272 research outputs found
Diatom species richness in Swiss springs increases with habitat complexity and elevation
Understanding the drivers of species richness gradients is a central challenge of ecological and biodiversity research in freshwater science. Species richness along elevational gradients reveals a great variety of patterns. Here, we investigate elevational changes in species richness and turnover between microhabitats in near-natural spring habitats across Switzerland. Species richness was determined for 175 subsamples from 71 near-natural springs, and Poisson regression was applied between species richness and environmental predictors. Compositional turnover was calculated between the different microhabitats within single springs using the Jaccard index based on observed species and the Chao index based on estimated species numbers. In total, 539 diatom species were identified. Species richness increased monotonically with elevation. Habitat diversity and elevation explaining some of the species richness per site. The Jaccard index for the measured compositional turnover showed a mean similarity of 70% between microhabitats within springs, whereas the Chao index which accounts for sampling artefacts estimated a turnover of only 37%. Thus, the commonly applied method of counting 500 valves led to an undersampling of the rare species and might need to be reconsidered when assessing diatom biodiversity
Native mass spectrometry can effectively predict PROTAC efficacy
Protein degraders, also known as proteolysis targeting chimeras (PROTACs), are bifunctional small molecules that promote cellular degradation of a protein of interest (POI). PROTACs act as molecular mediators, bringing an E3 ligase and a POI into proximity, thus promoting ubiquitination and degradation of the targeted POI. Despite their great promise as next-generation pharmaceutical drugs, the development of new PROTACs is challenged by the complexity of the system, which involves binary and ternary interactions between components. Here, we demonstrate the strength of native mass spectrometry (nMS), a label-free technique, to provide novel insight into PROTAC-mediated protein interactions. We show that nMS can monitor the formation of ternary E3-PROTAC-POI complexes and detect various intermediate species in a single experiment. A unique benefit of the method is its ability to reveal preferentially formed E3-PROTAC-POI combinations in competition experiments with multiple substrate proteins, thereby positioning it as an ideal high-throughput screening strategy during the development of new PROTACs
Tyrosine phosphorylation-dependent activation of phosphatidylinositide 3-kinase occurs upstream of Ca^(2+)-signalling induced by Fcy receptor cross-linking in human neutrophils
The effect of wortmannin on IgG-receptor (FcyR)-mediated
stimulation of human neutrophils was investigated. The Ca^(2+)
influx induced by clustering of both Fcy receptors was inhibited
by wortmannin, as was the release of Ca^(2+) from intracellular
stores. Wortmannin also inhibited, with the same efficacy, the
accumulation of Ins(1,4,5)P3 observed after FcyR stimulation,
but did not affect the increase in Ins(1,4,5)P3 induced by the
chemotactic peptide, formyl-methionine-leucine-phenylalanine.
Because wortmannin is, in the concentrations used here, an
inhibitor of PtdIns 3-kinase, these results suggested a role for
PtdIns 3-kinase upstream of Ca^(2+) signalling, induced by FcyR
cross-linking. Support for this notion was obtained by investigating
the effect of another inhibitor of PtdIns 3-kinase, LY
294002, and by studying the kinetics of PtdIns 3-kinase activation.
We found translocation of PtdIns 3-kinase to the plasma
membrane and increased PtdIns 3-kinase activity in the membrane
as soon as 5 s after FccR cross-linking, even before the
onset of the Ca^(2+) response. Moreover, the translocation of
PtdIns 3-kinase to the plasma membrane was inhibited by cocross-
linking of either FcyRIIa and FcyRIIIb with the tyrosine
phosphatase, CD45, indicating a requirement for protein tyrosine
phosphorylation in the recruitment of PtdIns 3-kinase to the
plasma membrane. Taken together, our results suggest a role for
PtdIns 3-kinase in early signal transduction events after FcyR
cross-linking in human neutrophils
Crossover Patient Outcomes for Targeted Lung Denervation in Moderate to Severe Chronic Obstructive Pulmonary Disease:AIRFLOW-2
BACKGROUND: Targeted Lung Denervation (TLD) is a potential new therapy for COPD. Radiofrequency energy is bronchoscopically delivered to the airways to disrupt pulmonary parasympathetic nerves, to reduce bronchoconstriction, mucus hypersecretion, and bronchial hyperreactivity. OBJECTIVES: This work assesses the effect of TLD on COPD exacerbations (AECOPD) in crossover subjects in the AIRFLOW-2 trial. METHOD: The AIRFLOW-2 trial is a multicentre, randomized, double-blind, sham-controlled crossover trial of TLD in COPD. Patients with symptomatic COPD on optimal medical therapy with an FEV1 of 30-60% predicted received either TLD or sham bronchoscopy in a 1:1 randomization. Those in the sham arm had the opportunity to cross into the treatment arm after 12 months. The primary end point was rate of respiratory adverse events. Secondary end points included adverse events, changes in lung function and health-related quality of life and symptom scores. RESULTS: Twenty patients were treated with TLD in the crossover phase and were subsequently followed up for 12 months (50% female, mean age 64.1 ± 6.9 years). After TLD, there was a trend towards a reduction in time to first AECOPD (hazard ratio 0.65, p = 0.28, not statistically significant) in comparison to sham follow-up period. There was also a reduction in time to first severe AECOPD in the crossover period (hazard ratio 0.38, p = 0.227, not statistically significant). Symptom scores and lung function showed stability. CONCLUSIONS: AIRFLOW-2 crossover data support that of the randomization phase, showing trends towards reduction in COPD exacerbations with TLD
Climatologies at high resolution for the earth's land surface areas
