Distribution of calcifying and silicifying phytoplankton in relation to environmental and biogeochemical parameters during the late stages of the 2005 North East Atlantic Spring Bloom

The late stage of the North East Atlantic (NEA) spring bloom was investigated during June 2005 along a transect section from 45 to 66 degrees N between 15 and 20 degrees W in order to characterize the contribution of siliceous and calcareous phytoplankton groups and describe their distribution in relation to environmental factors. We measured several biogeochemical parameters such as nutrients, surface trace metals, algal pigments, biogenic silica (BSi), particulate inorganic carbon (PIC) or calcium carbonate, particulate organic carbon, nitrogen and phosphorus (POC, PON and POP, respectively), as well as transparent exopolymer particles (TEP). Results were compared with other studies undertaken in this area since the JGOFS NABE program. Characteristics of the spring bloom generally agreed well with the accepted scenario for the development of the autotrophic community. The NEA seasonal diatom bloom was in the late stages when we sampled the area and diatoms were constrained to the northern part of our transect, over the Icelandic Basin (IB) and Icelandic Shelf (IS). Coccolithophores dominated the phytoplankton community, with a large distribution over the Rockall-Hatton Plateau (RHP) and IB. The Porcupine Abyssal Plain (PAP) region at the southern end of our transect was the region with the lowest biomass, as demonstrated by very low Chla concentrations and a community dominated by picophytoplankton. Early depletion of dissolved silicic acid (DSi) and increased stratification of the surface layer most likely triggered the end of the diatom bloom, leading to coccolithophore dominance. The chronic Si deficiency observed in the NEA could be linked to moderate Fe limitation, which increases the efficiency of the Si pump. TEP closely mirrored the distribution of both biogenic silica at depth and prymnesiophytes in the surface layer suggesting the sedimentation of the diatom bloom in the form of aggregates, but the relative contribution of diatoms and coccolithophores to carbon export in this area still needs to be resolved.

Effects of diatoms on reproduction and growth of marine copepods

Two hot spots in marine ecology, deleterious effects of diatoms and feeding selectivity of copepods, as well as new progress on these two issues achieved in the recent ten years, are reviewed. These two issues are considered correlated closely. Diatoms and their metabolites can induce deleterious effects on growth, reproduction and development of copepods, including increase of mortality and decrease of egg production, hatching and growth rates. Such negative effects, resulting from either chemical toxin or nutritional deficiency, can be conquered in natural environments by diverse feeding. It is therefore concluded that deleterious effects of diatoms observed in laboratory or during blooming period are only a special case that accommodation of feeding strategy of copepods is disabled. To understand their feeding strategy in natural environments is a prerequisite to explaining the mechanisms of deleterious effects caused by diatoms, and makes it possible to re-evaluate the energy flow in marine ecosystems.

基于输入和机械手扰动补偿的水下机器人控制实验研究

以搭建的自治水下机器人-机械手系统为对象,通过水池实验分析了载体分系统的响应特性。针对传统的反馈控制在载体控制中的不足,将输入补偿项和机械手扰动补偿项作为载体控制的前馈项,设计了水下机器人复合校正控制器。水池实验验证了方法的可行性和有效性。

