To assess the patient-level and societal burden of atopic dermatitis, we comprehensively reviewed the literature related to quality of life, social, economic, academic, and occupational impacts. Atopic dermatitis has profound impacts on patient and family quality of life. A conservative estimate of the annual costs of atopic dermatitis in the United States is $5.297 billion (in 2015 USD). People with atopic dermatitis may change their occupation because of their skin disease. Research gaps include quality of life assessments outside of tertiary care centers, impacts on partners and families of adult patients, and updated comprehensive cost estimates.

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DNA double-strand breaks (DSBs) are the most cytotoxic form of DNA damage, with their aberrant repair linked with carcinogenesis 1,2 . The conserved error-prone Non-Homologous End-Joining (NHEJ) pathway plays a key role in determining the effects of DSB-inducing agents used to treat cancer as well as the generation of antibody and T cell receptor diversity 2,3 . Here, we applied single-particle cryo-electron microscopy (EM) to visualize two key DNA-protein complexes formed by NHEJ factors. Ku, DNA-PKcs, LigIV-XRCC4, and XLF form a Long-range synaptic complex, in which the DNA ends are held ~115 Å apart. Two DNA end-bound Ku-DNA-PKcs subcomplexes are linked by DNA-PKcs-DNA-PKcs interactions and a LigIV-XRCC4-XLF-XRCC4-LigIV scaffold. The relative orientation of the DNA-PKcs molecules suggests a mechanism for auto-phosphorylation in trans, leading to dissociation of DNA-PKcs and transition into the Short-range synaptic complex. Within this complex, the Ku-bound DNA ends are aligned for processing and ligation by the XLF-anchored scaffold, and a single LigIV catalytic domain is stably associated with a nick between the two Ku molecules, suggesting that joining of both strands of a DSB involves both LigIV molecules.

NO plays critical roles in vascular function. We show that modulation of the eNOS serine 1179 (S1179) phosphorylation site affects vascular reactivity and determines stroke size in vivo. Transgenic mice expressing only a phosphomimetic (S1179D) form of eNOS show greater vascular reactivity, develop less severe strokes, and have improved cerebral blood flow in a middle cerebral artery occlusion model than mice expressing an unphosphorylatable (S1179A) form. These results provide a molecular mechanism by which multiple diverse cardiovascular risks, such as diabetes and obesity, may be centrally integrated by eNOS phosphorylation in vivo to influence blood flow and cardiovascular disease. They also demonstrate the in vivo relevance of posttranslational modification of eNOS in vascular function.