Non-invasive muscle contraction assay to study rodent models of sarcopenia

<p>Abstract</p> <p>Background</p> <p>Age-related sarcopenia is a disease state of loss of muscle mass and strength that affects physical function and mobility leading to falls, fractures, and disability. The need for therapies to treat age-related sarcopenia has attracted intensive preclinical research. To facilitate the discovery of these therapies, we have developed a non-invasive rat muscle functional assay system to efficiently measure muscle force and evaluate the efficacy of drug candidates.</p> <p>Methods</p> <p>The lower leg muscles of anesthetized rats are artificially stimulated with surface electrodes on the knee holders and the heel support, causing the lower leg muscles to push isometric pedals that are attached to force transducers. We developed a stimulation protocol to perform a fatigability test that reveals functional muscle parameters like maximal force, the rate of fatigue, fatigue-resistant force, as well as a fatigable muscle force index. The system is evaluated in a rat aging model and a rat glucocorticoid-induced muscle loss model</p> <p>Results</p> <p>The aged rats were generally weaker than adult rats and showed a greater reduction in their fatigable force when compared to their fatigue-resistant force. Glucocorticoid treated rats mostly lost fatigable force and fatigued at a higher rate, indicating reduced force from glycolytic fibers with reduced energy reserves.</p> <p>Conclusions</p> <p>The involuntary contraction assay is a reliable system to assess muscle function in rodents and can be applied in preclinical research, including age-related sarcopenia and other myopathy.</p

The role of iron minerals in laminae formation in Late Pleistocene sediments of the Caspian Sea

International audienceThe 995 cm long sediment core was collected from the Central basin of the Caspian Sea. The sedimentary sequence, which covers the Late Pleistocene and Holocene, is marked in its Late Pleistocene section by well-developed black and grey/brownish laminae, which promptly disappear under oxidising conditions.Studies of granulometry, major elements, carbonate and organic matter content, and magnetic parameters, were conducted at laminae scale. In non-magnetic parameters, only sulphur clearly changes between black and grey/brownish laminae. Magnetic parameters indicate the presence of high contents of iron sulphide (greigite) in black laminae, while low contents of iron oxide (magnetite) are detected in grey/brownish laminae. The lamination is due to early diagenesis in sediment just below the sea bed, related to the oxygenation state of the bottom water. Under poorly oxygenated conditions, greigite isformed in anoxic sediment, with increased oxygenation, detrital magnetite is preserved. Broadly similar processes were described from the Southern Caspian Sea basin. During the Late Pleistocene, both basins were subjected to the same, rhythmic ventilation of bottom waters. Efficient ventilation is most probablyrelated to the harshness of the winter (cold/mild winters) and thus production of more or less cold, dense descending waters, and the content of fresh water supply from the catchment area. These two processes can act annually, as well as on a longer time scale

The role of irion minerals in laminae formation in Late Pleistocene sédiments of the Caspian Sea

International audienceThe 995 cm long sediment core was collected from the Central basin of the Caspian Sea. The sedimentary sequence, which covers the Late Pleistocene and Holocene, is marked in its Late Pleistocene section by well-developed black and grey/brownish laminae, which promptly disappear under oxidising conditions. Studies of granulometry, major elements, carbonate and organic matter content, and magnetic parameters, were conducted at laminae scale. In non-magnetic parameters, only sulphur clearly changes between black and grey/brownish laminae. Magnetic parameters indicate the presence of high contents of iron sulphide (greigite) in black laminae, while low contents of iron oxide (magnetite) are detected in grey/brownish laminae. The lamination is due to early diagenesis in sediment just below the sea bed, related to the oxygenation state of the bottom water. Under poorly oxygenated conditions, greigite is formed in anoxic sediment, with increased oxygenation, detrital magnetite is preserved. Broadly similar processes were described from the Southern Caspian Sea basin. During the Late Pleistocene, both basins were subjected to the same, rhythmic ventilation of bottom waters. Efficient ventilation is most probably related to the harshness of the winter (cold/mild winters) and thus production of more or less cold, dense descending waters, and the content of fresh water supply from the catchment area. These two processes can act annually, as well as on a longer time scale

MRI and FDG PET/CT findings in a case of probable Heidenhain variant Creutzfeldt-Jakob disease.