基于工程地质力学的岩土工程加固理论、技术与实践

In the engineering reinforcement of-rock and soil mass, engineers must consider how to obtain better reinforcing effect at the cost of less reinforcing expense, which, in fact, is the aim of reinforcement design. In order to accomplish the purpose, they require not only researching the material used to reinforce and its structure, but also taking into account of several important geological factors, such as the structure and property of rock and soil mass. How to improve the reinforcing effect according to engineering geomechanical principle at the respect of the reinforcement of engineering soil and rock mass is studied and discussed in this paper. The author studies the theory, technology and practice of geotechnical reinforcement based on engineering geomechanics, taking example for the soil treatment of Zhengzhou Airport, the effect analysis of reinforcement to the slope on the left bank of Wuqiangxi Hydropower Station and the reinforcing design of the No. 102 Landslide and unique sand-slide slope on the Sichuan-Tibet Highway. The paper is comprised of two parts for the convenience of discussion. In the first part, from the first chapter to the fifth chapter, trying to perform the relevant research and application at the viewpoint of soil mass engineering geomechanics, the author mainly discusses the study of reinforcing soft ground soil through dynamical consolidation and its application. Then, in the second part, from the sixth chapter to the eleventh chapter, the study of new technologies in the rock slope reinforcement and their application are discussed. The author finds that not only better reinforcing effect can be gained in the research where the principle and method of rock mass engineering geomechanics is adopted, but also new reinforcing technologies can be put forward. Zhengzhou Airport is an important one in central plains. It lies on Yellow River alluvial deposit and the structure of stratum is complex and heterogeneous. The area of airport is very large, which can result in differential settlement easily, damage of airport and aircraft accident, whereas, there are no similar experiences to dispose the foundation, so the foundation treatment become a principal problem. During the process of treatment, the method of dynamic compaction was adopted after compared with other methods using the theory of synthetic integration. Dynamic compaction is an important method to consolidate foundation, which was successfully used in the foundation of Zhengzhou Airport. For fill foundation, controlling the thickness of fill so as to make the foundation treatment can reach the design demand and optimum thickness of the fill is a difficult problem. Considering this problem, the author proposed a calculation method to evaluate the thickness of fill. The method can consider not only the self-settlement of fill but also the settlement of the ground surface under applied load so as to ensure the settlement occurred during the using period can satisfy the design demand. It is proved that the method is correct after using it to choose reasonable energy of dynamic compaction to treat foundation. At the same time, in order to examine the effect of dynamic compaction, many monitor methods were adopted in the test such as static loading test, modulus of resilience test, deep pore pressure -test, static cone penetration test and the variation of the pore volume measurement. Through the tests, the author summarized the discipline of the accumulation and dissipation of pore pressure in Yellow River alluvial deposit under the action of dynamic compaction, gave a correct division of the property change of silt and clay under dynamic compaction, determined the bearing capacity of foundation after treatment and weighted the reinforcing effect of dynamic consolidation from the variation of the soil particle in microcosmic and the parameter of soil mass' density. It can be considered that the compactness of soil is in proportion to the energy of dynamic compaction. This conclusion provided a reference to the research of the "Problem of Soil Structure-the Central Problem of Soil Mechanics in 21 Century ". It is also important to strengthen rock mass for water conservancy and electric power engineering. Slip-resistance pile and anchoring adit full of reinforced concrete are usually adopted in engineering experience to strengthen rock mass and very important for engineering. But there also some deficiency such as the weakest section can't be highlighted, the monitor is inconvenient and the diameter of pile and adit is very large etc. The author and his supervisor professor Yangzhifa invented prestressed slip-resistance pile and prestressed anchoring adit full of reinforced concrete, utilizing the advantage that the prestressed structure has better anti-tensile characteristic (this invention is to be published). These inventions overcome the disadvantages of general slip-resistance pile and anchoring adit full of reinforced concrete and have the functions of engineering prospecting, strengthening, drainage and monitor simultaneous, so they have better strengthened effect and be more convenient for monitor and more economical than traditional methods. Drainage is an important factor in treatments of rock mass and slop. In view of the traditional drainage method that drainage pore often be clogged so as to resulted in incident, professor Yangzhifa invented the method and setting of guide penetration by fiber bundle. It would take good effect to use it in prestressed slip-resistance pile and anchoring adit full of reinforced concrete. In this paper, the author took example for anchoring adit full of reinforced concrete used to strengthen Wuqiangxi left bank to simulate the strengthened effect after consolidated by prestressed slip-resistance pile, took example for 102 landslide occurred along Sichuan-Tibet highway to simulate the application of slip-resistance pile and the new technology of drainage. At the same time the author proposed the treatment method of flowing sand in Sichuan-Tibet highway, which will benefit the study on strengthening similar engineering. There are five novelties in the paper with the author's theoretical study and engineering practice: 1. Summarizing the role of pore water pressure accumulation and dissipation of the Yellow River alluvial and diluvial soil under the action of dynamical consolidation, which has instructive significance in the engineering construction under the analogical engineering geological conditions in the future. It has not been researched by the predecessors. 2. Putting forward the concept of density D in microcosmic based on the microcosmical structure study of the soil sample. Adopting D to weight the reinforcing effect of dynamic consolidation is considered to be appropriate by the means of comparing the D values of Zhengzhou Airport's ground soil before with after dynamically consolidating reinforcement, so a more convenient balancing method can be provided for engineering practice. 3. According to the deep research into the soil mass engineering geology, engineering rock and soil science, soil mechanics, as well as considerable field experiments, improving the consolidating method in airport construction, from the conventional method, which is dynamically compactmg original ground surface firstly, then filling soil and dynamically layer-consolidating or layer-compacting at last to the upgraded method, which is performing dynamical consolidation after filling soil to place totally at the extent of the certain earth-filling depth. The result of the dynamical consolidation not only complies with the specifications, but also reduces the soil treatment investment by 10 million RMB. 4. Proposing the method for calculating the height of the filled soil by the means of estimating the potential displacement produced in the original ground surface and the filled earth soil under the possible load, selecting the appropriate dynamically-compacting power and determining the virtual height of the filled earth soil. The method is proved to be effective and scientific. 5. According to the thought of Engineering Geomechanics Metal-Synthetic Methodology (EGMS), patenting two inventions (to the stage of roclamation, with Professor Yang Zhi-fa, the cooperative tutor, and etc.) in which multi-functions, engineering geological investigation, reinforcement, drainage and strength remedy, are integrated all over in one body at the viewpoint of the breakage mechanism of the rock slope.

