DIAPHRAGM MUSCLE STRIP PREPARATION FOR EVALUATION OF GENE THERAPIES IN mdx MICE

1.  Duchenne muscular dystrophy (DMD), a severe muscle wasting disease of young boys with an incidence of one in every 3000, results from a mutation in the gene that encodes dystrophin. The absence of dystrophin expression in skeletal muscles and heart results in the degeneration of muscle fibres and, consequently, severe muscle weakness and wasting. The mdx mouse discovered in 1984, with some adjustments for differences, has proven to be an invaluable model for scientific investigations of dystrophy. 2.  The development of the diaphagm strip preparation provided an ideal experimental model for investigations of skeletal muscle impairments in structure and function induced by interactions of disease- and age-related factors. Unlike the limb muscles of the mdx mouse, which show adaptive changes in structure and function, the diaphragm strip preparation reflects accurately the deterioration in muscle structure and function observed in boys with DMD. 3.  The advent of sophisticated servo motors and force transducers interfaced with state-of-the-art software packages to drive complex experimental designs during the 1990s greatly enhanced the capability of the mdx mouse and the diaphragm strip preparation to evaluate more accurately the impact of the disease on the structure–function relationships throughout the life span of the mouse. 4.  Finally, during the 1990s and through the early years of the 21st century, many promising, sophisticated genetic techniques have been designed to ameliorate the devastating impact of muscular dystrophy on the structure and function of skeletal muscles. During this period of rapid development of promising genetic therapies, the combination of the mdx mouse and the diaphragm strip preparation has provided an ideal model for the evaluation of the success, or failure, of these genetic techniques to improve dystrophic muscle structure, function or both. With the 2 year life span of the mdx mouse, the impact of age-related effects can be studied in this model.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72970/1/j.1440-1681.2007.04865.x.pd

Group studio cycling; an effective intervention to improve cardio-metabolic health in overweight physically inactive individuals

Introduction: Supervised, laboratory based studies of high intensity interval training (HIIT) is effective at improving health markers in groups at risk of cardiovascular and metabolic disease. Studio cycling, incorporating aerobic and high intensity exercise, may offer a platform for the implementation of HIIT within the wider community. Methods: Eight, overweight, physically inactive (<1.5 hr·wk-1) but otherwise healthy volunteers completed eight weeks of supervised studio cycling lasting 20-50 minutes 3 times per week. Participants underwent assessment for maximal oxygen uptake (VO2max) body composition, blood lipids, glucose tolerance and insulin resistance before and after the intervention. Results: Adherence to training was >95%. Mean and peak intensity were equivalent to 83% and 97% of HRmax·VO2max increased from 27.1 ± 4.7 mL·kg·min-1 to 30.3 ± 4.3 mL·kg·min-1 (p < 0.0001). Body fat percentage was reduced by 13.6% from 31.8 ± 2.4% to 27.5 ± 4.5% (p < 0.05). Total cholesterol (4.8 ± 1.1 mmol·L-1 to 4.2 ± 1.2 mmol·L-1) and low-density lipoprotein cholesterol (2.6 ± 0.9 mmol·L-1 to 2.0 ± 1.2 mmol·L-1) were reduced (both p < 0.05). There were no significant differences to glucose tolerance or insulin resistance. Discussion: Group exercise is effective at improving the cardio-metabolic health in previously physically inactive overweight individuals. Coupled with the high adherence rate, studio cycling offers an effective intervention improving cardiovascular health in physically inactive cohorts. Conclusions: Studio cycling can be implemented as a highly effective high intensity interval training intervention for improving health in overweight, inactive individuals and may promote improved exercise adherence

Stellar spectroscopy: Fermions and holographic Lifshitz criticality

Electron stars are fluids of charged fermions in Anti-de Sitter spacetime. They are candidate holographic duals for gauge theories at finite charge density and exhibit emergent Lifshitz scaling at low energies. This paper computes in detail the field theory Green's function G^R(w,k) of the gauge-invariant fermionic operators making up the star. The Green's function contains a large number of closely spaced Fermi surfaces, the volumes of which add up to the total charge density in accordance with the Luttinger count. Excitations of the Fermi surfaces are long lived for w <~ k^z. Beyond w ~ k^z the fermionic quasiparticles dissipate strongly into the critical Lifshitz sector. Fermions near this critical dispersion relation give interesting contributions to the optical conductivity.Comment: 38 pages + appendices. 9 figure

Lattice potentials and fermions in holographic non Fermi-liquids: hybridizing local quantum criticality

