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Voraussetzung für die Entwicklung von Schutzstrategien für den Pflanzenartenschutz ist die Kenntnis über die Verteilung der Zentren der Artenvielfalt im Raum. Je nach Einbürgerungsstatus und Gefährdungssituation kommt verschiedenen Artengruppen dabei eine unterschiedliche Bedeutung zu. In der vorliegenden Studie werden für die Gesamtfläche der Bundesländer Niedersachsen und Bremen die im Niedersächsischen Pflanzenarten-Erfassungsprogramm (1982–2003) auf Messtischblatt-Quadranten- Ebene erhobenen Verbreitungsdaten von Gefäßpflanzensippen unter Berücksichtigung der Gesamtflorenliste (1.819 Sippen), ihres Einbürgerungsstatus (1.509 Indigene, 160 Archäophyten, 145 etablierte Neophyten) und ihrer Gefährdungssituation (ungefährdete und gefährdete Arten; davon 643 Sippen mit Rote-Liste-Status 1, 2, 3, G oder R) ausgewertet. Auf Basis der Gesamtliste ergibt sich eine inhomogene Verteilung der Sippendichte im Gesamtuntersuchungsraum, wobei die standörtlich relativ homogene Küste sowie das Tiefland – mit Ausnahme der großen Stromtäler (Weser, Aller, Elbe) – relativ artenarm sind und das standörtlich sehr heterogene Hügel- und Bergland grundsätzlich die höchsten Sippendichten aufweist. Unter Berücksichtigung des Einbürgerungsstatus zeigen die Archäophyten jeweils die größten Überschneidungsbereiche zu den Indigenen und etablierten Neophyten. Die Verbreitungsmuster der großen Gruppe der Indigenen ähneln denen der Gesamtliste, während sich die Archäophyten auf den Bremer Küstenraum, das Weser-Aller-Flachland, die Börden und das südliche Weser-Leine-Bergland konzentrieren. Die Zentren der Sippenvielfalt der etablierten Neophyten liegen vor allem in städtischen Ballungsräumen und erscheinen oftmals sehr punktuell. Die Rote-Liste-Arten sind in der Mehrzahl indigen (91 %), 8 % von ihnen sind Archäo-, nur 1 % Neophyten. Ihre Diversitätszentren sind außerordentlich differenziert: An der Küste gehören nur die isoliert liegenden Nordsee- Inseln dazu, während im Tiefland das Wendland, die Lüneburger Heide und das Elbe-Weser-Dreieck großflächige Diversitätszentren aufweisen. Im Hügel- und Bergland finden sich vor allem im Raum Göttingen, dem Weserbergland und am Harzrand gut abgegrenzte Zentren der Rote-Liste-Artendiversität. Viele dieser bedrohten Sippen sind vermutlich Spezialisten, die an natürliche oder naturnahe Habitate angepasst und somit nur in den wenigen Landschaftsbereichen anzutreffen sind, die die entsprechenden Habitatbedingungen bieten.
Introduction: Current prognostic gene expression profiles for breast cancer mainly reflect proliferation status and are most useful in ER-positive cancers. Triple negative breast cancers (TNBC) are clinically heterogeneous and prognostic markers and biology-based therapies are needed to better treat this disease.
Methods: We assembled Affymetrix gene expression data for 579 TNBC and performed unsupervised analysis to define metagenes that distinguish molecular subsets within TNBC. We used n = 394 cases for discovery and n = 185 cases for validation. Sixteen metagenes emerged that identified basal-like, apocrine and claudin-low molecular subtypes, or reflected various non-neoplastic cell populations, including immune cells, blood, adipocytes, stroma, angiogenesis and inflammation within the cancer. The expressions of these metagenes were correlated with survival and multivariate analysis was performed, including routine clinical and pathological variables.