学习困难儿童智力结构及其与心理语言、视动能力关系的研究

IQ Structure, Psycholinguistic and Visual-motor Abilities Study on Children Learning Disability TONG Fang Directed by professor Zhu Liqi (Developmental and educational psychology) ABSTRACT Objective To comprehensive analyze the IQ structures, and relationships among IQ, psychometric characteristics and visual-motor integration on children disability. At same time, to probe into the family factors that influenced IQ, psycholinguistic abilities and behavior of LD children. Method (1) Downloading the papers on children learning disability from www.cqvip.com and www.wanfangdata.com, in which, the articles were collected by key words from 1985 to 2005. To conduct meta-analysis on IQ construction, compare the case group and the control group, including full IQ, verbal and practice IQ. (2) Designed with model compared and self-compared, 59 diagnosed learning disability children, tested themes with WISC, ITPA and Berry’s VMI. WISC included 10 items, 5 of which subtotal to verbal and practice IQ respectively. IPTA included 10 items, too, 5 process of which subtotal to auditory and visual perception. The first 3 items shared representation level, the other 2 of that shared automatic level.VMI had one score. Analyzed factors and levels with description and Pearson Correlation. To probe to linguistic internal alternately functions of LD children, and compare the scores of groups in different IQ. (3) Analyzed the perspective questionnaire filled by parents. Early development facts compared with model groups. Factors relationships analyzed with Kendall correlation, KOM and Bartlett’s test of sphericity, Promax Rotation. Results: (1) There have been 319 papers related with LD, in which 36 with IQ and 14 valid reports have been analyzed by Meta. FIQ’s 95%CI (confidence interval) is 2.418 ~ 0.172, VIQ between the difficulty and non- difficulty group. C-WISC-R reports were 10 papers, of which, 95%CI of FIQ is 2.424 ~ 0.676, of VIQ is 2.314 ~ 1.196, of PIQ is 2.176 ~ 0.176. The VIQ comparing the PIQ, 95%CI is 1.1 ~ -0.07 in difficulty group and 0.5 ~ -0.0046 in non-difficult group. Nevertheless, in the other 4 tests, FIQ’s 95%CI is 2.00 ~ -0.818 between LD and NLD. (2) Children psycholinguistic abilities had strong relation with Berry’s VMI test excluding auditory reception, and with perceptive factor of intelligence excluding verbal expression. Auditory reception and visual closure had strong relation with FIQ and PIQ. Grammatic closure, visual association and manual expression had strong relation with concept factor. The representational and automatic levels are depended on integration of auditory and visual procession. Lower verbal expression (VE) let to lower expression process and low scores on representational level. Lower visual sequential memory (VSM) let to lower memory process and influenced automatic level. Groups compared by IQ 90 show that LD children with under IQ 90 had lower scores on items of IPTA than with up IQ 90 excluded verbal expression. It was proved that IQ administrated the linguistic ability. Nevertheless, general abilities deficiency didn’t show influencing on the types of the perceptive delay. There was mutual function among linguistic ability on LD children. Auditory and visual level are overlapped each other. Not only show higher Decoding and lower Encoding on Auditory perception, lower Decoding and higher Encoding on Visual perception, in representation, but also higher Sequential remember, lower Closure on Audition, and lower Sequential member, higher Closure on Vision, in Automation. Nevertheless, there was no different between Representational and Automatic level, which may be the relationship of parallel or evolution. (3) Major family factors were father’s education, occupation. Lower auditory perception related to unconcerned, lower visual perception related to premature delivery and written slowly. Threatened–abortion, childbirth-suffocated were known as influencing children’s IQ and later linguistic abilities. It wasn’t shown that dosage relationship with the types of perceptive delay. Conclusion: (1) The FIQ, VIQ and PIQ of Children with LD is lower than that of NLD group. There is no significantly different between VIQ and PIQ in LD and NLD groups. (2) The objectives of ITPA and WISC tests are differently. The psycholinguistic abilities had strong relation with perceptive factor and VMI. Some facts of IPTA related with FIQ. IQ had strong administration on linguistic abilities. There was mutual function among linguistic internal abilities. (3) Family facts on IQ and psycholinguistic abilities were Father’s education, abnormal pregnant and abortion. It would be pre-show development delay in early period.

