Efficacy of bortezomib in sarcomas with high levels of MAP17 (PDZK1IP1

Sarcomas are malignant tumors accounting for a high percentage of cancer morbidity and mortality in children and young adults. Surgery and radiation therapy are the accepted treatments for most sarcomas; however, patients with metastatic disease are treated with systemic chemotherapy. Many tumors display marginal levels of chemoresponsiveness, and new treatment approaches are needed. MAP17 is a small non-glycosylated membrane protein overexpressed in carcinomas. The levels of MAP17 could be used as a prognostic marker to predict the response to bortezomib in hematological malignancies and in breast tumors. Therefore, we analyzed the expression of this oncogene in sarcomas and its relationship with clinico-pathological features, as well as tested whether it can be used as a new biomarker to predict the therapeutic response to bortezomib and new therapies for sarcomas. We found that the levels of MAP17 were related to clinical features and poor survival in a cohort of 69 patients with different sarcoma types, not being restricted to any special subtype of tumor. MAP17 expression is associated with poor overall survival (p<0.001) and worse disease-free survival (p=0.002). Cell lines with high levels of MAP17 show a better response to bortezomib in vitro. Furthermore, patient-derived xenografts (PDX) with high levels of MAP17 respond to bortezomib in vivo. Our results showed that this response is due to the lower levels of NFκB and autophagy activation. Therefore, we suggest that MAP17 is a new biomarker to predict the efficacy of bortezomib as a new therapy for sarcomas.España, Consejeria de Ciencia e innovación CTS-6844 and CTS-1848Andalucia, Consejería de Salud PI-0029-2013Andalucia, Consejería de Salud PI-0096-2014Andalucia, Consejería de Salud PI-0306-201

Macro- and micro-geographic variation of short-beaked common dolphin’s whistles in the Mediterranean Sea and Atlantic Ocean

Author Posting. © The Author(s), 20113. This is the author's version of the work. It is posted here by permission of Taylor & Francis for personal use, not for redistribution. The definitive version was published in Ethology Ecology & Evolution 26 (2014): 392-404, doi:10.1080/03949370.2013.851122.Genetic studies have shown that there are small but significant differences between the short-beaked common dolphin populations in the Atlantic Ocean and those in the Mediterranean Sea. The short-beaked common dolphin is a highly vocal species with a wide sound production repertoire including whistles. Whistles are continuous, narrowband, frequency-modulated signals that can show geographic variation in dolphin species. This study tests whether the differences, highlighted by genetic studies, are recognisable in the acoustic features of short-beaked common dolphin’s whistles in the two adjacent areas of the Atlantic Ocean and the Mediterranean Sea. From a selected sample of good quality whistles (514 recorded in the Atlantic and 193 in the Mediterranean) 10 parameters of duration, frequency and frequency modulation were measured. Comparing data among basins, differences were found for duration and all frequency parameters except for minimum frequency. Modulation parameters showed the highest coefficient of variation. Through discriminant analysis we correctly assigned 75.7% of sounds to their basins. Furthermore, micro-geographic analysis revealed similarity between the sounds recorded around the Azores and the Canary archipelagos and between the Bay of Biscay and the Mediterranean Sea. Results are in agreement with the hypothesis proposed by previous genetic studies that two distinct populations are present, still supposing a gene flow between the basins. This study is the first to compare shortbeaked common dolphin’s whistles of the Atlantic Ocean and the Mediterranean areas.Data collection and processing in the Azores was conducted under projects POCTI/BSE/38991/01, PTDC/MAR/74071/2006 and M2.1.2/F/012/2011, supported by FCT (Fundação para a Ciência e a Tecnologia) and DRCTC/SRCTE (Secretaria Regional de Ciência, Tecnologia e Equipamentos), FEDER funds, the Competitiveness Factors Operational (COMPETE), QREN European Social Fund and Proconvergencia Açores Program. We acknowledge funds provided by FCT to LARSyS Associated Laboratory & IMAR-University of the Azores/ the Thematic Area E of the Strategic Project (OE & Compete) and by the DRCTC – Government of the Azores pluriannual funding. M.A. Silva was supported by an FCT postdoctoral grant (SFRH/ BPD/29841/2006). I. Cascão and R. Prieto were supported by FCT doctoral grants (SFRH/BD/ 41192/2007 and SFRH/BD/32520/2006, respectively) and R. Prieto by a research grant from the Azores Regional Fund for Science and Technology (M3.1.5/F/115/2012). Data collection by SECAC (Society for the Study of Cetaceans in the Canary Archipelago) was funded by the U.E. LIFE programme – project LIFE INDEMARES (LIFE 07/NAT/E/000732)- and the Fundación Biodiversidad, under the Spanish Ministry of Environment, Rural and Marine Affairs (project ZEC-TURSIOPS).2014-11-0

