RILEVANZA DEL SESSO NELLA MALATTIA DA COVID-19: QUANDO UN CROMOSOMA IN PIÙ FA LA DIFFERENZA!

Meta-analysis of epidemiological world-wide reports of SARS-CoV-2 patients requiring mechanical ventilation in intensive care units highlighted the male sex as a risk factor for severe, often fatal evolution of COVID-19 disease, as signaled by previous coronavirus infections. X chromosome inactivation (XCI), an epigenetic mechanism used by female somatic cells to equalize the dosage of X-linked genes between the sexes and the female advantage with mosaicism of the numerous immune-related genes and the increased expression of those escaping XCI determined a growing recognition of the unique biology of the X chromosome to account for females more robust immune response. In the wake of studies aimed at establishing the contribution of immune-regulatory X-linked genes to sex-specific differences of COVID-19 disease, the expression of TLR7, a gene of innate immune response encoding a member of Toll-like family receptors sensing the SARS-CoV-2 endosomal RNA, has been quantified in human female plasmacytoid dendritic cells which are high producers of interferons, acting as powerful viral inhibitors. The study confirmed that TLR7 escapes XCI promoting higher TLR7 mRNA and higher interferon mRNA at the single-cell level. The relevance of TLR7 signaling has been highlighted by a Dutch study exploring the presence of genetic variants among young men with severe COVID-19 which identified pathogenic TLR7 variants in two pairs of brothers (mean age 26 years) without medical history admitted to intensive care units due to SARS-CoV-2 acute respiratory syndrome, one of whom deceased due to septic shock. Whole exome sequencing of the patients identified “loss of function variants” of the X-chromosomal TLR7 and functional studies on their peripheral blood mononucleate cells after in vitro stimulation with a TLR7 agonist showed significant reduction of TLR7-specific mRNA and decreased mRNA expression of various interferon type I genes as compared to family members and controls. While rare mutations in TLR7 are unlikely to be a major drive of severe COVID-19 disease, their identification begins to unravel the molecular underpinning of COVID-19 infection highlighting TLR7 receptor as a critical node in recognizing SARS-CoV-2 and initiating an early immune response to clear the virus and prevent the development of COVID-19.

LA LEGGE GRAVITAZIONALE DELL’INVERSO DEL QUADRATO NEI PRINCIPIA DI NEWTON

We revisit the question concerning the accuracy of the inverse-square gravitational law, as raised in section IX, book I of Newton’s Principia, and in some sections of book III. We argue that the problem has been thoroughly discussed and basically solved by Newton himself. We point out in particular the relations with the well-known Bertrand’s theorem. Bertrand approached the same problem in more abstract terms. We remark, however, that much of Bertrand’s proof is essentially contained in Principia.

ROBERT GROSSETESTE: A MEDIEVAL THINKER WITH A LEGACY FOR MODERN SCIENCE

Robert Grosseteste (ca. 1170-1253) was one of the first scholars to embed the newly rediscovered ideas of Aristotle into medieval natural philosophy. In a series of short scientific treatises written between about 1215 and 1230 he focused on explaining why, rather than how, the natural world behaves as it does. He adopted a principle of subalternation in which complex phenomena could be understood in terms of simpler underlying behaviour that could be tested by observation. For example, he explained the features of the rainbow in terms of optics, which in turn could be explained by geometry. Grosseteste’s “Big Bang” theory of the formation of the universe, based on the expansion of light from a point, is founded on the need to explain the stability of solid matter. Although surviving manuscripts do contain almost no diagrams, it is evident that he thought both mathematically and pictorially in developing a unified model of natural phenomena. In a unique interdisciplinary collaboration between historians, philosophers, palaeographers, linguists, artists and scientists (www.ordered-universe.com) we have shown how detailed examination of Grosseteste’s science can stimulate both new contemporary scientific research and artistic creativity.

IL PUNTO DI VISTA DI UN REGOLATORE EPIGENETICO DELL’ESPRESSIONE GENICA, COMUNE A UOMO E PIANTE

The regulation of gene expression is at the heart of all the fundamental processes of living organisms. It is controlled by Transcriptional Factors which, by binding to specific DNA sequences of genomes, recruit protein machineries that modify the organization of chromatin (epigenetics). Our studies are focused on the NF-Y trimeric transcription factor, a crucial activator of gene expression in all eukaryotes. Two subunits have a structure similar to histones, the basic elements of chromatin, the third -NF-YA- confers specificity to the CCAAT box. I will illustrate how regulation of NF-Y complexes is important for two completely different gene expression systems: the neoplastic transformation of human cells, and the development of flowers in plants.

