Kinetic coupling of phosphate release, force generation and rate-limiting steps in the cross-bridge cycle

A basic goal in muscle research is to understand how the cyclic ATPase activity of cross-bridges is converted into mechanical force. A direct approach to study the chemo-mechanical coupling between P-i release and the force-generating step is provided by the kinetics of force response induced by a rapid change in [P-i]. Classical studies on fibres using caged-P-i discovered that rapid increases in [P-i] induce fast force decays dependent on final [P-i] whose kinetics were interpreted to probe a fast force-generating step prior to P-i release. However, this hypothesis was called into question by studies on skeletal and cardiac myofibrils subjected to P-i jumps in both directions (increases and decreases in [P-i]) which revealed that rapid decreases in [P-i] trigger force rises with slow kinetics, similar to those of calcium-induced force development and mechanically-induced force redevelopment at the same [P-i]. A possible explanation for this discrepancy came from imaging of individual sarcomeres in cardiac myofibrils, showing that the fast force decay upon increase in [P-i] results from so-called sarcomere 'give'. The slow force rise upon decrease in [P-i] was found to better reflect overall sarcomeres cross-bridge kinetics and its [P-i] dependence, suggesting that the force generation coupled to P-i release cannot be separated from the rate-limiting transition. The reasons for the different conclusions achieved in fibre and myofibril studies are re-examined as the recent findings on cardiac myofibrils have fundamental consequences for the coupling between P-i release, rate-limiting steps and force generation. The implications from P-i-induced force kinetics of myofibrils are discussed in combination with historical and recent models of the cross-bridge cycle

Science and Religion: Enemies for life?

The article published by Prof. Antonio Neviani in 1896 offered us an interesting opportunity to discuss about the teaching of human evolution in schools today. Already at the end of the nineteenth century, Neviani complained about the fact that the teaching of the theory of evolution was not present in schools. Here, we present the thought of Neviani and we invite to reflect on the prohibition, still present in some countries, of the teaching of Darwin's theory. (www.actabiomedica.it)

Cosmotellurism in Lombroso's work.

Background and aim of the work: Few know that Lombroso was also involved in epidemiological research. In particular, Lombroso’s scientific reflections on Medical Geography were addressed to the theme of climate influences and meteorological conditions on human conduct. The authors analyze the scientific production and the works of Lombroso devoted to medical geography. Discussion: Lombroso carried out accurate epidemiological investigations using the statistical method with great modernity, combining health data with geographical and climatic data to demonstrate the relationship between man, the environment and health in a social vision of preventive and curative medicine. Conclusions: The theory of Cosmotellurism in Lombroso’s work is not only a source of unquestionable interest in the History of Medicine. The heritage of Medical Geography within the pre-bacteriological medical culture can continue with its teachings to correctly address the clinician’s thinking even in the current historical context in which endemic and epidemic pathologies re-emerge in various parts of the world

A case of erosive polyarthropathy from Medieval northern Italy (12th–13th centuries)

Objective: To evaluate and differentially diagnose erosive skeletal lesions located on multiple joints of an individual archaeologically recovered in 2017. Materials: Skeletal remains of a well-preserved skeleton dating to the 12th–13th centuries from the Medieval church of San Biagio in Cittiglio (Varese, northern Italy). Methods: Macroscopic and radiographic imaging. Results: Erosive marginal symmetrical lesions are present on the metatarsophalangeal, metacarpophalangeal and interphalangeal joints of an adult male, aged 55–75 years. Osteolytic changes, in the form of pocket erosions, surface resorptions and pseudocyst formations, are also macroscopically observed on some carpal and tarsal bones and on several large peripheral joints. Conclusions: A careful differential diagnosis of the lesions and their macroscopic and radiological appearance are suggestive of a case of rheumatoid arthritis-like polyarthropathy. Significance: This case contributes to the debate regarding the antiquity of erosive polyarthropathies, providing additional evidence for the existence of these diseases in the Old World prior to the discovery of the Americas. Limitations: Small sample size limits discussion of the scope of the disease in antiquity. Suggestions for further research: This case highlights the need for further macroscopic, radiographic, and biomolecular studies of pre-modern European skeletal samples to investigate the hypothesized pre-existence of these pathological conditions in Europe prior to 1492