The extracellular Leucine-Rich Repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns

Correction to Dolan J, Walshe K, Alsbury S, Hokamp K, O'Keeffe S, Okafuji T, Miller SF, Tear G, Mitchell KJ: The extracellular leucine-rich repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns. BMC Genomics 2007, 8:320

Environmental toxic metal contaminants and risk of cardiovascular disease: systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis of epidemiological studies investigating the association of arsenic, lead, cadmium, mercury, and copper with cardiovascular disease. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Embase, and Web of Science searched up to December 2017. REVIEW METHODS: Studies reporting risk estimates for total cardiovascular disease, coronary heart disease, and stroke for levels of arsenic, lead, cadmium, mercury, or copper were included. Two investigators independently extracted information on study characteristics and outcomes in accordance with PRISMA and MOOSE guidelines. Relative risks were standardised to a common scale and pooled across studies for each marker using random effects meta-analyses. RESULTS: The review identified 37 unique studies comprising 348 259 non-overlapping participants, with 13 033 coronary heart disease, 4205 stroke, and 15 274 cardiovascular disease outcomes in aggregate. Comparing top versus bottom thirds of baseline levels, pooled relative risks for arsenic and lead were 1.30 (95% confidence interval 1.04 to 1.63) and 1.43 (1.16 to 1.76) for cardiovascular disease, 1.23 (1.04 to 1.45) and 1.85 (1.27 to 2.69) for coronary heart disease, and 1.15 (0.92 to 1.43) and 1.63 (1.14 to 2.34) for stroke. Relative risks for cadmium and copper were 1.33 (1.09 to 1.64) and 1.81 (1.05 to 3.11) for cardiovascular disease, 1.29 (0.98 to 1.71) and 2.22 (1.31 to 3.74) for coronary heart disease, and 1.72 (1.29 to 2.28) and 1.29 (0.77 to 2.17) for stroke. Mercury had no distinctive association with cardiovascular outcomes. There was a linear dose-response relation for arsenic, lead, and cadmium with cardiovascular disease outcomes. CONCLUSION: Exposure to arsenic, lead, cadmium, and copper is associated with an increased risk of cardiovascular disease and coronary heart disease. Mercury is not associated with cardiovascular risk. These findings reinforce the importance of environmental toxic metals in cardiovascular risk, beyond the roles of conventional behavioural risk factors.This work was not supported by any external grants or funding

Integrative metabolic flux analysis reveals an indispensable dimension of phenotypes.

Complete understanding of a biological system requires quantitation of metabolic fluxes that reflect its dynamic state. Various analytical chemistry tools, enzyme-based probes, and microscopy enable flux measurement. However, any method alone falls short of comprehensive flux quantitation. Here we show that integrating these techniques results in a systems-level quantitative map of absolute metabolic fluxes that constitute an indispensable dimension of characterizing phenotypes. Stable isotopes, mass spectrometry, and NMR spectroscopy reveal relative pathway fluxes. Biochemical probes reveal the physical rate of environmental changes. FRET-based and SRS-based microscopy reveal targeted metabolite and chemical bond formation. These techniques are complementary and can be computationally integrated to reveal actionable information on metabolism. Integrative metabolic flux analysis using various quantitative techniques advances biotechnology and medicine

The extracellular Leucine-Rich Repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns

BACKGROUND: Leucine-rich repeats (LRRs) are highly versatile and evolvable protein-ligand interaction motifs found in a large number of proteins with diverse functions, including innate immunity and nervous system development. Here we catalogue all of the extracellular LRR (eLRR) proteins in worms, flies, mice and humans. We use convergent evidence from several transmembrane-prediction and motif-detection programs, including a customised algorithm, LRRscan, to identify eLRR proteins, and a hierarchical clustering method based on TribeMCL to establish their evolutionary relationships. RESULTS: This yields a total of 369 proteins (29 in worm, 66 in fly, 135 in mouse and 139 in human), many of them of unknown function. We group eLRR proteins into several classes: those with only LRRs, those that cluster with Toll-like receptors (Tlrs), those with immunoglobulin or fibronectin-type 3 (FN3) domains and those with some other domain. These groups show differential patterns of expansion and diversification across species. Our analyses reveal several clusters of novel genes, including two Elfn genes, encoding transmembrane proteins with eLRRs and an FN3 domain, and six genes encoding transmembrane proteins with eLRRs only (the Elron cluster). Many of these are expressed in discrete patterns in the developing mouse brain, notably in the thalamus and cortex. We have also identified a number of novel fly eLRR proteins with discrete expression in the embryonic nervous system. CONCLUSION: This study provides the necessary foundation for a systematic analysis of the functions of this class of genes, which are likely to include prominently innate immunity, inflammation and neural development, especially the specification of neuronal connectivity

