88 research outputs found
Therapieoptimierungsstudie zur Behandlung des kleinzelligen Bronchialkarzinoms mit Epirubicin, Cyclophosphamid und Vincristin (EpiCO) versus Carboplatin, Etoposid und Vincristin (CEV)
Get PDFZiel der Studie war es, Wirksamkeit und Nebenwirkungsprofil zweier kombinierter Chemotherapieprotokolle mit Epirubicin, Cyclophosphamid und Vincristin (EpiCO) sowie Carboplatin, Etoposid und Vincristin (CEV) an insgesamt 216 Patienten mit fortgeschrittenem kleinzelligen Bronchialkarzinom zu prüfen. Es wurden die Ansprechraten, die Überlebenszeit, Dosisintensitäten und Toxizitäten in beiden Behandlungsarmen verglichen. Weiterhin erfolgten Subgruppenanalysen. Im Rahmen einer randomisierten, offenen, vergleichenden, multizentrischen Phase III-Studie wurden Patienten mit fortgeschrittenem, unbehandeltem kleinzelligen Bronchialkarzinom chemotherapiert. Aufgrund der im Trend günstigeren Remissions- und Überlebensdaten ist eine platinhaltige Kombination mit Carboplat/Etoposid zu empfehlen.The aim of this study is to examine the efficacy and side effect profiles of two protocols of combined chemotherapy consisting of epirubicin, cyclophosphamide, and vincristine (Epico) and carboplatin, etoposide, and vincristine (CEV), respectively, on a total of 216 patients with advanced NSCLC. Response rates, survival, dose intensity, and toxicity in both treatment arms were compared. Additionally, subgroup analyzes were performed. In a randomized, open, comparative, multicenter phase III trial, patients with advanced, untreated, small-cell lung cancer were treated with chemo therapy Due to the favorable trend in remission and survival data a platinum-containing combination Carboplat/etoposide is recommended.von Ute Nee
The method of instructing children rationally in the arts of writing and reading. By J. Neef.
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Molecular mechanism of co-transcriptional H3K36 methylation by SETD2
No full textAbstract H3K36me3 is a hallmark of actively and recently transcribed genes and contributes to cellular memory and identity. The deposition of H3K36me3 occurs co-transcriptionally when the methyltransferase SETD2 associates with RNA polymerase II. Here we present three cryo-EM structures of SETD2 bound to RNA polymerase II elongation complexes at different states of nucleosome passage. Together with functional probing, our results suggest a 3-step mechanism of transcription-coupled H3K36me3 deposition. First, binding to the elongation factor SPT6 tethers the catalytic SET domain in proximity to the upstream DNA. Second, RNA polymerase II nucleosome passage leads to the transfer of a hexasome from downstream to upstream, poised for methylation. Finally, continued transcription leads to upstream nucleosome reassembly, partial dissociation of the histone chaperone FACT and sequential methylation of both H3 tails, completing H3K36me3 deposition of an upstream nucleosome after RNA polymerase II passage
Manfred Max Neef y la revolución ambientalista para América Latina, 1932-2019 (in memoriam)
Get PDFWith the article, it is offered a tribute to the work of Manfred Max Neef, Chilean intellectual,
politician, ecologist and economist, Alternative Nobel Prize winner in Economics, a pioneer in ecological
criticism of both productivism and extractivism in Latin America. The methodology used in this work
is based on the review of the main books published by the author, such as Barefoot Economy (1982),
Development on a Human Scale (1986), The Lost Dimension (2007), and The Unmasked Economy
(2014). It is held as an assumption that Max Neef’s work fits into a Latin American theoretical body,
which breaks intellectually with macroeconomic models, be they developmentalist or neoliberal in
nature. The originality of his contribution is in the defense of the ecological foundations for human
development at a local scale.Con el artículo, se ofrece un homenaje a la obra de Manfred Max Neef, intelectual, político, eco-
logista y economista chileno, Premio Nobel Alternativo en Economía, pionero en la crítica ecológica,
tanto en el productivismo como en el extractivismo en América Latina. La metodología empleada
en este trabajo se funda en la revisión de los principales libros publicados por el autor, tales como
