The effect of baseline metabolic rate on pulmonary O₂ uptake kinetics during very heavy intensity exercise in boys and men

addresses: Children's Health and Exercise Research Centre, College of Life and Environmental Sciences, University of Exeter, UK.Copyright © 2012 Elsevier. NOTICE: this is the author’s version of a work that was accepted for publication in Respiratory Physiology and Neurobiology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Respiratory Physiology and Neurobiology, 2012, 180 (2-3), pp. 223 – 229 DOI: 10.1016/j.resp.2011.11.013This study tested the hypothesis that pulmonary VO₂ kinetics would be slowed during 'work-to-work' exercise in adults but not in children. Eight boys (mean age=12.5 ± 0.5 years) and nine men completed very heavy step transitions initiated from either 'unloaded' pedalling (U→VH) or unloaded-to-moderate cycling (i.e. U→M to M→VH). The phase II τ was significantly (p<0.05) lengthened in M→VH compared to U→M and U→VH in boys (30 ± 5 vs. 19 ± 5 vs. 21 ± 5 s) and men (49 ± 14 vs. 30 ± 5 vs. 34 ± 8 s). In U→VH, a greater relative VO₂ slow component temporally coincided with an increased linear iEMG slope in men compared boys (VO₂ slow component: 16 ± 3 vs. 11 ± 4%; iEMG slope: 0.19 ± 0.24 vs. -0.06 ± 0.14%, p<0.05). These results suggest that an age-linked modulation of VO₂ kinetics might be influenced by alterations in muscle fibre recruitment following the onset of exercise

Enhanced muscimol-induced behavioral responses after 6-OHDA lesions: relevance to susceptibility for self-mutilation behavior in neonatally lesioned rats

Adult rats lesioned with 6-hydroxydopamine (6-OHDA), either as neonates or as adults, demonstrated increased turning, compared to unlesioned controls, when muscimol was unilaterally microinjected into the substantia nigra reticulata (SNR). At the higher doses of muscimol, the lesioned rats were so intensely lateralized that circling was impeded. These data suggest a functional supersensitivity of receptors associated with GABA function in the SNR of 6-OHDA-lesioned rats. When 30 ng muscimol was administered bilaterally into the SNR, self-mutilation behavior (SMB) was observed in 2/11 of the control unlesioned rats, in 0/8 adult 6-OHDA-lesioned rats, and in 11/11 of the neonatally-lesioned rats tested. The ability of muscimol to produce SMB in the rats lesioned as neonates was dose related. Behavioral observations indicated that behaviors associated with SMB (self-biting and taffy pulling) were present in neonatal, but not adult lesioned rats. Behavioral responses to dopamine agonist administration were also different between rats lesioned as neonates and those lesioned as adults with 6-OHDA. These data support the view that lesions of dopaminergic neurons cause an increased functional responsiveness of receptors acted upon by muscimol in the SNR, and that the increased susceptibility for SMB in neonatally lesioned rats is determined by neurons distal to the GABA receptor complex in the SNR

Early postnatal administration of 5,7-dihydroxytryptamine: Effects on substance P and thyrotropin-releasing hormone neurons and terminals in rat brain

Substance P, thyrotropin-releasing hormone (TRH) and serotonin are putative neurotransmitters which have been proposed to coexist in some brain neurons Our previous immunocytochemical and biochemical studies have demonstrated that 85–100% of all serotonin neurons are destroyed following neonatal 5,7-dihydroxtryptamine (5,7-DHT) treatment In this study, we have determined the effect of neonatal 5,7-DHT and desipramine (DMI) treatment on the biochemical content and immunocytochemical localization of substance P and TRH throughout the brain Interestingly, we have observed that virtually all substance P- and TRH-immunoreactive cells in the ventral pons-medulla are destroyed by the neurotoxin. However, peptide-containing neurons in other regions were not affected Additionally, we measured the peptide content and found that TRH is significantly decreased in the spinal cord (−50%) and pons-medulla (−20%), but not in other brain regions Substance P content was not significantly altered in any region, even after a greater than 90% reduction of serotonin These data indicate that the co-localized substance P and TRH forms a small proportion of the total peptide in brai

