Genetic variation and exercise-induced muscle damage: implications for athletic performance, injury and ageing.

Prolonged unaccustomed exercise involving muscle lengthening (eccentric) actions can result in ultrastructural muscle disruption, impaired excitation-contraction coupling, inflammation and muscle protein degradation. This process is associated with delayed onset muscle soreness and is referred to as exercise-induced muscle damage. Although a certain amount of muscle damage may be necessary for adaptation to occur, excessive damage or inadequate recovery from exercise-induced muscle damage can increase injury risk, particularly in older individuals, who experience more damage and require longer to recover from muscle damaging exercise than younger adults. Furthermore, it is apparent that inter-individual variation exists in the response to exercise-induced muscle damage, and there is evidence that genetic variability may play a key role. Although this area of research is in its infancy, certain gene variations, or polymorphisms have been associated with exercise-induced muscle damage (i.e. individuals with certain genotypes experience greater muscle damage, and require longer recovery, following strenuous exercise). These polymorphisms include ACTN3 (R577X, rs1815739), TNF (-308 G>A, rs1800629), IL6 (-174 G>C, rs1800795), and IGF2 (ApaI, 17200 G>A, rs680). Knowing how someone is likely to respond to a particular type of exercise could help coaches/practitioners individualise the exercise training of their athletes/patients, thus maximising recovery and adaptation, while reducing overload-associated injury risk. The purpose of this review is to provide a critical analysis of the literature concerning gene polymorphisms associated with exercise-induced muscle damage, both in young and older individuals, and to highlight the potential mechanisms underpinning these associations, thus providing a better understanding of exercise-induced muscle damage

Estimates of live-tree carbon stores in the Pacific Northwest are sensitive to model selection

<p>Abstract</p> <p>Background</p> <p>Estimates of live-tree carbon stores are influenced by numerous uncertainties. One of them is model-selection uncertainty: one has to choose among multiple empirical equations and conversion factors that can be plausibly justified as locally applicable to calculate the carbon store from inventory measurements such as tree height and diameter at breast height (DBH). Here we quantify the model-selection uncertainty for the five most numerous tree species in six counties of northwest Oregon, USA.</p> <p>Results</p> <p>The results of our study demonstrate that model-selection error may introduce 20 to 40% uncertainty into a live-tree carbon estimate, possibly making this form of error the largest source of uncertainty in estimation of live-tree carbon stores. The effect of model selection could be even greater if models are applied beyond the height and DBH ranges for which they were developed.</p> <p>Conclusions</p> <p>Model-selection uncertainty is potentially large enough that it could limit the ability to track forest carbon with the precision and accuracy required by carbon accounting protocols. Without local validation based on detailed measurements of usually destructively sampled trees, it is very difficult to choose the best model when there are several available. Our analysis suggests that considering tree form in equation selection may better match trees to existing equations and that substantial gaps exist, in terms of both species and diameter ranges, that are ripe for new model-building effort.</p

Estimating uncertainty in ecosystem budget calculations

© The Authors, 2010. This article is distributed under the terms of the Creative Commons Attribution-Noncommercial License. The definitive version was published in Ecosystems 13 (2010): 239-248, doi:10.1007/s10021-010-9315-8.Ecosystem nutrient budgets often report values for pools and fluxes without any indication of uncertainty, which makes it difficult to evaluate the significance of findings or make comparisons across systems. We present an example, implemented in Excel, of a Monte Carlo approach to estimating error in calculating the N content of vegetation at the Hubbard Brook Experimental Forest in New Hampshire. The total N content of trees was estimated at 847 kg ha−1 with an uncertainty of 8%, expressed as the standard deviation divided by the mean (the coefficient of variation). The individual sources of uncertainty were as follows: uncertainty in allometric equations (5%), uncertainty in tissue N concentrations (3%), uncertainty due to plot variability (6%, based on a sample of 15 plots of 0.05 ha), and uncertainty due to tree diameter measurement error (0.02%). In addition to allowing estimation of uncertainty in budget estimates, this approach can be used to assess which measurements should be improved to reduce uncertainty in the calculated values. This exercise was possible because the uncertainty in the parameters and equations that we used was made available by previous researchers. It is important to provide the error statistics with regression results if they are to be used in later calculations; archiving the data makes resampling analyses possible for future researchers. When conducted using a Monte Carlo framework, the analysis of uncertainty in complex calculations does not have to be difficult and should be standard practice when constructing ecosystem budgets

The kinome of Phytophthora infestans reveals oomycete-specific innovations and links to other taxonomic groups