Economía descalza (1982), Desarrollo a escala humana (1986), La dimensión perdida (2007) y La
economía desenmascarada (2014). Se sostiene como supuesto que la obra de Max Neef se encuadra
en un cuerpo teórico latinoamericano, que rompe intelectualmente con los modelos macroeconómi-
cos, sean de corte desarrollista o de tipo neoliberal. La originalidad de su aporte se encuentra en la
defensa de los fundamentos ecológicos para el desarrollo humano a una escala local
FACT maintains chromatin architecture and thereby stimulates RNA polymerase II pausing during transcription in vivo
No full textFunder:
501100001659
Deutsche ForschungsgemeinschaftFunder:
501100004189
Max Planck Societ
IWS1 positions downstream DNA to globally stimulate Pol II elongation
Get PDFAbstract The protein IWS1 (Interacts with SPT6 1) is implicated in transcription-associated processes, but a direct role in RNA polymerase (Pol) II function is unknown. Here, we use multi-omics kinetic analysis after rapid depletion of IWS1 in human cells to show that loss of IWS1 results in a global decrease of RNA synthesis and a global reduction in Pol II elongation velocity. We then resolve the cryo-EM structure of the activated Pol II elongation complex with bound IWS1 and elongation factor ELOF1 and show that IWS1 acts as a scaffold and positions downstream DNA within the cleft of Pol II. In vitro assays show that the disordered C-terminal region of IWS1 that contacts the cleft of Pol II is responsible for stimulation of Pol II activity and is aided by ELOF1. Finally, we find that the defect in transcription upon IWS1 depletion leads to a decrease of histone H3 tri-methylation at residue lysine-36 (H3K36me3), but that this secondary effect is an indirect function of IWS1. In summary, our structure-function analysis establishes IWS1 as a Pol II-associated elongation factor that acts globally to stimulate Pol II elongation velocity and ensure proper co-transcriptional histone methylation
Author response: The synaptic ribbon is critical for sound encoding at high rates and with temporal precision
Get PDFWe studied the role of the synaptic ribbon for sound encoding at the synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) in mice lacking RIBEYE (RBEKO/KO). Electron and immunofluorescence microscopy revealed a lack of synaptic ribbons and an assembly of several small active zones (AZs) at each synaptic contact. Spontaneous and sound-evoked firing rates of SGNs and their compound action potential were reduced, indicating impaired transmission at ribbonless IHC-SGN synapses. The temporal precision of sound encoding was impaired and the recovery of SGN-firing from adaptation indicated slowed synaptic vesicle (SV) replenishment. Activation of Ca2+-channels was shifted to more depolarized potentials and exocytosis was reduced for weak depolarizations. Presynaptic Ca2+-signals showed a broader spread, compatible with the altered Ca2+-channel clustering observed by super-resolution immunofluorescence microscopy. We postulate that RIBEYE disruption is partially compensated by multi-AZ organization. The remaining synaptic deficit indicates ribbon function in SV-replenishment and Ca2+-channel regulation
Author response: Gender bias in scholarly peer review
No full textPeer review is the cornerstone of scholarly publishing and it is essential that peer reviewers are appointed on the basis of their expertise alone. However, it is difficult to check for any bias in the peer-review process because the identity of peer reviewers generally remains confidential. Here, using public information about the identities of 9000 editors and 43000 reviewers from the Frontiers series of journals, we show that women are underrepresented in the peer-review process, that editors of both genders operate with substantial same-gender preference (homophily), and that the mechanisms of this homophily are gender-dependent. We also show that homophily will persist even if numerical parity between genders is reached, highlighting the need for increased efforts to combat subtler forms of gender bias in scholarly publishing
Modelling Capillary Effects in Heterogeneous Porous Media
No full textElectrical Engineering, Mathematics and Computer Scienc
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