In fibroblasts, IL-17A response depends on CUX1 and IκBζ to engage the NF-κB complex to produce chemoattractants for neutrophil and monocyte recruitment.The AAA+ ATPase and bromodomain factor ATAD2/ANCCA is overexpressed in many types of cancer, but how it contributes to tumorigenesis is not understood. Here, we report that the Saccharomyces cerevisiae homolog Yta7ATAD2 is a deposition factor for the centromeric histone H3 variant Cse4CENP-A at the centromere in yeast. Yta7ATAD2 regulates the levels of centromeric Cse4CENP-A in that yta7∆ causes reduced Cse4CENP-A deposition, whereas YTA7 overexpression causes increased Cse4CENP-A deposition. Yta7ATAD2 coimmunoprecipitates with Cse4CENP-A and is associated with the centromere, arguing for a direct role of Yta7ATAD2 in Cse4CENP-A deposition. Furthermore, increasing centromeric Cse4CENP-A levels by YTA7 overexpression requires the activity of Scm3HJURP, the centromeric nucleosome assembly factor. Importantly, Yta7ATAD2 interacts in vivo with Scm3HJURP, indicating that Yta7ATAD2 is a cochaperone for Scm3HJURP The absence of Yta7 causes defects in growth and chromosome segregation with mutations in components of the inner kinetochore (CTF19/CCAN, Mif2CENP-C, Cbf1).  https://www.selleckchem.com/products/sd-208.html  Since Yta7ATAD2 is an AAA+ ATPase and potential hexameric unfoldase, our results suggest that it may unfold the Cse4CENP-A histone and hand it over to Scm3HJURP for subsequent deposition in the centromeric nucleosome. Furthermore, our findings suggest that ATAD2 overexpression may enhance malignant transformation in humans by misregulating centromeric CENP-A levels, thus leading to defects in kinetochore assembly and chromosome segregation.The ubiquity of phospho-ligands suggests that phosphate binding emerged at the earliest stage of protein evolution. To evaluate this hypothesis and unravel its details, we identified all phosphate-binding protein lineages in the Evolutionary Classification of Protein Domains database. We found at least 250 independent evolutionary lineages that bind small molecule cofactors and metabolites with phosphate moieties. For many lineages, phosphate binding emerged later as a niche functionality, but for the oldest protein lineages, phosphate binding was the founding function. Across some 4 billion y of protein evolution, side-chain binding, in which the phosphate moiety does not interact with the backbone at all, emerged most frequently. However, in the oldest lineages, and most characteristically in αβα sandwich enzyme domains, N-helix binding sites dominate, where the phosphate moiety sits atop the N terminus of an α-helix. This discrepancy is explained by the observation that N-helix binding is uniquely realized by short, contiguous sequences with reduced amino acid diversity, foremost Gly, Ser, and Thr. The latter two amino acids preferentially interact with both the backbone amide and the side-chain hydroxyl (bidentate interaction) to promote binding by short sequences. We conclude that the first αβα sandwich domains emerged from shorter and simpler polypeptides that bound phospho-ligands via N-helix sites.Proteins' interactions with ancient ligands may reveal how molecular recognition emerged and evolved. We explore how proteins recognize adenine a planar rigid fragment found in the most common and ancient ligands. We have developed a computational pipeline that extracts protein-adenine complexes from the Protein Data Bank, structurally superimposes their adenine fragments, and detects the hydrogen bonds mediating the interaction. Our analysis extends the known motifs of protein-adenine interactions in the Watson-Crick edge of adenine and shows that all of adenine's edges may contribute to molecular recognition. We further show that, on the proteins' side, binding is often mediated by specific amino acid segments ("themes") that recur across different proteins, such that different proteins use the same themes when binding the same adenine-containing ligands. We identify numerous proteins that feature these themes and are thus likely to bind adenine-containing ligands. Our analysis suggests that adenine binding has emerged multiple times in evolution. Copyright © 2020 the Author(s). Published by PNAS.This is the case of a previously healthy 15-month-old girl who initially presented to her primary pediatrician with a 2-week history of intermittent periorbital edema. The edema had improved by the time of the visit, and a urine specimen was unable to be obtained in the clinic. A routine fingerstick demonstrated anemia to 8.8 mg/dL, so the patient was started on ferrous sulfate. She then returned to the emergency department 1 month later with severe periorbital edema and pallor but no other significant symptoms. On physical examination, she was tachycardic with striking periorbital edema and an otherwise normal physical examination. She was noted to have a severe microcytic anemia (hemoglobin of 3.9 mg/dL and mean corpuscular volume of 53.1 fL) and hypoalbuminemia (albumin of 1.9 g/dL and total protein of 3.3 g/dL). The remainder of her electrolytes and liver function test results were within normal limits. A urinalysis was sent, which was negative for protein. Our panel of experts reviews her case to determine a unifying diagnosis for both her severe anemia and her hypoalbuminemia. Copyright © 2020 by the American Academy of Pediatrics.BACKGROUND AND OBJECTIVES National guidelines recommend against routine use of chest radiography (CXR) for community-acquired pneumonia (CAP) diagnosis in the pediatric emergency department (ED). Given that CXR is often used to exclude the diagnosis of CAP, a reduction in CXR use may result in overdiagnosis of CAP. We sought to evaluate trends in CXR use and assess the association between CXR performance and CAP diagnosis among children discharged from pediatric EDs. METHODS Children 3 months to 18 years of age discharged from 30 US EDs with (1) CAP or (2) fever or respiratory illness between 2008 and 2018 were included. Temporal trends in CXR use and rates of CAP diagnoses among patients with fever or respiratory illness were assessed. Correlation between hospital-level CXR use and CAP diagnosis rates were evaluated by using Spearman's correlation weighted by hospital volume. RESULTS CXR usage decreased from 86.6% to 80.4% (P less then .001) for patients with CAP and from 30.4% to 18.6% (P less then .001) for children with fever or respiratory illness over the 10-year study period.