The cytohesin paralog Sec7 of Dictyostelium discoideum is required for phagocytosis and cell motility

Background: Dictyostelium harbors several paralogous Sec7 genes that encode members of three subfamilies of the Sec7 superfamily of guanine nucleotide exchange factors. One of them is the cytohesin family represented by three members in D. discoideum, SecG, Sec7 and a further protein distinguished by several transmembrane domains. Cytohesins are characterized by a Sec7-PH tandem domain and have roles in cell adhesion and migration. Results: We study here Sec7. In vitro its PH domain bound preferentially to phosphatidylinositol 3,4-bisphosphate (PI(3,4) P-2), phosphatidylinositol 4,5-bisphosphate (PI(4,5)P-2) and phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P-3). When following the distribution of GFP-Sec7 in vivo we observed the protein in the cytosol and at the plasma membrane. Strikingly, when cells formed pseudopods, macropinosomes or phagosomes, GFP-Sec7 was conspicuously absent from areas of the plasma membrane which were involved in these processes. Mutant cells lacking Sec7 exhibited an impaired phagocytosis and showed significantly reduced speed and less persistence during migration. Cellular properties associated with mammalian cytohesins like cell-cell and cell-substratum adhesion were not altered. Proteins with roles in membrane trafficking and signal transduction have been identified as putative interaction partners consistent with the data obtained from mutant analysis. Conclusions: Sec7 is a cytosolic component and is associated with the plasma membrane in a pattern distinctly different from the accumulation of PI(3,4,5)P-3. Mutant analysis reveals that loss of the protein affects cellular processes that involve membrane flow and the actin cytoskeleton

Biomechanical comparison of bioabsorbable cervical spine interbody fusion cages

Study Design. In vitro biomechanical study of bioabsorbable cervical spine interbody fusion cages using a sheep model. Objectives: The purpose of this study was to evaluate the segmental stability provided by 2 new developed bioabsorbable cervical spine interbody fusion cages and to compare it with a tricortical iliac crest bone graft and a titanium meshed interbody fusion cage. Further, the biomechanical effect of an additional anterior plate instrumentation was determined. Summary and Background Data. Despite the initial favorable results, the long-term effects of metallic cage devices on spinal motion segments are still unknown. Furthermore, shortcomings of metallic cages like migration, adjacent level degeneration, stenotic myelopathy, and artifacts in postoperative radiologic assessment have already been reported. Bioabsorbable cages have been designed to avoid these complications. Currently, no information is available about the biomechanical properties of bioabsorbable cervical spine interbody fusion cages. Methods. Forty sheep cervical spines (C2-C5) were tested in flexion, extension, axial rotation, and lateral bending with a nondestructive stiffness method using a nonconstrained testing apparatus. First, the motion segment C3-C4 was tested intact. After complete discectomy, the following groups were evaluated: autologous iliac crest bone graft, titanium mesh cylinder (Harms, DePuy AcroMed), bioabsorbable PDLLA-cage (experimental), and bioabsorbable Resorbon cage ( Biomet Merck). Further, all implants were tested with an additional anterior plate instrumentation. The mean apparent stiffness, range of motion, neutral zone, and elastic zone were calculated from the corresponding load-displacement curves. Results. No significant difference in range of motion and segmental stiffness among the tricortical iliac crest bone graft, meshed titanium Harms cage, and PDLLA-cage could be determined. The Resorbon cage significantly (P < 0.05) decreased range of motion and increased stiffness in rotation and flexion in comparison to all tested implants and the intact motion segment. An additional anterior plate significantly (P < 0.05) decreased range of motion and increased stiffness in flexion and extension. Conclusion. In this study, bioabsorbable cages demonstrated biomechanical in vitro properties equal or superior to metallic cages. From the biomechanical point of view, bioabsorbable cages, especially the Resorbon cage, may be a viable alternative to current metallic interbody cage devices. However, animal experimental in vivo evaluation of bioabsorbable cervical spine interbody fusion cages still has to be performed

Task- and resting-state functional connectivity of brain regions related to affection and susceptible to concurrent cognitive demand.

A recent fMRI-study revealed neural responses for affective processing of stimuli for which overt attention irrespective of stimulus valence was required in the orbitofrontal cortex (OFC) and bilateral amygdala (AMY): activation decreased with increasing cognitive demand. To further characterize the network putatively related to this attenuation, we here characterized these regions with respect to their functional properties and connectivity patterns in task-dependent and task-independent states. All experiments of the BrainMap database activating the seed regions OFC and bilateral AMY were identified. Their functional characteristics were quantitatively inferred using the behavioral meta-data of the retrieved experiments. Task-dependent functional connectivity was characterized by meta-analytic connectivity modeling (MACM) of significant co-activations with these seed regions. Task-independent resting-state functional connectivity analysis in a sample of 100 healthy subjects complemented these analyses. All three seed regions co-activated with subgenual cingulum (SGC), precuneus (PCu) and nucleus accumbens (NAcc) in the task-dependent MACM analysis. Task-independent resting-state connectivity revealed significant coupling of the seeds only with the SGC, but not the PCu and the NAcc. The former region (SGC) moreover was shown to feature significant resting-state connectivity with all other regions implicated in the network connected to regions where emotional processing may be modulated by a cognitive distractor. Based on its functional profile and connectivity pattern, we suggest that the SGC might serve as a key hub in the identified network, as such linking autobiographic information [PCu], reward [NAcc], (reinforce) values [OFC] and emotional significance [AMY]. Such a role, in turn, may allow the SGC to influence the OFC and AMY to modulate affective processing

Make EU trade with Brazil sustainable

Brazil, home to one of the planet's last great forests, is currently in trade negotiations with its second largest trading partner, the European Union (EU). We urge the EU to seize this critical opportunity to ensure that Brazil protects human rights and the environment