Annual and semiannual cycles of midlatitude near-surface temperature and tropospheric baroclinicity: reanalysis data and AOGCM simulations

Abstract. Seasonal variability in near-surface air temperature and baroclinicity from the ECMWF ERA-Interim (ERAI) reanalysis and six coupled atmosphere–ocean general circulation models (AOGCMs) participating in the Coupled Model Intercomparison Project phase 3 and 5 (CMIP3 and CMIP5) are examined. In particular, the annual and semiannual cycles of hemispherically averaged fields are studied using spectral analysis. The aim is to assess the ability of coupled general circulation models to properly reproduce the observed amplitude and phase of these cycles, and investigate the relationship between near-surface temperature and baroclinicity (coherency and relative phase) in such frequency bands. The overall results of power spectra agree in displaying a statistically significant peak at the annual frequency in the zonally averaged fields of both hemispheres. The semiannual peak, instead, shows less power and in the NH seems to have a more regional character, as is observed in the North Pacific Ocean region. Results of bivariate analysis for such a region and Southern Hemisphere midlatitudes show some discrepancies between ERAI and model data, as well as among models, especially for the semiannual frequency. Specifically, (i) the coherency at the annual and semiannual frequency observed in the reanalysis data is well represented by models in both hemispheres, and (ii) at the annual frequency, estimates of the relative phase between near-surface temperature and baroclinicity are bounded between about ±15° around an average value of 220° (i.e., approximately 1-month phase shift), while at the semiannual frequency model phases show a wider dispersion in both hemispheres with larger errors in the estimates, denoting increased uncertainty and some disagreement among models. The most recent CMIP climate models (CMIP5) show several improvements when compared with CMIP3, but a degree of discrepancy still persists though masked by the large errors characterizing the semiannual frequency. These findings contribute to better characterizing the cyclic response of current global atmosphere–ocean models to the external (solar) forcing that is of interest for seasonal forecasts

Roar: detecting alternative polyadenylation with standard mRNA sequencing libraries

BACKGROUND: Post-transcriptional regulation is a complex mechanism that plays a central role in defining multiple cellular identities starting from a common genome. Modifications in the length of 3’UTRs have been found to play an important role in this context, since alternative 3’ UTRs could lead to differences for example in regulation by microRNAs and cellular localization of the transcripts thus altering their fate. RESULTS: We propose a strategy to identify the genes undergoing regulation of 3’ UTR length using RNA sequencing data obtained from standard libraries, thus widely applicable to data originally obtained to perform classical differential expression analyses. We decided to exploit previously annotated APA sites from public databases, in contrast with other approaches recently proposed in which the location of the APA site is inferred from the data together with the relative abundance of the isoforms. We demonstrate the reliability of our method by comparing it to the results of other microarray based or specific RNA-seq libraries methods and show that using APA sites databases results in higher sensitivity compared to de novo site prediction approach. CONCLUSIONS: We implemented the algorithm in a Bioconductor package to facilitate its broad usage in the scientific community. The ability of this approach to detect shortening from libraries with a number of reads comparable to that needed for differential expression analyses makes it useful for investigating if alternative polyadenylation is relevant in a certain biological process without requiring specific experimental assays. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-016-1254-8) contains supplementary material, which is available to authorized users

Efeito do Potato virus X no conteúdo de fenóis totais e alcalóides em folhas de Datura stramonium

The present paper reports results of the effect of Potato virus X (PVX) on the contents of total phenols and alkaloids in leaves of Datura stramonium. A significant decrease in the contents of phenols and alkaloids was observed in leaves inoculated with PVX (X-I). However, there was an increase in the percentage of phenols in leaves rubbed with phosphate buffer (C1-I) and in leaves from the nodes immediately above, possibly induced by mechanical injury. Gas chromatography/mass spectroscopy revealed amounts of scopolamine in samples submitted to all treatments, except X-I, in which the amount of this alkaloid was low. High amounts of an unidentified compound (molecular ion m/z 302 and a prominent peak at m/z 129) were noted in extracts from leaves X-I, C1-I and leaves from the nodes immediately above the leaves inoculated with PVX. It is suggested that the synthesis and accumulation of the unidentified compound is a result of stress from mechanical injury and virus inoculation.O presente trabalho relata resultados sobre a ação do Potato virus X (PVX) no conteúdo de fenóis totais e alcalóides em folhas de Datura stramonium. Uma diminuição significativa no conteúdo dessas substâncias foi observada nas folhas inoculadas com o PVX (X-I). Entretanto, houve um aumento na porcentagem de fenóis nas folhas friccionadas com tampão fosfato (C1-I) e nas acima das friccionadas, possivelmente induzido por injúria mecânica. Cromatografia gasosa/espectroscopia de massas revelou quantidades de escopolamina nas amostras submetidas a todos os tratamentos, exceto em X-I, no qual a quantidade deste alcalóide foi baixa. Altas quantidades de uma substância não identificada (íon molecular m/z 302 e um proeminente pico a m/z 129) foram notadas em extratos a partir de folhas dos tratamentos X-I, C1-I e nas acima das inoculadas com o PVX. Sugere-se que a síntese e acúmulo da substância não identificada é um resultado do estresse causado pela injúria mecânica e pelo vírus

