Feeding in flow extremes: dependence of cirrus form on wave-exposure in four barnacle species

Wave-exposure influences the form of many organisms. Curiously, the impact of flow extremes on feeding structures has received little attention. Barnacles extend feather-like legs to feed, and prior work revealed a highly precise association between leg length and water velocity in one species. To assess the generality of this flow-dependence, we quantified variation in four leg traits (ramus length, ramus diameter, seta length, and intersetal spacing) in four intertidal barnacles (Balanus glandula, Chthamalus dalli, Semibalanus cariosus, Pollicipes polymerus) over a wave-exposure gradient in the North-Eastern Pacific. All species exhibited a negative allometric relation between leg length and body mass. Proportionally longer feeding legs may permit smaller barnacles to avoid lower flow and particle flux associated with boundary layers. Although coefficients of allometry did not vary with wave-exposure, form differences among wave-exposures were substantial. Depending on the species, acorn barnacles of the same size from protected shores had feeding legs that were 37-80% longer and 18-25% thinner, and setae that were 36-50% longer and up to 25% more closely spaced, than those from exposed shores. Differences were less pronounced for the gooseneck barnacle, P. polymerus. Moreover, in situ water velocity explained an impressive percentage of overall leg-length variation: 92% in B. glandula, 67% in C. dalli, 91% in S. cariosus, and 92% in P. polymerus. Clearly, both size and shape of barnacle feeding legs respond to local flow conditions. This response appears widespread--across two orders of thoracican barnacles, Pedunculata and Sessilia, and two superfamilies of acorn barnacles (Balanoidea and Chthamaloidea)--and likely adaptive. Longer rami and setae would yield a larger feeding area in low flow, whereas shorter, stouter rami with shorter setae would be less vulnerable to damage in high flow. Finally, the proportionally most variable species was abundant in the widest range of habitats, suggesting that increased plasticity may permit a wider niche breadth.     

Strengthening medical appraisal: reactions to proposals for a new appraisal system to support revalidation

This paper introduces the first stage of the NHS Revalidation Support Team's (RST) proposals to strengthen medical appraisal. It reports on four focus groups held at London Deanery in 2010, with the aim of gauging initial reactions from general practitioners (GPs). The four groups consisted of two groups of appraisers and two groups of appraisees. After presentation of the proposals to strengthen appraisal, participants were invited to make comparisons between existing appraisal, and the new proposals, Interestingly, the matter which attracted most discussion was a proposal to include an element of self-assessment by the appraisee prior to appraisal, and not, as might have been expected, the proposals for assessment of the appraisee's progress towards revalidation by the appraiser. Since these focus groups, the model of strengthened medical appraisal referred to in this paper has been the subject of testing in the pathfinder pilot, a large scale pilot involving 3000 doctors in various settings in England. The evaluation of the pathfinder pilot was published (July 2011). After further refinement of the appraisal process, including taking into account new GMC and Royal College publications and more testing and piloting, the final version of medical appraisal to support revalidation, known as the Medical Appraisal Guide (MAG) is due to be published in March 2012, in time to permit the expected commencement of revalidation in late 2012.     

Lack of ADAM15 in mice is associated with increased osteoblast function and bone mass

The ADAMs (a disintegrin and metalloprotease) contribute to various biological functions including the development of tissues by taking part in cell-cell and cell-matrix interactions. We previously found that ADAM15 is prominently expressed in osteoblasts and to a lesser extent in osteoclasts. The aim of this study was to investigate a possible function of ADAM15 in bone. Adult ADAM15(-/-) mice displayed an increase in bone volume and thickness with an increase in the number and activity of osteoblasts, whereas osteoclasts were apparently unaffected. We found an increase in proliferation, alkaline phosphatase (ALP) staining and nodule deposition, and mineralization in cultures of ADAM15(-/-) osteoblasts compared to wild-type osteoblasts. We also observed an increase in β-catenin immunoreactivity in the nucleus of ADAM15(-/-) osteoblasts compared to wild-type, whereas β-catenin in the membrane/cytoplasm compartment appeared to undergo increased degradation. Furthermore, cyclin D1 and c-Jun, known downstream targets of β-catenin and effectors of cell activation, were found up-regulated in absence of ADAM15. This study indicates that ADAM15 is required for normal skeletal homeostasis and that its absence causes increased nuclear translocation of β-catenin in osteoblasts leading to increased osteoblast proliferation and function, which results in higher trabecular and cortical bone mass.     