不同干扰条件下社会认知偏离者两半球协同功能研究

Previous studies have witnessed some psychological or behavioral deviation (such as aggressive behavior) might have an association with cerebral hemisphere cooperative dysfunction, however, it is still unclear whether there is an association between individuals with social cognitive bias and their hemispheric cooperative functions especially while the interhemisphere cooperative processing is under the conditions of emotional interferences. The purpose of this study is to explore the differences between the social cognitive bias group and the normal group’s interhemispheric cooperative functional activity under the conditions of with or without interferences. Methods: According to Dodge’s (1993) model of “social-cognitive mechanisms in the development of conduct disorder and depression”, a 51 items of “social cognitive bias scale” was created and was used to screen the high score group. 20 male subjects was composed of high score group and other 23 matched the control group. Stimulus tachistoscopically presented to the bilateral visual field and compared with the central. Both group’s interhemispheric cooperative functional activity were observed and compared under the conditions of without interference- i.e. base level and with the emotional interferences of white noise level and negative evaluative feedback speech level while finishing: experiment one: Chinese word-figure Stroop analogue task; experiment two: two single Chinese Characters combination task. Heart rate and respiratory rate were simultaneously recorded as index of emotional changes. Results: ① The high score group showed a decrease in processing accuracy compared with the normal group under the condition of white noise interference level in experiment one. ② Still under the condition of white noise interference level, there were more reaction time and more errors were observed in high score group than normal in experiment two. ③ Both groups showed speed up effect and the strategic processing tendency of speed-accuracy trade-off effect under the condition of white noise interference level in both experiments. ④ Between group differences of interhemipheric cooperative function were not observed under the conditions of base level and the negative evaluative feedback speech level within both experiments. Conclusion: The results suggested that interhemispheric cooperative functional differences exists between the two groups, characterized as ① differences existed in interhemispheric cooperative processing strategy between the two groups, with the high score group presented “hierarchic” deficiency strategy. ② the appearance of the differences between the two groups were condition specified , and in this research it was only under the white noise interference condition. ③ the features of the differences between the two groups were the differences on multidimensional performances and with a deficit orientation in high score group. ④ the varieties of the differences were changing with cooperative tasks, as in this research the high score group performed worse in complementary cooperative task. In addition, both group adjusted the processing strategy respectively under the condition of white noise evoked emotional interference implied that the interaction between the interhemisphere cooperative processing and emotion might exist.