Results: Seventy-three percent of TNBC displayed basal-like molecular subtype that correlated with high histological grade and younger age. Survival of basal-like TNBC was not different from non basal-like TNBC. High expression of immune cell metagenes was associated with good and high expression of inflammation and angiogenesis-related metagenes were associated with poor prognosis. A ratio of high B-cell and low IL-8 metagenes identified 32% of TNBC with good prognosis (hazard ratio (HR) 0.37, 95% CI 0.22 to 0.61; P < 0.001) and was the only significant predictor in multivariate analysis including routine clinicopathological variables.
Conclusions: We describe a ratio of high B-cell presence and low IL-8 activity as a powerful new prognostic marker for TNBC. Inhibition of the IL-8 pathway also represents an attractive novel therapeutic target for this disease.
Background: Current prognostic gene signatures for breast cancer mainly reflect proliferation status and have limited value in triple-negative (TNBC) cancers. The identification of prognostic signatures from TNBC cohorts was limited in the past due to small sample sizes.
Methodology/Principal Findings: We assembled all currently publically available TNBC gene expression datasets generated on Affymetrix gene chips. Inter-laboratory variation was minimized by filtering methods for both samples and genes. Supervised analysis was performed to identify prognostic signatures from 394 cases which were subsequently tested on an independent validation cohort (n = 261 cases).
Conclusions/Significance: Using two distinct false discovery rate thresholds, 25% and <3.5%, a larger (n = 264 probesets) and a smaller (n = 26 probesets) prognostic gene sets were identified and used as prognostic predictors. Most of these genes were positively associated with poor prognosis and correlated to metagenes for inflammation and angiogenesis. No correlation to other previously published prognostic signatures (recurrence score, genomic grade index, 70-gene signature, wound response signature, 7-gene immune response module, stroma derived prognostic predictor, and a medullary like signature) was observed. In multivariate analyses in the validation cohort the two signatures showed hazard ratios of 4.03 (95% confidence interval [CI] 1.71–9.48; P = 0.001) and 4.08 (95% CI 1.79–9.28; P = 0.001), respectively. The 10-year event-free survival was 70% for the good risk and 20% for the high risk group. The 26-gene signatures had modest predictive value (AUC = 0.588) to predict response to neoadjuvant chemotherapy, however, the combination of a B-cell metagene with the prognostic signatures increased its response predictive value. We identified a 264-gene prognostic signature for TNBC which is unrelated to previously known prognostic signatures.
Parkinson’s disease (PD) is a neurodegenerative disorder frequent at old age characterized by atrophy of the nigrostriatal projection. Overexpression and A53T-mutation of the presynaptic, vesicle-associated chaperone alpha-synuclein are known to cause early-onset autosomal dominant PD. We previously generated mice with transgenic overexpression of human A53T-alpha-synuclein (A53T-SNCA) in dopaminergic substantia nigra neurons as a model of early PD. To elucidate the early and late effects of A53T-alpha-synuclein on the proteome of dopaminergic nerve terminals in the striatum, we now investigated expression profiles of young and old mice using two-dimensional fluorescence difference in gel electrophoresis (2D-DIGE) and mass spectrometry. In total, 15 proteins were upregulated and 2 downregulated. Mice before the onset of motor anomalies showed an upregulation of the spot containing 14-3-3 proteins, in particular the epsilon isoform, as well as altered levels of chaperones, vesicle trafficking and bioenergetics proteins. In old mice, the persistent upregulation of 14-3-3 proteins was aggravated by an increase of glial fibrillary acidic protein (GFAP) suggesting astrogliosis due to initial neurodegeneration. Independent immunoblots corroborated GFAP upregulation and 14-3-3 upregulation for the epsilon isoform, and also detected significant eta and gamma changes. Only for 14-3-3 epsilon a corresponding mRNA increase was observed in midbrain, suggesting it is transcribed in dopaminergic perikarya and accumulates as protein in presynapses, together with A53T-SNCA. 14-3-3 proteins associate with alpha-synuclein in vitro and in pathognomonic Lewy bodies of PD brains. They act as chaperones in signaling, dopamine synthesis and stress response. Thus, their early dysregulation probably reflects a response to alpha-synuclein toxicity.
Electronic supplementary material: The online version of this article (doi:10.1007/s00702-011-0717-3) contains supplementary material, which is available to authorized users.