42 research outputs found
Crisis Management in Action: Using a Simulation of the U.S. National Security Apparatus to Teach Foreign Policy Decision-Making Under Duress
no poles encodes a predicted E3 ubiquitin ligase required for early embryonic development of Drosophila
In a screen for cell-cycle regulators, we identified a Drosophila
maternal effect-lethal mutant that we named `no poles'
(nopo). Embryos from nopo females undergo mitotic arrest
with barrel-shaped, acentrosomal spindles during the rapid S-M cycles of
syncytial embryogenesis. We identified CG5140, which encodes a
candidate RING domain-containing E3 ubiquitin ligase, as the nopo
gene. A conserved residue in the RING domain is altered in our EMS-mutagenized
allele of nopo, suggesting that E3 ligase activity is crucial for
NOPO function. We show that mutation of a DNA checkpoint kinase, CHK2,
suppresses the spindle and developmental defects of nopo-derived
embryos, revealing that activation of a DNA checkpoint operational in early
embryos contributes significantly to the nopo phenotype.
CHK2-mediated mitotic arrest has been previously shown to occur in response to
mitotic entry with DNA damage or incompletely replicated DNA. Syncytial
embryos lacking NOPO exhibit a shorter interphase during cycle 11, suggesting
that they may enter mitosis prior to the completion of DNA replication. We
show that Bendless (BEN), an E2 ubiquitin-conjugating enzyme, interacts with
NOPO in a yeast two-hybrid assay; furthermore, ben-derived embryos
arrest with a nopo-like phenotype during syncytial divisions. These
data support our model that an E2-E3 ubiquitination complex consisting of
BEN-UEV1A (E2 heterodimer) and NOPO (E3 ligase) is required for the
preservation of genomic integrity during early embryogenesis
Improving Student Learning Through a Second Bite at the Apple: the Value of Second Runs of International Relations Simulations
Recommended from our members
Umbilical Cord Milking vs Delayed Cord Clamping and Associations with In-Hospital Outcomes among Extremely Premature Infants
ObjectiveTo compare in-hospital outcomes after umbilical cord milking vs delayed cord clamping among infants <29 weeks of gestation.Study designMulticenter retrospective study of infants born <29 weeks of gestation from 2016 to 2018 without congenital anomalies who received active treatment at delivery and were exposed to umbilical cord milking or delayed cord clamping. The primary outcome was mortality or severe (grade III or IV) intraventricular hemorrhage (IVH) by 36 weeks of postmenstrual age (PMA). Secondary outcomes assessed at 36 weeks of PMA were mortality, severe IVH, any IVH or mortality, and a composite of mortality or major morbidity. Outcomes were assessed using multivariable regression, incorporating mortality risk factors identified a priori, confounders, and center. A prespecified, exploratory analysis evaluated severe IVH in 2 gestational age strata, 22-246/7 and 25-286/7 weeks.ResultsAmong 1834 infants, 23.6% were exposed to umbilical cord milking and 76.4% to delayed cord clamping. The primary outcome, mortality or severe IVH, occurred in 21.1% of infants: 28.3% exposed to umbilical cord milking and 19.1% exposed to delayed cord clamping, with an aOR that was similar between groups (aOR 1.45, 95% CI 0.93, 2.26). Infants exposed to umbilical cord milking had higher odds of severe IVH (19.8% umbilical cord milking vs 11.8% delayed cord clamping, aOR 1.70 95% CI 1.20, 2.43), as did the 25-286/7 week stratum (14.8% umbilical cord milking vs 7.4% delayed cord clamping, aOR 1.89 95% CI 1.22, 2.95). Other secondary outcomes were similar between groups.ConclusionsThis analysis of extremely preterm infants suggests that delayed cord clamping is the preferred practice for placental transfusion, as umbilical cord milking exposure was associated with an increase in the adverse outcome of severe IVH.Trial registrationClinicalTrials.gov: NCT00063063
Recommended from our members
Cortisol awakening response and developmental outcomes at 6–7 years in children born extremely preterm
