Genotype and maternal environment affect belowground interactions between Arabidopsis thaliana and its competitors

Ecological interactions between different species are not fixed, but they may depend, at least to some extent, on the particular genotypes involved as well as on the environmental conditions experienced by previous generations. We used a set of natural genotypes of Arabidopsis thaliana, that previously experienced contrasting nutrient and herbivory conditions, to test for the influences of genetic variation and maternal effects on competitive interactions between Arabidopsis and the weedy annuals Anagallis arvensis and Senecio vulgaris. We used activated carbon to discriminate between resource competition and allelopathy components of plant-plant interactions. There was a clear competitive hierarchy: Senecio > Arabidopsis > Anagallis. Although we found no evidence for allelopathic potential of Arabidopsis, our results indicate that both Anagallis and Senecio exerted negative (direct or indirect) allelopathic effects on Arabidopsis. There were significant differences among Arabidopsis genotypes in their competitive effects on both neighbor species, as well as in their response to competition. Maternal environments significantly influenced not only the growth and fitness of Arabidopsis itself, but also its competitive effect on Anagallis. We found, however, no evidence that maternal environments affected the competitive effect on Senecio or overall competitive response of Arabidopsis. Generally, resource competition played a greater role than allelopathy, and genotype effects were more important than maternal effects. Our study demonstrates that ecological interactions, such as plant competition, are complex and multi-layered, and that, in particular, the influence of genetic variation on interactions with other species should not be overlooked.

A Dose-Response Strategy Reveals Differences between Normal-Weight and Obese Men in Their Metabolic and Inflammatory Responses to a High-Fat Meal.

A dose-response strategy may not only allow investigation of the impact of foods and nutrients on human health but may also reveal differences in the response of individuals to food ingestion based on their metabolic health status. In a randomized crossover study, we challenged 19 normal-weight (BMI: 20-25 kg/m(2)) and 18 obese (BMI: >30 kg/m(2)) men with 500, 1000, and 1500 kcal of a high-fat (HF) meal (60.5% energy from fat). Blood was taken at baseline and up to 6 h postprandially and analyzed for a range of metabolic, inflammatory, and hormonal variables, including plasma glucose, lipids, and C-reactive protein and serum insulin, glucagon-like peptide-1, interleukin-6 (IL-6), and endotoxin. Insulin was the only variable that could differentiate the postprandial response of normal-weight and obese participants at each of the 3 caloric doses. A significant response of the inflammatory marker IL-6 was only observed in the obese group after ingestion of the HF meal containing 1500 kcal [net incremental AUC (net iAUC) = 22.9 ± 6.8 pg/mL × 6 h, P = 0.002]. Furthermore, the net iAUC for triglycerides significantly increased from the 1000 to the 1500 kcal meal in the obese group (5.0 ± 0.5 mmol/L × 6 h vs. 6.0 ± 0.5 mmol/L × 6 h, P = 0.015) but not in the normal-weight group (4.3 ± 0.5 mmol/L × 6 h vs. 4.8 ± 0.5 mmol/L × 6 h, P = 0.31). We propose that caloric dose-response studies may contribute to a better understanding of the metabolic impact of food on the human organism. This study was registered at clinicaltrials.gov as NCT01446068.

Proximity of premolar roots to maxillary sinus: a radiographic survey using cone-beam computed tomography.

INTRODUCTION The proximity of the roots of the posterior maxillary teeth to the maxillary sinus is a constant challenge to the dental practitioner. Because the majority of studies have assessed the relationship regarding molars, the present study focused on premolars. METHODS Cone-beam computed tomographic images of 192 patients were reconstructed in sagittal, coronal, and axial planes to quantify the distances between the root apices of the maxillary premolars and the adjacent maxillary sinus. Measurements were taken for each root, and data were correlated with age, sex, side, and presence of both or absence of 1 of the 2 premolars. RESULTS A total of 296 teeth (177 first and 119 second premolars) were evaluated. The mean distances from buccal roots of the first premolars to the border of the maxillary sinus in the sagittal, coronal, and axial planes ranged from 5.15 ± 2.99 to 8.28 ± 6.27 mm. From palatal roots, the mean distances ranged from 4.20 ± 3.69 to 7.17 ± 6.14 mm. The mean distances of second premolars were markedly shorter in buccal roots between 2.32 ± 2.19 and 3.28 ± 3.17 mm and in palatal roots between 2.68 ± 3.58 and 3.80 ± 3.71 mm, respectively. The frequency of a premolar root protrusion into the maxillary sinus was very low in first premolars (0%-7.2%) but higher in second premolars (2.5%-13.6%). Sex, age, side, and presence/absence of premolars failed to significantly influence the mean distances between premolar roots and the maxillary sinus. CONCLUSIONS Based on the calculated mean distances of the present study, only few premolars (and if so second premolars) would present a risk of violating the border of the maxillary sinus during conventional or surgical endodontic treatment or in case of tooth extraction.

