A plant homologue to mammalian brain 14-3-3 protein and protein kinase C inhibitor

We have isolated cDNA clones of Spinacea oleracea L. and Oenothera hookeri of 930 and 1017 base pairs, respectively. The open reading frame deduced from the Oenothera sequence codes for a protein of a calculated molecular mass of 29 200. The primary amino acid sequence exhibits a very high degree (88%) of homology to the 14-3-3 protein from bovine brain, and protein kinase C inhibitor from sheep brain. Subsequently the plant protein was partially purified from leaf extract. The partially purified plant protein inhibited protein kinase C from sheep brain in a heterologous assay system. The active fraction consisted of 5–6 different polypeptides of similar molecular size. One of these proteins crossreacted with a peptide-specific antibody against protein kinase C inhibitor protein from sheep brain

Wirtschaft hacken: Von einem ganz normalen Unternehmer, der fast alles anders macht

Was wäre, wenn man alles ganz anders machen könnte? Seit beinahe zwei Jahrzehnten ist dies für den Unternehmer Uwe Lübbermann keine theoretische Frage mehr, sondern ein anhaltendes soziales und ökonomisches Experiment. Erstmals hat er es umgesetzt zusammen mit seinem "Getränke-und-mehr"-Kollektiv Premium: Rabatte für diejenigen, die nur geringe Mengen abnehmen; gleiches Gehalt für alle; im Internet frei verfügbare Rezepte für die hergestellten Getränke; keine schriftlichen Verträge und die Klärung sämtlicher Unternehmensbelange in einer konsensdemokratischen Struktur. Ausgehend von dem Willen, der unsozialen Dynamik des kapitalistischen Systems eigene Werte entgegenzusetzen, hat Premium über viele Jahre nicht nur ein krisensicheres, sozial orientiertes Unternehmen aufgebaut. Es ist vielmehr selbst zum anhaltenden Motor von Veränderung geworden - eine Software, die die Menschen, Unternehmen und Systeme, mit denen sie arbeitet, verändert, indem sie grundlegende Mechanismen außer Kraft setzt und durch andere ersetzt. Denn das Engagement für soziale und ökologische Fragen beeinflusst nicht nur Geschäftsentscheidungen, Abläufe und Kommunikationsweisen - es überträgt sich auf alle, die mit Lübbermann zusammenarbeiten und verwandelt sie. "Wirtschaft hacken" beschreibt diese Veränderungsmaschine erstmals ausführlich. Von innen und von außen, parteiisch und kritisch, zum Inspirieren und zum Nachbauen

Mirroring everyday clinical practice in clinical trial design: a new concept to improve the external validity of randomized double-blind placebo-controlled trials in the pharmacological treatment of major depression

Background: Randomized, double-blind, placebo-controlled trials constitute the gold standard in clinical research when testing the efficacy of new psychopharmacological interventions in the treatment of major depression. However, the blinded use of placebo has been found to influence clinical trial outcomes and may bias patient selection. Discussion: To improve clinical trial design in major depression so as to reflect clinical practice more closely we propose to present patients with a balanced view of the benefits of study participation irrespective of their assignment to placebo or active treatment. In addition every participant should be given the option to finally receive the active medication. A research agenda is outlined to evaluate the impact of the proposed changes on the efficacy of the drug to be evaluated and on the demographic and clinical characteristics of the enrollment fraction with regard to its representativeness of the eligible population. Summary: We propose a list of measures to be taken to improve the external validity of double-blind, placebocontrolled trials in major depression. The recommended changes to clinical trial design may also be relevant for other psychiatric as well as medical disorders in which expectations regarding treatment outcome may affect the outcome itself

Judicial Opinions 123-127

Opinion 123 places the epithet of the name Aeromonas punctata on the list of rejected epithets and clarifies the citation of authors of selected names within the genus Aeromonas. Opinion 124 denies the request to place Borreliella on the list of rejected names because the request is based on a misinterpretation of the Code, which is clarified. There are alternative ways to solve the perceived problem. Opinion 125 denies the request to place Lactobacillus fornicalis on the list of rejected names because the provided information does not yield a reason for rejection. Opinion 126 denies the request to place Prolinoborus and Prolinoborus fasciculus on the list of rejected names because a relevant type strain deposit was not examined. Opinion 127 grants the request to assign the strain deposited as ATCC 4720 as the type strain of Agrobacterium tumefaciens, thereby cor-recting the Approved Lists. These Opinions were ratified by the voting members of the International Committee on Systematics of Prokaryotes

Drug-induced eRF1 degradation promotes readthrough and reveals a new branch of ribosome quality control.

Suppression of premature termination codons (PTCs) by translational readthrough is a promising strategy to treat a wide variety of severe genetic diseases caused by nonsense mutations. Here, we present two potent readthrough promoters-NVS1.1 and NVS2.1-that restore substantial levels of functional full-length CFTR and IDUA proteins in disease models for cystic fibrosis and Hurler syndrome, respectively. In contrast to other readthrough promoters that affect stop codon decoding, the NVS compounds stimulate PTC suppression by triggering rapid proteasomal degradation of the translation termination factor eRF1. Our results show that this occurs by trapping eRF1 in the terminating ribosome, causing ribosome stalls and subsequent ribosome collisions, and activating a branch of the ribosome-associated quality control network, which involves the translational stress sensor GCN1 and the catalytic activity of the E3 ubiquitin ligases RNF14 and RNF25

Protein kinase c-β-dependent activation of NF-κB in stromal cells is indispensable for the survival of chronic lymphocytic leukemia B cells in vivo

Tumor cell survival critically depends on heterotypic communication with benign cells in the microenvironrnent. Here, we describe a survival signaling pathway activated in stromal cells by contact to B cells from patients with chronic lymphocytic leukemia (CLL). The expression of protein kinase C (PKC)-beta II and the subsequent activation of NF-kappa B in bone marrow stromal cells are prerequisites to support the survival of malignant B cells. PKC-beta knockout mice are insusceptible to CLL transplantations, underscoring the in vivo significance of the PKC-beta II-NF-kappa B signaling pathway in the tumor microenvironment. Upregulated stromal PKG-beta II in biopsies from patients with CLL, acute lymphoblastic leukemia, and mantle cell lymphoma suggests that this pathway may commonly be activated in a variety of hematological malignancies