Physiotherapists may stigmatise or feel unprepared to treat people with low back pain and psychosocial factors that influence recovery: a systematic review

Question: What are physiotherapists’ perceptions about identifying and managing the cognitive, psychological and social factors that may act as barriers to recovery for people with low back pain (LBP)? Design: Systematic review and qualitative metasynthesis of qualitative studies in which physiotherapists were questioned, using focus groups or semi-structured interviews, about identifying and managing cognitive, psychological and social factors in people with LBP. Participants: Qualified physiotherapists with experience in treating patients with LBP. Outcome measures: Studies were synthesised in narrative format and thematic analysis was used to provide a collective insight into the physiotherapists’ perceptions. Results: Three main themes emerged: physiotherapists only partially recognised cognitive, psychological and social factors in LBP, with most discussion around factors such as family, work and unhelpful patient expectations; some physiotherapists stigmatised patients with LBP as demanding, attention-seeking and poorly motivated when they presented with behaviours suggestive of these factors; and physiotherapists questioned the relevance of screening for these factors because they were perceived to extend beyond their scope of practice, with many feeling under-skilled in addressing them. Conclusion: Physiotherapists partially recognised cognitive, psychological and social factors in people with LBP. Physiotherapists expressed a preference for dealing with the more mechanical aspects of LBP, and some stigmatised the behaviours suggestive of cognitive, psychological and social contributions to LBP. Physiotherapists perceived that neither their initial training, nor currently available professional development training, instilled them with the requisite skills and confidence to successfully address and treat the multidimensional pain presentations seen in LBP

Physiotherapists report improved understanding of and attitude toward the cognitive, psychological and social dimensions of chronic low back pain after cognitive functional therapy training: a qualitative study

Question: What are physiotherapists’ perspectives on managing the cognitive, psychological and social dimensions of chronic low back pain after intensive biopsychosocial training? Design: Qualitative study design using semi-structured interviews to explore physiotherapists’ perceptions of their identification and treatment of the biopsychosocial dimensions of chronic low back pain after intensive Cognitive Functional Therapy (CFT) training. Participants: Thirteen qualified physiotherapists from four countries who had received specific CFT training. The training involved supervised implementation of CFT in clinical practice with patients. Interviews were audio-recorded and transcribed verbatim. An interpretive descriptive analysis was performed using a qualitative software package. Results: Four main themes emerged from the data: self-reported changes in understanding and attitudes; self-reported changes in professional practice; altered scope of practice; and increased confidence and satisfaction. Participants described increased understanding of the nature of pain, the role of patient beliefs, and a new appreciation of the therapeutic alliance. Changes in practice included use of new assessments, changes in communication, and adoption of a functional approach. Since undertaking CFT training, participants described a greater awareness of their role and scope of practice as clinicians in identifying and addressing these factors. Conclusion: Physiotherapists expressed confidence in their capacity and skill set to manage the biopsychosocial dimensions of chronic low back pain after CFT training, and identified a clear role for including these skills within the physiotherapy profession. Despite this, further clinical trials are needed to justify the time and cost of training, so that intensive CFT training may be made more readily accessible to clinicians, which to date has not been the case

The extracellular Leucine-Rich Repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns-5

