A novel role for proline- and acid-rich basic region leucine zipper (PAR bZIP) proteins in the transcriptional regulation of a BH3-only proapoptotic gene.

Proline- and acid-rich (PAR) basic region leucine zipper (bZIP) proteins thyrotroph embryonic factor (TEF), D-site-binding protein (DBP), and hepatic leukemia factor have been involved in neurotransmitter homeostasis and amino acid metabolism. Here we demonstrate a novel role for these proteins in the transcriptional control of a BH3-only gene. PAR bZIP proteins are able to transactivate the promoter of bcl-gS. This promoter is particularly responsive to TEF activation and is silenced by NFIL3, a repressor that shares the consensus binding site with PAR bZIP proteins. Consistently, transfection of TEF induces the expression of endogenous bcl-gS in cancer cells, and this induction is independent of p53. A naturally occurring variant of DBP (tDBP), lacking the transactivation domain, has been identified and shown to impede the formation of active TEF dimers in a competitive manner and to reduce the TEF-dependent induction of bcl-gS. Of note, treatment of cancer cells with etoposide induces TEF activation and promotes the expression of bcl-gS. Furthermore, blockade of bcl-gS or TEF expression by a small interfering RNA strategy or transfection with tDBP significantly reduces the etoposide-mediated apoptotic cell death. These findings represent the first described role for PAR bZIP proteins in the regulation of a gene involved in the execution of apoptosis

Developing a predictive modelling capacity for a climate change-vulnerable blanket bog habitat: Assessing 1961-1990 baseline relationships

Aim: Understanding the spatial distribution of high priority habitats and developing predictive models using climate and environmental variables to replicate these distributions are desirable conservation goals. The aim of this study was to model and elucidate the contributions of climate and topography to the distribution of a priority blanket bog habitat in Ireland, and to examine how this might inform the development of a climate change predictive capacity for peat-lands in Ireland. Methods: Ten climatic and two topographic variables were recorded for grid cells with a spatial resolution of 1010 km, covering 87% of the mainland land surface of Ireland. Presence-absence data were matched to these variables and generalised linear models (GLMs) fitted to identify the main climatic and terrain predictor variables for occurrence of the habitat. Candidate predictor variables were screened for collinearity, and the accuracy of the final fitted GLM was evaluated using fourfold cross-validation based on the area under the curve (AUC) derived from a receiver operating characteristic (ROC) plot. The GLM predicted habitat occurrence probability maps were mapped against the actual distributions using GIS techniques. Results: Despite the apparent parsimony of the initial GLM using only climatic variables, further testing indicated collinearity among temperature and precipitation variables for example. Subsequent elimination of the collinear variables and inclusion of elevation data produced an excellent performance based on the AUC scores of the final GLM. Mean annual temperature and total mean annual precipitation in combination with elevation range were the most powerful explanatory variable group among those explored for the presence of blanket bog habitat. Main conclusions: The results confirm that this habitat distribution in general can be modelled well using the non-collinear climatic and terrain variables tested at the grid resolution used. Mapping the GLM-predicted distribution to the observed distribution produced useful results in replicating the projected occurrence of the habitat distribution over an extensive area. The methods developed will usefully inform future climate change predictive modelling for Irelan

Machine learning algorithms performed no better than regression models for prognostication in traumatic brain injury

Objective: We aimed to explore the added value of common machine learning (ML) algorithms for prediction of outcome for moderate and severe traumatic brain injury. Study Design and Setting: We performed logistic regression (LR), lasso regression, and ridge regression with key baseline predictors in the IMPACT-II database (15 studies, n = 11,022). ML algorithms included support vector machines, random forests, gradient boosting machines, and artificial neural networks and were trained using the same predictors. To assess generalizability of predictions, we performed internal, internal-external, and external validation on the recent CENTER-TBI study (patients with Glasgow Coma Scale <13, n = 1,554). Both calibration (calibration slope/intercept) and discrimination (area under the curve) was quantified. Results: In the IMPACT-II database, 3,332/11,022 (30%) died and 5,233(48%) had unfavorable outcome (Glasgow Outcome Scale less than 4). In the CENTER-TBI study, 348/1,554(29%) died and 651(54%) had unfavorable outcome. Discrimination and calibration varied widely between the studies and less so between the studied algorithms. The mean area under the curve was 0.82 for mortality and 0.77 for unfavorable outcomes in the CENTER-TBI study. Conclusion: ML algorithms may not outperform traditional regression approaches in a low-dimensional setting for outcome prediction after moderate or severe traumatic brain injury. Similar to regression-based prediction models, ML algorithms should be rigorously validated to ensure applicability to new populations

