Project description:Double strand breaks pose unique problems for DNA repair, especially when broken ends possess complex structures that interfere with standard DNA transactions. Nonhomologous end joining can use multiple strategies to solve these problems. It further uses sophisticated means to ensure the strategy chosen provides the ideal balance of flexibility and accuracy.
Project description:E-cigarette usage (also known as e-cigarettes or vaping products) has increasingly been recognized as a global public health problem. One challenge in particular involves their marketing to minors (teenagers and children) and the rising prevalence of use in this population. E-cigarettes unnecessarily expose minors to health risks, these include respiratory health problems, such as exacerbations of asthma, bronchitis, and respiratory-tract irritation. Nicotine, commonly found in e-cigarettes, is also associated with cognitive impairment and neurodevelopmental problems. E-cigarettes are also risk factors for downstream substance use, including cigarettes and cannabis initiation (the gateway hypothesis), which compounds health risks in dual users. Current public health preventative and intervention studies are limited, and there is a clear need for more interventions that may prevent usage and assist with cessation in this vulnerable population. Physician education and screening uptake should also be enhanced. Stricter public health policy and protection measures are also needed on a global scale to limit e-cigarette exposure in minors.
Project description:Exposure to vaping is associated with a growing list of respiratory syndromes including an acute progressive form with life-threatening hypoxemic respiratory failure and pathologic changes of lung injury termed vaping-associated respiratory distress syndrome.Data sourcesCenter from Disease Control, Departments of Public Health, MEDLINE (via PubMed), and the Cochrane Library.Study selection data extraction and data synthesisCases, series, and public health reports of cases that met the Centers for Disease Control and Prevention case definition of vaping-associated respiratory disease were extracted by an author with perfect verification by a second. Cases were classified on the basis of toxin exposure, symptoms, oxygen saturation, progression to respiratory failure, and pathologic features, and a clinically actionable system of classification was based on expert opinion.ConclusionsThe reported spectrum of vaping-associated respiratory diseases allows clinical classification of cases into groups with distinct evaluation, management, and recommendations for prevention and follow-up. Clinical stratification also identifies a small proportion of vaping-exposed patients who are at risk for progression to hypoxemic respiratory failure and an acute respiratory distress syndrome-like illness.
Project description:Nonhomologous end joining (NHEJ) is the primary pathway of DNA double-strand-break repair in vertebrate cells, yet how NHEJ factors assemble a synaptic complex that bridges DNA ends remains unclear. To address the role of XRCC4-like factor (XLF) in synaptic-complex assembly, we used single-molecule fluorescence imaging in Xenopus laevis egg extract, a system that efficiently joins DNA ends. We found that a single XLF dimer binds DNA substrates just before the formation of a ligation-competent synaptic complex between DNA ends. The interaction of both globular head domains of the XLF dimer with XRCC4 is required for efficient formation of this synaptic complex. Our results indicate that, in contrast to a model in which filaments of XLF and XRCC4 bridge DNA ends, binding of a single XLF dimer facilitates the assembly of a stoichiometrically well-defined synaptic complex.