Die Salicylsäure (SA) ist ein wichtiges Signalmolekül bei der Regulation der pflanzlichen Pathogenabwehr. as-1-ähnliche cis-Elemente in den Promotoren von vielen Abwehrgenen vermitteln SA- und auch Auxin-induzierbare Genexpression. Diese Elemente werden vom ASF-1/SARP-Proteinkomplex erkannt, dessen Hauptkomponenten DNA-Bindeproteine aus der TGA-Familie der pflanzlichen bZIP-Transkriptionsfaktoren sind. In dieser Arbeit wurden Fusionsproteine von TGA2.1, TGA2.2 und TGA1a mit GFP unter der Kontrolle des HBT-Promotors transient in Pflanzenprotoplasten oder stabil in transgenen Pflanzen exprimiert und direkt in lebenden Zellen über Fluoreszenz- und konfokale Laser-Scanning-Mikroskopie visualisiert. Bei den mikroskopischen Analysen konnte die Fluoreszenz der drei TGA-GFP-Fusionsproteine überwiegend im Kern (mit Ausnahme des Nukleolus) beobachtet werden. Allerdings ließen sich biochemisch mit Hilfe eines Antiserums gegen die beiden C Termini der TGA-Faktoren auch geringe Mengen von TGA2.1-GFP und TGA2.2-GFP in cytosolischen Extrakten der entsprechenden transgenen Pflanzen nachweisen. Fusionen der C terminalen Anteile von TGA2.2 und TGA1a an den C Terminus von CHS-GFP wurden bei transienter Expression ebenfalls im Cytosol beobachtet. Es konnte nicht abschließend geklärt werden, ob dass auf das Fehlen der NLS oder auf die Anwesenheit einer NES zurück zu führen ist. Die TGA-GFP-Fusionsproteine konnten das as 1-Element in vitro in Gelretardationsanalysen erkennen und in Form von Homo-oder Heterodimeren daran binden. Die TGA-GFP-Fusionsproteine waren auch in der Lage, die Expression des frühen (immediate-early) GST-Gens Nt103 in Blättern nach Induktion mit Salicylsäure oder Auxin zu beeinflussen. TGA2.1-GFP und TGA2.2-GFP zeigten im allgemeinen einen positiven Effekt auf die Nt103-mRNA-Menge (2-4-facher Anstieg verglichen mit dem Wildtyp), wobei sich der Effekt stärker auf die SA-induzierte Expression auswirkte als auf die 2,4-D-Proben. TGA1a-GFP schien die Expression von Nt103 in Blättern in beiden Fällen leicht negativ oder gar nicht zu beeinflussen. Die Mobilitätsparameter der verschiedenen TGA-GFP-Fusionsproteine im Kern wurden mit Hilfe von FCS, kombiniert mit CLMS, untersucht. Während die Mobilität des Kontrollproteins TetR-GFP, dass keine endogenen Interaktionpartner hat, einheitlich war, schienen Subfraktionen der TGA-GFP Fusionproteine in ihrer Mobilität beeinflusst. Generell konnte zwischen einer mobileren und einer weniger mobilen Fraktion unterschieden werden. Bei manchen Messungen waren die TGA-Faktoren im Kern sogar gänzlich immobil. Die relative Anteil von weniger mobilen, bzw. immobilen und mobilen TGA-faktoren unterschied sich in den unterschiedlichen analysierten Zelltypen (längliche und echte Epidermiszellen, Schießzellen, Trichomzellen). Um einen eindeutigen Effekt von Salizylsäure auf die Mobilität der TGA-Faktoren festzumachen, sind wegen der großen Variabilität weitere Messungen nötig.