Activating BRAF and PIK3CA mutations cooperate to promote anaplastic thyroid carcinogenesis

UNLABELLED Thyroid malignancies are the most common type of endocrine tumors. Of the various histologic subtypes, anaplastic thyroid carcinoma (ATC) represents a subset of all cases but is responsible for a significant proportion of thyroid cancer-related mortality. Indeed, ATC is regarded as one of the more aggressive and hard to treat forms of cancer. To date, there is a paucity of relevant model systems to critically evaluate how the signature genetic abnormalities detected in human ATC contribute to disease pathogenesis. Mutational activation of the BRAF protooncogene is detected in approximately 40% of papillary thyroid carcinoma (PTC) and in 25% of ATC. Moreover, in ATC, mutated BRAF is frequently found in combination with gain-of-function mutations in the p110 catalytic subunit of PI3'-Kinase (PIK3CA) or loss-of-function alterations in either the p53 (TP53) or PTEN tumor suppressors. Using mice with conditional, thyrocyte-specific expression of BRAF(V600E), we previously developed a model of PTC. However, as in humans, BRAF(V600E)-induced mouse PTC is indolent and does not lead to rapid development of end-stage disease. Here, we use mice carrying a conditional allele of PIK3CA to demonstrate that, although mutationally activated PIK3CA(H1047R) is unable to drive transformation on its own, when combined with BRAF(V600E) in thyrocytes, this leads to development of lethal ATC in mice. Combined, these data demonstrate that the BRAF(V600E) cooperates with either PIK3CA(H1074R) or with silencing of the tumor-suppressor PTEN, to promote development of anaplastic thyroid carcinoma. IMPLICATIONS This genetically relevant mouse model of ATC will be an invaluable platform for preclinical testing of pathway-targeted therapies for the prevention and treatment of thyroid carcinoma.

Expositionsbasierte kognitive Therapie bei Depressionen

Depressionen können erfolgreich behandelt werden, doch die Nachhaltigkeit psychotherapeutischer Effekte ist weiterhin eine Herausforderung. Expositionsbasierte Kognitive Therapie (EBCT) versucht, gleichzeitig Symptomatik und Depressionsvulnerabilität durch verstärkte kognitiv-emotionale Verarbeitung zu verändern. Die EBCT umfasst drei Behandlungsphasen: Aufbauphase zur Stabilisierung und Stärkung inklusive Achtsamkeitsübungen, Expositionsphase zur Bearbeitung depressionsrelevanter Selbstanteile mit emotionsfokussierten Methoden und Konsolidierungsphase zum Transfer erworbener Fertigkeiten und Erkenntnisse in den Alltag. In empirischen Studien konnten Belege für die Umsetzbarkeit der Methodenintegration sowie Akzeptabilität der Behandlung erbracht werden. In einer Vergleichsstudie zeigten sich große und der kognitiven Verhaltenstherapie (KVT) vergleichbare Prä-Post-Effekte der EBCT. Die kognitiv-emotionale Verarbeitung erfolgte hauptsächlich in der Expositionsphase und sagte das Therapieergebnis vorher. Die EBCT ist ein Beispiel für die erfolgreiche Integration ursprünglich theoriefremder Interventionen in die KVT. Zukünftige Entwicklungen der Depressionstherapie werden diskutiert.

Evolutionary conservation of the U7 small nuclear ribonucleoprotein in Drosophila melanogaster.