听力障碍与听力正常群体视觉注意发展及其机制的比较

One of the most important functions in the individual development is the interaction and integration of each sensory input. There exist two competing theories, i.e. the deficiency theory and the compensatory theory, regarding the origin and nature of changes in visual functions observed after auditory deprivation. The deficiency theory proposed that integrative processes are essential for normal development. In contrast, the compensatory theory stated that the loss of one sense may be met by a greater reliance upon, therefore an enhancement of the remaining senses. Given that hearing impaired children’s learning depends primarily on visual information, it is important to recognize the differences of visual attention between them and their hearing age-mates. Differences among age groups could exist in either selectivity or sustained attention. Study 1 and study 2 explored the selective and sustained attention development of hearing impaired and hearing students with average cognitive ability, aged from 7 years to college students. The analysis and discussion of the results are based on the visual attention development as well as deficiency theory and compensatory theory. According to the results of the study 1 and study 2, the spatial distribution and controlling of the visual attention between hearing impaired and hearing students were also investigated in the study 3 and study 4. The present work showed that: Firstly, both hearing impaired and hearing participants had the similar developmental trajectory of the sustained attention. The ability of children’s sustained attention appeared to improve with age, and in adolescence it reached the peak. The hearing impaired participants had the comparable sustained attention skills to the matched hearing ones. Besides, the results of the hearing impaired participants showed that they could maintain their attention and vigilance on the current task over the observation period. Secondly, group differences of visual attention development were found between hearing impaired and hearing participants. In the childhood, the visual attention developmental speed of the hearing impaired children was slower than that of the hearing ones. The selective attention skill of the hearing impaired were not comparable to the hearing ones, however, their selective skill improved with age, so in the adulthood, hearing impaired students showed the slight advantage in the selective attention skill over the hearing ones. Thirdly, hearing impaired and hearing participants showed the similar spatial distribution in the attention resources. In the low perceptual load condition, both participants were suffered great interference of the distrator at the fixation. In contrast, in the high perceptual load condition, hearing impaired adults were suffered more interference of the peripheral distractor, which suggested that they distributed more attention resources to the peripheral field when faced difficult tasks. Fourthly, both groups showed similar processing in the visual attention tasks. That is, they both searched the target with only the color feature in a parallel way, but in a serial way while processing orientation feature and the features with the combination of the color and orientation. Furthermore, the results indicated that two groups show similar ways in the attention controlling. In summary, the present study showed that visual attention development was dependent upon the integration of multimodal sensory information. Because of the interaction and integration of the input from various sensory, it has a negative impact on the intact sensory at the early stage of one sensory loss, however, it can better the functions of other intact sensory gradually with development and practice.

道德强度对企业道德决策的影响及作用机制

Moral decision-making in business means the decisions involved in moral issues in business context. Moral intensity is a construct that captures the extent of issue-related moral imperative in a situation, which is one of the most important factors in the study of moral decision-making in business. Based on Issue-Contingent Model, the present study investigated the influence of moral intensity on moral decision-making in business (including moral recognition, moral judgment, and moral intent in the present study), and further focused on exploring the mechanism of moral intensity in moral decision-making in business. Recently, the studies in decision-making gave more emphasis to the role of emotions. The present study tried to include empathy into moral decision-making in business to explore the role of empathy in the relationship between moral intensity and moral decision-making in business, which would enrich and extend Issue-Contingent Model. The present study would also make up for a deficiency in the study of moral decision-making in business that overemphasized the rational reasoning and neglected the role of emotions. There were three parts in the present study. Firstly, study 1 replicated the former study and explored the relationship between perceived moral intensity and moral decision-making in business in China by questionnaire method. Secondly, study 2 focused on exploring the influence of the components of moral intensity on moral decision-making in business and empathic response by experimental method. Finally, study 3 explored the role of empathy in the relationship between moral intensity and moral decision-making in business. The results indicated that, 1.Perceived moral intensity was the significant predictor for moral decision- making in business. 2.Magnitude of consequence, social consensus, and probability of effect had significant effects on moral decision-making in business. Magnitude of consequence and probability of effect could influence empathic response significantly. 3.Empathic response played the role of mediator between moral intensity and moral decision-making in business. Empathic response completely mediated the relationship between moral intensity and moral recognition. Empathic response partly mediated the relationship between moral intensity and moral judgment, moral intent. Further analysis indicated that probability of effect and magnitude of consequence relied more on empathic response than social consensus to influence moral judgment and moral intent. Dispositional empathy could influence moral decision-making in business through perceived moral intensity and empathic response. 4.Controlled empathic levels could influence moral decision-making in business significantly. Empathic levels influenced the effect of probability of effect on moral decision-making in business, and did not influence the effect of magnitude of consequence and social consensus on moral decision-making in business. These findings not only contribute to enrich the models of moral decision- making in business, but also have significant practical applications in the training of moral decision-making in business.

