Coordinated balancing of muscle oxidative metabolism through PGC-1α increases metabolic flexibility and preserves insulin sensitivity

The peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) enhances oxidative metabolism in skeletal muscle. Excessive lipid oxidation and electron transport chain activity can, however, lead to the accumulation of harmful metabolites and impair glucose homeostasis. Here, we investigated the effect of over-expression of PGC-1α on metabolic control and generation of insulin desensitizing agents in extensor digitorum longus (EDL), a muscle that exhibits low levels of PGC-1α in the untrained state and minimally relies on oxidative metabolism. We demonstrate that PGC-1α induces a strictly balanced substrate oxidation in EDL by concomitantly promoting the transcription of activators and inhibitors of lipid oxidation. Moreover, we show that PGC-1α enhances the potential to uncouple oxidative phosphorylation. Thereby, PGC-1α boosts elevated, yet tightly regulated oxidative metabolism devoid of side products that are detrimental for glucose homeostasis. Accordingly, PI3K activity, an early phase marker for insulin resistance, is preserved in EDL muscle. Our findings suggest that PGC-1α coordinately coactivates the simultaneous transcription of gene clusters implicated in the positive and negative regulation of oxidative metabolism and thereby increases metabolic flexibility. Thus, in mice fed a normal chow diet, over-expression of PGC-1α does not alter insulin sensitivity and the metabolic adaptations elicited by PGC-1α mimic the beneficial effects of endurance training on muscle metabolism in this context

Copper(I) dye-sensitized solar cells with [Co(bpy)3]2+/3+ electrolyte

The hierarchical assembly of DSCs containing a new heteroleptic copper(I) complex with a phosphonic acid anchoring ligand is described; it is shown that conventional I−/I3− electrolytes may be replaced by [Co(bpy)3]2+/3+ with no loss in performance

Interactions of local climatic, biotic and hydrogeochemical processes facilitate phosphorus dynamics along an Everglades forest-marsh gradient

Ecosystem nutrient cycling is often complex because nutrient dynamics within and between systems are mediated by the interaction of biological and geochemical conditions operating at different temporal and spatial scales. Vegetated patches in semiarid and wetland landscapes have been shown to exemplify some of these patterns and processes. We investigated biological and geochemical factors suggested to contribute to phosphorus (P) movement and availability along a forest-marsh gradient in an Everglades tree island. Our study illustrated processes that are consistent with the chemohydrodynamic nutrient (CHNT) hypothesis and the trigger-transfer, pulse-reserve (TTPR) model developed for semiarid systems. Comparison with the TTPR model was constructive as it elaborated several significant patterns and processes of the tree island ecosystem including: (1) concentration of the limiting resource (P) in the source patch (High Head which constitutes the reserve) compared with the resource-poor landscape, (2) soil zone calcite precipitation requiring strong seasonality for evapotranspiration to promote conditions for secondary soil development and calcium phosphate reprecipitation, (3) rewetting of previously dry soils by early wet season precipitation events, and (4) antecedent conditions of the source patch, including landscape position that modulated the effect of the precipitation trigger. Thus, our study showed how water availability drives soil water P dynamics and, potentially, stability of mineral soil P in this tree island ecosystem. In landscapes with extensive water management, these processes can be asynchronous with the seasonality of hydrologic dynamics, tipping the balance between a sink and source of a limiting nutrient

Sustained Immune Tolerance Induction in Enzyme Replacement Therapy-Treated CRIM-Negative Patients with Infantile Pompe Disease

