A large body of experimental data have shown that aerobic exercise of different duration, intensity, and pattern affect molecular mechanisms regulating mitochondrial biogenesis in skeletal muscles. ...This review focuses on the effects of exercise duration and intensity on the molecular mechanisms of mitochondrial biogenesis regulation in skeletal muscles, namely PGC-1α-dependent signaling. Studies of the effects of acute exercise and exercise training showed that an increase in the duration of aerobic exercise from 30 to 90 min does not provide additional stimuli to activate signaling pathways regulating post-translational modification of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and expression of the PGC-1α gene (
PPARGC1A
). Conversely, exercise intensity substantially affects mitochondrial biogenesis due to the increase in the recruitment of type II muscle fibers with accompanying pronounced metabolic shift leading to the activation of signaling cascades and expression of genes regulating mitochondrial biogenesis. Therefore, intermittent exercise, which recruits type II muscle fibers, is more efficient in the activation of mitochondrial biogenesis than work-matched continuous exercise. In skeletal muscle adapted to aerobic training, intensity-dependent activation of mitochondrial biogenesis after acute exercise is associated primarily with the AMP-activated protein kinase/PGC-1α pathway, expression of PGC-1α-regulated genes, and expression of
PPARGC1A
from the alternative (distal) inducible promoter regulated by the cAMP response element-binding protein 1-related transcription factors and their coactivators. Elucidation of the effects of duration and intensity of aerobic exercise on the PGC-1α-dependent and -independent mechanisms of mitochondrial biogenesis is important for treatment of patients with various metabolic disorders, as well as for optimization of training in athletes.
We consider the ambitwistor description of N=4 supersymmetric extension of U(N) Yang-Mills theory on Minkowski space R3,1. It is shown that solutions of super-Yang-Mills equations are encoded in real ...analytic U(N)-valued functions on a domain in superambitwistor space LR5|6 of real dimension (5|6). This leads to a procedure for generating solutions of super-Yang-Mills equations on R3,1 via solving a Riemann-Hilbert-type factorization problem on two-spheres in LR5|6.
In 1978, Friedberg and Lee introduced the phenomenological soliton bag model of hadrons, generalizing the MIT bag model developed in 1974 shortly after the formulation of QCD. In this model, quarks ...and gluons are confined due to coupling with a real scalar field ρ, which tends to zero outside some compact region S⊂R3 determined dynamically from the equations of motion. The gauge coupling in the soliton bag model runs as the inverse power of ρ, already at the semiclassical level. We show that this model arises naturally as a consequence of introducing the warped product metric dsM2+ρ2dsG2 on the principal G-bundle P(M,G)≅M×G with a non-Abelian group G over Minkowski space M=R3,1. Confinement of quarks and gluons in a compact domain S⊂R3 is a consequence of the collapse of the bundle manifold M×G to M outside S due to shrinking of the group manifold G to a point. We describe the formation of such regions S as a dynamical process controlled by the order parameter field ρ.
Skeletal muscle tissue demonstrates global hypermethylation with age. However, methylome changes across the time-course of differentiation in aged human muscle derived cells, and larger coverage ...arrays in aged muscle tissue have not been undertaken. Using 850K DNA methylation arrays we compared the methylomes of young (27 ± 4.4 years) and aged (83 ± 4 years) human skeletal muscle and that of young/aged heterogenous muscle-derived human primary cells (HDMCs) over several time points of differentiation (0, 72 h, 7, 10 days). Aged muscle tissue was hypermethylated compared with young tissue, enriched for; pathways-in-cancer (including; focal adhesion, MAPK signaling, PI3K-Akt-mTOR signaling, p53 signaling, Jak-STAT signaling, TGF-beta and notch signaling), rap1-signaling, axon-guidance and hippo-signalling. Aged cells also demonstrated a hypermethylated profile in pathways; axon-guidance, adherens-junction and calcium-signaling, particularly at later timepoints of myotube formation, corresponding with reduced morphological differentiation and reductions in MyoD/Myogenin gene expression compared with young cells. While young cells showed little alterations in DNA methylation during differentiation, aged cells demonstrated extensive and significantly altered DNA methylation, particularly at 7 days of differentiation and most notably in focal adhesion and PI3K-AKT signalling pathways. While the methylomes were vastly different between muscle tissue and HDMCs, we identified a small number of CpG sites showing a hypermethylated state with age, in both muscle tissue and cells on genes KIF15, DYRK2, FHL2, MRPS33, ABCA17P. Most notably, differential methylation analysis of chromosomal regions identified three locations containing enrichment of 6-8 CpGs in the HOX family of genes altered with age. With HOXD10, HOXD9, HOXD8, HOXA3, HOXC9, HOXB1, HOXB3, HOXC-AS2 and HOXC10 all hypermethylated in aged tissue. In aged cells the same HOX genes (and additionally HOXC-AS3) displayed the most variable methylation at 7 days of differentiation versus young cells, with HOXD8, HOXC9, HOXB1 and HOXC-AS3 hypermethylated and HOXC10 and HOXC-AS2 hypomethylated. We also determined that there was an inverse relationship between DNA methylation and gene expression for HOXB1, HOXA3 and HOXC-AS3. Finally, increased physical activity in young adults was associated with oppositely regulating HOXB1 and HOXA3 methylation compared with age. Overall, we demonstrate that a considerable number of HOX genes are differentially epigenetically regulated in aged human skeletal muscle and HDMCs and increased physical activity may help prevent age-related epigenetic changes in these HOX genes.
