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

Metabolic response of Insulinoma 1E cells to glucose stimulation studied by fluorescence lifetime imaging

A cascade of highly regulated biochemical processes connects glucose stimulation to insulin secretion in specialized cells of mammalian pancreas, the β-cells. Given the importance of this process for systemic glucose homeostasis, noninvasive and fast strategies capable to monitor the response to glucose in living cells are highly desirable. Here, we use the phasor-based approach to Fluorescence Lifetime IMaging (FLIM) microscopy to quantify the ratio between protein-bound and free Nicotinamide adenine dinucleotide (phosphate) species in their reduced form (NAD(P)H), and the Insulinoma cell line INS-1E as a β-like cellular model. Phasor-FLIM analysis shows that the bound/free ratio of NAD(P)H species increases upon pulsed glucose stimulation. Such response is impaired by 48-hours preincubation of cells under hyperglycemic conditions. Phasor-FLIM concomitantly monitors the appearance of long-lifetime species (LLS) as characteristic products of hyperglycemia-induced oxidative stress

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

Single-cell imaging of α and β cell metabolic response to glucose in living human Langerhans islets

Here we use a combination of two-photon Fluorescence Lifetime Imaging Microscopy (FLIM) of NAD(P)H free/bound ratio in living HIs with post-fixation, immunofluorescence-based, cell-type identification. FLIM allowed to measure variations in the NAD(P)H free/bound ratio induced by glucose; immunofluorescence data allowed to identify single α and β cells; finally, matching of the two datasets allowed to assign metabolic shifts to cell identity. 312 α and 654 β cells from a cohort of 4 healthy donors, 15 total islets, were measured. Both α and β cells display a wide spectrum of responses, towards either an increase or a decrease in NAD(P)H free/bound ratio. Yet, if single-cell data are averaged according to the respective donor and correlated to donor insulin secretion power, a non-random distribution of metabolic shifts emerges: robust average responses of both α and β cells towards an increase of enzyme-bound NAD(P)H belong to the donor with the lowest insulin-secretion power; by contrast, discordant responses, with α cells shifting towards an increase of free NAD(P)H and β cells towards an increase of enzyme-bound NAD(P)H, correspond to the donor with the highest insulin-secretion power. Overall, data reveal neat anti-correlation of tissue metabolic responses with respect to tissue insulin secretion power

Differential CpG methylation at Nnat in the early establishment of beta cell heterogeneity

Aims/hypothesis: Beta cells within the pancreatic islet represent a heterogenous population wherein individual sub-groups of cells make distinct contributions to the overall control of insulin secretion. These include a subpopulation of highly connected ‘hub’ cells, important for the propagation of intercellular Ca2+ waves. Functional subpopulations have also been demonstrated in human beta cells, with an altered subtype distribution apparent in type 2 diabetes. At present, the molecular mechanisms through which beta cell hierarchy is established are poorly understood. Changes at the level of the epigenome provide one such possibility, which we explore here by focusing on the imprinted gene Nnat (encoding neuronatin [NNAT]), which is required for normal insulin synthesis and secretion. Methods: Single-cell RNA-seq datasets were examined using Seurat 4.0 and ClusterProfiler running under R. Transgenic mice expressing enhanced GFP under the control of the Nnat enhancer/promoter regions were generated for FACS of beta cells and downstream analysis of CpG methylation by bisulphite sequencing and RNA-seq, respectively. Animals deleted for the de novo methyltransferase DNA methyltransferase 3 alpha (DNMT3A) from the pancreatic progenitor stage were used to explore control of promoter methylation. Proteomics was performed using affinity purification mass spectrometry and Ca2+ dynamics explored by rapid confocal imaging of Cal-520 AM and Cal-590 AM. Insulin secretion was measured using homogeneous time-resolved fluorescence imaging. Results: Nnat mRNA was differentially expressed in a discrete beta cell population in a developmental stage- and DNA methylation (DNMT3A)-dependent manner. Thus, pseudo-time analysis of embryonic datasets demonstrated the early establishment of Nnat-positive and -negative subpopulations during embryogenesis. NNAT expression is also restricted to a subset of beta cells across the human islet that is maintained throughout adult life. NNAT+ beta cells also displayed a discrete transcriptome at adult stages, representing a subpopulation specialised for insulin production, and were diminished in db/db mice. ‘Hub’ cells were less abundant in the NNAT+ population, consistent with epigenetic control of this functional specialisation. Conclusions/interpretation: These findings demonstrate that differential DNA methylation at Nnat represents a novel means through which beta cell heterogeneity is established during development. We therefore hypothesise that changes in methylation at this locus may contribute to a loss of beta cell hierarchy and connectivity, potentially contributing to defective insulin secretion in some forms of diabetes. Data availability: The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD048465. Graphical Abstract