Preparation, thermoresponsive behavior, and preliminary biological study of functionalized poly(N-isopropylacrylamide-co-dopamine methacrylamide) copolymers with an organotin(IV) compound

Recent advances focused on smart polymers have demonstrated the numerous advantages regarding other structures because they can adapt the behavior depending on physicochemical properties. In this way, functionalized thermoresponsive polymers with organometallic complexes were profoundly analyzed. Consequently, novel catalytic systems or biomedical devices could be developed. This publication focuses on the facile preparation of poly(N-isopropylacrylamide-co-dopamine methacrylamide) copolymers functionalized with triphenyltin chloride by protonolysis through the -OH of catechol groups. The presence of hydrophobic organotin(IV) derivatives could modify the solubility, thermoresponsive behavior, and other properties regarding pure copolymers. Also, sensitive analysis of the microstructure could help to understand the changes associated with the lower critical solution temperature by rheology, UV-vis spectroscopy, and calorimetry. In addition, a preliminary biological study against MDA-MB-231 cancer cells and peripheral blood mononuclear cells showed that the functionalized copolymers could be a potential platform to be explored in the future in the fight against cancer.The financial support obtained from the National Science Foundation of China (21574086), Shenzhen Fundamental Research Funds (No. KC2014ZDZJ0001A), Shenzhen Sci & Tech research grant (ZDSYS201507141105130) and China Postdoctoral Science Foundation Grant (2018M633119) are acknowledged. Also, these researchers would like to thank the former Ministerio de Ciencia, Innovación y Universidades of Spain (current Ministerio de Ciencia e Innovación of Spain) for the grant RTI2018-094322-B-I00 and the Dirección General de Investigación e Innovación, Consejería de Educación e Investigación de la Comunidad de Madrid for the predoctoral grant PEJD-2017-PRE/BMD-3512 (I. M.-P.)

Microenvironmental hCAP-18/LL-37 promotes pancreatic ductal adenocarcinoma by activating its cancer stem cell compartment

This is the peer reviewed version of the following article: Microenvironmental hCAP-18/LL-37 promotes pancreatic ductal adenocarcinoma by activating its cancer stem cell compartment. Gut 64.12 (2015): 1921-1935 and which has been published in final form at http://dx.doi.org/10.1136/gutjnl-2014-308935OBJECTIVES: The tumour stroma/microenvironment not only provides structural support for tumour development, but more importantly it provides cues to cancer stem cells (CSCs) that regulate their self-renewal and metastatic potential. This is certainly true for pancreatic ductal adenocarcinomas (PDAC), where tumour-associated fibroblasts, pancreatic stellate cells and immune cells create an abundant paracrine niche for CSCs via microenvironment-secreted factors. Thus understanding the role that tumour stroma cells play in PDAC development and CSC biology is of utmost importance. DESIGN: Microarray analyses, tumour microarray immunohistochemical assays, in vitro co-culture experiments, recombinant protein treatment approaches and in vivo intervention studies were performed to understand the role that the immunomodulatory cationic antimicrobial peptide 18/LL-37 (hCAP-18/LL-37) plays in PDAC biology. RESULTS: We found that hCAP-18/LL-37 was strongly expressed in the stroma of advanced primary and secondary PDAC tumours and is secreted by immune cells of the stroma (eg, tumour-associated macrophages) in response to tumour growth factor-β1 and particularly CSC-secreted Nodal/ActivinA. Treatment of pancreatic CSCs with recombinant LL-37 increased pluripotency-associated gene expression, self-renewal, invasion and tumourigenicity via formyl peptide receptor 2 (FPR2)- and P2X purinoceptor 7 receptor (P2X7R)-dependent mechanisms, which could be reversed by inhibiting these receptors. Importantly, in a genetically engineered mouse model of K-Ras-driven pancreatic tumourigenesis, we also showed that tumour formation was inhibited by either reconstituting these mice with bone marrow from cathelicidin-related antimicrobial peptide (ie, murine homologue of hCAP-18/LL-37) knockout mice or by pharmacologically inhibiting FPR2 and P2X7R. CONCLUSIONS: Thus, hCAP-18/LL-37 represents a previously unrecognised PDAC microenvironment factor that plays a critical role in pancreatic CSC-mediated tumourigenesis.CH: ERC Advanced Investigator Grant (Pa-CSC 233460), European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement n° 256974 (EPC-TM-NET) and n° 602783 (CAM-PaC), the Subdirección General de Evaluación y Fomento de la Investigación, Fondo de Investigación Sanitaria (PS09/02129 & PI12/02643) and the Programa Nacional de Internacionalización de la I+D, Subprogramma: FCCI 2009 (PLE2009-0105; both Ministerio de Economía y Competitividad (es), Spain), BSJr: Rámon y Cajal Merit Award from the Ministerio de Economía y Competitividad, Spain and Clinic and Laboratory Integration Program (CLIP) grant from the Cancer Research Institute, NY, NY. MC: La Caixa Predoctoral Fellowshi

