Blattformen : 1. Alchemilla vulgaris - 2. Trollius europaeus - 3. Aconitum napellus - 4. Saxifraga - 5. Saxifraga caespitosa - 6. Hydrophyllum virginicum - 7. Alchemilla alpina - 8. Artemisia absinthium

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Blattformen : 1. Carduus, Distel - 2. Mulgedium alpinum - 3. + 4. Ranunculus alpestris - 5. Ranunculus glacialis - 6. Pedicularis sceptrum carolinum - 7.+8. Ranunculus auricomus - 9. Lactua muralis, Lattich - 10. Crepis pippau

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Sermons on 1. Hypocrisy and cruelty. 2. Drunkenness. 3. Bribery. 4. Oppression. 5. Unjust judges. 6. The sluggard. 7. Murder. 8. Gaming. 9. Public robbery. 10. The unnatural mother. 11. Forbidding marriage. 12. Parsons and tithes.

Mode of access: Internet.

Operator's manual : fixture, lathe, metal cutting for 2 inch diameter round or 2 inch square stock, 360 degree index ring, 12-1/2 high, 5 wide, 3-7/8 vertical travel (Numeric Products Company model 312) (3465-022-8817).

"29 November 1967."

Gut content, fatty acid composition and metabolic rates of the amphipod Anonyx sarsi during POLARSTERN cruise ARK-XIX/1, ice station PS64/070-6

During a winter expedition to the western Barents Sea in March 2003, benthic amphipods of the species Anonyx sarsi were observed directly below pack ice. Only males and juveniles [16.0-37.0 mm long, 16.2-120.8 mg dry mass (DM)] were collected. Guts contained macroalgal fibres, fish eggs and flesh from large carrion. Amphipods had very low levels of total lipids (2.7-17.2% DM). Analysis of lipid biomarkers showed that some of the specimens had preyed on pelagic copepods. Individual respiration rates ranged over 0.4-1.7 ml O2/day (mean: 1.2 ml, SD: 0.5 ml). Individual ammonia excretion rates varied between 7.8 ��g and 49.3 ��g N/day (mean: 30.7 ��g, SD: 15.2 ��g). The atomic O:N ratio ranged over 35 to 71 (mean: 55, SD: 14), indicating lipid-dominated metabolism. Mass-specific respiration ranged over 9.8-16.6 ml O2/day/g DM (mean: 13.1 ml, SD: 2.2 ml). The metabolic rates of A. sarsi were twice as high as those of the truly sympagic amphipod Gammarus wilkitzkii, which is better adapted to the under-ice habitat by its energy-saving attached lifestyle. It is concluded that males and juveniles of A. sarsi were actively searching for food in the water column and at the ice underside, but that the nutritional status of the amphipods in late Arctic winter was generally very poor.

A critical review of both the synthesis approach and the receptor profile of the 8-chloro-1-(2���,4���-dichlorophenyl)-N-piperidin-1-yl-1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3-carboxamide and analogue derivatives

We thank European Commission (project ���PET BRAIN: Mapping the brain with PET radiolabeled cannabinoid CB1 ligands���; FP7-People-2009-IAPP; Grant Agreement N.25142).

The impact of phosphoinositide metabolic enzymes in glioblastoma: a tale of phosphoinositide-specific phospholipase C PLC��1 and 5-phosphatase SKIP