Palmitoylethanolamide counteracts autistic-like behaviours in BTBR T+tf/J mice: Contribution of central and peripheral mechanisms

Abstract Autism spectrum disorders (ASD) are a group of heterogeneous neurodevelopmental conditions characterized by impaired social interaction, and repetitive stereotyped behaviours. Interestingly, functional and inflammatory gastrointestinal diseases are often reported as a comorbidity in ASDs, indicating gut-brain axis as a novel emerging approach. Recently, a central role for peroxisome-proliferator activated receptor (PPAR)-α has been addressed in neurological functions, associated with the behaviour. Among endogenous lipids, palmitoylethanolamide (PEA), a PPAR-α agonist, has been extensively studied for its anti-inflammatory effects both at central and peripheral level. Based on this background, the aim of this study was to investigate the pharmacological effects of PEA on autistic-like behaviour of BTBR T+tf/J mice and to shed light on the contributing mechanisms. Our results showed that PEA reverted the altered behavioural phenotype of BTBR mice, and this effect was contingent to PPAR-α activation. Moreover, PEA was able to restore hippocampal BDNF signalling pathway, and improve mitochondrial dysfunction, both pathological aspects, known to be consistently associated with ASDs. Furthermore, PEA reduced the overall inflammatory state of BTBR mice, reducing the expression of pro-inflammatory cytokines at hippocampal, serum, and colonic level. The analysis of gut permeability and the expression of colonic tight junctions showed a reduction of leaky gut in PEA-treated BTBR mice. This finding together with PEA effect on gut microbiota composition suggests an involvement of microbiota-gut-brain axis. In conclusion, our results demonstrated a therapeutic potential of PEA in limiting ASD symptoms, through its pleiotropic mechanism of action, supporting neuroprotection, anti-inflammatory effects, and the modulation of gut-brain axis

miR-221/222 control luminal breast cancer tumor progression by regulating different targets

α6β4 integrin is an adhesion molecule for laminin receptors involved in tumor progression. We present a link between β4 integrin expression and miR-221/222 in the most prevalent human mammary tumor: luminal invasive carcinomas (Lum-ICs). Using human primary tumors that display different β4 integrin expression and grade, we show that miR-221/222 expression inversely correlates with tumor proliferating index, Ki67. Interestingly, most high-grade tumors express β4 integrin and low miR-221/222 levels. We ectopically transfected miR-221/222 into a human-derived mammary tumor cell line that recapitulates the luminal subtype to investigate whether miR-221/222 regulates β4 expression. We demonstrate that miR-221/222 overexpression results in β4 expression downregulation, breast cancer cell proliferation, and invasion inhibition. The role of miR-221/222 in driving β4 integrin expression is also confirmed via mutating the miR-221/222 seed sequence for β4 integrin 3′UTR. Furthermore, we show that these 2 miRNAs are also key breast cancer cell proliferation and invasion regulators, via the post-transcriptional regulation of signal transducer and activator of transcription 5A (STAT5A) and of a disintegrin and metalloprotease-17 (ADAM-17). We further confirm these data by silencing ADAM-17, using a dominant-negative or an activated STAT5A form. miR-221/222-driven β4 integrin, STAT5A, and ADAM-17 did not occur in MCF-10A cells, denoted “normal” breast epithelial cells, indicating that the mechanism is cancer cell-specific.   These results provide the first evidence of a post-transcriptional mechanism that regulates β4 integrin, STAT5A, and ADAM-17 expression, thus controlling breast cancer cell proliferation and invasion. Pre-miR-221/222 use in the aggressive luminal subtype may be a powerful therapeutic anti-cancer strategy