TERMOELETTRICITÀ: DALL’ARCO DI ALESSANDRO VOLTA AI GENERATORI TERMOELETTRICI FERRO-LIQUIDI

We start this concise review from the exciting history of thermoelectricity in which such names as Luigi Galvani, Alessandro Volta, Thomas Seebeck, Walter Nernst, William Tompson, Georg Wilhelm Hegel and many others have been involved. We then move on to the main concepts in description of thermoelectric phenomena, discuss how to increase their magnitude and efficiency, formulate the requirements for modern thermoelectric materials and present thermoelectric applications that are already available.

TMek: UN MICROCHIP PER DIAGNOSTICARE LA MALARIA IN MODO QUANTITATIVO E RAPIDO

Despite the huge efforts for malaria eradication, this infectious disease still represents a critical issue worldwide, with 3.5 billion people still at risk, 229 million new cases and 409.000 deaths in 2019. The infection is caused by the Plasmodiun parasite which attacks red blood cells, feeds on hemoglobin and transform it into hemozoin nanocrystals. In this paper we report on a novel pan-malaria test (TMek), based on the paramagnetic properties of hemozoin nanocrystals, which allows for the automatic quantification of infected red blood cells (i-RBCs) on a microchip. Exploiting the competition between gravity and magnetic forces, i-RBCs in a whole blood specimen are captured on micromagnetic concentrators and electrically detected, allowing for the measurement of their concentration with a limit of sensitivity down to 10 parasites/μl.

NUOVE ESCHE PER PESCARE NEL MARE MAGNUM DELL’EREDITÀ CULTURALE

We describe here a novel tool for exploring documents pertaining to the world Cultural Heritage while avoiding their contamination or damage. Known under the acronym EVA, it consists of a plastic foil of Ethylene Vinyl Acetate studded with strong cation and anion resins admixed with C8 and C18 hydrophobic beads. When applied to any surface such foils can harvest any type of surface material, which is then eluted and analysed via standard means, such as GS/MS (typically for metabolites), MS/MS (for peptide and protein analysis), X-ray (for elemental analysis). We briefly review here a number of past data, such as screening of original documents by Bulgakov, Chekov, Casanova, Kepler, while dealing in extenso with very recent data, pertaining to Orwell and Stalin and analysis of the skin of an Egyptian mummy. The technique was also successfully applied to paintings, such as the Donna Nuda at the Hermitage in St. Petersburg, attributed to Leonardo and his school. This novel methodology represents a formidable tool for exploring the past life of famous authors, scientist and literates in that it can detect traces of their pathologies and even drug consumption left by saliva and sweat traces on their original hand-written documents.

RECENTI SVILUPPI NELLA RISONANZA MAGNETICA NUCLEARE A PAVIA

Nuclear Magnetic Resonance (NMR) is a crucial experimental technique for the study of matter in several fields and applications, as for example in physics, chemistry, materials science, biology, medicine and food science. By means of this technique, the NMR group of the University of Pavia (UniPV) has given valuable scientific contributions to the Condensed Matter Physics and to the Physics applied to the Biomedical sector. In this note we’ll illustrate some of the most relevant results produced by the researchers of the group within decades of work carried out with passion and dedication, with examples regarding the Molecular Magnets, the High Tc Superconductors, the contrast agents and the hyperpolarization of molecules for Magnetic Resonance Imaging. We’ll also report some preliminary results obtained at the Preclinical Imaging Facility of UniPV, recently founded with the key contribution of the NMR group.

ARCHITETTURA MOLECOLARE DI FATTORI DI TRASCRIZIONE DEL DNA

Transcription factors are proteins involved in one of the most important molecular processes in living cells: the expression of genes through a mechanism called “transcription”. Transcription factors, their structure, and function are the topic of the seminar which also includes an overview of the current level of knowledge, the potentialities and problems in this research field, and the possible applications.

NOTA SUI LIMITI FISIOLOGICI DELLE IMMERSIONI PROFONDE IN APNEA

This article discusses the limits of deep breath-hold diving in humans. After a short historical introduction and a discussion of the evolution of depth records, the classical theories of breath-hold diving limits are presented and discussed, namely that of the ratio between total lung capacity and residual volume and that of blood shift, implying an increase in central blood volume. Then the current vision is introduced, based on the principles of the energetics of muscular exercise. The new vision has turned the classical vision upside down, moving the discussion to a different level. A direct consequence of the new theory is the importance of having large lung volumes at the start of a dive, in order to increase body oxygen stores. I finally discuss the role of anaerobic lactic metabolism as a possible mechanism of oxygen preservation, thus prolonging breath-hold duration.