A dynamical model of genetic networks describes cell differentiation

Cell differentiation is a complex phenomenon whereby a stem cell becomes progressively more specialized and eventually gives rise to a specific cell type. Differentiation can be either stochastic or, when appropriate signals are present, it can be driven to take a specific route. Induced pluripotency has also been recently obtained by overexpressing some genes in a differentiated cell. Here we show that a stochastic dynamical model of genetic networks can satisfactorily describe all these important features of differentiation, and others. The model is based on the emergent properties of generic genetic networks, it does not refer to specific control circuits and it can therefore hold for a wide class of lineages. The model points to a peculiar role of cellular noise in differentiation, which has never been hypothesized so far, and leads to non trivial predictions which could be subject to experimental testing

A Dynamical Model of Genetic Networks for Cell Differentiation

A mathematical model is proposed which is able to describe the most important features of cell differentiation, without requiring specific detailed assumptions concerning the interactions which drive the phenomenon. On the contrary, cell differentiation is described here as an emergent property of a generic model of the underlying gene regulatory network, and it can therefore be applied to a variety of different organisms. The model points to a peculiar role of cellular noise in differentiation and leads to non trivial predictions which could be subject to experimental testing. Moreover, a single model proves able to describe several different phenomena observed in various differentiation processes

Oxidative functionalization of organic compounds promoted by nonheme Fe and Mn complexes

Nonheme iron and manganese complexes are versatile and environmentally sustainable catalysts able to promote the oxidation of a broad range of organic compounds with interesting synthetic application. Careful simple modification in the design of this catalytic systems, can contribute to change significantly their selectivity and efficiency. In this Ph.D. thesis, some aspects related to the mechanistic analysis and catalytic activity of three different nonheme catalytic systems: aminopyridine iron complexes, imine iron complexes and aminopyridine supramolecular iron and manganese complexes, have been investigated in detail. The occurrence of an electron transfer-oxygen rebound process in the oxidation of aryl sulfides promoted by two tetradentate ([(PDP)FeII] and [(BPMCN)FeII]) and two pentadentate ([(N4Py)FeII] and [(Bn-TPEN)FeII]) aminopyridine iron complexes, has been highlighted through detailed product and kinetic studies of the oxidation of two series of aromatic sulfides (aryl 1-methyl-1-phenylethyl sulfides and aryl diphenylmethyl sulfides) whose corresponding radical cations are characterized by high C-S fragmentation rate constants. Using aryl 1-methyl-1-phenylethyl sulfides as substrates, it has been possible, moreover, to estimate the rate constants of the oxygen rebound process (kOT) from the reduced nonheme iron-oxo complexes to the sulfide radical cations. A bioinspired supramolecular version of the aminopyridine iron and manganese complexes, [(PDP)FeII] and [(PDP)MnII] containing benzo-18-crown-6 ether as receptor that reversibly bind the substrate, has been prepared. The ditopic catalysts have been applied with success to achieve high site-selective C-H functionalization on C8 and C9 methylene positions of a series of linear protonated primary amines thanks to reversible pre-association between ammonium moiety and the benzo-18-crown-6 ether recognition sites. Imine based iron complexes represent another interesting class of nonheme catalysts. Iminopyridine iron(II) complex, easily prepared in situ by self-assembly of cheap and commercially available 2 picolylaldehyde, 2 picolylamine, and Fe(OTf)2, in a 2:2:1 ratio, displayed good-to-moderate efficiency in the oxidation of aliphatic alcohols with H2O2. Quite surprisingly, benzylic alcohols are oxidized to aromatic ketones with low efficiency due to strong competitive aromatic hydroxylation. The remarkable selectivity for the oxidation of the aromatic ring in benzylic alcohols, has been exploited in the oxidation of alkyl aromatic compounds. In the presence of an aliphatic chain, the catalyst is highly selective for the aromatic nucleus hydroxylation with a selectivity pattern that closely matched that of electrophilic aromatic substitutions with a metal–based SEAr pathway, without a significant involvement of free diffusing radical pathways. A low efficiency in the oxidation of electron rich benzylic alcohols has been also observed, moreover, for the MnII/pyridine carboxylic acid/butanedione catalytic system. The analysis of the inhibition process of this catalytic system by catechol and guaiacol substrates indicated that the Mn/inhibitor ratio is a key parameter for the activity/inactivity of the system. The right proportion between them may prevents an irreversible deactivation of the complex. Finally, the fundamental importance of the identification of the active intermediates involved in the catalytic cycles, has prompted us to project an innovative approach consisting in the simultaneously use of time-resolved Energy Dispersive X-Ray Absorption (EDXAS) and UV/Vis spectroscopies with millisecond resolution to follow the time evolution of the catalyst activation processes. The excellent results obtained for the evolution of [(TPA)FeII(CH3CN)2]2+ with H2O2 and CH3COOOH, could give the opportunity to follow the evolution of less know systems and to detect and quantitatively monitor some elusive species, such as FeV intermediates

Precise optical timing of PSR J1023+0038, the first millisecond pulsar detected with Aqueye+ in Asiago

We report the first detection of an optical millisecond pulsar with the fast photon counter Aqueye+ in Asiago. This is an independent confirmation of the detection of millisecond pulsations from PSR J1023+0038 obtained with SiFAP at the Telescopio Nazionale Galileo. We observed the transitional millisecond pulsar PSR J1023+0038 with Aqueye+ mounted at the Copernicus telescope in January 2018. Highly significant pulsations were detected. The rotational period is in agreement with the value extrapolated from the X-ray ephemeris, while the time of passage at the ascending node is shifted by $11.55 \pm 0.08$ s from the value predicted using the orbital period from the X-rays. An independent optical timing solution is derived over a baseline of a few days, that has an accuracy of $\sim 0.007$ in pulse phase ($\sim 12$ $\mu$s in time). This level of precision is needed to derive an accurate coherent timing solution for the pulsar and to search for possible phase shifts between the optical and X-ray pulses using future simultaneous X-ray and optical observations.Comment: 6 pages, 4 figures, accepted for publication in Monthly Notices of the Royal Astronomical Society Letter

