TREX exposes the RNA binding domain of Nxf1 to enable mRNA export

The metazoan TREX complex is recruited to mRNA during nuclear RNA processing and functions in exporting mRNA to the cytoplasm. Nxf1 is an mRNA export receptor, which binds processed mRNA and transports it through the nuclear pore complex. At present, the relationship between TREX and Nxf1 is not understood. Here we show that Nxf1 uses an intramolecular interaction to inhibit its own RNA binding activity. When the TREX subunits Aly and Thoc5 make contact with Nxf1, Nxf1 is driven into an open conformation, exposing its RNA binding domain, allowing RNA binding. Moreover, the combined knockdown of Aly and Thoc5 drastically reduces the amount of Nxf1 bound to mRNA in vivo and also causes a severe mRNA export block. Together, our data indicate that TREX provides a license for mRNA export by driving Nxf1 into a conformation capable of binding mRNA

Clinical aspects of incorporating cord clamping into stabilisation of preterm infants

Fetal to neonatal transition is characterised by major pulmonary and haemodynamic changes occurring in a short period of time. In the international neonatal resuscitation guidelines, comprehensive recommendations are available on supporting pulmonary transition and delaying clamping of the cord in preterm infants. Recent experimental studies demonstrated that the pulmonary and haemodynamic transition are intimately linked, could influence each other and that the timing of umbilical cord clamping should be incorporated into the respiratory stabilisation. We reviewed the current knowledge on how to incorporate cord clamping into stabilisation of preterm infants and the physiological-based cord clamping (PBCC) approach, with the infant's transitional status as key determinant of timing of cord clamping. This approach could result in optimal timing of cord clamping and has the potential to reduce major morbidities and mortality in preterm infants

Становище Заславського римо-католицького деканату в ХІХ столітті (The situation of the Zaslavsky Roman-Catholic Deanery in the 19th century)

Стаття присвячена аналізу римо-католицизму на Заславщині у ХІХ ст. Доведено, що становище Заславського римо-католицького деканату протягом ХІХ століття погіршувалося, що відповідало загальним тенденціям ситуації РКЦ в Російській імперії. (The article is devoted to the analysis of Roman Catholicism in Zaslavsk region in the 19th century. It is proved that the situation of Zaslavsky Roman Catholic deanery during the 19th century worsened, which corresponded to the general tendencies of the situation of the RCC in the Russian Empire.

Causes of Death Following PCI Versus CABG in Complex CAD 5-Year Follow-Up of SYNTAX

AbstractBackgroundThere are no data available on specific causes of death from randomized trials that have compared coronary artery bypass grafting (CABG) with percutaneous coronary intervention (PCI).ObjectivesThe purpose of this study was to investigate specific causes of death, and its predictors, after revascularization for complex coronary disease in patients.MethodsAn independent Clinical Events Committee consisting of expert physicians who were blinded to the study treatment subclassified causes of death as cardiovascular (cardiac and vascular), noncardiovascular, or undetermined according to the trial protocol. Cardiac deaths were classified as sudden cardiac, related to myocardial infarction (MI), and other cardiac deaths.ResultsIn the randomized cohort, there were 97 deaths after CABG and 123 deaths after PCI during a 5-year follow-up. After CABG, 49.4% of deaths were cardiovascular, with the greatest cause being heart failure, arrhythmia, or other causes (24.6%), whereas after PCI, the majority of deaths were cardiovascular (67.5%) and as a result of MI (29.3%). The cumulative incidence rates of all-cause death were not significantly different between CABG and PCI (11.4% vs. 13.9%, respectively; p = 0.10), whereas there were significant differences in terms of cardiovascular (5.8% vs. 9.6%, respectively; p = 0.008) and cardiac death (5.3% vs. 9.0%, respectively; p = 0.003), which were caused primarily by a reduction in MI-related death with CABG compared with PCI (0.4% vs. 4.1%, respectively; p <0.0001). Treatment with PCI versus CABG was an independent predictor of cardiac death (hazard ratio: 1.55; 95% confidence interval: 1.09 to 2.33; p = 0.045). The difference in MI-related death was seen largely in patients with diabetes, 3-vessel disease, or high SYNTAX (TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries) trial scores.ConclusionsDuring a 5-year follow-up, CABG in comparison with PCI was associated with a significantly reduced rate of MI-related death, which was the leading cause of death after PCI. Treatments following PCI should target reducing post-revascularization spontaneous MI. Furthermore, secondary preventive medication remains essential in reducing events post-revascularization. (TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX]; NCT00114972

Comparison of Two Respiratory Support Strategies for Stabilization of Very Preterm Infants at Birth: A Matched-Pairs Analysis

