A dynamic role of mastermind-like 1. A journey through the main (path)ways between development and cancer

Major signaling pathways, such as Notch, Hedgehog (Hh), Wnt/β-catenin and Hippo, are targeted by a plethora of physiological and pathological stimuli, ultimately resulting in the modulation of genes that act coordinately to establish specific biological processes. Many biological programs are strictly controlled by the assembly of multiprotein complexes into the nucleus, where a regulated recruitment of specific transcription factors and coactivators on gene promoter region leads to different transcriptional outcomes. MAML1 results to be a versatile coactivator, able to set up synergistic interlinking with pivotal signaling cascades and able to coordinate the network of cross-talking pathways. Accordingly, despite its original identification as a component of the Notch signaling pathway, several recent reports suggest a more articulated role for MAML1 protein, showing that it is able to sustain/empower Wnt/β-catenin, Hh and Hippo pathways, in a Notch-independent manner. For this reason, MAML1 may be associated to a molecular “switch”, with the function to control the activation of major signaling pathways, triggering in this way critical biological processes during embryonic and post-natal life. In this review, we summarize the current knowledge about the pleiotropic role played by MAML proteins, in particular MAML1, and we recapitulate how it takes part actively in physiological and pathological signaling networks. On this point, we also discuss the contribution of MAML proteins to malignant transformation. Accordingly, genetic alterations or impaired expression of MAML proteins may lead to a deregulated crosstalk among the pathways, culminating in a series of pathological disorders, including cancer development. Given their central role, a better knowledge of the molecular mechanisms that regulate the interplay of MAML proteins with several signaling pathways involved in tumorigenesis may open up novel opportunities for an attractive molecular targeted anticancer therapy

Antenatal corticosteroid treatment for the prevention of peri-intraventricular haemorrhage in preterm newborns: a retrospective cohort study using transfontanelle ultrasonography

Objective: The objective of this study was to assess the correlation between antenatal corticosteroids and peri-intraventricular haemorrhage (PIVH) using transfontanelle ultrasonography, as well as to evaluate the risk factors for its incidence. Methods: We performed a retrospective cohort study using medical records of preterm newborns. The protocol for maternal corticoid administration for foetal lung maturation included dexamethasone 4 mg (intramuscular) 8/8 hours per 48 hours, with one cycle per week. The diagnosis of periintraventricular haemorrhage was based on transfontanelle ultrasonography, using the Papile's classification. The following risk factors for peri-intraventricular haemorrhage were assessed: birth weight, gestational age at delivery, type of delivery, newborn's sex, surfactant administration, premature rupture of membranes and previous history of infection during the current pregnancy. The student's t-test and chi-square test were used for statistical analysis. Results: Our sample population included 184 preterm newborns. Transfontanelle ultrasonography revealed peri-intraventricular haemorrhage in 32 (74.4%) and periventricular leukomalacia in 11 (25.6%) newborns. Grade I haemorrhage was found in 20 (62.5%), grade II in five (15.6%), and grade III in seven (21.8%) newborns, as in accordance with Papile's classification. Vaginal delivery (p = 0.010), birth weight <1500 g (p = 0.024), gestational age at delivery ≤32 weeks (p = 0.018), and previous history of infection during pregnancy (p = 0.013) were considered risk factors for peri-intraventricular haemorrhage in preterm newborns. Conclusion: Maternal corticoid administration for foetal lung maturation showed a protective effect against peri-intraventricular haemorrhage in preterm newborns. The risk factors for peri-intraventricular haemorrhage were determined

MINT, the molecular interaction database: 2012 update

The Molecular INTeraction Database (MINT, http://mint.bio.uniroma2.it/mint/) is a public repository for protein-protein interactions (PPI) reported in peer-reviewed journals. The database grows steadily over the years and at September 2011 contains approximately 235,000 binary interactions captured from over 4750 publications. The web interface allows the users to search, visualize and download interactions data. MINT is one of the members of the International Molecular Exchange consortium (IMEx) and adopts the Molecular Interaction Ontology of the Proteomics Standard Initiative (PSI-MI) standards for curation and data exchange. MINT data are freely accessible and downloadable at http://mint.bio.uniroma2.it/mint/download.do. We report here the growth of the database, the major changes in curation policy and a new algorithm to assign a confidence to each interaction

Reproducibility of fetal heart volume by 3D-sonography using the XI VOCAL method

<p>Abstract</p> <p>Background</p> <p>To assess the reliability of fetal heart volume measurement by three-dimensional sonography (3DUS) using the eXtended Imaging Virtual Organ Computer-aided AnaLysis (XI VOCAL) method.</p> <p>Methods</p> <p>This reliability study enrolled 30 pregnant women with singleton healthy pregnancies between 19 and 34 weeks of gestation. All volume acquirements were performed with a convex volumetric transducer (C3-7ED) coupled to an Accuvix XQ sonography device (Medison, Korea). The XI VOCAL 10 planes was the method of choice for volumetric measurement. 3D datasets were analyzed by two observers (EQSB and HJFM); fetal heart volume was measured twice by the first and once by the second observer to calculate intra and interobserver reproducibility. Statistical analysis used pareated Student's t test (p) and calculated Intraclass correlation coefficients (ICC). Bland-Altman plots were also constructed.</p> <p>Results</p> <p>We observed an excellent intra- and interobserver reliability for fetal cardiac volume assessed by XI VOCAL. For the intraobserver the ICC was 0.998 (95% CI: 0.997; 0.999), with mean of differences of 0.12 cm³(95% limits of agreement: -0.84; +0.84; p = 0.130). For interobserver the ICC was 0.899 (95%CI: 0.996; 0.998), mean of differences 0.05 cm³(95% limits of agreement: -0.84; +0.84; p = 0.175).</p> <p>Conclusion</p> <p>Fetal cardiac volume assessed by 3DUS using XI VOCAL method is highly reproducible between 19 to 34 gestational weeks.</p

