94 research outputs found
Metabolic and vascular determinants of impaired cognitive performance and abnormalities on brain magnetic resonance imaging in patients with type 2 diabetes
Evidence for biological roots in the transgenerational transmission of intimate partner violence
Intimate partner violence is a ubiquitous and devastating phenomenon for which effective interventions and a clear etiological understanding are still lacking. A major risk factor for violence perpetration is childhood exposure to violence, prompting the proposal that social learning is a major contributor to the transgenerational transmission of violence. Using an animal model devoid of human cultural factors, we showed that male rats became highly aggressive against their female partners as adults after exposure to non-social stressful experiences in their youth. Their offspring also showed increased aggression toward females in the absence of postnatal father–offspring interaction or any other exposure to violence. Both the females that cohabited with the stressed males and those that cohabited with their male offspring showed behavioral (including anxiety- and depression-like behaviors), physiological (decreased body weight and basal corticosterone levels) and neurobiological symptoms (increased activity in dorsal raphe serotonergic neurons in response to an unfamiliar male) resembling the alterations described in abused and depressed women. With the caution required when translating animal work to humans, our findings extend current psychosocial explanations of the transgenerational transmission of intimate partner violence by strongly suggesting an important role for biological factors
BioGPS: an extensible and customizable portal for querying and organizing gene annotation resources
BioGPS is a community based customisable gene annotation portal bringing together gene annotation resources on to a single platform
Alternative Splicing in the Differentiation of Human Embryonic Stem Cells into Cardiac Precursors
The role of alternative splicing in self-renewal, pluripotency and tissue lineage specification of human embryonic stem cells (hESCs) is largely unknown. To better define these regulatory cues, we modified the H9 hESC line to allow selection of pluripotent hESCs by neomycin resistance and cardiac progenitors by puromycin resistance. Exon-level microarray expression data from undifferentiated hESCs and cardiac and neural precursors were used to identify splice isoforms with cardiac-restricted or common cardiac/neural differentiation expression patterns. Splice events for these groups corresponded to the pathways of cytoskeletal remodeling, RNA splicing, muscle specification, and cell cycle checkpoint control as well as genes with serine/threonine kinase and helicase activity. Using a new program named AltAnalyze (http://www.AltAnalyze.org), we identified novel changes in protein domain and microRNA binding site architecture that were predicted to affect protein function and expression. These included an enrichment of splice isoforms that oppose cell-cycle arrest in hESCs and that promote calcium signaling and cardiac development in cardiac precursors. By combining genome-wide predictions of alternative splicing with new functional annotations, our data suggest potential mechanisms that may influence lineage commitment and hESC maintenance at the level of specific splice isoforms and microRNA regulation
Is body size at birth related to circadian salivary cortisol levels in adulthood? Results from a longitudinal cohort study
<p>Abstract</p> <p>Background</p> <p>The hypothesis of fetal origins of adult disease has during the last decades received interest as an explanation of chronic, e.g. cardiovascular, disease in adulthood stemming from fetal environmental conditions. Early programming and enduring dysregulations of the hypothalamic-pituitary-adrenal (HPA axis), with cortisol as its end product, has been proposed as a possible mechanism by which birth weight influence later health status. However, the fetal origin of the adult cortisol regulation has been insufficiently studied. The present study aims to examine if body size at birth is related to circadian cortisol levels at 43 years.</p> <p>Methods</p> <p>Participants were drawn from a prospective cohort study (n = 752, 74.5%). Salivary cortisol samples were collected at four times during one day at 43 years, and information on birth size was collected retrospectively from delivery records. Information on body mass during adolescence and adulthood and on health behavior, medication and medical conditions at 43 years was collected prospectively by questionnaire and examined as potential confounders. Participants born preterm or < 2500 g were excluded from the main analyses.</p> <p>Results</p> <p>Across the normal spectrum, size at birth (birth weight and ponderal index) was positively related to total (area under the curve, AUC) and bedtime cortisol levels in the total sample. Results were more consistent in men than in women. Descriptively, participants born preterm or < 2500 g also seemed to display elevated evening and total cortisol levels. No associations were found for birth length or for the cortisol awakening response (CAR).</p> <p>Conclusions</p> <p>These results are contradictory to previously reported negative associations between birth weight and adult cortisol levels, and thus tentatively question the assumption that only low birth weight predicts future physiological dysregulations.</p
The Spread of Tomato Yellow Leaf Curl Virus from the Middle East to the World
The ongoing global spread of Tomato yellow leaf curl virus (TYLCV; Genus Begomovirus, Family Geminiviridae) represents a serious looming threat to tomato production in all temperate parts of the world. Whereas determining where and when TYLCV movements have occurred could help curtail its spread and prevent future movements of related viruses, determining the consequences of past TYLCV movements could reveal the ecological and economic risks associated with similar viral invasions. Towards this end we applied Bayesian phylogeographic inference and recombination analyses to available TYLCV sequences (including those of 15 new Iranian full TYLCV genomes) and reconstructed a plausible history of TYLCV's diversification and movements throughout the world. In agreement with historical accounts, our results suggest that the first TYLCVs most probably arose somewhere in the Middle East between the 1930s and 1950s (with 95% highest probability density intervals 1905–1972) and that the global spread of TYLCV only began in the 1980s after the evolution of the TYLCV-Mld and -IL strains. Despite the global distribution of TYLCV we found no convincing evidence anywhere other than the Middle East and the Western Mediterranean of epidemiologically relevant TYLCV variants arising through recombination. Although the region around Iran is both the center of present day TYLCV diversity and the site of the most intensive ongoing TYLCV evolution, the evidence indicates that the region is epidemiologically isolated, which suggests that novel TYLCV variants found there are probably not direct global threats. We instead identify the Mediterranean basin as the main launch-pad of global TYLCV movements
Ghrelin Modulates the fMRI BOLD Response of Homeostatic and Hedonic Brain Centers Regulating Energy Balance in the Rat
The orexigenic gut-brain peptide, ghrelin and its G-protein coupled receptor, the growth hormone secretagogue receptor
1a (GHS-R1A) are pivotal regulators of hypothalamic feeding centers and reward processing neuronal circuits of the brain.