<p>Abstract</p> <p>Background</p> <p>Oomycetes are a large group of economically and ecologically important species. Its most notorious member is <it>Phytophthora infestans</it>, the cause of the devastating potato late blight disease. The life cycle of <it>P. infestans </it>involves hyphae which differentiate into spores used for dispersal and host infection. Protein phosphorylation likely plays crucial roles in these stages, and to help understand this we present here a genome-wide analysis of the protein kinases of <it>P. infestans </it>and several relatives. The study also provides new insight into kinase evolution since oomycetes are taxonomically distant from organisms with well-characterized kinomes.</p> <p>Results</p> <p>Bioinformatic searches of the genomes of <it>P. infestans</it>, <it>P. ramorum</it>, and <it>P. sojae </it>reveal they have similar kinomes, which for <it>P. infestans </it>contains 354 eukaryotic protein kinases (ePKs) and 18 atypical kinases (aPKs), equaling 2% of total genes. After refining gene models, most were classifiable into families seen in other eukaryotes. Some ePK families are nevertheless unusual, especially the tyrosine kinase-like (TKL) group which includes large oomycete-specific subfamilies. Also identified were two tyrosine kinases, which are rare in non-metazoans. Several ePKs bear accessory domains not identified previously on kinases, such as cyclin-dependent kinases with integral cyclin domains. Most ePKs lack accessory domains, implying that many are regulated transcriptionally. This was confirmed by mRNA expression-profiling studies that showed that two-thirds vary significantly between hyphae, sporangia, and zoospores. Comparisons to neighboring taxa (apicomplexans, ciliates, diatoms) revealed both clade-specific and conserved features, and multiple connections to plant kinases were observed. The kinome of <it>Hyaloperonospora arabidopsidis</it>, an oomycete with a simpler life cycle than <it>P. infestans</it>, was found to be one-third smaller. Some differences may be attributable to gene clustering, which facilitates subfamily expansion (or loss) through unequal crossing-over.</p> <p>Conclusion</p> <p>The large sizes of the <it>Phytophthora </it>kinomes imply that phosphorylation plays major roles in their life cycles. Their kinomes also include many novel ePKs, some specific to oomycetes or shared with neighboring groups. Little experimentation to date has addressed the biological functions of oomycete kinases, but this should be stimulated by the structural, evolutionary, and expression data presented here. This may lead to targets for disease control.</p

Prótesis de cuerpo vertebral JR: dispositivo modular, anatómico y expandible, con función de jaula y placa diseñada ad hoc para estabilizar la columna después de corpectomía

