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Analyzing the effect of Meningococcal Vaccinations With Manufactured Controls.
© 2020, García-González et al.eLife is making changes to its policies on peer review in response to the impact of COVID-19 on the scientific community. © 2020, Eisen et al.Protein ubiquitination is a very diverse post-translational modification leading to protein degradation or delocalization, or altering protein activity. In Arabidopsis thaliana, two E3 ligases, BIG BROTHER (BB) and DA2, activate the latent peptidases DA1, DAR1 and DAR2 by mono-ubiquitination at multiple sites. Subsequently, these activated peptidases destabilize various positive growth regulators. Here, we show that two ubiquitin-specific proteases, UBP12 and UBP13, deubiquitinate DA1, DAR1 and DAR2, hence reducing their peptidase activity. Overexpression of UBP12 or UBP13 strongly decreased leaf size and cell area, and resulted in lower ploidy levels. Mutants in which UBP12 and UBP13 were downregulated produced smaller leaves that contained fewer and smaller cells. Remarkably, neither UBP12 nor UBP13 were found to be cleavage substrates of the activated DA1. Our results therefore suggest that UBP12 and UBP13 work upstream of DA1, DAR1 and DAR2 to restrict their protease activity and hence fine-tune plant growth and development. © 2020, Vanhaeren et al.STUDY OBJECTIVES The relationship between obstructive sleep apnea (OSA) and heart failure (HF) incidence in postmenopausal women has been understudied given the limited representation of women in heart failure studies. We investigated the relationship between OSA risk factors and HF and its subtypes in postmenopausal women. C176 METHODS We performed a prospective analysis on the adjudicated HF outcomes in the Women's Health Initiative from enrollment (1993-1998) to September 30, 2016. HF with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF) were defined as adjudicated acute HF hospitalization with EF ≥45% or less then 45%, respectively. We employed Cox regression to examine the association between OSA risk factors and symptoms (individually and using a summary risk score) and time to first hospitalized HF. RESULTS Of 42,362 women, 2205 (5.21%) developed all HF, 1162 (2.74%) women developed HFpEF, and 679 (1.60%) developed HFrEF. Individual OSA risk factors and symptoms, including obesity (HR=1.33, 95% CI 1.20-1.48), snoring (HR=1.30, 95% CI 1.16-1.46), and hypertension (HR=1.45, 95% CI 1.35-1.56), were positively associated with risk of HF and HFpEF but only hypertension was associated with HFrEF. When examined as a summary risk score compared to those with none of the OSA risk factors, presence of each additional factor was significantly associated with increased risk of hospitalized HF in a dose-response fashion for HFpEF (p-trend less then 0.001), but not HFrEF (p-trend 0.26). CONCLUSIONS OSA risk factors and symptoms were associated with HFpEF, but not HFrEF, among postmenopausal women and are largely dependent on BMI, snoring, and hypertension. © 2020 American Academy of Sleep Medicine.Children with rare genetic diseases that cause respiratory dysregulation are at particularly high mortality risk due development of respiratory failure. The Tectonin beta-propeller containing protein 2 (TECPR2) mutations are proposed to cause autophagy defect affecting axonal integrity and development of progressive neurodegenerative and neuromuscular disease. Published TECPR2 mutation cases have described high prevalence of respiratory failure. We review respiratory pathology in previously published cases and a new case of a 5-year-old girl with previously undescribed TECPR2 mutation demonstrating progressive central apnea due to respiratory cycle dysregulation. This is the first TECPR2 mutation case to demonstrate an ataxic (Biot's) breathing pattern with consistently inconsistent inspiratory and expiratory times and with relatively intact chemoreception during sleep. Therefore, we propose that the central apnea index alone, may not be the appropriate marker for mortality risk. Rather, the morbidity and mortality associated with TECPR2 mutations is multisystem in nature and this burden complicates the ultimate needs for ventilation support and prognosis. © 2020 American Academy of Sleep Medicine.STUDY OBJECTIVES There is a well-established association between headache disorders and sleep disturbances in children, but it is unknown if sleep disturbance plays a role in pediatric intracranial hypertension. The objective of this study was to examine sleep issues related to pediatric intracranial hypertension. METHODS Patients with intracranial hypertension who were followed in the Pediatric Intracranial Hypertension Clinic were recruited between July 2017 and September 2018. Demographic data was collected from the electronic medical record in addition to patient and parent completed questionnaires. Information on sleep behaviors was gathered using the Children's Sleep Habits Questionnaire, and control data was obtained from patient siblings. Statistical analyses were performed using paired t-tests or two-sample t-tests, as appropriate. RESULTS Sixty-two pairs of patients and matched sibling controls were compared. There was a statistically significant difference in total sleep disturbance score (control mean 44.3; patient mean 48.1; n=33 pairs, t=-2.2, p=0.035) as well as subscale scores of sleep onset delay (control mean 1.4; patient mean 1.7; n=52 pairs, t=-2.53, p=0.014), parasomnias (control mean 8.5; patient mean 9.5; n=42 pairs, t=-2.59, p=0.013), and sleep disordered breathing (control mean 3.1; patient mean 3.4; n=44 pairs, t=-2.61, p=0.013). There was no difference found in bedtime resistance, sleep duration, sleep anxiety, night wakings, and daytime sleepiness subscales. Furthermore, there was no difference in total sleep disturbance score between patient subsets including primary versus secondary intracranial hypertension, body mass index, pubertal status, presence of headaches, or intracranial hypertension treatment. CONCLUSIONS This observational study suggests that pediatric intracranial hypertension is associated with a modest increase in sleep disturbances. © 2020 American Academy of Sleep Medicine.
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