Mammalian myosin I alpha, I beta, and I gamma: new widely expressed genes of the myosin I family.

A polymerase chain reaction strategy was devised to identify new members of the mammalian myosin I family of actin-based motors. Using cellular RNA from mouse granular neurons and PC12 cells, we have cloned and sequenced three 1.2-kb polymerase chain reaction products that correspond to novel mammalian myosin I genes designated MMI alpha, MMI beta, MMI gamma. The pattern of expression for each of the myosin I's is unique: messages are detected in diverse tissues including the brain, lung, kidney, liver, intestine, and adrenal gland. Overlapping clones representing full-length cDNAs for MMI alpha were obtained from mouse brain. These encode a 1,079 amino acid protein containing a myosin head, a domain with five calmodulin binding sites, and a positively charged COOH-terminal tail. In situ hybridization reveals that MMI alpha is highly expressed in virtually all neurons (but not glia) in the postnatal and adult mouse brain and in neuroblasts of the cerebellar external granular layer. Expression varies in different brain regions and undergoes developmental regulation. Myosin I's are present in diverse organisms from protozoa to vertebrates. This and the expression of three novel members of this family in brain and other mammalian tissues suggests that they may participate in critical and fundamental cellular processes

Prevention of neurological injuries during mandibular third molar surgery: technical notes

Surgery to the mandibular third molar is common, and injuries to the inferior alveolar nerve and the lingual nerve are well-recognized complications of this procedure. The aim of these technical notes is to describe operative measures for reducing neurological complications during mandibular third molar surgery. The following procedure should be used to prevent damage to the inferior alveolar nerve: a well-designed mucoperiosteal flap, to obtain appropriate access to the surgical area; a conservative ostectomy on the distal and distal-lingual side; tooth sectioning, to facilitate its removal by decreasing the retention zones; tooth dislocation in the path of withdrawal imposed by the curvature of the root apex; and careful socket debridement, when the roots of the extracted tooth are in intimate contact with the mandibular canal. To prevent injury to the lingual nerve, it is important (I) to assess the integrity of the mandibular inner cortex and exclude the presence of fenestration, which could cause the dislocation of the tooth or its fragment into the sublingual or submandibular space; (II) to avoid inappropriate or excessive dislocation proceedings, in order to prevent lingual cortex fracture; (III) to perform horizontal mesial-distal crown sectioning of the lingually inclined tooth; (IV) to protect the lingual flap with a retractor showing the cortical ridge; and (V) to pass the suture not too apically and from the inner side in a buccal-lingual direction in the retromolar are

A summary of the BARREL campaigns: Technique for studying electron precipitation.

BARREL observed electron precipitation over wide range of energy and timescalesPrecipitating electron distribution is determined using spectroscopy for 19 January 2013 eventBARREL timing data has accuracy within sampling interval of 0.05 s

Chiral transition-metal complexes as Brønsted-acid catalysts for the asymmetric Friedel-Crafts hydroxyalkylation of indoles.

The Friedel-Crafts reaction between 3,3,3-trifluoropyruvates and indoles is efficiently catalysed by the iridium complex [(η5-C 5Me5)Ir{(R)-Prophos}(H2O)][SbF 6]2 (1) with up to 84% ee. Experimental data and theoretical calculations support a mechanism involving the Brønsted-acid activation of the pyruvate carbonyl by the protons of the coordinated water molecule in 1. Water is not dissociated during the process and, therefore, the catalytic reaction occurs with no direct interaction between the substrates and the metal. This journal is © the Partner Organisations 2014.The authors acknowledge the Ministerio de Economía y Competitividad (MINECO, Grants CTQ2006-03030/BQU, CTQ2009-10303/BQU, CTQ2011-27033 and Consolider Ingenio 2010 CSD2006-003), Gobierno de Aragón (Grupo Consolidado: Catálisis Homogénea Enantioselectiva), Generalitat de Catalunya (2009SGR0259) and the ICIQ foundation for financial support. A. S. and R. R. acknowledge MINECO for predoctoral fellowships. S. D.-G. acknowledges MINECO for a “Torres Quevedo” contract.Peer Reviewe

γ-Linolenic acid increases expression of key regulators of lipid metabolism in human skeletal muscle cells

