoretically. We show that at nanoscale dimensions, the non-polar hexagonal system exhibits degenerate quasi-one-dimensional electron gases at the hexagon corners, which transition to a core-centered electron gas at lower doping. In contrast, polar triangular core/shell nanowires show either a non-degenerate electron gas on the polar face or a single quasi-one-dimensional electron gas at the corner opposite the polar face, depending on the termination of the polar face. More generally, our results indicate that electron gases in closed nanoscale systems are qualitatively different from their bulk counterparts.Comment: 16 pages, 7 figures. To appear in Nano Letters. Corrected some typo

Discussing prognosis with older people with musculoskeletal pain: a cross-sectional study in general practice

<p>Abstract</p> <p>Background</p> <p>Prognosis has been described as an important but neglected branch of clinical science. While patients' views have been sought in the context of life-threatening illness, similar research is lacking for patients presenting with common, non-life-threatening musculoskeletal complaints. The aim of this study was to gauge whether and why older patients with musculoskeletal pain think prognostic information is important, and how often they felt prognosis was discussed in the general practice consultation.</p> <p>Methods</p> <p>A cross-sectional survey of consecutive patients aged 50 years of over presenting with non-inflammatory musculoskeletal pain to 5 Central Cheshire general practices. The frequency of responses to the prognostic questions were described and the association with sociodemographic, presenting pain complaint, and psychosocial variables explored using logistic regression.</p> <p>Results</p> <p>502 participants (77%) responded to the postal questionnaire. 165 (33%) participants reported discussing prognosis in the consultation with their GP. Discussions about prognosis were more often reported by male patients (OR 1.72, 95% CI 1.09, 2.71) and those for whom this was their first consultation (OR 1.81, 95% CI 1.16, 2.80). 402 (82%) participants thought that prognostic information was important. This was highest among those currently in paid employment (OR 2.95, 95% CI 1.33, 6.57). The reasons patients gave for believing prognostic information was important included 'knowing for the sake of knowing' and planning future activity. Reasons for not believing prognostic information to be important included the belief that progression of pain was inevitable and that nothing could be done to help.</p> <p>Conclusion</p> <p>Prognostic information is thought to be important amongst older people with musculoskeletal pain yet discussions occur infrequently in primary care. Barriers to effective prognostic communication and the exact information needs of patients are still unknown and warrant further research.</p

Open-label randomized trial of titrated disease management for patients with hypertension: Study design and baseline sample characteristics

Despite the availability of efficacious treatments, only half of patients with hypertension achieve adequate blood pressure (BP) control. This paper describes the protocol and baseline subject characteristics of a 2-arm, 18-month randomized clinical trial of titrated disease management (TDM) for patients with pharmaceutically-treated hypertension for whom systolic blood pressure (SBP) is not controlled (≥140mmHg for non-diabetic or ≥130mmHg for diabetic patients). The trial is being conducted among patients of four clinic locations associated with a Veterans Affairs Medical Center. An intervention arm has a TDM strategy in which patients' hypertension control at baseline, 6, and 12 months determines the resource intensity of disease management. Intensity levels include: a low-intensity strategy utilizing a licensed practical nurse to provide bi-monthly, non-tailored behavioral support calls to patients whose SBP comes under control; medium-intensity strategy utilizing a registered nurse to provide monthly tailored behavioral support telephone calls plus home BP monitoring; and high-intensity strategy utilizing a pharmacist to provide monthly tailored behavioral support telephone calls, home BP monitoring, and pharmacist-directed medication management. Control arm patients receive the low-intensity strategy regardless of BP control. The primary outcome is SBP. There are 385 randomized (192 intervention; 193 control) veterans that are predominately older (mean age 63.5 years) men (92.5%). 61.8% are African American, and the mean baseline SBP for all subjects is 143.6mmHg. This trial will determine if a disease management program that is titrated by matching the intensity of resources to patients' BP control leads to superior outcomes compared to a low-intensity management strategy