We consider Yang–Mills theory with a compact gauge group G on Minkowski space R3,1 and compare the introduction of masses of gauge bosons using the Stueckelberg and Higgs mechanisms. The Stueckelberg ...field ϕ is identified with a G-frame on the gauge vector bundle E and the kinetic term for ϕ leads to the mass of the gauge bosons. The Stueckelberg mechanism is extended to the Higgs mechanism by adding to the game a scalar field describing rescaling of metric on fibres of E. Thus, we associate Higgs fields as well as running coupling parameters with conformal geometry on fibres of gauge bundles. In particular, a running coupling tending to zero or to infinity is equivalent to an unbounded expansion of G-fibres or its contraction to a point. We also discuss scale connection, space-time dependent Higgs vacua and compactly supported gauge and quark fields as an attribute of confinement.
A
bstract
We consider pure SU(2) Yang-Mills theory on four-dimensional de Sitter dS
4
and anti-de Sitter AdS
4
spaces and construct various solutions to the Yang-Mills equations. On de Sitter space ...we reduce the Yang-Mills equations via an SU(2)-equivariant ansatz to Newtonian mechanics of a particle moving in
ℝ
3
under the influence of a quartic potential. Then we describe magnetic and electric-magnetic solutions, both Abelian and non-Abelian, all having finite energy and finite action. A similar reduction on anti-de Sitter space also yields Yang-Mills solutions with finite energy and action. We propose a lower bound for the action on both backgrounds. Employing another metric on AdS
4
, the SU(2) Yang-Mills equations are reduced to an analytic continuation of the above particle mechanics from
ℝ
3
to
ℝ
2
,
1
. We discuss analytical solutions to these equations, which produce infinite-action configurations. After a Euclidean continuation of dS
4
and AdS
4
we also present self-dual (instanton-type) Yang-Mills solutions on these backgrounds.
A
bstract
We consider Yang-Mills theory with a compact structure group
G
on four-dimensional de Sitter space dS
4
. Using conformal invariance, we transform the theory from dS
4
to the finite ...cylinder
I
×
S
3
, where
I
= (
−π/
2
, π/
2) and
S
3
is the round three-sphere. By considering only bundles
P
→
I
×
S
3
which are framed over the temporal boundary
∂
I
×
S
3
, we introduce additional degrees of freedom which restrict gauge transformations to be identity on
∂
I
×
S
3
. We study the consequences of the framing on the variation of the action, and on the Yang-Mills equations. This allows for an infinite-dimensional moduli space of Yang-Mills vacua on dS
4
. We show that, in the low-energy limit, when momentum along
I
is much smaller than along
S
3
, the Yang-Mills dynamics in dS
4
is approximated by geodesic motion in the infinite-dimensional space
M
vac
of gauge-inequivalent Yang-Mills vacua on
S
3
. Since
M
vac
≅
C
∞
(
S
3
,
G
)
/G
is a group manifold, the dynamics is expected to be integrable.
The attempt to characterize the process of “building of friendship” within the socialist bloc on the example of relations between the USSR and the GDR is made in the article. The leadership of these ...countries sought to establish the most friendly relations, the basis for which was a memorial consensus based on the unconditional acceptance by the official German side of the Soviet view of the events of World War II. However, at the level of interpersonal contacts, the “negative tail” of the communicative memory of the events of 1941—1945 persisted (moving into the “zone of silence”), even despite the widespread introduction of institutions, practices and rituals of friendship into relations between citizens of the two countries, a vivid example of which was regularly mass festivals of friendship between the youth of the USSR and the GDR, held in the 1970s and 1980s. In general, the author of the article concludes that the project of constructing the Soviet-German friendship was not effective enough not only because of the hidden memorial contradictions, but also because of the lack of a promising picture of a common future. By the 1970s and 1980s, citizens of the two countries, especially young people, had not received a clear, realistic idea of the future joint development of their countries within the framework of the common project of socialist integration, which contributed to the growth of skepticism in this direction and, as a result, became one of the reasons for the collapse of the socialist bloc in the late 1980s.
A brief survey of the studies in the area of adsorption decrease in the strength (the Rehbinder effect) of metals and rocks is given. The modern considerations about the nature of this effect are ...considered. The mechanisms and features of fracturing of materials in the contact with adsorption-active environments.
The presence of diffuse anaplasia in Wilms tumours (DAWT) is associated with TP53 mutations and poor outcome. As patients receive intensified treatment, we sought to identify whether TP53 mutational ...status confers additional prognostic information.
We studied 40 patients with DAWT with anaplasia in the tissue from which DNA was extracted and analysed for TP53 mutations and 17p loss. The majority of cases were profiled by copy number (n = 32) and gene expression (n = 36) arrays. TP53 mutational status was correlated with patient event-free and overall survival, genomic copy number instability and gene expression profiling.
From the 40 cases, 22 (55%) had TP53 mutations (2 detected only after deep-sequencing), 20 of which also had 17p loss (91%); 18 (45%) cases had no detectable mutation but three had 17p loss. Tumours with TP53 mutations and/or 17p loss (n = 25) had an increased risk of recurrence as a first event (p = 0.03, hazard ratio (HR), 3.89; 95% confidence interval (CI), 1.26-16.0) and death (p = 0.04, HR, 4.95; 95% CI, 1.36-31.7) compared to tumours lacking TP53 abnormalities. DAWT carrying TP53 mutations showed increased copy number alterations compared to those with wild-type, suggesting a more unstable genome (p = 0.03). These tumours showed deregulation of genes associated with cell cycle and DNA repair biological processes.
This study provides evidence that TP53 mutational analysis improves risk stratification in DAWT. This requires validation in an independent cohort before clinical use as a biomarker.
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