Control of skeletal muscle fat metabolism is regulated acutely through Peroxisome Proliferator Activated Receptor (PPAR) δ activation and its downstream intracellular targets. The purpose of this study was to determine whether fatty acids with high binding affinity for PPARδ can elevate the expression of genes related to fatty acid oxidation and indicators of mitochondrial biogenesis in cultured human skeletal myotubes. Myotubes were treated for 72 hours with one of four conditions: (i) Control (CON); (ii) Eicosapentaenoic acid (EPA 250μM); (iii) γ-linolenic acid (γ-LA 250μM); (iv) PPARδ Agonist (GW501516 10nM). Incubation with γ-LA induced increases in the gene expression of CD36 (p= 0.005), HADHA (p= 0.022) and PDK4 (p=0.025) in comparison with CON, with no further differences observed between conditions. Furthermore, intensity of MitoTracker® Red immunostaining in myotubes increased following incubation with γ-LA (p≤ 0.001) and EPA (p= 0.005) however these trends were not mirrored in the expression of PGC-1α as might be expected. Overall, γ-LA elevates levels the transcription of key intracellular regulators of lipid metabolism and transport in human myotubes, which may be clinically beneficial in the control of metabolic diseases

Sexually transmitted infection diagnoses, sexualised drug use and associations with pre-exposure prophylaxis use among men who have sex with men in the UK

Previous research has focused on acceptability of pre-exposure prophylaxis (PrEP) use, but few community-based studies have been conducted regarding actual use, and PrEP use in the context of sexualised drug use remains understudied. A national online cross-sectional study recruited men who have sex with men (MSM) via social media (April–June 2018). Multivariable logistic regression was used to investigate factors associated with PrEP use. Bivariate analyses compared engaging in condomless anal intercourse (CAI) under the influence of specific drugs and recent sexually transmitted infection (STI) diagnoses (past 12 months) between MSM taking PrEP and those not. Overall, 6% (99/1581) MSM reported current PrEP use. Factors associated with PrEP use were increasing age, recent genitourinary medicine (GUM) attendance (95% versus 45%, aOR = 6.25, 95%CI 2.05, 19.03), an HIV test in the past three months (89% versus 23%, aOR = 14.22, 95%CI 6.76, 29.90), and recent engagement in chemsex (21% versus 4%, aOR = 3.56, 95%CI 1.78, 7.11). MSM taking PrEP were more likely to have had an STI diagnosis (42% versus 8%), most commonly chlamydia (26% versus 3%) and gonorrhoea (25% versus 4%). Considering the elevated levels of self-reported STI diagnoses among those on PrEP, there was a high level of engagement with sexual health services, which may help reduce onward STI transmission

The influence of the allometric scale on the relationship between running economy and biomechanical variables in distance runners

Studies have demonstrated the need for the use of parameters that diminish the effect of body mass, for intra and inter group comparison, in individuals with different masses in order to provide a different analysis on the behaviour of the relation between running economy (RE) and biomechanical variables (BVs). The allometric scale is represented by a regression equation that indicates the behaviour of a physiological variable in relation to the variable mass (RE=a.xb), where x is body mass in (kg) and the dimensionless coefficient a is characteristic of the species analysed, and the dimensionless exponent b determines the percentage of mass to be associated with the physiological variable. The influence of the allometric scale (b=-1; -0.75; -0.73; -0.67) on the relationship between RE and BVs - stride length (SL), relative stride length (RSL), stride rate (SR), stride time (ST), support time (SUPT) and balance time (BALT) - at 12 km.h-1, was analysed in nine elite runners. Factorial analysis and Pearson's Correlation Coefficient test (r) with P<0.05 were used. A decrease in the explanation power of the RE was observed, with the use of the allometric exponent, due to the BVs, as well as a reduction of the correlation coefficients between SL versus RE, ST versus RE and SR versus RE. The BALT presented a higher correlation where b=-0.75. The RSL and SUPT presented non-significant correlations. The variables SL, ST, SR and BALT were the most effective predictors of the RE, Where: b=-1, the allometric scale was most efficient to predict the running performance

Model-based contextual policy search for data-efficient generalization of robot skills

In robotics, lower-level controllers are typically used to make the robot solve a specific task in a fixed context. For example, the lower-level controller can encode a hitting movement while the context defines the target coordinates to hit. However, in many learning problems the context may change between task executions. To adapt the policy to a new context, we utilize a hierarchical approach by learning an upper-level policy that generalizes the lower-level controllers to new contexts. A common approach to learn such upper-level policies is to use policy search. However, the majority of current contextual policy search approaches are model-free and require a high number of interactions with the robot and its environment. Model-based approaches are known to significantly reduce the amount of robot experiments, however, current model-based techniques cannot be applied straightforwardly to the problem of learning contextual upper-level policies. They rely on specific parametrizations of the policy and the reward function, which are often unrealistic in the contextual policy search formulation. In this paper, we propose a novel model-based contextual policy search algorithm that is able to generalize lower-level controllers, and is data-efficient. Our approach is based on learned probabilistic forward models and information theoretic policy search. Unlike current algorithms, our method does not require any assumption on the parametrization of the policy or the reward function. We show on complex simulated robotic tasks and in a real robot experiment that the proposed learning framework speeds up the learning process by up to two orders of magnitude in comparison to existing methods, while learning high quality policies

