Regulation of OPA1-mediated mitochondrial fusion by leucine zipper/EF-hand-containing transmembrane protein-1 plays a role in apoptosis

Carboxyl-terminal modulator protein (CTMP) is a tumor suppressor-like binding partner of Protein kinase B (PKB/Akt) that negative regulates this kinase. In the course of our recent work, we identified that CTMP is consistently associated with leucine zipper/EF-hand-containing transmembrane-1 (LETM1). Here, we report that adenovirus-LETM1 increased the sensitivity of HeLa cells to apoptosis, induced by either staurosporine or actinomycin D. As shown previously, LETM1 localized to the inner mitochondrial membrane. Electron-microscopy analysis of adenovirus-LETM1 transduced cells revealed that mitochondrial cristae were swollen in these cells, a phenotype similar to that observed in optic atrophy type-1 (OPA1)-ablated cells. OPA1 cleavage was increased in LETM1-overexpressing cells, and this phenotype was reversed by overexpression of OPA1 variant-7, a cleavage resistant form of OPA1. Taken together, these data suggest that LETM1 is a novel binding partner for CTMP that may play an important role in mitochondrial fragmentation via OPA1-cleavage. (C) 2009 Elsevier Inc. All rights reserved

The Paralax Infrastructure: Automatic Parallelization With a Helping Hand

Speeding up sequential programs on multicores is a challenging problem that is in urgent need of a solution. Automatic parallelization of irregular pointer-intensive codes, exempli?ed by the SPECint codes, is a very hard problem. This paper shows that, with a helping hand, such auto-parallelization is possible and fruitful. This paper makes the following contributions: (i) A compiler framework for extracting pipeline-like parallelism from outer program loops is presented. (ii) Using a light-weight programming model based on annotations, the programmer helps the compiler to ?nd thread-level parallelism. Each of the annotations speci?es only a small piece of semantic information that compiler analysis misses, e.g. stating that a variable is dead at a certain program point. The annotations are designed such that correctness is easily veri?ed. Furthermore, we present a tool for suggesting annotations to the programmer. (iii) The methodology is applied to autoparallelize several SPECint benchmarks. For the benchmark with most parallelism (hmmer), we obtain a scalable 7-fold speedup on an AMD quad-core dual processor. The annotations constitute a parallel programming model that relies extensively on a sequential program representation. Hereby, the complexity of debugging is not increased and it does not obscure the source code. These properties could prove valuable to increase the ef?ciency of parallel programming.

Racism, masculine peer-group relations and the schooling of African/Caribbean infant boys

The past decade has witnessed the publication of a growing number of important ethnographic studies investigating the schooling experiences of Black students. Their focus has largely been upon student-teacher relations during the students' last few years of compulsory schooling. What they have highlighted is the complexity of racism and the varied nature of Black students' experiences of schooling. Drawing upon data from a year-long ethnographic study of an inner-city, multi-ethnic primary school, this paper aims to compliment these studies in two ways. Firstly the paper will broaden the focus to examine how student peer-group relations play an integral role, within the context of student-teacher relations, in shaping many Black students' schooling experiences. By focussing on African/Caribbean infant boys, it will be shown how student-teacher relations on the one hand, and peer-group relations on the other, form a continuous feed-back loop; the products of each tending to exacerbate and inflate the other. Secondly, by concentrating on infant children, the paper will assess the extent to which these resultant processes and practices are also evident for Black pupils at the beginning of their school careers - at the ages of five and six.

Crowd Control? Depictions of the Many in Anglo-Saxon Literature, with Particular Reference to the Old English Legend of the Seven Sleepers

This article argues for the distinctiveness of the presentation of crowds in the Old English version of the Legend of the Seven Sleepers . In traditional Old English poetry, crowds are mostly conspicuous by their absence, since the social groupings portrayed are typically those ofthe lord's retinue and the fellowship of the hall. In writings deriving from Latin traditions (in Anglo-Latin, Old English prose and strands of Old English poetry) such as historiography andhagiography, crowds are presented in highly conventional terms based on literary models. The crowd scenes in the Legend of the Seven Sleepers , on the other hand, have an immediacy and urgency that seem based on real-life experience of Anglo-Saxon England rather than simply imitative of the work's Latin (ultimately Greek) source or of other literary models. Drawing upon crowd theory and historical studies, the article demonstrates that the crowds in this text are presented in “domesticated” Anglo-Saxon terms and may be seen as reflective of growing urbanization in late Anglo-Saxon England. “Real” crowds are glimpsed elsewhere in Anglo-Saxon literature but in the Legend of the Seven Sleepers they are particularly foregrounded; this text also presents the literature's liveliest picture of town life more generally.

