Refine
Year of publication
- 2017 (741) (remove)
Document Type
- Journal article (394)
- Doctoral Thesis (242)
- Complete part of issue (52)
- Preprint (12)
- Review (12)
- Book (8)
- Conference Proceeding (7)
- Jahresbericht (4)
- Book article / Book chapter (4)
- Master Thesis (2)
- Report (2)
- Working Paper (2)
Language
- English (504)
- German (232)
- French (3)
- Multiple languages (2)
Keywords
- Würzburg (51)
- Wuerzburg (50)
- Wurzburg (50)
- Universität (48)
- University (45)
- Hadron-Hadron scattering (experiments) (28)
- High energy physics (26)
- medicine (14)
- physics (12)
- Medicine (11)
Institute
- Theodor-Boveri-Institut für Biowissenschaften (78)
- Universität - Fakultätsübergreifend (47)
- Physikalisches Institut (46)
- Graduate School of Life Sciences (35)
- Medizinische Klinik und Poliklinik I (25)
- Institut für Psychologie (24)
- Institut für Theoretische Physik und Astrophysik (24)
- Neurologische Klinik und Poliklinik (24)
- Medizinische Klinik und Poliklinik II (21)
- Fakultät für Physik und Astronomie (20)
Schriftenreihe
Sonstige beteiligte Institutionen
- Johns Hopkins School of Medicine, Baltimore, MD, U.S. (4)
- Institut für Optik und Atomare Physik, Technische Universität Berlin, 10623 Berlin, Germany (2)
- Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama 226-8503, Japan (2)
- CERN (Geneva, Switzerland) (1)
- Deutsches Zentrum für Herzinsuffizienz (1)
- Didaktik der Chemie (1)
- Endokrinologie (1)
- Fraunhofer Institut für Silicatforschung ISC (1)
- Fraunhofer-Institut für Silicatforschung (1)
- Fraunhofer-Institut für Silicatforschung ISC (1)
ResearcherID
- D-3057-2014 (1)
- M-1240-2017 (1)
- N-8985-2015 (1)
Background
Identification of families at risk for ovarian cancer offers the opportunity to consider prophylactic surgery thus reducing ovarian cancer mortality. So far, identification of potentially affected families in Germany was solely performed via family history and numbers of affected family members with breast or ovarian cancer. However, neither the prevalence of deleterious variants in \(BRCA1/2\) in ovarian cancer in Germany nor the reliability of family history as trigger for genetic counselling has ever been evaluated.
Methods
Prospective counseling and germline testing of consecutive patients with primary diagnosis or with platinum-sensitive relapse of an invasive epithelial ovarian cancer. Testing included 25 candidate and established risk genes. Among these 25 genes, 16 genes (\(ATM\), \(BRCA1\), \(BRCA2\), \(CDH1\), \(CHEK2\), \(MLH1\), \(MSH2\), \(MSH6\), \(NBN\), \(PMS2\), \(PTEN\), \(PALB2\), \(RAD51C\), \(RAD51D\), \(STK11\), \(TP53\)) were defined as established cancer risk genes. A positive family history was defined as at least one relative with breast cancer or ovarian cancer or breast cancer in personal history.
Results
In total, we analyzed 523 patients: 281 patients with primary diagnosis of ovarian cancer and 242 patients with relapsed disease. Median age at primary diagnosis was 58 years (range 16–93) and 406 patients (77.6%) had a high-grade serous ovarian cancer. In total, 27.9% of the patients showed at least one deleterious variant in all 25 investigated genes and 26.4% in the defined 16 risk genes. Deleterious variants were most prevalent in the \(BRCA1\) (15.5%), \(BRCA2\) (5.5%), \(RAD51C\) (2.5%) and \(PALB2\) (1.1%) genes. The prevalence of deleterious variants did not differ significantly between patients at primary diagnosis and relapse. The prevalence of deleterious variants in \(BRCA1/2\) (and in all 16 risk genes) in patients <60 years was 30.2% (33.2%) versus 10.6% (18.9%) in patients \(\geq\)60 years. Family history was positive in 43% of all patients. Patients with a positive family history had a prevalence of deleterious variants of 31.6% (36.0%) versus 11.4% (17.6%) and histologic subtype of high grade serous ovarian cancer versus other showed a prevalence of deleterious variants of 23.2% (29.1%) and 10.2% (14.8%), respectively. Testing only for \(BRCA1/2\) would miss in our series more than 5% of the patients with a deleterious variant in established risk genes.
