Anthropic Impact Effect on the Distribution of Stramonita haemastoma (Linnaeus 1766) (Gastropoda: Muricidae) In the North Coast of Tenerife

Las zonas costeras han sido históricamente un lugar de asentamiento humano y de aprovechamiento de recursos por su elevada productividad. En las islas Canarias concretamente, el marisqueo de la «púrpura» o «cañadilla» (Stramonita haemastoma) ha sido uno de los principales motivos de explotación del intermareal isleño. El objetivo del presente estudio fue analizar el efecto del impacto antrópico sobre la distribución, abundancia y tamaño de este molusco. Para ello, se muestrearon dos zonas del norte de Tenerife, la Punta del Hidalgo y Finca El Apio, lugares muy homogéneos en sus características físicas, pero con una diferencia importante, su cercanía al núcleo urbano. Los resultados muestran diferencias en la abundancia y la talla de Stramonita haemastoma entre las dos localidades, encontrando mayor número de individuos, así como individuos de mayor tamaño, en la localidad menos impactada por el ser humano. Del mismo modo, se muestra un cambio en la distribución natural de esta especie. Este estudio podría ser una herramienta para la gestión adecuada y sostenible de este recurso, a través del conocimiento de su estado actual.Historically coastal areas have been a human settlement place and exploitation area for its resources and its high productivity. In the Canary Islands, one of the main reasons to exploit the islands intertidal zone has been the shellfishing of “purpura o cañadilla” (Stramonita haemastoma). The main objetive of this study was to analyze the human impact’s effect on the distribution, abundance and size of this mollusk. To do so, we sampled two locations at the North of Tenerife, with similar characteristics, la Punta del Hidalgo and Finca El Apio. The results show differences on the abundance and size of Stramonita haemastoma among localities, being more abundant and larger at the less human-impacted locality. In addition, there are changes in the natural distribution of this species. This study could be useful tool for sustainable management actions of this resource throughout the knowledge of its actual status

Velusetrag rescues GI dysfunction, gut inflammation and dysbiosis in a mouse model of Parkinson's disease

: In patients with Parkinson's disease (PD), constipation is common, and it appears in a prodromal stage before the hallmark motor symptoms. The present study aimed to investigate whether Velusetrag, a selective 5‑HT4 receptor agonist, may be a suitable candidate to improve intestinal motility in a mouse model of PD. Five months old PrP human A53T alpha-synuclein transgenic (Tg) mice, which display severe constipation along with decreased colonic cholinergic transmission already at 3 months, were treated daily with the drug for 4 weeks. Velusetrag treatment reduced constipation by significantly stimulating both the longitudinal and circular-driven contractions and improved inflammation by reducing the level of serum and colonic IL1β and TNF-α and by decreasing the number of GFAP-positive glia cells in the colon of treated mice. No significant downregulation of the 5-HT4 receptor was observed but instead Velusetrag seemed to improve axonal degeneration in Tgs as shown by an increase in NF-H and VAChT staining. Ultimately, Velusetrag restored a well-balanced intestinal microbial composition comparable to non-Tg mice. Based on these promising data, we are confident that Velusetrag is potentially eligible for clinical studies to treat constipation in PD patients

Neuregulins increase mitochondrial oxidative capacity and insulin sensitivity in skeletal muscle cells

OBJECTIVE Neuregulins are growth factors that are essential for myogenesis and regulate muscle metabolism. The addition of a recombinant neuregulin-1 isoform, heregulin-β1177-244 (Hrg), containing 3 nmol/l of the bioactive epidermal growth factor-like domain, to developing L6E9 myocytes has acute and chronic effects on glucose uptake and enhances myogenesis. Here, we studied the metabolic adaptation of myocytes to chronic treatments with Hrg. RESEARCH DESIGN AND METHODS L6E9 and C2C12 myocytes were chronically treated with low concentrations of Hrg (3 pmol/l) that do not induce myogenesis. We analyzed the effects of Hrg on cellular oxidative metabolism and insulin sensitivity and explored the mechanisms of action. RESULTS Hrg increased the cell content of GLUT4 without affecting basal glucose uptake. Glucose and palmitate oxidation increased in Hrg-treated cells, whereas lactate release decreased. Hrg increased the abundance of oxidative phosphorylation (OXPHOS) subunits, enhanced mitochondrial membrane potential, and induced the expression of peroxisome proliferator-activated receptor (PPAR)γ coactivator1α and PPARδ. Furthermore, we identified PPARδ as an essential mediator of the stimulatory effects of Hrg on the expression of OXPHOS subunits. The higher oxidative capacity of L6E9 myotubes after neuregulin treatment also paralleled an increase in insulin sensitivity and insulin signaling potency. CONCLUSIONS These results indicate that neuregulins act as key modulators of oxidative capacity and insulin sensitivity in muscle cells

