Charge Form Factor and Cluster Structure of 6^6Li Nucleus

The charge form factor of ${}^6$Li nucleus is considered on the basis of its cluster structure. The charge density of ${}^6$Li is presented as a superposition of two terms. One of them is a folded density and the second one is a sum of ${}^4$He and the deuteron densities. Using the available experimental data for ${}^4$He and deuteron charge form factors, a good agreement of the calculations within the suggested scheme is obtained with the experimental data for the charge form factor of ${}^6$Li, including those in the region of large transferred momenta.Comment: 12 pages 5 figure

The type 2 cannabinoid receptor regulates susceptibility to osteoarthritis in mice

SummaryObjectiveCannabinoid receptors and their ligands have been implicated in the regulation of various physiological processes but their role in osteoarthritis has not been investigated. The aim of this study was to evaluate the role of the type 2 cannabinoid receptor (Cnr2) in regulating susceptibility to osteoarthritis in mice.MethodsWe analysed the severity of knee osteoarthritis as assessed by the Osteoarthritis Research Society International (OARSI) scoring system in mice with targeted deletion of Cnr2 (Cnr2−/−) and wild type (WT) littermates. Studies were conducted in mice subjected to surgical destabilisation of the medial meniscus (DMM) and in those with spontaneous age-related osteoarthritis (OA).ResultsOsteoarthritis was more severe following DMM in the medial compartment of the knee in Cnr2−/− compared with WT mice (mean ± sem score = 4.9 ± 0.5 vs 3.6 ± 0.3; P = 0.017). Treatment of WT mice with the CB2-selective agonist HU308 following DMM reduced the severity of OA in the whole joint (HU308 = 8.4 ± 0.2 vs vehicle = 10.4 ± 0.6; P = 0.007). Spontaneous age related osteoarthritis was also more severe in the medial compartment of the knee in 12-month old Cnr2−/− mice compared with WT (5.6 ± 0.5 vs 3.5 ± 0.3, P = 0.008). Cultured articular chondrocytes from Cnr2−/− mice produced less proteoglycans in vitro than wild type chondrocytes.ConclusionThese studies demonstrate that the Cnr2 pathway plays a role in the pathophysiology of osteoarthritis in mice and shows that pharmacological activation of CB2 has a protective effect. Further studies of the role of cannabinoid receptors in the pathogenesis of osteoarthritis in man are warranted

Broad-spectrum in vitro activity of macrophage infectivity potentiator inhibitors against Gram-negative bacteria and Leishmania major

Background The macrophage infectivity potentiator (Mip) protein, which belongs to the immunophilin superfamily, is a peptidyl-prolyl cis/trans isomerase (PPIase) enzyme. Mip has been shown to be important for virulence in a wide range of pathogenic microorganisms. It has previously been demonstrated that small-molecule compounds designed to target Mip from the Gram-negative bacterium Burkholderia pseudomallei bind at the site of enzymatic activity of the protein, inhibiting the in vitro activity of Mip. Objectives In this study, co-crystallography experiments with recombinant B. pseudomallei Mip (BpMip) protein and Mip inhibitors, biochemical analysis and computational modelling were used to predict the efficacy of lead compounds for broad-spectrum activity against other pathogens. Methods Binding activity of three lead compounds targeting BpMip was verified using surface plasmon resonance spectroscopy. The determination of crystal structures of BpMip in complex with these compounds, together with molecular modelling and in vitro assays, was used to determine whether the compounds have broad-spectrum antimicrobial activity against pathogens. Results Of the three lead small-molecule compounds, two were effective in inhibiting the PPIase activity of Mip proteins from Neisseria meningitidis, Klebsiella pneumoniae and Leishmania major. The compounds also reduced the intracellular burden of these pathogens using in vitro cell infection assays. Conclusions These results indicate that Mip is a novel antivirulence target that can be inhibited using small-molecule compounds that prove to be promising broad-spectrum drug candidates in vitro. Further optimization of compounds is required for in vivo evaluation and future clinical applications

