Mice lacking sialyltransferase ST3Gal-II develop late-onset obesity and insulin resistance

Sialyltransferases are a family of 20 gene products in mice and humans that transfer sialic acid from its activated precursor, CMP-sialic acid, to the terminus of glycoprotein and glycolipid acceptors. ST3Gal-II (coded by the St3gal2 gene) transfers sialic acid preferentially to the three positions of galactose on the Galβ1-3GalNAc terminus of gangliosides GM1 and GD1b to synthesize GD1a and GT1b, respectively. Mice with a targeted disruption of St3gal2 unexpectedly displayed lateonset obesity and insulin resistance. At 3 months of age, St3gal2-null mice were the same weight as their wild type (WT) counterparts, but by 13 months on standard chow they were visibly obese, 22% heavier and with 37% greater fat/lean ratio than WT mice. St3gal2-null mice became hyperglycemic and displayed impaired glucose tolerance by 9 months of age. They had sharply reduced insulin responsiveness despite equivalent pancreatic islet morphology. Analyses of insulin receptor (IR) tyrosine kinase substrate IRS-1 and downstream target Akt revealed decreased insulininduced phosphorylation in adipose tissue but not liver or skeletal muscle of St3gal2-null mice. Thin-layer chromatography and mass spectrometry revealed altered ganglioside profiles in the adipose tissue of St3gal2-null mice compared to WT littermates. Metabolically, St3gal2-null mice display a reduced respiratory exchange ratio compared to WT mice, indicating a preference for lipid oxidation as an energy source. Despite their altered metabolism, St3gal2-null mice were hyperactive. We conclude that altered ganglioside expression in adipose tissue results in diminished IR sensitivity and late-onset obesity.Fil: Lopez, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina. Johns Hopkins University School of Medicine; Estados UnidosFil: Aja, Susan. Johns Hopkins University School of Medicine; Estados UnidosFil: Aoki, Kazuhiro. University of Georgia; GreciaFil: Seldin, Marcus M.. Johns Hopkins University School of Medicine; Estados UnidosFil: Lei, Xia. Johns Hopkins University School of Medicine; Estados UnidosFil: Ronnett, Gabriele V. Johns Hopkins University School of Medicine; Estados UnidosFil: Wong, G. William. Johns Hopkins University School of Medicine; Estados UnidosFil: Schnaar, Ronald L.. Johns Hopkins University School of Medicine; Estados Unido

Different hydrogen-bonded chains in the crystal structures of three alkyl N-[(E )-1-(2-benzylidene-1-methylhydrazinyl)-3- hydroxy-1-oxopropan-2-yl]carbamates

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Adoption Process for the Model Aquatic Health Code: An Example

In 2014 the U.S. Centers for Disease Control and Prevention (CDC) published the first edition of the Model Aquatic Health Code (MAHC). This document represented the inaugural introduction of a federal policy guideline with a direct focus in the area of aquatic venue operation and maintenance with the sole purpose of improving the nature of public health in the field. The Indiana State Department of Health (ISDH) began the review and adoption process soon after the policy’s release. The ISDH process is proposed as one method for others to consider. The background and history of the MAHC are presented in this manuscript along with an overview of the adoption process to date that has been employed by the State of Indiana. In addition, information is provided on the Diffusion of Innovations Theory (DIT) as a possible method for assessing the long-term adoption of the MAHC on a national level

Advancing Community‐Based Research with Urban American Indian Populations: Multidisciplinary Perspectives

The US has witnessed significant growth among urban American Indian (AI) populations in recent decades, and concerns have been raised that these populations face equal or greater degrees of disadvantage than their reservation counterparts. Surprisingly little urban AI research or community work has been documented in the literature, and even less has been written about the influences of urban settings on community‐based work with these populations. Given the deep commitments of community psychology to empowering disadvantaged groups and understanding the impact of contextual factors on the lives of individuals and groups, community psychologists are well suited to fill these gaps in the literature. Toward informing such efforts, this work offers multidisciplinary insights from distinct idiographic accounts of community‐based behavioral health research with urban AI populations. Accounts are offered by three researchers and one urban AI community organization staff member, and particular attention is given to issues of community heterogeneity, geography, membership, and collaboration. Each first‐person account provides “lessons learned” from the urban context in which the research occurred. Together, these accounts suggest several important areas of consideration in research with urban AIs, some of which also seem relevant to reservation‐based work. Finally, the potential role of research as a tool of empowerment for urban AI populations is emphasized, suggesting future research attend to the intersections of identity, sense of community, and empowerment in urban AI populations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/117185/1/ajcp9643.pd