Background: Glioblastoma multiforme (GBM) is one of the deadliest and most aggressive form of primary brain tumor. Unfortunately, current GBM treatment therapies are not effective in treating GBM patients. They usually experience very poor prognosis with a median survival of approximately 12 months. Only 3-5% survive up to 3 years or more. A large-scale gene profile study revealed that several genes involved in essential cellular processes are altered in GBM, thus, explaining why existing therapies are not effective. The survival of GBM patients depends on understanding the molecular and key signaling events associated with these altered physiological processes in GBM. Phosphoinositides (PI) form just a tiny fraction of the total lipid content in humans, however they are implicated in almost all essential biological processes, such as acting as second messengers in spatio-temporal regulation of cell signaling, cytoskeletal reorganization, cell adhesion, migration, apoptosis, vesicular trafficking, differentiation, cell cycle and post-translational modifications. Interestingly, these essential processes are altered in GBM. More importantly, incoming reports have associated PI metabolism, which is mediated by several PI phosphatases such as SKIP, lipases such as PLC��1, and other kinases, to regulate GBM associated cellular processes. Even as PLC��1 and SKIP are involved in regulating aberrant cellular processes in several other cancers, very few studies, of which majority are in-silico-based, have focused on the impact of PLC��1 and SKIP in GBM. Hence, it is important to employ clinical, in vitro, and in vivo GBM models to define the actual impact of PLC��1 and SKIP in GBM. AIM: Since studies of PLC��1 and SKIP in GBM are limited, this study aimed at determining the pathological impact of PI metabolic enzymes, PLCB1 and SKIP, in GBM patient samples, GBM cell line models, and xenograft models for SKIP. Results: For the first time, this study confirmed through qPCR that PLC��1 gene expression is lower in human GBM patient samples. Moreover, PLC��1 gene expression inversely correlates with pathological grades of glioma; it decreases as glioma grades increases or worsens. Silencing PLC��1 in U87MG GBM cells produces a dual impact in GBM by participating in both pro-tumoral and anti-tumoral roles. PLC��1 knockdown cells were observed to have more migratory abilities, increased cell to extracellular matrix (ECM) adhesion, transition from epithelial phenotype to mesenchymal phenotype through the upregulation of EMT transcription factors Twist1 and Slug, and mesenchymal marker, vimentin. On the other hand, p-Akt and p-mTOR protein expression were downregulated in PLC��1 knockdown cells. Thus, the oncogenic pathway PI3K/Akt/mTOR pathway is inhibited during PLC��1 knockdown. Consistently, cell viability in PLC��1 knockdown cells were significantly decreased compared to controls. As for SKIP, this study demonstrated that about 48% of SKIP colocalizes with nuclear PtdIns(4,5)P2 to nuclear speckles and that SKIP knockdown alters nuclear PtdIns(4,5)P2 in a cell-type dependent manner. In addition, SKIP silencing increased tumor volume and weight in xenografts than controls by reducing apoptosis and increasing viability. All in all, these data confirm that PLC��1 and SKIP are involved in GBM pathology and a complete understanding of their roles in GBM may be beneficial.

Tracing lineage by phenotypic and genotypic markers in Salmonella enterica subsp. enterica serovar 1,4,[5],12:i:- and Salmonella Typhimurium isolated in state of S��o Paulo, Brazil

Fifty-three Salmonella 1,4,[5],12:i:- and 45 Salmonella Typhimurium strains were characterised using phage typing, plasmid profiles and pulsed-field gel electrophoresis (PFGE) for comparison. The majority of the strains were subdivided into definitive type (DT) 41 (22.6%) and DT 193 (18%) and the 60-MDa plasmid was detected in 94.3% and 84.4% of strains, respectively. Genetic diversity was observed among all strains and 90% presented a > 70% similarity through PFGE analysis. These results suggest a close relationship between Salmonella 1,4,[5],12:i:- and Salmonella Typhimurium at the serotype level.

Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial.

BACKGROUND: In 2004, a randomised phase III trial by the European Organisation for Research and Treatment of Cancer (EORTC) and National Cancer Institute of Canada Clinical Trials Group (NCIC) reported improved median and 2-year survival for patients with glioblastoma treated with concomitant and adjuvant temozolomide and radiotherapy. We report the final results with a median follow-up of more than 5 years. METHODS: Adult patients with newly diagnosed glioblastoma were randomly assigned to receive either standard radiotherapy or identical radiotherapy with concomitant temozolomide followed by up to six cycles of adjuvant temozolomide. The methylation status of the methyl-guanine methyl transferase gene, MGMT, was determined retrospectively from the tumour tissue of 206 patients. The primary endpoint was overall survival. Analyses were by intention to treat. This trial is registered with Clinicaltrials.gov, number NCT00006353. FINDINGS: Between Aug 17, 2000, and March 22, 2002, 573 patients were assigned to treatment. 278 (97%) of 286 patients in the radiotherapy alone group and 254 (89%) of 287 in the combined-treatment group died during 5 years of follow-up. Overall survival was 27.2% (95% CI 22.2-32.5) at 2 years, 16.0% (12.0-20.6) at 3 years, 12.1% (8.5-16.4) at 4 years, and 9.8% (6.4-14.0) at 5 years with temozolomide, versus 10.9% (7.6-14.8), 4.4% (2.4-7.2), 3.0% (1.4-5.7), and 1.9% (0.6-4.4) with radiotherapy alone (hazard ratio 0.6, 95% CI 0.5-0.7; p<0.0001). A benefit of combined therapy was recorded in all clinical prognostic subgroups, including patients aged 60-70 years. Methylation of the MGMT promoter was the strongest predictor for outcome and benefit from temozolomide chemotherapy. INTERPRETATION: Benefits of adjuvant temozolomide with radiotherapy lasted throughout 5 years of follow-up. A few patients in favourable prognostic categories survive longer than 5 years. MGMT methylation status identifies patients most likely to benefit from the addition of temozolomide. FUNDING: EORTC, NCIC, N��lia and Amadeo Barletta Foundation, Schering-Plough.

