Redox balance is key to explaining full vs. partial switching to low-yield metabolism

<p>Abstract</p> <p>Background</p> <p>Low-yield metabolism is a puzzling phenomenon in many unicellular and multicellular organisms. In abundance of glucose, many cells use a highly wasteful fermentation pathway despite the availability of a high-yield pathway, producing many ATP molecules per glucose, <it>e.g</it>., oxidative phosphorylation. Some of these organisms, including the lactic acid bacterium <it>Lactococcus lactis</it>, downregulate their high-yield pathway in favor of the low-yield pathway. Other organisms, including <it>Escherichia coli </it>do not reduce the flux through the high-yield pathway, employing the low-yield pathway in parallel with a fully active high-yield pathway. For what reasons do some species use the high-yield and low-yield pathways concurrently and what makes others downregulate the high-yield pathway? A classic rationale for metabolic fermentation is overflow metabolism. Because the throughput of metabolic pathways is limited, influx of glucose exceeding the pathway's throughput capacity is thought to be redirected into an alternative, low-yield pathway. This overflow metabolism rationale suggests that cells would only use fermentation once the high-yield pathway runs at maximum rate, but it cannot explain why cells would decrease the flux through the high-yield pathway.</p> <p>Results</p> <p>Using flux balance analysis with molecular crowding (FBAwMC), a recent extension to flux balance analysis (FBA) that assumes that the total flux through the metabolic network is limited, we investigate the differences between <it>Saccharomyces cerevisiae </it>and <it>L. lactis </it>that downregulate the high-yield pathway at increasing glucose concentrations, and <it>E. coli</it>, which keeps the high-yield pathway functioning at maximal rate. FBAwMC correctly predicts the metabolic switching mode in these three organisms, suggesting that metabolic network architecture is responsible for differences in metabolic switching mode. Based on our analysis, we expect gradual, "overflow-like" switching behavior in organisms that have an additional energy-yielding pathway that does not consume NADH (<it>e.g</it>., acetate production in <it>E. coli</it>). Flux decrease through the high-yield pathway is expected in organisms in which the high-yield and low-yield pathways compete for NADH. In support of this analysis, a simplified model of metabolic switching suggests that the extra energy generated during acetate production produces an additional optimal growth mode that smoothens the metabolic switch in <it>E. coli</it>.</p> <p>Conclusions</p> <p>Maintaining redox balance is key to explaining why some microbes decrease the flux through the high-yield pathway, while other microbes use "overflow-like" low-yield metabolism.</p

Epidemiology of Coxiella burnetii infection in Africa: a OneHealth systematic review

Background: Q fever is a common cause of febrile illness and community-acquired pneumonia in resource-limited settings. Coxiella burnetii, the causative pathogen, is transmitted among varied host species, but the epidemiology of the organism in Africa is poorly understood. We conducted a systematic review of C. burnetii epidemiology in Africa from a “One Health” perspective to synthesize the published data and identify knowledge gaps.&lt;p&gt;&lt;/p&gt; Methods/Principal Findings: We searched nine databases to identify articles relevant to four key aspects of C. burnetii epidemiology in human and animal populations in Africa: infection prevalence; disease incidence; transmission risk factors; and infection control efforts. We identified 929 unique articles, 100 of which remained after full-text review. Of these, 41 articles describing 51 studies qualified for data extraction. Animal seroprevalence studies revealed infection by C. burnetii (&#8804;13%) among cattle except for studies in Western and Middle Africa (18–55%). Small ruminant seroprevalence ranged from 11–33%. Human seroprevalence was &#60;8% with the exception of studies among children and in Egypt (10–32%). Close contact with camels and rural residence were associated with increased seropositivity among humans. C. burnetii infection has been associated with livestock abortion. In human cohort studies, Q fever accounted for 2–9% of febrile illness hospitalizations and 1–3% of infective endocarditis cases. We found no studies of disease incidence estimates or disease control efforts.&lt;p&gt;&lt;/p&gt; Conclusions/Significance: C. burnetii infection is detected in humans and in a wide range of animal species across Africa, but seroprevalence varies widely by species and location. Risk factors underlying this variability are poorly understood as is the role of C. burnetii in livestock abortion. Q fever consistently accounts for a notable proportion of undifferentiated human febrile illness and infective endocarditis in cohort studies, but incidence estimates are lacking. C. burnetii presents a real yet underappreciated threat to human and animal health throughout Africa.&lt;p&gt;&lt;/p&gt

