First direct observation of a nearly ideal graphene band structure

Angle-resolved photoemission and X-ray diffraction experiments show that multilayer epitaxial graphene grown on the SiC(000-1) surface is a new form of carbon that is composed of effectively isolated graphene sheets. The unique rotational stacking of these films cause adjacent graphene layers to electronically decouple leading to a set of nearly independent linearly dispersing bands (Dirac cones) at the graphene K-point. Each cone corresponds to an individual macro-scale graphene sheet in a multilayer stack where AB-stacked sheets can be considered as low density faults.Comment: 5 pages, 4 figure

Activation of Serine One-Carbon Metabolism by Calcineurin A beta 1 Reduces Myocardial Hypertrophy and Improves Ventricular Function

Background In response to pressure overload, the heart develops ventricular hypertrophy that progressively decompensates and leads to heart failure. This pathological hypertrophy is mediated, among others, by the phosphatase calcineurin and is characterized by metabolic changes that impair energy production by mitochondria. Objectives The authors aimed to determine the role of the calcineurin splicing variant CnAβ1 in the context of cardiac hypertrophy and its mechanism of action. Methods Transgenic mice overexpressing CnAβ1 specifically in cardiomyocytes and mice lacking the unique C-terminal domain in CnAβ1 (CnAβ1Δi12 mice) were used. Pressure overload hypertrophy was induced by transaortic constriction. Cardiac function was measured by echocardiography. Mice were characterized using various molecular analyses. Results In contrast to other calcineurin isoforms, the authors show here that cardiac-specific overexpression of CnAβ1 in transgenic mice reduces cardiac hypertrophy and improves cardiac function. This effect is mediated by activation of serine and one-carbon metabolism, and the production of antioxidant mediators that prevent mitochondrial protein oxidation and preserve ATP production. The induction of enzymes involved in this metabolic pathway by CnAβ1 is dependent on mTOR activity. Inhibition of serine and one-carbon metabolism blocks the beneficial effects of CnAβ1. CnAβ1Δi12 mice show increased cardiac hypertrophy and declined contractility. Conclusions The metabolic reprogramming induced by CnAβ1 redefines the role of calcineurin in the heart and shows for the first time that activation of the serine and one-carbon pathway has beneficial effects on cardiac hypertrophy and function, paving the way for new therapeutic approaches

Transcriptome and proteome mapping in the sheep atria reveal molecular featurets of atrial fibrillation progression.

Atrial fibrillation (AF) is a progressive cardiac arrhythmia that increases the risk of hospitalization and adverse cardiovascular events. There is a clear demand for more inclusive and large-scale approaches to understand the molecular drivers responsible for AF, as well as the fundamental mechanisms governing the transition from paroxysmal to persistent and permanent forms. In this study, we aimed to create a molecular map of AF and find the distinct molecular programmes underlying cell type-specific atrial remodelling and AF progression. We used a sheep model of long-standing, tachypacing-induced AF, sampled right and left atrial tissue, and isolated cardiomyocytes (CMs) from control, intermediate (transition), and late time points during AF progression, and performed transcriptomic and proteome profiling. We have merged all these layers of information into a meaningful three-component space in which we explored the genes and proteins detected and their common patterns of expression. Our data-driven analysis points at extracellular matrix remodelling, inflammation, ion channel, myofibril structure, mitochondrial complexes, chromatin remodelling, and genes related to neural function, as well as critical regulators of cell proliferation as hallmarks of AF progression. Most important, we prove that these changes occur at early transitional stages of the disease, but not at later stages, and that the left atrium undergoes significantly more profound changes than the right atrium in its expression programme. The pattern of dynamic changes in gene and protein expression replicate the electrical and structural remodelling demonstrated previously in the sheep and in humans, and uncover novel mechanisms potentially relevant for disease treatment. Transcriptomic and proteomic analysis of AF progression in a large animal model shows that significant changes occur at early stages, and that among others involve previously undescribed increase in mitochondria, changes to the chromatin of atrial CMs, and genes related to neural function and cell proliferation.This work was supported by the Spanish government (BFU2017-84914-P to M.M.; FPI Fellowship to A.A.-F.; FPU Fellowship to R.R.), and in part by grants to J.J. from the National Heart, Lung and Blood Institute (R01 grant HL122352 NIH/NHLBI), the Leducq Foundation (Transatlantic Network of Excellence Program on Structural Alterations in the Myocardium and the Substrate for Cardiac Fibrillation), and the University of Michigan Health System–Peking University Health Science Center Joint Institute for Translational and Clinical Research (UMHS-PUHSC; project: Molecular Mechanisms of Fibrosis and the Progression from Paroxysmal to Persistent Atrial Fibrillation). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S

Cosmic Ray Mass Measurements with LOFAR

In the dense core of LOFAR individual air showers are detected by hundreds of dipole antennas simultaneously. We reconstruct Xmax by using a hybrid technique that combines a two-dimensional fit of the radio profile to CoREAS simulations and a one-dimensional fit of the particle density distribution. For high-quality detections, the statistical uncertainty on Xmax is smaller than 20 g/cm2. We present results of cosmic-ray mass analysis in the energy regime of 1017 - 1017.5 eV. This range is of particular interest as it may harbor the transition from a Galactic to an extragalactic origin of cosmic rays

