Methylthioadenosine (MTA) inhibits melanoma cell proliferation and in vivo tumor growth

BACKGROUND: Melanoma is the most deadly form of skin cancer without effective treatment. Methylthioadenosine (MTA) is a naturally occurring nucleoside with differential effects on normal and transformed cells. MTA has been widely demonstrated to promote anti-proliferative and pro-apoptotic responses in different cell types. In this study we have assessed the therapeutic potential of MTA in melanoma treatment. METHODS: To investigate the therapeutic potential of MTA we performed in vitro proliferation and viability assays using six different mouse and human melanoma cell lines wild type for RAS and BRAF or harboring different mutations in RAS pathway. We also have tested its therapeutic capabilities in vivo in a xenograft mouse melanoma model and using variety of molecular techniques and tissue culture we investigated its anti-proliferative and pro-apoptotic properties. RESULTS: In vitro experiments showed that MTA treatment inhibited melanoma cell proliferation and viability in a dose dependent manner, where BRAF mutant melanoma cell lines appear to be more sensitive. Importantly, MTA was effective inhibiting in vivo tumor growth. The molecular analysis of tumor samples and in vitro experiments indicated that MTA induces cytostatic rather than pro-apoptotic effects inhibiting the phosphorylation of Akt and S6 ribosomal protein and inducing the down-regulation of cyclin D1. CONCLUSIONS: MTA inhibits melanoma cell proliferation and in vivo tumor growth particularly in BRAF mutant melanoma cells. These data reveal a naturally occurring drug potentially useful for melanoma treatment

HRFlexToT: A High Dynamic Range ASIC for Time-of-Flight Positron Emission Tomography

Time-of-Flight positron emission tomography scanners demand fast and efficient photo sensors and scintillators coupled to fast readout electronics. This article presents the high resolution flexible Time-over-Threshold (HRFlexToT), a 16-channel application-specific-integrated circuit for silicon photomultipliers (SiPM) anode readout manufactured using XFAB 0.18- \mu \text{m} CMOS technology. The main features of the HRFlexToT are a linear Time-over-Threshold with an extended dynamic range (10 bits) for energy measurement, low power consumption (≈ 3.5 mW/ch), and an excellent timing response. The experimental measurements show an energy linearity error of ≈ 3% and an energy resolution of about 12% at 511 keV. Single-photon time resolution measurements performed using an Fondazione Bruno Kessler (FBK) SiPM NUV-HD ( 4 \times 4 mm2 pixel, 40- \mu \text{m} cell) and a Hamamatsu SiPM S13360-3050CS are around 142 and 167 ps full width at half maximum (FWHM), respectively. Coincidence time resolution (CTR) measurements with small cross-section pixelated crystals (LSO:Ce,Ca 0.4%, 2 \times 2 \times 5 mm3) coupled to the same Hamamatsu S13360-3050CS and FBK NUV-HD sensors yield a CTR of 117 ps and 119 ps, respectively. Measurements performed with a large cross-section monolithic crystal (LFS crystal measuring 25 \times 25 \times 20 mm3) and a Hamamatsu SiPM array S13361-6050NE-04 show a CTR of 324 ps FWHM after time-walk and time-skew correction

Dextran sulfate from Leuconostoc mesenteroides B512F exerts potent antiviral activity against SARS-CoV-2 in vitro and in vivo

The emergent human coronavirus SARS-CoV-2 and its resistance to current drugs makes the need for new potent treatments for COVID-19 patients strongly necessary. Dextran sulfate (DS) polysaccharides have long demonstrated antiviral activity against different enveloped viruses in vitro. However, their poor bioavailability has led to their abandonment as antiviral candidates. Here, we report for the first time the broad-spectrum antiviral activity of a DS-based extrapolymeric substance produced by the lactic acid bacterium Leuconostoc mesenteroides B512F. Time of addition assays with SARS-CoV-2 pseudoviruses in in vitro models confirm the inhibitory activity of DSs in the early stages of viral infection (viral entry). In addition, this exopolysaccharide substance also reports broad-spectrum antiviral activity against several enveloped viruses such as SARS-CoV-2, HCoV229E, HSV-1, in in vitro models and in human lung tissue. The toxicity and antiviral capacity of DS from L. mesenteroides was tested in vivo in mouse models which are susceptible to SARS-CoV-2 infection. The described DS, administered by inhalation, a new route of administration for these types of polymers, shows strong inhibition of SARS-CoV-2 infection in vivo, significantly reducing animal mortality and morbidity at non-toxic doses. Therefore, we suggest that it may be considered as a potential candidate for antiviral therapy against SARS-CoV-2Financial support for the study was provided by the REACT-EU 2021 grant from Comunidad de Madrid to the Project COVTRAVI19-CM, Plataformas y modelos preclínicos para el abordaje multidisciplinar en COVID-19 y en respuesta a futuras pandemia