Plataforma virtual de entrenamiento: Fit Train Perú

El presente modelo de negocio consiste en la creación de una plataforma virtual de entrenamiento dedicada a las personas que deseen incorporar la actividad física a su rutina diaria. Este servicio consta de clases grabadas y en vivo de las disciplinas que despiertan más interés en los usuarios, como rutinas de cardio, fuerza, Body Combat, yoga, pilates y ejercicios de alta intensidad. El segmento de clientes a los que está dirigido este emprendimiento pertenecen a todos los peruanos del NSE A y B, entre 18 a 55 años. De esta manera, Fit Train Perú ofrece dos tipos de membresías al público objetivo. La membresía básica consta de clases grabadas y la Premium que son clases en vivo. El objetivo principal de Fit Train Perú es incentivar la práctica del ejercicio físico en las personas, con el fin de que mejoren su salud y calidad de vida a largo plazo.The present business model consists in the creation of a virtual entertainment platform that’s dedicated to the people that wish to incorporate physical activity to their daily schedule. This service has recorded classes and live classes from disciplines that spark the most interest in users, such as cardio routines, strength, body combat, yoga, Pilates and high intensity exercises. The segment of clients that this entrepreneurship aims for is Peruvians from social economic level A and B between 18 and 55 years old. Fit Train Peru offers two types of memberships to the target audiences. The basic membership consists of recorded classes and the premium membership has live classes. The main objective of Fit Train Peru is to incentivize the practice of physical exercise in people, with the aim of improving their health and quality of life in the long term.Trabajo de investigació

Coupled C, H, N, S and Fe biogeochemical cycles operating in the continental deep subsurface of the Iberian Pyrite Belt

Microbial activity is a major contributor to the biogeochemical cycles that make up the life support system of planet Earth. A 613 m deep geomicrobiological perforation and a systematic multi-analytical characterization revealed an unexpected diversity associated with the rock matrix microbiome that operates in the subsurface of the Iberian Pyrite Belt (IPB). Members of 1 class and 16 genera were deemed the most representative microorganisms of the IPB deep subsurface and selected for a deeper analysis. The use of fluorescence in situ hybridization allowed not only the identification of microorganisms but also the detection of novel activities in the subsurface such as anaerobic ammonium oxidation (ANAMMOX) and anaerobic methane oxidation, the co-occurrence of microorganisms able to maintain complementary metabolic activities and the existence of biofilms. The use of enrichment cultures sensed the presence of five different complementary metabolic activities along the length of the borehole and isolated 29 bacterial species. Genomic analysis of nine isolates identified the genes involved in the complete operation of the light-independent coupled C, H, N, S and Fe biogeochemical cycles. This study revealed the importance of nitrate reduction microorganisms in the oxidation of iron in the anoxic conditions existing in the subsurface of the IPBFP7 Ideas: European Research Council, Grant/Award Number: ERC Advanced Grant #250-35

Functional Frailty, Dietary Intake, and Risk of Malnutrition. Are Nutrients Involved in Muscle Synthesis the Key for Frailty Prevention?

Frailty is a reversible condition, which is strongly related to physical function and nutri tional status. Different scales are used to screened older adults and their risk of being frail, however, Short Physical Performance Battery (SPPB) may be more adequate than others to measure physical function in exercise interventions and has been less studied. Thus, the main aims of our study were: (1) to describe differences in nutritional intakes by SPPB groups (robust, pre-frail and frail); (2) to study the relationship between being at risk of malnourishment and frailty; and (3) to describe differences in nutrient intake between those at risk of malnourishment and those without risk in the no-frail individuals. One hundred one participants (80.4 ± 6.0 year old) were included in this cross sectional study. A validated semi-quantitative food frequency questionnaire was used to determine food intake and Mini Nutritional Assessment to determine malnutrition. Results revealed differences for the intake of carbohydrates, n-3 fatty acids (n3), and saturated fatty acids for frail, pre-frail, and robust individuals and differences in vitamin D intake between frail and robust (all p < 0.05). Those at risk of malnutrition were approximately 8 times more likely to be frail than those with no risk. Significant differences in nutrient intake were found between those at risk of malnourishment and those without risk, specifically in: protein, PUFA n-3, retinol, ascorbic acid, niacin equivalents, folic acid, magnesium, and potassium, respectively. Moreover, differences in alcohol were also observed showing higher intake for those at risk of malnourishment (all p < 0.05). In conclusion, nutrients related to muscle metabolism showed to have different intakes across SPPB physical function groups. The intake of these specific nutrients related with risk of malnourishment need to be promoted in order to prevent frailty

An optimized MNK1b aptamer, apMNKQ2, and its potential use as a therapeutic agent in breast cancer

