Mechanism of muscle protein degradation in Cancer Cachexia

A protein-mobilising factor of estimated molecular weight 24 KDa (p24) was purified both from the cachexia-inducing MAC 16 tumour and the urine of cachectic cancer patients by a combination of ammonium sulphate precipitation and affinity chromatography using a monoclonal antibody developed against the murine material. Administration of p24 to non tumour-bearing mice caused a decrease in body weight 24 h after the first injection, which was attenuated by prior treatment with the monoclonal antibody. Loss of body weight was accompanied by an accelerated loss of skeletal muscle protein, as determined by the release of tyrosine from this tissue. This was associated with an increased release of PGE2 and both protein degradation and PGE2 release were attenuated by the monoclonal antibody. Loss of protein mass arose from both a decrease in the rate of protein synthesis and an elevation of protein breakdown; the latter due to an activation of the ubiquitin-proteasome proteolytic system. In isolated muscle, p24 was capable of promoting protein breakdown and this was also associated with increased PGE2 levels. Both tyrosine and PGE2 release, were inhibited by PGE2 inhibitors and a specific inhibitor of cPLA2. When added to muscle cells in culture, p24 caused an elevation in the rates of total and myofibrillar protein breakdown and a depression in the rate of protein synthesis which was inhabitable by short-term incubation in insulin, suggesting that p24 may inhibit protein synthesis by causing an arrest in the translational process

Assessment of plasma chitotriosidase activity, CCL18/PARC concentration and NP-C suspicion index in the diagnosis of Niemann-Pick disease type C: A prospective observational study

Background: Niemann-Pick disease type C (NP-C) is a rare, autosomal recessive neurodegenerative disease caused by mutations in either the NPC1 or NPC2 genes. The diagnosis of NP-C remains challenging due to the non-specific, heterogeneous nature of signs/symptoms. This study assessed the utility of plasma chitotriosidase (ChT) and Chemokine (C-C motif) ligand 18 (CCL18)/pulmonary and activation-regulated chemokine (PARC) in conjunction with the NP-C suspicion index (NP-C SI) for guiding confirmatory laboratory testing in patients with suspected NP-C. Methods: In a prospective observational cohort study, incorporating a retrospective determination of NP-C SI scores, two different diagnostic approaches were applied in two separate groups of unrelated patients from 51 Spanish medical centers (n = 118 in both groups). From Jan 2010 to Apr 2012 (Period 1), patients with =2 clinical signs/symptoms of NP-C were considered ''suspected NP-C'' cases, and NPC1/NPC2 sequencing, plasma chitotriosidase (ChT), CCL18/PARC and sphingomyelinase levels were assessed. Based on findings in Period 1, plasma ChT and CCL18/PARC, and NP-C SI prediction scores were determined in a second group of patients between May 2012 and Apr 2014 (Period 2), and NPC1 and NPC2 were sequenced only in those with elevated ChT and/or elevated CCL18/PARC and/or NP-C SI =70. Filipin staining and 7-ketocholesterol (7-KC) measurements were performed in all patients with NP-C gene mutations, where possible. Results: In total across Periods 1 and 2, 10/236 (4%) patients had a confirmed diagnosis o NP-C based on gene sequencing (5/118 4.2%] in each Period): all of these patients had two causal NPC1 mutations. Single mutant NPC1 alleles were detected in 8/236 (3%) patients, overall. Positive filipin staining results comprised three classical and five variant biochemical phenotypes. No NPC2 mutations were detected. All patients with NPC1 mutations had high ChT activity, high CCL18/PARC concentrations and/or NP-C SI scores =70. Plasma 7-KC was higher than control cut-off values in all patients with two NPC1 mutations, and in the majority of patients with single mutations. Family studies identified three further NP-C patients. Conclusion: This approach may be very useful for laboratories that do not have mass spectrometry facilities and therefore, they cannot use other NP-C biomarkers for diagnosis

Global maps of soil temperature.

Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2 m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km <sup>2</sup> resolution for 0-5 and 5-15 cm soil depth. These maps were created by calculating the difference (i.e. offset) between in situ soil temperature measurements, based on time series from over 1200 1-km <sup>2</sup> pixels (summarized from 8519 unique temperature sensors) across all the world's major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean = 3.0 ± 2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6 ± 2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (-0.7 ± 2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications

Registro Español de Trasplante Cardiaco. XXXI Informe Oficial de la Asociación de Insuficiencia Cardiaca de la Sociedad Española de Cardiología

Introducción y objetivos Se presentan las características clínicas y los resultados de los trasplantes cardiacos realizados en España con la actualización correspondiente a 2019. Métodos Se describen las características clínicas y los resultados de los trasplantes cardiacos realizados en 2019, así como las tendencias de estos en el periodo 2010-2018. Resultados En 2019 se realizaron 300 trasplantes (8.794 desde 1984; 2.745 entre 2010 y 2019). Respecto a años previos, los cambios más llamativos son el descenso hasta el 38% de los trasplantes realizados en código urgente, y la consolidación en el cambio de asistencia circulatoria pretrasplante, con la práctica desaparición del balón de contrapulsación (0, 7%), la estabilización del uso del oxigenador extracorpóreo de membrana (9, 6%) y el aumento de los dispositivos de asistencia ventricular (29%). La supervivencia en el trienio 2016-2018 es similar a la del trienio 2013-2015 (p = 0, 34), y ambas mejores que la del trienio 2010-2012 (p = 0, 002 y p = 0, 01 respectivamente). Conclusiones Se mantienen estables tanto la actividad del trasplante cardiaco en España como los resultados en supervivencia en los últimos 2 trienios. Hay una tendencia a realizar menos trasplantes urgentes, la mayoría con dispositivos de asistencia ventricular. Introduction and objectives: The present report describes the clinical characteristics and outcomes of heart transplants in Spain and updates the data to 2019. Methods: We describe the clinical characteristics and outcomes of heart transplants performed in Spain in 2019, as well as trends in this procedure from 2010 to 2018. Results: In 2019, 300 transplants were performed (8794 since 1984; 2745 between 2010 and 2019). Compared with previous years, the most notable findings were the decreasing rate of urgent transplants (38%), and the consolidation of the type of circulatory support prior to transplant, with an almost complete disappearance of counterpulsation balloon (0.7%), stabilization in the use of extracorporeal membrane oxygenation (9.6%), and an increase in the use of ventricular assist devices (29.0%). Survival from 2016 to 2018 was similar to that from 2013 to 2015 (P = .34). Survival in both these periods was better than that from 2010 to 2012 (P = .002 and P = .01, respectively). Conclusions: Heart transplant activity has remained stable during the last few years, as have outcomes (in terms of survival). There has been a trend to a lower rate of urgent transplants and to a higher use of ventricular assist devices prior to transplant

Mechanisms of muscle protein degradation in cancer cachexia

SIGLEAvailable from British Library Document Supply Centre-DSC:DXN015373 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