TEC, Trigger and Check, preparing LOFAR for Lunar observations

One of the main ways to use radio to detect Ultra High Energy Neutrinos and Cosmic Rays is the Lunar Askaryan technique, that uses the Moon as a target and searches for nanosecond pulses with large radio telescopes. To use low frequency aperture arrays, such as LOFAR and the SKA, pose new challenges and possibilities in detection techniques of short radio pulses and to measure the Total Electron Content (TEC). As a prepatory work, we have used other measurements that use similar techniques, or that can answer a specific question, with the LOFAR radio telescope. This contribution reports on our work on triggering on short radio signals, post-event imaging of radio signals from buffered data and methods to determine the TEC-value

Towards real-time identification of cosmic rays with LOw-Frequency ARray radio antennas

Contains fulltext : 173576.pdf (publisher's version ) (Open Access

COX7A2L genetic variants determine cardiorespiratory fitness in mice and human

Benegiamo et al. identify genetic variants of the mitochondrial supercomplex assembly factor COX7A2L in the skeletal muscle of mice and humans that promote cardiorespiratory fitness.Mitochondrial respiratory complexes form superassembled structures called supercomplexes. COX7A2L is a supercomplex-specific assembly factor in mammals, although its implication for supercomplex formation and cellular metabolism remains controversial. Here we identify a role for COX7A2L for mitochondrial supercomplex formation in humans. By using human cis-expression quantitative trait loci data, we highlight genetic variants in the COX7A2L gene that affect its skeletal muscle expression specifically. The most significant cis-expression quantitative trait locus is a 10-bp insertion in the COX7A2L 3 ' untranslated region that increases messenger RNA stability and expression. Human myotubes harboring this insertion have more supercomplexes and increased respiration. Notably, increased COX7A2L expression in the muscle is associated with lower body fat and improved cardiorespiratory fitness in humans. Accordingly, specific reconstitution of Cox7a2l expression in C57BL/6J mice leads to higher maximal oxygen consumption, increased lean mass and increased energy expenditure. Furthermore, Cox7a2l expression in mice is induced specifically in the muscle upon exercise. These findings elucidate the genetic basis of mitochondrial supercomplex formation and function in humans and show that COX7A2L plays an important role in cardiorespiratory fitness, which could have broad therapeutic implications in reducing cardiovascular mortality.Peer reviewe

Urbanization and Altitude Are Associated with Low Kidney Function in Peru.

Background: Kidney health needs to be studied in low- and middle-income countries with populations living at high altitude and undergoing urbanization. We studied whether greater level of urbanization was associated with worse kidney function and higher hemoglobin was associated with worse kidney function at high altitude. Methods: Cross-sectional analysis of population-based studies in Peru including five sites at different altitude above the sea level and urbanization level (in decreasing order of urbanization): Lima (sea level), Arequipa (2335 m), urban Puno (3825 m), Tumbes (sea level), and rural Puno (3825 m). The exposures were urbanization and altitude as per study site, and hemoglobin (g/dL). The outcome was the estimated glomerular filtration rate (eGFR). Results: Four thousand two hundred eight people were studied: mean age was 57.4 years (standard deviation: 12.4) and 51.9% were women. In comparison to rural Puno, eGFR was similar in Lima; in comparison to rural Puno, Arequipa, urban Puno, and Tumbes had worse eGFR, for example, in Arequipa, β = -8.07 (95% confidence interval [CI]: -10.90 to -5.24). Intermediate (β = -8.60; 95% CI: -10.55 to -6.66) and high (β = -11.21; 95% CI: -14.19 to -8.24) altitude were negatively correlated with eGFR when only urban places were analyzed. At high altitude, there was a trend for a negative association between hemoglobin and eGFR: β = -1.09 (95% CI: -2.22 to 0.04). Conclusions: Apparently, higher altitude and level of urbanization, except for one highly urbanized site, were associated with worse kidney function. Our findings suggest that some of the adverse impact of high altitude on kidney function has been balanced by the lower risk conferred by rural environments

Mitochondrial DNA mutations affect calcium handling in differentiated neurons

Mutations in the mitochondrial genome are associated with a wide range of neurological symptoms, but many aspects of the basic neuronal pathology are not understood. One candidate mechanism, given the well-established role of mitochondria in calcium buffering, is a deficit in neuronal calcium homoeostasis. We therefore examined calcium responses in the neurons derived from various ‘cybrid’ embryonic stem cell lines carrying different mitochondrial DNA mutations. Brief (∼50 ms), focal glutamatergic stimuli induced a transient rise in intracellular calcium concentration, which was visualized by bulk loading the cells with the calcium dye, Oregon Green BAPTA-1. Calcium entered the neurons through N-methyl-d-aspartic acid and voltage-gated calcium channels, as has been described in many other neuronal classes. Intriguingly, while mitochondrial mutations did not affect the calcium transient in response to single glutamatergic stimuli, they did alter the responses to repeated stimuli, with each successive calcium transient decaying ever more slowly in mitochondrial mutant cell lines. A train of stimuli thus caused intracellular calcium in these cells to be significantly elevated for many tens of seconds. These results suggest that calcium-handling deficits are likely to contribute to the pathological phenotype seen in patients with mitochondrial DNA mutations