PICH promotes sister chromatid disjunction and co-operates with topoisomerase II in mitosis

PICH is a SNF2 family DNA translocase that binds to ultra-fine DNA bridges (UFBs) in mitosis. Numerous roles for PICH have been proposed from protein depletion experiments, but a consensus has failed to emerge. Here, we report that deletion of PICH in avian cells causes chromosome structural abnormalities, and hypersensitivity to an inhibitor of Topoisomerase II (Topo II), ICRF-193. ICRF-193-treated PICH-/- cells undergo sister chromatid non-disjunction in anaphase, and frequently abort cytokinesis. PICH co-localises with Topo IIα on UFBs and at the ribosomal DNA locus, and the timely resolution of both structures depends on the ATPase activity of PICH. Purified PICH protein strongly stimulates the catalytic activity of Topo II in vitro. Consistent with this, a human PICH-/- cell line exhibits chromosome instability and chromosome condensation and decatenation defects similar to those of ICRF-193-treated cells. We propose that PICH and Topo II cooperate to prevent chromosome missegregation events in mitosis

Antenatal and postnatal corticosteroid and resuscitation induced lung injury in preterm sheep

<p>Abstract</p> <p>Background</p> <p>Initiation of ventilation using high tidal volumes in preterm lambs causes lung injury and inflammation. Antenatal corticosteroids mature the lungs of preterm infants and postnatal corticosteroids are used to treat bronchopulmonary dysplasia.</p> <p>Objective</p> <p>To test if antenatal or postnatal corticosteroids would decrease resuscitation induced lung injury.</p> <p>Methods</p> <p>129 d gestational age lambs (n = 5-8/gp; term = 150 d) were operatively delivered and ventilated after exposure to either 1) no medication, 2) antenatal maternal IM Betamethasone 0.5 mg/kg 24 h prior to delivery, 3) 0.5 mg/kg Dexamethasone IV at delivery or 4) Cortisol 2 mg/kg IV at delivery. Lambs then were ventilated with no PEEP and escalating tidal volumes (<it>V</it>_T) to 15 mL/kg for 15 min and then given surfactant. The lambs were ventilated with <it>V</it>_T8 mL/kg and PEEP 5 cmH₂0 for 2 h 45 min.</p> <p>Results</p> <p>High V_Tventilation caused a deterioration of lung physiology, lung inflammation and injury. Antenatal betamethasone improved ventilation, decreased inflammatory cytokine mRNA expression and alveolar protein leak, but did not prevent neutrophil influx. Postnatal dexamethasone decreased pro-inflammatory cytokine expression, but had no beneficial effect on ventilation, and postnatal cortisol had no effect. Ventilation increased liver serum amyloid mRNA expression, which was unaffected by corticosteroids.</p> <p>Conclusions</p> <p>Antenatal betamethasone decreased lung injury without decreasing lung inflammatory cells or systemic acute phase responses. Postnatal dexamethasone or cortisol, at the doses tested, did not have important effects on lung function or injury, suggesting that corticosteroids given at birth will not decrease resuscitation mediated injury.</p

Erratum: Sequence data and association statistics from 12,940 type 2 diabetes cases and controls.

This corrects the article DOI: 10.1038/sdata.2017.179

Effects of abstinence on brain morphology in alcoholism: A MRI study

Chronic alcohol abuse leads to morphological changes of the brain. We investigated if these volumetric changes are reversible after a period of abstinence. For this reason 41 male and 15 female alcohol patients underwent MRI-scanning after in-patient detoxification (baseline) entering alcoholism treatment programs, and between 6 and 9 months later (follow-up), in a phase of convalescence. Additionally, 29 male and 16 female control subjects were examined. The MRI-scans were delineated and the resulting regions of interest, volumes of lateral ventricles and prefrontal lobes were expressed relatively to total brain volume. Compared to control subjects alcohol patients showed bilaterally decreased prefrontal lobes (11% reduction) and increased lateral ventricles (up to 42% enlargement). The extent of the ventricular increase was depending on patient’s additional psychiatric diagnosis, showing smaller lateral ventricles in patients with additional personality disorder. While at follow-up the size of prefrontal lobes remained unchanged, volumes of the lateral ventricles decreased (5–6% reduction) in alcohol patients with abstinence and improved drinking behavior, especially in patients that underwent only one detoxification. The extent of the ventricular enlargement correlated with the elevation of alcohol related laboratory measures (mean corpuscular volume, gamma-glutamyl transpeptidase). In conclusion this study confirms the hypothesis that alcoholism causes brain damages that are partially reversible. It should be analyzed in further studies with larger sample sizes, if complete brain regeneration is possible maintaining abstinence over a longer period

An Approximate Bayesian Estimator Suggests Strong, Recurrent Selective Sweeps in Drosophila

The recurrent fixation of newly arising, beneficial mutations in a species reduces levels of linked neutral variability. Models positing frequent weakly beneficial substitutions or, alternatively, rare, strongly selected substitutions predict similar average effects on linked neutral variability, if the product of the rate and strength of selection is held constant. We propose an approximate Bayesian (ABC) polymorphism-based estimator that can be used to distinguish between these models, and apply it to multi-locus data from Drosophila melanogaster. We investigate the extent to which inference about the strength of selection is sensitive to assumptions about the underlying distributions of the rates of substitution and recombination, the strength of selection, heterogeneity in mutation rate, as well as the population's demographic history. We show that assuming fixed values of selection parameters in estimation leads to overestimates of the strength of selection and underestimates of the rate. We estimate parameters for an African population of D. melanogaster (ŝ∼2E−03, ) and compare these to previous estimates. Finally, we show that surveying larger genomic regions is expected to lend much more discriminatory power to the approach. It will thus be of great interest to apply this method to emerging whole-genome polymorphism data sets in many taxa