The Influence of a High Fat Diet on Mice with and without Myosin Light Chain Kinase: Implications for Muscle Thermogenesis and Obesity

Work performed at the cellular level suggests that skeletal myosin light chain kinase (skMLCK) mediated phosphorylation of myosin participates in the regulation of muscle thermogenesis. The purpose of this study was to investigate the effect of skMLCK ablation, and resultant loss of myosin phosphorylation, on murine physiology and metabolism. To this end, we compared the morphology and metabolic rate of wildtype and skMLCK absent mice (skMLCK-/- ) in response to 10 weeks of high fat feeding. A larger metabolic challenge better tests the hypothesis that the ability to phosphorylate myosin RLC will aid wildtype mice (WT) in counteracting the obesogenic effects of a HFD more effectively than skMLCK-/- mice. Adult mice (8-12 weeks) of both genotypes were housed at 30°C (thermoneutrality) and randomly assigned to either a control or high fat feeding group (n = 8 per genotype, total of 32 mice). All mice were weighed twice weekly while dual-energy X-ray absorptiometry (DXA) was used at baseline and at week 10 to detect changes in fat and fat-free mass. Metabolic measures such as kcal output as well as behavioural measures such as locomotion, fine movement and food intake were assessed biweekly. At the conclusion of the study, all mice were euthanized, and epididymal white adipose tissue, inguinal white adipose tissue and brown adipose tissue were removed and weighed. Based on cellular studies, it was expected that the absence of myosin phosphorylation would render the skMLCK-/- genotype more susceptible to weight gain than the WT genotype. Contrary to our hypothesis, in vitro data did not translate to effects on whole-body metabolism. WT mice were similarly susceptible to the same morphological and metabolic changes as the skMLCK-/- group when exposed to a high fat diet. Both genotypes consumed the same amount, however, the skMLCK-/- mice were less active and yet, both genotypes gained the same amount of weight. This may suggest a compensatory thermogenic pathway may be at play

Diagnostic value of far-IR water ice features in T Tauri disks

This paper investigates how the far-IR water ice features can be used to infer properties of disks around T Tauri stars and the water ice thermal history. We explore the power of future observations with SOFIA/HIRMES and SPICA's proposed far-IR instrument SAFARI. A series of detailed radiative transfer disk models around a representative T Tauri star are used to investigate how the far-IR water ice features at 45 and 63 micron change with key disk properties: disk size, grain sizes, disk dust mass, dust settling, and ice thickness. In addition, a series of models is devised to calculate the water ice emission features from warmup, direct deposit and cooldown scenarios of the water ice in disks. Photodesorption from icy grains in disk surfaces weakens the mid-IR water ice features by factors 4-5. The far-IR water ice emission features originate from small grains at the surface snow line in disks at distance of 10-100 au. Unless this reservoir is missing in disks (e.g. transitional disks with large cavities), the feature strength is not changing. Grains larger than 10 micron do not contribute to the features. Grain settling (using turbulent description) is affecting the strength of the ice features by at most 15%. The strength of the ice feature scales with the disk dust mass and water ice fraction on the grains, but saturates for dust masses larger than 1.e-4 Msun and for ice mantles that increase the dust mass by more than 50%. The various thermal histories of water ice leave an imprint on the shape of the features (crystalline/amorphous) as well as on the peak strength and position of the 45 micron feature. SOFIA/HIRMES can only detect crystalline ice features much stronger than simulated in our standard T Tauri disk model in deep exposures (1 hr). SPICA/SAFARI can detect the typical ice features in our standard T Tauri disk model in short exposures (10 min). (abbreviated)Comment: accepted for publication in A&

Tell us how to engage you!:Asking polar stakeholders about their engagement preferences

The changes the polar regions face are too complex to be tackled by single scientific disciplines and in isolation from societal actors. Therefore, the call for polar research projects that engage with stakeholders outside academia increases. The ideal set-up of these projects is envisioned as an inclusive and action-oriented process that brings scientists and stakeholders together to identify pressing issues of societal and scientific relevance and to develop research projects that produce practical outcomes. However, working across disciplines and knowledge systems can be challenging. To better understand stakeholders’ motivation for engaging in polar science projects, to learn what stages of a project they are interested in and what their preferred modes of engagement are, stakeholders were surveyed as part of the EU-funded project EU-PolarNet. The results suggest that while most academic survey participants are eager to participate from problem definition to dissemination of results, most non-academic survey participants preferred interaction at the stages when results were disseminated and used for informed decision-making. The survey results have their limitations, yet they provide a basis for important future approaches to stakeholder engagement in polar research projects. They show that stakeholders prefer to engage in different stages of a research project depending on their specific needs and interests, while also acknowledging that additional support may be required to enable meaningful engagement throughout the research process

The SDGs and the Arctic: The need for polar indicators

Our understanding of the Arctic rests to a great extent on the capacity to build long-term observations series. The overall aim of these scientifically based observations is to reach a sustainable development that counter-acts the troublesome future scenario we foresee today. While major drivers of climate change are found outside the Arctic, there is nevertheless a strong need also for the four million people that live in the Arctic to act responsible in order to create capacity for sustainable development. The UN Sustainable Development Goals (SDGs) offer an important framework for both guiding a sustainable development of the region, as well as for improving existing and developing new observation and monitoring systems for the Arctic. This allows an approach where the challenges, changes and the adaptation potential of societies and the ecological systems can be well monitored

'Rapid speed of response to ECT in bipolar depression: A chart review

Objective: To validate a faster speed of response to electroconvulsive therapy (ECT) for bipolar depression (BPD) compared to major depressive disorder (MDD) Method: Retrospective chart review on an ECT cohort in an academic hospital setting. Speed of response was defined by the number of ECT treatments needed for response or remission. Results: Sixty-four depressed patients were included, of whom 53 (MDD: 40, BPD: 13) could be analyzed. The bipolar group responded faster with a mean difference of 3.3 fewer ECT treatments to meet response criteria (MDD 10.4 vs. BPD 7.1, p = 0.054). When using mixed effects regression models for the response/remitter group (n = 35), a faster response for the bipolar group (AIC 252.83 vs 258.55, χ2 = 11.72, p = 0.008) was shown. Other factors, such as psychotic features or comorbidity, did not influence the speed of response. Conclusion: This chart review of an ECT cohort in an naturalistic academic hospital setting shows an evident and clinically relevant faster speed of response in bipolar depression

Designed Spiroketal Protein Modulation

Spiroketals are structural motifs found in many biologically active natural products, which has stimulated considerable efforts toward their synthesis and interest in their use as drug lead compounds. Despite this, the use of spiroketals, and especially bisbenzanulated spiroketals, in a structure-based drug discovery setting has not been convincingly demonstrated. Herein, we report the rational design of a bisbenzannulated spiroketal that potently binds to the retinoid X receptor (RXR) thereby inducing partial coactivator recruitment. We solved the crystal structure of the spiroketal-hRXR alpha-TIF2 ternary complex, and identified a canonical allosteric mechanism as a possible explanation for the partial agonist behavior of our spiroketal. Our cocrystal structure, the first of a designed spiroketal-protein complex, suggests that spiroketals can be designed to selectively target other nuclear receptor subtypes