Headache : A striking prodromal and persistent symptom, predictive of COVID-19 clinical evolution

To define headache characteristics and evolution in relation to COVID-19 and its inflammatory response. This is a prospective study, comparing clinical data and inflammatory biomarkers of COVID-19 patients with and without headache, recruited at the Emergency Room. We compared baseline with 6-week follow-up to evaluate disease evolution. Of 130 patients, 74.6% (97/130) had headache. In all, 24.7% (24/97) of patients had severe pain with migraine-like features. Patients with headache had more anosmia/ageusia (54.6% vs. 18.2%; p < 0.0001). Clinical duration of COVID-19 was shorter in the headache group (23.9 ± 11.6 vs. 31.2 ± 12.0 days; p = 0.028). In the headache group, IL-6 levels were lower at the ER (22.9 (57.5) vs. 57.0 (78.6) pg/mL; p = 0.036) and more stable during hospitalisation. After 6 weeks, of 74 followed-up patients with headache, 37.8% (28/74) had ongoing headache. Of these, 50% (14/28) had no previous headache history. Headache was the prodromal symptom of COVID-19 in 21.4% (6/28) of patients with persistent headache (p = 0.010). Headache associated with COVID-19 is a frequent symptom, predictive of a shorter COVID-19 clinical course. Disabling headache can persist after COVID-19 resolution. Pathophysiologically, its migraine-like features may reflect an activation of the trigeminovascular system by inflammation or direct involvement of SARS-CoV-2, a hypothesis supported by concomitant anosmia

Espècie porcina: manual lesional de suport per al dictamen de carns fresques

Escorxador; Porcí; Carn; Control oficialMatadero; Porcino; Carne; Control oficialSlaughterhouse; Swine; Meat; Official controlLa inspecció post mortem que efectua el col·lectiu de veterinaris oficials d’escorxador és una part important dels controls oficials relatius a la carn fresca i, com a tal, és un dels elements que condiciona que es dictamini com a apta o no per al consum humà i que s’hagin de notificar les malalties de declaració obligatòria. Els escorxadors són entorns òptims per observar i registrar les particularitats de la variada patologia animal que s’hi presenta. Aquesta informació, si és compartida, pot esdevenir una eina molt útil i interessant per al col·lectiu de professionals. En conseqüència, es va crear una comunitat de pràctica (CoP) per a l’espècie porcina. L’autoria d’aquest manual és de veterinaris oficials d’escorxador de la Generalitat de Catalunya. El contingut s’ha volgut transmetre per mitjà de fitxes que contenen informació científica, tècnica i legal per a cada una de les malalties i lesions que s’hi descriuen. Alhora, les fitxes s’il·lustren amb imatges obtingudes als diferents escorxadors de Catalunya. Així, doncs, sabem que els manuals es presenten encara incomplets i, per això, es preveu poder completar-los en futures edicions.La inspección post mortem que efectúa el colectivo de veterinarios oficiales de matadero es una parte importante de los controles oficiales relativos a la carne fresca y, como tal, es uno de los elementos que condiciona que se dictamine como apta o no para el consumo humano y que deban notificarse las enfermedades de declaración obligatoria. Los mataderos son entornos óptimos para observar y registrar las particularidades de la variada patología animal que se presenta. Esta información, si es compartida, puede convertirse en una herramienta muy útil e interesante para el colectivo de profesionales. En consecuencia, se creó una comunidad de práctica (CoP) para la especie porcina. La autoría de este manual es de veterinarios oficiales de matadero de la Generalitat de Catalunya. El contenido se ha querido transmitir por medio de fichas que contienen información científica, técnica y legal para cada una de las enfermedades y lesiones que se describen. Asimismo, las fichas se ilustran con imágenes obtenidas en los diferentes mataderos de Cataluña. Así pues, sabemos que los manuales se presentan todavía incompletos y, por eso, se prevé poder completarlos en futuras ediciones.The post-mortem inspection carried out by the group of official slaughterhouse veterinarians is an important part of the official controls related to fresh meat and, as such, is one of the elements that determines whether or not it is deemed fit for human consumption and Notifiable diseases must be notified. Slaughterhouses are optimal environments to observe and record the particularities of the varied animal pathology that occurs. This information, if shared, can become a very useful and interesting tool for the group of professionals. Accordingly, a community of practice (CoP) for swine was created. The authorship of this manual is official slaughterhouse veterinarians of the Generalitat de Catalunya. The content has been conveyed through sheets containing scientific, technical and legal information for each of the diseases and injuries described. Likewise, the sheets are illustrated with images obtained in the different slaughterhouses in Catalonia. Thus, we know that the manuals are still incomplete and, therefore, it is expected to be able to complete them in future editions

On the causes of economic growth in Europe: why did agricultural labour productivity not converge between 1950 and 2005?