INTRODUCCIÓN: debido a los resultados clínicos no satisfactorios con instrumentaciones posteriores en los casos de tumor vertebral y a las carencias económicas de nuestros pacientes para adquirir los sistemas disponibles en el mercado, fue diseñada una prótesis de cuerpo vertebral para estabilizar la columna después de una corpectomía. OBJETIVO: describir las características estructurales y funcionales de la prótesis JR, las pruebas biomecánicas en cadáver y la técnica quirúrgica en el paciente. MÉTODOS: primeramente fue realizado un estudio anatómico detallado de los cuerpos vertebrales. Se obtuvo el diseño de un dispositivo modular, anatómico y expandible. Sus componentes una vez ensamblados hacen un implante con función dual de jaula y placa lateral expandibles. Posteriormente se efectuó un ensayo de propiedades biomecánicas en cadáver y se implantó un dispositivo en un paciente con metástasis en cuerpo vertebral. RESULTADOS: las radiografías que le fueron tomadas al cadáver, posterior a la colocación del implante, no mostraron pérdida de la fijación. Al levantar el cadáver se generaron momentos de flexión en sentido lateral con brazos de palanca de 80 cm de largo, por lo que la prótesis fue demandada en su punto más vulnerable con una fuerza de aproximadamente 588 N. Con la rotación, flexión y extensión forzadas, la estabilidad se conservó y no se visualizó movimiento del implante. Se colocó el dispositivo en una mujer de 50 años con cáncer metastásico de tiroides que afectaba L3. El dolor mejoró en el postoperatorio inmediato, así como su función motora que le permitió caminar con una columna estable e indolora por siete años. No se observó fracaso del implante. CONCLUSIÓN: la función dual de jaula y placa integrada en la prótesis de cuerpo vertebral establece una ventaja mecánica comparada con la función de la jaula y de la placa separadamente, ya que el diseño de la prótesis permite aplicar fuerza axial y fijación lateral al mismo tiempo, a través de solo un implante. Los resultados de la colocación del implante en paciente son satisfactorios.INTRODUÇÃO: devido aos resultados clínicos não satisfatórios com instrumentações posteriores nos casos de tumor vertebral e às carências econômicas dos nossos pacientes para adquirir os sistemas disponíveis no mercado, foi desenhada uma prótese de corpo vertebral para estabilizar a coluna depois de uma corpectomia. OBJETIVO: descrever as características estruturais e funcionais da prótese JR, as provas biomecânicas no cadáver e a técnica cirúrgica no paciente. MÉTODOS: primeiro foi realizado um estudo anatômico detalhado dos corpos vertebrais. Obteve-se o desenho de um dispositivo modular, anatômico e expansível. Seus componentes uma vez ensamblados fazem um implante com função dual de jaula e placa lateral expansível. Posteriormente, realizou-se um ensaio de propriedades biomecânicas em cadáver e se implantou um dispositivo num paciente com metástase no corpo vertebral. RESULTADOS: as radiografias que foram tiradas do cadáver, posterior à colocação do implante não mostraram perda da fixação. Ao levantar o cadáver se geraram momentos de flexão no sentido lateral com braços de palanca de 80 cm de longitude, neste caso a prótese foi desafiada no seu ponto mais vulnerável com uma força de aproximadamente 588 N. Com a rotação, flexão e extensão forçadas, a estabilidade se conservou e não foram visualizados movimentos do implante. Colocou-se o dispositivo numa mulher de 50 anos com câncer metastático de tiroides que afeitava L3. A dor melhorou nos pós-operatório imediato, assim como sua função motora, a qual permitiu que a paciente caminhasse com uma coluna estável e indolor por sete anos. Não se observou fracasso do implante. CONCLUSÃO: a função dual de jaula e placa integrada na prótese de corpo vertebral estabelece uma vantagem mecânica comparada com a função de jaula e placa separadamente, uma vez que o desenho da prótese permite aplicar força axial e fixação lateral ao mesmo tempo, por meio de um só implante. Os resultados da colocação do implante no paciente foram satisfatórios.INTRODUCTION: due to the unsatisfactory results obtained with posterior instrumentations in cases of vertebral tumors and to the economical limitations of our patients for acquiring the systems available in the market, a vertebral body prosthesis to stabilize the spine after corpectomy was designed. OBJECTIVE: to describe the structural and functional characteristics of the JR prosthesis, the biomechanical assays in cadaver and the surgical technique on the patient. METHODS: firstly, it was performed a detailed anatomical study of the vertebral bodies. A design of a modular, anatomical and expandable device was obtained. Its components once assembled make an implant with expandable cage and plate dual function. Afterwards, a biomechanical assay was performed in a cadaver and the device was implanted in a patient with vertebral body metastasis. RESULTS: the radiographs extracted from the cadaver after implant location did not show loss of fixation. When the cadaver was raised, flexion moments were generated laterally with levers 80 cm long; therefore, the prosthesis was demanded in its most vulnerable point with a force of approximately 588 N. With rotation, flexion and extensions forced, stability was preserved and no movement was observed. The device was implanted in a 50-year-old woman with metastatic thyroid cancer affecting L3. Pain improved in the postoperative immediate, as well as its motor function, which allowed her to walk with a stable and painless spine for seven years. No implant failure was observed. CONCLUSION: the dual cage function and plate integrated in a single device offers a mechanical advantage, compared with the cages and plates used separately, since the prosthesis design permits to apply a distraction axial force with lateral fixation at the same time, through one implant. The results of the implant placement in the patient were satisfactory

Diversity dynamics in New Caledonia: towards the end of the museum model?

<p>Abstract</p> <p>Background</p> <p>The high diversity of New Caledonia has traditionally been seen as a result of its Gondwanan origin, old age and long isolation under stable climatic conditions (the museum model). Under this scenario, we would expect species diversification to follow a constant rate model. Alternatively, if New Caledonia was completely submerged after its breakup from Gondwana, as geological evidence indicates, we would expect species diversification to show a characteristic slowdown over time according to a diversity-dependent model where species accumulation decreases as space is filled.</p> <p>Results</p> <p>We reanalyze available datasets for New Caledonia and reconstruct the phylogenies using standardized methodologies; we use two ultrametrization alternatives; and we take into account phylogenetic uncertainty as well as incomplete taxon sampling when conducting diversification rate constancy tests. Our results indicate that for 8 of the 9 available phylogenies, there is significant evidence for a diversification slowdown. For the youngest group under investigation, the apparent lack of evidence of a significant slowdown could be because we are still observing the early phase of a logistic growth (i.e. the clade may be too young to exhibit a change in diversification rates).</p> <p>Conclusions</p> <p>Our results are consistent with a diversity-dependent model of diversification in New Caledonia. In opposition to the museum model, our results provide additional evidence that original New Caledonian biodiversity was wiped out during the episode of submersion, providing an open and empty space facilitating evolutionary radiations.</p

Perturbation Analysis of Heterochromatin-Mediated Gene Silencing and Somatic Inheritance

