Bioinformatic detection of E47, E2F1 and SREBP1 transcription factors as potential regulators of genes associated to acquisition of endometrial receptivity

<p>Abstract</p> <p>Background</p> <p>The endometrium is a dynamic tissue whose changes are driven by the ovarian steroidal hormones. Its main function is to provide an adequate substrate for embryo implantation. Using microarray technology, several reports have provided the gene expression patterns of human endometrial tissue during the window of implantation. However it is required that biological connections be made across these genomic datasets to take full advantage of them. The objective of this work was to perform a research synthesis of available gene expression profiles related to acquisition of endometrial receptivity for embryo implantation, in order to gain insights into its molecular basis and regulation.</p> <p>Methods</p> <p>Gene expression datasets were intersected to determine a consensus endometrial receptivity transcript list (CERTL). For this cluster of genes we determined their functional annotations using available web-based databases. In addition, promoter sequences were analyzed to identify putative transcription factor binding sites using bioinformatics tools and determined over-represented features.</p> <p>Results</p> <p>We found 40 up- and 21 down-regulated transcripts in the CERTL. Those more consistently increased were C4BPA, SPP1, APOD, CD55, CFD, CLDN4, DKK1, ID4, IL15 and MAP3K5 whereas the more consistently decreased were OLFM1, CCNB1, CRABP2, EDN3, FGFR1, MSX1 and MSX2. Functional annotation of CERTL showed it was enriched with transcripts related to the immune response, complement activation and cell cycle regulation. Promoter sequence analysis of genes revealed that DNA binding sites for E47, E2F1 and SREBP1 transcription factors were the most consistently over-represented and in both up- and down-regulated genes during the window of implantation.</p> <p>Conclusions</p> <p>Our research synthesis allowed organizing and mining high throughput data to explore endometrial receptivity and focus future research efforts on specific genes and pathways. The discovery of possible new transcription factors orchestrating the CERTL opens new alternatives for understanding gene expression regulation in uterine function.</p

Real-time evaluation of the on-board comfort of standing passenger in bus transit services

Bus on-board comfort may be intended as a multidimensional concept declined according to several attributes (e.g., vibrations, the load factor, the driving style, etc.) and represents a key factor of service quality. Thus, its measurement is crucial for public transport companies as it can support for the monitoring, evaluation and implementation of specific actions to improve their services. The objective of this paper is to build a numerical scale for real-time measurement of bus on-board comfort. This is pursued integrating subjective measurements of the driving style provided by the passengers with objective ones of longitudinal and transversal accelerations data collected by Intelligent Transportation System tools. The results are very useful because they represent a contribution to establish a comfort scale in a real operational environment, as a tool to regulate the driver's behavior: each driver is in the position of real-time monitoring the quality of a bus ride regarding on-board comfort level

Using texture analysis in the development of a potential radiomic signature for early identification of hepatic metastasis in colorectal cancer

Background: Radiomics allows information not readily available to the naked eye to be extracted from high resolution imaging modalities such as CT. Identifying that a cancer has already metastasised at the time of presentation through a radiomic signature will affect the treatment pathway. The ability to recognise the existence of metastases earlier will have a significant impact on the survival outcomes. / Aim: To create a novel radiomic signature using textural analysis in the evaluation of synchronous liver metastases in colorectal cancer. / Methods: CT images at baseline and subsequent surveillance over a 5-year period of patients with colorectal cancer were processed using textural analysis software. Comparison was made between those patients who developed liver metastases and those that remained disease free to detect differences in the ‘texture’ of the liver. / Results: A total of 24 patients were divided into two matched groups for comparison. Significant differences between the two groups scores when using the textural analysis programme were found on coarse filtration (p = 0.044). Patients that went on to develop metastases an average of 18 months after presentation had higher levels of hepatic heterogeneity on CT. / Conclusion: This initial study demonstrates the potential of using a textural analysis programme to build a radiomic signature to predict the development of hepatic metastases in rectal cancer patients otherwise thought to have clear staging CT scans at time of presentation

