TY - JOUR A1 - Hausoel, A. A1 - Karolak, M. A1 - Şaşιoğlu, E. A1 - Lichtenstein, A. A1 - Held, K. A1 - Katanin, A. A1 - Toschi, A. A1 - Sangiovanni, G. T1 - Local magnetic moments in iron and nickel at ambient and Earth's core conditions JF - Nature Communications N2 - Some Bravais lattices have a particular geometry that can slow down the motion of Bloch electrons by pre-localization due to the band-structure properties. Another known source of electronic localization in solids is the Coulomb repulsion in partially filled d or f orbitals, which leads to the formation of local magnetic moments. The combination of these two effects is usually considered of little relevance to strongly correlated materials. Here we show that it represents, instead, the underlying physical mechanism in two of the most important ferromagnets: nickel and iron. In nickel, the van Hove singularity has an unexpected impact on the magnetism. As a result, the electron–electron scattering rate is linear in temperature, in violation of the conventional Landau theory of metals. This is true even at Earth’s core pressures, at which iron is instead a good Fermi liquid. The importance of nickel in models of geomagnetism may have therefore to be reconsidered. KW - ferromagnetism KW - electronic properties and materials KW - magnetic properties and materials KW - nickel KW - iron Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170681 VL - 8 IS - 16062 ER - TY - JOUR A1 - Haunert, Jan-Henrik A1 - Wolff, Alexander T1 - Beyond maximum independent set: an extended integer programming formulation for point labeling JF - ISPRS International Journal of Geo-Information N2 - Map labeling is a classical problem of cartography that has frequently been approached by combinatorial optimization. Given a set of features in a map and for each feature a set of label candidates, a common problem is to select an independent set of labels (that is, a labeling without label–label intersections) that contains as many labels as possible and at most one label for each feature. To obtain solutions of high cartographic quality, the labels can be weighted and one can maximize the total weight (rather than the number) of the selected labels. We argue, however, that when maximizing the weight of the labeling, the influences of labels on other labels are insufficiently addressed. Furthermore, in a maximum-weight labeling, the labels tend to be densely packed and thus the map background can be occluded too much. We propose extensions of an existing model to overcome these limitations. Since even without our extensions the problem is NP-hard, we cannot hope for an efficient exact algorithm for the problem. Therefore, we present a formalization of our model as an integer linear program (ILP). This allows us to compute optimal solutions in reasonable time, which we demonstrate both for randomly generated point sets and an existing data set of cities. Moreover, a relaxation of our ILP allows for a simple and efficient heuristic, which yielded near-optimal solutions for our instances. KW - integer linear programming KW - cartographic requirements KW - map labeling KW - point-feature label placement KW - NP-hard Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158960 VL - 6 IS - 11 ER - TY - JOUR A1 - Hassan, Musa A. A1 - Vasquez, Juan J. A1 - Guo-Liang, Chew A1 - Meissner, Markus A1 - Siegel, T. Nicolai T1 - Comparative ribosome profiling uncovers a dominant role for translational control in \(Toxoplasma\) \(gondii\) JF - BMC Genomics N2 - Background The lytic cycle of the protozoan parasite \(Toxoplasma\) \(gondii\), which involves a brief sojourn in the extracellular space, is characterized by defined transcriptional profiles. For an obligate intracellular parasite that is shielded from the cytosolic host immune factors by a parasitophorous vacuole, the brief entry into the extracellular space is likely to exert enormous stress. Due to its role in cellular stress response, we hypothesize that translational control plays an important role in regulating gene expression in \(Toxoplasma\) during the lytic cycle. Unlike transcriptional profiles, insights into genome-wide translational profiles of \(Toxoplasma\) \(gondii\) are lacking. Methods We have