238 research outputs found

    The effect of previous wingate performance using one body region on subsequent wingate performance using a different body region

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    The 30 second Wingate Anaerobic Test (WAnT) is the gold standard measure of anaerobic performance. The present investigation aimed to determine if a previous WAnT using one body region significantly affected a subsequent WAnT using a different body region. Twelve male university students (n = 12, 23 ± 2 years, 84 ± 16.1 kg, 178.5 ± 7.4 cm) volunteered to complete two repeated WAnT protocols (either lower body WAnT followed by an upper body WAnTor vice versa) on two separate testing occasions. The upper body WAnT was conducted on a modified electromagnetically braked cycle ergometer using a flywheel braking force corresponding to 5% bodyweight. The lower body WAnT was conducted on an electronically braked cycle ergometer using a flywheel braking force corresponding to 7.5% bodyweight. Participants had a 1 minute rest period for transition between WAnTs. Data are reported as mean ± standard deviation. No significant differences were identified in power indices for the lower body between 30 s WAnTs. When the upper body WAnT was performed 2nd, absolute peak power (p < 0.01), mean power (p < 0.001) and relative mean power (p < 0.001) were significantly lower compared to when the upper body WAnT was performed 1st. The value of maximum revolutions per minute was significantly lower (p < 0.001) when the upper body WAnT was performed after the lower body WAnT, compared to when it was performed 1st (193.3 ± 11.4 1st vs 179.8 ± 14.4 2nd). Previous upper body sprint exercise does not significantly affect lower body sprint exercise; however, previous lower body sprint exercise severely compromises subsequent upper body sprint performance

    Acquired neuromyotonia in children with CASPR2 and LGI1 antibodies

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    Acquired neuromyotonia is a form of peripheral nerve hyperexcitability. In adults, pathogenic antibodies that target the extracellular domains of leucine-rich glioma-inactivated protein 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) have been reported. We describe three paediatric patients with acquired neuromyotonia and CASPR2 and LGI1 serum antibodies. They all presented with acute-onset myokymia and pain in the lower limbs; one patient also had muscle weakness. Electromyography was suggestive of peripheral nerve hyperexcitability. Two patients improved without immunotherapy; one treated patient remained immunotherapy-dependent. Although not fatal, acquired paediatric neuromyotonia can be disabling. It is amenable to symptomatic treatment or may undergo spontaneous recovery. More severe cases may require rational immunotherapy. What this paper adds: The symptoms of neuromyotonia may resolve spontaneously or may require sodium channel blockers. Patients with debilitating symptoms who are refractory to symptomatic therapy may require immunotherapy

    Developing lithium chemistry of 1,2-dihydropyridines : from kinetic intermediates to isolable characterized compounds

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    Generally considered kinetic intermediates in addition reactions of alkyllithiums to pyridine, 1-lithio-2-alkyl-1,2-dihydropyridines have been rarely isolated or characterized. This study develops their "isolated" chemistry. By a unique stoichiometric (that is 1:1, alkyllithium:pyridine ratios) synthetic approach using tridentate donors we show it is possible to stabilize and hence crystallize monomeric complexes where alkyl is tert-butyl. Theoretical calculations probing the donor-free parent tert-butyl species reveal 12 energetically similar stereoisomers in two distinct cyclotrimeric (LiN)3 conformations. NMR studies (including DOSY spectra) and thermal volatility analysis compare new sec-butyl and iso-butyl isomers showing the former is a hexane soluble efficient hydrolithiation agent converting benzophenone to lithium diphenylmethoxide. Emphasizing the criticalness of stoichiometry, reaction of nBuLi/Me6TREN with two equivalents of pyridine results in non-alkylated 1-lithio-1,4-dihydropyridine·Me6TREN and 2-n-butylpyridine, implying mechanistically the kinetic 1,2-n-butyl intermediate hydrolithiates the second pyridine

    Neutralization of Diverse Human Cytomegalovirus Strains Conferred by Antibodies Targeting Viral gH/gL/pUL128-131 Pentameric Complex

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    Human cytomegalovirus (HCMV) is the leading cause of congenital viral infection, and developing a prophylactic vaccine is of high priority to public health. We recently reported a replication-defective human cytomegalovirus with restored pentameric complex glycoprotein H (gH)/gL/pUL128-131 for prevention of congenital HCMV infection. While the quantity of vaccine-induced antibody responses can be measured in a viral neutralization assay, assessing the quality of such responses, including the ability of vaccine-induced antibodies to cross-neutralize the field strains of HCMV, remains a challenge. In this study, with a panel of neutralizing antibodies from three healthy human donors with natural HCMV infection or a vaccinated animal, we mapped eight sites on the dominant virus-neutralizing antigen-the pentameric complex of glycoprotein H (gH), gL, and pUL128, pUL130, and pUL131. By evaluating the site-specific antibodies in vaccine immune sera, we demonstrated that vaccination elicited functional antiviral antibodies to multiple neutralizing sites in rhesus macaques, with quality attributes comparable to those of CMV hyperimmune globulin. Furthermore, these immune sera showed antiviral activities against a panel of genetically distinct HCMV clinical isolates. These results highlighted the importance of understanding the quality of vaccine-induced antibody responses, which includes not only the neutralizing potency in key cell types but also the ability to protect against the genetically diverse field strains. IMPORTANCE HCMV is the leading cause of congenital viral infection, and development of a preventive vaccine is a high public health priority. To understand the strain coverage of vaccine-induced immune responses in comparison with natural immunity, we used a panel of broadly neutralizing antibodies to identify the immunogenic sites of a dominant viral antigen-the pentameric complex. We further demonstrated that following vaccination of a replication-defective virus with the restored pentameric complex, rhesus macaques can develop broadly neutralizing antibodies targeting multiple immunogenic sites of the pentameric complex. Such analyses of site-specific antibody responses are imperative to our assessment of the quality of vaccine-induced immunity in clinical studies

    The genetic map and comparative analysis with the physical map of Trypanosoma brucei

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    Trypanosoma brucei is the causative agent of African sleeping sickness in humans and contributes to the debilitating disease ‘Nagana’ in cattle. To date we know little about the genes that determine drug resistance, host specificity, pathogenesis and virulence in these parasites. The availability of the complete genome sequence and the ability of the parasite to undergo genetic exchange have allowed genetic investigations into this parasite and here we report the first genetic map of T.brucei for the genome reference stock TREU 927, comprising of 182 markers and 11 major linkage groups, that correspond to the 11 previously identified chromosomes. The genetic map provides 90% probability of a marker being 11 cM from any given locus. Its comparison to the available physical map has revealed the average physical size of a recombination unit to be 15.6 Kb/cM. The genetic map coupled with the genome sequence and the ability to undertake crosses presents a new approach to identifying genes relevant to the disease and its prevention in this important pathogen through forward genetic analysis and positional cloning
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