DPDnet: A Robust People Detector using Deep Learning with an Overhead Depth Camera

In this paper we propose a method based on deep learning that detects multiple people from a single overhead depth image with high reliability. Our neural network, called DPDnet, is based on two fully-convolutional encoder-decoder neural blocks based on residual layers. The Main Block takes a depth image as input and generates a pixel-wise confidence map, where each detected person in the image is represented by a Gaussian-like distribution. The refinement block combines the depth image and the output from the main block, to refine the confidence map. Both blocks are simultaneously trained end-to-end using depth images and head position labels. The experimental work shows that DPDNet outperforms state-of-the-art methods, with accuracies greater than 99% in three different publicly available datasets, without retraining not fine-tuning. In addition, the computational complexity of our proposal is independent of the number of people in the scene and runs in real time using conventional GPUs

DisPhaseDB: An integrative database of diseases related variations in liquid–liquid phase separation proteins

Motivation: Proteins involved in liquid–liquid phase separation (LLPS) and membraneless organelles (MLOs) are recognized to be decisive for many biological processes and also responsible for several diseases. The recent explosion of research in the area still lacks tools for the analysis and data integration among different repositories. Currently, there is not a comprehensive and dedicated database that collects all disease-related variations in combination with the protein location, biological role in the MLO, and all the metadata available for each protein and disease. Disease-related protein variants and additional features are dispersed and the user has to navigate many databases, with a different focus, formats, and often not user friendly. Results: We present DisPhaseDB, a database dedicated to disease-related variants of liquid–liquid phase separation proteins. It integrates 10 databases, contains 5,741 proteins, 1,660,059 variants, and 4,051 disease terms. It also offers intuitive navigation and an informative display. It constitutes a pivotal starting point for further analysis, encouraging the development of new computational tools. The database is freely available at http://disphasedb.leloir.org.ar.Fil: Navarro, Alvaro Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Orti, Fernando Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Martinez Perez, Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Alonso, Macarena. Fundación Instituto Leloir; ArgentinaFil: Simonetti, Franco Lucio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Iserte, Javier Alonso. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Marino Buslje, Cristina. Fundación Instituto Leloir; Argentin

Identifying SARS-CoV-2 'memory' NK cells from COVID-19 convalescent donors for adoptive cell therapy

COVID-19 disease is the manifestation of syndrome coronavirus 2 (SARS-CoV-2) infection, which is causing a worldwide pandemic. This disease can lead to multiple and different symptoms, being lymphopenia associated with severity one of the most persistent. Natural killer cells (NK cells) are part of the innate immune system, being fighting against virus-infected cells one of their key roles. In this study, we determined the phenotype of NK cells after COVID-19 and the main characteristic of SARS-CoV-2-specific-like NK population in the blood of convalescent donors. CD57+ NKG2C+ phenotype in SARS-CoV-2 convalescent donors indicates the presence of 'memory'/activated NK cells as it has been shown for cytomegalovirus infections. Although the existence of this population is donor dependent, its expression may be crucial for the specific response against SARS-CoV-2, so that, it gives us a tool for selecting the best donors to produce off-the-shelf living drug for cell therapy to treat COVID-19 patients under the RELEASE clinical trial (NCT04578210)

The nature of circulating CD27+CD43+ B cells

Letter to the Editor.-- et al.M.C. van Zelm is supported by fellowships from the Erasmus University Rotterdam (EUR-Fellowship) and the Erasmus MC, and by Veni grant 916.110.90 from ZonMW/NWO.Peer Reviewe