DDRprot: a database of DNA damage response-related proteins

The DNA Damage Response (DDR) signalling network is an essential system that protects the genome’s integrity. The DDRprot database presented here is a resource that integrates manually curated information on the human DDR network and its sub-pathways. For each particular DDR protein, we present detailed information about its function. If involved in post-translational modifications (PTMs) with each other, we depict the position of the modified residue/s in the three-dimensional structures, when resolved structures are available for the proteins. All this information is linked to the original publication from where it was obtained. Phylogenetic information is also shown, including time of emergence and conservation across 47 selected species, family trees and sequence alignments of homologues. The DDRprot database can be queried by different criteria: pathways, species, evolutionary age or involvement in (PTM). Sequence searches using hidden Markov models can be also used.E.A.-L. was supported by the European Commission grant [FP7-REGPOT-2012-2013-1; A.A. was partially supported by the Spanish Ministry of Science and Innovation grant [PS09/02111].Peer reviewe

Scaling analysis of the magnetic monopole mass and condensate in the pure U(1) lattice gauge theory

We observe the power law scaling behavior of the monopole mass and condensate in the pure compact U(1) gauge theory with the Villain action. In the Coulomb phase the monopole mass scales with the exponent \nu_m=0.49(4). In the confinement phase the behavior of the monopole condensate is described with remarkable accuracy by the exponent \beta_{exp}=0.197(3). Possible implications of these phenomena for a construction of a strongly coupled continuum U(1) gauge theory are discussed.Comment: Added references [1

ORCA-EFCD consensus report on clinical recommendation for caries diagnosis. Paper I:caries lesion detection and depth assessment

OBJECTIVES: The aim of the present consensus paper was to provide recommendations for clinical practice considering the use of visual examination, dental radiography and adjunct methods for primary caries detection.MATERIALS AND METHODS: The executive councils of the European Organisation for Caries Research (ORCA) and the European Federation of Conservative Dentistry (EFCD) nominated ten experts each to join the expert panel. The steering committee formed three work groups that were asked to provide recommendations on (1) caries detection and diagnostic methods, (2) caries activity assessment and (3) forming individualised caries diagnoses. The experts responsible for "caries detection and diagnostic methods" searched and evaluated the relevant literature, drafted this manuscript and made provisional consensus recommendations. These recommendations were discussed and refined during the structured process in the whole work group. Finally, the agreement for each recommendation was determined using an anonymous Delphi survey.RESULTS: Recommendations (N = 8) were approved and agreed upon by the whole expert panel: visual examination (N = 3), dental radiography (N = 3) and additional diagnostic methods (N = 2). While the quality of evidence was found to be heterogeneous, all recommendations were agreed upon by the expert panel.CONCLUSION: Visual examination is recommended as the first-choice method for the detection and assessment of caries lesions on accessible surfaces. Intraoral radiography, preferably bitewing, is recommended as an additional method. Adjunct, non-ionising radiation methods might also be useful in certain clinical situations.CLINICAL RELEVANCE: The expert panel merged evidence from the scientific literature with practical considerations and provided recommendations for their use in daily dental practice.</p

ORCA-EFCD consensus report on clinical recommendation for caries diagnosis. Paper I:caries lesion detection and depth assessment

OBJECTIVES: The aim of the present consensus paper was to provide recommendations for clinical practice considering the use of visual examination, dental radiography and adjunct methods for primary caries detection.MATERIALS AND METHODS: The executive councils of the European Organisation for Caries Research (ORCA) and the European Federation of Conservative Dentistry (EFCD) nominated ten experts each to join the expert panel. The steering committee formed three work groups that were asked to provide recommendations on (1) caries detection and diagnostic methods, (2) caries activity assessment and (3) forming individualised caries diagnoses. The experts responsible for "caries detection and diagnostic methods" searched and evaluated the relevant literature, drafted this manuscript and made provisional consensus recommendations. These recommendations were discussed and refined during the structured process in the whole work group. Finally, the agreement for each recommendation was determined using an anonymous Delphi survey.RESULTS: Recommendations (N = 8) were approved and agreed upon by the whole expert panel: visual examination (N = 3), dental radiography (N = 3) and additional diagnostic methods (N = 2). While the quality of evidence was found to be heterogeneous, all recommendations were agreed upon by the expert panel.CONCLUSION: Visual examination is recommended as the first-choice method for the detection and assessment of caries lesions on accessible surfaces. Intraoral radiography, preferably bitewing, is recommended as an additional method. Adjunct, non-ionising radiation methods might also be useful in certain clinical situations.CLINICAL RELEVANCE: The expert panel merged evidence from the scientific literature with practical considerations and provided recommendations for their use in daily dental practice.</p

Energy or information? The role of seed availability for reproductive decisions in edible dormice

The edible dormouse is a specialized seed predator which is highly adapted to the fluctuations of food availability caused by mast seeding of beech and oak trees. Dormice produce young just in time with maximum food availability, and can completely skip reproduction in years with a lack of seeding. Because their decision to reproduce or not in any particular year is made long before the ripe seeds are available, it seems that dormice can anticipate the upcoming mast situation. We tested the hypothesis that the presence of high caloric food in spring affects their reproductive decision. Therefore, we supplementary fed dormice in a field experiment from spring to early summer with sunflower seeds, which also contain a high amount of energy. Supplemental feeding caused significant increases in the proportion of reproducing females and reproductively active males. These results suggest that edible dormice may use the occurrence of an energy rich food resource to predict the autumnal mast situation. Further, our data indicate that the decision to reproduce was not the result of an increased body mass due to the consumption of surplus food, but that sufficient seed abundance acts as an environmental signal to which dormice adjust their reproduction

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe