A novel mode of capping protein-regulation by Twinfilin

Cellular actin assembly is controlled at the barbed ends of actin filaments, where capping protein (CP) limits polymerization. Twinfilin is a conserved in vivo binding partner of CP, yet the significance of this interaction has remained a mystery. Here, we discover that the C-terminal tail of Twinfilin harbors a CP-interacting (CPI) motif, identifying it as a novel CPI-motif protein. Twinfilin and the CPI-motif protein CARMIL have overlapping binding sites on CP. Further, Twinfilin binds competitively with CARMIL to CP, protecting CP from barbed-end displacement by CARMIL. Twinfilin also accelerates dissociation of the CP inhibitor V-1, restoring CP to an active capping state. Knockdowns of Twinfilin and CP each cause similar defects in cell morphology, and elevated Twinfilin expression rescues defects caused by CARMIL hyperactivity. Together, these observations define Twinfilin as the first \u27pro-capping\u27 ligand of CP and lead us to propose important revisions to our understanding of the CP regulatory cycle

Prevalence, practice patterns, and evidence for chronic neck pain

The primary objectives of this study were to estimate the prevalence of chronic neck pain in North Carolina, to describe health care use (providers, treatments and diagnostic testing) for chronic neck pain and to correlate health care use with current best evidence

Low Back Pain and Lumbar Spine Osteoarthritis: How Are They Related?

Lumbar spine osteoarthritis (OA) is very common, with estimates of prevalence ranging from 40–85 %. The process of degeneration of the spine has commonly been classified as OA (disc space narrowing together with vertebral osteophyte formation); however, anatomically, the facet joint is the only synovial joint in the spine that has a similar pathological degenerative process to appendicular joints. Low back pain (LBP) is also a common condition, with nearly 80 % of Americans experiencing at least one episode of LBP in their lifetime. The complex relationship between spine radiographs and LBP has many clinical and research challenges. Specific conservative treatments for spine degeneration have not been established; there has, however, been recent interest in use of exercise therapy, because of some moderate benefits in treating chronic LBP. An understanding of the relationship between spine degeneration and LBP may be improved with further population-based research in the areas of genetics, biomarkers, and pain pathways

The prevalence and effect of burnout on graduate healthcare students

Burnout is a growing epidemic among professional healthcare students. Unaddressed burnout has been shown to have psychological and performance related detriments. The purpose of this scoping literature review was to investigate the prevalence of burnout and its effects on the psychological, professional, empathetic ability, and academic acuity of graduate healthcare students. Inclusion criteria included English language papers published within the last 10 years and subjects in graduate healthcare professional programs. This search encompassed 8,214 articles. After title and abstract screening, 127 articles remained and were sorted into five domains of interest: etiology, professionalism, mental health, empathy, and academic performance. After duplicates were removed, 27 articles remained for the scoping review. Graduate level healthcare students had higher levels of burnout than age matched peers and the general population. The high prevalence of burnout within graduate healthcare students can have an effect on their mental health, empathy, and professional conduct. Understanding the occurrence and effects of burnout within graduate healthcare programs allows faculty and administration to plan curriculum, and provide information to students to understand, recognize, and create opportunities to decrease burnout in order to create long lasting quality clinicians

CONDOR: a database resource of developmentally associated conserved non-coding elements

<p>Abstract</p> <p>Background</p> <p>Comparative genomics is currently one of the most popular approaches to study the regulatory architecture of vertebrate genomes. Fish-mammal genomic comparisons have proved powerful in identifying conserved non-coding elements likely to be distal <it>cis-</it>regulatory modules such as enhancers, silencers or insulators that control the expression of genes involved in the regulation of early development. The scientific community is showing increasing interest in characterizing the function, evolution and language of these sequences. Despite this, there remains little in the way of user-friendly access to a large dataset of such elements in conjunction with the analysis and the visualization tools needed to study them.</p> <p>Description</p> <p>Here we present CONDOR (COnserved Non-coDing Orthologous Regions) available at: <url>http://condor.fugu.biology.qmul.ac.uk</url>. In an interactive and intuitive way the website displays data on > 6800 non-coding elements associated with over 120 early developmental genes and conserved across vertebrates. The database regularly incorporates results of ongoing <it>in vivo </it>zebrafish enhancer assays of the CNEs carried out in-house, which currently number ~100. Included and highlighted within this set are elements derived from duplication events both at the origin of vertebrates and more recently in the teleost lineage, thus providing valuable data for studying the divergence of regulatory roles between paralogs. CONDOR therefore provides a number of tools and facilities to allow scientists to progress in their own studies on the function and evolution of developmental <it>cis</it>-regulation.</p> <p>Conclusion</p> <p>By providing access to data with an approachable graphics interface, the CONDOR database presents a rich resource for further studies into the regulation and evolution of genes involved in early development.</p

Lumbar spine radiographic features and demographic, clinical, and radiographic knee, hip and hand osteoarthritis: The Johnston County Osteoarthritis Project