Conclusions
26.4% of all patients harbor at least one deleterious variant in established risk genes. The threshold of 10% mutation rate which is accepted for reimbursement by health care providers in Germany was observed in all subgroups analyzed and neither age at primary diagnosis nor histo-type or family history sufficiently enough could identify a subgroup not eligible for genetic counselling and testing. Genetic testing should therefore be offered to every patient with invasive epithelial ovarian cancer and limiting testing to \(BRCA1/2\) seems to be
not sufficient.
Ratios of top-quark pair to \(Z\)-boson cross sections measured from proton-proton collisions at the LHC centre-of-mass energies of \(\sqrt{s}\) = 13 TeV, 8 TeV, and 7 TeV are presented by the ATLAS Collaboration. Single ratios, at a given \(\sqrt{s}\) for the two processes and at different \(\sqrt{s}\) for each process, as well as double ratios of the two processes at different \(\sqrt{s}\), are evaluated. The ratios are constructed using previously published ATLAS measurements of the \({t\overline{t}}\) and \(Z\)-boson production cross sections, corrected to a common phase space where required, and a new analysis of \(Z\) → ℓ\(^+\)ℓ\(^-\) where ℓ = \(e, µ\) at \(\sqrt{s}\) = 13 TeV performed with data collected in 2015 with an integrated luminosity of 3.2 fb\(^−1\). Correlations of systematic uncertainties are taken into account when evaluating the uncertainties in the ratios. The correlation model is also used to evaluate the combined cross section of the \(Z\) → \(e\)\(^+\)\(e\)\(^−\) and the \(Z\) → \(µ\)\(^+\)\(µ\)\(^−\) channels for each \(\sqrt{s}\) value. The results are compared to calculations performed at next-to-next-to-leading-order accuracy using recent sets of parton distribution functions. The data demonstrate significant power to constrain the gluon distribution function for the Bjorken-\(x\) values near 0.1 and the light-quark sea for \(x\) < 0.02.
\(Ambra1\) is linked to autophagy and neurodevelopment. Heterozygous \(Ambra1\) deficiency induces autism-like behavior in a sexually dimorphic manner. Extraordinarily, autistic features are seen in female mice only, combined with stronger Ambra1 protein reduction in brain compared to males. However, significance of \(AMBRA1\) for autistic phenotypes in humans and, apart from behavior, for other autism-typical features, namely early brain enlargement or increased seizure propensity, has remained unexplored. Here we show in two independent human samples that a single normal \(AMBRA1\) genotype, the intronic SNP rs3802890-AA, is associated with autistic features in women, who also display lower \(AMBRA1\) mRNA expression in peripheral blood mononuclear cells relative to female GG carriers. Located within a non-coding RNA, likely relevant for mRNA and protein interaction, rs3802890 (A versus G allele) may affect its stability through modification of folding, as predicted by \(in\) \(silico\) analysis. Searching for further autism-relevant characteristics in \(Ambra1^{+/−}\) mice, we observe reduced interest of female but not male mutants regarding pheromone signals of the respective other gender in the social intellicage set-up. Moreover, altered pentylentetrazol-induced seizure propensity, an \(in\) \(vivo\) readout of neuronal excitation–inhibition dysbalance, becomes obvious exclusively in female mutants. Magnetic resonance imaging reveals mild prepubertal brain enlargement in both genders, uncoupling enhanced brain dimensions from the primarily female expression of all other autistic phenotypes investigated here. These data support a role of \(AMBRA1/Ambra1\) partial loss-of-function genotypes for female autistic traits. Moreover, they suggest \(Ambra1\) heterozygous mice as a novel multifaceted and construct-valid genetic mouse model for female autism.
