Insulin and GLP-1 infusions demonstrate the onset of adipose-specific insulin resistance in a large fasting mammal: potential glucogenic role for GLP-1.

Prolonged food deprivation increases lipid oxidation and utilization, which may contribute to the onset of the insulin resistance associated with fasting. Because insulin resistance promotes the preservation of glucose and oxidation of fat, it has been suggested to be an adaptive response to food deprivation. However, fasting mammals exhibit hypoinsulinemia, suggesting that the insulin resistance-like conditions they experience may actually result from reduced pancreatic sensitivity to glucose/capacity to secrete insulin. To determine whether fasting results in insulin resistance or in pancreatic dysfunction, we infused early- and late-fasted seals (naturally adapted to prolonged fasting) with insulin (0.065 U/kg), and a separate group of late-fasted seals with low (10 pM/kg) or high (100 pM/kg) dosages of glucagon-like peptide-1 (GLP-1) immediately following a glucose bolus (0.5g/kg), and measured the systemic and cellular responses. Because GLP-1 facilitates glucose-stimulated insulin secretion, these infusions provide a method to assess pancreatic insulin-secreting capacity. Insulin infusions increased the phosphorylation of insulin receptor and Akt in adipose and muscle of early and late fasted seals; however the timing of the signaling response was blunted in adipose of late fasted seals. Despite the dose-dependent increases in insulin and increased glucose clearance (high dose), both GLP-1 dosages produced increases in plasma cortisol and glucagon, which may have contributed to the glucogenic role of GLP-1. Results suggest that fasting induces adipose-specific insulin resistance in elephant seal pups, while maintaining skeletal muscle insulin sensitivity, and therefore suggests that the onset of insulin resistance in fasting mammals is an evolved response to cope with prolonged food deprivation

Pathways to recovery among homeless people with mental illness: Is impulsiveness getting in the way?

Objective: This study investigates the association between impulsiveness and six dimensions of recovery among homeless people with mental illness. Method: The sample was composed of 418 participants of a randomized controlled trial of Housing First, a recovery-oriented program that provides immediate access to permanent housing. The reliable change index method was used to provide an estimate of the statistical and clinical significance of the change from baseline to 24 months (i.e., clinically meaningful improvement), on outcomes that pertain to recovery dimensions: psychiatric symptoms (clinical), physical health and substance use problems (physical), residential stability (functional), arrests (criminological), community integration (social), and hope and personal confidence (existential). We tested for the effect of impulsiveness, assessed with the Barratt Impulsiveness Scale–11, on clinically meaningful improvement on each specific outcome, adjusting for age, gender and intervention assignment, as both intervention arms were included in the analysis. Results: For every increase in total impulsiveness score by one standard deviation, the odds of experiencing clinically meaningful improvement decreased by 29% (OR = 0.71, 95% CI, 0.55 to 0.91) on the clinical dimension and by 53% (OR = 0.47, 95% CI, 0.32 to 0.68) on the existential dimension. However, changes in outcomes pertaining to physical, functional, criminological, and social dimensions were not significantly influenced by impulsiveness. Conclusions: Findings highlight the importance of addressing impulsiveness in the context of recovery-oriented interventions for homeless people with mental illness. Further research may be required to improve interventions that are responsive to unique needs of impulsive individuals to support clinical and existential recovery.Objectif : La présente étude porte sur l’association entre l’impulsivité et six dimensions du rétablissement chez des personnes en situation d’itinérance vivant avec une maladie mentale. Méthode : L’échantillon est composé de 418 participants à un essai randomisé contrôlé de l’approche Logement d’abord, un programme axé sur le rétablissement qui offre un accès immédiat à un logement permanent. La méthode de l’indicateur de changement fiable a été utilisée afin de fournir une estimation de la signification statistique et clinique du changement de l’entrée dans l’étude à 24 mois (c.-à-d., une amélioration cliniquement significative) pour les mesures qui ont trait aux dimensions du rétablissement: symptômes psychiatriques (clinique), santé physique et problèmes liés à l’utilisation de substances (physique), stabilité résidentielle (fonctionnelle), arrestations (criminologique), intégration communautaire (social) et espoir et confiance en soi (existentiel). Nous avons testé l’effet de l’impulsivité, évaluée à l’aide de l’échelle d’impulsivité de Barratt, sur l’amélioration cliniquement significative pour chaque mesure, en ajustant pour l’âge, le genre et l’assignation à une intervention, les deux volets de l’intervention étant inclus dans l’analyse. Résultats : Pour chaque augmentation du score total d’impulsivité d’un écart-type, les probabilités de connaître une amélioration cliniquement significative diminuaient de 29% (RC = 0,71; IC à 95% 0,55 à 0,91) pour la dimension clinique et de 53% (RC = 0,47; IC à 95% 0,32 à 0,68) pour la dimension existentielle. Toutefois, les dimensions physique, fonctionnelle, criminologique et sociale n’étaient pas influencées significativement par l’impulsivité. Conclusions : Les résultats soulignent l’importance de prendre en compte l’impulsivité dans le contexte d’interventions axées sur le rétablissement pour les personnes en situation d’itinérance vivant avec une maladie mentale. Des recherches futures pourraient être nécessaires pour améliorer les interventions afin qu’elles soutiennent mieux le rétablissement clinique et existentiel en répondant aux besoins uniques des personnes impulsives