These systems operate in a cooperative manner and receive a wide array of neuronal hormone/transmitter messages and
metabolic signals. Functional magnetic resonance imaging was employed in the current study to map BOLD responses to
ghrelin in different brain regions with special reference on homeostatic and hedonic regulatory centers of energy balance.
Experimental groups involved male, ovariectomized female and ovariectomized estradiol-replaced rats. Putative modulation
of ghrelin signaling by endocannabinoids was also studied. Ghrelin-evoked effects were calculated as mean of the BOLD
responses 30 minutes after administration. In the male rat, ghrelin evoked a slowly decreasing BOLD response in all studied
regions of interest (ROI) within the limbic system. This effect was antagonized by pretreatment with GHS-R1A antagonist
JMV2959. The comparison of ghrelin effects in the presence or absence of JMV2959 in individual ROIs revealed significant
changes in the prefrontal cortex, nucleus accumbens of the telencephalon, and also within hypothalamic centers like the
lateral hypothalamus, ventromedial nucleus, paraventricular nucleus and suprachiasmatic nucleus. In the female rat, the
ghrelin effects were almost identical to those observed in males. Ovariectomy and chronic estradiol replacement had no
effect on the BOLD response. Inhibition of the endocannabinoid signaling by rimonabant significantly attenuated the
response of the nucleus accumbens and septum. In summary, ghrelin can modulate hypothalamic and mesolimbic
structures controlling energy balance in both sexes. The endocannabinoid signaling system contributes to the
manifestation of ghrelin’s BOLD effect in a region specific manner. In females, the estradiol milieu does not influence the
BOLD response to ghrelin
Identification and Pathway Analysis of microRNAs with No Previous Involvement in Breast Cancer
microRNA expression signatures can differentiate normal and breast cancer tissues and can define specific clinico-pathological phenotypes in breast tumors. In order to further evaluate the microRNA expression profile in breast cancer, we analyzed the expression of 667 microRNAs in 29 tumors and 21 adjacent normal tissues using TaqMan Low-density arrays. 130 miRNAs showed significant differential expression (adjusted P value = 0.05, Fold Change = 2) in breast tumors compared to the normal adjacent tissue. Importantly, the role of 43 of these microRNAs has not been previously reported in breast cancer, including several evolutionary conserved microRNA*, showing similar expression rates to that of their corresponding leading strand. The expression of 14 microRNAs was replicated in an independent set of 55 tumors. Bioinformatic analysis of mRNA targets of the altered miRNAs, identified oncogenes like ERBB2, YY1, several MAP kinases, and known tumor-suppressors like FOXA1 and SMAD4. Pathway analysis identified that some biological process which are important in breast carcinogenesis are affected by the altered microRNA expression, including signaling through MAP kinases and TP53 pathways, as well as biological processes like cell death and communication, focal adhesion and ERBB2-ERBB3 signaling. Our data identified the altered expression of several microRNAs whose aberrant expression might have an important impact on cancer-related cellular pathways and whose role in breast cancer has not been previously described
Intimate partner violence against women in the Erbil city of the Kurdistan region, Iraq
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Criteria for the definition of Pituitary Tumor Centers of Excellence (PTCOE): A Pituitary Society Statement
Introduction
With the goal of generate uniform criteria among centers dealing with pituitary tumors and to enhance patient care, the Pituitary Society decided to generate criteria for developing Pituitary Tumors Centers of Excellence (PTCOE).
Methods
To develop that task, a group of ten experts served as a Task Force and through two years of iterative work an initial draft was elaborated. This draft was discussed, modified and finally approved by the Board of Directors of the Pituitary Society. Such document was presented and debated at a specific session of the Congress of the Pituitary Society, Orlando 2017, and suggestions were incorporated. Finally the document was distributed to a large group of global experts that introduced further modifications with final endorsement.
Results
After five years of iterative work a document with the ideal criteria for a PTCOE is presented.
Conclusions
Acknowledging that very few centers in the world, if any, likely fulfill the requirements here presented, the document may be a tool to guide improvements of care delivery to patients with pituitary disorders. All these criteria must be accommodated to the regulations and organization of Health of a given country
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