Genetic testing to predict weight loss and diabetes remission and long-term sustainability after bariatric surgery : a pilot study

Introduction: The aim of this pilot study was to assess genetic predisposition risk scores (GPS) in type 2 diabetic and non-diabetic patients in order to predict the better response to bariatric surgery (BS) in terms of either weight loss or diabetes remission. Research Design and Methods: A case-control study in which 96 females (47 with type 2 diabetes) underwent Roux-en-Y gastric by-pass were included. The DNA was extracted from saliva samples and SNPs were examined and grouped into 3 GPS. ROC curves were used to calculate sensitivity and specificity. Results: A highly sensitive and specific predictive model of response to BS was obtained by combining the GPS in non-diabetic subjects. This combination was different in diabetic subjects and highly predictive of diabetes remission. Additionally, the model was able to predict the weight regain and type 2 diabetes relapse after 5 years' follow-up. Conclusions: Genetic testing is a simple, reliable and useful tool for implementing personalized medicine in type 2 diabetic patients equiring BS

Heat identification by 17\u3b2-estradiol and progesterone quantification in individual raw milk samples by enzyme immunoassay

Background: There is a substantial decline in first-service-pregnancy-rate in dairy cows. In this regard, future prospects are to measure milk hormones on-farm and progesterone levels in milk are not enough to precise ovulation unless connected to other data. The objectives of this study were to investigate whether 17\u3b2-estradiol could be measured from individual cow milk samples using a commercially available non-radiolabelled enzyme immunoassay kit (EIA) with no previously reported milk application, and whether those detections could precisely illustrate 17\u3b2-estradiol pre-ovulation peak in spite of its limited concentration and short manifestation in milk. Results: Milk sample treatments for progesterone and 17\u3b2-estradiol EIA measurements are described. Hormonal profiles from daily milk samples of six different cows were reported and 17\u3b2-estradiol pre-ovulation peak was visualized in all cases. Heat detection was possible by EIA using one every 2 days milking samples in almost all studied cases. Only in one case, morning and afternoon milking samples were required to visualize the 17\u3b2-estradiol pre-ovulation peak. Conclusions: 17\u3b2-estradiol EIA quantification in raw milk is a reliable, rapid, economic and a precise method to describe cow heat along with EIA progesterone determination

Prediction of Recurrent Pregnancy Loss by a New Thrombophilia Based Genetic Risk Score

We  examined the predictive ability of the new thrombophilia-based genetic risk score that has been developed (TiC-RPL)  to acutely determine the risk of recurrent pregnancy loss (RPL) closely related to thrombophilia and to compare it with the ability of the classical genetic thrombophilia variants F5 rs6025 and F2 rs1799963. This is a case-control observational study, with retrospective data analysis. We included 180 healthy women with at least one uncomplicated pregnancy to term and no previous miscarriage and 184 cases of idiopathic recurrent pregnancy loss (RPL). The predictive ability was assessed in terms of discrimination (AUC), sensitivity, specificity, positive and negative predictive values (PPV, NPV), and positive and negative likelihood ratios (PLR and NLR). TiC-RPL has a better AUC (95 CI) than F5 rs6025+F2 rs1799963 [0.763 (0.715-0.811) vs 0.540 (0.514-0.567); p<0.0001], with a sensitivity of 70.65%, a specificity of 67.78%, a PPV of 69.15%, an NPV of 69.32%, a PLR of 2.19, and an NLR of 0.43. Our results show that the new score TiC-RPL is significantly better than F5 rs6025+F2 rs1799963 in identifying RPL women in whom RPL appears to be associated with thrombophilia. This identification can guide a personalized approach in the prevention of RPL

Phase I clinical trial of an intranodally administered mRNA-based therapeutic vaccine against HIV-1 infection

OBJECTIVE: The efficacy of therapeutic vaccines against HIV-1 infection has been modest. New inerts to redirect responses to vulnerable sites are urgently needed to improve these results.DESIGN: We performed the first-in-human clinical trial with naked mRNA (iHIVARNA) combining a dendritic cell activation strategy (TriMix:CD40L+CD70+caTLR4 RNA) with a novel HIV immunogen sequences (HTI immunogen).METHODS: A dose escalation, phase I clinical trial was performed in 21 chronic HIV-1-infected patients under ART who received three intranodal doses of mRNA (weeks 0, 2 and 4

A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic.