performed genome-wide ribosome profiling, coupled with high throughput RNA sequencing, in intracellular and extracellular \(Toxoplasma\) \(gondii\) parasites to investigate translational control during the lytic cycle. Results Although differences in transcript abundance were mostly mirrored at the translational level, we observed significant differences in the abundance of ribosome footprints between the two parasite stages. Furthermore, our data suggest that mRNA translation in the parasite is potentially regulated by mRNA secondary structure and upstream open reading frames. Conclusion We show that most of the \(Toxoplasma\) genes that are dysregulated during the lytic cycle are translationally regulated. KW - Biology KW - Ribosome profiling KW - RNA-sequencing KW - Translation efficiency KW - Toxoplasma gondii KW - Apicomplexan Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172376 VL - 18 ER - TY - JOUR A1 - Harter, Philipp A1 - Hauke, Jan A1 - Heitz, Florian A1 - Reuss, Alexander A1 - Kommoss, Stefan A1 - Marmé, Frederik A1 - Heimbach, André A1 - Prieske, Katharina A1 - Richters, Lisa A1 - Burges, Alexander A1 - Neidhardt, Guido A1 - de Gregorio, Nikolaus A1 - El-Balat, Ahmed A1 - Hilpert, Felix A1 - Meier, Werner A1 - Kimmig, Rainer A1 - Kast, Karin A1 - Sehouli, Jalid A1 - Baumann, Klaus A1 - Jackisch, Christian A1 - Park-Simon, Tjoung-Won A1 - Hanker, Lars A1 - Kröber, Sandra A1 - Pfisterer, Jacobus A1 - Gevensleben, Heidrun A1 - Schnelzer, Andreas A1 - Dietrich, Dimo A1 - Neunhöffer, Tanja A1 - Krockenberger, Mathias A1 - Brucker, Sara Y. A1 - Nürnberg, Peter A1 - Thiele, Holger A1 - Altmüller, Janine A1 - Lamla, Josefin A1 - Elser, Gabriele A1 - du Bois, Andreas A1 - Hahnen, Eric A1 - Schmutzler, Rita T1 - Prevalence of deleterious germline variants in risk genes including \(BRCA1/2\) in consecutive ovarian cancer patients (AGO-TR-1) JF - PLoS ONE N2 - 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. KW - medicine KW - Genetic causes of cancer KW - ovarian cancer KW - cancer risk factors KW - histology KW - cancer detection and diagnosis KW - breast cancer KW - genetic testing KW - human genetics Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173553 VL - 12 IS - 10 ER - TY - JOUR A1 - Hankir, Mohammed K. A1 - Patt, Marianne A1 - Patt, Jörg T. W. A1 - Becker, Georg A. A1 - Rullmann, Michael A1 - Kranz, Mathias A1 - Deuther-Conrad, Winnie A1 - Schischke, Kristin A1 - Seyfried, Florian A1 - Brust, Peter A1 - Hesse, Swen A1 - Sabri, Osama A1 - Krügel, Ute A1 - Fenske, Wiebke T1 - Suppressed fat appetite after Roux-en-Y gastric bypass surgery associates with reduced brain mu-opioid receptor availability in diet-induced obese male rats JF - Frontiers in Neuroscience N2 - Brain μ-opioid receptors (MORs) stimulate high-fat (HF) feeding and have been implicated in the distinct long term outcomes on body weight of bariatric surgery and dieting. Whether alterations in fat appetite specifically following these disparate weight loss interventions relate to changes in brain MOR signaling is unknown. To address this issue, diet-induced obese male rats underwent either Roux-en-Y gastric bypass (RYGB) or sham surgeries. Postoperatively, animals were placed on a two-choice diet consisting of low-fat (LF) and HF food and sham-operated rats were further split into ad libitum fed (Sham-LF/HF) and body weight-matched (Sham-BWM) to RYGB groups. An additional set of sham-operated rats always only on a LF diet (Sham-LF) served as lean controls, making four experimental groups in total. Corresponding to a stage of weight loss maintenance for RYGB rats, two-bottle fat preference tests in conjunction with small-animal positron emission tomography (PET) imaging studies with the selective MOR radioligand [\(^{11}\)C]carfentanil were performed. Brains were subsequently collected and MOR protein levels in the hypothalamus, striatum, prefrontal cortex and orbitofrontal cortex were analyzed by Western Blot. We found that only the RYGB group presented with intervention-specific changes: having markedly suppressed intake and preference for high concentration fat emulsions, a widespread reduction in [\(^{11}\)C]carfentanil binding potential (reflecting MOR availability) in various brain regions, and a