Objective: Respiratory support for stabilizing very preterm infants at birth varies between centers. We retrospectively compared two strategies that involved either increasing continuous positive airway pressures (CPAP), or increasing oxygen supplementation.Methods: Matched-pairs of infants (&lt;28 weeks of gestation) were born either at the Leiden University Medical Center [low-pressure: CPAP 5–8 cmH2O and/or positive pressure ventilation (PPV) and fraction of inspired oxygen (FiO2) 0.3–1.0; n = 27], or at the University Hospital of Cologne (high-pressure: CPAP 12–35 cmH2O, no PPV and FiO2 0.3–0.4; n = 27). Respiratory support was initiated non-invasively via facemask at both units. Infants (n = 54) were matched between centers for gestational age and birth weight, to compare physiological and short-term clinical outcomes.Results: In the low-pressure group, 20/27 (74%) infants received 1–2 sustained inflations (20, 25 cm H2O) and 22/27 (81%) received PPV (1:19–3:01 min) using pressures of 25–27 cm H2O. Within 3 min of birth [median (IQR)], mean airway pressures [12 (6–15) vs. 19 (16–23) cmH2O, p &lt; 0.001] and FiO2 [0.30 (0.28–0.31) vs. 0.22 (0.21–0.30), p &lt; 0.001] were different in low- vs. high-pressure groups, respectively. SpO2 and heart rates were similar. After 3 min, higher FiO2 levels [0.62 (0.35–0.98) vs. 0.28 (0.22–0.38), p = 0.005] produced higher SpO2 levels [77 (50–92) vs. 53 (42–69)%, p &lt; 0.001] in the low-pressure group, but SpO2/FiO2 and heart rates were similar. While intubation rates during admission were significantly different (70 vs. 30%, p = 0.013), pneumothorax rates (4 vs. 19%, p = 0.125) and the occurrence of spontaneous intestinal perforations (0 vs. 15%, p = 0.125) were similar between groups.Conclusion: Infants (&lt;28 weeks) can be supported non-invasively at birth with either higher or lower pressures and while higher-pressure support may require less oxygen, it does not eliminate the need for oxygen supplementation. Future studies need to examine the effect of high pressures and pressure titration in the delivery room

Paradigm of tunable clustering using binarization of consensus partition matrices (Bi-CoPaM) for gene discovery

Copyright @ 2013 Abu-Jamous et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Clustering analysis has a growing role in the study of co-expressed genes for gene discovery. Conventional binary and fuzzy clustering do not embrace the biological reality that some genes may be irrelevant for a problem and not be assigned to a cluster, while other genes may participate in several biological functions and should simultaneously belong to multiple clusters. Also, these algorithms cannot generate tight clusters that focus on their cores or wide clusters that overlap and contain all possibly relevant genes. In this paper, a new clustering paradigm is proposed. In this paradigm, all three eventualities of a gene being exclusively assigned to a single cluster, being assigned to multiple clusters, and being not assigned to any cluster are possible. These possibilities are realised through the primary novelty of the introduction of tunable binarization techniques. Results from multiple clustering experiments are aggregated to generate one fuzzy consensus partition matrix (CoPaM), which is then binarized to obtain the final binary partitions. This is referred to as Binarization of Consensus Partition Matrices (Bi-CoPaM). The method has been tested with a set of synthetic datasets and a set of five real yeast cell-cycle datasets. The results demonstrate its validity in generating relevant tight, wide, and complementary clusters that can meet requirements of different gene discovery studies.National Institute for Health Researc

SCAMP:standardised, concentrated, additional macronutrients, parenteral nutrition in very preterm infants: a phase IV randomised, controlled exploratory study of macronutrient intake, growth and other aspects of neonatal care

<p>Abstract</p> <p>Background</p> <p>Infants born <29 weeks gestation are at high risk of neurocognitive disability. Early postnatal growth failure, particularly head growth, is an important and potentially reversible risk factor for impaired neurodevelopmental outcome. Inadequate nutrition is a major factor in this postnatal growth failure, optimal protein and calorie (macronutrient) intakes are rarely achieved, especially in the first week. Infants <29 weeks are dependent on parenteral nutrition for the bulk of their nutrient needs for the first 2-3 weeks of life to allow gut adaptation to milk digestion. The prescription, formulation and administration of neonatal parenteral nutrition is critical to achieving optimal protein and calorie intake but has received little scientific evaluation. Current neonatal parenteral nutrition regimens often rely on individualised prescription to manage the labile, unpredictable biochemical and metabolic control characteristic of the early neonatal period. Individualised prescription frequently fails to translate into optimal macronutrient delivery. We have previously shown that a standardised, concentrated neonatal parenteral nutrition regimen can optimise macronutrient intake.</p> <p>Methods</p> <p>We propose a single centre, randomised controlled exploratory trial of two standardised, concentrated neonatal parenteral nutrition regimens comparing a standard macronutrient content (maximum protein 2.8 g/kg/day; lipid 2.8 g/kg/day, dextrose 10%) with a higher macronutrient content (maximum protein 3.8 g/kg/day; lipid 3.8 g/kg/day, dextrose 12%) over the first 28 days of life. 150 infants 24-28 completed weeks gestation and birthweight <1200 g will be recruited. The primary outcome will be head growth velocity in the first 28 days of life. Secondary outcomes will include a) auxological data between birth and 36 weeks corrected gestational age b) actual macronutrient intake in first 28 days c) biomarkers of biochemical and metabolic tolerance d) infection biomarkers and other intravascular line complications e) incidence of major complications of prematurity including mortality f) neurodevelopmental outcome at 2 years corrected gestational age</p> <p>Trial registration</p> <p>Current controlled trials: <a href="http://www.controlled-trials.com/ISRCTN76597892">ISRCTN76597892</a>; EudraCT Number: 2008-008899-14</p