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Background: Factors predicting survival in men with lymph node-positive prostate cancer are still poorly defined. Patients and Methods: 193 prostate cancer patients with histopathologically proven lymph node involvement with a median follow-up of 7.3 years were studied. 94% of patients received immediate hormonal therapy. Kaplan-Meier curves were calculated to evaluate overall survival rates and compared with the log-rank test. Cumulative disease-specific and competing mortality rates were calculated by competing risk analysis and compared with the Pepe-Mori test. Cox proportional hazard models were used to determine the independent significance of predictors of all-cause mortality. Results: Age (70 years or older vs. younger), Gleason score (8–10 vs. 7 or lower) and the number of involved nodes (3 or more vs. 1–2) were identified as independent predictors of all-cause mortality. When patients with 0–1 of these risk factors were compared with those with 2–3 risk factors, all-cause (rates after 10 years 21% vs. 71%, p < 0.0001), disease-specific (12 vs. 37%, p = 0.009) and competing mortality (9 vs. 33%, p = 0.02) differed significantly. Conclusions: Some of the excess mortality in patients with poor-risk lymph node-positive prostate cancer may be attributed to increased competing mortality, possibly caused by an interaction between comorbid diseases and hormonally treated persistent or progressive prostate cancer. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

There is increasing interest in the use of adjuvant hormonal therapies, which are given after the resection or destruction of all gross disease, in early-stage prostate cancer, as a significant proportion of patients experience progression and/or die from the disease despite undergoing therapy with curative intent. Several retrospective studies suggest that adjuvant hormonal therapy may improve long-term outcome after radical surgery in men with positive lymph nodes, although this approach has yet to be studied in a prospective setting. No studies of adjuvant therapy for patients with extracapsular extension at surgery have been completed, but in an interim analysis of an open controlled trial, adjuvant flutamide significantly improved progression-free survival at 4 years. Three prospective studies in the radiotherapy setting have shown that adjuvant luteinizing hormone-releasing hormone (LH-RH) agonist therapy significantly improves progression-free and/or overall survival. Future studies need to define patient subgroups who will benefit most from adjuvant therapy. The side effects of the different therapeutic options also need to be compared. It is hoped that many of the outstanding questions concerning adjuvant hormonal therapy will be answered by the ongoing Bicalutamide Early Prostate Cancer Programme. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Ghana has experienced a remarkable degradation and depletion of its forest resources over the last 100 years. This process has undermined the socio-economic and socio-cultural importance of the forests for millions of rural people who depend on the resource to support their livelihood. Many rural households have over the past three decades developed strategies to minimize the effects of forest depletion on their livelihood. The establishment of smallholder forest plantation on agricultural land has emerged as an important form of land-use for households to diversify their sources of income and also improve their socio-economic well-being. The main objective of the study was to identify and analyze the endogenous and exogenous factors inducing farm household’s decision to establish farm forest plantation and to analyze its financial contribution to household’s income and livelihood strategies. The study involved a survey of 280 randomly selected farm households from five communities in the Offinso district in Ghana. The multi-stage stratified random sampling technique was used to select as many as 165 households with farm forest plantation as well as 115 without farm forest plantation. A mixture of tools including semi-structured questionnaire, focus group discussions, wealth ranking, forest inventory and market surveys were used to collect the required data. Results from logistic regression analysis revealed that the age of the household head, the number of years of education of the household head, the amount of household labor, the size of household landholding, the ownership of permanent land, the availability of non-agricultural land and household’s participation in past forest plantation development projects are the most important endogenous factors influencing the farm household’s decision to establish farm forest plantation. On the other hand, exogenous factors such as the availability of market and buyers for farm forest products and farm household’s satisfaction with market prices for farm forest products positively influenced the household’s decision to establish farm forest plantation. Prohibitive rules and