Regulation of the Fanconi anemia pathway by a CUE ubiquitin-binding domain in the FANCD2 protein

The Fanconi anemia (FA)-BRCA pathway is critical for the repair of DNA interstrand crosslinks (ICLs) and the maintenance of chromosome stability. A key step in FA-BRCA pathway activation is the covalent attachment of monoubiquitin to FANCD2 and FANCI. Monoubiquitinated FANCD2 and FANCI localize in chromatin-associated nuclear foci where they interact with several well-characterized DNA repair proteins. Importantly, very little is known about the structure, function, and regulation of FANCD2. Herein, we describe the identification and characterization of a CUE (coupling of ubiquitin conjugation to endoplasmic reticulum degradation) ubiquitin-binding domain (UBD) in FANCD2, and demonstrate that the CUE domain mediates noncovalent binding to ubiquitin in vitro. We show that although mutation of the CUE domain destabilizes FANCD2, the protein remains competent for DNA damage-inducible monoubiquitination and phosphorylation. Importantly, we demonstrate that the CUE domain is required for interaction with FANCI, retention of monoubiquitinated FANCD2, and FANCI in chromatin, and for efficient ICL repair. Our results suggest a model by which heterodimerization of monoubiquitinated FANCD2 and FANCI in chromatin is mediated in part through a noncovalent interaction between the FANCD2 CUE domain and monoubiquitin covalently attached to FANCI, and that this interaction shields monoubiquitinated FANCD2 from polyubiquitination and proteasomal degradation.     

Pilot study to measure cleaning effectiveness in health care

Environmental surfaces are likely to contribute to the transmission of health care-associated pathogens. The present study aimed to determine the most effective regimen or product for removing bioburden. An adenosine triphosphate assessment technique was used to compare cleaning methods and products for removing bioburden from soiled surfaces. Of the regimens or products tested, 2-step cleaning most thoroughly removed bioburden. The 2-in-1 products were no more effective in removing bioburden than a 1-step clean using a neutral detergent.     

Nonalcoholic fatty liver disease: pathologic patterns and biopsy evaluation in clinical research

Nonalcoholic fatty liver disease (NAFLD) results in histologically complex specific and nonspecific injury patterns. In clinical research of NAFLD, the liver biopsy evaluation provides a wealth of information on the architectural arrangement and severity of a variety of histologic changes, including steatosis, inflammation, cellular injury, and fibrosis. This information is summarized as an overall diagnostic category, such steatosis or steatohepatitis and the severity of the injury can be graded and staged. Histopathologic disease classification in NAFLD is related to but separate from evaluation of individual histologic lesions. The patient population under study may affect the prevalence of histologic findings and in particular, pediatric patients with NAFLD may show a higher prevalence of zone 1 steatosis and periportal fibrosis as compared with adult populations. For the purposes of clinical research, it is important to provide the pathologist with biopsies that are adequate to classify the disease process as well as to grade and stage the changes. A current understanding of NAFLD pathologic classification, as well as nuances of grading and staging, is presented in this review.