Geomorphological characteristics of the Wabash River, USA: Influence on fish assemblages.

River hydrogeomorphology is a potential predictor of ecosystem and assemblage variation. We tested for fish assemblage variation as a function of hydrogeomorphology in a Midwestern US large river, the Wabash River. Fish data were classified by taxonomy and traits and we tested if assemblages varied with river hydrogeomorphology or river distance, defined into 10-km distinct reaches. Three unique geomorphological units, Functional Process Zones (FPZ), were identified using an ArcGIS hydrogeomorphic model, based primarily on channel width, floodplain width, and down valley slope. Five locations were identified as FPZ A with narrow stream channel, high down valley slope, and an expansive floodplain. Ten locations were identified as FPZ B with a wide river channel and wide floodplain. Thirty-five locations were identified as FPZ C with wide river channel and a constrained floodplain. The sites were categorized into three stream orders: 5, 6, and 7. We found hydrogeomorphology classified by unique FPZs or by river distance influenced taxonomic and functional fish assemblages for the Wabash River. There was high overlap among fish occurrences among FPZs, but nine species resulted as significant indicators of specific FPZs. Five traits were significant indicators of FPZs: an intermediate Swim Factor score, medium tolerance to silt, small-large stream size preference, and two Shape Factor categories. Our conclusions are that fish assemblages respond strongly to local geomorphology and river distance, fitting the riverine ecosystem synthesis and the river continuum concept.

Animal and in silico models for the study of sarcomeric cardiomyopathies.

Over the past decade, our understanding of cardiomyopathies has improved dramatically, due to improvements in screening and detection of gene defects in the human genome as well as a variety of novel animal models (mouse, zebrafish, and drosophila) and in silico computational models. These novel experimental tools have created a platform that is highly complementary to the naturally occurring cardiomyopathies in cats and dogs that had been available for some time. A fully integrative approach, which incorporates all these modalities, is likely required for significant steps forward in understanding the molecular underpinnings and pathogenesis of cardiomyopathies. Finally, novel technologies, including CRISPR/Cas9, which have already been proved to work in zebrafish, are currently being employed to engineer sarcomeric cardiomyopathy in larger animals, including pigs and non-human primates. In the mouse, the increased speed with which these techniques can be employed to engineer precise 'knock-in' models that previously took years to make via multiple rounds of homologous recombination-based gene targeting promises multiple and precise models of human cardiac disease for future study. Such novel genetically engineered animal models recapitulating human sarcomeric protein defects will help bridging the gap to translate therapeutic targets from small animal and in silico models to the human patient with sarcomeric cardiomyopathy.

Altered myofilament stoichiometry in response to heart failure in a cardioprotective α-myosin heavy chain transgenic rabbit model.

PURPOSE: Decreases in α myosin heavy chain (α-MHC) is a common feature of human heart failure (HF), whereas α-MHC overexpression in transgenic (TG) rabbits is cardioprotective against tachycardia-induced cardiomyopathy (TIC). Hypothesizing that MHC isoform content alterations would impact sarcomere and mitochondrial energetics protein complement, we investigated the impact of α-MHC overexpression on global cardiac protein expression. EXPERIMENTAL DESIGN: Protein expression was assessed by two-dimensional gel electrophoresis and MS on the extracts from TG and nontransgenic (NTG) rabbits under TIC or sham-operated conditions. RESULTS: We observed significant changes in the levels of actin, myosin light chain 2, and desmin between the left ventricular (LV) tissue of TG and NTG animals. The proteome was broadly impacted, with significant changes in mitochondrial energetics and chaperone protein families. No changes were observed in total cellular MHC or in myofibril-associated MHC. In myofibrils isolated from TG(sham) animals, only actin levels were altered in TG(sham) compared with NTG(sham) animals, suggesting careful myofibril assembly regulation. CONCLUSIONS AND CLINICAL RELEVANCE: These data suggest that myofibril protein composition may protect against TIC, emphasizing protein interconnectivity and demonstrating the need for broad-based proteomic studies in understanding targeted genetic manipulations. This study identifies the targets for future development of cardioprotective agents and elucidates tachycardia-induced heart failure pathways.

The high-low amputation ratio: a deeper insight into diabetic foot care?

The purpose of this study was to propose and evaluate a high to low (Hi-Lo) amputation ratio as a potential additional quality measure giving further insight into high-risk foot surveillance beyond foot screening examinations. As part of the Dartmouth Atlas of Health Care project, a secondary analysis was performed on Medicare administrative data. Amputation rates were adjusted for age, gender, and race. This included 37,808 minor (foot-level) amputations and 44,599 major amputations from 1996 to 1997. We also calculated the longitudinal national trends in the Hi-Lo ratio with data from the Centers for Disease Control and Prevention from 1992 to 2002. The adjusted mean Hi-Lo ratio was 1.35 (standard deviation, 0.42). The lowest ratio was 0.56, and the highest ratio was 3.43. The correlation coefficient for the Hi-Lo ratio with major amputation rate was 0.48 (P < .0001; R2 = 0.23). Similar correlations were found for the highest and lowest percentiles for major and minor rates. The Centers for Disease Control and Prevention data of the Hi-Lo ratio using the crude and age-adjusted rates suggest stable trends in the ratio over a decade. The Hi-Lo measure demonstrates face validity, yet only a small proportion of the variance is described by local propensity to perform major amputation or by major amputation rates alone. The United States has relied on a foot screening measure alone, perhaps explaining why major amputation rates have not substantively declined. If we are to reduce the amputation burden, we should begin with a straightforward measure that can be implemented at most any center.