The population of close double white dwarfs in the Galaxy

We present a new model for the Galactic population of close double white dwarfs. The model accounts for the suggestion of the avoidance of a substantial spiral-in during mass transfer between a giant and a main-sequence star of comparable mass and for detailed cooling models. It agrees well with the observations of the local sample of white dwarfs if the initial binary fraction is close to 50% and an ad hoc assumption is made that white dwarfs with mass less than about 0.3 solar mass cool faster than the models suggest. About 1000 white dwarfs brighter than V=15 have to be surveyed for detection of a pair which has total mass greater than the Chandrasekhar mass and will merge within 10 Gyr.Comment: 15 pages, 7 figures, to appear in Proc. ``The influence of binaries on stellar population studies'', Brussels, August 2000 (Kluwer, D. Vanbeveren ed.

Pre-cooling for endurance exercise performance in the heat: a systematic review.

PMCID: PMC3568721The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1741-7015/10/166. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Endurance exercise capacity diminishes under hot environmental conditions. Time to exhaustion can be increased by lowering body temperature prior to exercise (pre-cooling). This systematic literature review synthesizes the current findings of the effects of pre-cooling on endurance exercise performance, providing guidance for clinical practice and further research

Greenhouse gas emissions in The Netherlands 1990-2012 : National Inventory Report 2014

In 2012 is de totale uitstoot van broeikasgassen van Nederland, zoals CO2, methaan en lachgas, met ongeveer 1,7 procent gedaald ten opzichte van 2011. Deze daling komt vooral door een lager brandstofgebruik in de energie- en transportsector. Dit lijkt een gevolg van de economische recessie, waardoor emissies door elektriciteitsproductie en het wegtransport in Nederland zijn afgenomen. Cijfers De totale broeikasgasemissie wordt uitgedrukt in CO2-equivalenten en bedraagt in 2012 191,7 teragram (megaton of miljard kilogram) . Ten opzichte van de uitstoot in het Kyoto-basisjaar (213,2 Tg CO2-equivalenten) is dit een afname van ongeveer 10 procent. Het basisjaar, dat afhankelijk van het broeikasgas 1990 of 1995 is, dient voor het Kyoto-protocol als referentie voor de uitstoot van broeikasgassen. De uitstoot van de overige broeikasgassen zoals lachgas en methaan is sinds het basisjaar met 51 procent afgenomen. De CO2-uitstoot daarentegen is in deze periode met 4 procent gestegen. Landen zijn voor het Kyoto-protocol verplicht om de totale uitstoot van broeikasgassen op twee manieren te rapporteren: met en zonder het soort landgebruik en de verandering daarin. Dit is namelijk van invloed op de uitstoot van broeikasgassen. Voorbeelden zijn natuurontwikkeling (dat CO2 bindt) of ontbossing (waardoor CO2 wordt uitgestoten). In bovengenoemde getallen zijn deze zogeheten LULUCF-emissies (Land Use, Land Use Change and Forestry) niet meegenomen. Overige onderdelen inventarisatie Het RIVM stelt jaarlijks op verzoek van het Ministerie van Infrastructuur en Milieu (IenM) de inventarisatie van broeikasgasemissies op. De inventarisatie bevat trendanalyses om ontwikkelingen in de uitstoot van broeikasgassen tussen 1990 en 2012 te verklaren, en een analyse van de onzekerheid in deze getallen. Ook is aangegeven welke bronnen het meest aan deze onzekerheid bijdragen. Daarnaast biedt de inventarisatie documentatie van de gebruikte berekeningsmethoden, databronnen en toegepaste emissiefactoren. Met deze inventarisatie voldoet Nederland aan de nationale rapportageverplichtingen voor 2012 van het Klimaatverdrag van de Verenigde Naties (UNFCCC), van het Kyoto-Protocol en van het Bewakingsmechanisme Broeikasgassen van de Europese Unie.Total greenhouse gas emissions from the Netherlands in 2012 decreased by approximately 1.7 per cent, compared with 2011 emissions. This decrease is mainly the result of decreased fuel combustion in the Energy sector (increased electricity import) and in road transport. In 2012, total direct greenhouse gas emissions (excluding emissions from LULUCF - land use, land use change and forestry) in the Netherlands amounted to 191.7 Tg CO2 eq. This is approximately 10 per cent below the emissions in the base year (213.2 Tg CO2 eq.). The 51% reduction in the non-CO2 emissions in this period is counterbalanced by 4 per cent increase in CO2 emissions since 1990. This report documents the Netherlands' 2014 annual submission of its greenhouse gas emissions inventory in accordance with the guidelines provided by the United Nations Framework Convention on Climate Change (UNFCCC), the Kyoto Protocol and the European Union's Greenhouse Gas Monitoring Mechanism. The report comprises explanations of observed trends in emissions; a description of an assessment of key sources and their uncertainty; documentation of methods, data sources and emission factors applied; and a description of the quality assurance system and the verification activities performed on the data.Ministerie van I&

