Cytosine-to-Uracil Deamination by SssI DNA Methyltransferase

The prokaryotic DNA(cytosine-5)methyltransferase M.SssI shares the specificity of eukaryotic DNA methyltransferases (CG) and is an important model and experimental tool in the study of eukaryotic DNA methylation. Previously, M.SssI was shown to be able to catalyze deamination of the target cytosine to uracil if the methyl donor S-adenosyl-methionine (SAM) was missing from the reaction. To test whether this side-activity of the enzyme can be used to distinguish between unmethylated and C5-methylated cytosines in CG dinucleotides, we re-investigated, using a sensitive genetic reversion assay, the cytosine deaminase activity of M.SssI. Confirming previous results we showed that M.SssI can deaminate cytosine to uracil in a slow reaction in the absence of SAM and that the rate of this reaction can be increased by the SAM analogue 5’-amino-5’-deoxyadenosine. We could not detect M.SssI-catalyzed deamination of C5-methylcytosine (m5C). We found conditions where the rate of M.SssI mediated C-to-U deamination was at least 100-fold higher than the rate of m5C-to-T conversion. Although this difference in reactivities suggests that the enzyme could be used to identify C5-methylated cytosines in the epigenetically important CG dinucleotides, the rate of M.SssI mediated cytosine deamination is too low to become an enzymatic alternative to the bisulfite reaction. Amino acid replacements in the presumed SAM binding pocket of M.SssI (F17S and G19D) resulted in greatly reduced methyltransferase activity. The G19D variant showed cytosine deaminase activity in E. coli, at physiological SAM concentrations. Interestingly, the C-to-U deaminase activity was also detectable in an E. coli ung+ host proficient in uracil excision repair

Evaluation and Management of Anal Intraepithelial Neoplasia in HIV-Negative and HIV-Positive Men Who Have Sex with Men

The incidence of human papillomavirus (HPV)–associated anal cancer in men who have sex with men (MSM) is striking and has not been mitigated by the use of highly active antiretroviral therapy. Detection and treatment of high-grade anal intraepithelial neoplasia (HGAIN) may reduce the incidence of anal cancer. Anal cytology is a useful tool to detect HGAIN; annual screening of HIV-positive MSM and biennial screening of HIV-negative MSM appears to be cost-effective. MSM with abnormal cytology should be referred for high-resolution anoscopy and biopsy. Individuals with HGAIN should receive treatment; treatment modalities for HGAIN demonstrate moderate efficacy and are usually well tolerated, but greater study is required to determine which treatment is optimal. Large prospective studies are needed to document the efficacy of screening and treatment of HGAIN on anal cancer incidence. The HPV vaccine holds promise for primary prevention of anal cancer in MSM, but significant implementation challenges remain

Identification of ICF categories relevant for nursing in the situation of acute and early post-acute rehabilitation

<p>Abstract</p> <p>Background</p> <p>The recovery of patients after an acute episode of illness or injury depends both on adequate medical treatment and on the early identification of needs for rehabilitation care. The process of early beginning rehabilitation requires efficient communication both between health professionals and the patient in order to effectively address all rehabilitation goals. The currently used nursing taxonomies, however, are not intended for interdisciplinary use and thus may not contribute to efficient rehabilitation management and an optimal patient outcome. The ICF might be the missing link in this communication process. The objective of this study was to identify the categories of the International Classification of Functioning, Disability and Health (ICF) categories relevant for nursing care in the situation of acute and early post-acute rehabilitation.</p> <p>Methods</p> <p>First, in a consensus process, "Leistungserfassung in der Pflege" (LEP) nursing interventions relevant for the situation of acute and early post-acute rehabilitation were selected. Second, in an integrated two-step linking process, two nursing experts derived goals of LEP nursing interventions from their practical knowledge and selected corresponding ICF categories most relevant for patients in acute and post-acute rehabilitation (ICF Core Sets).</p> <p>Results</p> <p>Eighty-seven percent of ICF Core Set categories could be linked to goals of at least one nursing intervention variable of LEP. The ICF categories most frequently linked with LEP nursing interventions were respiration functions, experience of self and time functions and focusing attention. Thirteen percent of ICF Core Set categories could not be linked with LEP nursing interventions. The LEP nursing interventions which were linked with the highest number of different ICF-categories of all were "therapeutic intervention", "patient-nurse communication/information giving" and "mobilising".</p> <p>Conclusion</p> <p>The ICF Core Sets for the acute hospital and early post-acute rehabilitation facilities are highly relevant for rehabilitation nursing. Linking nursing interventions with ICF Core Set categories is a feasible way to analyse nursing. Using the ICF Core Sets to describe goals of nursing interventions both facilitates inter-professional communication and respects patient's needs. The ICF may thus be a useful framework to set nursing intervention goals.</p

Wnt4 Enhances Murine Hematopoietic Progenitor Cell Expansion Through a Planar Cell Polarity-Like Pathway

Background: While the role of canonical (b-catenin-mediated) Wnt signaling in hematolymphopoiesis has been studied extensively, little is known of the potential importance of non-canonical Wnt signals in hematopoietic cells. Wnt4 is one of the Wnt proteins that can elicit non-canonical pathways. We have previously shown that retroviral overexpression of Wnt4 by hematopoietic cells increased thymic cellularity as well as the frequency of early thymic progenitors and bone marrow hematopoietic progenitor cells (HPCs). However, the molecular pathways responsible for its effect in HPCs are not known. Methodology/Principal Findings: Here we report that Wnt4 stimulation resulted in the activation of the small GTPase Rac1 as well as Jnk kinases in an HPC cell line. Jnk activity was necessary, while b-catenin was dispensable, for the Wnt4-mediated expansion of primary fetal liver HPCs in culture. Furthermore, Jnk2-deficient and Wnt4 hemizygous mice presented lower numbers of HPCs in their bone marrow, and Jnk2-deficient HPCs showed increased rates of apoptosis. Wnt4 also improved HPC activity in a competitive reconstitution model in a cell-autonomous, Jnk2-dependent manner. Lastly, we identified Fz6 as a receptor for Wnt4 in immature HPCs and showed that the absence of Wnt4 led to a decreased expression of four polarity complex genes. Conclusions/Significance: Our results establish a functional role for non-canonical Wnt signaling in hematopoiesis throug

Gender and the Communication of Emotion Via Touch

We reanalyzed a data set consisting of a U.S. undergraduate sample (N = 212) from a previous study (Hertenstein et al. 2006a) that showed that touch communicates distinct emotions between humans. In the current reanalysis, we found that anger was communicated at greater-than-chance levels only when a male comprised at least one member of a communicating dyad. Sympathy was communicated at greater-than-chance levels only when a female comprised at least one member of the dyad. Finally, happiness was communicated only if females comprised the entire dyad. The current analysis demonstrates gender asymmetries in the accuracy of communicating distinct emotions via touch between humans

Improvements in task performance after practice are associated with scale-free dynamics of brain activity

202405 bcrcVersion of RecordOthersNational Science Foundation(National Science Foundation (NSF))TKF FoundationNational Institute on Alcohol Abuse and Alcoholism(United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Alcohol Abuse & Alcoholism (NIAAA))Grossman Institute for Neuroscience, Quantitative Biology, and Human Behavior from the University of ChicagoPublishedC