6-Hydroxydopamine Treatments Enhance Behavioral Responses to Intracerebral Microinjection of D1- and D2-Dopamine Agonists into Nucleus Accumbens and Striatum Without Changing Dopamine Antagonist Binding

Behavioral responses to D1 and D2-dopamine agonists are enhanced when these agonists are administered systemically to 6-hydroxydopamine (6-OHDA)-lesioned rats. In the present investigation, microinjection of SKF-38393, a D1-dopamine agonist, into the nucleus accumbens of adult rats lesioned as neonates with 6-OHDA produced a dose-related increase in locomotor activity that was enhanced markedly compared to control. LY-171555, a D2-agonist, elicited less locomotor activity than did SKF-38393 after microinjection into this site. Administration of SKF-38393 or LY-171555 into the nucleus accumbens did not increase locomotion in unlesioned rats at the doses administered to lesioned animals. In adult-6-OHDA-lesioned rats, microinjection of SKF-38393 into the nucleus accumbens also increased locomotion more than did LY-171555. As described previously, systemic administration of SKF-38393 produced little locomotion in adult-6-OHDA-lesioned rats, whereas LY-171555 produced a markedly enhanced response. Administration of SKF-38393 or LY-171555 into the caudate nucleus of neonatally and adult-6-OHDA-lesioned rats produced negligible locomotor activity, but did induce stereotypic behaviors similar to those observed after systemic treatment with these drugs. Stereotypic behaviors occurred to a greater degree in the 6-OHDA-lesioned rats than in unlesioned controls. A regional specificity for certain behaviors induced by dopamine agonist administration was observed. In spite of the enhanced behavioral responses of D1 and D2-dopamine agonists after microinjection into the brain of 6-OHDA-lesioned rats, binding of [3H]spiperone (D2-receptor antagonist ligand) and [3H]SCH 23390 (D1-receptor antagonist ligand) to tissue from striatum and nucleus accumbens was not altered significantly. In contrast to this lack of change in binding characteristics in 6-OHDA-lesioned rats, blockade of dopaminergic transmission with haloperidol treatment caused an elevation of [3H]spiperone binding sites in striatum without affecting affinity for the site. However, chronic haloperidol treatment did not alter significantly [3H]SCH 23390 binding to striatal membranes. These latter findings suggest that chronic dopamine receptor blockade need not produce the same adaptive mechanisms as destruction of dopamine-containing neurons. Thus, a change in receptor characteristics as measured by dopamine antagonist binding does not account for the behavioral supersensitivity observed after D1- and D2-dopamine agonist administration to neonatally or adult-6-OHDA-treated rats

The realistic performance achievable with mycobacterial automated culture systems in high and low prevalence settings

<p>Abstract</p> <p>Background</p> <p>Diagnostic tests are generally used in situations with similar pre-test probability of disease to where they were developed. When these tests are applied in situations with very different pre-test probabilities of disease, it is informative to model the likely implications of known characteristics of test performance in the new situation. This is the case for automated <it>Mycobacterium tuberculosis </it>(MTB) liquid culture systems for tuberculosis case detection which were developed and are widely used in low burden settings but are only beginning to be applied on a large scale in high burden settings.</p> <p>Methods</p> <p>Here we model the performance of MTB liquid culture systems in high and low tuberculosis (TB) prevalence settings using detailed published data concentrating on the likely frequency of cross-contamination events.</p> <p>Results</p> <p>Our model predicts that as the TB prevalence in the suspect population increases there is an exponential increase in the risk of MTB cross-contamination events expected in otherwise negative samples, even with equivalent technical performance of the laboratories. Quality control and strict cross-contamination measures become increasingly critical as the burden of MTB infection among TB suspects increases. Even under optimal conditions the realistically achievable specificity of these systems in high burden settings will likely be significantly below that obtained in low TB burden laboratories.</p> <p>Conclusions</p> <p>Liquid culture systems can play a valuable role in TB case detection in laboratories in high burden settings, but laboratory workers, policy makers and clinicians should be aware of the increased risks, independent of laboratory proficiency, of cross-contamination events in high burden settings.</p

Alt Event Finder: a tool for extracting alternative splicing events from RNA-seq data.