downregulation of striatal and prefrontal MOR protein levels compared to the remaining groups. These findings suggest that the suppressed fat appetite caused by RYGB surgery is due to reduced brain MOR signaling, which may contribute to sustained weight loss unlike the case for dieting. KW - bariatric surgery KW - caloric-restriction KW - fat appetite KW - Brain μ-opioid receptors KW - positron emission tomography imaging Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-181130 VL - 10 ER - TY - JOUR A1 - Hampe, Irene A. I. A1 - Friedman, Justin A1 - Edgerton, Mira A1 - Morschhäuser, Joachim T1 - An acquired mechanism of antifungal drug resistance simultaneously enables Candida albicans to escape from intrinsic host defenses JF - PLoS Pathogens N2 - The opportunistic fungal pathogen Candida albicans frequently produces genetically altered variants to adapt to environmental changes and new host niches in the course of its life-long association with the human host. Gain-of-function mutations in zinc cluster transcription factors, which result in the constitutive upregulation of their target genes, are a common cause of acquired resistance to the widely used antifungal drug fluconazole, especially during long-term therapy of oropharyngeal candidiasis. In this study, we investigated if C. albicans also can develop resistance to the antimicrobial peptide histatin 5, which is secreted in the saliva of humans to protect the oral mucosa from pathogenic microbes. As histatin 5 has been shown to be transported out of C. albicans cells by the Flu1 efflux pump, we screened a library of C. albicans strains that contain artificially activated forms of all zinc cluster transcription factors of this fungus for increased FLU1 expression. We found that a hyperactive Mrr1, which confers fluconazole resistance by upregulating the multidrug efflux pump MDR1 and other genes, also causes FLU1 overexpression. Similarly to the artificially activated Mrr1, naturally occurring gain-of-function mutations in this transcription factor also caused FLU1 upregulation and increased histatin 5 resistance. Surprisingly, however, Mrr1-mediated histatin 5 resistance was mainly caused by the upregulation of MDR1 instead of FLU1, revealing a previously unrecognized function of the Mdr1 efflux pump. Fluconazole-resistant clinical C. albicans isolates with different Mrr1 gain-of-function mutations were less efficiently killed by histatin 5, and this phenotype was reverted when MRR1 was deleted. Therefore, antimycotic therapy can promote the evolution of strains that, as a consequence of drug resistance mutations, simultaneously have acquired increased resistance against an innate host defense mechanism and are thereby better adapted to certain host niches. KW - antimicrobial resistance KW - transcriptional control KW - Candida albicans KW - transcription factors KW - mutation KW - hyperexpression techniques KW - antifungals KW - point mutation Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158883 VL - 13 IS - 9 ER - TY - JOUR A1 - Halder, Luke D. A1 - Abdelfatah, Mahmoud A. A1 - Jo, Emeraldo A. H. A1 - Jacobsen, Ilse D. A1 - Westermann, Martin A1 - Beyersdorf, Niklas A1 - Lorkowski, Stefan A1 - Zipfel, Peter F. A1 - Skerka, Christine T1 - Factor H binds to extracellular DNA traps released from human blood monocytes in response to Candida albicans JF - Frontiers in Immunology N2 - Upon systemic infection with human pathogenic yeast Candida albicans (C. albicans), human monocytes and polymorph nuclear neutrophilic granulocytes are the first immune cells to respond and come into contact with C. albicans. Monocytes exert immediate candidacidal activity and inhibit germination, mediate phagocytosis, and kill fungal cells. Here, we show that human monocytes spontaneously respond to C. albicans cells via phagocytosis, decondensation of nuclear DNA, and release of this decondensed DNA in the form of extracellular traps (called monocytic extracellular traps: MoETs). Both subtypes of monocytes (CD14\(^{++}\)CD16\(^−\)/CD14\(^+\)CD16\(^+\)) formed MoETs within the first hours upon contact with C. albicans. MoETs were characterized by the presence of citrullinated histone, myeloperoxidase, lactoferrin, and elastase. MoETs were also