Decreased Expression Of apM1 in Omental and Subcutaneous Adipose Tissue of Humans With Type 2 Diabetes

We have screened a subtracted cDNA library in order to identify differentially expressed genes in omental adipose tissue of human patients with Type 2 diabetes. One clone (#1738) showed a marked reduction in omental adipose tissue from patients with Type 2 diabetes. Sequencing and BLAST analysis revealed clone #1738 was the adipocyte-specific secreted protein gene apM1 (synonyms ACRP30, AdipoQ, GBP28). Consistent with the murine orthologue, apM1 mRNA was expressed in cultured human adipocytes and not in preadipocytes. Using RT-PCR we confirmed that apM1 mRNA levels were significantly reduced in omental adipose tissue of obese patients with Type 2 diabetes compared with lean and obese normoglycemic subjects. Although less pronounced, apM1 mRNA levels were reduced in subcutaneous adipose tissue of Type 2 diabetic patients. Whereas the biological function of apM1 is presently unknown, the tissue specific expression, structural similarities to TNFα and the dysregulated expression observed in obese Type 2 diabetic patients suggest that this factor may play a role in the pathogenesis of insulin resistance and Type 2 diabetes

Research Priorities for Achieving Healthy Marine Ecosystems and Human Communities in a Changing Climate

ABSTRACT: The health of coastal human communities and marine ecosystems are at risk from a host of anthropogenic stressors, in particular, climate change. Because ecological health and human well-being are inextricably connected, effective and positive responses to current risks require multidisciplinary solutions. Yet, the complexity of coupled social-ecological systems has left many potential solutions unidentified or insufficiently explored. The urgent need to achieve positive social and ecological outcomes across local and global scales necessitates rapid and targeted multidisciplinary research to identify solutions that have the greatest chance of promoting benefits for both people and nature. To address these challenges, we conducted a forecasting exercise with a diverse, multidisciplinary team to identify priority research questions needed to promote sustainable and just marine social-ecological systems now and into the future, within the context of climate change and population growth. In contrast to the traditional reactive cycle of science and management, we aimed to generate questions that focus on what we need to know, before we need to know it. Participants were presented with the question, "If we were managing oceans in 2050 and looking back, what research, primary or synthetic, would wish we had invested in today?" We first identified major social and ecological events over the past 60 years that shaped current human relationships with coasts and oceans. We then used a modified Delphi approach to identify nine priority research areas and 46 questions focused on increasing sustainability and well-being in marine social-ecological systems. The research areas we identified include relationships between ecological and human health, access to resources, equity, governance, economics, resilience, and technology. Most questions require increased collaboration across traditionally distinct disciplines and sectors for successful study and implementation. By identifying these questions, we hope to facilitate the discourse, research, and policies needed to rapidly promote healthy marine ecosystems and the human communities that depend upon them

Toxicokinetic Triage for Environmental Chemicals

Toxicokinetic (TK) models link administered doses to plasma, blood, and tissue concentrations. High-throughput TK (HTTK) performs in vitro to in vivo extrapolation to predict TK from rapid in vitro measurements and chemical structure-based properties. A significant toxicological application of HTTK has been “reverse dosimetry,” in which bioactive concentrations from in vitro screening studies are converted into in vivo doses (mg/kg BW/day). These doses are predicted to produce steady-state plasma concentrations that are equivalent to in vitro bioactive concentrations. In this study, we evaluate the impact of the approximations and assumptions necessary for reverse dosimetry and develop methods to determine whether HTTK tools are appropriate or may lead to false conclusions for a particular chemical. Based on literature in vivo data for 87 chemicals, we identified specific properties (eg, in vitro HTTK data, physico-chemical descriptors, and predicted transporter affinities) that correlate with poor HTTK predictive ability. For 271 chemicals we developed a generic HT physiologically based TK (HTPBTK) model that predicts non-steady-state chemical concentration time-courses for a variety of exposure scenarios. We used this HTPBTK model to find that assumptions previously used for reverse dosimetry are usually appropriate, except most notably for highly bioaccumulative compounds. For the thousands of man-made chemicals in the environment that currently have no TK data, we propose a 4-element framework for chemical TK triage that can group chemicals into 7 different categories associated with varying levels of confidence in HTTK predictions. For 349 chemicals with literature HTTK data, we differentiated those chemicals for which HTTK approaches are likely to be sufficient, from those that may require additional data

Knee movement patterns of injured and uninjured adolescent basketball players when landing from a jump: A case-control study

BACKGROUND: A common knee injury mechanism sustained during basketball is landing badly from a jump. Landing is a complex task and requires good coordination, dynamic muscle control and flexibility. For adolescents whose coordination and motor control has not fully matured, landing badly from a jump can present a significant risk for injury. There is currently limited biomechanical information regarding the lower limb kinetics of adolescents when jumping, specifically regarding jump kinematics comparing injured with uninjured adolescents. This study reports on an investigation of biomechanical differences in landing patterns of uninjured and injured adolescent basketball players. METHODS: A matched case-control study design was employed. Twenty-two basketball players aged 14–16 years participated in the study: eleven previously knee-injured and eleven uninjured players matched with cases for age, gender, weight, height and years of play, and playing for the same club. Six high-speed, three-dimensional Vicon 370 cameras (120 Hz), Vicon biomechanical software and SAS Version 8 software were employed to analyse landing patterns when subjects performed a "jump shot". Linear correlations determined functional relationships between the biomechanical performance of lower limb joints, and paired t-tests determined differences between the normalised peak biomechanical parameters. RESULTS: The average peak vertical ground reaction forces between the cases and controls were similar. The average peak ground reaction forces between the cases and controls were moderately correlated (r = -0.47). The control (uninjured) players had significantly greater hip and knee flexion angles and significantly greater eccentric activity on landing than the uninjured cases (p < 0.01). CONCLUSION: The findings of the study indicate that players with a history of knee injuries had biomechanically compromised landing techniques when compared with uninjured players matched for gender, age and club. Descriptions (norms) of expected levels of knee control, proprioceptive acuity and eccentric strength relative to landing from a jump, at different ages and physical developmental stages, would assist clinicians and coaches to identify players with inappropriate knee performance comparable to their age or developmental stage

Reagents and methods for the solid-phase synthesis of protein-EDTA for use in affinity cleaving

Synthetic procedures for the introduction of the metal chelator ethylenediaminetetraacetic acid (EDTA) at unique amino acid positions of proteins by solid-phase methods are described. Two protected derivatives of EDTA compatible with Merrifield solid-phase protein synthesis employing N-tert-butyloxycarbonyl- (Boc-) protected amino acids were developed. The first reagent is a dipeptide with three of four carboxyl groups of EDTA protected as benzyl esters and the fourth coupled to a γ-aminobutanoic acid linker, referred to as tribenzyl-EDTA-CABA (BEG). A second reagent is the tricyclohexyl ester of EDTA, TCE. BEG and TCE allow the modification of the NH_2 terminus and/or lysine side chains of resin-bound peptides and proteins. Upon deprotection and cleavage from the resin, a protein is produced with EDTA at a defined amino acid position. The availability of protein-EDTA conjugates extends the affinity cleaving method to the study of protein-DNA complexes in solution