Objective—1) To determine the prevalence of lumbar spine individual radiographic features (IRF) of disc space narrowing (DSN), osteophytes (OST) and facet joint osteoarthritis (FOA). 2) To describe the frequencies of demographic, clinic and radiographic knee, hip and hand osteoarthritis (OA) across lumbar spine IRF. 3) To determine factors associated with lumbar spine IRF. Methods—A cross-sectional study of 840 participants enrolled in the Johnston County OA Project (2003-4). Sample-based prevalence estimates were generated for each lumbar spine IRF. Associations between lumbar spine IRF and demographic, clinical and peripheral joint OA were determined with logistic regression models. Results—Sample-based prevalence estimates were similar for DSN (57.6%) and FOA (57.9%) but higher for OST (88.1%) with significant differences across race and gender. Hand and knee OA frequencies increased across IRF whereas the effect was absent for hip OA. African Americans had lower odds of FOA (adjusted odds ratio [aOR]=0.45 (95% CI 0.32, 0.62)) while there was no racial association with DSN and OST. Low back symptoms were associated with DSN (aOR=1.37 (95% CI 1.04, 1.80)) but not OST or FOA. Knee OA was associated with OST (aOR=1.62 (95% CI 1.16, 2.27)) and FOA (aOR=1.69 (95% CI 1.15, 2.49)) but not DSN. Hand OA was associated with FOA (aOR=1.67 (95% CI 1.20, 2.28)) but not with DSN or OST. No associations were found with hip OA. Conclusion—These findings underscore the importance of analyzing lumbar spine IRF separately as the associations with demographic, clinic and radiographic knee, hip and hand OA differ widely

Complications, revision fusions, readmissions, and utilization over a 1-year period after bone morphogenetic protein use during primary cervical spine fusions

Nationwide estimates examining Bone Morphogenetic Protein (BMP) use with cervical spine fusions have been limited to perioperative outcomes

Denying equality: an analysis of arguments against lowering the age of consent for sex between men

This paper takes a human rights approach to lesbian and gay oppression and critically explores the arguments used to oppose equality in the debates about the age of consent for sex between men. A thematic analysis of Hansard and newspaper reports produced in Britain during the 1990s showed that opponents of the amendment to equalise the age of consent countered with three key arguments laying claim to ethical principles overriding the principle of equality. These were: (1) Principles of right and wrong take precedence over equality; (2) Principles of democracy take precedence over equality; (3) Principles of care and protection take precedence over equality. Two additional arguments (the health risks of anal intercourse, and escalating demands for gay rights) are also outlined. Our findings are discussed with reference to debates on other lesbian and gay rights issues, and we consider the ways in which we might best counter these arguments. </p

Mobility of Taxol in Microtubule Bundles

Mobility of taxol inside microtubules was investigated using fluorescence recovery after photobleaching (FRAP) on flow-aligned bundles. Bundles were made of microtubules with either GMPCPP or GTP at the exchangeable site on the tubulin dimer. Recovery times were sensitive to bundle thickness and packing, indicating that taxol molecules are able to move laterally through the bundle. The density of open binding sites along a microtubule was varied by controlling the concentration of taxol in solution for GMPCPP samples. With > 63% sites occupied, recovery times were independent of taxol concentration and, therefore, inversely proportional to the microscopic dissociation rate, k_{off}. It was found that 10*k_{off} (GMPCPP) ~ k_{off} (GTP), consistent with, but not fully accounting for, the difference in equilibrium constants for taxol on GMPCPP and GTP microtubules. With < 63% sites occupied, recovery times decreased as ~ [Tax]^{-1/5} for both types of microtubules. We conclude that the diffusion of taxol along the microtubule interior is hindered by rebinding events when open sites are within ~7 nm of each other.Comment: pre print forma

Early Evolution of Conserved Regulatory Sequences Associated with Development in Vertebrates

Comparisons between diverse vertebrate genomes have uncovered thousands of highly conserved non-coding sequences, an increasing number of which have been shown to function as enhancers during early development. Despite their extreme conservation over 500 million years from humans to cartilaginous fish, these elements appear to be largely absent in invertebrates, and, to date, there has been little understanding of their mode of action or the evolutionary processes that have modelled them. We have now exploited emerging genomic sequence data for the sea lamprey, Petromyzon marinus, to explore the depth of conservation of this type of element in the earliest diverging extant vertebrate lineage, the jawless fish (agnathans). We searched for conserved non-coding elements (CNEs) at 13 human gene loci and identified lamprey elements associated with all but two of these gene regions. Although markedly shorter and less well conserved than within jawed vertebrates, identified lamprey CNEs are able to drive specific patterns of expression in zebrafish embryos, which are almost identical to those driven by the equivalent human elements. These CNEs are therefore a unique and defining characteristic of all vertebrates. Furthermore, alignment of lamprey and other vertebrate CNEs should permit the identification of persistent sequence signatures that are responsible for common patterns of expression and contribute to the elucidation of the regulatory language in CNEs. Identifying the core regulatory code for development, common to all vertebrates, provides a foundation upon which regulatory networks can be constructed and might also illuminate how large conserved regulatory sequence blocks evolve and become fixed in genomic DNA