Effects of age and sex on epigenetic modification induced by an acute physical exercise

It has been observed that, after 2\u200ahours of aerobic exercise, plasma interleukin-6 (IL-6) increases whereas nuclear concentrations of enzyme DNA methyltransferase (DNMT) 3B significantly decreased in peripheral blood mononuclear cells (PBMCs), with no change observed in DNMT3A. The aim of the present study was to detect differences in these changes induced by exercise in plasma IL-6 levels as well as in PBMC nuclear concentrations of DNMT3A and DNMT3B, in relation to age and sex. Four groups were studied: 12 young men (24.8\u200a\ub1\u200a1.77 years old), 12 young women (23.8\u200a\ub1\u200a1.81 years old), 12 adult men (45.8\u200a\ub1\u200a1.82 years old), 12 adult women (mean 44.5\u200a\ub1\u200a2.07 years old). Participants had to run at 60% of maximal oxygen consumption (VO2max) for 120\u200aminutes, interspersed with sprints at 90% of VO2max for the last 30\u200aseconds of every 10\u200aminutes. About 250\u200a\u3bcL of PBMCs (1\u200a 7\u200a10 cells) were treated with 100\u200a\u3bcL of either pre-exercise plasma or post-exercise plasma and nuclear DNMT3A and DNMT3B concentrations were quantified. No change in nuclear concentration of DNMT3A following the exercise was observed. Conversely, nuclear concentrations of DNMT3B significantly decreased, with a reduction of about 78% in young men, 72% in young women, 61% in adult men, and 53% in adult women. Moreover, a strong positive correlation between the nuclear concentration of DNMT3B in PBMC following stimulation with post-exercise plasma and post-exercise plasma concentrations of IL-6 was observed in all the 4 studied groups. This study confirms that a single bout of endurance exercise is sufficient to decrease nuclear concentrations of DNMT3B and thus protein upregulation. Moreover, the epigenetic mechanisms induced by exercise apparently cause more intense changes in men than in women and that, in both of them, this effect seems to decrease with age

Flexibility of Gender Stereotypes: Italian Study on Comparative Gender-consistent and Gender-inconsistent Information

The topic of this study is flexibility in gender stereotyping linked to attribution of toys, socio-cognitive traits, and occupations in 160 Italian children aged 6 to 12 years. We used the Gender Toys Choice, the Gender Traits Choice, and the Gender Jobs Choice, a selected set of colored cards containing masculine and feminine stimuli to assign to a male or female or both male and female silhouette (the flexible-choice technique). In order to verify the change of flexibility in gender stereotyping, we made use of four cartoon stories with male and female characters with typical or atypical traits and performing gender-consistent or gender-inconsistent activities. Results indicated that the exposure to cartoon stories with gender-inconsistent information rather than cartoon stories with gender-consistent information increased flexibility in gender stereotyping, showing age differences in favor of children aged 11-12. Implications in relation to the developmental-constructivist approach were noted

Reduction of mdx mouse muscle degeneration by low-intensity endurance exercise: a proteomic analysis in quadriceps muscle of exercised versus sedentary mdx mice

In our recent study was shown a significant recovery of damaged skeletal muscle of mice with x-linked muscular dystrophy (mdx) following low-intensity endurance exercise, probably by reducing the degeneration of dystrophic muscle. Consequently, in the present work we aimed to identify proteins involved in the observed reduction of degenerating fibers. To this end, we used proteomic analysis to evaluate changes in the protein profile of quadriceps dystrophic muscles of exercised versus sedentary mdx mice. Four protein spots were found to be significantly changed and were identified as three isoforms of Carbonic anhydrase 3 (CA3) and superoxide dismutase [Cu-Zn] (SODC). Protein levels of CA3 isoforms were significantly up-regulated in quadriceps of sedentary mdx mice and were completely restored to wild type mice values, both sedentary and exercised, in quadriceps of exercised mdx mice. Protein levels of SODC were down-regulated in quadriceps of sedentary mdx mice and were significantly restored to wild type mice values, both sedentary and exercised, in quadriceps of exercised mdx mice. Western blot data were in agreement with those obtained using proteomic analysis and revealed the presence of one more CA3 isoform that was significantly changed. Based on data found in the present study, it seems that low-intensity endurance exercise may in part contribute to reduce cell degeneration process in mdx muscles, by counteracting oxidative stress