Dynamic Visualization of mTORC1 Activity in Living Cells

SummaryThe mechanistic target of rapamycin complex 1 (mTORC1) senses diverse signals to regulate cell growth and metabolism. It has become increasingly clear that mTORC1 activity is regulated in time and space inside the cell, but direct interrogation of such spatiotemporal regulation is challenging. Here, we describe a genetically encoded mTORC1 activity reporter (TORCAR) that exhibits a change in FRET in response to phosphorylation by mTORC1. Co-imaging mTORC1 activity and calcium dynamics revealed that a growth-factor-induced calcium transient contributes to mTORC1 activity. Dynamic activity maps generated with the use of subcellularly targeted TORCAR uncovered mTORC1 activity not only in cytosol and at the lysosome but also in the nucleus and at the plasma membrane. Furthermore, a wide distribution of activities was observed upon growth factor stimulation, whereas leucine ester, an amino acid surrogate, induces more compartmentalized activities at the lysosome and in the nucleus. Thus, mTORC1 activities are spatiotemporally regulated in a signal-specific manner

Patterns of regional diastolic function in the normal human left ventricle: An ultrafast computed tomographic study

AbstractThe detailed evaluation of regional diastolic filling at multiple ventricular levels in the normal human left ventricle has not previously been reported. Ultrafast computed tomography was used to characterize global and regional early diastolic filling in the left ventricle of 11 normal male volunteers. Regional early diastolic filling data from six distinct ventricular levels (apex to base) were fit to a third-order polynomial curve, and the peak rate of diastolic filling and time of peak filling were determined. Peak filling rate was 259 ± 17 ml/s (±SEM) as a global average, where peak filling rate referenced to end-diastolic volume and stroke volume across the levels examined was 3.78 ± 0.17 s−and 4.83 ± 0.20 s−respectively. Average filling fraction was 39 ± I%, and time to peak filling from end-systole was 145 ± 5 ms.Regional (tomographic) peak filling rates, except for the most apical level examined, were not statistically different across the ventricle. Filling fraction and time to peak filling were remarkably constant from one level to another. However, reference of regional peak filling rate to regional end-diastolic volume demonstrated significant nonuniformity from apex (120% of average for all levels) to base (87% of average for all levels). Peak filling rate referenced to tomographic stroke volume was less variable and not statistically different across the ventricle as a whole.In conclusion, values of regional absolute early peak diastolic ventricular filling rate or values normalized for regional end-diastolic volume are characteristically nonuniform across the left ventricle, whereas other variables such as filling fraction, time to peak filling and regional peak filling rate referenced to regional stroke volume are highly uniform. This confirms an intimate relation between rates of regional diastolic filling and regional ventricular size and stroke volume in the normal human heart

Different conformations and packing motifs in the crystal structures of four thiophene--carbohydrazide--pyridine derivatives

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Racial Disparities in Blood Pressure Control and Treatment Differences in a Medicaid Population, North Carolina, 2005-2006

Introduction: Racial disparities in prevalence and control of high blood pressure are well-documented. We studied blood pressure control and interventions received during the course of a year in a sample of black and white Medicaid recipients with high blood pressure and examined patient, provider, and treatment characteristics as potential explanatory factors for racial disparities in blood pressure control. Methods: We retrospectively reviewed the charts of 2,078 black and 1,436 white North Carolina Medicaid recipients who had high blood pressure managed in primary care practices from July 2005 through June 2006. Documented provider responses to high blood pressure during office visits during the prior year were reviewed. Results: Blacks were less likely than whites to have blood pressure at goal (43.6% compared with 50.9%, P = .001). Blacks above goal were more likely than whites above goal to have been prescribed 4 or more antihypertensive drug classes (24.7% compared with 13.4%, P < .001); to have had medication adjusted during the prior year (46.7% compared with 40.4%, P = .02); and to have a documented provider response to high blood pressure during office visits (35.7% compared with 30.0% of visits, P = .02). Many blacks (28.0%) and whites (34.3%) with blood pressure above goal had fewer than 2 antihypertensive drug classes prescribed. Conclusion: In this population with Medicaid coverage and access to primary care, blacks were less likely than whites to have their blood pressure controlled. Blacks received more frequent intervention and had greater use of combination antihypertensive therapy. Care patterns observed in the usual management of high blood pressure were not sufficient to achieve treatment goals or eliminate disparities

Picosecond X-ray Absorption Spectroscopy of Photochemical Transient Species in Solution

A photoinduced Fe(II) spin crossover reaction in solution is studied with ultrafast x-ray absorption spectroscopy. The iron-nitrogen bond lengthens by 0.21+-0.03 Angstrom in the high-spin transient excited state relative to the ground state