ISSCR standards for the use of human stem cells in basic research.

The laboratory culture of human stem cells seeks to capture a cellular state as an in vitro surrogate of a biological system. For the results and outputs from this research to be accurate, meaningful, and durable, standards that ensure reproducibility and reliability of the data should be applied. Although such standards have been previously proposed for repositories and distribution centers, no widely accepted best practices exist for laboratory research with human pluripotent and tissue stem cells. To fill that void, the International Society for Stem Cell Research has developed a set of recommendations, including reporting criteria, for scientists in basic research laboratories. These criteria are designed to be technically and financially feasible and, when implemented, enhance the reproducibility and rigor of stem cell research

Performance of the AMBFTK board for the FastTracker processor for the ATLAS detector upgrade

Modern experiments at hadron colliders search for extremely rare processes hidden in a very large background. As the experiment complexity and the accelerator backgrounds and luminosity increase we need increasingly complex and exclusive selections. The FastTracker (FTK) processor for the ATLAS experiment offers extremely powerful, very compact and low power consumption processing units for the future, which is essential for increased efficiency and purity in the Level 2 trigger selection through the intensive use of tracking. Pattern recognition is performed with Associative Memories (AM). The AMBFTK board and the AMchip04 integrated circuit have been designed specifically for this purpose. We report on the preliminary test results of the first prototypes of the AMBFTK board and of the AMchip04

Molecular mechanism and functional role of brefeldin A-mediated ADP-ribosylation of CtBP1/BARS

ADP-ribosylation is a posttranslational modification that modulates the functions of many target proteins. We previously showed that the fungal toxin brefeldin A (BFA) induces the ADP-ribosylation of C-terminal-binding protein-1 short-form/BFA-ADP-ribosylation substrate (CtBP1-S/BARS), a bifunctional protein with roles in the nucleus as a transcription factor and in the cytosol as a regulator of membrane fission during intracellular trafficking and mitotic partitioning of the Golgi complex. Here, we report that ADP-ribosylation of CtBP1-S/BARS by BFA occurs via a nonconventional mechanism that comprises two steps: (i) synthesis of a BFA-ADP-ribose conjugate by the ADP-ribosyl cyclase CD38 and (ii) covalent binding of the BFA-ADP-ribose conjugate into the CtBP1-S/BARS NAD(+)-binding pocket. This results in the locking of CtBP1-S/BARS in a dimeric conformation, which prevents its binding to interactors known to be involved in membrane fission and, hence, in the inhibition of the fission machinery involved in mitotic Golgi partitioning. As this inhibition may lead to arrest of the cell cycle in G2, these findings provide a strategy for the design of pharmacological blockers of cell cycle in tumor cells that express high levels of CD38

Diacylglycerol-Stimulated Endocytosis of Transferrin in Trypanosomatids Is Dependent on Tyrosine Kinase Activity

Small molecule regulation of cell function is an understudied area of trypanosomatid biology. In Trypanosoma brucei diacylglycerol (DAG) stimulates endocytosis of transferrin (Tf). However, it is not known whether other trypanosomatidae respond similarly to the lipid. Further, the biochemical pathways involved in DAG signaling to the endocytic system in T. brucei are unknown, as the parasite genome does not encode canonical DAG receptors (e.g. C1-domains). We established that DAG stimulates endocytosis of Tf in Leishmania major, and we evaluated possible effector enzymes in the pathway with multiple approaches. First, a heterologously expressed glycosylphosphatidylinositol phospholipase C (GPI-PLC) activated endocytosis of Tf 300% in L. major. Second, exogenous phorbol ester and DAGs promoted Tf endocytosis in L. major. In search of possible effectors of DAG signaling, we discovered a novel C1-like domain (i.e. C1_5) in trypanosomatids, and we identified protein Tyr kinases (PTKs) linked with C1_5 domains in T. brucei, T. cruzi, and L. major. Consequently, we hypothesized that trypanosome PTKs might be effector enzymes for DAG signaling. General uptake of Tf was reduced by inhibitors of either Ser/Thr or Tyr kinases. However, DAG-stimulated endocytosis of Tf was blocked only by an inhibitor of PTKs, in both T. brucei and L. major. We conclude that (i) DAG activates Tf endocytosis in L. major, and that (ii) PTKs are effectors of DAG-stimulated endocytosis of Tf in trypanosomatids. DAG-stimulated endocytosis of Tf may be a T. brucei adaptation to compete effectively with host cells for vertebrate Tf in blood, since DAG does not enhance endocytosis of Tf in human cells

Virus Movements on the Plasma Membrane Support Infection and Transmission between Cells

How viruses are transmitted across the mucosal epithelia of the respiratory, digestive, or excretory tracts, and how they spread from cell to cell and cause systemic infections, is incompletely understood. Recent advances from single virus tracking experiments have revealed conserved patterns of virus movements on the plasma membrane, including diffusive motions, drifting motions depending on retrograde flow of actin filaments or actin tail formation by polymerization, and confinement to submicrometer areas. Here, we discuss how viruses take advantage of cellular mechanisms that normally drive the movements of proteins and lipids on the cell surface. A concept emerges where short periods of fast diffusive motions allow viruses to rapidly move over several micrometers. Coupling to actin flow supports directional transport of virus particles during entry and cell-cell transmission, and local confinement coincides with either nonproductive stalling or infectious endocytic uptake. These conserved features of virus–host interactions upstream of infectious entry offer new perspectives for anti-viral interference

Going against the herd: psychological and cultural factors underlying the 'vaccination confidence gap'

By far the most common strategy used in the attempt to modify negative attitudes toward vaccination is to appeal to evidence-based reasoning. We argue, however, that focusing on science comprehension is inconsistent with one of the key facts of cognitive psychology: Humans are biased information processors and often engage in motivated reasoning. On this basis, we hypothesised that negative attitudes can be explained primarily by factors unrelated to the empirical evidence for vaccination; including some shared attitudes that also attract people to complementary and alternative medicine (CAM). In particular, we tested psychosocial factors associated with CAM endorsement in past research; including aspects of spirituality, intuitive (vs analytic) thinking styles, and the personality trait of openness to experience. These relationships were tested in a cross-sectional, stratified CATI survey (N = 1256, 624 Females). Whilst educational level and thinking style did not predict vaccination rejection, psychosocial factors including: preferring CAM to conventional medicine (OR .49, 95% CI .36 .83, 95% CI .71 to vaccination. Furthermore, for 9 of the 12 CAMs surveyed, utilisation in the last 12 months was associated with lower levels of vaccination endorsement. From this we suggest that vaccination scepticism appears to be the outcome of a particular cultural and psychological orientation leading to unwillingness to engage with the scientific evidence. Vaccination compliance might be increased either by building general confidence and understanding of evidence-based medicine, or by appealing to features usually associated with CAM, e.g.–.66), endorsement of spirituality as a source of knowledge (OR–.96), and openness (OR .86, 95% CI .74–.99), all predicted negative attitudes‘strengthening your natural resistance to disease’