Deletion of the mammalian INDY homolog mimics aspects of dietary restriction and protects against adiposity and insulin resistance in mice

Reduced expression of the Indy (I'm Not Dead, Yet) gene in D.?melanogaster and its homolog in C.?elegans prolongs life span and in D.?melanogaster augments mitochondrial biogenesis in a manner akin to caloric restriction. However, the cellular mechanism by which Indy does this is unknown. Here, we report on the knockout mouse model of the mammalian Indy (mIndy) homolog, SLC13A5. Deletion of mIndy in mice (mINDY(-/-) mice) reduces hepatocellular ATP/ADP ratio, activates hepatic AMPK, induces PGC-1α, inhibits ACC-2, and reduces SREBP-1c levels. This signaling network promotes hepatic mitochondrial biogenesis, lipid oxidation, and energy expenditure and attenuates hepatic de novo lipogenesis. Together, these traits protect mINDY(-/-) mice from the adiposity and insulin resistance that evolve with high-fat feeding and aging. Our studies demonstrate a profound effect of mIndy on mammalian energy metabolism and suggest that mINDY might be a therapeutic target for the treatment of obesity and type 2 diabetes.     

Sonic hedgehog shedding results in functional activation of the solubilized protein

All Hedgehog (Hh) proteins are released from producing cells despite being synthesized as N- and C-terminally lipidated, membrane-tethered molecules. Thus, a cellular mechanism is needed for Hh solubilization. We previously suggested that a disintegrin and metalloprotease (ADAM)-mediated shedding of Sonic hedgehog (ShhNp) from its lipidated N and C termini results in protein solubilization. This finding, however, seemed at odds with the established role of N-terminal palmitoylation for ShhNp signaling activity. We now resolve this paradox by showing that N-palmitoylation of ShhNp N-terminal peptides is required for their proteolytic removal during solubilization. These peptides otherwise block ShhNp zinc coordination sites required for ShhNp binding to its receptor Patched (Ptc), explaining the essential yet indirect role of N-palmitoylation for ShhNp function. We suggest a functional model in which membrane-tethered multimeric ShhNp is at least partially autoinhibited in trans but is processed into fully active, soluble multimers upon palmitoylation-dependent cleavage of inhibitory N-terminal peptides.     

Borderline Personality and the Detection of Angry Faces

Background

Many studies have assessed emotion recognition in patients with Borderline Personality Disorder and considerable evidence has been accumulated on patients’ ability to categorize emotions. In contrast, their ability to detect emotions has been investigated sparsely. The only two studies that assessed emotion detection abilities found contradictory evidence on patients’ ability to detect angry faces.

Methods

To clarify whether patients with Borderline Personality Disorder show enhanced detection of angry faces, we conducted three experiments: a laboratory study (n = 53) with a clinical sample and two highly powered web studies that measured Borderline features (n₁ = 342, n₂ = 220). Participants in all studies completed a visual search paradigm, and the reaction times for the detection of angry vs. happy faces were measured.

Results

Consistently, data spoke against enhanced detection of angry faces in the Borderline groups, indicated by non-significant group (Borderline vs. healthy control) × target (angry vs. happy) interactions, despite highly satisfactory statistical power to detect even small effects.

Conclusions

In contrast to emotion categorization, emotion detection appears to be intact in patients with Borderline Personality Disorder and individuals high in Borderline features. The importance of distinguishing between these two processes in future studies is discussed.     

Structure–function relationships of four compression wood types: micromechanical properties at the tissue and fibre level

The mechanisms behind compressive stress generation in gymnosperms are not yet fully understood. Investigating the structure–function relationships at the tissue and cell level, however, can provide new insights. Severe compression wood of all species lacks a S3 layer, has a high microfibril angle in the S2 layer and a high lignin content. Additionally, special features like helical cavities or spiral thickenings appear, which are not well understood in terms of their mechanical relevance, but need to be examined with regard to evolutionary trends in compression wood development. Thin compression wood foils and isolated tracheids of four gymnosperm species [Ginkgo biloba L., Taxus baccata L., Juniperus virginiana L., Picea abies (L.) Karst.] were investigated. The tracheids were isolated mechanically by peeling them out of the solid wood using fine tweezers. In contrast to chemical macerations, the cell wall components remained in their original condition. Tensile properties of tissue foils and tracheids were measured in a microtensile apparatus under wet conditions. Our results clearly show an evolutionary trend to a much more flexible compression wood. An interpretation with respect to compressive stress generation is discussed.     