FhCaBP4: A Fasciola hepatica calcium binding protein with EF-hand and dynein light chain domains

In trematodes, there is a family of proteins which combine EF-hand-containing domains with dynein light chain (DLC)-like domains. A member of this family from the liver fluke, Fasciola hepatica-FhCaBP4-has been identified and characterised biochemically. FhCaBP4 has an N-terminal domain containing two imperfect EF-hand sequences and a C-terminal dynein light chain-like domain. Molecular modelling predicted that the two domains are joined by a flexible linker. Native gel electrophoresis demonstrated that FhCaBP4 binds to calcium, manganese, barium and strontium ions, but not to magnesium or zinc ions. The hydrophobic, fluorescent probe 8-anilinonaphthalene-1-sulphonate bound more tightly to FhCaBP4 in the presence of calcium ions. This suggests that the protein undergoes a conformational change on ion binding which increases the number of non-polar residues on the surface. FhCaBP4 was protected from limited proteolysis by the calmodulin antagonist W7, but not by trifluoperazine or praziquantel. Protein-protein cross-linking experiments showed that FhCaBP4 underwent calcium ion-dependent dimerisation. Since DLCs are commonly dimeric, it is likely that FhCaBP4 dimerises through this domain. The molecular model reveals that the calcium ion-binding site is located close to a key sequence in the DLC-like domain, suggesting a plausible mechanism for calcium-dependent dimerisation.

FhCaBP3: A Fasciola hepatica calcium binding protein with EF-hand and dynein light chain domains

A DNA sequence encoding a protein with predicted EF-hand and dynein light chain binding domains was identified in a Fasciola hepatica EST library. Sequence analysis of the encoded protein revealed that the most similar known protein was the Fasciola gigantica protein FgCaBP3 and so this newly identified protein was named FhCaBP3. Molecular modelling of FhCaBP3 predicted a highly flexible N-terminal region, followed by a domain containing two EF-hand motifs the second of which is likely to be a functioning divalent ion binding site. The C-terminal domain of the protein contains a dynein light chain like region. Interestingly, molecular modelling predicts that calcium ion binding to the N-terminal domain destabilises the ß-sheet structure of the C-terminal domain. FhCaBP3 can be expressed in, and purified from, Escherichia coli. The recombinant protein dimerises and the absence of calcium ions appeared to promote dimerisation. Native gel shift assays demonstrated that the protein bound to calcium and manganese ions, but not to magnesium, barium, zinc, strontium, nickel, copper or cadmium ions. FhCaBP3 interacted with the calmodulin antagonists trifluoperazine, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide and chlorpromazine as well as the myosin regulatory light chain-binding drug praziquantel. Despite sequence and structural similarities to other members of the same protein family from F. hepatica, FhCaBP3 has different biochemical properties to the other well characterised family members, FH22 and FhCaBP4. This suggests that each member of this trematode calcium-binding family has discrete functional roles within the organism.