Ki67 expression levels are a better marker of reduced melanoma growth following MEK inhibitor treatment than phospho-ERK levels

The loss of tumour phospho-extracellular responsive kinase (pERK) positivity is the major treatment biomarker for mitogen-activated protein kinase/extracellular responsive kinase (MEK) inhibitors. Here, we demonstrate that there is a poor correlation between pERK inhibition and the anti-proliferative effects of MEK inhibitors in melanoma cells. We suggest that Ki67 is a better biomarker for future clinical studies

Eating Disorder Behaviors Are Increasing: Findings from Two Sequential Community Surveys in South Australia

Background: evidence for an increase in the prevalence of eating disorders is inconsistent. Our aim was to determine change in the population point prevalence of eating disorder behaviors over a 10-year period. \ud \ud Methodology/Principal Findings: eating disorder behaviors were assessed in consecutive general population surveys of men and women conducted in 1995 (n = 3001, 72% respondents) and 2005 (n = 3047, 63.1% respondents). Participants were randomly sampled from households in rural and metropolitan South Australia. There was a significant (all p,0.01) and over two-fold increase in the prevalence of binge eating, purging (self-induced vomiting and/or laxative or diuretic misuse) and strict dieting or fasting for weight or shape control among both genders. The most common diagnosis in 2005 was either binge eating disorder or other ‘‘eating\ud disorders not otherwise specified’’ (EDNOS; n = 119, 4.2%). \ud \ud Conclusions/Significance: in this population sample the point prevalence of eating disorder behaviors increased over the past decade. Cases of anorexia nervosa and bulimia nervosa, as currently defined, remain uncommon

Efficiency of two-phase methods with focus on a planned population-based case-control study on air pollution and stroke

<p>Abstract</p> <p>Background</p> <p>We plan to conduct a case-control study to investigate whether exposure to nitrogen dioxide (NO₂) increases the risk of stroke. In case-control studies, selective participation can lead to bias and loss of efficiency. A two-phase design can reduce bias and improve efficiency by combining information on the non-participating subjects with information from the participating subjects. In our planned study, we will have access to individual disease status and data on NO₂exposure on group (area) level for a large population sample of Scania, southern Sweden. A smaller sub-sample will be selected to the second phase for individual-level assessment on exposure and covariables. In this paper, we simulate a case-control study based on our planned study. We develop a two-phase method for this study and compare the performance of our method with the performance of other two-phase methods.</p> <p>Methods</p> <p>A two-phase case-control study was simulated with a varying number of first- and second-phase subjects. Estimation methods: <it>Method 1</it>: Effect estimation with second-phase data only. <it>Method 2</it>: Effect estimation by adjusting the first-phase estimate with the difference between the adjusted and unadjusted second-phase estimate. The first-phase estimate is based on individual disease status and residential address for all study subjects that are linked to register data on NO₂-exposure for each geographical area. <it>Method 3</it>: Effect estimation by using the expectation-maximization (EM) algorithm without taking area-level register data on exposure into account. <it>Method 4</it>: Effect estimation by using the EM algorithm and incorporating group-level register data on NO₂-exposure.</p> <p>Results</p> <p>The simulated scenarios were such that, unbiased or marginally biased (< 7%) odds ratio (OR) estimates were obtained with all methods. The efficiencies of method 4, are generally higher than those of methods 1 and 2. The standard errors in method 4 decreased further when the case/control ratio is above one in the second phase. For all methods, the standard errors do not become substantially reduced when the number of first-phase controls is increased.</p> <p>Conclusion</p> <p>In the setting described here, method 4 had the best performance in order to improve efficiency, while adjusting for varying participation rates across areas.</p