16 pags., 8 figs.Breast cancer is the most commonly diagnosed and leading cause of cancer death among women worldwide. Mitogen-activated protein kinase-interacting kinases (MNKs) promote the expression of several oncogenic proteins and are overexpressed in several types of cancer. In human cells, there are four isoforms of MNKs. The truncated isoform MNK1b, first described in our laboratory, has a higher basal activity and is constitutively active. Aptamers are emerging in recent years as potential therapeutic agents that show significant advantages over drugs of other nature. We have previously obtained and characterized a highly specific aptamer against MNK1b, named apMNK2F, with a dissociation constant in the nanomolar range, which produces significant inhibition of proliferation, migration, and colony formation in breast cancer cells. Furthermore, its sequence analysis predicted two G-quadruplex structures. In this work, we show the optimization process of the aptamer to reduce its size, improving its stability. The obtained aptamer, named apMNKQ2, is able to inhibit proliferation, colony formation, migration, and invasion in breast cancer cells. In murine models of breast cancer, apMNKQ2 has demonstrated its efficacy in reducing tumor volume and the number of metastases. In conclusion, apMNKQ2 could be used as an anti-tumor drug in the future.C.P.-D. was supported by grant RTC-2014-1986-1 from the Ministry of Economy and Competitiveness (Spain). R.F.-M... by predoctoral contract (PEJD-2018-BMD-4416) from the Community of Madrid (Spain) and FPU19/02929 from the Ministry of Science, Innovation and Universities (Spain). R.C.-B. for predoctoral contracts (PEJD 2016-BMD-2145 and 2018-BMD-9201) from the Community of Madrid and grant RTC2019-07227-1. M. EM., and V.M.G. are researchers at FIBio-HRC. Supported by grants RTC2019-07227-1, PID2020-116620GB-T.I.00, and PID2019-105417RB-I00, funded by MCIN/ AEI /10.13039/501100011033 (Ministry of Economy and Competitiveness, Spain).Peer reviewe

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected

Decadal prediction of the North Atlantic subpolar gyre in the HiGEM high-resolution climate model

This paper presents an analysis of initialised decadal hindcasts of the North Atlantic subpolar gyre (SPG) using the HiGEM model, which has a nominal grid-spacing of 90 km in the atmosphere, and 1/3 ∘∘ in the ocean. HiGEM decadal predictions (HiGEM-DP) exhibit significant skill at capturing 0–500 m ocean heat content in the SPG, and outperform historically forced transient integrations and persistence for up to a decade ahead. An analysis of case-studies of North Atlantic decadal change, including the 1960s cooling, the mid-1990s warming, and the post-2005 cooling, show that changes in ocean circulation and heat transport dominate the predictions of the SPG. However, different processes are found to dominate heat content changes in different regions of the SPG. Specifically, ocean advection dominates in the east, but surface fluxes dominate in the west. Furthermore, compared to previous studies, we find a smaller role for ocean heat transport changes due to ocean circulation anomalies at the latitudes of the SPG, and, for the 1960s cooling, a greater role for surface fluxes. Finally, HiGEM-DP predicts the observed positive state of the North Atlantic Oscillation in the early 1990s. These results support an important role for the ocean in driving past changes in the North Atlantic region, and suggest that these changes were predictable

Assessment of a New ROS1 Immunohistochemistry Clone (SP384) for the Identification of ROS1 Rearrangements in Patients with Non–Small Cell Lung Carcinoma: the ROSING Study

Introduction: The ROS1 gene rearrangement has become an important biomarker in NSCLC. The College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology testing guidelines support the use of ROS1 immunohistochemistry (IHC) as a screening test, followed by confirmation with fluorescence in situ hybridization (FISH) or a molecular test in all positive results. We have evaluated a novel anti-ROS1 IHC antibody (SP384) in a large multicenter series to obtain real-world data. Methods: A total of 43 ROS1 FISH-positive and 193 ROS1 FISH-negative NSCLC samples were studied. All specimens were screened by using two antibodies (clone D4D6 from Cell Signaling Technology and clone SP384 from Ventana Medical Systems), and the different interpretation criteria were compared with break-apart FISH (Vysis). FISH-positive samples were also analyzed with next-generation sequencing (Oncomine Dx Target Test Panel, Thermo Fisher Scientific). Results: An H-score of 150 or higher or the presence of at least 70% of tumor cells with an intensity of staining of 2+ or higher by the SP384 clone was the optimal cutoff value (both with 93% sensitivity and 100% specificity). The D4D6 clone showed similar results, with an H-score of at least 100 (91% sensitivity and 100% specificity). ROS1 expression in normal lung was more frequent with use of the SP384 clone (p < 0.0001). The ezrin gene (EZR)-ROS1 variant was associated with membranous staining and an isolated green signal FISH pattern (p = 0.001 and p = 0.017, respectively). Conclusions: The new SP384 ROS1 IHC clone showed excellent sensitivity without compromising specificity, so it is another excellent analytical option for the proposed testing algorithm