Description: The transcription factors Gli2 (glioma-associated factor 2), which is a transactivator of Sonic Hedgehog (Shh) signalling, and myocyte enhancer factor 2C (MEF2C) play important roles in the development of embryonic heart muscle and enhance cardiomyogenesis in stem cells. Although the physiological importance of Shh signalling and MEF2 factors in heart development is well known, the mechanistic understanding of their roles is unclear. Here, we demonstrate that Gli2 and MEF2C activated each other's expression while enhancing cardiomyogenesis in differentiating P19 EC cells. Furthermore, dominant-negative mutant proteins of either Gli2 or MEF2C repressed each other's expression, while impairing cardiomyogenesis in P19 EC cells. In addition, chromatin immunoprecipitation (ChIP) revealed association of Gli2 to the Mef2c gene, and of MEF2C to the Gli2 gene in differentiating P19 cells. Finally, co-immunoprecipitation studies showed that Gli2 and MEF2C proteins formed a complex, capable of synergizing on cardiomyogenesis-related promoters containing both Gli- and MEF2-binding elements. We propose a model whereby Gli2 and MEF2C bind each other's regulatory elements, activate each other's expression and form a protein complex that synergistically activates transcription, enhancing cardiac muscle development. This model links Shh signalling to MEF2C function during cardiomyogenesis and offers mechanistic insight into their in vivo functions.

Description: The reconstruction of the history of rearrangements and the reconstruction of ancestral genomes are some of the challenges of bioinformatics today. Many algorithms already exist, treating one or the other question but none treating both. These reconstructions are interdependent and we argue on the interest of treating both problems in parallel to lead to a richer and more complete output. We also argue on the importance of redefining several steps of these algorithms to improve both reconstructions: the identification of synteny blocks has to be as precise as possible, and the treatment of multiple genomes has to be based on pairwise comparisons to ensure the most detailed reconstructions. In this article, we highlight novel solutions to these points and focus on the need of explicitly treating overlapping, included, duplicated and unsigned synteny blocks. To do so, we introduce the new notion of synteny pack , which is a representation of local hypothetical intermediate ancestral genomes. We discuss a number of examples on yeast genomes to illustrate the importance of such a definition.

Description: We present DES13S2cmm, the first spectroscopically-confirmed superluminous supernova (SLSN) from the Dark Energy Survey (DES). We briefly discuss the data and search algorithm used to find this event in the first year of DES operations, and outline the spectroscopic data obtained from the European Southern Observatory (ESO) Very Large Telescope to confirm its redshift ( z  = 0.663 ± 0.001 based on the host-galaxy emission lines) and likely spectral type (Type I). Using this redshift, we find $M^{\rm peak}_U=-21.05^{+0.10}_{-0.09}$ for the peak, rest-frame U -band absolute magnitude, and find DES13S2cmm to be located in a faint, low-metallicity (sub-solar), low stellar-mass host galaxy (log ( M /M ) = 9.3 ± 0.3), consistent with what is seen for other SLSNe-I. We compare the bolometric light curve of DES13S2cmm to 14 similarly well-observed SLSNe-I in the literature and find that it possesses one of the slowest declining tails (beyond +30 d rest-frame past peak), and is the faintest at peak. Moreover, we find the bolometric light curves of all SLSNe-I studied herein possess a dispersion of only 0.2–0.3 mag between +25 and +30 d after peak (rest frame) depending on redshift range studied; this could be important for ‘standardizing’ such supernovae, as is done with the more common Type Ia. We fit the bolometric light curve of DES13S2cmm with two competing models for SLSNe-I – the radioactive decay of 56 Ni, and a magnetar – and find that while the magnetar is formally a better fit, neither model provides a compelling match to the data. Although we are unable to conclusively differentiate between these two physical models for this particular SLSN-I, further DES observations of more SLSNe-I should break this degeneracy, especially if the light curves of SLSNe-I can be observed beyond 100 d in the rest frame of the supernova.

Description: We report on the growth and structural and morphologic characterization of stacked layers of self-assembled GeSn dots grown on Si (100) substrates by molecular beam epitaxy at low substrate temperature T = 350 °C. Samples consist of layers (from 1 up to 10) of Ge 0.96 Sn 0.04 self-assembled dots separated by Si spacer layers, 10 nm thick. Their structural analysis was performed based on transmission electron microscopy, atomic force microscopy, and Raman scattering. We found that up to 4 stacks of dots could be grown with good dot layer homogeneity, making the GeSn dots interesting candidates for optoelectronic device applications.

Description: Metallic nanoantennas can be used to enhance the efficiency of optical device operation by re-distributing electromagnetic energy. Here, we investigate the effect of a random distribution of disc-shaped Al nanoantennas of different diameters deposited on Ge-on-Si PIN-photodetectors on the wavelength-dependent responsivity. We compare our experimental results to simulations and find that the largest responsivity enhancement is obtained for wavelengths that correspond to energies at or below the bandgap energy of Ge. We argue that this is the result of antenna-mediated scattering of light into waveguide modes within the Ge-on-Si PIN-photodetectors, which is effectively influenced by nanoantenna size, and we discuss a possible application of the concept for integrated biosensing.