regulations relating to the harvesting of trees and transportation of timber from private lands and uncertainty in tree tenure as a result of ambiguous policy framework, however, negatively influenced the decision to establish smallholder forest plantation on their agricultural land. The results from household income portfolio analysis show that cash income from selling farm forest products contributed an average of $273.6 to total household’s income in one agricultural season. This amount accounted for 17.6% of total household’s income and represented the second most important source of income after agriculture. The profitability of different land-uses practiced by the households was analyzed using a conventional economic method (Net Present Value). The results from a comparative financial analysis show that the establishment of teak plantation on agricultural land inter-cropped with food crops is the most profitable form of land use for the households compared to pure teak plantation and maize-plantain cultivation. The results of the study underscore the potential contribution of smallholder farm forest plantation to increase the overall household’s income and thereby improve household’s well-being. / Ghana hat während der letzten 100 Jahre eine bemerkenswerte Degradation und Verminderung seines Waldvorkommens erlebt. Dieser Prozess hat die sozio-ökonomische und sozial-kulturelle Bedeutung des Waldes als Einkommensquelle zur Unterstützung des Lebensunterhalts für Millionen ländlicher Einwohner geschwächt. Während der letzen 30 Jahre haben viele Kleinbauern Haushalte Strategien entwickelt um den Effekt, den die Verminderung des Waldvorkommens auf ihren Lebensunterhalt hat, zu minimieren. Die Anlage kleinflächiger Forstplantagen auf Ackerland hat sich dabei als wichtige Form der Landnutzung erwiesen, da sie eine Einkommensquelle zusätzlich zu den vorhandenen bedeuten. Sie haben das Potential, die sozio-ökonomiche Situation der Bevölkerung zu verbessern. Ziel der Studie war die Identifizierung von internen und externen Faktoren, die bedeutend zur Entscheidung von Haushalten über die Errichtung kleinflächiger Forstplantagen beitragen. Desweiteren sollten der finanzielle Beitrag der Forstplantagen zum Einkommen und zu Strategien der Kleinbauern analysiert werden. Für die Sudie werden Datensätze von 280 zufällig ausgewählten landwirtschaftlichen Haushalten aus fünf Gemeinden im Offinso Distrikt in Ghana erfasst. Die mehrstufig aufgebaute zufällige Auswahltechnik wurde benutzt, um die 165 Haushalte mit Forstplantagen und 115 Haushalten ohne Forstplantagen für die Studie auszuwählen. Mehrere Instrumente, wurden genutzt um die benötigten Daten zu sammeln darunter vor allem semi-strukturierte Befragungen, fokusierte Gruppendiskussionen, Wohlstandsranking der Haushalte und eine Forstinventur. Ergebnisse einer logistischen Regressionsanalyse ergaben, dass das Alter des Haushaltsvorstands, die Anzahl der Ausbildungsjahre des Haushaltsvorstands, die Anzahl der im Haushalt vorhandenen Arbeitskräfte, die Größe des dem Haushalt zur Verfügung stehenden Ackerlandes, das Eigentum an Ackerland, verfügbare nicht-landwirtschaftlich nutzbare Flächen und die Teilnahme der Haushalte an Projekten zur Forstplantagenentwicklung die wichtigsten internen Faktoren für die Entscheidung der Kleinbauern zur Errichtung von kleinflächiger Forstpantagen darstellen. Andererseits beeinflussten externe Faktoren wie das Vorhandensein von Markt und Käufern für Produkte der Forstplantagen und die Zufriedenheit der Haushalte mit den gebotenen Marktpreisen für diese Produkte die Entscheidung der Kleinbauern zur Errichtung von Forstplantagen positiv. Demgegenüber beeinflussten Verbote und einschränkende Regelungen zur Ernte und zum Transport von Bäumen auf Privatland und die Unsicherheit bezüglich des Eigentums an den Bäumen als Ergebniss unklarer politischer Vorgaben die Entscheidung zur Errichtung von kleinflächiger Forstplantagen auf Ackerland negativ. Das Ergebniss der Analyse verschiedene Haushaltseinkommensquellen zeigt, dass das Jahreseinkommen der Haushalte mit Forstplantagen höher ist als das der Haushalte ohne Forstplantagen. Der Beitrag zum Jahreseinkommen aus dem Verkauf von Produkten der kleinflächiger Forstplantagen betrug im Durchschnitt 273,6 USD in einer landwirtschaftlichen Saison. Dies entsprach 17,6 % des gesamten Haushaltseinkommens und stellte somit die zweitwichtigste Einkommensquelle nach der Landwirtschaft dar. Die Rentabilität der verschiedenen Landnutzungsarten wurde mit der Kapitalwertmethode (Net Present Value) ermittelt. Diese vergleichende Analyse zeigte, dass kleinflächiger Forstplantagen auf Agrarland bei gleichzeitigem Anbau von Nahrungsmittel die profitabelste Art der Landnutzung für die Haushalte im Vergeich zu ausschließlichem Teakanbau und zum Anbau von Mais mit Kochbanane ist. Die Ergebnisse der Studie unterstreichen das Potential kleinflächiger Forstplantagen, einen Beitrag zur Steigerung des gesamten Haushaltseinkommens und zur Verbesserung des Lebensstandards der Haushalte leisten zu können.

