Profilin isoforms in Dictyostelium discoideum

AbstractEukaryotic cells contain a large number of actin binding proteins of different functions, locations and concentrations. They bind either to monomeric actin (G-actin) or to actin filaments (F-actin) and thus regulate the dynamic rearrangement of the actin cytoskeleton. The Dictyostelium discoideum genome harbors representatives of all G-actin binding proteins including actobindin, twinfilin, and profilin. A phylogenetic analysis of all profilins suggests that two distinguishable groups emerged very early in evolution and comprise either vertebrate and viral profilins or profilins from all other organisms. The newly discovered profilin III isoform in D. discoideum shows all functions that are typical for a profilin. However, the concentration of the third isoform in wild type cells reaches only about 0.5% of total profilin. In a yeast-2-hybrid assay profilin III was found to bind specifically to the proline-rich region of the cytoskeleton-associated vasodilator-stimulated phosphoprotein (VASP). Immunolocalization studies showed similar to VASP the profilin III isoform in filopodia and an enrichment at their tips. Cells lacking the profilin III isoform show defects in cell motility during chemotaxis. The low abundance and the specific interaction with VASP argue against a significant actin sequestering function of the profilin III isoform

The UbiB family member Cqd1 forms a novel membrane contact site in mitochondria

Mitochondria are essential organelles of eukaryotic cells and are characterized by their unique and complex membrane system. They are confined from the cytosol by an envelope consisting of two membranes. Signals, metabolites, proteins and lipids have to be transferred across these membranes via proteinaceous contact sites to keep mitochondria functional. In the present study, we identified a novel mitochondrial contact site in Saccharomyces cerevisiae that is formed by the inner membrane protein Cqd1 and the outer membrane proteins Por1 and Om14. Similar to what is found for the mitochondrial porin Por1, Cqd1 is highly conserved, suggesting that this complex is conserved in form and function from yeast to human. Cqd1 is a member of the UbiB protein kinase-like family (also called aarF domain-containing kinases). It was recently shown that Cqd1, in cooperation with Cqd2, controls the cellular distribution of coenzyme Q by a yet unknown mechanism. Our data suggest that Cqd1 is additionally involved in phospholipid homeostasis. Moreover, overexpression of CQD1 and CQD2 causes tethering of mitochondria to the endoplasmic reticulum, which might explain the ability of Cqd2 to rescue ERMES deletion phenotypes

DETERMINAÇÃO DAS CARACTERÍSTICAS DE TOXICIDADE AMBIENTAL DO PERCOLADO DE UM ATERRO DE RESÍDUOS INDUSTRIAIS PERIGOSOS (ESTUDO DE CASO)

The aim of this study was to evaluate the environmental toxicity of hazardous industrial waste from landfill leachate of the one industrial solid waste center from the Rio Grande do Sul state, Brazil. The physical and chemical characteristics, as well as the ecotoxicity with Daphnia magna and toxicity and mutagenicity with Allium cepa were determined. The results of the row leachate sample indicated that the physical and chemical characteristics are compatible with the limit values imputed for treated wastewaters. Absence of acute ecotoxicity was also detected, however a significant (P<0.01) larger frequency of micronuclei was verified when compared with the results of the negative control, suggesting a genotóxico effect of this wast, although not significant alterations in the mitotic index and root growth was observed.Este estudo teve como objetivo determinar as características de toxicidade ambiental do resíduo percolado do aterro de resíduos industriais perigosos de uma central de resíduos industriais do estado do Rio Grande do Sul. As características físicas, químicas, de ecotoxicidade com Daphnia magna e toxicidade e mutagenicidade com Allium cepa foram determinadas. Os resultados indicaram características físicas e químicas dentro dos limites estabelecidos para efluentes tratados e ausência de ecotoxicidade aguda. Contudo, foi observada uma frequência significativamente aumentada de micronúcleos (P < 0,01) na raiz em crescimento, exposta ao percolado comparado com o controle, sugerindo um efeito genotóxico deste resíduo, apesar de não apresentar alterações significativas no índice mitótico e crescimento radicular

German ambulatory care physicians' perspectives on clinical guidelines – a national survey

BACKGROUND: There has been little systematic research about the extent to which German physicians accept or reject the concept and practice of a) clinical practice guidelines (CPG) and b) evidence based medicine (EBM) The aim of this study was to investigate German office-based physicians' perspective on CPGs and EBM and their application in medical practice. METHODS: Structured national telephone survey of ambulatory care physicians, four thematic blocks with 21 questions (5 point Likert scale). 511 office-based general practitioners and specialists. Main outcome measures were the application of Clinical Practice Guidelines in daily practice, preference for sources of guidelines and degree of knowledge and acceptance of EBM. In the data analysis Pearson's correlation coefficient was used for explorative analysis of correlations. The comparison of groups was performed by Student's t-test. Chi(2 )test was used to investigate distribution of two or more categorical variables. RESULTS: Of the total study population 55.3% of physicians reported already using guidelines in the treatment of patients. Physicians in group practices (GrP) as well as general practitioners (GP) agreed significantly more with the usefulness of guidelines as a basis for patient care than doctors in single practices (SP) or specialists (S) (Student's t-test mean GP 2.57, S 2.84, p < 0.01; mean GrP 2.55, SP 2.80, p < 0.05). 33.1% of the participants demonstrated a strong rejection to the application of guidelines in patient care. Acceptance of guidelines from a governmental institution was substantially lower than from physician networks or medical societies (36.2% vs. 53.4% vs. 62.0%). 73.8% of doctors interpret EBM as a combination of scientific research and individual medical knowledge; 80% regard EBM as the best basis for patient care. CONCLUSION: Despite a majority of physicians accepting and applying CPGs a large group remains that is critical and opposed to the utilization of CPGs in daily practice and to the concept of EBM in general. Doctors in single practice and specialists appear to be more critical than physicians in group practices and GPs. Future research is needed to evaluate the willingness to acquire necessary knowledge and skills for the promotion and routine application of CPGs