Estimating the global burden of endemic canine rabies

Background: Rabies is a notoriously underreported and neglected disease of lowincome countries. This study aims to estimate the public health and economic burden of rabies circulating in domestic dog populations, globally and on a country-by-country basis, allowing an objective assessment of how much this preventable disease costs endemic countries.<p></p> Methodology/Principal Findings: We established relationships between rabies mortality and rabies prevention and control measures, which we incorporated into a model framework. We used data derived from extensive literature searches and questionnaires on disease incidence, control interventions and preventative measures within this framework to estimate the disease burden. The burden of rabies impacts on public health sector budgets, local communities and livestock economies, with the highest risk of rabies in the poorest regions of the world. This study estimates that globally canine rabies causes approximately 59,000 (95% Confidence Intervals: 25- 159,000) human deaths, over 3.7 million (95% CIs: 1.6-10.4 million) disability-adjusted life years (DALYs) and 8.6 billion USD (95% CIs: 2.9-21.5 billion) economic losses annually. The largest component of the economic burden is due to premature death (55%), followed by direct costs of post-exposure prophylaxis (PEP, 20%) and lost income whilst seeking PEP (15.5%), with only limited costs to the veterinary sector due to dog vaccination (1.5%), and additional costs to communities from livestock losses (6%).<p></p> Conclusions/Significance: This study demonstrates that investment in dog vaccination, the single most effective way of reducing the disease burden, has been inadequate and that the availability and affordability of PEP needs improving. Collaborative investments by medical and veterinary sectors could dramatically reduce the current large, and unnecessary, burden of rabies on affected communities. Improved surveillance is needed to reduce uncertainty in burden estimates and to monitor the impacts of control efforts.<p></p&gt

Identification of p130Cas/ErbB2-dependent invasive signatures in transformed mammary epithelial cells

Understanding transcriptional changes during cancer progression is of crucial importance to develop new and more efficacious diagnostic and therapeutic approaches. It is well known that ErbB2 is overexpressed in about 25% of human invasive breast cancers. We have previously demonstrated that p130Cas overexpression synergizes with ErbB2 in mammary cell transformation and promotes ErbB2-dependent invasion in three-dimensional (3D) cultures of human mammary epithelial cells. Here, by comparing coding and non-coding gene expression profiles, we define the invasive signatures associated with concomitant p130Cas overexpression and ErbB2 activation in 3D cultures of mammary epithelial cells. Specifically, we have found that genes involved in amino acids synthesis (CBS, PHGDH), cell motility, migration (ITPKA, PRDM1), and angiogenesis (HEY1) are upregulated, while genes involved in inflammatory response (SAA1, S100A7) are downregulated. In parallel, we have shown that the expression of specific miRNAs is altered. Among these, miR-200b, miR-222, miR-221, miR-R210, and miR-424 are upregulated, while miR-27a, miR-27b, and miR-23b are downregulated. Overall, this study presents, for the first time, the gene expression changes underlying the invasive behavior following p130Cas overexpression in an ErbB2 transformed mammary cell model

Distribución espacial a gran escala de la megafauna de aguas profundas en fondos arrastrables del Mediterráneo

