Retrospect, insights and foresights: Biological control of Anobium puntcatum with Spathius exarator: Presentation

Biological control using beneficial organisms is getting more and more important in Integrated Pest Management. An effective strategy in the fight against the most common timber pest species, the furniture beetle Anobium punctatum, is based on the parasitoid wasp species Spathius exarator. This braconid wasp parasitizes its host species by piercing its ovipositor directly through the wood surface followed by oviposition onto the beetle larva. After feeding on the larva and pupation, the adult wasp emerges through a tiny 0.5 mm wide wood hole, which can be clearly distinguished from the 2 mm wide hole of A. punctatum. This enables us to observe easily the treatment success as each new S. exarator exit hole is equivalent to one killed beetle larva. Between 2012 and 2017, the braconid wasps were introduced into about 80 A. punctatum infested buildings. At least twelve treatments over a period of up to three years were performed. On exactly defined areas, the newly emerged exit holes of A. punctatum and S. exarator were counted and the parasitisation rate was calculated. Here we present pooled data of 29 A. punctatum infested churches, successfully treated and monitored over a period of one to five years. Furthermore, as a representative sample, we show the results of one church over a period of six years. We demonstrate the biological control of the common furniture beetle with this braconid wasp as an efficient, sustainable alternative to conventional residual methods. However, after a period of up to three years intensive treatment, a continuous monitoring-program with necessary additional single treatments should follow.Biological control using beneficial organisms is getting more and more important in Integrated Pest Management. An effective strategy in the fight against the most common timber pest species, the furniture beetle Anobium punctatum, is based on the parasitoid wasp species Spathius exarator. This braconid wasp parasitizes its host species by piercing its ovipositor directly through the wood surface followed by oviposition onto the beetle larva. After feeding on the larva and pupation, the adult wasp emerges through a tiny 0.5 mm wide wood hole, which can be clearly distinguished from the 2 mm wide hole of A. punctatum. This enables us to observe easily the treatment success as each new S. exarator exit hole is equivalent to one killed beetle larva. Between 2012 and 2017, the braconid wasps were introduced into about 80 A. punctatum infested buildings. At least twelve treatments over a period of up to three years were performed. On exactly defined areas, the newly emerged exit holes of A. punctatum and S. exarator were counted and the parasitisation rate was calculated. Here we present pooled data of 29 A. punctatum infested churches, successfully treated and monitored over a period of one to five years. Furthermore, as a representative sample, we show the results of one church over a period of six years. We demonstrate the biological control of the common furniture beetle with this braconid wasp as an efficient, sustainable alternative to conventional residual methods. However, after a period of up to three years intensive treatment, a continuous monitoring-program with necessary additional single treatments should follow

Ladeinfrastruktur für Elektromobilität im Jahr 2050 in Deutschland

Im Rahmen dieser Arbeit soll der mit dem Markthochlauf von Elektrofahrzeugen einhergehende Aufbau von Ladeinfrastruktur unter quantitativen und finanziellen Aspekten untersucht werden. Ziel ist es, die notwendige Anzahl an Ladepunkten und die Höhe der Gesamtinvestitionen für Ladeinfrastruktur bei einer Quote von 100% Elektrofahrzeugen im privaten Verkehr im Jahr 2050 in Deutschland zu simulieren. In diesem Zuge werden das Mobilitätsverhalten der deutschen Bevölkerung analysiert und mögliche Standorte für Ladesäulen auf ihre Funktionalitätsanforderungen geprüft. Mithilfe spezifischer Annahmen für ein Best- und ein Worst-Case-Szenario kann auf Basis dessen eine Simulation der Ladeinfrastruktur entwickelt werden. Die Ergebnisse der Simulation zeigen, dass mit einem quantitativen Bedarf für rund 40 Millionen Ladepunkte und einem Investitionsvolumen von 80 bis 110 Milliarden Euro gerechnet werden kann. Abschließend wird die Simulation evaluiert und die Plausibilität der Ergebnisse geprüft

Expression and regulation of CCL18 in synovial fluid neutrophils of patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is characterized by the recruitment of leukocytes and the accumulation of inflammatory mediators within the synovial compartment. Release of the chemokine CCL18 has been widely attributed to antigen-presenting cells, including macrophages and dendritic cells. This study investigates the production of CCL18 in polymorphonuclear neutrophils (PMN), the predominant cell type recruited into synovial fluid (SF). Microarray analysis, semiquantitative and quantitative reverse transcriptase polymerase chain reaction identified SF PMN from patients with RA as a novel source for CCL18 in diseased joints. Highly upregulated expression of other chemokine genes was observed for CCL3, CXCL8 and CXCL10, whereas CCL21 was downregulated. The chemokine receptor genes were differentially expressed, with upregulation of CXCR4, CCRL2 and CCR5 and downregulation of CXCR1 and CXCR2. In cell culture experiments, expression of CCL18 mRNA in blood PMN was induced by tumor necrosis factor α, whereas synthesis of CCL18 protein required additional stimulation with a combination of IL-10 and vitamin D3. In comparison, recruited SF PMN from patients with RA were sensitized for CCL18 production, because IL-10 alone was sufficient to induce CCL18 release. These results suggest a release of the T cell-attracting CCL18 by PMN when recruited to diseased joints. However, its production is tightly regulated at the levels of mRNA expression and protein synthesis

