Inspiratory muscle training reduces blood lactate concentration during volitional hyperpnoea

Although reduced blood lactate concentrations ([lac−]B) have been observed during whole-body exercise following inspiratory muscle training (IMT), it remains unknown whether the inspiratory muscles are the source of at least part of this reduction. To investigate this, we tested the hypothesis that IMT would attenuate the increase in [lac−]B caused by mimicking, at rest, the breathing pattern observed during high-intensity exercise. Twenty-two physically active males were matched for 85% maximal exercise minute ventilation (V˙Emax) and divided equally into an IMT or a control group. Prior to and following a 6 week intervention, participants performed 10 min of volitional hyperpnoea at the breathing pattern commensurate with 85% V˙Emax

Childhood Incident Asthma and Traffic-Related Air Pollution at Home and School

Background: Traffic-related air pollution has been associated with adverse cardiorespiratory effects, including increased asthma prevalence. However, there has been little study of effects of traffic exposure at school on new-onset asthma. Objectives: We evaluated the relationship of new-onset asthma with traffic-related pollution near homes and schools. Methods: Parent-reported physician diagnosis of new-onset asthma (n = 120) was identified during 3 years of follow-up of a cohort of 2,497 kindergarten and first-grade children who were asthma- and wheezing-free at study entry into the Southern California Children's Health Study. We assessed traffic-related pollution exposure based on a line source dispersion model of traffic volume, distance from home and school, and local meteorology. Regional ambient ozone, nitrogen dioxide (NO2), and particulate matter were measured continuously at one central site monitor in each of 13 study communities. Hazard ratios (HRs) for new-onset asthma were scaled to the range of ambient central site pollutants and to the residential interquartile range for each traffic exposure metric. Results: Asthma risk increased with modeled traffic-related pollution exposure from roadways near homes [HR 1.51; 95% confidence interval (CI), 1.25-1.82] and near schools (HR 1.45; 95% CI, 1.06-1.98). Ambient NO2 measured at a central site in each community was also associated with increased risk (HR 2.18; 95% CI, 1.18-4.01). In models with both NO2 and modeled traffic exposures, there were independent associations of asthma with traffic-related pollution at school and home, whereas the estimate for NO2 was attenuated (HR 1.37; 95% CI, 0.69-2.71). Conclusions: Traffic-related pollution exposure at school and homes may both contribute to the development of asthma. Editor's SummaryTraffic-related air pollution has been associated with adverse cardiorespiratory effects, including increased asthma prevalence. McConnell et al. (p. 1021) evaluated the relationship of new-onset asthma with traffic-related pollution near homes and schools. Parent-reported physician diagnosis of new-onset asthma was identified during 3 years of follow-up of a cohort of kindergarten and first-grade children who were asthma- and wheezing-free at study entry into the Southern California Children's Health Study. Traffic-related pollution exposure was assessed based on a line source dispersion model of traffic volume, distance from home and school, and local meteorology. Regional ambient ozone, nitrogen dioxide (NO2), and particulate matter were measured continuously at one central site monitor in each of 13 study communities. The authors report an increase in asthma risk with modeled traffic-related pollution exposure from roadways near homes and schools. Ambient NO2 was also associated with increased risk. Models that included both NO2 and modeled traffic exposures suggested independent associations of asthma with traffic-related pollution at school and at home, whereas the estimate for NO2 was attenuated. The authors conclude that traffic-related pollution exposure at school and home may both contribute to the development of asthma

High energy emission from microquasars

The microquasar phenomenon is associated with the production of jets by X-ray binaries and, as such, may be associated with the majority of such systems. In this chapter we briefly outline the associations, definite, probable, possible, and speculative, between such jets and X-ray, gamma-ray and particle emission.Comment: Contributing chapter to the book Cosmic Gamma-Ray Sources, K.S. Cheng and G.E. Romero (eds.), to be published by Kluwer Academic Publishers, Dordrecht, 2004. (19 pages

Mouse nuclear myosin I knock-out shows interchangeability and redundancy of myosin isoforms in the cell nucleus.

