Guldbrandsenstage9262

52 (95%CI 1.30-1.74) while these civilian-involved events corresponded to Rt of 1.43 (95%CI 1.21-1.35). Untargeted events corresponded to Rt of 1.18 (95%CI 1.02-1.35); among these, militia/political or ville morte events increased transmission. CONCLUSION Ebola-targeted violence, primarily driven by civilian-involved events, had the largest impact on EVD transmission. © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.Base editing is a genome-editing approach that employs the CRISPR/Cas system to precisely install point mutations within the genome. A deaminase enzyme is fused to a deactivated Cas and enables transition conversions. The diversified repertoire of base editors provides a wide range of base editing possibilities. However, existing base editors cannot induce transversion substitutions and activate only within a specified region relative to the binding site, thus, they cannot precisely correct every point mutation. Here, we present BE-FF (Base Editors Functional Finder), a novel computational tool that identifies suitable base editors to correct the translated sequence erred by a point mutation. When a precise correction is impossible, BE-FF aims to mutate bystander nucleotides in order to induce synonymous corrections that will correct the coding sequence. To measure BE-FF practicality, we analysed a database of human pathogenic point mutations. Out of the transition mutations, 60.9% coding sequences could be corrected. Notably, 19.4% of the feasible corrections were not achieved by precise corrections but only by synonymous corrections. Moreover, 298 cases of transversion-derived pathogenic mutations were detected to be potentially repairable by base editing via synonymous corrections, although base editing is considered impractical for such mutations. © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.BACKGROUND Growth and development might lead to anchorage loss during orthodontic treatment, such as the mesial drift of molars, the compensation characteristics of upper molars following mandibular growth, or the angulation of molars before treatment. Different anchorage reinforcement devices have been developed to prevent mechanical anchorage loss, but the anchorage loss resulting from physiological factors should also be taken into account. OBJECTIVE To explore the efficacy of a new strategy to control physiologic anchorage compared with that of the conventional straight-wire appliance. TRIAL DESIGN Randomized controlled trial (RCT). METHODS Participants of Han ethnicity were randomized into the physiologic anchorage spee-wire system (PASS) group or McLaughlin-Bennett-Trevisi (MBT™) straight-wire group by minimization random allocation. The eligibility criteria were patients with a Class I or II molar relationship, permanent dentition (11-35 years old), fixed appliances involving the extraction of at leastwithout additional anchorage devices could attain well anchorage control by considering the dentoalveolar compensation of anchor teeth. REGISTRATION This RCT was registered at the Chinese Clinical Trial Registry (Chictr.org.cn) ChiCTR-TRC-13003260. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email journals.permissions@oup.com.The assembly of double-stranded DNA viruses, from phages to herpesviruses, is strongly conserved. Terminase enzymes processively excise and package monomeric genomes from a concatemeric DNA substrate. The enzymes cycle between a stable maturation complex that introduces site-specific nicks into the duplex and a dynamic motor complex that rapidly translocates DNA into a procapsid shell, fueled by ATP hydrolysis. These tightly coupled reactions are catalyzed by terminase assembled into two functionally distinct nucleoprotein complexes; the maturation complex and the packaging motor complex, respectively. We describe the effects of nucleotides on the assembly of a catalytically competent maturation complex on viral DNA, their effect on maturation complex stability and their requirement for the transition to active packaging motor complex. ATP plays a major role in regulating all of these activities and may serve as a 'nucleotide switch' that mediates transitions between the two complexes during processive genome packaging. These biological processes are recapitulated in all of the dsDNA viruses that package monomeric genomes from concatemeric DNA substrates and the nucleotide switch mechanism may have broad biological implications with respect to virus assembly mechanisms. © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.Di (2-ethylhexyl) phthalate (DEHP) is a plasticizer frequently leached out from polyvinyl chloride (PVC) products and is quickly metabolized to its monoester equivalent mono(2-ethylhexyl) phthalate (MEHP) once enters organisms. Exposure to DEHP/MEHP through food chain intake has been shown to modified metabolism but its effect on the development of metabolic myopathy of skeletal muscle (SKM) has not been revealed so far. Here, we found that MEHP repressed myogenic terminal differentiation of proliferating myoblasts (PMB) and confluent myoblasts (CMB) but had weak effect on this process once it had been initiated. The transition of mitochondria (MITO) morphology from high efficient filamentary network to low efficient vesicles was triggered by MEHP, implying its negative effects on MITO functions. The impaired MITO functions was further demonstrated by reduced MITO DNA (mtDNA) level and SDH enzyme activity as well as highly increased reactive oxygen species (ROS) in cells after MEHP treatment. The expression of metabolic genes, including PDK4, CPT1b, UCP2, and HO1, was highly increased by MEHP and the promoters of PDK4 and CPT1b were also activated by MEHP. Additionally, the stability of some subunits in the oxidative phosphorylation system (OXPHOS) complexes was found to be reduced by MEHP, implying defective oxidative metabolism in MITO and which was confirmed by repressed palmitic acid oxidation in MEHP-treated cells. Besides, MEHP also blocked insulin-induced glucose uptake. Taken together, our results suggest that MEHP is inhibitory to myogenesis and is harmful to MITO functions in SKM, so its exposure should be avoided or limited. © 2020 The Author(s).Backgroud Pre-eclampsia (PE) is a common pregnancy-induced hypertension disease. Some case-control studies reported the association between Vascular endothelial growth factor (VEGF) gene polymorphisms (rs3025039，rs2010963) and PE risk. However, these associations were inconsistent in several studies. Therefore, we conducted this meta-analysis to assess the role of VEGF gene polymorphisms in PE more precisely. METHODS Eligible studies were searched in PubMed, Embase, Web of Science and Chinese (CNKI and WanFang) databases. Statistical analyses were performed by Stata 12.0 software. Odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength of the association. In addition, subgroup analyses, sensitive analyses and publication bias analyses were performed to further assess this meta-analysis. RESULTS Totally, 21 studies were included in the meta-analysis covering 2,018 cases and 2,632 controls. There were significant associations between VEGF polymorphisms (rs3025039，rs2010963) and PE risk in the overall populations. In the subgroup analyses, we found that rs3025039 polymorphism was associated with the increased risk of PE amongst Chinese. As for rs2010963 polymorphism, a significant association was observed in subgroup of Caucasian. CONCLUSION The present study suggested that the two VEGF gene polymorphisms (rs3025039，rs2010963) are associated with increased risk of PE in different ethnic groups, which means that the targets may be useful genetic markers for early prediction of PE. Copyright 2020 The Author(s).BACKGROUND Juberg-Hayward syndrome (JHS; MIM 216100) is a rare autosomal recessive malformation syndrome, characterized by cleft lip/palate, microcephaly, ptosis, short stature, hypoplasia or aplasia of thumbs, and dislocation of radial head and fusion of humerus and radius leading to elbow restriction. OBJECTIVE To report for the first time the molecular aetiology of JHS. Pimicotinib mw PATIENT AND METHODS Clinical and radiographic examination, whole exome sequencing, Sanger sequencing, mutant protein model construction, and in situ hybridization of Esco2 expression in mouse embryos were performed. RESULTS Clinical findings of the patient consisted of repaired cleft lip/palate, microcephaly, ptosis, short stature, delayed bone age, hypoplastic fingers and thumbs, clinodactyly of the fifth fingers, and humeroradial synostosis leading to elbow restriction. Intelligence is normal. Whole exome sequencing of the whole family showed a novel homozygous base substitution c.1654C>T in ESCO2 of the proband. The sister was homozygous for the wildtype variant. Parents were heterozygous for the mutation. The mutation is predicted to cause premature stop codon p.Arg552Ter. Mutations in ESCO2, a gene involved in cohesin complex formation, are known to cause Roberts/SC phocomelia syndrome. Roberts/SC phocomelia syndrome and JHS share similar clinical findings, including autosomal recessive inheritance, short stature, cleft lip/palate, severe upper limb anomalies, and hypoplastic digits. Esco2 expression during the early development of lip, palate, eyelid, digits, upper limb, and lower limb and truncated protein model are consistent with the defect. CONCLUSIONS Our study showed that Roberts/SC phocomelia syndrome and JHS are allelic and distinct entities. This is the first report demonstrating that mutation in ESCO2 causes JHS, a cohesinopathy. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email journals.permissions@oup.com.Skeletally diverse and complex aza-cyclopenta(cd)diindene, pyrrolo(3,4-d)pyridine-13-carboxamide, and furo-pyrrolo(1,2-a)imidazole-4-carboxamide fused polyheterocyclic hybrid scaffolds and a furo(2,3-b)furan core have been accessed via one-pot three-component reaction by exploiting the build/couple/pair strategy of diversity oriented synthesis (DOS). This protocol is metal free, has a good substrate scope and affords products with good to excellent yields and regio- and chemo-selectivity. The heterocyclic skeletons obtained in this study mimic natural products such as eupolauramine, gracilamine and presilphiperfolanol.Time-resolved infra-red (TRIR) spectroscopy has been used to demonstrate that photolysis of [Mn(C^N)(CO)4] (C^N = bis-(4-methoxyphenyl)methanimine) in heptane solution results in ultra-fast CO dissociation and ultimate formation of a rare Mn-containing dinitrogen complex fac-[Mn(C^N)(CO)3(N2)] with a diagnostic stretching mode for a terminal-bound N[triple bond, length as m-dash]N ligand at 2249 cm-1. An isotopic shift to 2174 cm-1 was observed when the reaction was performed under 15N2 and the band was not present when the experiment was undertaken under an atmosphere of argon, reinforcing this assignment. An intermediate solvent complex fac-[Mn(C^N)(CO)3(heptane)] was identified which is formed in less than 2 ps, indicating that CO-release occurs on an ultra-fast timescale. The heptane ligand is labile and is readily displaced by both N2 and water to give fac-[Mn(C^N)(CO)3(N2)] and fac-[Mn(C^N)(CO)3(OH2)] respectively. The fac-[Mn(C^N)(CO)3(heptane)] framework showed a significant affinity for N2, as performing the reaction under air produced significant amounts of fac-[Mn(C^N)(CO)3(N2)].