Neurovirul��ncia e neuroinvasividade de herpesv��rus bovinos tipos 1 e 5 em coelhos

Com o objetivo de avaliar a capacidade dos herpesv��rus bovinos tipos 1 e 5 (BHV-1 e BHV-5) de invadir e replicar no sistema nervoso central (SNC) (neuroinvasividade), bem como sua capacidade de induzir doen��a neurol��gica (neurovirul��ncia), coelhos com 30 a 35 dias de idade foram inoculados com uma amostra do Herpesv��rus da Encefalite Bovina (BHV-5; amostra EVI 88/95) ou com amostras de BHV-1 (Los Angeles ou Cooper), pelas vias intratecal (IT) e intranasal (IN). A inocula����o da amostra de BHV-5, tanto pela via IT como IN, induziu sinais cl��nicos neurol��gicos em 100% (12/12) dos coelhos inoculados. Os exames histopatol��gicos revelaram um quadro de meningoencefalite n��o-purulenta multifocal, caracterizada por gliose multifocal e infiltrados perivasculares. O v��rus foi isolado de v��rias ��reas do SNC desses animais. As amostras de BHV-1, quando inoculadas pela via IT, n��o foram neurovirulentas. A amostra Los Angeles de BHV-1, quando administrada pela via IN, induziu sinais respirat��rios severos, al��m de sinais neurol��gicos em 57% (4/7) dos animais inoculados. Entretanto, o exame histopatol��gico destes quatro animais revelou vasculite e trombose no pulm��o e c��rebro, este ��ltimo apresentando focos de necrose neuronal, por��m sem les��es indicativas de encefalite. Isso sugere que os sinais neurol��gicos foram, provavelmente, conseq��entes a preju��zos no fluxo sang����neo encef��lico, e n��o a danos neuronais provocados pela inocula����o desse v��rus. A amostra Cooper de BHV-1, quando inoculada pela via IN, induziu apenas sinais leves de infec����o respirat��ria. Estes resultados indicam que apenas a amostra de BHV-5 foi capaz de invadir e replicar no enc��falo dos coelhos quando inoculada tanto por via IN como IT, apresentando neuroinvasividade e neurovirul��ncia. �� poss��vel que estas observa����es tenham rela����o com o fato de amostras de BHV-5 freq��entemente causarem encefalites, em contraposi����o a infec����es pelo BHV-1, onde encefalites s��o raramente observadas.

Serum neutralization with different types and subtypes of bovine herpesvirus 1 and 5

The serum neutralization (SN) test is the gold standard method to measure neutralizing antibodies to bovine herpesviruses. However, in view of the further subdivisions of bovine herpesviruses in types/subtypes, defining which virus to use at challenge in SN tests may be difficult. In view of that, this study was carried out to re-evaluate (SN) sensitivity with different types/subtypes of bovine herpesviruses types 1 (BoHV-1) and 5 (BoHV-5) as challenge viruses. Bovine sera (n=810) were collected from two distinct geographic regions and tested by SN with three type 1 viruses (BoHV-1.1 strains "Los Angeles" and "EVI123/98"; BoHV-1.2a strain "SV265/96") and three type 5 viruses (BoHV-5a strain "EVI88/95"; BoHV-5b strain "A663" and BoHV-5c "ISO97/95"). SN tests were performed with a 1 hour incubation of the serum-virus mixtures at 37��C against 100 TCID50 of each of the viruses. SN sensitivity varied greatly depending on the challenge virus used in the test. The highest sensitivity (327 positive/810 total sera tested; 40.37%) was attained when the positive results to the six viruses were added together. No association could be found between any particular type or subtype of virus and the sensitivity of the test. When positive results to each single strain were considered, SN sensitivity varied from 41.7% to 81.7%, depending on the virus and the geographic region of origin of the sera. Variation was detected even when challenge viruses belonged to the same subtype, where disagreement between positive results reached 41%. These results indicate that one hour incubation SN tests against single viruses, as performed here, may display a significantly low sensitivity (p=0.05); performing SN tests against a number of different viruses may increase considerably SN sensitivity. Furthermore, the choice of virus used for challenge is critical in SN tests. In addition, sera from different geographic regions may give rise to disagreeing results with different strains of BoHV-1 and BoHV-5. This might be particularly relevant for control programs and in international trade, were maximum sensitivity should be targeted.