Extreme exercise enhances chromogranin A levels correlating with stress levels but not with cardiac burden

OBJECTIVE: Stress and heart failure are associated with increased systemic levels of chromogranin A (CGA). Here we analyzed the effects of marathon running on systemic CGA levels and the association with cardiac burden and stress. METHODS: We recruited 47 lean and obese runners for a 10week training program aiming at running a marathon. Heart rates, individual fitness and marathon finishing times were monitored. CGA, proBNP and troponin T levels were analyzed by ELISA. RESULTS: We found a significant increase of CGA (+51%; p<0.01) in lean runners after marathon. The obese group showed the highest troponin T (0.22ng/ml; p<0.01) and proBNP (176.6ng/ml; p<0.01) levels. There were no correlations between proBNP, troponin T and CGA. An inverse correlation (r=-0.45; p<0.01) was found between CGA and finishing times. CONCLUSION: Marathon running is associated with increased CGA levels. However, this does not seem to reflect cardiac burden but rather marathon induced stress

Exercise-induced alterations of retinal vessel diameters and cardiovascular risk reduction in obesity

BACKGROUND: The retinal microcirculation is affected early in the process of atherosclerosis and retinal vessel caliber is an emerging cardiovascular risk factor. Obesity is associated with vascular dysfunction. Here, we investigate the effect of regular exercise on retinal vessel diameters in lean and obese runners. We analyze a possible link to alterations of the nitric oxide (NO)-asymmetric dimethylarginine (ADMA) pathway. METHODS: Retinal vessel diameters were assessed by means of a static vessel analyzer (SVA-T) in 15 obese athletes (OA), 14 lean amateur athletes (AA) and 17 lean elite athletes (EA) following a 10 week training program. ADMA serum levels were detected by ELISA and dimethylarginine dimethylaminohydrolase (DDAH) -1/-2 mRNA-expression in peripheral mononuclear cells (PBMC) was analyzed by real time PCR. RESULTS: At baseline, the mean (±SD) arteriolar to venular diameter ratio (AVR) was impaired in obese (OA: 0.81±0.05) compared to lean subjects (AA: 0.87±0.07; EA: 0.94±0.05). The individual fitness levels correlated with AVR (rho=+0.66; P<0.001) and the training program improved AVR in all groups (P<0.001), normalising AVR in the obese (OA: 0.86±0.1). A training-induced arteriolar dilatation was found in OA (P=0.01), which was accompanied by a significant decrease of ADMA levels (0.56±0.12-0.46±0.12 μmoll(-1); P<0.028). DDAH-1 mRNA levels in PBMC increased in all groups (P<0.01). CONCLUSIONS: Cardiovascular fitness and body composition affect retinal vessel diameters. Regular exercise reverses the subclinical impairment of the retinal microvasculature in obesity by inducing retinal arteriolar dilatation. The NO/ADMA pathway may play a key role in the training-induced improvement of microvascular function, which has the potential to counteract progression of small vessel disease

NUDT2 initiates viral RNA degradation by removal of 5′-phosphates

AbstractWhile viral replication processes are largely understood, comparably little is known on cellular mechanisms degrading viral RNA. Some viral RNAs bear a 5′-triphosphate (PPP-) group that impairs degradation by the canonical 5′-3′ degradation pathway. Here we show that the Nudix hydrolase 2 (NUDT2) trims viral PPP-RNA into monophosphorylated (P)-RNA, which serves as a substrate for the 5′-3′ exonuclease XRN1. NUDT2 removes 5′-phosphates from PPP-RNA in an RNA sequence- and overhang-independent manner and its ablation in cells increases growth of PPP-RNA viruses, suggesting an involvement in antiviral immunity. NUDT2 is highly homologous to bacterial RNA pyrophosphatase H (RppH), a protein involved in the metabolism of bacterial mRNA, which is 5′-tri- or diphosphorylated. Our results show a conserved function between bacterial RppH and mammalian NUDT2, indicating that the function may have adapted from a protein responsible for RNA turnover in bacteria into a protein involved in the immune defense in mammals.</jats:p

NUDT2 initiates viral RNA degradation by removal of 5'-phosphates.