Comparison of diurnal variations, gestational age and gender related differences in fetal heart rate (FHR) parameters between appropriate-for-gestational-age (AGA) and small-for-gestational-age (SGA) fetuses in the home environment

Objective To assess the influence of gender, time of the day and gestational age on fetal heart rate (FHR) parameters between appropriate-for-gestational-age (AGA) and small-for-gestational age (SGA) fetuses using a portable fetal ECG monitor employed in the home setting. Methods We analysed and compared the antenatal FHR data collected in the home setting on 61 healthy pregnant women with singleton pregnancies from 24 weeks gestation. Of the 61 women, 31 had SGA fetuses (estimated fetal weight below the tenth gestational centile) and 30 were pregnant with AGA fetuses. FHR recordings were collected for up to 20 h. Two 90 min intervals were deliberately chosen retrospectively with respect to signal recording quality, one during day-time and one at night-time for comparison. Results Overall, success rate of the fetal abdominal ECG in the AGA fetuses was 75.7% compared to 48.6% in the SGA group. Based on randomly selected episodes of heart rate traces where recording quality exceeded 80% we were able to show a marginal difference between day and night-time recordings in AGA vs. SGA fetuses beyond 32 weeks of gestation. A selection bias in terms of covering different representation periods of fetal behavioural states cannot be excluded. In contrast to previous studies, we neither controlled maternal diet and activity nor measured maternal blood hormone and heart rate as all mothers were monitored in the home environment. Conclusion Based on clinically unremarkable, but statistically significant differences in the FHR parameters between the AGA and SGA group we suggest that further studies with large sample size are required to assess the clinical value of antenatal fetal ECG monitoring

Effect of malaria on placental volume measured using three-dimensional ultrasound: a pilot study

Background: The presence of malaria parasites and histopathological changes in the placenta are associated with a reduction in birth weight, principally due to intrauterine growth restriction. The aim of this study was to examine the feasibility of studying early pregnancy placental volumes using three-dimensional (3D) ultrasound in a malaria endemic area, as a small volume in the second trimester may be an indicator of intra-uterine growth restriction and placental insufficiency. Methods: Placenta volumes were acquired using a portable ultrasound machine and a 3D ultrasound transducer and estimated using the Virtual Organ Computer-aided AnaLysis (VOCAL) image analysis software package. Intraobserver reliability and limits of agreement of the placenta volume measurements were calculated. Polynomial regression models for the mean and standard deviation as a function of gestational age for the placental volumes of uninfected women were created and tested. Based on these equations each measurement was converted into a z -score. The z-scores of the placental volumes of malaria infected and uninfected women were then compared. Results: Eighty-four women (uninfected = 65; infected = 19) with a posterior placenta delivered congenitally normal, live born, single babies. The mean placental volumes in the uninfected women were modeled to fit 5th, 10th, 50th, 90th and 95th centiles for 14-24 weeks’ gestation. Most placenta volumes in the infected women were below the 50th centile for gestational age; most of those with Plasmodium falciparum were below the 10th centile. The 95% intra-observer limits of agreement for first and second measurements were ± 37.0 mL and ± 25.4 mL at 30 degrees and 15 degrees rotation respectively. Conclusion: The new technique of 3D ultrasound volumetry of the placenta may be useful to improve our understanding of the pathophysiological constraints on foetal growth caused by malaria infection in early pregnancy

A manually annotated Actinidia chinensis var. chinensis (kiwifruit) genome highlights the challenges associated with draft genomes and gene prediction in plants

Most published genome sequences are drafts, and most are dominated by computational gene prediction. Draft genomes typically incorporate considerable sequence data that are not assigned to chromosomes, and predicted genes without quality confidence measures. The current Actinidia chinensis (kiwifruit) 'Hongyang' draft genome has 164\ua0Mb of sequences unassigned to pseudo-chromosomes, and omissions have been identified in the gene models

View Sheed Assessment for Urban Renovation Strategies: Landscape Values Perception Plays a Role for Urban Development

The starting position for this research is to consider “viewshed analysis” as a useful basis of the development of spatial planning practices aimed at the protection of the territorial landscape values. Considering the specific case study of the Potenza town, the scope of this work is to ensure landscape protection and to encourage design that look to the redevelopment of specific areas of the urban fabric actually classified as degraded. Together with the analytical approach based on view sheed analysis, local survey and classifications, and land suitability approach, a proposal had been developed in terms of strategic objectives to be included in a wider process of urban regeneration