University of Basel

About: University of Basel is a education organization based out in Basel, Basel-Stadt, Switzerland. It is known for research contribution in the topics: Population & Transplantation. The organization has 25084 authors who have published 52975 publications receiving 2388002 citations. The organization is also known as: Universität Basel & Basel University.

DNA-binding factors shape the mouse methylome at distal regulatory regions

Abstract: Methylation of cytosines is an essential epigenetic modification in mammalian genomes, yet the rules that govern methylation patterns remain largely elusive To gain insights into this process, we generated base-pair-resolution mouse methylomes in stem cells and neuronal progenitors Advanced quantitative analysis identified low-methylated regions (LMRs) with an average methylation of 30% These represent CpG-poor distal regulatory regions as evidenced by location, DNase I hypersensitivity, presence of enhancer chromatin marks and enhancer activity in reporter assays LMRs are occupied by DNA-binding factors and their binding is necessary and sufficient to create LMRs A comparison of neuronal and stem-cell methylomes confirms this dependency, as cell-type-specific LMRs are occupied by cell-type-specific transcription factors This study provides methylome references for the mouse and shows that DNA-binding factors locally influence DNA methylation, enabling the identification of active regulatory regions

Natalizumab plus Interferon Beta-1a for Relapsing Multiple Sclerosis

Abstract: Background Interferon beta is used to modify the course of relapsing multiple sclerosis. Despite interferon beta therapy, many patients have relapses. Natalizumab, an α 4 integrin antagonist, appeared to be safe and effective alone and when added to interferon beta-1a in preliminary studies. Methods We randomly assigned 1171 patients who, despite interferon beta-1a therapy, had had at least one relapse during the 12-month period before randomization to receive continued interferon beta-1a in combination with 300 mg of natalizumab (589 patients) or placebo (582 patients) intravenously every 4 weeks for up to 116 weeks. The primary end points were the rate of clinical relapse at 1 year and the cumulative probability of disability progression sustained for 12 weeks, as measured by the Expanded Disability Status Scale, at 2 years. Results Combination therapy resulted in a 24 percent reduction in the relative risk of sustained disability progression (hazard ratio, 0.76; 95 percent confidence interval, 0.61 to 0.96; P = 0.02). Kaplan–Meier estimates of the cumulative probability of progression at two years were 23 percent with combination therapy and 29 percent with interferon beta-1a alone. Combination therapy was associated with a lower annualized rate of relapse over a two-year period than was interferon beta-1a alone (0.34 vs. 0.75, P<0.001) and with fewer new or enlarging lesions on T 2 -weighted magnetic resonance imaging (0.9 vs. 5.4, P<0.001). Adverse events associated with combination therapy were anxiety, pharyngitis, sinus congestion, and peripheral edema. Two cases of progressive multifocal leukoencephalopathy, one of which was fatal, were diagnosed in natalizumab-treated patients. Conclusions Natalizumab added to interferon beta-1a was significantly more effective than interferon beta-1a alone in patients with relapsing multiple sclerosis. Additional research is needed to elucidate the benefits and risks of this combination treatment. (ClinicalTrials.gov number, NCT00030966.)

Antifungal Hydrolases in Pea Tissue II. Inhibition of Fungal Growth by Combinations of Chitinase and β-1,3-Glucanase

Abstract: Chitinase and β-1,3-glucanase purified from pea pods acted synergistically in the degradation of fungal cell walls. The antifungal potential of the two enzymes was studied directly by adding protein preparations to paper discs placed on agar plates containing germinated fungal spores. Protein extracts from pea pods infected with Fusarium solani f.sp. phaseoli, which contained high activities of chitinase and β-1,3-glucanase, inhibited growth of 15 out of 18 fungi tested. Protein extracts from uninfected pea pods, which contained low activities of chitinase and β-1,3-glucanase, did not inhibit fungal growth. Purified chitinase and β-1,3-glucanase, tested individually, did not inhibit growth of most of the test fungi. Only Trichoderma viride was inhibited by chitinase alone, and only Fusarium solani f.sp. pisi was inhibited by β-1,3-glucanase alone. However, combinations of purified chitinase and β-1,3-glucanase inhibited all fungi tested as effectively as crude protein extracts containing the same enzyme activities. The pea pathogen, Fusarium solani f.sp. pisi, and the nonpathogen of peas, Fusarium solani f.sp. phaseoli, were similarly strongly inhibited by chitinase and β-1,3-glucanase, indicating that the differential pathogenicity of the two fungi is not due to differential sensitivity to the pea enzymes. Inhibition of fungal growth was caused by the lysis of the hyphal tips.

Induction of autophagy by spermidine promotes longevity

Abstract: Ageing results from complex genetically and epigenetically programmed processes that are elicited in part by noxious or stressful events that cause programmed cell death. Here, we report that administration of spermidine, a natural polyamine whose intracellular concentration declines during human ageing, markedly extended the lifespan of yeast, flies and worms, and human immune cells. In addition, spermidine administration potently inhibited oxidative stress in ageing mice. In ageing yeast, spermidine treatment triggered epigenetic deacetylation of histone H3 through inhibition of histone acetyltransferases (HAT), suppressing oxidative stress and necrosis. Conversely, depletion of endogenous polyamines led to hyperacetylation, generation of reactive oxygen species, early necrotic death and decreased lifespan. The altered acetylation status of the chromatin led to significant upregulation of various autophagy-related transcripts, triggering autophagy in yeast, flies, worms and human cells. Finally, we found that enhanced autophagy is crucial for polyamine-induced suppression of necrosis and enhanced longevity.

A world-wide study of high altitude treeline temperatures

Abstract: Aim At a coarse scale, the treelines of the world`s mountains seem to follow a common isotherm, but the evidence for this has been indirect so far. Here we aim at underpinning this with facts. Location We present the results of a data-logging campaign at 46 treeline sites between 68degrees N and 42degrees S. Methods We measured root-zone temperatures with an hourly resolution over 1-3 years per site between 1996 and 2003. Results Disregarding taxon-, landuse- or fire-driven tree limits, high altitude climatic treelines are associated with a seasonal mean ground temperature of 6.7 degreesC (+/-0.8 SD; 2.2 K amplitude of means for different climatic zones), a surprisingly narrow range. Temperatures are higher (7-8 degreesC) in the temperate and Mediterranean zone treelines, and are lower in equatorial treelines (5-6 degreesC) and in the subarctic and boreal zone (6-7 degreesC). While air temperatures are higher than soil temperatures in warm periods, and are lower than soil temperatures in cold periods, daily means of air and soil temperature are almost the same at 6-7 degreesC, a physics driven coincidence with the global mean temperature at treeline. The length of the growing season, thermal extremes or thermal sums have no predictive value for treeline altitude on a global scale. Some Mediterranean (Fagus spp.) and temperate South Hemisphere treelines (Nothofagus spp.) and the native treeline in Hawaii (Metrosideros) are located at substantially higher isotherms and represent genus-specific boundaries rather than boundaries of the life-form tree. In seasonal climates, ground temperatures in winter (absolute minima) reflect local snow pack and seem uncritical. Main conclusions The data support the hypothesis of a common thermal threshold for forest growth at high elevation, but also reflect a moderate region and substantial taxonomic influence.