Revista de Vertebrados de la Estación Biológica de Doñana

Tiempo y orden de aparición de las escamas en el salmón del Atlántico (Salmo salar)Estudios sobre el sapo corredor (Bufo calamita) en el sur de España.III. ReproducciónInfluencia de las carecterísticas del medio acuático sobre las poblaciones de larvas de anfibios en lala Reserva Biológica de Doñana(Huelva, EspañaDieta de la cigüeñuela (Himantopus himantopus) en las salinas del estuario del GuadianaOrientación y selección del lugar del nido en el gorrión moruno (Passer hispaniolensis)la avifauna de las Vegas Bajas del Guadianala reproducción de la malvasía (Oxyura leucocephala) en el sur de la provincia de Córdoba, España.La alimentación de la curruca cabecinegra (Sylvia melanocephala, Gmelin 1788) en olivares de la provincia de Jaén (otoño-invierno)Consideraciones sobre el efecto de los conejos y los grandes herbívoros en los pastizales de la Vera de DoñanaAnálisis factorial de las expresiones faciales del babuino sagrado (Papio hamadryas)Contaminación xenobiótica del Parque Nacionalde Doñana. II. Residuos de insecticidas organoclorados, bifenilos policlorados, (PGBs) y metales pesados en Falconiformes y StrigiformesTransferencia total y del y bioacumulación de mercurio y metilmercurio en ecosistemas del Parque Nacional de DoñanaNota sobre la alimentación de larvas de anfibios: I. Pleurodeles waltl en charcas temporaleNota sobre nuevas especies parasitada por el críalo (Clamator glandarius) en EspañaEstructura de la jerarquización en la predación de huevos y pichones en Spheniscus magellanicusPasser domesticus, nueva specie para Bolivia¿Están realmente subalimentados los cernícalos primilla en el valle del Guadalquivir durante el periodo no reproductor?.Nidificación del paiño común (Hydrobates pelagicus) en las Islas Canarias.Nuevos datos sobre la presencia del visón europeo (Mustela lutreola L.) en NavarraLa población de gamos del Parque Nacional de Doñana en 1979Puntualización a la nota "predacción de Falco peregrino y Falco subbuteo sobre quirópteros" de Aymerich y García de Castro aparecida en el vol. 9 de esta revista.Peer reviewe

Identification of c-Kit gene mutations in patients with polycythemia vera

Imatinib mesylate has recently been reported to have clinical activity in the treatment of polycythemia vera (PV), suggesting the involvement of one of the kinases targeted by this inhibitor, including c-Kit and PDGFR. Activating c-Kit mutations have been identified in patients with mastocytosis and other myeloid disorders such as acute myeloid leukemia. Thus, we wanted to analyze the presence of mutations of c-Kit in polycythemia vera patients. We found that 7 out of 20 patients carried missense mutations in the c-Kit gene whereas no sequence variation was detected in 15 healthy controls

Identification of c-Kit gene mutations in patients with polycythemia vera

Imatinib mesylate has recently been reported to have clinical activity in the treatment of polycythemia vera (PV), suggesting the involvement of one of the kinases targeted by this inhibitor, including c-Kit and PDGFR. Activating c-Kit mutations have been identified in patients with mastocytosis and other myeloid disorders such as acute myeloid leukemia. Thus, we wanted to analyze the presence of mutations of c-Kit in polycythemia vera patients. We found that 7 out of 20 patients carried missense mutations in the c-Kit gene whereas no sequence variation was detected in 15 healthy controls

Spillover event of recombinant Lagovirus europaeus/GI.2 into the Iberian hare (Lepus granatensis) in Spain

Viruses that affect lagomorphs have decades of reported history of spillover events. One of these viruses is the causative agent of the so-called rabbit or ‘lagomorph’ haemorrhagic disease (e.g. Lagovirus europaeus/GI.1 and L. europaeus/GI.2). In particular, L. europaeus/GI.2 has shown a great capacity to recombine with existing lagoviruses. In fact, it has replaced the former GI.1 genotype in the wild, and recently, an increase on spillover events has been detected among several lagomorph species including European and North American species of hares. In this study, we report for the first time the infection of a wild Iberian hare with GI.2 (RHDV2/b), potential shedding and associated histopathological alterations. We identify the recombinant GI.4P-GI.2 as causative of the infection and discuss plausible causes regarding the origin of the spillover event and its potential consequences for the Iberian hare wild populations, which is an endemic species of the Iberian Peninsula as well as an important game and prey species for many predators, including endangered species