Adubação fosfatada para manutenção de pastagem de brachiaria decumbens no cerrado.

2001

Comprehensive assessment of alcohol-related brain damage (ARBD): gap or chasm in the evidence?

Alcohol-related brain damage (ARBD) is primarily caused by chronic alcohol misuse and thiamine deficiency, and results in a broad range of impairments. Despite the increasing incidence of ARBD in the UK in recent decades, it is currently underdiagnosed, managed inappropriately and treated inadequately. Moreover, information about assessments for individuals with ARBD is currently absent from clinical guidelines and policy documents. The aim of this paper was to review the evidence relating to the neurological, neuropsychological, psychosocial, physical and nutritional assessment of individuals with ARBD to identify appropriate assessment tools that could be used to measure and monitor the impact of ARBD over time. A systematic online database search revealed a total of 160 separate references, 133 of which were rejected and two of which could not be accessed. Twenty-five papers were included in the review, including six neuroimaging studies, 17 neuropsychological studies and two studies using psychosocial methods of assessment. A lack of evidence for nutritional and physical assessment of individuals with ARBD was found. The review findings are inconclusive; most instruments currently used in ARBD research have not specifically been validated for use within an ARBD context. Further research is required to identify comprehensive methods of ARBD assessment.

Phenotype consequences of myophosphorylase dysfunction: insights from the McArdle mouse model

McArdle disease, caused by inherited deficiency of the enzyme muscle glycogen phosphorylase (GP-MM), is arguably the paradigm of exercise intolerance. The recent knock-in (p.R50X/p.R50X) mouse disease model allows an investigation of the phenotypic consequences of muscle glycogen unavailability and the physiopathology of exercise intolerance. We analysed, in 2-month-old mice [wild-type (wt/wt), heterozygous (p.R50X/wt) and p.R50X/p.R50X)], maximal endurance exercise capacity and the molecular consequences of an absence of GP-MM in the main glycogen metabolism regulatory enzymes: glycogen synthase, glycogen branching enzyme and glycogen debranching enzyme, as well as glycogen content in slow-twitch (soleus), intermediate (gastrocnemius) and glycolytic/fast-twitch (extensor digitorum longus; EDL) muscles.

McArdle disease: a unique study model in sports medicine

McArdle disease is arguably the paradigm of exercise intolerance in humans. This disorder is caused by inherited deficiency of myophosphorylase, the enzyme isoform that initiates glycogen breakdown in skeletal muscles. Because patients are unable to obtain energy from their muscle glycogen stores, this disease provides an interesting model of study for exercise physiologists, allowing insight to be gained into the understanding of glycogen-dependent muscle functions. Of special interest in the field of muscle physiology and sports medicine are also some specific (if not unique) characteristics of this disorder, such as the so-called 'second wind' phenomenon, the frequent exercise-induced rhabdomyolysis and myoglobinuria episodes suffered by patients (with muscle damage also occurring under basal conditions), or the early appearance of fatigue and contractures, among others. In this article we review the main pathophysiological features of this disorder leading to exercise intolerance as well as the currently available therapeutic possibilities.