Regulatory T cells (Tregs) prevent autoimmunity but limit antitumor immunity. The canonical NF-\(\kappa\)B signaling pathway both activates immunity and promotes thymic Treg development. Here, we report that mature Tregs continue to require NF-\(\kappa\)B signaling through I\(\kappa\)B-kinase \(\beta\) (IKK\(\beta\)) after thymic egress. Mice lacking IKK\(\beta\) in mature Tregs developed scurfy-like immunopathology due to death of peripheral FoxP3\(^+\) Tregs. Also, pharmacological IKK\(\beta\) inhibition reduced Treg numbers in the circulation by ~50% and downregulated FoxP3 and CD25 expression and STAT5 phosphorylation. In contrast, activated cytotoxic T lymphocytes (CTLs) were resistant to IKK\(\beta\) inhibition because other pathways, in particular nuclear factor of activated T cells (NFATc1) signaling, sustained their survival and expansion. In a melanoma mouse model, IKK\(\beta\) inhibition after CTL cross-priming improved the antitumor response and delayed tumor growth. In conclusion, prolonged IKK\(\beta\) inhibition decimates circulating Tregs and improves CTL responses when commenced after tumor vaccination, indicating that IKK\(\beta\) represents a druggable checkpoint.
MicroRNAs (miRNAs) are class of small RNA molecules with major impact on gene regulation. We analyzed the potential of miRNAs secreted from pre-implantation embryos into the embryonic culture media as biomarkers to predict successful pregnancy. Using microarray analysis, we profiled the miRNome of the 56 spent culture media (SCM) after embryos transfer and found a total of 621 miRNAs in the SCM. On average, we detected 163 miRNAs in SCM of samples with failed pregnancies, but only 149 SCM miRNAs of embryos leading to pregnancies. MiR-634 predicted an embryo transfer leading to a positive pregnancy with an accuracy of 71% and a sensitivity of 85%. Among the 621 miRNAs, 102 (16.4%) showed a differential expression between positive and negative outcome of pregnancy with miR-29c-3p as the most significantly differentially expressed miRNA. The number of extracellular vehicles was lower in SCM with positive outcomes (3.8 × 10\(^9\)/mL EVs), as compared to a negative outcome (7.35 × 10\(^9\)/mL EVs) possibly explaining the reduced number of miRNAs in the SCM associated with failed pregnancies. The analysis of the miRNome in the SCM of couples undergoing fertility treatment lays the ground towards development of biomarkers to predict successful pregnancy and towards understanding the role of embryonic miRNAs found in the SCM.
Same- and opposite-sign charge asymmetries are measured in lepton+jets \({t\overline{t}}\) events in which a \(b\)-hadron decays semileptonically to a soft muon, using data corresponding to an integrated luminosity of 20.3 fb\(^{−1}\) from proton-proton collisions at a centre-of-mass energy of \(\sqrt{s}\) = 8 TeV collected with the ATLAS detector at the Large Hadron Collider at CERN. The charge asymmetries are based on the charge of the lepton from the top-quark decay and the charge of the soft muon from the semileptonic decay of a \(b\)-hadron and are measured in a fiducial region corresponding to the experimental acceptance. Four CP asymmetries (one mixing and three direct) are measured and are found to be compatible with zero and consistent with the Standard Model.
