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Chromatin remodeling plays important roles in gene regulation during development, differentiation and in disease. The chromatin remodeling enzyme CHD4 is a component of the NuRD and ChAHP complexes that are involved in gene repression. Here, we report the cryo-electron microscopy (cryo-EM) structure of Homo sapiens CHD4 engaged with a nucleosome core particle in the presence of the non-hydrolysable ATP analogue AMP-PNP at an overall resolution of 3.1 Å. The ATPase motor of CHD4 binds and distorts nucleosomal DNA at superhelical location (SHL) +2, supporting the 'twist defect' model of chromatin remodeling. CHD4 does not induce unwrapping of terminal DNA, in contrast to its homologue Chd1, which functions in gene activation. Our structure also maps CHD4 mutations that are associated with human cancer or the intellectual disability disorder Sifrim-Hitz-Weiss syndrome.Microbial fitness screens are a key technique in functional genomics. We present an all-in-one solution, pyphe, for automating and improving data analysis pipelines associated with large-scale fitness screens, including image acquisition and quantification, data normalisation, and statistical analysis. Pyphe is versatile and processes fitness data from colony sizes, viability scores from phloxine B staining or colony growth curves, all obtained with inexpensive transilluminating flatbed scanners. We apply pyphe to show that the fitness information contained in late endpoint measurements of colony sizes is similar to maximum growth slopes from time series. We phenotype gene-deletion strains of fission yeast in 59,350 individual fitness assays in 70 conditions, revealing that colony size and viability provide complementary, independent information. check details Viability scores obtained from quantifying the redness of phloxine-stained colonies accurately reflect the fraction of live cells within colonies. Pyphe is user-friendly, open-source and fully documented, illustrated by applications to diverse fitness analysis scenarios.Objective To investigate the efficacy of silver diamine fluoride (SDF) with 5% fluoride varnish (FV) in treating cavitated caries in young children and to explore the association between SDF treatment and oral-health-related quality of life (OHRQoL). Methods Children with active dentinal caries in primary teeth underwent treatment with 38% SDF and 5% FV at baseline and 4 months later. Treated lesions were assessed 4 and 8 months after baseline. Child-level analysis focused on classifying SDF treatment as completely successful if all of a child's treated lesions were arrested or incompletely successful if at least 1 lesion was not arrested. The Early Childhood Oral Health Impact Scale questionnaire was completed at second and third visits. Statistical analyses included descriptive and bivariate methods. A p value ≤ 0.05 was considered significant. Results This pilot study enrolled 40 children with 239 caries lesions; mean age 40.2 ± 14.9 months and 45% male. Lesion arrest rates after 1 and 2 applications of SDF were 74.1% and 96.2%, respectively. Children who reportedly brushed twice daily were more likely to be in the completely successful group compared with those who brushed less (p = 0.006). Those in the completely successful group had a significantly lower mean baseline dmft score than those in the incompletely successful group (p = 0.048). No significant difference in OHRQoL was observed between the 2 groups. Conclusions SDF with 5% FV is an effective approach to the management of early childhood caries; more than 1 application is recommended, along with regular follow up of patients and twice daily brushing. OHRQoL was not found to be affected by the level of success of SDF treatment.Current epidemiological data suggest that the prevalence of diabetes in Canada is increasing. Patients with poor glycemic control are more prone to oral manifestations of diabetes, including periodontal disease, salivary gland dysfunction, halitosis, burning mouth sensation, delayed wound healing and increased susceptibility to infections. Diabetic patients are also at risk of experiencing an intraoperative diabetic emergency in the dental office. Therefore, dentists must appreciate and implement important dental management considerations while providing care to diabetic patients. In this article, we discuss the diagnosis, oral findings, dental care and emergency management of diabetic patients.Electronic cigarettes (e‑cigarettes) are widely available, and their use is increasing worldwide. They are promoted as a safer alternative to combustible cigarette smoking and as an effective smoking cessation aid. E‑cigarettes are designed to provide smokers with the desired nicotine dose without burning tobacco. They contain flavoured humectants that include nicotine in concentrations of 0-36 mg/mL. Evidence suggests that e‑cigarettes are a better nicotine delivery method than combustible cigarettes and have reduced adverse general and oral health effects, compared with combustible cigarettes. However, although e‑cigarettes might be an acceptable harm-reduction strategy, the differential effects of e‑cigarettes and combustible cigarettes have been based on self-reported perceptions. In addition, a growing number of young people, who have never engaged in combustible cigarette smoking, are smoking e‑cigarettes, which may not be harmless. We analyzed peer-reviewed publications available through PubMed to summarize the effects of e‑cigarettes on oral health.Insect-bacterial symbioses are ubiquitous, but there is still much to uncover about how these relationships establish, persist and evolve. The tsetse endosymbiont Sodalis glossinidius displays intriguing metabolic adaptations to its microenvironment, but the process by which this relationship evolved remains to be elucidated. The recent chance discovery of the free-living species of the genus Sodalis, Sodalis praecaptivus, provides a serendipitous starting point from which to investigate the evolution of this symbiosis. Here, we present a flux balance model for S. praecaptivus and empirically verify its predictions. Metabolic modelling is used in combination with a multi-objective evolutionary algorithm to explore the trajectories that S. glossinidius may have undertaken from this starting point after becoming internalized. The order in which key genes are lost is shown to influence the evolved populations, providing possible targets for future in vitro genetic manipulation. This method provides a detailed perspective on possible evolutionary trajectories for S.
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