Nuclear myosin I (NM1) is a nuclear isoform of the well-known "cytoplasmic" Myosin 1c protein (Myo1c). Located on the 11(th) chromosome in mice, NM1 results from an alternative start of transcription of the Myo1c gene adding an extra 16 amino acids at the N-terminus. Previous studies revealed its roles in RNA Polymerase I and RNA Polymerase II transcription, chromatin remodeling, and chromosomal movements. Its nuclear localization signal is localized in the middle of the molecule and therefore directs both Myosin 1c isoforms to the nucleus. In order to trace specific functions of the NM1 isoform, we generated mice lacking the NM1 start codon without affecting the cytoplasmic Myo1c protein. Mutant mice were analyzed in a comprehensive phenotypic screen in cooperation with the German Mouse Clinic. Strikingly, no obvious phenotype related to previously described functions has been observed. However, we found minor changes in bone mineral density and the number and size of red blood cells in knock-out mice, which are most probably not related to previously described functions of NM1 in the nucleus. In Myo1c/NM1 depleted U2OS cells, the level of Pol I transcription was restored by overexpression of shRNA-resistant mouse Myo1c. Moreover, we found Myo1c interacting with Pol II. The ratio between Myo1c and NM1 proteins were similar in the nucleus and deletion of NM1 did not cause any compensatory overexpression of Myo1c protein. We observed that Myo1c can replace NM1 in its nuclear functions. Amount of both proteins is nearly equal and NM1 knock-out does not cause any compensatory overexpression of Myo1c. We therefore suggest that both isoforms can substitute each other in nuclear processes

Fundamental Limits on Wavelength, Efficiency and Yield of the Charge Separation Triad

In an attempt to optimize a high yield, high efficiency artificial photosynthetic protein we have discovered unique energy and spatial architecture limits which apply to all light-activated photosynthetic systems. We have generated an analytical solution for the time behavior of the core three cofactor charge separation element in photosynthesis, the photosynthetic cofactor triad, and explored the functional consequences of its makeup including its architecture, the reduction potentials of its components, and the absorption energy of the light absorbing primary-donor cofactor. Our primary findings are two: First, that a high efficiency, high yield triad will have an absorption frequency more than twice the reorganization energy of the first electron transfer, and second, that the relative distance of the acceptor and the donor from the primary-donor plays an important role in determining the yields, with the highest efficiency, highest yield architecture having the light absorbing cofactor closest to the acceptor. Surprisingly, despite the increased complexity found in natural solar energy conversion proteins, we find that the construction of this central triad in natural systems matches these predictions. Our analysis thus not only suggests explanations for some aspects of the makeup of natural photosynthetic systems, it also provides specific design criteria necessary to create high efficiency, high yield artificial protein-based triads

Spatial Variation in Foraging Behaviour of a Marine Top Predator (Phoca vitulina) Determined by a Large-Scale Satellite Tagging Program

The harbour seal (Phoca vitulina) is a widespread marine predator in Northern Hemisphere waters. British populations have been subject to rapid declines in recent years. Food supply or inter-specific competition may be implicated but basic ecological data are lacking and there are few studies of harbour seal foraging distribution and habits. In this study, satellite tagging conducted at the major seal haul outs around the British Isles showed both that seal movements were highly variable among individuals and that foraging strategy appears to be specialized within particular regions. We investigated whether these apparent differences could be explained by individual level factors: by modelling measures of trip duration and distance travelled as a function of size, sex and body condition. However, these were not found to be good predictors of foraging trip duration or distance, which instead was best predicted by tagging region, time of year and inter-trip duration. Therefore, we propose that local habitat conditions and the constraints they impose are the major determinants of foraging movements. Specifically the distance to profitable feeding grounds from suitable haul-out locations may dictate foraging strategy and behaviour. Accounting for proximity to productive foraging resources is likely to be an important component of understanding population processes. Despite more extensive offshore movements than expected, there was also marked fidelity to the local haul-out region with limited connectivity between study regions. These empirical observations of regional exchange at short time scales demonstrates the value of large scale electronic tagging programs for robust characterization of at-sea foraging behaviour at a wide spatial scale