formed in response to Staphylococcus aureus and Escherichia coli, indicating a general reaction of monocytes to infectious microbes. MoET induction differs from extracellular trap formation in macrophages as MoETs are not triggered by simvastatin, an inhibitor of cholesterol synthesis and inducer of extracellular traps in macrophages. Extracellular traps from both monocytes and neutrophils activate complement and C3b is deposited. However, factor H (FH) binds via C3b to the extracellular DNA, mediates cofactor activity, and inhibits the induction of the inflammatory cytokine interleukin-1 beta in monocytes. Altogether, the results show that human monocytes release extracellular DNA traps in response to C. albicans and that these traps finally bind FH via C3b to presumably support clearance without further inflammation. KW - Candida KW - monocytes KW - DNA traps KW - MPO KW - factor H Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-181127 VL - 7 ER - TY - JOUR A1 - Halboth, Florian A1 - Roces, Flavio T1 - The construction of ventilation turrets in Atta vollenweideri leaf-cutting ants: Carbon dioxide levels in the nest tunnels, but not airflow or air humidity, influence turret structure JF - PLoS ONE N2 - Nest ventilation in the leaf-cutting ant Atta vollenweideri is driven via a wind-induced mechanism. On their nests, workers construct small turrets that are expected to facilitate nest ventilation. We hypothesized that the construction and structural features of the turrets would depend on the colony’s current demands for ventilation and thus might be influenced by the prevailing environmental conditions inside the nest. Therefore, we tested whether climate-related parameters, namely airflow, air humidity and CO\(_{2}\) levels in the outflowing nest air influenced turret construction in Atta vollenweideri. In the laboratory, we simulated a semi-natural nest arrangement with fungus chambers, a central ventilation tunnel providing outflow of air and an aboveground building arena for turret construction. In independent series, different climatic conditions inside the ventilation tunnel were experimentally generated, and after 24 hours, several features of the built turret were quantified, i.e., mass, height, number and surface area (aperture) of turret openings. Turret mass and height were similar in all experiments even when no airflow was provided in the ventilation tunnel. However, elevated CO\(_{2}\) levels led to the construction of a turret with several minor openings and a larger total aperture. This effect was statistically significant at higher CO\(_{2}\) levels of 5% and 10% but not at 1% CO\(_{2}\). The construction of a turret with several minor openings did not depend on the strong differences in CO\(_{2}\) levels between the outflowing and the outside air, since workers also built permeated turrets even when the CO\(_{2}\) levels inside and outside were both similarly high. We propose that the construction of turrets with several openings and larger opening surface area might facilitate the removal of CO\(_{2}\) from the underground nest structure and could therefore be involved in the control of nest climate in leaf-cutting ants. KW - carbon dioxide KW - animal sociality KW - ants KW - fungi KW - humidity KW - social systems KW - nesting habits KW - fungal structure Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159133 VL - 12 IS - 11 ER - TY - JOUR A1 - Hagemann, Christine A1 - Streng, Andrea A1 - Kraemer, Alexander A1 - Liese, Johannes G. T1 - Heterogeneity in coverage for measles and varicella vaccination in toddlers – analysis of factors influencing parental acceptance JF - BMC Public Health N2 - Background: In 2004, routine varicella vaccination was introduced in Germany for children aged 11–14 months. Routine measles vaccination had already been introduced in 1973 for the same age group, but coverage is still too low (<95%) in some areas to eliminate measles. The present study assessed varicella and measles vaccination coverage and determinants of parental acceptance in two study regions, situated in Northern and Southern Bavaria (Germany). Methods: From 2009 to 2011, annual cross-sectional parent surveys were performed on random samples of 600 children aged 18–36 