Background Physical and mental health is important for coping with the high requirements of medical studies that are associated with a higher risk for severe stress, insomnia, smoking, harmful alcohol consumption and easier access to drugs. Health behaviors of medical students influence not just their own health but also the health of their future patients. We examined whether socio-cultural factors can explain differences in students’ health status and health-promoting behaviors. Methods A multicenter cross-sectional survey in Germany (Dresden, Munich) and Hungary (Budapest, Pécs) enclosed international medical students in their 1st, 3rd and 5th academic years. The students were invited to voluntarily and anonymously complete a questionnaire on different aspects of health behavior during obligatory seminars and lectures in 2014. The response rate of the total sample was 56.2 % (n = 2935); the subgroup analysis enclosed data of German (n = 1289), Hungarian (n = 1057) and Norwegian (n = 148) students. Results A high number of Norwegian students (84.5 %) assessed their health status as very good/excellent. In comparison, only 60.3 % of the Hungarian and 70.7 % of the German participants reported a very good/excellent health status. The distributions were comparable between the study sites. Although gender, financial situation and nationality were significant health status predictors, they could explain only 8.2 % of the total variance of health status in the multivariable model. A comparably high number of Hungarian students (95.3 % vs. 67.4 % German and 56.7 % Norwegian) reported that they can currently do a lot/very much for their health. In contrast, a significant number of Norwegians (73.0 % vs. 63.7 % Hungarian and 51.5 % German) reported that they currently do a lot/very much for their health (chi2-test, p ≤ 0.001). Financial situation, study site and study year were the strongest predictors for health promotion activities (Nagelkerkes R2 = 0.06). Conclusions Based on our study, gender and study year played only a minor role in the health status and health promotion beliefs and activities of medical students. Structural (study site) and somewhat socio-cultural factors (nationality, financial situation) mainly explained the differences regarding health promoting behaviors. Obligatory, free-of-charge courses for health promotion (activity and relaxation) should be included in study curriculums.

Background Physical and mental health is important for coping with the high requirements of medical studies that are associated with a higher risk for severe stress, insomnia, smoking, harmful alcohol consumption and easier access to drugs. Health behaviors of medical students influence not just their own health but also the health of their future patients. We examined whether socio-cultural factors can explain differences in students’ health status and health-promoting behaviors. Methods A multicenter cross-sectional survey in Germany (Dresden, Munich) and Hungary (Budapest, Pécs) enclosed international medical students in their 1st, 3rd and 5th academic years. The students were invited to voluntarily and anonymously complete a questionnaire on different aspects of health behavior during obligatory seminars and lectures in 2014. The response rate of the total sample was 56.2 % (n = 2935); the subgroup analysis enclosed data of German (n = 1289), Hungarian (n = 1057) and Norwegian (n = 148) students. Results A high number of Norwegian students (84.5 %) assessed their health status as very good/excellent. In comparison, only 60.3 % of the Hungarian and 70.7 % of the German participants reported a very good/excellent health status. The distributions were comparable between the study sites. Although gender, financial situation and nationality were significant health status predictors, they could explain only 8.2 % of the total variance of health status in the multivariable model. A comparably high number of Hungarian students (95.3 % vs. 67.4 % German and 56.7 % Norwegian) reported that they can currently do a lot/very much for their health. In contrast, a significant number of Norwegians (73.0 % vs. 63.7 % Hungarian and 51.5 % German) reported that they currently do a lot/very much for their health (chi2-test, p ≤ 0.001). Financial situation, study site and study year were the strongest predictors for health promotion activities (Nagelkerkes R2 = 0.06). Conclusions Based on our study, gender and study year played only a minor role in the health status and health promotion beliefs and activities of medical students. Structural (study site) and somewhat socio-cultural factors (nationality, financial situation) mainly explained the differences regarding health promoting behaviors. Obligatory, free-of-charge courses for health promotion (activity and relaxation) should be included in study curriculums.

Purpose: To evaluate the validity of the Gleason score after neoadjuvant hormonal treatment as predictor of diseasespecific mortality after radical prostatectomy. Patients and Methods: A total of 2,880 patients with a complete data set and a mean follow-up of 10.3 years were studied; 425 of them (15%) had a history of hormonal treatment prior to surgery. The cumulative incidence of deaths from prostate cancer was determined by univariate and multivariate competing risk analysis. Cox proportional hazard models for competing risks were used to study combined effects of the variables on prostate cancer-specific mortality. Results: A higher portion of specimens with a history of neoadjuvant hormonal treatment were assigned Gleason scores of 8–10 (28 vs. 17%, p < 0.0001). The mortality curves in the Gleason score strata <8 vs. 8–10 were at large congruent in patients with and without neoadjuvant hormonal treatment. In patients with neoadjuvant hormonal treatment, a Gleason score of 8–10 was an independent predictor of prostate cancer-specific mortality; the hazard ratio was, however, somewhat lower than in patients without neoadjuvant hormonal treatment. Conclusion: This study suggests that the prognostic value of the post-radical prostatectomy Gleason score is not meaningfully jeopardized by heterogeneous neoadjuvant hormonal treatment in a routine clinical setting.