While viral replication processes are largely understood, comparably little is known on cellular mechanisms degrading viral RNA. Some viral RNAs bear a 5'-triphosphate (PPP-) group that impairs degradation by the canonical 5'-3' degradation pathway. Here we show that the Nudix hydrolase 2 (NUDT2) trims viral PPP-RNA into monophosphorylated (P)-RNA, which serves as a substrate for the 5'-3' exonuclease XRN1. NUDT2 removes 5'-phosphates from PPP-RNA in an RNA sequence- and overhang-independent manner and its ablation in cells increases growth of PPP-RNA viruses, suggesting an involvement in antiviral immunity. NUDT2 is highly homologous to bacterial RNA pyrophosphatase H (RppH), a protein involved in the metabolism of bacterial mRNA, which is 5'-tri- or diphosphorylated. Our results show a conserved function between bacterial RppH and mammalian NUDT2, indicating that the function may have adapted from a protein responsible for RNA turnover in bacteria into a protein involved in the immune defense in mammals

Verification strategy for the MICADO cold optics

MICADO is a first light instrument for the ELT: it will provide diffraction limited imaging, in standard, astrometric, and coronagraphic modes, and long-slit spectroscopy at near-infrared wavelengths, covering a 19” FoV with a 1.5 mas/px sampling, or a 50.5” FoV with a 4.5 mas/px sampling. The challenging scientific goals in terms of sensitivity, resolution, astrometric precision, and contrast at small inner working angles have been translated in technical requirements and flowed down to the sub-systems. Each sub-system shall undergo a verification campaign and demonstrate the required performance before the integration at higher system level. In this paper, we describe the planned strategy for the optomechanical characterization of the Cold Optics, i.e. the three opto-mechanical sub-systems, which represent the backbone of the MICADO Cryostat. Given the demanding requirements applied to the performance of the Cold Optics, a proper support equipment for the correct execution of the tests has been designed. Tests will be performed in warm conditions and the most significant will be repeated in a cold environment, representative of the MICADO cryostat

Multi-omics characterization of the monkeypox virus infection

Multiple omics analyzes of Vaccinia virus (VACV) infection have defined molecular characteristics of poxvirus biology. However, little is known about the monkeypox (mpox) virus (MPXV) in humans, which has a different disease manifestation despite its high sequence similarity to VACV. Here, we perform an in-depth multi-omics analysis of the transcriptome, proteome, and phosphoproteome signatures of MPXV-infected primary human fibroblasts to gain insights into the virus-host interplay. In addition to expected perturbations of immune-related pathways, we uncover regulation of the HIPPO and TGF-beta pathways. We identify dynamic phosphorylation of both host and viral proteins, which suggests that MAPKs are key regulators of differential phosphorylation in MPXV-infected cells. Among the viral proteins, we find dynamic phosphorylation of H5 that influenced the binding of H5 to dsDNA. Our extensive dataset highlights signaling events and hotspots perturbed by MPXV, extending the current knowledge on poxviruses. We use integrated pathway analysis and drug-target prediction approaches to identify potential drug targets that affect virus growth. Functionally, we exemplify the utility of this approach by identifying inhibitors of MTOR, CHUK/IKBKB, and splicing factor kinases with potent antiviral efficacy against MPXV and VACV. Multi-omics profiling of monkeypox virus infected human primary cells was used to characterize the infection process and to prioritize potential antiviral drug targets

The MICADO first light imager for the ELT: Overview of the near infrared mosaic detector subsystem

MICADO, a Multi-AO Imaging Camera for Deep Observations, is a first light imager for the European Large Telescope (ELT). It is being designed and built by a consortium of partners from 6 different countries across Europe and led by the Max Planck Institute for Extraterrestrial Physics (MPE) in Garching. The European Southern Observatory (ESO) is responsible for delivering the near infrared detector subsystem to the instrument. This subsystem includes nine Hawaii-4RG-15 (H4RG-15) near infrared detectors (2.5 mu m cut-off) mounted in a compact 3x3 mosaic at the heart of the instrument. They will operate at a nominal temperature of 82K using an array of cryogenic preamplifiers located at the back of the focal plane plate, close to the detectors. This paper presents an overview of this detector subsystem, including the measured performance of two of the H4RG-15 science detectors already characterised in a custom-built test facility at ESO. Special readout modes have been developed for the instrument and for AO corrections to one of the ELT mirrors and these are described. The design of the focal plane, its thermal analysis and the focal plane flatness measurement system being setup at ESO is also presented. This paper also provides a brief description of the new detector controllers (NGCII) being developed at ESO for all the ELT and future VLT (Very Large Telescope) science detector systems and presents the specific controller configuration which must be implemented for the MICADO detectors