La fuerza de la cooperación: las empresas recuperadas en Italia

Si bien las empresas argentinas recuperadas están ampliamente estudiadas, la literatura científica sobre los casos italianos es incipiente y poco sistematizada. En Italia (pero también en otros países europeos), el proceso de recuperación se configura como poco conflictivo y apoyado por un vasto aparato legislativo (como la Ley Marcora) y por el apoyo del mundo de la cooperación. De hecho, las empresas recuperadas representan una forma peculiar de crear nuevas cooperativas, definidas con el nombre de Workers' Buyout (WBO), término que indica la reestructuración, rescate o conversión de una empresa por parte de los empleados, que compran la propiedad

Insights into the Metabolomic Diversity of Latilactobacillus sakei

: Latilactobacillus sakei (L. sakei), widely used as a starter culture in fermented sausages, is a species adapted to meat environments. Its ability to survive for a long time in such products is due to the exploitation of different metabolic pathways to gain energy (hexose and pentose sugar fermentation, amino acids catabolism, etc.). Since L. sakei demonstrates high phenotypic and metabolic strain biodiversity, in this work, a metabolomic approach was used to compare five strains of different origins. They were cultivated in a defined medium with glucose or ribose at two concentrations, and analyzed through nuclear magnetic resonance (1H-NMR) spectroscopy to monitor amino acid consumptions and accumulation of organic acids and aroma compounds. The results showed that all the strains were able to use arginine, especially when cultivated with ribose, while serine was consumed mainly in the presence of glucose. Aroma compounds (i.e., diacetyl and acetoin) were mainly accumulated in samples with ribose. These aspects are relevant for starter cultures selection, to confer specific features to fermented sausages, and to optimize the fermentations. Moreover, the use of 1H-NMR allowed the fast identification of different classes of compounds (without derivatization or extraction procedures), providing a powerful tool to increase the knowledge of the metabolic diversity of L. sakei

Emerging Role of Cellular Prion Protein in the Maintenance and Expansion of Glioma Stem Cells

Cellular prion protein (PrPC) is a membrane-anchored glycoprotein representing the physiological counterpart of PrP scrapie (PrPSc), which plays a pathogenetic role in prion diseases. Relatively little information is however available about physiological role of PrPC. Although PrPC ablation in mice does not induce lethal phenotypes, impairment of neuronal and bone marrow plasticity was reported in embryos and adult animals. In neurons, PrPC stimulates neurite growth, prevents oxidative stress-dependent cell death, and favors antiapoptotic signaling. However, PrPC activity is not restricted to post-mitotic neurons, but promotes cell proliferation and migration during embryogenesis and tissue regeneration in adult. PrPC acts as scaold to stabilize the binding between dierent membrane receptors, growth factors, and basement proteins, contributing to tumorigenesis. Indeed, ablation of PrPC expression reduces cancer cell proliferation and migration and restores cell sensitivity to chemotherapy. Conversely, PrPC overexpression in cancer stem cells (CSCs) from dierent tumors, including gliomas\u2014the most malignant brain tumors\u2014is predictive for poor prognosis, and correlates with relapses. The mechanisms of the PrPC role in tumorigenesis and its molecular partners in this activity are the topic of the present review, with a particular focus on PrPC contribution to glioma CSCs multipotency, invasiveness, and tumorigenicity

Psychiatric rehabilitation patterns in Italy: Results from the Italian Society of Psychosocial Rehabilitation (SIRP) survey

IntroductionPsychiatric rehabilitation can be considered a bidirectional technique, designed to allow patients to achieve their personal target, focusing on the individuals' strengths and challenges related to these targets and also on the community organizations in which they will live them out. Unfortunately, psychiatric rehabilitation is too often not considered a first line treatment. Moreover, rehabilitation has been confused with a generic and rough practice, consisting of extemporary actions and aimless entertainments designed to fill "the time passing". MethodsThe aim of this study was to increase the knowledge and awareness about the state of the art of different systems of management and funding of psychosocial rehabilitation in the Italian "real-world" rehabilitative settings, using a specifically developed questionnaire. ResultsThe data obtained are positive for some aspects of the rehabilitation interventions, in particular for the use of validated tools for the evaluation and revision of projects and for the trend to work on a team, even though the scarcity of evidence-based rehabilitation interventions applied in Italian psychiatric services is less encouraging. ConclusionThis survey presents, at least partially, the "real-world" of rehabilitation in Italy so that we can lay the foundations for the definition of an updated, validated and shared network of what is implemented in the context of psychiatric rehabilitation

Spin-down rate of the transitional millisecond pulsar PSR J1023+0038 in the optical band with Aqueye+

We present a timing analysis of the transitional millisecond pulsar PSR J1023+0038 using observations taken between January 2018 and January 2020 with the high time resolution photon counter Aqueye+ mounted at the 1.82 m Copernicus telescope in Asiago. We report the first measurement of the timing solution and the frequency derivative of PSR J1023+0038 based entirely on optical data. The spin-down rate of the pulsar is $(-2.53 \pm 0.04) \times 10^{-15}$ Hz$^2$, which is $\sim$20% slower than that measured from the X-ray observations taken in 2013-2016 and $\sim$5% faster than that measured in the radio band during the rotation-powered state.Comment: 6 pages, 4 figures, accepted for publication in Monthly Notices of the Royal Astronomical Society Letter