Changes in cis- and trans-regulatory elements are among the prime sources of genetic and phenotypical variation at species level. The introduction of cis- and trans- regulatory variation has played important roles in driving diversity, phenotypical differentiation, and evolution of humans. Therefore, variation that occurs on cis- and trans- regulatory elements becomes imperative to better understanding of human genetic diversity and its evolution. In this research, around 3360 gene regulatory factors (GRF) from the human genome were catalogued. This catalog includes genes that code for proteins that perform gene regulatory activities such DNA-depending transcription, RNA polymerase II transcription cofactor and co-repressor activity, chromatin binding and remodeling, among other 218 regulatory functions. This GRF catalog allowed us to initially explore how some GRF genes have evolved in humans, archaic humans (Neandertal and Denisovan) and non-human primate species. We discussed the likely phenotypical and medical effects that evolutionary changes in GRF genes may have introduced into the human genome; for instance, traits associated to speech and language capabilities, genomic recombination hotspots, diseases, among others. By using genome-wide datasets, we additionally looked for GRFs likely to be candidates for positive selection in three human populations: Utah Residents with Northern and Western Ancestry (CEU), Han Chinese in Beijing (CHB), and Yoruba in Ibadan (YRI). As result, we produced a set of candidates that gathers genes that may have contributed in shaping the phenotypical diversity currently observed in these populations; for instance, by introducing regulatory diversity at population-specific level. We additionally identified six GRF classes enriched for genes located in regions that are likely candidates for positive selection at population specific level. We found that out of the 41 DNA-binding GRF classes classified so far, six groups exhibited enrichment for genes located on regions that may have been under positive selection: C2H2 zinc finger, KRAB-ZNF zinc finger, Homeo domain, Tryptophan cluster, Fork head/winged helix and, and High-mobility HMG domain. We additionally identified three KRAB-ZNF gene clusters, in the chromosomes one, three, and 16, for the Asian population that exhibit regions with extended haplotype homozygosity EHH (larger than 100 kb). This EHH suggests that these regions have undergone positive selection in CHB population. Finally, considering that a representative fraction of the phenotypic diversity observed between humans and its closely related species are likely explained by changes in cis-regulatory elements (CREs), we investigated putative binding sites for the transcription factor GABPa. Using ChIP-Seq data generated from a human cell line (HEK293T), 11,619 putative GABPa CREs were found, Out of which 224 are putative human-specific. To experimentally validate the transcriptional activity of these human-specific CREs, reporter gene essays and knock-down experiments were performed. Our results supported the functionality of these human-specific GABPa CREs and suggest that at least 1,215 genes are primary targets of GABPa. Finally, further analyses depict scenarios that put together transcriptional regulation by GABPa and the evolution of particular human traits; for instance, cognitive abilities, breast morphology, lipids and glucose metabolic pathways, among others.

Patients and methods: Malignant supratentorial glioma (anaplastic astrocytoma, oligoastrocytoma, oligodendroglioma and glioblastoma incl. gliosarcoma), age 16-70y, KPS 50-100. Postoperative randomization to chemotherapy with either BCNU (B) (80 mg/m2 x 3 every 6 weeks) alone or additional VM 26 (V) (50 mg/m2 x 3 every 6 weeks) starting concomitant with radiotherapy. Central histopathological review was required. Primary endpoints were survival time (ST) and progression free survival (PFS) . In addition confirmative analysis of prognostic factors and their interaction with therapy was performed. Results: Eligible: 501 of 522 randomized pts: 82% WHO grade IV gliomas, 18% grade III gliomas. 57% male, mean KPS 74, mean age 50.9 years. The high incidence of lung toxicity – with a cumulative risk of 19% during the first year - was alarming. Survival was not significantly different ( median 50.3 (B) versus 52.4 (V) (weeks), but an increase in long term survivors was observed (18 months: 29% B, 34% V, 5 years 5% B, 12% V) and PFS showed a significant difference with a median of 31.4 (B) versus 34.3 (V) weeks. Qualitative interaction between KPS and therapy (p < 0.01) was demonstrated: pts with a KPS ≥ 70 benefited from additional VM26, those with reduced KPS < 70 did better with BCNU-monotherapy. Conclusion: Adding VM26 to BCNU is effective in the chemotherapy of malignant gliomas. Because of the demonstrated interaction with therapy performance status, not tumor grade is the crucial factor to determine application and aggressiveness of chemotherapy. With risk adapted therapy a significant proportion of patients even with glioblastoma survive for years in good general condition. BCNU should be replaced by an equipotent alkylans to avoid the unacceptable high rate of lung toxicity.