One session of remote ischemic preconditioning does not improve vascular function in acute normobaric and chronic hypobaric hypoxia

Application of repeated short duration bouts of ischemia to the limbs, termed remote ischemic preconditioning (RIPC), is a novel technique that may have protective effects on vascular function during hypoxic exposures. In separate parallel-design studies, at sea-level (SL; n=16), and after 8-12 days at high-altitude (HA; n=12; White Mountain, 3800m), participants underwent either a sham protocol or one session of 4x5 minutes of dual-thigh cuff occlusion with 5-minutes recovery. Brachial artery flow-mediated dilation (FMD; ultrasound), pulmonary artery systolic pressure (PASP; echocardiography), and internal carotid artery flow (ICA; ultrasound) were measured at SL in normoxia and isocapnic hypoxia [end-tidal PO (PETO ) maintained to 50mmHg], and during normal breathing at HA. The hypoxic ventilatory response (HVR) was measured at each location. All measures at SL and HA were obtained at baseline (BL), 1 hour, 24 hours, and 48 hours post-RIPC or sham. At SL, RIPC produced no changes in FMD, PASP, ICA flow, end-tidal gases or HVR in normoxia or hypoxia. At HA, although HVR increased 24 hours post RIPC compared to BL (2.05{plus minus}1.4 vs. 3.21{plus minus}1.2 L•min-1•%SaO2-1, p<0.01), there were no significant differences in FMD, PASP, ICA flow, resting end-tidal gases. Accordingly, a single session of RIPC is insufficient to evoke changes in peripheral, pulmonary, and cerebral vascular function in healthy adults. Although chemosensitivity may increase following RIPC at HA, this did not confer any vascular changes. The utility of a single RIPC session seems unremarkable during acute and chronic hypoxia

Predicting Decisions in Human Social Interactions Using Real-Time fMRI and Pattern Classification

Negotiation and trade typically require a mutual interaction while simultaneously resting in uncertainty which decision the partner ultimately will make at the end of the process. Assessing already during the negotiation in which direction one's counterpart tends would provide a tremendous advantage. Recently, neuroimaging techniques combined with multivariate pattern classification of the acquired data have made it possible to discriminate subjective states of mind on the basis of their neuronal activation signature. However, to enable an online-assessment of the participant's mind state both approaches need to be extended to a real-time technique. By combining real-time functional magnetic resonance imaging (fMRI) and online pattern classification techniques, we show that it is possible to predict human behavior during social interaction before the interacting partner communicates a specific decision. Average accuracy reached approximately 70% when we predicted online the decisions of volunteers playing the ultimatum game, a well-known paradigm in economic game theory. Our results demonstrate the successful online analysis of complex emotional and cognitive states using real-time fMRI, which will enable a major breakthrough for social fMRI by providing information about mental states of partners already during the mutual interaction. Interestingly, an additional whole brain classification across subjects confirmed the online results: anterior insula, ventral striatum, and lateral orbitofrontal cortex, known to act in emotional self-regulation and reward processing for adjustment of behavior, appeared to be strong determinants of later overt behavior in the ultimatum game. Using whole brain classification we were also able to discriminate between brain processes related to subjective emotional and motivational states and brain processes related to the evaluation of objective financial incentives

To Be or Not to Be a Flatworm: The Acoel Controversy

Since first described, acoels were considered members of the flatworms (Platyhelminthes). However, no clear synapomorphies among the three large flatworm taxa - the Catenulida, the Acoelomorpha and the Rhabditophora - have been characterized to date. Molecular phylogenies, on the other hand, commonly positioned acoels separate from other flatworms. Accordingly, our own multi-locus phylogenetic analysis using 43 genes and 23 animal species places the acoel flatworm Isodiametra pulchra at the base of all Bilateria, distant from other flatworms. By contrast, novel data on the distribution and proliferation of stem cells and the specific mode of epidermal replacement constitute a strong synapomorphy for the Acoela plus the major group of flatworms, the Rhabditophora. The expression of a piwi-like gene not only in gonadal, but also in adult somatic stem cells is another unique feature among bilaterians. These two independent stem-cell-related characters put the Acoela into the Platyhelminthes-Lophotrochozoa clade and account for the most parsimonious evolutionary explanation of epidermal cell renewal in the Bilateria. Most available multigene analyses produce conflicting results regarding the position of the acoels in the tree of life. Given these phylogenomic conflicts and the contradiction of developmental and morphological data with phylogenomic results, the monophyly of the phylum Platyhelminthes and the position of the Acoela remain unresolved. By these data, both the inclusion of Acoela within Platyhelminthes, and their separation from flatworms as basal bilaterians are well-supported alternatives