Like-charge attraction through hydrodynamic interaction

We demonstrate that the attractive interaction measured between like-charged colloidal spheres near a wall can be accounted for by a nonequilibrium hydrodynamic effect. We present both analytical results and Brownian dynamics simulations which quantitatively capture the one-wall experiments of Larsen and Grier (Nature 385, p. 230, 1997).Comment: 10 pages, 4 figure

Hydrodynamic Coupling of Two Brownian Spheres to a Planar Surface

We describe direct imaging measurements of the collective and relative diffusion of two colloidal spheres near a flat plate. The bounding surface modifies the spheres' dynamics, even at separations of tens of radii. This behavior is captured by a stokeslet analysis of fluid flow driven by the spheres' and wall's no-slip boundary conditions. In particular, this analysis reveals surprising asymmetry in the normal modes for pair diffusion near a flat surface.Comment: 4 pages, 4 figure

CO\u3csub\u3e2\u3c/sub\u3e Recycling Using Microalgae for the Production of Fuels

CO2 capture and recycle using microalgae was demonstrated at a coal-fired power plant (Duke Energy’s East Bend Station, Kentucky). Using an in-house designed closed loop, vertical tube photobioreactor, Scenedesmus acutus was cultured using flue gas as the CO2 source. Algae productivity of 39 g/(m2 day) in June–July was achieved at significant scale (18,000 L), while average daily productivity slightly in excess of 10 g/(m2 day) was demonstrated in the month of December. A protocol for low-cost algae harvesting and dewatering was developed, and the conversion of algal lipids—extracted from the harvested biomass—to diesel-range hydrocarbons via catalytic deoxygenation was demonstrated. Assuming an amortization period of 10 years, calculations suggest that the current cost of capturing and recycling CO2 using this approach will fall close to $1,600/ton CO2, the main expense corresponding to the capital cost of the photobioreactor system and the associated installation cost. From this it follows that future cost reduction measures should focus on the design of a culturing system which is less expensive to build and install. In even the most optimistic scenario, the cost of algae-based CO2 capture is unlikely to fall below$225/ton, corresponding to a production cost of ~$400/ton biomass. Hence, the value of the algal biomass produced will be critical in determining the overall economics of CO2 capture and recycle

CO\u3csub\u3e2\u3c/sub\u3e Recycling Using Microalgae for the Production of Fuels

CO2 capture and recycle using microalgae was demonstrated at a coal-fired power plant (Duke Energy’s East Bend Station, Kentucky). Using an in-house designed closed loop, vertical tube photobioreactor, Scenedesmus acutus was cultured using flue gas as the CO2 source. Algae productivity of 39 g/(m2 day) in June–July was achieved at significant scale (18,000 L), while average daily productivity slightly in excess of 10 g/(m2 day) was demonstrated in the month of December. A protocol for low-cost algae harvesting and dewatering was developed, and the conversion of algal lipids—extracted from the harvested biomass—to diesel-range hydrocarbons via catalytic deoxygenation was demonstrated. Assuming an amortization period of 10 years, calculations suggest that the current cost of capturing and recycling CO2 using this approach will fall close to $1,600/ton CO2, the main expense corresponding to the capital cost of the photobioreactor system and the associated installation cost. From this it follows that future cost reduction measures should focus on the design of a culturing system which is less expensive to build and install. In even the most optimistic scenario, the cost of algae-based CO2 capture is unlikely to fall below$225/ton, corresponding to a production cost of ~$400/ton biomass. Hence, the value of the algal biomass produced will be critical in determining the overall economics of CO2 capture and recycle

Ontogenetic changes in skeletal muscle fiber type, fiber diameter and myoglobin concentration in the Northern elephant seal (Mirounga angustirostris)