BACKGROUND: Cross-reactive immunological material-negative (CRIM-negative) infantile Pompe disease (IPD) patients develop an immune response against enzyme replacement therapy (ERT) with alglucosidase alfa that nullifies ERT efficacy. Prophylactic immune tolerance induction (ITI) with rituximab, methotrexate, and IVIG successfully prevents development of deleterious rhGAA IgG antibodies; however, safety, likelihood of success, and long-term efficacy of ITI in a larger cohort remain unknown. METHODS: Clinical data were analyzed for 19 CRIM-negative IPD patients who received ITI with rituximab, methotrexate, and IVIG in the ERT-naive setting (ERT+ITI) and compared to a historical cohort of 10 CRIM-negative IPD patients on ERT monotherapy. RESULTS: ITI was safely tolerated, although infections were reported in 4 patients. Fourteen (74%) ERT+ITI patients were alive, with a median age of 44.2 months at their final assessment. The eldest survivor was 103.9 months old, with 100.2 months of follow-up after initiation of ERT+ITI. Death (n = 5) occurred at a median age of 29.2 months and was unrelated to the administration of ITI. Fifteen patients either did not seroconvert (n = 8) or maintained low titers (n = 7; defined as titers of /=51,200 at or beyond 6 months on ERT). Left ventricular mass index (LVMI) decreased from a median of 248.5 g/m2 at baseline to 76.8 g/m2 at a median time from ERT+ITI initiation to 59 weeks. ERT+ITI significantly improved overall survival (P = 0.001), eliminated/reduced antibodies at values o

The Lingering Effects of an Artificial Blind Spot

BACKGROUND: When steady fixation is maintained on the centre of a large patch of texture, holes in the periphery of the texture rapidly fade from awareness, producing artificial scotomata (i.e., invisible areas of reduced vision, like the natural ‘blind spot’). There has been considerable controversy about whether this apparent ‘filling in’ depends on a low-level or high-level visual process. Evidence for an active process is that when the texture around the scotomata is suddenly removed, phantasms of the texture appear within the previous scotomata. METHODOLOGY: To see if these phantasms were equivalent to real low-level signals, we measured contrast discrimination for real dynamic texture patches presented on top of the phantasms. PRINCIPAL FINDINGS: Phantasm intensity varied with adapting contrast. Contrast discrimination depended on both (real) pedestal contrast and phantasm intensity, in a manner indicative of a common sensory threshold. The phantasms showed inter-ocular transfer, proving that their effects are cortical rather than retinal. CONCLUSIONS: We show that this effect is consistent with a tonic spreading of the adapting texture into the scotomata, coupled with some overall loss of sensitivity. Our results support the view that ‘filling in’ happens at an early stage of visual processing, quite possibly in primary visual cortex (V1)

Sigmund Exner's (1887) einige beobachtungen über bewegungsnachbilder (some observations on movement aftereffects):an illustrated translation with commentary

In his original contribution, Exner’s principal concern was a comparison between the properties of different aftereffects, and particularly to determine whether aftereffects of motion were similar to those of color and whether they could be encompassed within a unified physiological framework. Despite the fact that he was unable to answer his main question, there are some excellent—so far unknown—contributions in Exner’s paper. For example, he describes observations that can be related to binocular interaction, not only in motion aftereffects but also in rivalry. To the best of our knowledge, Exner provides the first description of binocular rivalry induced by differently moving patterns in each eye, for motion as well as for their aftereffects. Moreover, apart from several known, but beautifully addressed, phenomena he makes a clear distinction between motion in depth based on stimulus properties and motion in depth based on the interpretation of motion. That is, the experience of movement, as distinct from the perception of movement. The experience, unlike the perception, did not result in a motion aftereffect in depth

Greater temperature sensitivity of plant phenology at colder sites: implications for convergence across northern latitudes

Warmer temperatures are accelerating the phenology of organisms around the world. Temperature sensitivity of phenology might be greater in colder, higher latitude sites than in warmer regions, in part because small changes in temperature constitute greater relative changes in thermal balance at colder sites. To test this hypothesis, we examined up to 20 years of phenology data for 47 tundra plant species at 18 high-latitude sites along a climatic gradient. Across all species, the timing of leaf emergence and flowering was more sensitive to a given increase in summer temperature at colder than warmer high-latitude locations. A similar pattern was seen over time for the flowering phenology of a widespread species, Cassiope tetragona. These are among the first results highlighting differential phenological responses of plants across a climatic gradient and suggest the possibility of convergence in flowering times and therefore an increase in gene flow across latitudes as the climate warms