Overexpression of Mcl-1 exacerbates lymphocyte accumulation and autoimmune kidney disease in lpr mice

Cell death by apoptosis has a critical role during embryonic development and in maintaining tissue homeostasis. In mammals, there are two converging apoptosis pathways: the ‘extrinsic’ pathway, which is triggered by engagement of cell surface ‘death receptors’ such as Fas/APO-1; and the ‘intrinsic’ pathway, which is triggered by diverse cellular stresses, and is regulated by prosurvival and pro-apoptotic members of the Bcl-2 family of proteins. Pro-survival Mcl-1, which can block activation of the proapoptotic proteins, Bax and Bak, appears critical for the survival and maintenance of multiple haemopoietic cell types. To investigate the impact on haemopoiesis of simultaneously inhibiting both apoptosis pathways, we introduced the vavP-Mcl-1 transgene, which causes overexpression of Mcl-1 protein in all haemopoietic lineages, into Faslpr/lpr mice, which lack functional Fas and are prone to autoimmunity. The combined mutations had a modest impact on myelopoiesis, primarily an increase in the macrophage/monocyte population in Mcl-1tg/lpr mice compared with lpr or Mcl-1tg mice. The impact on lymphopoiesis was striking, with a marked elevation in all major lymphoid subsets, including the non-conventional double-negative (DN) T cells (TCRβ+ CD4– CD8– B220+ ) characteristic of Faslpr/lpr mice. Of note, the onset of autoimmunity was markedly accelerated in Mcl-1tg/lpr mice compared with lpr mice, and this was preceded by an increase in immunoglobulin (Ig)-producing cells and circulating autoantibodies. This degree of impact was surprising, given the relatively mild phenotype conferred by the vavP-Mcl-1 transgene by itself: a two- to threefold elevation of peripheral B and T cells, no significant increase in the non-conventional DN T-cell population and no autoimmune disease. Comparison of the phenotype with that of other susceptible mice suggests that the development of autoimmune disease in Mcl-1tg/lpr mice may be influenced not only by Ig-producing cells but also other haemopoietic cell types

The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Effects of an exhaustive exercise on motor skill learning and on the excitability of primary motor cortex and supplementary motor area

We examined, on 28 healthy adult subjects, the possible correlations of an exhaustive exercise, and the consequent high blood lactate levels, on immediate (explicit) and delayed (implicit) motor execution of sequential finger movements (cognitive task). Moreover, we determined with transcranial magnetic stimulation whether changes in motor performance are associated with variations in excitability of primary motor area (M1) and supplementary motor area (SMA). We observed that, after an acute exhaustive exercise, the large increase of blood lactate is associated with a significant worsening of both explicit and implicit sequential visuomotor task paradigms, without gender differences. We also found that, at the end of the exhaustive exercise, there is a change of excitability in both M1 and SMA. In particular, the excitability of M1 was increased whereas that of SMA decreased and, also in this case, without gender differences. These results support the idea that an increase of blood lactate after an exhaustive exercise appears to have a protective effect at level of primary cortical areas (as M1), although at the expense of efficiency of adjacent cortical regions (as SMA)

Representation of movement velocity in the rat's interpositus nucleus during passive forelimb movements

The interpositus nucleus (IN) receives a large amount of sensory information from the limbs and, in turn, elaborates signals for movement control. In this paper, we tried to gather evidence on the possibility that neurons in the IN may elaborate sensory representations of the forelimb kinematics and, particularly, of the movement velocity vector. For this purpose, the forepaw of anesthetized rats was attached to a computer-controlled robot arm displaced passively along two types of trajectories (circular and figure eight), with the limb joints unconstrained. The firing activity of single cells was recorded and related to limb position and the two components of the movement velocity vector, namely, movement speed and direction. By using multiple regression analysis, we found that 12 out of 85 (14%) neurons were modulated by position, 18 out of 85 (21%) neurons were modulated by direction, 24 out of 85 (28%) neurons were modulated by movement speed, and 31 out of 85 (37%) neurons were sensitive to the full movement velocity vector. Most of the neurons modulated only by the speed component of the velocity vector (19 out of 24) were located in the posterior portion of the IN, whereas neurons in the anterior portion were mostly related to both components of the velocity vector. These results suggest that sensory information related to whole-limb movement velocity may be encoded by the IN, indicating also that the posterior interpositus may preferentially represent movement speed