A Good Practice is a practice that works well, produces good results, and is recommended as a model. MACVIA-ARIA Sentinel Network (MASK), the new Allergic Rhinitis and its Impact on Asthma (ARIA) initiative, is an example of a Good Practice focusing on the implementation of multi-sectoral care pathways using emerging technologies with real life data in rhinitis and asthma multi-morbidity. The European Union Joint Action on Chronic Diseases and Promoting Healthy Ageing across the Life Cycle (JA-CHRODIS) has developed a checklist of 28 items for the evaluation of Good Practices. SUNFRAIL (Reference Sites Network for Prevention and Care of Frailty and Chronic Conditions in community dwelling persons of EU Countries), a European Union project, assessed whether MASK is in line with the 28 items of JA-CHRODIS. A short summary was proposed for each item and 18 experts, all members of ARIA and SUNFRAIL from 12 countries, assessed the 28 items using a Survey Monkey-based questionnaire. A visual analogue scale (VAS) from 0 (strongly disagree) to 100 (strongly agree) was used. Agreement equal or over 75% was observed for 14 items (50%). MASK is following the JA-CHRODIS recommendations for the evaluation of Good Practices.
A measurement of the \(ZZ\) production cross section in the \(ℓ^−ℓ^+ℓ^{′−}ℓ^{′+}\) and \(ℓ^−ℓ^+{ν\overline{ν}}\) channels (ℓ = e, µ) in proton-proton collisions at \(\sqrt{s}\) = 8TeV at the Large Hadron Collider at CERN, using data corresponding to an integrated luminosity of 20.3 fb\(^{−1}\) collected by the ATLAS experiment in 2012 is presented. The fiducial cross sections for \(ZZ\) → \(ℓ^−ℓ^+ℓ^{′−}ℓ^{′+}\) and \(ZZ\) → \(ℓ^−ℓ^+{ν\overline{ν}}\) are measured in selected phase-space regions. The total cross section for \(ZZ\) events produced with both \(Z\) bosons in the mass range 66 to 116GeV is measured from the combination of the two channels to be 7.3 ± 0.4(stat) ± 0.3 (syst)\(^{−0.2}_{−0.1}\) (lumi) pb, which is consistent with the Standard Model prediction of 6.6\(^{+0.7}_{−0.6}\) pb. The differential cross sections in bins of various kinematic variables are presented. The differential event yield as a function of the transverse momentum of the leading \(Z\) boson is used to set limits on anomalous neutral triple gauge boson couplings in \(ZZ\) production.
Automatic orienting to unexpected changes in the environment is a pre-requisite for adaptive behavior. One prominent mechanism of automatic attentional control is the Orienting Response (OR). Despite the fundamental significance of the OR in everyday life, only little is known about how the OR is affected by healthy aging. We tested this question in two age groups (19–38 and 55–72 years) and measured skin-conductance responses (SCRs) and event-related brain potentials (ERPs) to novels (i.e., short environmental sounds presented only once in the experiment; 10% of the trials) compared to standard sounds (600 Hz sinusoidal tones with 200 ms duration; 90% of the trials). Novel and standard stimuli were presented in four conditions differing in the inter-stimulus interval (ISI) with a mean ISI of either 10, 3, 1, or 0.5 s (blocked presentation). In both age groups, pronounced SCRs were elicited by novels in the 10 s ISI condition, suggesting the elicitation of stable ORs. These effects were accompanied by pronounced N1 and frontal P3 amplitudes in the ERP, suggesting that automatic novelty processing and orientation of attention are effective in both age groups. Furthermore, the SCR and ERP effects declined with decreasing ISI length. In addition, differences between the two groups were observable with the fastest presentation rates (i.e., 1 and 0.5 s ISI length). The most prominent difference was a shift of the peak of the frontal positivity from around 300 to 200 ms in the 19–38 years group while in the 55–72 years group the amplitude of the frontal P3 decreased linearly with decreasing ISI length. Taken together, this pattern of results does not suggest a general decline in processing efficacy with healthy aging. At least with very rare changes (here, the novels in the 10 s ISI condition) the OR is as effective in healthy older adults as in younger adults. With faster presentation rates, however, the efficacy of the OR decreases. This seems to result in a switch from novelty to deviant processing in younger adults, but less so in the group of older adults.