High resolution information on climatic conditions is essential to many
applications in environmental and ecological sciences. Here we present the
CHELSA Climatologies at high resolution for the earths land surface areas data
of downscaled model output temperature and precipitation estimates of the ERA
Interim climatic reanalysis to a high resolution of 30 arc seconds. The
temperature algorithm is based on statistical downscaling of atmospheric
temperatures. The precipitation algorithm incorporates orographic predictors
including wind fields, valley exposition, and boundary layer height with a
subsequent bias correction. The resulting data consist of a monthly temperature
and precipitation climatology for the years 1979 to 2013. We compare the data
derived from the CHELSA algorithm with other standard gridded products and
station data from the Global Historical Climate Network. We compare the
performance of the new climatologies in species distribution modelling and show
that we can increase the accuracy of species range predictions. We further show
that CHELSA climatological data has a similar accuracy as other products for
temperature but that its predictions of precipitation patterns are better
Global patterns and drivers of phylogenetic structure in island floras
Islands are ideal for investigating processes that shape species assemblages because they are isolated and have discrete boundaries. Quantifying phylogenetic assemblage structure allows inferences in-situ speciation. Here, we link phylogenetic assemblage structure to island characteristics across 393 islands worldwide and 37,041 vascular plant species (representing angiosperms overall, palms and ferns). Physical and bioclimatic factors, especially those impeding colonization and promoting speciation, explained more variation in phylogenetic structure of angiosperms overall (49%) and palms (52%) than of ferns consistent with their dispersal- and speciation-related traits and climatic adaptations. Phylogenetic diversity was negatively related to isolation for palms, but unexpectedly it was positively related large-seeded, animal-dispersed palm family whereas colonization from biogeographically distinct in-situ among taxonomic groups on islands, which sheds light on the origin of insular plant diversity.</p
Tumor cell network integration in glioma represents a stemness feature
BACKGROUND: Malignant gliomas including glioblastomas are characterized by a striking cellular heterogeneity, which includes a subpopulation of glioma cells that becomes highly resistant by integration into tumor microtube (TM)-connected multicellular networks. METHODS: A novel functional approach to detect, isolate, and characterize glioma cell subpopulations with respect to in vivo network integration is established, combining a dye staining method with intravital two-photon microscopy, Fluorescence-Activated Cell Sorting (FACS), molecular profiling, and gene reporter studies. RESULTS: Glioblastoma cells that are part of the TM-connected tumor network show activated neurodevelopmental and glioma progression gene expression pathways. Importantly, many of them revealed profiles indicative of increased cellular stemness, including high expression of nestin. TM-connected glioblastoma cells also had a higher potential for reinitiation of brain tumor growth. Long-term tracking of tumor cell nestin expression in vivo revealed a stronger TM network integration and higher radioresistance of the nestin-high subpopulation. Glioblastoma cells that were both nestin-high and network-integrated were particularly able to adapt to radiotherapy with increased TM formation. CONCLUSION: Multiple stem-like features are strongly enriched in a fraction of network-integrated glioma cells, explaining their particular resilience
No evidence for intervention-associated DNA methylation changes in monocytes of patients with posttraumatic stress disorder
DNA methylation patterns can be responsive to environmental influences. This observation has sparked interest in the potential for psychological interventions to influence epigenetic processes. Recent studies have observed correlations between DNA methylation changes and therapy outcome. However, most did not control for changes in cell composition. This study had two aims: first, we sought to replicate therapy-associated changes in DNA methylation of commonly assessed candidate genes in isolated monocytes from 60 female patients with post-traumatic stress disorder (PTSD). Our second, exploratory goal was to identify novel genomic regions with substantial pre-to-post intervention DNA methylation changes by performing whole-genome bisulfite sequencing (WGBS) in two patients with PTSD. Equivalence testing and Bayesian analyses provided evidence against physiologically meaningful intervention-associated DNA methylation changes in monocytes of PTSD patients in commonly investigated target genes (NR3C1, FKBP5, SLC6A4, OXTR). Furthermore, WGBS yielded only a limited set of candidate regions with suggestive evidence of differential DNA methylation pre- to post-therapy. These differential DNA methylation patterns did not prove replicable when investigated in the entire cohort. We conclude that there is no evidence for major, recurrent intervention-associated DNA methylation changes in the investigated genes in monocytes of patients with PTSD
Multifunctional shadeâtree management in tropical agroforestry landscapes â a review
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87099/1/j.1365-2664.2010.01939.x.pd
Devenirs militants:Introduction
PrĂ©senter un dossier sur lâengagement qui mette sur le mĂȘme plan les pratiques militantes dans les partis politiques, les organisations syndicales, le monde associatif et plus gĂ©nĂ©ralement les entreprises de mouvement social, pourra paraĂźtre osĂ©. Câest que, pendant longtemps, le militantisme a Ă©tĂ© pensĂ© sous les seules espĂšces du travail partisan et syndical, dans un contexte oĂč la dĂ©finition de la participation politique demeurait Ă©troitement cantonnĂ©e Ă lâaction dite « conventionnelle ». [Premier paragraphe de l'article
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