Myosin Isoform-Dependent Effect of Omecamtiv Mecarbil on the Regulation of Force Generation in Human Cardiac Muscle.

Omecamtiv mecarbil (OM) is a small molecule that has been shown to improve the function of the slow human ventricular myosin (MyHC) motor through a complex perturbation of the thin/thick filament regulatory state of the sarcomere mediated by binding to myosin allosteric sites coupled to inorganic phosphate (Pi) release. Here, myofibrils from samples of human left ventricle (β-slow MyHC-7) and left atrium (α-fast MyHC-6) from healthy donors were used to study the differential effects of μmolar [OM] on isometric force in relaxing conditions (pCa 9.0) and at maximal (pCa 4.

Calcified uterine leiomyoma from an 18th-century nunnery in North Italy.

Objective: To develop a differential diagnosis of a mass retrieved alongside skeletal remains in the crypt of the church of Santissima Annunziata of Valenza (Province of Alessandria, Northern Italy).

Material: A calcified mass measuring 40 × 39 mm and 17.62 × 16.

Elongated styloid process of an autopsied skull from the Cemetery of Santa Maria Maggiore in Vercelli, 18-19 century (Piedmont, northern Italy).

We discuss the coexistence of a postmortem cut and a pathological alteration, recorded on a skeleton belonging to an adult man that was discovered during the archaeological investigations of the cemetery of the Church of Santa Maria Maggiore in Vercelli (northern Italy, 18-19 century). The skull presents an oblique cleft, which from the top of the frontal bone bends towards the occipital, and the left styloid process is elongated compared to normal values (48 mm). The elongated styloid process is due to the ossification of the styloid ligament which has several possible causes.

Corrigendum: Calcium handling maturation and adaptation to increased substrate stiffness in human iPSC-derived cardiomyocytes: the impact of full-length dystrophin deficiency.

[This corrects the article DOI: 10.3389/fphys.2022.

A possible case of orbital osteomyelitis from the medieval cemetery of Sant' Agostino in Caravate (Varese, Northern Italy).

Objectives: This paper aims to present one of the first osteoarchaeological cases of orbital osteomyelitis and provides the best diagnostic criteria to identify its pathophysiological changes.

Materials: A well-preserved skeleton of an adult male from the medieval cemetery of Sant' Agostino in Caravate, Italy.

Methods: Macroscopic, tomographic, and histological analyses were performed using standard methods.

Ablation of palladin in adult heart causes dilated cardiomyopathy associated with intercalated disc abnormalities.

Palladin (PALLD) belongs to the PALLD/myopalladin (MYPN)/myotilin family of actin-associated immunoglobulin-containing proteins in the sarcomeric Z-line. PALLD is ubiquitously expressed in several isoforms, and its longest 200 kDa isoform, predominantly expressed in striated muscle, shows high structural homology to MYPN. gene mutations are associated with human cardiomyopathies, whereas the role of PALLD in the heart has remained unknown, partly due to embryonic lethality of PALLD knockout mice.

Slower Calcium Handling Balances Faster Cross-Bridge Cycling in Human HCM.

Background: The pathogenesis of -associated hypertrophic cardiomyopathy (HCM) is still unresolved. In our HCM patient cohort, a large and well-characterized population carrying the :c772G>A variant (p.Glu258Lys, E258K) provides the unique opportunity to study the basic mechanisms of -HCM with a comprehensive translational approach.

Calcium handling maturation and adaptation to increased substrate stiffness in human iPSC-derived cardiomyocytes: The impact of full-length dystrophin deficiency.

Cardiomyocytes differentiated from human induced Pluripotent Stem Cells (hiPSC- CMs) are a unique source for modelling inherited cardiomyopathies. In particular, the possibility of observing maturation processes in a simple culture dish opens novel perspectives in the study of early-disease defects caused by genetic mutations before the onset of clinical manifestations. For instance, calcium handling abnormalities are considered as a leading cause of cardiomyocyte dysfunction in several genetic-based dilated cardiomyopathies, including rare types such as Duchenne Muscular Dystrophy (DMD)-associated cardiomyopathy.

A possible case of "kissing" osteochondroma and multiple enchondromas in a medieval skeleton from the church of Sant' Agostino in Caravate (Northern Italy).

This work presents the neoplastic bone changes found in the lower limb of a medieval skeleton from the church of Sant' Agostino in Caravate (Northern Italy). After briefly assessing the individual's overall pathological picture, a differential diagnosis for the neoplastic changes is now proposed. These changes were analysed macroscopically and radiographically and subsequently evaluated considering the paleopathological and clinical literature available.

The harder the climb the better the view: The impact of substrate stiffness on cardiomyocyte fate.

The quest for novel methods to mature human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for cardiac regeneration, modelling and drug testing has emphasized a need to create microenvironments with physiological features. Many studies have reported on how cardiomyocytes sense substrate stiffness and adapt their morphological and functional properties. However, these observations have raised new biological questions and a shared vision to translate it into a tissue or organ context is still elusive.

