Hyperglycemia Has a Greater Impact on Left Ventricle Function in South Asians Than in Europeans

OBJECTIVE Diabetes is associated with left ventricular (LV) diastolic and systolic dysfunction. South Asians may be at particular risk of developing LV dysfunction owing to a high prevalence of diabetes. We investigated the role of diabetes and hyperglycemia in LV dysfunction in a community-based cohort of older South Asians and white Europeans. RESEARCH DESIGN AND METHODS Conventional and Doppler echocardiography was performed in 999 participants (542 Europeans and 457 South Asians aged 58–86 years) in a population-based study. Anthropometry, fasting bloods, coronary artery calcification scoring, blood pressure, and renal function were measured. RESULTS Diabetes and hyperglycemia across the spectrum of HbA1c had a greater adverse effect on LV function in South Asians than Europeans (N-terminal-probrain natriuretic peptide β ± SE 0.09 ± 0.04, P = 0.01, vs. −0.04 ± 0.05, P = 0.4, P for HbA1c/ethnicity interaction 0.02), diastolic function (E/e′ 0.69 ± 0.12, P < 0.0001, vs. 0.09 ± 0.2, P = 0.6, P for interaction 0.005), and systolic function (s′ −0.11 ± 0.06, P = 0.04, vs. 0.14 ± 0.09, P = 0.1, P for interaction 0.2). Multivariable adjustment for hypertension, microvascular disease, LV mass, coronary disease, and dyslipidemia only partially accounted for the ethnic differences. Adverse LV function in diabetic South Asians could not be accounted for by poorer glycemic control or longer diabetes duration. CONCLUSIONS Diabetes and hyperglycemia have a greater adverse effect on LV function in South Asians than Europeans, incompletely explained by adverse risk factors. South Asians may require earlier and more aggressive treatment of their cardiometabolic risk factors to reduce risks of LV dysfunction

Molecular signatures of cell migration in C. elegans Q neuroblasts.

Metazoan cell movement has been studied extensively in vitro, but cell migration in living animals is much less well understood. In this report, we have studied the Caenorhabditis elegans Q neuroblast lineage during larval development, developing live animal imaging methods for following neuroblast migration with single cell resolution. We find that each of the Q descendants migrates at different speeds and for distinct distances. By quantitative green fluorescent protein imaging, we find that Q descendants that migrate faster and longer than their sisters up-regulate protein levels of MIG-2, a Rho family guanosine triphosphatase, and/or down-regulate INA-1, an integrin alpha subunit, during migration. We also show that Q neuroblasts bearing mutations in either MIG-2 or INA-1 migrate at reduced speeds. The migration defect of the mig-2 mutants, but not ina-1, appears to result from a lack of persistent polarization in the direction of cell migration. Thus, MIG-2 and INA-1 function distinctly to control Q neuroblast migration in living C. elegans

Scientists as Midwives to Cluster Emergence: An Institutional Work Framework

The question of how embedded actors can create institutions that support cluster emergence remains unsolved in the cluster and national innovation systems literature. The present paper extends the recent literature on institutional entrepreneurship and institutional work to solve this paradox of embedded agency in the context of science-based clusters. Building on a longitudinal single case study of a functional foods cluster in Finland, we present an institutional work framework for cluster formation. We argue that, in addition to ideational, material and bridging work, authentic leadership work is critical for cluster emergence. The results of the study highlight the opportunities that scientists have to act as midwives to cluster formation, but they also show that well-functioning clusters need a broader support base.Peer reviewe

Artificial Synthesis of Conjugated Microporous Polymers via Sonogashira-Hagihara Coupling

Amorphous network materials are becoming increasingly important with applications, for example, as supercapacitors, battery anodes, and proton conduction membranes. The design of these materials is hampered by the amorphous nature of the structure and sensitivity to synthetic conditions. Here, we show that through artificial synthesis, fully mimicking the catalytic formation cycle, and full synthetic conditions, we can generate structural models that can fully describe the physical properties of these amorphous network materials. This opens up pathways for the rational design where complex structural influences, such as the solvent and catalyst choice, can be taken into account

Promoting activity, independence and stability in early dementia and mild cognitive impairment (PrAISED): development of an intervention for people with mild cognitive impairment and dementia

This series of articles for rehabilitation in practice aims to cover a knowledge element of the rehabilitation medicine curriculum. Nevertheless, they are intended to be of interest to a multidisciplinary audience. The competency addressed in this article is an understanding of how to develop an intervention for people with mild cognitive impairment and dementia to promote their independence, stability, and physical activit

Improving the Quality of Dentistry (IQuaD):a cluster factorial randomised controlled trial comparing the effectiveness and cost-benefit of oral hygiene advice and/or periodontal instrumentation with routine care for the prevention and management of periodontal disease in dentate adults attending dental primary care