We study lattice effects in strongly coupled systems of fermions at a finite density described by a holographic dual consisting of fermions in Anti-de-Sitter space in the presence of a Reissner-Nordstrom black hole. The lattice effect is encoded by a periodic modulation of the chemical potential with a wavelength of order of the intrinsic length scales of the system. This corresponds with a highly complicated "band structure" problem in AdS, which we only manage to solve in the weak potential limit. The "domain wall" fermions in AdS encoding for the Fermi surfaces in the boundary field theory diffract as usually against the periodic lattice, giving rise to band gaps. However, the deep infrared of the field theory as encoded by the near horizon AdS2 geometry in the bulk reacts in a surprising way to the weak potential. The hybridization of the fermions bulk dualizes into a linear combination of CFT1 "local quantum critical" propagators in the bulk, characterized by momentum dependent exponents displaced by lattice Umklapp vectors. This has the consequence that the metals showing quasi-Fermi surfaces cannot be localized in band insulators. In the AdS2 metal regime, where the conformal dimension of the fermionic operator is large and no Fermi surfaces are present at low T/\mu, the lattice gives rise to a characteristic dependence of the energy scaling as a function of momentum. We predict crossovers from a high energy standard momentum AdS2 scaling to a low energy regime where exponents found associated with momenta "backscattered" to a lower Brillioun zone in the extended zone scheme. We comment on how these findings can be used as a unique fingerprint for the detection of AdS2 like "pseudogap metals" in the laboratory.Comment: 42 pages, 5 figures; v2, minor correction, to appear in JHE

Cooper pairing near charged black holes

We show that a quartic contact interaction between charged fermions can lead to Cooper pairing and a superconducting instability in the background of a charged asymptotically Anti-de Sitter black hole. For a massless fermion we obtain the zero mode analytically and compute the dependence of the critical temperature T_c on the charge of the fermion. The instability we find occurs at charges above a critical value, where the fermion dispersion relation near the Fermi surface is linear. The critical temperature goes to zero as the marginal Fermi liquid is approached, together with the density of states at the Fermi surface. Besides the charge, the critical temperature is controlled by a four point function of a fermionic operator in the dual strongly coupled field theory.Comment: 1+33 pages, 4 figure

Semi-Holographic Fermi Liquids

We show that the universal physics of recent holographic non-Fermi liquid models is captured by a semi-holographic description, in which a dynamical boundary field is coupled to a strongly coupled conformal sector having a gravity dual. This allows various generalizations, such as a dynamical exponent and lattice and impurity effects. We examine possible relevant deformations, including multi-trace terms and spin-orbit effects. We discuss the matching onto the UV theory of the earlier work, and an alternate description in which the boundary field is integrated out.Comment: 26 pages, 4 figures; v2: typos corrected and report number adde

Holographic and Wilsonian Renormalization Groups

We develop parallels between the holographic renormalization group in the bulk and the Wilsonian renormalization group in the dual field theory. Our philosophy differs from most previous work on the holographic RG; the most notable feature is the key role of multi-trace operators. We work out the forms of various single- and double-trace flows. The key question, `what cutoff on the field theory corresponds to a radial cutoff in the bulk?' is left unanswered, but by sharpening the analogy between the two sides we identify possible directions.Comment: 31 pages, 3 figures. v2: Minor clarifications. Added reference

Effects of a school-based intervention on active commuting to school and health-related fitness

Background: Active commuting to school has declined over time, and interventions are needed to reverse this trend. The main objective was to investigate the effects of a school-based intervention on active commuting to school and health-related fitness in school-age children of Southern Spain. Methods: A total of 494 children aged 8 to 11 years were invited to participate in the study. The schools were non-randomly allocated (i.e., school level allocation) into the experimental group (EG) or the control group (CG). The EG received an intervention program for 6 months (a monthly activity) focused on increasing the level of active commuting to school and mainly targeting children’s perceptions and attitudes. Active commuting to school and health-related fitness (i.e., cardiorespiratory fitness, muscular fitness and speed-agility), were measured at baseline and at the end of the intervention. Children with valid data on commuting to school at baseline and follow-up, sex, age and distance from home to school were included in the final analysis (n = 251). Data was analyzed through a factorial ANOVA and the Bonferroni post-hoc test. Results: At follow up, the EG had higher rates of cycling to school than CG for boys only (p = 0.04), but not for walking to school for boys or girls. The EG avoided increases in the rates of passive commuting at follow up, which increased in the CG among girls for car (MD = 1.77; SE = 0.714; p = 0.010) and bus (MD = 1.77; SE = 0.714; p = 0.010) modes. Moreover, we observed significant interactions and main effects between independent variables (study group, sex and assessment time point) on health-related fitness (p < 0.05) over the 6-month period between groups, with higher values in the control group (mainly in boys). Conclusion: A school-based intervention focused on increasing active commuting to school was associated with increases in rates of cycling to school among boys, but not for walking to school or health-related fitness. However, the school-based intervention avoided increases in rates of passive commuting in the experimental group, which were significantly increased in girls of the control group