Five brains of alienated criminals. Neurological investigations of early twentieth century criminal anthropology.

Background: For the followers of criminal anthropology, during the second half of the 19th and the beginning of the 20th century, the association "anatomical anomaly - psyche anomaly" represented an immediate diagnostic tool to identify mental illness and consequently the tendency to become a criminal. In this article, we analyse a clinical report published in 1900 in which the author, Dr. Saporito, described five brains of alienated criminals from the Aversa asylum.

Alpha and beta myosin isoforms and human atrial and ventricular contraction.

Human atrial and ventricular contractions have distinct mechanical characteristics including speed of contraction, volume of blood delivered and the range of pressure generated. Notably, the ventricle expresses predominantly β-cardiac myosin while the atrium expresses mostly the α-isoform. In recent years exploration of the properties of pure α- & β-myosin isoforms have been possible in solution, in isolated myocytes and myofibrils.

Accessory sacroiliac joints and the iliosacral complex: two case studies from a medieval and post-medieval cemetery in northern Italy.

The detection of parturition markers on archaeological pelvic bones is relevant for the reconstruction of the biological profiles of female individuals, in whose life history pregnancy represents a crucial biological event. During a preliminary study on a sample of 18 individuals from the medieval and post-medieval cemetery of San Biagio in Cittiglio (northern Italy), two skeletons exhibited evidence of noteworthy bony projections at the sacroiliac level. In clinical studies, these occurrences can be connected to several biological variables such as age, obesity, and multiple births, suggesting that they are a possible consequence of weight-bearing stresses.

Myopalladin knockout mice develop cardiac dilation and show a maladaptive response to mechanical pressure overload.

Myopalladin (MYPN) is a striated muscle-specific immunoglobulin domain-containing protein located in the sarcomeric Z-line and I-band. gene mutations are causative for dilated (DCM), hypertrophic, and restrictive cardiomyopathy. In a yeast two-hybrid screening, MYPN was found to bind to titin in the Z-line, which was confirmed by microscale thermophoresis.

The fate of stillborns. Perceptions from a historical, anthropological and bioethical reasoning.

Issues of disposal of fetal remains and related parental distress do not concern only the present. This contribution aims at offering a glimpse of what grieving management concerning perinatal death must have been in ancient times. The discussion of the topic of death and treatment of perinatal remains is based on historical, anthropological, and bioethical reasoning, in a dialogue that contributes to the current debate on fetal personhood.

A Severe Case of Biparietal Thinning in a Medieval Skull From a Northern Italy Necropolis.

This study aims at presenting a case of symmetrical and bilateral thinning observed in a skull belonging to the skeleton of a mature woman from the medieval cemetery of Caravate (north Italy). Macroscopical, radiological, and histological analyses were performed to investigate the condition. The analyses allowed us to detect a progressive loss of both the outer table and the diploe, and the sparing of the inner table.

Five autopsy reports of rib fractures in the mental hospital of Reggio Emilia (1874-5): pathogenesis proposal in defence of the 'non-restraint' system.

At the end of the nineteenth century, recurrent cases of rib fractures were recorded in psychiatric asylums, opening a long chapter of discussions about the application of the 'non-restraint' system. Here we present a brief discussion of an article written by Enrico Morselli about five cases of rib fractures in the mental asylum of Reggio Emilia, in 1874-5. Morselli, a supporter of the ideas of 'non-restraint', suggested a common pathological cause.

Mavacamten has a differential impact on force generation in myofibrils from rabbit psoas and human cardiac muscle.

Mavacamten (MYK-461) is a small-molecule allosteric inhibitor of sarcomeric myosins being used in preclinical/clinical trials for hypertrophic cardiomyopathy treatment. A better understanding of its impact on force generation in intact or skinned striated muscle preparations, especially for human cardiac muscle, has been hindered by diffusional barriers. These limitations have been overcome by mechanical experiments using myofibrils subject to perturbations of the contractile environment by sudden solution changes.

T-tubule remodeling in human hypertrophic cardiomyopathy.

The highly organized transverse T-tubule membrane system represents the ultrastructural substrate for excitation-contraction coupling in ventricular myocytes. While the architecture and function of T-tubules have been well described in animal models, there is limited morpho-functional data on T-tubules in human myocardium. Hypertrophic cardiomyopathy (HCM) is a primary disease of the heart muscle, characterized by different clinical presentations at the various stages of its progression.

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.

To Save a Corpse from Decomposition - the Purpose of Petrification in the Second Half of the 19th Century.

We present this interesting note on the petrification of corpses, published in 1890 in the Italian Journal of Natural Sciences. After a brief review of the oldest forms of embalming, the author, Michele Martone, presents petrification as the only way to obtain the perfect conservation of the corpse. CONCLUSION: This scientific note presents some considerations regarding the constant search of humanity to arrest, if not the death of a person, the decomposition of their body.

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.