BackgroundExtremely preterm (EPT) birth has been related to dysregulation of stress responses and behavioral/learning problems at school age. Early adverse experiences can blunt HPA axis reactivity. We hypothesized that an attenuated cortisol awakening response would be associated with developmental and behavioral problems at school age in EPT children.MethodsThis secondary analysis of a sub-cohort of the SUPPORT study included children born between 24 and 27 weeks, evaluated at 6-7 years with a neurodevelopmental battery and cortisol measures. Differences were tested between EPT and a term-born group. Relationships of cortisol awakening response to test scores were analyzed.ResultsCortisol was measured in 110 EPT and 29 term-born 6-7 year olds. Unadjusted WISC-IV and NEPSY-II scores were significantly worse among EPT children only. Conners Parent Rating Scale behavior scores were significantly worse among EPT children. After adjusting for covariates, blunted cortisol awakening responses were found to be associated with poorer scores on memory tests and greater problems with inattention for the EPT group (p < 0.05) only.ConclusionsAmong children born EPT, we identified an association of blunted cortisol awakening response with memory and inattention problems. This may have implications related to stress reactivity and its relationship to learning problems in children born EPT.ClinicaltrialsGov idExtended Follow-up at School Age for the SUPPORT Neuroimaging and Neurodevelopmental Outcomes (NEURO) Cohort: NCT00233324.ImpactIn children born EPT, stress reactivity may have a relationship to learning problems. Cortisol awakening response should be a component for follow-up in EPT born children. Components of executive function, such as memory and attention, are related to stress reactivity
Recommended from our members
Admission Temperature and Associated Mortality and Morbidity among Moderately and Extremely Preterm Infants
ObjectiveTo evaluate the temperature distribution among moderately preterm (MPT, 29-33 weeks) and extremely preterm (EPT, <29 weeks) infants upon neonatal intensive care unit (NICU) admission in 2012-2013, the change in admission temperature distribution for EPT infants between 2002-2003 and 2012-2013, and associations between admission temperature and mortality and morbidity for both MPT and EPT infants.Study designProspectively collected data from 18 centers in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network were used to examine NICU admission temperature of inborn MPT and EPT infants. Associations between admission temperature and mortality and morbidity were determined by multivariable logistic regression. EPT infants from 2002-2003 and 2012-2013 were compared.ResultsMPT and EPT cohorts consisted of 5818 and 3213 infants, respectively. The distribution of admission temperatures differed between the MPT vs EPT (P < .01), including the percentage <36.5°C (38.6% vs 40.9%), 36.5°C-37.5°C (57.3% vs 52.9%), and >37.5°C (4.2% vs 6.2%). For EPT infants in 2012-2013 compared with 2002-2003, the percentage of temperatures between 36.5°C and 37.5°C more than doubled and the percentage of temperatures >37.5°C more than tripled. Admission temperature was inversely associated with in-hospital mortality.ConclusionsLow and high admission temperatures are more frequent among EPT than MPT infants. Compared with a decade earlier, fewer EPT infants experience low admission temperatures but more have elevated temperatures. In spite of a change in distribution of NICU admission temperature, an inverse association between temperature and mortality risk persists
Recommended from our members
Association between Policy Changes for Oxygen Saturation Alarm Settings and Neonatal Morbidity and Mortality in Infants Born Very Preterm
ObjectiveTo determine the impact of policy changes for pulse oximetry oxygen saturation (SpO2) alarm limits on neonatal mortality and morbidity among infants born very preterm.Study designThis was a retrospective cohort study of infants born very preterm in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants were classified based on treatment at a hospital with an SpO2 alarm policy change and study epoch (before vs after policy change). We used a generalized linear mixed model to determine the effect of hospital group and epoch on the primary outcomes of mortality and severe retinopathy of prematurity (ROP) and secondary outcomes of necrotizing enterocolitis, bronchopulmonary dysplasia, and any ROP.ResultsThere were 3809 infants in 10 hospitals with an SpO2 alarm policy change and 3685 infants in 9 hospitals without a policy change. The nature of most policy changes was to narrow the SpO2 alarm settings. Mortality was lower in hospitals without a policy change (aOR 0.63; 95% CI 0.50-0.80) but did not differ between epochs in policy change hospitals. The odds of bronchopulmonary dysplasia were greater for hospitals with a policy change (aOR 1.65; 95% CI 1.36-2.00) but did not differ for hospitals without a policy change. Severe ROP and necrotizing enterocolitis did not differ between epochs for either group. The adjusted odds of any ROP were lower in recent years in both hospital groups.ConclusionsChanging SpO2 alarm policies was not associated with reduced mortality or increased severe ROP among infants born very preterm