Acknowledgements The authors wish to thank Mark Forrest and the programming team at CHaRT; Cynthia Fraser, our information specialist, for assistance with referencing; Moira Swan, who was the dental research nurse and part of the OA team in Newcastle upon Tyne; Louise Campbell for secretarial support and data management; our original statistician in the group, Andy Elders; senior IT manager Gladys Macpherson; senior trial administrator at the TCOD Marilyn Laird; Luke Vale for his involvement with the design of the health economic analysis at the inception of the trial; Maria Dimitrova, who assisted the health economists in the collection of unit costs; staff of the Scottish Primary Care Research Network, who assisted with screening eligible patients at dental practices; staff of the North East Commissioning Support Unit who assisted with research payments to dental practices in the north-east; members of the TMC and Periodontal Advisory Group for their ongoing advice and support of the trial; the independent members of the TSC and DMC; and the staff at recruitment sites who facilitated recruitment, treatment and follow-up of trial participants. The Health Services Research Unit and the Health Economics Research Unit is core funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorate.Peer reviewedPublisher PD

Protein interactions in Xenopus germ plasm RNP particles

Hermes is an RNA-binding protein that we have previously reported to be found in the ribonucleoprotein (RNP) particles of Xenopus germ plasm, where it is associated with various RNAs, including that encoding the germ line determinant Nanos1. To further define the composition of these RNPs, we performed a screen for Hermes-binding partners using the yeast two-hybrid system. We have identified and validated four proteins that interact with Hermes in germ plasm: two isoforms of Xvelo1 (a homologue of zebrafish Bucky ball) and Rbm24b and Rbm42b, both RNA-binding proteins containing the RRM motif. GFP-Xvelo fusion proteins and their endogenous counterparts, identified with antisera, were found to localize with Hermes in the germ plasm particles of large oocytes and eggs. Only the larger Xvelo isoform was naturally found in the Balbiani body of previtellogenic oocytes. Bimolecular fluorescence complementation (BiFC) experiments confirmed that Hermes and the Xvelo variants interact in germ plasm, as do Rbm24b and 42b. Depletion of the shorter Xvelo variant with antisense oligonucleotides caused a decrease in the size of germ plasm aggregates and loosening of associated mitochondria from these structures. This suggests that the short Xvelo variant, or less likely its RNA, has a role in organizing and maintaining the integrity of germ plasm in Xenopus oocytes. While GFP fusion proteins for Rbm24b and 42b did not localize into germ plasm as specifically as Hermes or Xvelo, BiFC analysis indicated that both interact with Hermes in germ plasm RNPs. They are very stable in the face of RNA depletion, but additive effects of combinations of antisense oligos suggest they may have a role in germ plasm structure and may influence the ability of Hermes protein to effectively enter RNP particles

Inhibition of Rac controls NPM–ALK-dependent lymphoma development and dissemination

Nucleophosmin-anaplastic lymphoma kinase (NPM–ALK) is a tyrosine kinase oncogene responsible for the pathogenesis of the majority of human ALK-positive lymphomas. We recently reported that it activated the Rac1 GTPase in anaplastic large-cell lymphoma (ALCL), leading to Rac-dependent formation of active invadopodia required for invasiveness. Herein, we went further into the study of this pathway and used the inhibitor of Rac, NSC23766, to validate its potential as a molecular target in ALCL in vitro and in vivo in a xenograft model and in a conditional model of NPM–ALK transgenic mice. Our data demonstrate that Rac regulates important effectors of NPM–ALK-induced transformation such as Erk1/2, p38 and Akt. Moreover, inhibition of Rac signaling abrogates NPM–ALK-elicited disease progression and metastasis in mice, highlighting the potential of small GTPases and their regulators as additional therapic targets in lymphomas

Cdc42 antagonizes Rho1 activity at adherens junctions to limit epithelial cell apical tension

In epithelia, cells are arranged in an orderly pattern with a defined orientation and shape. Cadherin containing apical adherens junctions (AJs) and the associated actomyosin cytoskeleton likely contribute to epithelial cell shape by providing apical tension. The Rho guanosine triphosphatases are well known regulators of cell junction formation, maintenance, and function. Specifically, Rho promotes actomyosin activity and cell contractility; however, what controls and localizes this Rho activity as epithelia remodel is unresolved. Using mosaic clonal analysis in the Drosophila melanogaster pupal eye, we find that Cdc42 is critical for limiting apical cell tension by antagonizing Rho activity at AJs. Cdc42 localizes Par6-atypical protein kinase C (aPKC) to AJs, where this complex limits Rho1 activity and thus actomyosin contractility, independent of its effects on Wiskott-Aldrich syndrome protein and p21-activated kinase. Thus, in addition to its role in the establishment and maintenance of apical-basal polarity in forming epithelia, the Cdc42-Par6-aPKC polarity complex is required to limit Rho activity at AJs and thus modulate apical tension so as to shape the final epithelium