Re-localization of cellular protein SRp20 during poliovirus infection: bridging a viral IRES to the host cell translation apparatus

Poliovirus IRES-mediated translation requires the functions of certain canonical as well as non-canonical factors for the recruitment of ribosomes to the viral RNA. The interaction of cellular proteins PCBP2 and SRp20 in extracts from poliovirus-infected cells has been previously described, and these two proteins were shown to function synergistically in viral translation. To further define the mechanism of ribosome recruitment for the initiation of poliovirus IRES-dependent translation, we focused on the role of the interaction between cellular proteins PCBP2 and SRp20. Work described here demonstrates that SRp20 dramatically re-localizes from the nucleus to the cytoplasm of poliovirus-infected neuroblastoma cells during the course of infection. Importantly, SRp20 partially co-localizes with PCBP2 in the cytoplasm of infected cells, corroborating our previous in vitro interaction data. In addition, the data presented implicate the presence of these two proteins in viral translation initiation complexes. We show that in extracts from poliovirus-infected cells, SRp20 is associated with PCBP2 bound to poliovirus RNA, indicating that this interaction occurs on the viral RNA. Finally, we generated a mutated version of SRp20 lacking the RNA recognition motif (SRp20ΔRRM) and found that this protein is localized similar to the full length SRp20, and also partially co-localizes with PCBP2 during poliovirus infection. Expression of this mutated version of SRp20 results in a ～100 fold decrease in virus yield for poliovirus when compared to expression of wild type SRp20, possibly via a dominant negative effect. Taken together, these results are consistent with a model in which SRp20 interacts with PCBP2 bound to the viral RNA, and this interaction functions to recruit ribosomes to the viral RNA in a direct or indirect manner, with the participation of additional protein-protein or protein-RNA interactions.     

Task shifting and integration of HIV care into primary care in South Africa: The development and content of the streamlining tasks and roles to expand treatment and care for HIV (STRETCH) intervention

Background

The Veterans Health Administration (VHA) oversees the largest integrated healthcare system in the United States. The feasibility of a large-scale, nationwide, group-randomized implementation trial of VHA outpatient practices has not been reported. We describe the recruitment and enrollment of such a trial testing a clinician-directed, Internet-delivered intervention for improving the care of postmyocardial infarction patients with multiple comorbidities.

Methods

With a recruitment goal of 200 eligible community-based outpatient clinics, parent VHA facilities (medical centers) were recruited because they oversee their affiliated clinics and the research conducted there. Eligible facilities had at least four VHA-owned and -operated primary care clinics, an affiliated Institutional Review Board (IRB), and no ongoing, potentially overlapping, quality-improvement study. Between December 2003 and December 2005, in two consecutive phases, we used initial and then intensified recruitment strategies.

Results

Overall, 48 of 66 (73%) eligible facilities were recruited. Of the 219 clinics and 957 clinicians associated with the 48 facilities, 168 (78%) clinics and 401 (42%) clinicians participated. The median time from initial facility contact to clinic enrollment was 222 days, which decreased by over one-third from the first to the second recruitment phase (medians: 323 and 195 days, respectively; p < .001), when more structured recruitment with physician recruiters was implemented and a dedicated IRB manager was added to the coordinating center staff.

Conclusions

Large group-randomized trials benefit from having dedicated physician investigators and IRB personnel involved in recruitment. A large-scale, nationally representative, group-randomized trial of community-based clinics is feasible within the VHA or a similar national healthcare system.     

Wnt5a regulates midbrain dopaminergic axon growth and guidance

During development, precise temporal and spatial gradients are responsible for guiding axons to their appropriate targets. Within the developing ventral midbrain (VM) the cues that guide dopaminergic (DA) axons to their forebrain targets remain to be fully elucidated. Wnts are morphogens that have been identified as axon guidance molecules. Several Wnts are expressed in the VM where they regulate the birth of DA neurons. Here, we describe that a precise temporo-spatial expression of Wnt5a accompanies the development of nigrostriatal projections by VM DA neurons. In mice at E11.5, Wnt5a is expressed in the VM where it was found to promote DA neurite and axonal growth in VM primary cultures. By E14.5, when DA axons are approaching their striatal target, Wnt5a causes DA neurite retraction in primary cultures. Co-culture of VM explants with Wnt5a-overexpressing cell aggregates revealed that Wnt5a is capable of repelling DA neurites. Antagonism experiments revealed that the effects of Wnt5a are mediated by the Frizzled receptors and by the small GTPase, Rac1 (a component of the non-canonical Wnt planar cell polarity pathway). Moreover, the effects were specific as they could be blocked by Wnt5a antibody, sFRPs and RYK-Fc. The importance of Wnt5a in DA axon morphogenesis was further verified in Wnt5a-/- mice, where fasciculation of the medial forebrain bundle (MFB) as well as the density of DA neurites in the MFB and striatal terminals were disrupted. Thus, our results identify a novel role of Wnt5a in DA axon growth and guidance.