706 research outputs found
Mitochondrial heat-shock protein hsp60 is essential for assembly of proteins imported into yeast mitochondria
A nuclear encoded mitochondrial heat-shock protein hsp60 is required for the assembly into oligomeric complexes of proteins imported into the mitochondrial matrix. hsp60 is a member of the 'chaperonin' class of protein factors, which include the Escherichia coli groEL protein and the Rubisco subunit-binding protein of chloroplast
Stochastic Modelling Approach to the Incubation Time of Prionic Diseases
Transmissible spongiform encephalopathies like the bovine spongiform
encephalopathy (BSE) and the Creutzfeldt-Jakob disease (CJD) in humans are
neurodegenerative diseases for which prions are the attributed pathogenic
agents. A widely accepted theory assumes that prion replication is due to a
direct interaction between the pathologic (PrPsc) form and the host encoded
(PrPc) conformation, in a kind of an autocatalytic process. Here we show that
the overall features of the incubation time of prion diseases are readily
obtained if the prion reaction is described by a simple mean-field model. An
analytical expression for the incubation time distribution then follows by
associating the rate constant to a stochastic variable log normally
distributed. The incubation time distribution is then also shown to be log
normal and fits the observed BSE data very well. The basic ideas of the
theoretical model are then incorporated in a cellular automata model. The
computer simulation results yield the correct BSE incubation time distribution
at low densities of the host encoded protein
Intensive induction chemotherapy with C-BOP/BEP for intermediate- and poor-risk metastatic germ cell tumours (EORTC trial 30948)
New chemotherapy regimens are continuously explored in patients with high-risk malignant germ cell tumours (MGCTs). This multicentre phase II trial assessed the efficacy and toxicity of C-BOP/BEP chemotherapy in intermediate and poor prognosis MGCT (IGCCCG criteria). C-BOP/BEP treatment consisted of cycles of cisplatin, vincristine, bleomycin and carboplatin, followed by one cycle of vincristine and bleomycin and three cycles of BEP (bleomycon, etoposide, cisplatin). The trial was designed to demonstrate a 1-year progression-free survival rate of 80%, that is, to exclude a 1-year rate of 70% or less, with a one-sided significance level of 5%. Secondary end points included toxicity, overall survival and the postchemotherapy complete response rate. In total, 16 European hospitals entered 66 eligible patients (intermediate prognosis group: 37; poor prognosis group: 29). A total of 45 patients (68.2%, 95% confidence interval (95% CI): 56.9–79.4%) achieved a complete response (intermediate prognosis: 30; poor prognosis: 15). After a median observation time of 40.4 months (range: 13.7–66.3), the 1-year progression-free survival rate was 81.8% 95% CI: 72.5–91.1%). The 2-year overall survival was 84.5% (95% CI: 75.6–93.3%). In all, 51 patients experienced at least one episode of WHO grade 3/4 leucopenia, and at least one event of grade 3/4 thrombocytopenia occurred in 30 patients. There was no toxic death. With an 82% 1-year progression-free survival and a lower limit of the 95% CI above 70%, the efficacy of C-BOP/BEP is comparable to that of published alternative chemotherapy schedules in high-risk MGCT patients. The treatment's toxicity is manageable in a multicentre setting. In poor prognosis patients, C-BOP/BEP should be compared to standard chemotherapy of four cycles of BEP
Survival from testicular cancer in England and Wales up to 2001
www.bjcancer.com For many years testicular cancer has been the prime example of the tumour that is chemocurable, even when metastatic. The disappointment in oncology is that these results have so far not been replicated in the more common solid tumours. Why this should be is not clear but germ-cell tumours retain sensitivity to chemotherapy in vitro and a number of mechanisms including reduced DNA repair capacity and proneness to apoptosis have been proposed (Mayer et al, 2003). Most patients with testicular cancer present after finding a lump in the testicle that may or may not be painful. A small proportion of patients present with symptoms of metastatic disease. With the exception of some patients with metastatic disease, initial treatment after first assessment is to remove the tumour by inguinal orchidectomy. Patients are staged by tumour marke
What anti-realism about hinges could possibly be?
The paper addresses the issue of what epistemic anti-realism could possibly be, in the context of “hinge epistemology.” According to this new epistemological trend, justification depends on evidence together with
general background assumptions—for example, that there is an external world, that our sense organs are
mostly reliable, that we are not the victims of persistent and lucid dreams what has regularly happened in
the past will happen in the future, that people are generally reliable informants, and so on. The paper then
addresses two issues. First, whether these assumptions are arbitrary, as relativists would claim. Second,
how we should conceive of their metaphysical status. It responds negatively to the first question and puts
forward an anti-realist conception of hinges to respond to the latter. Central to the proposal is that the kind
of truth that can be predicated of hinges is of a minimalist kind. The paper also explores the compatibility
of minimalism about hinges' truth and alethic pluralism
Biogenesis of mitochondrial porin
We review here the present knowledge about the pathway of import and assembly of porin into mitochondria and compare it to those of other mitochondrial proteins. Porin, like all outer mitochondrial membrane proteins studied so far is made as a precursor without a cleavble lsquosignalrsquo sequence; thus targeting information must reside in the mature sequence. At least part of this information appears to be located at the amino-terminal end of the molecule. Transport into mitochondria can occur post-translationally. In a first step, the porin precursor is specifically recognized on the mitochondrial surface by a protease sensitive receptor. In a second step, porin precursor inserts partially into the outer membrane. This step is mediated by a component of the import machinery common to the import pathways of precursor proteins destined for other mitochondrial subcompartments. Finally, porin is assembled to produce the functional oligomeric form of an integral membrane protein wich is characterized by its extreme protease resistance
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