The large-scale distribution pattern of megafauna communities along the Mediterranean middle slope was explored. The study was conducted between 500 and 800 m depth where deep-water fishery occurs. Although community studies carried out deeper than 500 m are partly available for some geographic areas, few large-scale comparative studies have been carried out. Within the framework of the MEDITS survey programme, we compared the megafauna community structure in ten geographical sub-areas (GSAs) along the Mediterranean coasts. Additionally, the spatial distribution of fishing was analysed using vessel monitoring by satellite information. Overall, the community showed a significant difference between sub-areas, with a decreasing eastward pattern in abundance and biomass. Longitude was the main factor explaining variation among sub-areas (by generalized additive models). However, we found a region which did not follow the general pattern. GSA 6 (northern Spain) showed significantly lower abundance and a different composition structure to the adjacent areas. The decrease in community descriptors (i.e. abundance and biomass) in this area is probably a symptom of population changes induced by intense fishery exploitation. Overall, a combination of environmental variables and human-induced impacts appears to influence the bentho-pelagic communities along the slope areas of the Mediterranean.En este estudio se describe la estructura y patrones de distribución de la comunidad de megafauna que habita en el margen continental medio a lo largo del Mediterráneo. El estudio se realizó entre los 500 y 800 m, coincidiendo espacialmente con las pesquerías de profundidad. A pesar de que se conoce parcialmente la estructura de las comunidades que habitan por debajo de 500 m, existe la necesidad de estudiar estas comunidades a una escala espacial más amplia. Dentro del marco del proyecto internacional MEDITS, se comparó la estructura de las comunidades en diez sub-áreas geográficas (GSAs) a lo largo de las costas mediterráneas. Además se analizó la distribución espacial del esfuerzo pesquero utilizando la información de los datos de seguimiento de buques. En general los resultados mostraron diferencias significativas entre subáreas mostrando un patrón decreciente en los valores de biomasa hacia el este, siendo la longitud el principal factor explicativo del modelo de distribución (GAMs). Sin embargo, encontramos una subárea que no seguía el patrón general, la GSA6 (norte de España). La GSA6 mostró una biomasa y estructura de la comunidad diferente a las áreas adyacentes. La disminución de la biomasa en esta área parece ser un síntoma de los cambios poblaciones causados por la elevada intensidad de pesca en la zona. Los resultados sugieren que la distribución y estructura de las comunidades bento-pelágicas parecen estar moduladas por la combinación de las variables ambientales y los impactos producidos por la actividad humana

MSC-Regulated MicroRNAs Converge on the Transcription Factor FOXP2 and Promote Breast Cancer Metastasis

SummaryMesenchymal stem/stromal cells (MSCs) are progenitor cells shown to participate in breast tumor stroma formation and to promote metastasis. Despite expanding knowledge of their contributions to breast malignancy, the underlying molecular responses of breast cancer cells (BCCs) to MSC influences remain incompletely understood. Here, we show that MSCs cause aberrant expression of microRNAs, which, led by microRNA-199a, provide BCCs with enhanced cancer stem cell (CSC) properties. We demonstrate that such MSC-deregulated microRNAs constitute a network that converges on and represses the expression of FOXP2, a forkhead transcription factor tightly associated with speech and language development. FOXP2 knockdown in BCCs was sufficient in promoting CSC propagation, tumor initiation, and metastasis. Importantly, elevated microRNA-199a and depressed FOXP2 expression levels are prominent features of malignant clinical breast cancer and are associated significantly with poor survival. Our results identify molecular determinants of cancer progression of potential utility in the prognosis and therapy of breast cancer

Melusin gene (ITGB1BP2) nucleotide variations study in hypertensive and cardiopathic patients

<p>Abstract</p> <p>Background</p> <p>Melusin is a muscle specific signaling protein, required for compensatory hypertrophy response in pressure-overloaded heart. The role of Melusin in heart function has been established both by loss and gain of function experiments in murine models. With the aim of verifying the hypothesis of a potential role of the Melusin encoding gene, <it>ITGB1BP2</it>, in the modification of the clinical phenotype of human cardiomyopathies, we screened the <it>ITGB1BP2 </it>gene looking for genetic variations possibly associated to the pathological phenotype in three selected groups of patients affected by hypertension and dilated or hypertrophic cardiomyopathy</p> <p>Methods</p> <p>We analyzed <it>ITGB1BP2 </it>by direct sequencing of the 11 coding exons and intron flanking sequences in 928 subjects, including 656 hypertensive or cardiopathic patients and 272 healthy individuals.</p> <p>Results</p> <p>Only three nucleotide variations were found in patients of three distinct families: a C>T missense substitution at position 37 of exon 1 causing an amino acid change from His-13 to Tyr in the protein primary sequence, a duplication (IVS6+12_18dupTTTTGAG) near the 5'donor splice site of intron 6, and a silent 843C>T substitution in exon 11.</p> <p>Conclusions</p> <p>The three variations of the <it>ITGB1BP2 </it>gene have been detected in families of patients affected either by hypertension or primary hypertrophic cardiomyopathy; however, a clear genotype/phenotype correlation was not evident. Preliminary functional results and bioinformatic analysis seem to exclude a role for IVS6+12_18dupTTTTGAG and 843C>T in affecting splicing mechanism.</p> <p>Our analysis revealed an extremely low number of variations in the <it>ITGB1BP2 </it>gene in nearly 1000 hypertensive/cardiopathic and healthy individuals, thus suggesting a high degree of conservation of the melusin gene within the populations analyzed.</p