Intrinsic molecular signature of breast cancer in a population-based cohort of 412 patients

BACKGROUND: Molecular markers and the rich biological information they contain have great potential for cancer diagnosis, prognostication and therapy prediction. So far, however, they have not superseded routine histopathology and staging criteria, partly because the few studies performed on molecular subtyping have had little validation and limited clinical characterization. METHODS: We obtained gene expression and clinical data for 412 breast cancers obtained from population-based cohorts of patients from Stockholm and Uppsala, Sweden. Using the intrinsic set of approximately 500 genes derived in the Norway/Stanford breast cancer data, we validated the existence of five molecular subtypes – basal-like, ERBB2, luminal A/B and normal-like – and characterized these subtypes extensively with the use of conventional clinical variables. RESULTS: We found an overall 77.5% concordance between the centroid prediction of the Swedish cohort by using the Norway/Stanford signature and the k-means clustering performed internally within the Swedish cohort. The highest rate of discordant assignments occurred between the luminal A and luminal B subtypes and between the luminal B and ERBB2 subtypes. The subtypes varied significantly in terms of grade (p < 0.001), p53 mutation (p < 0.001) and genomic instability (p = 0.01), but surprisingly there was little difference in lymph-node metastasis (p = 0.31). Furthermore, current users of hormone-replacement therapy were strikingly over-represented in the normal-like subgroup (p < 0.001). Separate analyses of the patients who received endocrine therapy and those who did not receive any adjuvant therapy supported the previous hypothesis that the basal-like subtype responded to adjuvant treatment, whereas the ERBB2 and luminal B subtypes were poor responders. CONCLUSION: We found that the intrinsic molecular subtypes of breast cancer are broadly present in a diverse collection of patients from a population-based cohort in Sweden. The intrinsic gene set, originally selected to reveal stable tumor characteristics, was shown to have a strong correlation with progression-related properties such as grade, p53 mutation and genomic instability

The evolution of gene expression and the transcriptome–phenotype relationship

Changes in gene expression underlie the adaptive evolution in many complex phenotypes, and the recent increase in the availability of multi-species comparative transcriptome data has made it possible to scan whole transcriptomes for loci that have experienced adaptive changes in expression. However, despite the increase in data availability, current models of gene expression evolution often do not account for the complexities and inherent noise associated with transcriptome data. Additionally, in contrast to current models of gene sequence evolution, models of transcriptome evolution often lack the sophistication to effectively determine whether transcriptional differences between species or within a clade are the result of neutral or adaptive processes. In this review, we discuss the tools, methods and models that define our current understanding of the relationship between gene expression and complex phenotype evolution. Our goal is to summarize what we know about the evolution of global gene expression patterns underlying complex traits, as well to identify some of the questions that remain to be answered

Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology

Circulating levels of adiponectin, an adipocyte-secreted protein associated with cardiovascular and metabolic risk, are highly heritable. To gain insights into the biology that regulates adiponectin levels, we performed an exome array meta-analysis of 265,780 genetic variants in 67,739 individuals of European, Hispanic, African American, and East Asian ancestry. We identified 20 loci associated with adiponectin, including 11 that had been reported previously (p .60) spanning as much as 900 kb. To identify potential genes and mechanisms through which the previously unreported association signals act to affect adiponectin levels, we assessed cross-trait associations, expression quantitative trait loci in subcutaneous adipose, and biological pathways of nearby genes. Eight of the nine loci were also associated (p <1 x 10(-4)) with at least one obesity or lipid trait. Candidate genes include PRKAR2A, PTH1R, and HDAC9, which have been suggested to play roles in adipocyte differentiation or bone marrow adipose tissue. Taken together, these findings provide further insights into the processes that influence circulating adiponectin levels.Peer reviewe

Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity.

Leptin influences food intake by informing the brain about the status of body fat stores. Rare LEP mutations associated with congenital leptin deficiency cause severe early-onset obesity that can be mitigated by administering leptin. However, the role of genetic regulation of leptin in polygenic obesity remains poorly understood. We performed an exome-based analysis in up to 57,232 individuals of diverse ancestries to identify genetic variants that influence adiposity-adjusted leptin concentrations. We identify five novel variants, including four missense variants, in LEP, ZNF800, KLHL31, and ACTL9, and one intergenic variant near KLF14. The missense variant Val94Met (rs17151919) in LEP was common in individuals of African ancestry only, and its association with lower leptin concentrations was specific to this ancestry (P = 2 × 10-16, n = 3,901). Using in vitro analyses, we show that the Met94 allele decreases leptin secretion. We also show that the Met94 allele is associated with higher BMI in young African-ancestry children but not in adults, suggesting that leptin regulates early adiposity