An Observational Overview of Solar Flares

We present an overview of solar flares and associated phenomena, drawing upon a wide range of observational data primarily from the RHESSI era. Following an introductory discussion and overview of the status of observational capabilities, the article is split into topical sections which deal with different areas of flare phenomena (footpoints and ribbons, coronal sources, relationship to coronal mass ejections) and their interconnections. We also discuss flare soft X-ray spectroscopy and the energetics of the process. The emphasis is to describe the observations from multiple points of view, while bearing in mind the models that link them to each other and to theory. The present theoretical and observational understanding of solar flares is far from complete, so we conclude with a brief discussion of models, and a list of missing but important observations.Comment: This is an article for a monograph on the physics of solar flares, inspired by RHESSI observations. The individual articles are to appear in Space Science Reviews (2011

Neonatal consultation at a distance

Background: Infant transport can be costly, time consuming and risky for both the infant and transport-team. For some infants, telemedicine may improve care, avoid transport and save money. Methods: We conducted an informal retrospective review of the first 10 telemedicine consultations provided from a tertiary perinatal centre to four referring hospitals. Sessions were recorded to allow evaluation of the content of each consultation. Cases of avoided transport were identified by analysis of the recordings and by interviewing the clinicians involved in the consultations. Potential savings resulting from avoided retrievals was estimated in Australian Dollars (AUD) at 2009 prices (AUD 1GUSD0Æ86). Results: Nine consultations were led by a consultant neonatologist and one by a senior registrar. In all cases a paediatrician attended at the referring sites. During sessions, visual information included radiological images (n = 7); infant observation (n = 7); viewing of the patient monitor (n = 2) and ventilator (n = 2). Telemedicine was used to manage requests for infant retrieval (n = 4) and requests for a second opinion (n = 6). This resulted in transport to the RBWH (n = 2), another intensive care nursery (n = 1) and prevented retrieval (n = 3). The total estimated saving from avoided retrievals was $23 618 (Table 1). Conclusion: These early results suggest that neonatal teleconsultation is effective. Anecdotally, the visual information increased safety and confidence in the formulation of local management plans. An infant may be managed in their own community, avoiding costly and risky transport to a tertiary facility using teleconsultation. Further research will formally assess the clinical and economic benefits over a longer time period

Peptidyl-prolyl isomerase ppiB Is essential for proteome homeostasis and virulence in Burkholderia pseudomallei

Burkholderia pseudomallei is the causative agent of melioidosis, a disease endemic to Southeast Asia and northern Australia. Mortality rates in these areas are high even with antimicrobial treatment, and there are few options for effective therapy. Therefore, there is a need to identify antibacterial targets for the development of novel treatments. Cyclophilins are a family of highly conserved enzymes important in multiple cellular processes. Cyclophilins catalyze the cis-trans isomerization of xaa-proline bonds, a rate-limiting step in protein folding which has been shown to be important for bacterial virulence. B. pseudomallei carries a putative cyclophilin B gene, ppiB, the role of which was investigated. A B. pseudomallei ΔppiB (BpsΔppiB) mutant strain demonstrates impaired biofilm formation and reduced motility. Macrophage invasion and survival assays showed that although the BpsΔppiB strain retained the ability to infect macrophages, it had reduced survival and lacked the ability to spread cell to cell, indicating ppiB is essential for B. pseudomallei virulence. This is reflected in the BALB/c mouse infection model, demonstrating the requirement of ppiB for in vivo disease dissemination and progression. Proteomic analysis demonstrates that the loss of PpiB leads to pleiotropic effects, supporting the role of PpiB in maintaining proteome homeostasis. The loss of PpiB leads to decreased abundance of multiple virulence determinants, including flagellar machinery and alterations in type VI secretion system proteins. In addition, the loss of ppiB leads to increased sensitivity toward multiple antibiotics, including meropenem and doxycycline, highlighting ppiB inhibition as a promising antivirulence target to both treat B. pseudomallei infections and increase antibiotic efficacy