The objective of this study is to make a further contribution to the debate on the causes of economic growth in the European Continent. It explains why agricultural labour productivity differences did not converge between 1950 and 2005 in Europe. We propose an econometric model, one combining both proximate and fundamental causes of economic growth. The results show that the continuous exit of labour power from the sector, coupled with the increased use of productive factors originating in other sectors of the economy, caused the efficiency of agricultural workers to rise. However, we offer a complete explanation of the role played by institutions and geographical factors. Thus, we detect a direct and inverse relation between membership of the EU and the Communist bloc and the productivity of agricultural labour. In addition, strong support for agriculture affected productivity negatively

Global assessment of marine plastic exposure risk for oceanic birds

Plastic pollution is distributed patchily around the world’s oceans. Likewise, marine organisms that are vulnerable to plastic ingestion or entanglement have uneven distributions. Understanding where wildlife encounters plastic is crucial for targeting research and mitigation. Oceanic seabirds, particularly petrels, frequently ingest plastic, are highly threatened, and cover vast distances during foraging and migration. However, the spatial overlap between petrels and plastics is poorly understood. Here we combine marine plastic density estimates with individual movement data for 7137 birds of 77 petrel species to estimate relative exposure risk. We identify high exposure risk areas in the Mediterranean and Black seas, and the northeast Pacific, northwest Pacific, South Atlantic and southwest Indian oceans. Plastic exposure risk varies greatly among species and populations, and between breeding and non-breeding seasons. Exposure risk is disproportionately high for Threatened species. Outside the Mediterranean and Black seas, exposure risk is highest in the high seas and Exclusive Economic Zones (EEZs) of the USA, Japan, and the UK. Birds generally had higher plastic exposure risk outside the EEZ of the country where they breed. We identify conservation and research priorities, and highlight that international collaboration is key to addressing the impacts of marine plastic on wide-ranging species

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Global assessment of marine plastic exposure risk for oceanic birds

Plastic pollution is distributed patchily around the world's oceans. Likewise, marine organisms that are vulnerable to plastic ingestion or entanglement have uneven distributions. Understanding where wildlife encounters plastic is crucial for targeting research and mitigation. Oceanic seabirds, particularly petrels, frequently ingest plastic, are highly threatened, and cover vast distances during foraging and migration. However, the spatial overlap between petrels and plastics is poorly understood. Here we combine marine plastic density estimates with individual movement data for 7137 birds of 77 petrel species to estimate relative exposure risk. We identify high exposure risk areas in the Mediterranean and Black seas, and the northeast Pacific, northwest Pacific, South Atlantic and southwest Indian oceans. Plastic exposure risk varies greatly among species and populations, and between breeding and non-breeding seasons. Exposure risk is disproportionately high for Threatened species. Outside the Mediterranean and Black seas, exposure risk is highest in the high seas and Exclusive Economic Zones (EEZs) of the USA, Japan, and the UK. Birds generally had higher plastic exposure risk outside the EEZ of the country where they breed. We identify conservation and research priorities, and highlight that international collaboration is key to addressing the impacts of marine plastic on wide-ranging species.B.L.C., C.H., and A.M. were funded by the Cambridge Conservation Initiative’s Collaborative Fund sponsored by the Prince Albert II of Monaco Foundation. E.J.P. was supported by the Natural Environment Research Council C-CLEAR doctoral training programme (Grant no. NE/S007164/1). We are grateful to all those who assisted with the collection and curation of tracking data. Further details are provided in the Supplementary Acknowledgements. Any use of trade, firm, or product names is for descriptive purposes only and does not imply endorsement by the U.S. Government.Peer reviewe

Global assessment of marine plastic exposure risk for oceanic birds

Plastic pollution is distributed patchily around the world’s oceans. Likewise, marine organisms that are vulnerable to plastic ingestion or entanglement have uneven distributions. Understanding where wildlife encounters plastic is crucial for targeting research and mitigation. Oceanic seabirds, particularly petrels, frequently ingest plastic, are highly threatened, and cover vast distances during foraging and migration. However, the spatial overlap between petrels and plastics is poorly understood. Here we combine marine plastic density estimates with individual movement data for 7137 birds of 77 petrel species to estimate relative exposure risk. We identify high exposure risk areas in the Mediterranean and Black seas, and the northeast Pacific, northwest Pacific, South Atlantic and southwest Indian oceans. Plastic exposure risk varies greatly among species and populations, and between breeding and non-breeding seasons. Exposure risk is disproportionately high for Threatened species. Outside the Mediterranean and Black seas, exposure risk is highest in the high seas and Exclusive Economic Zones (EEZs) of the USA, Japan, and the UK. Birds generally had higher plastic exposure risk outside the EEZ of the country where they breed. We identify conservation and research priorities, and highlight that international collaboration is key to addressing the impacts of marine plastic on wide-ranging species