Muscle Fatigue from the Perspective of a Single Crossbridge

The repeated intense stimulation of skeletal muscle rapidly decreases its force- and motion-generating capacity. This type of fatigue can be temporally correlated with the accumulation of metabolic by-products, including phosphate (Pi) and protons (H+). Experiments on skinned single muscle fibers demonstrate that elevated concentrations of these ions can reduce maximal isometric force, unloaded shortening velocity, and peak power, providing strong evidence for a causative role in the fatigue process. This seems to be due, in part, to their direct effect on muscle’s molecular motor, myosin, because in assays using isolated proteins, these ions directly inhibit myosin’s ability to move actin. Indeed, recent work using a single molecule laser trap assay has revealed the specific steps in the crossbridge cycle affected by these ions. In addition to their direct effects, these ions also indirectly affect myosin by decreasing the sensitivity of the myofilaments to calcium, primarily by altering the ability of the muscle regulatory proteins, troponin and tropomyosin, to govern myosin binding to actin. This effect seems to be partially due to fatigue-dependent alterations in the structure and function of specific subunits of troponin. Parallel efforts to understand the molecular basis of muscle contraction are providing new technological approaches that will allow us to gain unprecedented molecular detail of the fatigue process. This will be crucial to fully understand this ubiquitous phenomenon and develop appropriately targeted therapies to attenuate the debilitating effects of fatigue in clinical populations

Self-Esteem in Second Life: An inWorld Group Intervention for Women with Disabilities

We are developing and investigating the feasibility of a self-esteem enhancement intervention in Second Life for women with physical disabilities. We adapted the curriculum of a previously tested workshop intervention to include features unique to this environment. Results of the beta test were very positive. Everyone involved showed considerable enthusiasm for exploring the new world of SL. The group leaders were challenged to resolve technical problems on every occasion, but these diminished and were perceived as manageable as the intervention progressed. Beta testers gave positive ratings to the information presented, organization, and usefulness of the intervention and found it very enjoyable although fatigue and stress limited the participation of some. They appreciated the use of Internet technology as an accommodation to their disability, in place of requiring transportation and additional energy expenditure to attend face-to-face meetings. Research issues related to engagement, measurement, and participant safety, as well as future research directions, are discussed. We conclude that SL has great potential for delivering health promotion interventions to women with physical disabilities

Temporal Adaptive Changes in Contractility and Fatigability of Diaphragm Muscles from Streptozotocin-Diabetic Rats

Diabetes is characterized by ventilatory depression due to decreased diaphragm (DPH) function. This study investigated the changes in contractile properties of rat DPH muscles over a time interval encompassing from 4 days to 14 weeks after the onset of streptozotocin-induced diabetes, with and without insulin treatment for 2 weeks. Maximum tetanic force in intact DPH muscle strips and recovery from fatiguing stimulation were measured. An early (4-day) depression in contractile function in diabetic DPH was followed by gradual improvement in muscle function and fatigue recovery (8 weeks). DPH contractile function deteriorated again at 14 weeks, a process that was completely reversed by insulin treatment. Maximal contractile force and calcium sensitivity assessed in Triton-skinned DPH fibers showed a similar bimodal pattern and the same beneficial effect of insulin treatment. While an extensive analysis of the isoforms of the contractile and regulatory proteins was not conducted, Western blot analysis of tropomyosin suggests that the changes in diabetic DPH response depended, at least in part, on a switch in fiber type

Mgm101: A double-duty Rad52-like protein

Mgm101 has well-characterized activity for the repair and replication of the mitochondrial genome. Recent work has demonstrated a further role for Mgm101 in nuclear DNA metabolism, contributing to an S-phase specific DNA interstrand cross-link repair pathway that acts redundantly with a pathway controlled by Pso2 exonuclease. Due to involvement of FANCM, FANCJ and FANCP homologues (Mph1, Chl1 and Slx4), this pathway has been described as a Fanconi anemia-like pathway. In this pathway, Mgm101 physically interacts with the DNA helicase Mph1 and the MutSα (Msh2/Msh6) heterodimer, but its precise role is yet to be elucidated. Data presented here suggests that Mgm101 functionally overlaps with Rad52, supporting previous suggestions that, based on protein structure and biochemical properties, Mgm101 and Rad52 belong to a family of proteins with similar function. In addition, our data shows that this overlap extends to the function of both proteins at telomeres, where Mgm101 is required for telomere elongation during chromosome replication in rad52 defective cells. We hypothesize that Mgm101 could, in Rad52-like manner, preferentially bind single-stranded DNAs (such as at stalled replication forks, broken chromosomes and natural chromosome ends), stabilize them and mediate single-strand annealing-like homologous recombination event to prevent them from converting into toxic structures