Influenza Virus Respiratory Infection and Transmission Following Ocular Inoculation in Ferrets

While influenza viruses are a common respiratory pathogen, sporadic reports of conjunctivitis following human infection demonstrates the ability of this virus to cause disease outside of the respiratory tract. The ocular surface represents both a potential site of virus replication and a portal of entry for establishment of a respiratory infection. However, the properties which govern ocular tropism of influenza viruses, the mechanisms of virus spread from ocular to respiratory tissue, and the potential differences in respiratory disease initiated from different exposure routes are poorly understood. Here, we established a ferret model of ocular inoculation to explore the development of virus pathogenicity and transmissibility following influenza virus exposure by the ocular route. We found that multiple subtypes of human and avian influenza viruses mounted a productive virus infection in the upper respiratory tract of ferrets following ocular inoculation, and were additionally detected in ocular tissue during the acute phase of infection. H5N1 viruses maintained their ability for systemic spread and lethal infection following inoculation by the ocular route. Replication-independent deposition of virus inoculum from ocular to respiratory tissue was limited to the nares and upper trachea, unlike traditional intranasal inoculation which results in virus deposition in both upper and lower respiratory tract tissues. Despite high titers of replicating transmissible seasonal viruses in the upper respiratory tract of ferrets inoculated by the ocular route, virus transmissibility to naïve contacts by respiratory droplets was reduced following ocular inoculation. These data improve our understanding of the mechanisms of virus spread following ocular exposure and highlight differences in the establishment of respiratory disease and virus transmissibility following use of different inoculation volumes and routes

Minute ventilation of cyclists, car and bus passengers: an experimental study

<p>Abstract</p> <p>Background</p> <p>Differences in minute ventilation between cyclists, pedestrians and other commuters influence inhaled doses of air pollution. This study estimates minute ventilation of cyclists, car and bus passengers, as part of a study on health effects of commuters' exposure to air pollutants.</p> <p>Methods</p> <p>Thirty-four participants performed a submaximal test on a bicycle ergometer, during which heart rate and minute ventilation were measured simultaneously at increasing cycling intensity. Individual regression equations were calculated between heart rate and the natural log of minute ventilation. Heart rates were recorded during 280 two hour trips by bicycle, bus and car and were calculated into minute ventilation levels using the individual regression coefficients.</p> <p>Results</p> <p>Minute ventilation during bicycle rides were on average 2.1 times higher than in the car (individual range from 1.3 to 5.3) and 2.0 times higher than in the bus (individual range from 1.3 to 5.1). The ratio of minute ventilation of cycling compared to travelling by bus or car was higher in women than in men. Substantial differences in regression equations were found between individuals. The use of individual regression equations instead of average regression equations resulted in substantially better predictions of individual minute ventilations.</p> <p>Conclusion</p> <p>The comparability of the gender-specific overall regression equations linking heart rate and minute ventilation with one previous American study, supports that for studies on the group level overall equations can be used. For estimating individual doses, the use of individual regression coefficients provides more precise data. Minute ventilation levels of cyclists are on average two times higher than of bus and car passengers, consistent with the ratio found in one small previous study of young adults. The study illustrates the importance of inclusion of minute ventilation data in comparing air pollution doses between different modes of transport.</p