Happiness on Tap: Piped Water Adoption in Urban Morocco

We study the demand for household water connections in urban Morocco, and the effect of such connections on household welfare. In the northern city of Tangiers, among homeowners without a private connection to the city’s water grid, a random subset was offered a simplified procedure to purchase a household connection on credit (at a zero percent interest rate). Take-up was high, at 69%. Because all households in our sample had access to the water grid through free public taps (often located fairly close to their homes), household connections did not lead to any improvement in the quality of the water households consumed; and despite significant increase in the quantity of water consumed, we find no change in the incidence of waterborne illnesses. Nevertheless, we find that households are willing to pay a substantial amount of money to have a private tap at home. Being connected generates important time gains, which are used for leisure and social activities, rather than productive activities. Because water is often a source of tension between households, household connections improve social integration and reduce conflict. Overall, within 6 months, self-reported well-being improved substantially among households in the treatment group, despite the financial cost of the connection. Our results suggest that facilitating access to credit for households to finance lump sum quality-of-life investments can significantly increase welfare, even if those investments do not result in income or health gains

High energy photon-neutrino elastic scattering

The one-loop helicity amplitudes for the elastic scattering process $\gamma\nu\to\gamma\nu$ in the Standard Model are computed at high center of mass energies. A general decomposition of the amplitudes is utilized to investigate the validity of some of the key features of our results. In the center of mass, where $\sqrt{s} = 2\omega$, the cross section grows roughly as $\omega^6$ to near the threshold for $W$-boson production, $\sqrt{s} = m_W$. Although suppressed at low energies, we find that the elastic cross section exceeds the cross section for $\gamma\nu\to\gamma\gamma\nu$ when $\sqrt{s}>13$ GeV. We demonstrate that the scattered photons are circularly polarized and the net value of the polarization is non-zero. Astrophysical implications of high energy photon-neutrino scattering are discussed.Comment: 9 pages, 7 figures, RevTeX

A genome-wide association study identifies a susceptibility locus for biliary atresia on 2p16.1 within the gene EFEMP1

Biliary atresia (BA) is a rare pediatric cholangiopathy characterized by fibrosclerosing obliteration of the extrahepatic bile ducts, leading to cholestasis, fibrosis, cirrhosis, and eventual liver failure. The etiology of BA remains unknown, although environmental, inflammatory, infectious, and genetic risk factors have been proposed. We performed a genome-wide association study (GWAS) in a European-American cohort of 343 isolated BA patients and 1716 controls to identify genetic loci associated with BA. A second GWAS was performed in an independent European-American cohort of 156 patients with BA and other extrahepatic anomalies and 212 controls to confirm the identified candidate BA-associated SNPs. Meta-analysis revealed three genome-wide significant BA-associated SNPs on 2p16.1 (rs10865291, rs6761893, and rs727878; P < 5 ×10-8), located within the fifth intron of the EFEMP1 gene, which encodes a secreted extracellular protein implicated in extracellular matrix remodeling, cell proliferation, and organogenesis. RNA expression analysis showed an increase in EFEMP1 transcripts from human liver specimens isolated from patients with either BA or other cholestatic diseases when compared to normal control liver samples. Immunohistochemistry demonstrated that EFEMP1 is expressed in cholangiocytes and vascular smooth muscle cells in liver specimens from patients with BA and other cholestatic diseases, but it is absent from cholangiocytes in normal control liver samples. Efemp1 transcripts had higher expression in cholangiocytes and portal fibroblasts as compared with other cell types in normal rat liver. The identification of a novel BA-associated locus, and implication of EFEMP1 as a new BA candidate susceptibility gene, could provide new insights to understanding the mechanisms underlying this severe pediatric disorder

αSynuclein control of mitochondrial homeostasis in human-derived neurons is disrupted by mutations associated with Parkinson’s disease