A review of the methodological features of systematic reviews in maternal medicine

Background In maternal medicine, research evidence is scattered making it difficult to access information for clinical decision making. Systematic reviews of good methodological quality are essential to provide valid inferences and to produce usable evidence summaries to guide management. This review assesses the methodological features of existing systematic reviews in maternal medicine, comparing Cochrane and non-Cochrane reviews in maternal medicine. Methods Medline, Embase, Database of Reviews of Effectiveness (DARE) and Cochrane Database of Systematic Reviews (CDSR) were searched for relevant reviews published between 2001 and 2006. We selected those reviews in which a minimum of two databases were searched and the primary outcome was related to the maternal condition. The selected reviews were assessed for information on framing of question, literature search and methods of review. Results Out of 2846 citations, 68 reviews were selected. Among these, 39 (57%) were Cochrane reviews. Most of the reviews (50/68, 74%) evaluated therapeutic interventions. Overall, 54/68 (79%) addressed a focussed question. Although 64/68 (94%) reviews had a detailed search description, only 17/68 (25%) searched without language restriction. 32/68 (47%) attempted to include unpublished data and 11/68 (16%) assessed for the risk of missing studies quantitatively. The reviews had deficiencies in the assessment of validity of studies and exploration for heterogeneity. When compared to Cochrane reviews, other reviews were significantly inferior in specifying questions (OR 20.3, 95% CI 1.1–381.3, p = 0.04), framing focussed questions (OR 30.9, 95% CI 3.7- 256.2, p = 0.001), use of unpublished data (OR 5.6, 95% CI 1.9–16.4, p = 0.002), assessment for heterogeneity (OR 38.1, 95%CI 2.1, 688.2, p = 0.01) and use of meta-analyses (OR 3.7, 95% CI 1.3–10.8, p = 0.02). Conclusion This study identifies areas which have a strong influence on maternal morbidity and mortality but lack good quality systematic reviews. Overall quality of the existing systematic reviews was variable. Cochrane reviews were of better quality as compared to other reviews. There is a need for good quality systematic reviews to inform practice in maternal medicine

Rituximab monitoring and redosing in pediatric neuromyelitis optica spectrum disorder.

Abstract OBJECTIVE: To study rituximab in pediatric neuromyelitis optica (NMO)/NMO spectrum disorders (NMOSD) and the relationship between rituximab, B cell repopulation, and relapses in order to improve rituximab monitoring and redosing. METHODS: Multicenter retrospective study of 16 children with NMO/NMOSD receiving 652 rituximab courses. According to CD19 counts, events during rituximab were categorized as "repopulation," "depletion," or "depletion failure" relapses (repopulation threshold CD19 6510 7 10(6) cells/L). RESULTS: The 16 patients (14 girls; mean age 9.6 years, range 1.8-15.3) had a mean of 6.1 events (range 1-11) during a mean follow-up of 6.1 years (range 1.6-13.6) and received a total of 76 rituximab courses (mean 4.7, range 2-9) in 42.6-year cohort treatment. Before rituximab, 62.5% had received azathioprine, mycophenolate mofetil, or cyclophosphamide. Mean time from rituximab to last documented B cell depletion and first repopulation was 4.5 and 6.8 months, respectively, with large interpatient variability. Earliest repopulations occurred with the lowest doses. Significant reduction between pre- and post-rituximab annualized relapse rate (ARR) was observed (p = 0.003). During rituximab, 6 patients were relapse-free, although 21 relapses occurred in 10 patients, including 13 "repopulation," 3 "depletion," and 4 "depletion failure" relapses. Of the 13 "repopulation" relapses, 4 had CD19 10-50 7 10(6) cells/L, 10 had inadequate monitoring ( 641 CD19 in the 4 months before relapses), and 5 had delayed redosing after repopulation detection. CONCLUSION: Rituximab is effective in relapse prevention, but B cell repopulation creates a risk of relapse. Redosing before B cell repopulation could reduce the relapse risk further. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that rituximab significantly reduces ARR in pediatric NMO/NMOSD. This study also demonstrates a relationship between B cell repopulation and relapses