In memoriam: Silvano Adami

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Parathyroid tumors: Molecular signatures

Parathyroid tumors are rare endocrine neoplasms affecting 0.1–0.3% of the general population, including benign parathyroid adenomas (PAs; about 98% of cases), intermediate atypical parathyroid adenomas (aPAs; 1.2–1.3% of cases) and malignant metastatic parathyroid carcinomas (PCs; less than 1% of cases). These tumors are characterized by a variable spectrum of clinical phenotypes and an elevated cellular, histological and molecular heterogeneity that make it difficult to pre-operatively distinguish PAs, aPAs and PCs. Thorough knowledge of genetic, epigenetic, and molecular signatures, which characterize different parathyroid tumor subtypes and drive different tumorigeneses, is a key step to identify potential diagnostic biomarkers able to distinguish among different parathyroid neoplastic types, as well as provide novel therapeutic targets and strategies for these rare neoplasms, which are still a clinical and therapeutic challenge. Here, we review the current knowledge on gene mutations and epigenetic changes that have been associated with the development of different clinical types of parathyroid tumors, both in familial and sporadic forms of these endocrine neoplasms

Congenital metabolic bone disorders as a cause of bone fragility

Bone fragility is a pathological condition caused by altered homeostasis of the mineralized bone mass with deterioration of the microarchitecture of the bone tissue, which results in a reduction of bone strength and an increased risk of fracture, even in the absence of high-impact trauma. The most common cause of bone fragility is primary osteoporosis in the elderly. However, bone fragility can manifest at any age, within the context of a wide spectrum of congenital rare bone metabolic diseases in which the inherited genetic defect alters correct bone modeling and remodeling at different points and aspects of bone synthesis and/or bone resorption, leading to defective bone tissue highly prone to long bone bowing, stress fractures and pseudofractures, and/or fragility fractures. To date, over 100 different Mendelian-inherited metabolic bone disorders have been identified and included in the OMIM database, associated with germinal heterozygote, compound heterozygote, or homozygote mutations, affecting over 80 different genes involved in the regulation of bone and mineral metabolism. This manuscript reviews clinical bone phenotypes, and the associated bone fragility in rare congenital metabolic bone disorders, following a disease taxonomic classification based on deranged bone metabolic activity

Bayesian modelling captures inter-individual differences in social belief computations in the putamen and insula

Computational models of social learning and decision-making provide mechanistic tools to investigate the neural mechanisms that are involved in understanding other people. While most studies employ explicit instructions to learn from social cues, everyday life is characterized by the spontaneous use of such signals (e.g., the gaze of others) to infer on internal states such as intentions. To investigate the neural mechanisms of the impact of gaze cues on learning and decision-making, we acquired behavioural and fMRI data from 50 participants performing a probabilistic task, in which cards with varying winning probabilities had to be chosen. In addition, the task included a computer-generated face that gazed towards one of these cards providing implicit advice. Participants\u2019 individual belief trajectories were inferred using a hierarchical Gaussian filter (HGF) and used as predictors in a linear model of neuronal activation. During learning, social prediction errors were correlated with activity in inferior frontal gyrus and insula. During decision-making, the belief about the accuracy of the social cue was correlated with activity in inferior temporal gyrus, putamen and pallidum while the putamen and insula showed activity as a function of individual differences in weighting the social cue during decision-making. Our findings demonstrate that model-based fMRI can give insight into the behavioural and neural aspects of spontaneous social cue integration in learning and decision-making. They provide evidence for a mechanistic involvement of specific components of the basal ganglia in subserving these processes

Light Ion Accelerating Line (L3IA): Test Experiment at ILIL-PW

The construction of a novel Laser driven Light Ions Acceleration Line(L3IA) is progressing rapidly towards the operation, following the recent upgrade of the ILIL-PW laser facility. The Line was designed following the pilot experimental activity carried out earlier at the same facility to define design parameters and to identify main components including target control and diagnostic equipment, also in combination with the numerical simulations for the optimization of laser and target parameters. A preliminary set of data was acquired following the successful commissioning of the laser system >100 TW upgrade. Data include output from a range of different ion detectors and optical diagnostics installed for qualification of the laser-target interaction. An overview of the results is given along with a description of the relevant upgraded laser facility and features.Comment: 6 pages, 7 figures, 18 references, presented at the EAAC 201

Investigating the Justice System Response to Domestic Violence in Missouri

One in four women will experience domestic violence in their lifetimes. Each year, 5.3 million domestic violence assaults occur in the United States alone and domestic violence is the leading cause of injury to women. Yet, despite the prevalence of domestic violence, little empirical research on the justice system\u27s response to it exists. This paper seeks to describe a state funded project that was created to assess and compare responses to domestic violence throughout the state of Missouri. The project lasted for three years and was conducted by an interdisciplinary team of University of Missouri-Columbia (MU) professors and students

In Vitro Effects of PTH (1-84) on Human Skeletal Muscle-Derived Satellite Cells

Parathyroid hormone (PTH) is a hormone secreted by the parathyroid glands. Despite its well-known characterized anabolic and catabolic actions on the skeleton, the in vitro effects of PTH on skeletal muscle cells are limited and generally performed on animal models. The aim of this study was to evaluate the effects of a short impulse of PTH (1-84) on the proliferation and the differentiation of skeletal muscle satellite cells isolated from human biopsies. The cells were exposed for 30 min to different concentrations of PTH (1-84), from 10−6 mol/L to 10−12 mol/L. ELISA was used to assay cAMP and the myosin heavy-chain (MHC) protein. The proliferation was assayed by BrdU and the differentiation by RealTime-qPCR. A statistical analysis was performed by ANOVA followed by Bonferroni’s test. No significant variations in cAMP and the proliferation were detected in the isolated cells treated with PTH. On the other hand, 10−7 mol/L PTH on differentiated myotubes has shown significant increases in cAMP (p ≤ 0.05), in the expression of myogenic differentiation genes (p ≤ 0.001), and in the MHC protein (p ≤ 0.01) vs. untreated controls. This work demonstrates for the first time the in vitro effects of PTH (1-84) on human skeletal muscle cells and it opens new fields of investigation in muscle pathophysiology

Ribosomal selection of mRNAs with degenerate initiation triplets

To assess the influence of degenerate initiation triplets on mRNA recruitment by ribosomes, five mRNAs identical but for their start codon (AUG, GUG, UUG, AUU and AUA) were offered to a limiting amount of ribosomes, alone or in competition with an identical AUGmRNA bearing a mutation conferring different electrophoretic mobility to the product. Translational efficiency and competitiveness of test mRNAs toward this AUGmRNA were determined quantifying the relative amounts of the electrophoretically separated wt and mutated products synthesized in vitro and found to be influenced to different extents by the nature of their initiation triplet and by parameters such as temperature and nutrient availability in the medium. The behaviors of AUAmRNA, UUGmRNA and AUGmRNA were the same between 20 and 40°C whereas the GUG and AUUmRNAs were less active and competed poorly with the AUGmRNA, especially at low temperature. Nutrient limitation and preferential inhibition by ppGpp severely affected activity and competitiveness of all mRNAs bearing non-AUG starts, the UUGmRNA being the least affected. Overall, our data indicate that beyond these effects exclusively due to the degenerate start codons within an optimized translational initiation region, an important role is played by the context in which the rare start codons are present