Creutzfeldt-Jakob disease (CJD) is a neurodegenerative disease caused by the accumulation of a pathogenic isoform of a prion protein in neurons that is responsible for subacute dementia. The Heidenhain variant is an atypical form of CJD in which visual signs are predominant. This is a report of the case of a 65-year-old man with probable CJD of the Heidenhain variant, with topographical concordance between findings on magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose (FDG) photopenic areas on positron emission tomography (PET)/computed tomography (CT) for cortical parietooccipital lesions

In vivo reduction in ATP cost of contraction is not related to fatigue level in stimulated rat gastrocnemius muscle

We tested whether the reduction in ATP cost of contraction during in vivo stimulation of rat gastrocnemius muscle was related to fatigue level.Muscles (n = 44) were electrically stimulated to perform 6 min repeated isometric contractions at different frequencies; one non-fatiguing protocol (stimulation at 0.8 Hz) and five fatiguing protocols (2, 3.2, 4, 5.2 and 7.6 Hz) were used. Anaerobic and oxidative ATP turnover rates were measured non-invasively using 31P-magnetic resonance spectroscopy.At the onset of the stimulation period, no signs of fatigue were measured in the six protocols and ATP cost of contraction did not differ significantly (P = 0.45) among protocols (mean value of 1.76 ± 0.11 mm (N s)−1).For the six protocols, ATP cost of contraction was significantly reduced (P < 0.05) at the end of the stimulation period when compared with the initial value. This reduction did not differ significantly (P = 0.61) among the five fatiguing protocols (averaging 35 ± 3 % of initial value), whereas isometric force decreased significantly as stimulation frequency increased. No significant correlation (P = 0.87, r2= 0.01) was observed between isometric force and ATP cost of contraction at the end of the stimulation period. In addition, this reduction was significantly lower (P < 0.05) for the non-fatiguing protocol (67 ± 9 % of initial value) when compared with the fatiguing protocols.These results demonstrate that (i) the reduction in ATP cost of contraction during in vivo stimulation of rat gastrocnemius muscle is not related to the fatigue level; (ii) surprisingly, this reduction was significantly larger during the fatiguing protocols compared with the non-fatiguing protocol

The glacial-post glacial transition in the southern Caspian Sea.

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Finite-Tree Analysis for Constraint Logic-Based Languages

Logic languages based on the theory of rational, possibly infinite, trees have much appeal in that rational trees allow for faster unification (due to the safe omission of the occurs-check) and increased expressivity (cyclic terms can provide very e#cient representations of grammars and other useful objects). Unfortunately, the use of infinite rational trees has problems. For instance, many of the built-in and library predicates are ill-defined for such trees and need to be supplemented by run-time checks whose cost may be significant. Moreover, some widely-used program analysis and manipulation techniques are correct only for those parts of programs working over finite trees. It is thus important to obtain, automatically, a knowledge of the program variables (the finite variables) that, at the program points of interest, will always be bound to finite terms. For these reasons, we propose here a new dataflow analysis, based on abstract interpretation, that captures such information. We present a parametric domain where a simple component for recording finite variables is coupled, in the style of the open product construction of Cortesi et al., with a generic domain (the parameter of the construction) providing sharing information. The sharing domain is abstractly specified so as to guarantee the correctness of the combined domain and the generality of the approach. This finite-tree analysis domain is further enhanced by coupling it with a domain of Boolean functions, called finite-tree dependencies, that precisely captures how the finiteness of some variables influences the finiteness of other variables. We also summarize our experimental results showing how finite-tree analysis, enhanced with finite-tree dependencies, is a practical means of obtaining precise finitenes..

The glacial-post glacial transition in the southern Caspian Sea

International audienc