Repetitive sequences in eukaryotic genomes induce chromatin-mediated gene-silencing of juxtaposed genes. Many components that promote or antagonize silencing have been identified, but how heterochromatin causes variegated and heritable changes in gene expression remains mysterious. We have used inducible mis-expression in the Drosophila eye to recover new factors that alter silencing caused by the bwD allele, an insertion of repetitive satellite DNA that silences a bw+ allele on the homologous chromosome. Inducible modifiers allow perturbation of silencing at different times in development, and distinguish factors that affect establishment or maintenance of silencing. We find that diverse chromatin and RNA processing factors can de-repress silencing. Most factors are effective even in differentiated cells, implying that silent chromatin remains plastic. However, over-expression of the bantam microRNA or the crooked-legs (crol) zinc-finger protein only de-repress silencing when expressed in cycling cells. Over-expression of crol accelerates the cell cycle, and this is required for de-repression of silencing. Strikingly, continual over-expression of crol converts the speckled variegation pattern of bwD into sectored variegation, where de-repression is stably inherited through mitotic divisions. Over-expression of crol establishes an open chromatin state, but the factor is not needed to maintain this state. Our analysis reveals that active chromatin states can be efficiently inherited through cell divisions, with implications for the stable maintenance of gene expression patterns through development

Vascular Dysfunction Induced in Offspring by Maternal Dietary Fat Involves Altered Arterial Polyunsaturated Fatty Acid Biosynthesis

Nutrition during development affects risk of future cardiovascular disease. Relatively little is known about whether the amount and type of fat in the maternal diet affect vascular function in the offspring. To investigate this, pregnant and lactating rats were fed either 7%(w/w) or 21%(w/w) fat enriched in either18:2n-6, trans fatty acids, saturated fatty acids, or fish oil. Their offspring were fed 4%(w/w) soybean oil from weaning until day 77. Type and amount of maternal dietary fat altered acetylcholine (ACh)-mediated vaso-relaxation in offspring aortae and mesenteric arteries, contingent on sex. Amount, but not type, of maternal dietary fat altered phenylephrine (Pe)-induced vasoconstriction in these arteries. Maternal 21% fat diet decreased 20:4n-6 concentration in offspring aortae. We investigated the role of Δ6 and Δ5 desaturases, showing that their inhibition in aortae and mesenteric arteries reduced vasoconstriction, but not vaso-relaxation, and the synthesis of specific pro-constriction eicosanoids. Removal of the aortic endothelium did not alter the effect of inhibition of Δ6 and Δ5 desaturases on Pe-mediated vasoconstriction. Thus arterial smooth muscle 20:4n-6 biosynthesis de novo appears to be important for Pe-mediated vasoconstriction. Next we studied genes encoding these desaturases, finding that maternal 21% fat reduced Fads2 mRNA expression and increased Fads1 in offspring aortae, indicating dysregulation of 20:4n-6 biosynthesis. Methylation at CpG −394 bp 5′ to the Fads2 transcription start site predicted its expression. This locus was hypermethylated in offspring of dams fed 21% fat. Pe treatment of aortae for 10 minutes increased Fads2, but not Fads1, mRNA expression (76%; P<0.05). This suggests that Fads2 may be an immediate early gene in the response of aortae to Pe. Thus both amount and type of maternal dietary fat induce altered regulation of vascular tone in offspring though differential effects on vaso-relaxation, and persistent changes in vasoconstriction via epigenetic processes controlling arterial polyunsaturated fatty acid biosynthesis

A Genome-Wide Survey of Switchgrass Genome Structure and Organization

The perennial grass, switchgrass (Panicum virgatum L.), is a promising bioenergy crop and the target of whole genome sequencing. We constructed two bacterial artificial chromosome (BAC) libraries from the AP13 clone of switchgrass to gain insight into the genome structure and organization, initiate functional and comparative genomic studies, and assist with genome assembly. Together representing 16 haploid genome equivalents of switchgrass, each library comprises 101,376 clones with average insert sizes of 144 (HindIII-generated) and 110 kb (BstYI-generated). A total of 330,297 high quality BAC-end sequences (BES) were generated, accounting for 263.2 Mbp (16.4%) of the switchgrass genome. Analysis of the BES identified 279,099 known repetitive elements, >50,000 SSRs, and 2,528 novel repeat elements, named switchgrass repetitive elements (SREs). Comparative mapping of 47 full-length BAC sequences and 330K BES revealed high levels of synteny with the grass genomes sorghum, rice, maize, and Brachypodium. Our data indicate that the sorghum genome has retained larger microsyntenous regions with switchgrass besides high gene order conservation with rice. The resources generated in this effort will be useful for a broad range of applications