Intra-colony channels in E. coli function as a nutrient uptake system

The ability of microorganisms to grow as aggregated assemblages has been known for many years, however their structure has remained largely unexplored across multiple spatial scales. The development of the Mesolens, an optical system which uniquely allows simultaneous imaging of individual bacteria over a 36 mm2 field of view, has enabled the study of mature Escherichia coli macro-colony biofilm architecture like never before. The Mesolens enabled the discovery of intra-colony channels on the order of 10 μm in diameter, that are integral to E. coli macro-colony biofilms and form as an emergent property of biofilm growth. These channels have a characteristic structure and re-form after total mechanical disaggregation of the colony. We demonstrate that the channels are able to transport particles and play a role in the acquisition of and distribution of nutrients through the biofilm. These channels potentially offer a new route for the delivery of dispersal agents for antimicrobial drugs to biofilms, ultimately lowering their impact on public health and industry

A Fiber-Optic Fluorescence Microscope Using a Consumer-Grade Digital Camera for In Vivo Cellular Imaging

BACKGROUND: Early detection is an essential component of cancer management. Unfortunately, visual examination can often be unreliable, and many settings lack the financial capital and infrastructure to operate PET, CT, and MRI systems. Moreover, the infrastructure and expense associated with surgical biopsy and microscopy are a challenge to establishing cancer screening/early detection programs in low-resource settings. Improvements in performance and declining costs have led to the availability of optoelectronic components, which can be used to develop low-cost diagnostic imaging devices for use at the point-of-care. Here, we demonstrate a fiber-optic fluorescence microscope using a consumer-grade camera for in vivo cellular imaging. METHODS: The fiber-optic fluorescence microscope includes an LED light, an objective lens, a fiber-optic bundle, and a consumer-grade digital camera. The system was used to image an oral cancer cell line labeled with 0.01% proflavine. A human tissue specimen was imaged following surgical resection, enabling dysplastic and cancerous regions to be evaluated. The oral mucosa of a healthy human subject was imaged in vivo, following topical application of 0.01% proflavine. FINDINGS: The fiber-optic microscope resolved individual nuclei in all specimens and tissues imaged. This capability allowed qualitative and quantitative differences between normal and precancerous or cancerous tissues to be identified. The optical efficiency of the system permitted imaging of the human oral mucosa in real time. CONCLUSION: Our results indicate this device as a useful tool to assist in the identification of early neoplastic changes in epithelial tissues. This portable, inexpensive unit may be particularly appropriate for use at the point-of-care in low-resource settings

Pediatricians and nutritionists knowledge about treatment of cow milk allergy in infants