Description: Plectin, a versatile 500-kDa cytolinker protein, is essential for muscle fiber integrity and function. The most common disease caused by mutations in the human plectin gene, epidermolysis bullosa simplex with muscular dystrophy (EBS-MD), is characterized by severe skin blistering and progressive muscular dystrophy. Besides displaying pathological desmin-positive protein aggregates and degenerative changes in the myofibrillar apparatus, skeletal muscle specimens of EBS-MD patients and plectin-deficient mice are characterized by massive mitochondrial alterations. In this study, we demonstrate that structural and functional alterations of mitochondria are a primary aftermath of plectin deficiency in muscle, contributing to myofiber degeneration. We found that in skeletal muscle of conditional plectin knockout mice (MCK-Cre/cKO), mitochondrial content was reduced, and mitochondria were aggregated in sarcoplasmic and subsarcolemmal regions and were no longer associated with Z-disks. Additionally, decreased mitochondrial citrate synthase activity, respiratory function and altered adenosine diphosphate kinetics were characteristic of plectin-deficient muscles. To analyze a mechanistic link between plectin deficiency and mitochondrial alterations, we comparatively assessed mitochondrial morphology and function in whole muscle and teased muscle fibers of wild-type, MCK-Cre/cKO and plectin isoform-specific knockout mice that were lacking just one isoform (either P1b or P1d) while expressing all others. Monitoring morphological alterations of mitochondria, an isoform P1b-specific phenotype affecting the mitochondrial fusion–fission machinery and manifesting with upregulated mitochondrial fusion-associated protein mitofusin-2 could be identified. Our results show that the depletion of distinct plectin isoforms affects mitochondrial network organization and function in different ways.

Description: Introduction As the accurate diagnosis and treatment of gestational diabetes mellitus (GDM) is of increasing importance; new diagnostic approaches for the assessment of GDM in early pregnancy were recently suggested. We evaluate the diagnostic power of an ‘early’ oral glucose tolerance test (OGTT) 75 g and glycosylated fibronectin (glyFn) for GDM screening in a normal cohort. Methods and analysis In a prospective cohort study, 748 singleton pregnancies are recruited in 6 centres in Switzerland, Austria and Germany. Women are screened for pre-existing diabetes mellitus and GDM by an ‘early’ OGTT 75 g and/or the new biomarker, glyFn, at 12–15 weeks of gestation. Different screening strategies are compared to evaluate the impact on detection of GDM by an OGTT 75 g at 24–28 weeks of gestation as recommended by the International Association of Diabetes and Pregnancy Study Groups (IADPSG). A new screening algorithm is created by using multivariable risk estimation based on ‘early’ OGTT 75 g and/or glyFn results, incorporating maternal risk factors. Recruitment began in May 2014. Ethics and dissemination This study received ethical approval from the ethics committees in Basel, Zurich, Vienna, Salzburg and Freiburg. It was registered under http://www.ClinicalTrials.gov (NCT02035059) on 12 January 2014. Data will be presented at international conferences and published in peer-reviewed journals. Trial registration number NCT02035059.

Description: Objective Diarrhoea is a significant contributer to morbidity and is among the leading causes of death of children living in poverty. As such, the incidence, duration and severity of diarrhoeal episodes in the household are often key variables of interest in a variety of community-based studies. However, there currently exists no means of defining diarrhoeal severity that are (A) specifically designed and adapted for community-based studies, (B) associated with poorer child outcomes and (C) agreed on by the majority of researchers. Clinical severity scores do exist and are used in healthcare settings, but these tend to focus on relatively moderate-to-severe dehydrating and dysenteric disease, require trained observation of the child and, given the variability of access and utilisation of healthcare, fail to sufficiently describe the spectrum of disease in the community setting. Design Longitudinal cohort study. Setting Santa Clara de Nanay, a rural community in the Northern Peruvian Amazon. Participants 442 infants and children 0–72 months of age. Main outcome measures Change in weight over 1-month intervals and change in length/height over 9-month intervals. Results Diarrhoeal episodes with symptoms of fever, anorexia, vomiting, greater number of liquid stools per day and greater number of total stools per day were associated with poorer weight gain compared with episodes without these symptoms. An instrument to measure the severity was constructed based on the duration of these symptoms over the course of a diarrhoeal episode. Conclusions In order to address limitations of existing diarrhoeal severity scores in the context of community-based studies, we propose an instrument comprised of diarrhoea-associated symptoms easily measured by community health workers and based on the association of these symptoms with poorer child growth. This instrument can be used to test the impact of interventions on the burden of diarrhoeal disease.

Description: The origin of the deep subgap states in amorphous indium gallium zinc oxide (a-IGZO), whether intrinsic to the amorphous structure or not, has serious implications for the development of p -type transparent amorphous oxide semiconductors. We report that the deep subgap feature in a-IGZO originates from local variations in the oxygen coordination and not from oxygen vacancies. This is shown by the positive correlation between oxygen composition and subgap intensity as observed with X-ray photoelectron spectroscopy. We also demonstrate that the subgap feature is not intrinsic to the amorphous phase because the deep subgap feature can be removed by low-temperature annealing in a reducing environment. Atomistic calculations of a-IGZO reveal that the subgap state originates from certain oxygen environments associated with the disorder. Specifically, the subgap states originate from oxygen environments with a lower coordination number and/or a larger metal-oxygen separation.