Rodent models for resolving extremes of exercise and health

The extremes of exercise capacity and health are considered a complex interplay between genes and the environment. In general, the study of animal models has proven critical for deep mechanistic exploration that provides guidance for focused and hypothesis driven discovery in humans. Hypotheses underlying molecular mechanisms of disease, and gene/tissue function can be tested in rodents in order to generate sufficient evidence to resolve and progress our understanding of human biology. Here we provide examples of three alternative uses of rodent models that have been applied successfully to advance knowledge that bridges our understanding of the connection between exercise capacity and health status. Firstly we review the strong association between exercise capacity and all-cause morbidity and mortality in humans through artificial selection on low and high exercise performance in the rat and the consequent generation of the "energy transfer hypothesis". Secondly we review specific transgenic and knock-out mouse models that replicate the human disease condition and performance. This includes human glycogen storage diseases (McArdle and Pompe) and α-actinin-3 deficiency. Together these rodent models provide an overview of the advancements of molecular knowledge required for clinical translation. Continued study of these models in conjunction with human association studies will be critical to resolving the complex gene-environment interplay linking exercise capacity, health, and disease.

Xanthine oxidase pathway and muscle damage: Insights from McArdle disease

The intent of this review is to summarize current body of knowledge on the potential implication of the xanthine oxidase pathway (XO) on skeletal muscle damage. The possible involvement of the XO pathway in muscle damage is exemplified by the role of XO inhibitors (e.g., allopurinol) in attenuating muscle damage. Reliance on this pathway (as well as on the purine nucleotide cycle) could be exacerbated in conditions of low muscle glycogen availability. Thus, we also summarize current hypotheses on the etiology of both baseline and exertional muscle damage in McArdle disease, a condition caused by inherited deficiency of myophosphorylase. Because myophosphorylase catalyzes the first step of muscle glycogen breakdown, patients are unable to obtain energy from their muscle glycogen stores. Finally, we provide preliminary data from our laboratory on the potential implication of the XO pathway in the muscle damage that is commonly experienced by these patients.

Muscle signaling in exercise intolerance: Insights from the McArdle mouse model

We recently generated a knock-in mouse model (PYGM p.R50X/p.R50X) of McArdle disease (myophosphorylase deficiency). One mechanistic approach to unveil the molecular alterations caused by myophosphorylase deficiency, which is arguably the paradigm of 'exercise intolerance', is to compare the skeletal-muscle tissue of McArdle, heterozygous, and healthy (wild type (wt)) mice. We analyzed in quadriceps muscle of p.R50X/p.R50X (n=4), p.R50X/wt (n=6) and wt/wt mice (n=5) (all male, 8 wk-old) molecular markers of energy-sensing pathways, oxidative phosphorylation (OXPHOS) and autophagy/proteasome systems, oxidative damage and sarcoplamic reticulum (SR) Ca handling. We found a significant group effect for total AMPK (tAMPK) and ratio of phosphorylated (pAMPK)/tAMPK (P=0.012 and 0.033), with higher mean values in p.R50X/p.R50X mice vs. the other two groups. The absence of massive accumulation of ubiquitinated proteins, autophagosomes or lysosomes in p.R50X/p.R50X mice suggested no major alterations in autophagy/proteasome systems. Citrate synthase activity was lower in p.R50X/p.R50X mice vs. the other two groups (P=0.036) but no statistical effect existed for respiratory chain complexes. We found higher levels of 4-hydroxy-2-nonenal-modified proteins in p.R50X/p.R50X and p.R50X/wt mice compared with the wt/wt group (P=0.011). Sarco(endo)plasmic reticulum ATPase 1 (SERCA1) levels detected at 110kDa tended to be higher in p.R50X/p.R50X and p.R50X/wt mice compared with wt/wt animals (P=0.076), but their enzyme activity was normal. We also found an accumulation of phosphorylated SERCA1 in p.R50X/p.R50X animals. Myophosphorylase deficiency causes alterations in sensory energetic pathways together with some evidence of oxidative damage and alterations in Ca handling but with no major alterations in OXPHOS capacity or autophagy/ubiquitination pathways, which suggests that the muscle tissue of patients is likely to adapt overall favorably to exercise training interventions.