OBJECTIVE: Evaluate the knowledge of pediatricians and nutritionists regarding the exclusion diet of cow milk and derivates, with emphasis on questions related to the nutrition of children submitted to such diet. METHODS: Cross-sectional study that enrolled pediatricians (n=53) and nutritionists (n=29) from public hospitals in São Paulo, Brazil, during 2005. Data was collected through self-administered questionnaires. RESULTS: The age of the professionals varied from 21 to 50 years old. Regarding professional experience, 41.2% were graduated for less than five years and 91.6% had a specialization course, masters and/or PhD degree. The vast majority of professionals (97.5%) confirmed that they regularly evaluated the diet of children that needed exclusion of cow milk. However, only 48% of the professionals conducted a more detailed evaluation of the diet, including calculations of food ingestion. Only 38.7% of the professionals compared child s food ingestion with some recommended pattern. Recommendations for daily ingestion of calcium by children up to the age of 36 months were properly mentioned by 22% of the pediatricians and 60.7% of the nutritionists (p=0.001). Inadequate cow milk substitute products were recommended by 66% of the pediatricians and by 48.3% of the nutritionists. Regarding labels of industrialized products, 81.6% of the pediatricians and 96.4% of the nutritionists advised the parents to look for all terms that could indicate the presence of cow milk protein. CONCLUSIONS: Pediatricians and nutritionists made conceptual errors in their main recommendations regarding the treatment of cow milk protein allergy.OBJETIVO: Avaliar o conhecimento de pediatras e nutricionistas sobre a dieta de exclusão do leite de vaca e seus derivados, com ênfase em questões relacionadas à nutrição da criança. MÉTODOS: Estudo transversal descritivo, do qual participaram pediatras (n=53) e nutricionistas (n=29), vinculados a hospitais públicos do Município de São Paulo, no ano de 2005. Os dados foram coletados por questionário auto-administrado. RESULTADOS: A idade dos profissionais variou de 21 a 50 anos. Quanto ao tempo de graduação, 41,2% eram formados a menos de cinco anos e 91,6% possuíam especialização, mestrado e/ou doutorado. A maioria (97,5%) afirmou avaliar a dieta de crianças submetidas à exclusão do leite de vaca, entretanto, somente 48% o faziam de forma mais detalhadas, incluindo o cálculo da ingestão alimentar. Apenas 38,7% comparam a ingestão alimentar da criança com algum padrão de recomendação. A recomendação diária da ingestão de cálcio para crianças com até 36 meses foi corretamente assinalada por 22% dos pediatras e 60,7% dos nutricionistas (p=0,001). Produtos não adequados como substitutos do leite de vaca seriam recomendados por 66% dos pediatras e 48,3% dos nutricionistas. Com relação à leitura de rótulos de produtos industrializados, 81,6% dos pediatras e 96,4% dos nutricionistas orientam os pais a ler todos os termos que indicam a presença das proteínas do leite de vaca. CONCLUSÕES: Os pediatras e nutricionista demonstraram erro conceitual no que se refere às principais recomendações terapêuticas na alergia às proteínas do leite de vaca.Universidade Federal de São Paulo (UNIFESP)UNIFESPUNIFESPSciEL

A Network of Conserved Damage Survival Pathways Revealed by a Genomic RNAi Screen

Damage initiates a pleiotropic cellular response aimed at cellular survival when appropriate. To identify genes required for damage survival, we used a cell-based RNAi screen against the Drosophila genome and the alkylating agent methyl methanesulphonate (MMS). Similar studies performed in other model organisms report that damage response may involve pleiotropic cellular processes other than the central DNA repair components, yet an intuitive systems level view of the cellular components required for damage survival, their interrelationship, and contextual importance has been lacking. Further, by comparing data from different model organisms, identification of conserved and presumably core survival components should be forthcoming. We identified 307 genes, representing 13 signaling, metabolic, or enzymatic pathways, affecting cellular survival of MMS–induced damage. As expected, the majority of these pathways are involved in DNA repair; however, several pathways with more diverse biological functions were also identified, including the TOR pathway, transcription, translation, proteasome, glutathione synthesis, ATP synthesis, and Notch signaling, and these were equally important in damage survival. Comparison with genomic screen data from Saccharomyces cerevisiae revealed no overlap enrichment of individual genes between the species, but a conservation of the pathways. To demonstrate the functional conservation of pathways, five were tested in Drosophila and mouse cells, with each pathway responding to alkylation damage in both species. Using the protein interactome, a significant level of connectivity was observed between Drosophila MMS survival proteins, suggesting a higher order relationship. This connectivity was dramatically improved by incorporating the components of the 13 identified pathways within the network. Grouping proteins into “pathway nodes” qualitatively improved the interactome organization, revealing a highly organized “MMS survival network.” We conclude that identification of pathways can facilitate comparative biology analysis when direct gene/orthologue comparisons fail. A biologically intuitive, highly interconnected MMS survival network was revealed after we incorporated pathway data in our interactome analysis