Transcriptome-wide association study of breast cancer risk by estrogen-receptor status

Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta-analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER-). We further compared associations with ER+ and ER- subtypes, using a case-only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER- breast cancer. We further identified 30 TWAS-significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast-cancer gene in three of six regions harboring multiple TWAS-significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER- breast cancer.Peer reviewe

Analysis of the individual radio sensitivity of breast cancer patients

Hintergrund und Ziele Die Ausprägung strahlentherapiebedingter Nebenwirkungen ist deutlich von der individuellen Strahlenempfindlichkeit der behandelten Patienten geprägt. Daher könnte die Bestimmung der Strahlenempfindlichkeit vor Beginn einer Therapie eine Aussage über die individuelle Reaktion auf die geplante Strahlentherapie ermöglichen. Bei stärker strahlenempfindlichen oder strahlenresistenten Patienten könnte so eine Dosisanpassung erfolgen. Wir haben ein Kollektiv von Brustkrebspatientinnen auf die individuelle Strahlenempfindlichkeit untersucht. Methoden Von 129 Probanden wurden periphere Blutproben entnommen und so 67 Brustkrebspatientinnen und 62 gesunde Personen durch 3- Farb-Fluoreszenz in situ Hybridisierung auf ihre individuelle Strahlen-empfindlichkeit getestet. Zum einen wurden Blutproben vor dem Beginn einer adjuvanten Strahlentherapie entnommen und mit 2 Gy in vitro bestrahlt. Zum anderen wurden nach 5 Einzeldosen von je 1,8 Gy und einer Pause von 72 h (dies entspricht einer Woche in vivo Strahlentherapie) Blutproben entnommen. Auch die Blutproben der Kontrollpersonen wurden mit 2 Gy in vitro bestrahlt. Die Chromosomen 1, 2 und 4 der Lymphozyten- DNA wurden angefärbt und anschließend die Brüche pro Mitose als Marker für die individuelle Strahlenempfindlichkeit analysiert. Ergebnisse und Beobachtungen Brustkrebspatientinnen reagierten im Vergleich zu den gesunden Kontrollpersonen empfindlicher auf Strahlung. Außerdem waren die Brüche pro Mitose- Werte im Kollektiv der Brustkrebspatientinnen weiter gestreut. Dabei stellte sich heraus, dass Untergruppen von je neun stärker strahlensensiblen und neun strahlenresistenten Patientinnen gebildet werden können. Zudem reagierte eine Untergruppe von Patientinnen im Alter zwischen 40 und 50 Jahren stärker auf Strahlung als jüngere und ältere Vergleichsgruppen. Die Bestimmung der individuellen Strahlen-empfindlichkeit durch Brüche pro Mitose- Werte nach einer Woche in vivo Bestrahlung zeigte jedoch keine ausreichend hohen Messwerte, welche Unterschiede zwischen den Patientinnen vorhersagen könnten. Schlussfolgerungen Im Kollektiv der Brustkrebspatientinnen können Untergruppen von stärker strahlensensiblen und strahlenresistenten Patientinnen identifiziert werden, welche eine individuelle Therapieumstellung erhalten könnten. Dabei zeigt vor allem die Gruppe von Patientinnen im Alter zwischen 40 und 50 Jahren eine erhöhte Strahlenempfindlichkeit. Die Analyse von in vivo bestrahlten Blutlymphozyten ist jedoch vermutlich aufgrund der relativ niedrigen deponierten Dosis nicht geeignet um eine Aussage über die individuelle Strahlenempfindlichkeit zu machen.Background Individual radiosensitivity has a crucial impact on radiotherapy related side effects. A prediction of individual radiosensitivity could avoid these side effects. Our aim was to study a breast cancer collective for its variation of individual radiosensitivity. Methods Peripheral blood samples were obtained from 129 individuals. 67 breast cancer patients and 62 healthy and age matched individuals were looked at and their individual radiosensitivity was estimated by a 3-color Fluorescence in situ hybridization approach. Blood samples were obtained (i) before starting adjuvant radiotherapy and were in vitro irradiated by 2 Gy; (ii) after 5 single doses of 1.8 Gy and after 72 h had elapsed. DNA of lymphocytes was probed with whole chromosome painting for chromosomes 1, 2 and 4. The rate of breaks per metaphase was analyzed and used as a predictor of individual radiosensitivity. Results Breast cancer patients were distinctly more radio-sensitive compared to healthy controls. Additionally the distribution of the cancer patients’ radiosensitivity was broader. A subgroup of 9 rather radio-sensitive and 9 rather radio-resistant patients was identified. A subgroup of patients aged between 40 and 50 was distinctly more radio-sensitive than younger or older patients. The in vivo irradiation approach was not applicable to detect individual radiosensitivity. Conclusion In the breast cancer collective a distinctly resistant and sensitive subgroup is identified, which could be subject for treatment adjustment. Especially in the range of age 40 to 50 patients have an increased radiosensitivity. An in vivo irradiation in a breast cancer collective is not suitable to estimate individual radiosensitivity due to a low deposed dose