months in the Bavarian regions of both Munich and Würzburg. Logistic regression models were used to identify factors associated with varicella and measles vaccination. Results: In 2009, 2010 and 2011, vaccination coverage was lower in Munich than in Würzburg, for both varicella (Munich 53%, 67%, 69% vs. Würzburg 72%, 81%, 83%) and for measles (Munich 88%, 89%, 91% vs. Würzburg 92%, 93%, 95%). Recommendation by the physician was the main independent factor associated with varicella vaccination in both regions (adjusted odd ratios (OR) with 95% confidence interval (CI): Munich OR 19.7, CI 13.6–28.6; Würzburg OR 34.7, CI 22.6–53.2). Attendance at a childcare unit was positively associated with a higher acceptance of varicella vaccination in Munich (OR 1.5, CI 1.1–2.2). Regarding measles vaccination, attendance at a childcare unit was positively associated in both regions (Munich OR 2.0; CI 1.3–3.0; Würzburg OR 1.8; CI 1.1–3.1), and a higher level of parental school education was negatively associated in Würzburg (OR 0.5, CI 0.3–0.9). Conclusions: Vaccination rates differed between regions, with rates constantly higher in Würzburg. Within each region, vaccination rates were lower for varicella than for measles. Measles vaccination status was mainly dependent upon socio-demographic factors (attendance at a childcare unit, parental school education), whereas for the more recently introduced varicella vaccination recommendation by the physician had the strongest impact. Hence, different strategies are needed to further improve vaccination rates for both diseases. KW - varicella KW - measles KW - vaccination KW - coverage KW - surveillance KW - pediatric Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157827 VL - 17 IS - 724 ER - TY - JOUR A1 - Haertle, Larissa A1 - Maierhofer, Anna A1 - Böck, Julia A1 - Lehnen, Harald A1 - Böttcher, Yvonne A1 - Blüher, Matthias A1 - Schorsch, Martin A1 - Potabattula, Ramya A1 - El Hajj, Nady A1 - Appenzeller, Silke A1 - Haaf, Thomas T1 - Hypermethylation of the non-imprinted maternal MEG3 and paternal MEST alleles is highly variable among normal individuals JF - PLoS ONE N2 - Imprinted genes show parent-specific activity (functional haploidy), which makes them particularly vulnerable to epigenetic dysregulation. Here we studied the methylation profiles of oppositely imprinted genes at single DNA molecule resolution by two independent parental allele-specific deep bisulfite sequencing (DBS) techniques. Using Roche (GSJunior) next generation sequencing technology, we analyzed the maternally imprinted MEST promoter and the paternally imprinted MEG3 intergenic (IG) differentially methylated region (DMR) in fetal cord blood, adult blood, and visceral adipose tissue. Epimutations were defined as paternal or maternal alleles with >50% aberrantly (de)methylated CpG sites, showing the wrong methylation imprint. The epimutation rates (range 2–66%) of the paternal MEST and the maternal MEG3 IG DMR allele, which should be completely unmethylated, were significantly higher than those (0–15%) of the maternal MEST and paternal MEG3 alleles, which are expected to be fully methylated. This hypermethylation of the non-imprinted allele (HNA) was independent of parental origin. Very low epimutation rates in sperm suggest that HNA occurred after fertilization. DBS with Illumina (MiSeq) technology confirmed HNA for the MEST promoter and the MEG3 IG DMR, and to a lesser extent, for the paternally imprinted secondary MEG3 promoter and the maternally imprinted PEG3 promoter. HNA leads to biallelic methylation of imprinted genes in a considerable proportion of normal body cells (somatic mosaicism) and is highly variable between individuals. We propose that during development and differentiation maintenance of differential methylation at most imprinting control regions may become to some extent redundant. The accumulation of stochastic and environmentally-induced methylation errors on the non-imprinted allele may increase epigenetic diversity between cells and individuals. KW - DNA methylation KW - genomic imprinting KW - polymerase chain reaction KW - blood KW - epigenetics KW - sequence alignment KW - sperm Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170433 VL - 12 IS - 8 ER -