The etiology of Parkinson’s disease (PD) converges on a common pathogenic pathway of mitochondrial defects in which α-Synuclein (αSyn) is thought to play a role. However, the mechanisms by which αSyn and its disease-associated allelic variants cause mitochondrial dysfunction remain unknown. Here, we analyzed mitochondrial axonal transport and morphology in human-derived neurons overexpressing wild-type (WT) αSyn or the mutated variants A30P or A53T, which are known to have differential lipid affinities. A53T αSyn was enriched in mitochondrial fractions, inducing significant mitochondrial transport defects and fragmentation, while milder defects were elicited by WT and A30P. We found that αSyn-mediated mitochondrial fragmentation was linked to expression levels in WT and A53T variants. Targeted delivery of WT and A53T αSyn to the outer mitochondrial membrane further increased fragmentation, whereas A30P did not. Genomic editing to disrupt the N-terminal domain of αSyn, which is important for membrane association, resulted in mitochondrial elongation without changes in fusion-fission protein levels, suggesting that αSyn plays a direct physiological role in mitochondrial size maintenance. Thus, we demonstrate that the association of αSyn with the mitochondria, which is modulated by protein mutation and dosage, influences mitochondrial transport and morphology, highlighting its relevance in a common pathway impaired in PD.Fil: Pozo Devoto, Victorio Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia ; ArgentinaFil: Dimopoulos, Nicolás. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Alloatti, Matías. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia ; ArgentinaFil: Pardi, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Saez, Trinidad María de Los Milagros. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Otero, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia ; ArgentinaFil: Cromberg, Lucas Eneas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia ; ArgentinaFil: Marin Burgin, Antonia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Scassa, Maria Elida. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Stokin, Gorazd B.. Anne’s University Hospital; República ChecaFil: Schinder, Alejandro Fabián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Sevlever, Gustavo. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Falzone, Tomas Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

The association between diurnal sleep patterns and emotions in infants and toddlers attending nursery

Background: Childcare programs often include mandatory naptime during the day. Loss of daytime sleep could lead to a moderate-to-large decrease in self-regulation, emotion processing, and learning in early childhood. Nevertheless, daytime sleep has been less accurately studied than nighttime sleep. This study aims to explore the relationship between diurnal sleep habits in nursery settings, nocturnal sleep quality, and post-nap emotional intensity in infants and toddlers. Methods: Data of 92 children (52 girls, 40 boys) aged 6 to 36 months were obtained. Sleep habits as well as positive and negative emotions were monitored by educators during nursery times through a sleep and emotion diary for two weeks. Results: Explorative analyses showed that diurnal sleep hours decreased across age groups (except for females aged 25–36 months) and that all age groups had a lower amount of nocturnal sleep than is recommended by the National Sleep Foundation. Partial correlation analysis showed significant correlation between daytime sleep onset latency and positive emotions. Mediation analyses showed that daytime napping is relevant for emotional functioning independently of nocturnal sleep quality. Conclusions: Daytime sleep in early childhood seems to be linked to the management of positive and negative emotions and could play a role in healthy development of emotional processes

CARD15 genotyping in inflammatory bowel disease patients by multiplex pyrosequencing

[No abstract available

ONE LOOP QED VERTEX IN ANY COVARIANT GAUGE: ITS COMPLETE ANALYTIC FORM

The one loop vertex in QED is calculated in arbitrary covariant gauges as an analytic function of its momenta. The vertex is decomposed into a longitudinal part, that is fully responsible for ensuring the Ward and Ward-Takahashi identities are satisfied, and a transverse part. The transverse part is decomposed into 8 independent components each being separately free of kinematic singularities in $\bf any$ covariant gauge in a basis that modifies that proposed by Ball and Chiu. Analytic expressions for all 11 components of the ${O(\alpha)}$ vertex are given explicitly in terms of elementary functions and one Spence function. These results greatly simplify in particular kinematic regimes.Comment: 35 pages, latex, 2 figures, Complete postscript file available from: ftp://cpt1.dur.ac.uk/pub/preprints/dtp95/dtp9506/dtp9406.p