A tale of two GRB-SNe at a common redshift of z=0.54

none74We present ground-based and Hubble Space Telescope optical observations of the optical transients (OTs) of long-duration Gamma Ray Bursts (GRBs) 060729 and 090618, both at a redshift of z=0.54. For GRB 060729, bumps are seen in the optical light curves (LCs), and the late-time broad-band spectral energy distributions (SEDs) of the OT resemble those of local Type Ic supernovae (SNe). For GRB 090618, the dense sampling of our optical observations has allowed us to detect well-defined bumps in the optical LCs, as well as a change in colour, that are indicative of light coming from a core-collapse SN. The accompanying SNe for both events are individually compared with SN1998bw, a known GRB supernova, and SN1994I, a typical Type Ic supernova without a known GRB counterpart, and in both cases the brightness and temporal evolution more closely resemble SN1998bw. We also exploit our extensive optical and radio data for GRB 090618, as well as the publicly available Swift-XRT data, and discuss the properties of the afterglow at early times. In the context of a simple jet-like model, the afterglow of GRB 090618 is best explained by the presence of a jet-break at t − to > 0.5 d. We then compare the rest-frame, peak V-band absolute magnitudes of all of the GRB and X-Ray Flash (XRF)-associated SNe with a large sample of local Type Ibc SNe, concluding that, when host extinction is considered, the peak magnitudes of the GRB/XRF-SNe cannot be distinguished from the peak magnitudes of non-GRB/XRF SNe.noneZ. Cano; D. Bersier; C. Guidorzi; R. Margutti; K.M Svensson; S. Kobayashi; A. Melandri; K. Wiersema; A. Pozanenko; A.J. van der Horst; G. G. Pooley; A. Fernandez-Soto; A.J. Castro-Tirado; A. de Ugarte Postigo; M. Im; A.P. Kamble; D. Sahu; M. Alexander; Jorge Alonso-Lorite; G. Anupama; J. L. Bibby; M. J. Burgdorf; N. Clay; P.A. Curran; T. A. Fatkhullin; A. S. Fruchter; P. Garnavich; A. Gomboc; J. Gorosabel; J. F. Graham; U. Gurugubelli; J. Haislip; K. Huang; A. Huxor; M. Ibrahimov; Y. Jeon; Y-B. Jeon; K. Ivarsen; D. Kasen; E. Klunko; C. Kouveliotou; A. LaCluyze; A. J. Levan; V. Loznikov; P.A. Mazzali; C. Mottram; C. G. Mundell; P.E. Nugent; M. Nysewander; P. T. OBrien; W. -K. Park; V. Peris; E. Pian; D. Reichart; J. E. Rhoads; E. Rol; V. Rumyantsev; V. Scowcroft; D. Shakhovskoy; E. Small; R. J. Smith; V. V. Sokolov; R.L.C. Starling; I. Steele; R. Strom; N. R. Tanvir; Y. Tsapras; Y. Urata; O. Vaduvescu; A. Volnova; A. Volvach; R. A. M. J. Wijers; S. E. Woosley; D. R. YoungZ., Cano; D., Bersier; Guidorzi, Cristiano; R., Margutti; K. M., Svensson; S., Kobayashi; A., Melandri; K., Wiersema; A., Pozanenko; A. J., van der Horst; G. G., Pooley; A., Fernandez Soto; A. J., Castro Tirado; A., de Ugarte Postigo; M., Im; A. P., Kamble; D., Sahu; M., Alexander; Jorge Alonso, Lorite; G., Anupama; J. L., Bibby; M. J., Burgdorf; N., Clay; P. A., Curran; T. A., Fatkhullin; A. S., Fruchter; P., Garnavich; A., Gomboc; J., Gorosabel; J. F., Graham; U., Gurugubelli; J., Haislip; K., Huang; A., Huxor; M., Ibrahimov; Y., Jeon; Y. B., Jeon; K., Ivarsen; D., Kasen; E., Klunko; C., Kouveliotou; A., Lacluyze; A. J., Levan; V., Loznikov; P. A., Mazzali; C., Mottram; C. G., Mundell; P. E., Nugent; M., Nysewander; P. T., Obrien; W. K., Park; V., Peris; E., Pian; D., Reichart; J. E., Rhoads; E., Rol; V., Rumyantsev; V., Scowcroft; D., Shakhovskoy; E., Small; R. J., Smith; V. V., Sokolov; R. L. C., Starling; I., Steele; R., Strom; N. R., Tanvir; Y., Tsapras; Y., Urata; O., Vaduvescu; A., Volnova; A., Volvach; R. A. M. J., Wijers; S. E., Woosley; D. R., Youn