Effect of a multifaceted intervention on adherence to hand hygiene among healthcare workers:A cluster-randomized trial

OBJECTIVES. Adherence to hand hygiene among healthcare workers (HCWs) is widely believed to be a key factor in reducing the spread of healthcare-associated infection. The objective of this study was to evaluate the impact of a multifaceted intervention to increase rates of adherence to hand hygiene among HCWs and to assess the effect on the incidence of hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) colonization. DESIGN. Cluster-randomized controlled trial. SETTING. Thirty hospital units in 3 tertiary care hospitals in Hamilton, Ontario, Canada. INTERVENTION. After a 3-month baseline period of data collection, 15 units were randomly assigned to the intervention arm (with performance feedback, small-group teaching seminars, and posters) and 15 units to usual practice. Hand hygiene was observed during randomly selected 15-minute periods on each unit, and the incidence of MRSA colonization was measured using weekly surveillance specimens from June 2007 through May 2008. RESULTS. We found that 3,812 (48.2%) of 7,901 opportunities for hand hygiene in the intervention group resulted in adherence, compared with 3,205 (42.6%) of 7,526 opportunities in the control group (P <.001; independent t test). There was no reduction in the incidence of hospital-acquired MRSA colonization in the intervention group. CONCLUSION. Among HCWs in Ontario tertiary care hospitals, the rate of adherence to hand hygiene had a statistically significant increase of 6% with a multifaceted intervention, but the incidence of MRSA colonization was not reduced.

Hand-related rather than goal-related source of gaze-dependent errors in memory-guided reaching

Mechanisms for visuospatial cognition are often inferred directly from errors in behavioral reports of remembered target direction. For example, gaze-centered target representations for reach were first inferred from reach overshoots of target location relative to gaze. Here, we report evidence for the hypothesis that these gaze-dependent reach errors stem predominantly from misestimates of hand rather than target position, as was assumed in all previous studies. Subjects showed typical gaze-dependent overshoots in complete darkness, but these errors were entirely suppressed by continuous visual feedback of the finger. This manipulation could not affect target representations, so the suppressed gaze-dependent errors must have come from misestimates of hand position, likely arising in a gaze-dependent transformation of hand position signals into visual coordinates. This finding has broad implications for any task involving localization of visual targets relative to unseen limbs, in both healthy individuals and patient populations, and shows that response-related transformations cannot be ignored when deducing the sources of gaze-related errors.

Adaptations of lateral hand movements to early and late visual occlusion in catching

Recent studies suggested that the control of hand movements in catching involves continuous vision-based adjustments. More insight into these adjustments may be gained by examining the effects of occluding different parts of the ball trajectory. Here, we examined the effects of such occlusion on lateral hand movements when catching balls approaching from different directions, with the occlusion conditions presented in blocks or in randomized order. The analyses showed that late occlusion only had an effect during the blocked presentation, and early occlusion only during the randomized presentation. During the randomized presentation movement biases were more leftward if the preceding trial was an early occlusion trial. The effect of early occlusion during the randomized presentation suggests that the observed leftward movement bias relates to the rightward visual acceleration inherent to the ball trajectories used, while its absence during the blocked presentation seems to reflect trial-by-trial adaptations in the visuomotor gain, reminiscent of dynamic gain control in the smooth pursuit system. The movement biases during the late occlusion block were interpreted in terms of an incomplete motion extrapolation--a reduction of the velocity gain--caused by the fact that participants never saw the to-be-extrapolated part of the ball trajectory. These results underscore that continuous movement adjustments for catching do not only depend on visual information, but also on visuomotor adaptations based on non-visual information.

Re-Envisioning the Artist Hero Through Two Cole Porter Biopics

Songwriter Cole Porter is unusual in having had two biopics based on his life: Night and Day (1946) starring Cary Grant, and De-Lovely (2004), starring Kevin Kline. The differences in the treatment of the character of Cole Porter between the films are striking, and indicate a change in the way that society envisions its artists, and the very act of creativity. Night and Day was conceived partly as a showcase of Porter's songs, but also as a means of providing inspiration to soldiers returning wounded from World War II, based on Porter's recovery from a traumatic riding accident. It depicts Porter as an everyman following a trajectory of achievement, from having little to great success, which was positioned as easy to emulate. De-Lovely, on the other hand, is about the relationship between Porter and his wife Linda, and the way that his creativity was influenced by his changing relationships with various people. Drawing on the work on biopics of scholars such as G.F.Custen, together with research into the shifting ideas of how creativity operates and is popularly understood, this article uses these biopics as case studies to examine the representation of changing concepts of the artist and the act of creativity through Hollywood film. It also considers how these changing conceptions and representations connect to shifts in American society.