The U7 snRNP involved in histone RNA 3' end processing is related to but biochemically distinct from spliceosomal snRNPs. In vertebrates, the Sm core structure assembling around the noncanonical Sm-binding sequence of U7 snRNA contains only five of the seven standard Sm proteins. The missing Sm D1 and D2 subunits are replaced by U7-specific Sm-like proteins Lsm10 and Lsm11, at least the latter of which is important for histone RNA processing. So far, it was unknown if this special U7 snRNP composition is conserved in invertebrates. Here we describe several putative invertebrate Lsm10 and Lsm11 orthologs that display low but clear sequence similarity to their vertebrate counterparts. Immunoprecipitation studies in Drosophila S2 cells indicate that the Drosophila Lsm10 and Lsm11 orthologs (dLsm10 and dLsm11) associate with each other and with Sm B, but not with Sm D1 and D2. Moreover, dLsm11 associates with the recently characterized Drosophila U7 snRNA and, indirectly, with histone H3 pre-mRNA. Furthermore, dLsm10 and dLsm11 can assemble into U7 snRNPs in mammalian cells. These experiments demonstrate a strong evolutionary conservation of the unique U7 snRNP composition, despite a high degree of primary sequence divergence of its constituents. Therefore, Drosophila appears to be a suitable system for further genetic studies of the cell biology of U7 snRNPs.

Ms. hebr. oct. 93 - Midrash Tehilim

Vorbesitzer: Eljāqīm Carmoly; Abraham Merzbacher

Impact of p53 Status on Radiosensitization of Tumor Cells by MET Inhibition-Associated Checkpoint Abrogation

Signaling via the MET receptor tyrosine kinase has been implicated in crosstalk with cellular responses to DNA damage. Our group previously demonstrated that MET inhibition in tumor cells with deregulated MET activity results in radiosensitization via downregulation of the ATR-CHK1-CDC25 pathway, a major signaling cascade responsible for intra-S and G2/M cell cycle arrest following DNA damage. Here we aimed at studying the potential therapeutic application of ionizing radiation in combination with a MET inhibitor, EMD-1214063, in p53-deficient cancer cells that harbor impaired G1/S checkpoint regulation upon DNA damage. We hypothesized that upon MET inhibition, p53-deficient cells would bypass both G1/S and G2/M checkpoints, promoting premature mitotic entry with substantial DNA lesions and cell death in a greater extent than p53-proficient cells. Our data suggest that p53-deficient cells are more susceptible to EMD-1214063 and combined treatment with irradiation than wildtype p53 lines as inferred from elevated γH2AX expression and increased cytotoxicity. Furthermore, cell cycle distribution profiling indicates constantly lower G1 and higher G2/M population as well as higher expression of a mitotic marker p-histone H3 following the dual treatment in p53 knockdown isogenic variant, compared to the parental counterpart. IMPLICATIONS The concept of MET inhibition-mediated radiosensitization enhanced by p53 deficiency is of high clinical relevance, since p53 is frequently mutated in numerous types of human cancer. The current data point for a therapeutic advantage for an approach combining MET targeting along with DNA damaging agents for MET positive/p53 negative tumors.

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Fingerprint nach Ex. der HAAB Weimar und der UB Frankfurt

Ains Judenbüechlins verlegung: darin ain Christ

gantzer Christenhait zu schmach / will es geschehe den Juden unrecht in bezichtigung der Christen kinder mordt [[Elektronische Ressource]] / Durch Doctor Joh. Ecken

(Table S1) Diatom species richness from the Early Pleistocene to present

The extent to which the spatial distribution of marine planktonic microbes is controlled by local environmental selection or dispersal is poorly understood. Our ability to separate the effects of these two biogeographic controls is limited by the enormous environmental variability both in space and through time. To circumvent this limitation, we analyzed fossil diatom assemblages over the past ~1.5 million years from the world oceans and show that these eukaryotic microbes are not limited by dispersal. The lack of dispersal limitation in marine diatoms suggests that the biodiversity at the microbial level fundamentally differs from that of macroscopic animals and plants for which geographic isolation is a common component of speciation.