Store-Operated Ca2+ Entry (SOCE) Contributes to Normal Skeletal Muscle Contractility in young but not in aged skeletal muscle

Muscle atrophy alone is insufficient to explain the significant decline in contractile force of skeletal muscle during normal aging. One contributing factor to decreased contractile force in aging skeletal muscle could be compromised excitation-contraction (E-C) coupling, without sufficient available Ca2+ to allow for repetitive muscle contractility, skeletal muscles naturally become weaker. Using biophysical approaches, we previously showed that store-operated Ca2+ entry (SOCE) is compromised in aged skeletal muscle but not in young ones. While important, a missing component from previous studies is whether or not SOCE function correlates with contractile function during aging. Here we test the contribution of extracellular Ca2+ to contractile function of skeletal muscle during aging. First, we demonstrate graded coupling between SR Ca2+ release channel-mediated Ca2+ release and activation of SOCE. Inhibition of SOCE produced significant reduction of contractile force in young skeletal muscle, particularly at high frequency stimulation, and such effects were completely absent in aged skeletal muscle. Our data indicate that SOCE contributes to the normal physiological contractile response of young healthy skeletal muscle and that defective extracellular Ca2+ entry through SOCE contributes to the reduced contractile force characteristic of aged skeletal muscle

Assessing children’s implicit attitudes using the Affect Misattribution Procedure

In the current research we examined whether the Affect Misattribution Procedure (AMP; Payne et al., 2005) could be successfully adapted as an implicit measure of children’s attitudes. We tested this possibility in three studies with 5 to 10 year old children. In Study 1 we found evidence that children misattribute affect elicited by attitudinally positive (e.g., cute animals) and negative (e.g., aggressive animals) primes to neutral stimuli (inkblots). In Study 2, we found that, as expected, children’s responses following flower and insect primes were moderated by gender. Girls (but not boys) were more likely to judge inkblots as pleasant when they followed flower primes. Children in Study 3 showed predicted affect misattribution following happy as compared to sad face primes. In addition, children’s responses on this child-friendly AMP predicted their self-reported empathy; the greater children’s spontaneous misattribution of affect following happy and sad primes, the more children reported feeling the joy and pain of others. These studies provide evidence that the AMP can be adapted as an implicit measure of children’s attitudes and the results of Study 3 offer novel insight into individual differences in children’s affective responses to the emotional expressions of other

Design of a videogame to explore morality

A number of video games involve moral narratives or require the player to make moral decisions and research from psychologists has helped to understand the effects video game content can have on how individuals behave. Recent research has started to examine the role of morality in video games: however, there are many inconsistencies in the findings. We propose that some of these inconsistencies could be due to using commercial video games for research purposes, which contain biases such as familiarity with the game and favourite characters. The process of playing video games requires consideration of Human Computer Interaction (HCI); i.e., how the game is designed and then how it is received by the player. The aim of this poster is to highlight the work being conducted to design a game in order to investigate how moral decisions are made in video games. The design of video games usually draws on an understanding of HCI to produce play that is entertaining and engaging for the player. The game development process in this research draws on a fusion of psychology and HCI, and by drawing on theories of morality the design of the game will be grounded in psychology, as well as entertainment. Through fusing video game design principles, HCI and psychology, this work is novel in terms of a methodological as well as theoretical contribution to the area

The Pierre Auger Observatory III: Other Astrophysical Observations

Astrophysical observations of ultra-high-energy cosmic rays with the Pierre Auger ObservatoryComment: Contributions to the 32nd International Cosmic Ray Conference, Beijing, China, August 201