© The Author(s), 2014. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Frontiers in Physiology 5 (2014): 217, doi:10.3389/fphys.2014.00217.Northern elephant seals (Mirounga angustirostris) (NES) are known to be deep, long-duration divers and to sustain long-repeated patterns of breath-hold, or apnea. Some phocid dives remain within the bounds of aerobic metabolism, accompanied by physiological responses inducing lung compression, bradycardia, and peripheral vasoconstriction. Current data suggest an absence of type IIb fibers in pinniped locomotory musculature. To date, no fiber type data exist for NES, a consummate deep diver. In this study, NES were biopsied in the wild. Ontogenetic changes in skeletal muscle were revealed through succinate dehydrogenase (SDH) based fiber typing. Results indicated a predominance of uniformly shaped, large type I fibers and elevated myoglobin (Mb) concentrations in the longissimus dorsi (LD) muscle of adults. No type II muscle fibers were detected in any adult sampled. This was in contrast to the juvenile animals that demonstrated type II myosin in Western Blot analysis, indicative of an ontogenetic change in skeletal muscle with maturation. These data support previous hypotheses that the absence of type II fibers indicates reliance on aerobic metabolism during dives, as well as a depressed metabolic rate and low energy locomotion. We also suggest that the lack of type IIb fibers (adults) may provide a protection against ischemia reperfusion (IR) injury in vasoconstricted peripheral skeletal muscle.Funding was provided by the Baylor University Faculty Research Investment Program (StephenJ.Trumble)

High-Throughput Characterization of Viral and Cellular Protein Expression Patterns During JC Polyomavirus Infection

JC polyomavirus (JCPyV) is a ubiquitous human pathogen and the causative agent of a fatal demyelinating disease in severely immunocompromised individuals. Due to the lack of successful pharmacological interventions, the study of JCPyV infection strategies in a rapid and highly sensitive manner is critical for the characterization of potential antiviral therapeutics. Conventional methodologies for studying viral infectivity often utilize the detection of viral proteins through immunofluorescence microscopy-based techniques. While these methodologies are well established in the field, they require significant time investments and lack a high-throughput modality. Scanning imager-based detection methods like the In-cell Western (ICW)TM have been previously utilized to overcome these challenges incurred by traditional microscopy-based infectivity assays. This automated technique provides not only rapid detection of viral infection status, but can also be optimized to detect changes in host-cell protein expression during JCPyV challenge. Compared to traditional manual determinations of infectivity through microscopy-based techniques, the ICW provides an expeditious and robust determination of JCPyV infection. The optimization of the ICW for the detection of viral and cellular proteins during JCPyV infection provides significant time and cost savings by diminishing sample preparation time and increasing resource utilization. While the ICW cannot provide single-cell analysis information and is limited in the detection of quantitation of low-expressing proteins, this assay provides a high-throughput system to study JCPyV, previously unavailable to the field. Thus, the high-throughput nature and dynamic experimental range of the ICW can be applied to the study of JCPyV infection

A Careful Look at Binding Site Reorganization in the even-skipped Enhancers of Drosophila and Sepsids

Organismic and Evolutionary Biolog

Identification of PSD-95 in the Postsynaptic Density Using MiniSOG and EM Tomography

Combining tomography with electron microscopy (EM) produces images at definition sufficient to visualize individual protein molecules or molecular complexes in intact neurons. When freeze-substituted hippocampal cultures in plastic sections are imaged by EM tomography, detailed structures emerging from 3D reconstructions reveal putative glutamate receptors and membrane-associated filaments containing scaffolding proteins such as postsynaptic density (PSD)-95 family proteins based on their size, shape, and known distributions. In limited instances, structures can be identified with enhanced immuno-Nanogold labeling after light fixation and subsequent freeze-substitution. Molecular identification of structure can be corroborated in their absence after acute protein knockdown or gene knockout. However, additional labeling methods linking EM level structure to molecules in tomograms are needed. A recent development for labeling structures for TEM employs expression of endogenous proteins carrying a green fluorescent tag, miniSOG, to photoconvert diaminobenzidine (DAB) into osmiophilic polymers. This approach requires initial mild chemical fixation but many of structural features in neurons can still be discerned in EM tomograms. The photoreaction product, which appears as electron-dense, fine precipitates decorating protein structures in neurons, may diffuse to fill cytoplasm of spines, thus obscuring specific localization of proteins tagged with miniSOG. Here we develop an approach to minimize molecular diffusion of the DAB photoreaction product in neurons, which allows miniSOG tagged molecule/complexes to be identified in tomograms. The examples reveal electron-dense clusters of reaction product labeling membrane-associated vertical filaments, corresponding to the site of miniSOG fused at the C-terminal end of PSD-95-miniSOG, allowing identification of PSD-95 vertical filaments at the PSD. This approach, which results in considerable improvement in the precision of labeling PSD-95 in tomograms without complications due to the presence of antibody complexes in immunogold labeling, may be applicable for identifying other synaptic proteins in intact neurons