The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Desenvolupament d'eines d'alta ressolució per al cribatge (screening) de l'activitat de fàrmacs

Projecte de recerca elaborat a partir d’una estada a la Satandford University, EEUU, entre 2007 i 2009. Els darrers anys, hi ha hagut un avanç espectacular en la tecnologia aplicada a l’anàlisi del genoma i del proteoma (microarrays, PCR quantitativa real time, electroforesis dos dimensions, espectroscòpia de masses, etc.) permetent la resolució de mostres complexes i la detecció quantitativa de diferents gens i proteïnes en un sol experiment. A més a més, la seva importància radica en la capacitat d’identificar potencials dianes terapèutiques i possibles fàrmacs, així com la seva aplicació en el disseny i desenvolupament de noves eines de diagnòstic. L’aplicabilitat de les tècniques actuals, però, està limitada al nivell al que el teixit pot ser disseccionat. Si bé donen valuosa informació sobre expressió de gens i proteïnes implicades en una malaltia o en resposta a un fàrmac per exemple, en cap cas, s’obté una informació in situ ni es pot obtenir informació espacial o una resolució temporal, així com tampoc s’obté informació de sistemes in vivo. L’objectiu d’aquest projecte és desenvolupar i validar un nou microscopi, d’alta resolució, ultrasensible i de fàcil ús, que permeti tant la detecció de metabòlits, gens o proteïnes a la cèl•lula viva en temps real com l’estudi de la seva funció. Obtenint així una descripció detallada de les interaccions entre proteïnes/gens que es donen dins la cèl•lula. Aquest microscopi serà un instrument sensible, selectiu, ràpid, robust, automatitzat i de cost moderat que realitzarà processos de cribatge d’alt rendiment (High throughput screening) genètics, mèdics, químics i farmacèutics (per aplicacions diagnòstiques i de identificació i selecció de compostos actius) de manera més eficient. Per poder realitzar aquest objectius el microscopi farà ús de les més noves tecnologies: 1)la microscopia òptica i d’imatge, per millorar la visualització espaial i la sensibilitat de l’imatge; 2) la utilització de nous mètodes de detecció incloent els més moderns avanços en nanopartícules; 3) la creació de mètodes informàtics per adquirir, emmagatzemar i processar les imatges obtingudes.Report for the scientific sojourn at the Standford University, USA, from 2007 to 2009. The overall objective of this proposal is the establishment of an innovative, automated screening instrument for high-throughput and high-content screens. The project will allow standardized, robust, automated, ultrasensitive, high-resolution analysis of RNAs, proteins and other cellular components at cellular and subcellular resolution. The generic technology for toponome analysis will be widely applicable in biomedical research and commercially relevant. Such an instrument is urgently needed by the genome research community as to the availability of complete genome sequences for biomedical research and the upcoming numerous opportunities for high-throughput and high-content assays at a genome-wide scale. Detailed knowledge of the tissues and cells that express particular genes is mandatory. While microarrays provide general information on gene expression patterns, both their resolution and accuracy are inherently limited to the level at which tissues can be dissected. Therefore innovative instruments must allow in situ localisation of genes and proteins at high speed and with high spatial and temporal resolution at high-throughput. The main goal of the proposed effort is to develop an innovative screening platform suitable for high-throughput and high-content cell-based assays and to demonstrate its suitability for high resolution in situ techniques. This instrument, will not only provide the basis for intelligent and efficient high-content screens, it is also designed for low cost genetic, medical, chemical and pharmaceutical screens. The integration of novel technologies into a common platform concept, the development of efficient cell-based screens, and the demonstration of the feasibility of this approach will constitute a significant competitive advantage for these SMEs and, ultimately, for the European Pharmaceutical and AgroBiotech Industry