Structural and functional alterations of the cell nucleus in skeletal muscle wasting: the evidence in situ

The histochemical and ultrastructural analysis of the nuclear components involved in RNA transcription and splicing can reveal the occurrence of cellular dysfunctions eventually related to the onset of a pathological phenotype. In recent years, nuclear histochemistry at light and electron microscopy has increasingly been used to investigate the basic mechanisms of skeletal muscle diseases; the in situ study of nuclei of myofibres and satellite cells proved to be crucial for understanding the pathogenesis of skeletal muscle wasting in sarcopenia, myotonic dystrophy and laminopathies

Selberg integrals in 1D random Euclidean optimization problems

We consider a set of Euclidean optimization problems in one dimension, where the cost function associated to the couple of points $x$ and $y$ is the Euclidean distance between them to an arbitrary power $p\ge1$, and the points are chosen at random with flat measure. We derive the exact average cost for the random assignment problem, for any number of points, by using Selberg's integrals. Some variants of these integrals allows to derive also the exact average cost for the bipartite travelling salesman problem.Comment: 9 pages, 2 figure

Is altitude training an efficient treatment for obesity?

Worldwide, about half the adult population is considered overweight as defined by a body mass index (BMI - calculated by body weight divided by height squared) ratio in excess of 25 kg.m-2. Of these individuals, half are clinically obese (with a BMI in excess of 30) and these numbers are still increasing, notably in developing countries such as those of the Middle East region. Obesity is a disorder characterised by increased mass of adipose tissue (excessive fat accumulation) that is the result of a systemic imbalance between food intake and energy expenditure. Although factors such as family history, sedentary lifestyle, urbanisation, income and family diet patterns determine obesity prevalence, the main underlying causes are poor knowledge about food choice and lack of physical activity3. Current obesity treatments include dietary restriction, pharmacological interventions and ultimately, bariatric surgery. The beneficial effects of physical activity on weight loss through increased energy expenditure and appetite modulation are also firmly established. Another viable option to induce a negative energy balance, is to incorporate hypoxia per se or combine it with exercise in an individual's daily schedule. This article will present recent evidence suggesting that combining hypoxic exposure and exercise training might provide a cost-effective strategy for reducing body weight and improving cardio-metabolic health in obese individuals. The efficacy of this approach is further reinforced by epidemiological studies using large-scale databases, which evidence a negative relationship between altitude of habitation and obesity. In the United States, for instance, obesity prevalence is inversely associated with altitude of residence and urbanisation, after adjusting for temperature, diet, physical activity, smoking and demographic factors

A linear optical coupler for cryogenic detectors

Abstract We present an improved version of a linear low-noise optical coupler having differential input and capable of driving a twisted cable to long distances, avoiding ground loops and electromagnetic interference. Owing to device optimization, this circuit version is able to be fast. Its frequency bandwidth is about 900 kHz, more than ten times larger than our previous implementation. The optical coupler presented is therefore suitable to be used with most of the applications with cryogenic detectors

Novel applications of long-established histochemical techniques to study nanoparticle-cell interactions at transmission electron microscopy

Alcian blue staining has been used to visualise nanoparticles at transmission electron microscop

Routinely frozen biopsies of human skeletal muscle are suitable for morphological and immunocytochemical analyses at transmission electron microscopy

The aim of the present investigation was to evaluate whether routinely frozen biopsies of human skeletal muscle may be suitable for morphological and immunocytochemical analyses at transmission electron microscopy. The fixation/embedding protocols we successfully used for decades to process fresh mammalian tissues have been applied to frozen muscle biopsies stored for one to four years in liquid nitrogen. After 2.5% glutaraldehyde -2% paraformaldehyde - 1% OsO4 fixation and embedding in epoxy resin, the ultrastructural morphology of myofibres and satellite cells as well as of their organelles and inclusions proved to be well preserved. As expected, after 4% paraformaldehyde - 0.5% glutaraldehyde fixation and embedding in LR White resin, the morphology of membrane-bounded organelles was relatively poor, although myofibrillar and sarcomeric organization was still recognizable. On the contrary, the myonuclei were excellently preserved and, after conventional staining with uranyl acetate, showed an EDTA-like effect, i.e. the bleaching of condensed chromatin, which allows the visualization of RNP-containing structures. These samples proved to be suitable for immunocytochemical analyses of both cytoskeletal and nuclear components, whereas the poor mitochondrial preservation makes unreliable any in situ investigation on these organelles

Time course of muscle activation, energetics and mechanics of running in minimalist and traditional cushioned shoes during level running.

The study aimed to compare the ankle muscles activation, biomechanics and energetics of running in male runners during submaximal level run using minimalist (MinRS) and traditional cushioned (TrdRS) running shoes. During 45-min running in MinRS and TrdRS, the ankle muscles pre- and co-activation, biomechanics, and energetics of running of 16 male endurance runners (25.5 ± 3.5 yr) were assessed using surface electromyography (tibialis anterior and gastrocnemius lateralis), instrumented treadmill and indirect calorimetry, respectively. The net energy cost of running (C <sub>r</sub> ) was similar for both conditions (P = 0.25) with a significant increase over time (P < 0.0001). Step frequency (P < 0.001), and total mechanical work (P = 0.001) were significantly higher in MinRS than in TrdRS with no evolution over time (P = 0.28 and P = 0.85, respectively). The ankle muscles pre- and co-activation during the contact phase did not differ between the two shoe conditions (P ≥ 0.33) or over time (P ≥ 0.15). In conclusion, during 45-min running, Cr and muscle pre- and co-activation were not significantly different between MinRS and TrdRS with significantly higher step frequency and total mechanical work noted in the former than in the latter. Moreover, C <sub>r</sub> significantly increased during the 45-min trial in both shoe conditions along with no significant change over time in muscle activation and biomechanical variables

Cultured myoblasts from patients affected by myotonic dystrophy type 2 exhibit senescence-related features: ultrastructural evidence

Myotonic dystrophy type 2 (DM2) is an autosomal dominant disorder caused by the expansion of the tetranucleotidic repeat (CCTG)n in the first intron of the Zinc Finger Protein-9 gene. In DM2 tissues, the expanded mutant transcripts accumulate in nuclear focal aggregates where splicing factors are sequestered, thus affecting mRNA processing. Interestingly, the ultrastructural alterations in the splicing machinery observed in the myonuclei of DM2 skeletal muscles are reminiscent of the nuclear changes occurring in age-related muscle atrophy. Here, we investigated in vitro structural and functional features of satellite cell-derived myoblasts from biceps brachii, in the attempt to investigate cell senescence indices in DM2 patients by ultrastructural cytochemistry. We observed that in satellite cell-derived DM2 myoblasts, cell-senescence alterations such as cytoplasmic vacuolization, reduction of the proteosynthetic apparatus, accumulation of heterochromatin and impairment of the pre-mRNA maturation pathways occur earlier than in myoblasts from healthy patients. These results, together with preliminary in vitro observations on the early onset of defective structural features in DM2 myoblast derived-myotubes, suggest that the regeneration capability of DM2 satellite cells may be impaired, thus contributing to the muscular dystrophy in DM2 patients

Hyaluronic acid-based nanocomplexes as novel drug-nanocarriers to treat myotonic dystrophy

Hyaluronic acid-based nanocomplexes have been developpend as novel drug-nanocarriers to treat myotonic dystroph