BACKGROUND: Alternative splicing increases proteome diversity by expressing multiple gene isoforms that often differ in function. Identifying alternative splicing events from RNA-seq experiments is important for understanding the diversity of transcripts and for investigating the regulation of splicing. RESULTS: We developed Alt Event Finder, a tool for identifying novel splicing events by using transcript annotation derived from genome-guided construction tools, such as Cufflinks and Scripture. With a proper combination of alignment and transcript reconstruction tools, Alt Event Finder is capable of identifying novel splicing events in the human genome. We further applied Alt Event Finder on a set of RNA-seq data from rat liver tissues, and identified dozens of novel cassette exon events whose splicing patterns changed after extensive alcohol exposure. CONCLUSIONS: Alt Event Finder is capable of identifying de novo splicing events from data-driven transcript annotation, and is a useful tool for studying splicing regulation

Mapping quantitative trait Loci for resistance to downy mildew in pearl millet: field and glasshouse screens detect the same QTL

Downy mildew, caused by the pathogen Sclerospora graminicola (Sacc.) J. Schrot, can cause devastating yield losses in pearl millet [Pennisetum glaucum (L.) R. Br.]. Breeding for resistance to downy mildew is facilitated by an artificial glasshouse screening method that can be used worldwide. Quantitative trait loci (QTLs) mapping was used to determine whether resistance QTLs identified under field conditions in India were also detected in glasshouse screens carried out in India and the UK. Quantitative trait loci were mapped using 114 individual pearl millet progeny derived from a resistant x susceptible cross: molecular marker mapping was carried out in an F2 population with restriction fragment length polymorphisms (RFLPs), and disease incidence was assessed on F4 families. Composite interval mapping (CIM) was used to detect associations between F4 family means and marker genotypes. Despite key environmental and methodological differences between the disease screens, the same two QTLs were detected in each screening environment. One QTL had a major effect and explained up to 60% of the phenotypic variation, while the other had a minor effect and explained up to 16% of the phenotypic variation. Two additional QTLs were also consistently detected across screens by examining pair-wise marker interactions. Multiple-trait interval mapping detected all of the QTLs that had been detected in individual screens, including the QTLs that had only been detected by examining pair-wise marker interactions, demonstrating its increased power over single trait mapping. Quantitative trait locus x environment interactions were significant at each QTL due to differences in the magnitude, rather than direction, of QTL effects. The differences in magnitude appeared to be a consequence of the degree of normality of the disease distribution, rather than any differences between screening methods

Teamwork delivers biotechnology products to Indian small-holder crop-livestock producers: Pearl millet hybrid “HHB 67 Improved” enters seed delivery pipeline

HHB 67, released in 1990 by CCS Haryana Agricultural University, is one such single-cross pearl millet hybrid. HHB 67 is highly popular because of its extra-early maturity (it needs less than 65 days from sowing to grain maturity) and is now grown on over 500 000 ha in Haryana and Rajasthan, India. Recent surveys have indicated that this hybrid is starting to succumb to downy mildew (DM; caused by the pseudo-fungus Sclerospora graminicola), showing up to 30% incidence in farmers' fields. By rapidly adopting hybrid "HHB 67 Improved", farmers in Haryana and Rajasthan can avoid grain production losses of Rs36 crores (US$8 million) which would be expected in the first year of a major DM outbreak on the original HHB 67