Loss of GH3 function does not affect phytochrome-mediated development in a moss, Physcomitrella patens

Auxin-induced gene expression is described for a variety of different genes including the SAUR-, Aux/IAA- and GH3-families, members of which have been found in seed plants. The precise function of GH3-like proteins in plant development is not well characterised yet. Mutant analysis in Arabidopsis thaliana indicates a possible role for GH3-like proteins in connecting auxin and light signal transduction. Here, we report the isolation of three different GH3-like homologues from a lower land plant, the moss Physcomitrella patens. Two of the GH3-like homologues were chosen for further characterisation. Both genes are expressed in gametophytic tissues, with expression starting very early in moss development. Knockout plants were generated and analysed. In comparison to white-light growth, cultivation of the wild type and knockout plants under red-light conditions resulted in a delay in gametophytic tissue development. The leafy moss plants displayed an elongated phenotype. Growth delay and elongation were even stronger under far-red light conditions. No obvious differences between wild type and knockout plants could be detected under the examined conditions, indicating functional redundancy of the two genes.     

Multi-modality imaging identifies key times for annexin V imaging as an early predictor of therapeutic outcome

Radiolabeled annexin V may provide an early indication of the success or failure of anticancer therapy on a patient-by-patient basis as an in vivo marker of tumor cell killing. An important question that remains is when, after initiation of treatment, should annexin V imaging be performed. To address this issue, we obtained simultaneous in vivo measurements of tumor burden and uptake of radiolabeled annexin V in the syngeneic orthotopic murine BCL1 lymphoma model using in vivo bioluminescence imaging (BLI) and small animal single-photon emission computed tomography (SPECT). BCL1 cells labeled for fluorescence and bioluminescence assays (BCL1-gfp/luc) were injected into mice at a dose that leads to progressive disease within two to three weeks. Tumor response was followed by BLI and SPECT before and after treatment with a single dose of 10 mg/kg doxorubicin. Biodistribution analyses revealed a biphasic increase of annexin V uptake within the tumor-bearing tissues of mice. An early peak occurring before actual tumor cells loss was observed between 1 and 5 hr after treatment, and a second longer sustained rise from 9 to 24 hr after therapy, which heralds the onset of tumor cell loss as confirmed by BLI. Multimodality imaging revealed the temporal patterns of tumor cell loss and annexin V uptake revealing a better understanding of the timing of radiolabeled annexin V uptake for its development as a marker of therapeutic efficacy.     

Assessing the Eco-efficiency of End-of-Pipe Technologies with the Environmental Cost Efficiency Indicator

The concept of eco-efficiency is increasingly being applied to judge the combined environmental and economic performance of product systems, processes, and/or companies. Ecoefficiency is often defined as the ratio of economic value added to environmental impact added. This definition is not appropriate for end-of-pipe treatment technologies because these technologies aim at improving the environmental performance of technical processes at the cost of financial expense. Therefore, an indicator for the assessment of end-of-pipe technologies has been proposed. This indicator, called environmental cost efficiency (ECE), is defined as the ratio of net environmental benefits to the difference in costs. ECE is applied to four end-of-pipe technologies for the treatment of municipal solid waste: sanitary landfill, mechanical-biological treatment, modern grate incineration, and a staged thermal process (pyrolysis and gasification). A life-cycle assessment was performed on these processes to quantify the net environmental benefit. Moreover, the approximate net costs (costs minus benefits) were quantified. The results show that, relative to grate incineration, sanitary landfills and mechanical-biological treatment are less costly but environmentally more harmful. We calculated the ECE for all combinations of technologies. The results indicate that the staged thermal process may be the most environmentally cost-efficient alternative to all other treatment technologies in the long run, followed by mechanical-biological treatment and grate incineration.