<p><b>Copyright information:</b></p><p>Taken from "The extracellular Leucine-Rich Repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns"</p><p>http://www.biomedcentral.com/1471-2164/8/320</p><p>BMC Genomics 2007;8():320-320.</p><p>Published online 14 Sep 2007</p><p>PMCID:PMC2235866.</p><p></p>our-coded by chemical properties: blue: acidic; green: hydroxyl/amine/basic/Q; magenta: basic; red: small, hydrophobic (including aliphatic Y). Brackets indicate the extent of predicted motifs, including signal sequence (SS), six LRRs (the notch under the bracket indicates the end of the conserved N-terminal portion of each LRR), LRR-CT domain, fibronectin type-3 (FN3) domain and a transmembrane domain (TM). No recognizable LRR-NT domain was predicted. Note that the final LRR comprises the highly conserved N-terminal half-repeat only (consensus: LxxLxxLxLxxN). Identical residues are indicated by an asterisk, highly conservative substitutions by two dots and conservative substitutions by a single dot

The extracellular Leucine-Rich Repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns-7

<p><b>Copyright information:</b></p><p>Taken from "The extracellular Leucine-Rich Repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns"</p><p>http://www.biomedcentral.com/1471-2164/8/320</p><p>BMC Genomics 2007;8():320-320.</p><p>Published online 14 Sep 2007</p><p>PMCID:PMC2235866.</p><p></p>(E15), A, D; postnatal day zero (P0), B, E; and postnatal day 9 (P9), C, F). is strongly expressed in globus pallidus and interneurons in cortex and hippocampus, while is expressed in striatum and in projection neurons in cortex and hippocampus. Arrowheads in A and B indicate presumed interneurons migrating towards cortex. Abbreviations: cp, cortical plate; Cx, cortex; DG(vz), ventricular zone of dentate gyrus; gcl, granule cell layer (of dentate gyrus); GP, globus pallidus; hab, habenula; hc, hippocampus; hi, hilus (of dentate gyrus); hy, hypothalamus; pcl; pyramidal cell layer (of hippocampus); SB, subiculum; sp, subplate; so, stratum oriens (of hippocampus), str, striatum. Scale bar: E15, 200 microns; P0 and P9, 500 microns

Testes and brain gene expression in precocious male and adult maturing atlantic salmon (salmo salar)

Background: The male Atlantic salmon generally matures in fresh water upon returning after one or several years at sea. Some fast-growing male parr develop an alternative life strategy where they sexually mature before migrating to the oceans. These so called 'precocious' parr or 'sneakers' can successfully fertilise adult female eggs and so perpetuate their line. We have used a custom-built cDNA microarray to investigate gene expression changes occurring in the salmon gonad and brain associated with precocious maturation. The microarray has been populated with genes selected specifically for involvement in sexual maturation (precocious and adult) and in the parr-smolt transformation. Results: Immature and mature parr collected from a hatchery-reared stock in January were significantly different in weight, length and condition factor. Changes in brain expression were small - never more than 2-fold on the microarray, and down-regulation of genes was much more pronounced than up-regulation. Significantly changing genes included isotocin, vasotocin, cathepsin D, anamorsin and apolipoprotein E. Much greater changes in expression were seen in the testes. Among those genes in the testis with the most significant changes in expression were anti-Mullerian hormone, collagen 1A, and zinc finger protein (Zic1), which were down-regulated in precocity and apolipoproteins E and C-1, lipoprotein lipase and anti-leukoproteinase precursor which were up-regulated in precocity. Expression changes of several genes were confirmed in individual fish by quantitative PCR and several genes (anti-Mullerian hormone, collagen 1A, beta-globin and guanine nucleotide binding protein (G protein) beta polypeptide 2-like 1 (GNB2L1) were also examined in adult maturing testes. Down-regulation of anti-Mullerian hormone was judged to be greater than 160-fold for precocious males and greater than 230-fold for November adult testes in comparison to July testes by this method. For anti-Mullerian hormone and guanine nucleotide binding protein beta polypeptide 2-like 1 expression changes in precocious males mirrored mature adults (November) but for collagen 1A and beta-globin the pattern was more complex. Conclusions: Expression changes in the fish brain during the process of precocious sexual maturation were small compared to those in the testes. Microarray analysis suggested down-regulation of housekeeping functions and up-regulation of a small number of specific processes. Transcriptional changes in the testes were much more pronounced with anti-Mullerian hormone playing a major role. Expression profiles for mature parr and maturing adult testes indicate subtle differences in gene expression between these two related groups