The epidemiology of premature aging and associated comorbidities

Hutchinson-Gilford Progeria Syndrome and Werner syndrome, also known as childhood- and adulthood-progeria, respectively, represent two of the best characterized human progeroid diseases with clinical features mimicking physiological aging at an early age. The discovery of their genetic basis has led to the identification of several gene mutations leading to a spectrum of progeroid phenotypes ranging from moderate and mild-severe to very aggressive forms. In parallel, the creation of disease registers and databases provided available data for the design of relatively large-scale epidemiological studies, thereby allowing a better understanding of the nature and frequency of the premature aging-associated signs and symptoms. The aim of this article is to review the most recent findings concerning the epidemiology of premature aging disorders, their genetic basis, and the most recent reports on the frequency of associated diseases

Sviluppo ed applicazione di uno schema a bassa diffusivita' numerica per l'analisi di stabilita' della circolazione naturale con fluidi a pressione supercritica

L’analisi di stabilità per i circuiti in circolazione naturale con fluidi supercritici rappresenta un interessante argomento di studio; ad oggi, numerosi gruppi di ricerca nel mondo stanno raccogliendo dati sia di natura sperimentale che numerica attraverso la realizzazione di modelli specifici. Nei lavori precedenti a questa tesi (Ambrosini, et al., 2012) è stato realizzato un programma di simulazione per l’analisi di stabilità di circuiti in circolazione naturale con fluidi supercritici basato sulla risoluzione delle equazioni di conservazione in forma monodimensionale, attraverso una loro discretizzazione con uno schema di primo ordine. Il programma dava la possibilità di simulare modelli realistici dei circuiti sperimentali e, tramite una linearizzazione delle equazioni transitorie, poteva generare mappe di stabilità in funzione di diverse variabili. Lo scopo di questa tesi è quello di includere uno schema a bassa diffusione numerica all’interno del programma. In particolare è stato implementato un schema upwind di secondo ordine in una forma a volumi finiti con una definizione appropriata della ‘donor cell’ per l’equazione di conservazione dell’energia. Il risultato ottenuto è stato un basso impatto della diffusione numerica sui risultati, anche utilizzando un basso numero di nodi per discretizzare il dominio computazionale. Il programma è stato applicato con successo rispetto ai dati disponibili in termini numerici e sperimentali. Il ‘tool’, adesso, può esser usato come mezzo di studio rispetto alla circolazione naturale con fluidi supercritici riguardo alla scelta del modello di scambio termico più appropriato, escudendo la possibilità di avere effetti dovuta alla discretizzazione numerica. Stability of natural circulation loops with fluids at supercritical pressure represents an interesting research subject allowing for advanced model development and application. At present time several researchers worldwide are collecting data both in experimental and numerical activities with the realization of specific models. In a previous step of the research whose latest results are reported in this thesis (Ambrosini, et al., 2012), a computer programme was developed aiming at setting up a tool based on 1D balance equations for the linear and the nonlinear stability analysis of natural circulation loops, with main attention to those equipped with fluids at supercritical pressure. The monodimensional equations are discretized by a first order numerical scheme. This tool allows a realistic modeling of experimental facilities and, through a linearization of transient equations, generates stability maps as a function of several variables of investigation. The aim of this thesis is inclusion a low diffusion numerical scheme into the program; in particular, a second order upwind scheme in a “donor cell” form (for the energy equation) is adopted thus achieving a very low impact of numerical diffusion even with relatively coarse nodalizations. The resulting program has been applied with success to relevant available data, from both theoretical and experimental analyses. Now, the programme can be used as a tool for discussing the important issues of the selection of the most appropriate correlations for heat transfer and friction in natural circulation conditions with supercritical pressure fluids, allowing for excluding a priori a too large effect of the numerical discretisation on the obtained results

Optical and Chemical Properties of Fragaria ananassa and Galena: Potential Photosensitizers in a Natural Dye-Sensitized Solar Cell

Dye is one of the major components for high power conversion efficiency in a dye-sensitized solar cell. There are challenges natural dyes encounter, especially with quick degradation of the dye molecules. This work considered mineral dye in comparison with plant dye to address the challenge of degradation of natural plant dyes. The optical properties and functional groups of the two natural dyes were studied in this work. The absorption spectra, the optical band gaps and the absorption coefficients of the dyes were reported and found to be suitable for use as photosensitizers in a dye-sensitized solar cell (DSSC), as they absorb in the visible region of the electromagnetic radiation. The functional groups were studied by carrying out Fourier transform infrared spectroscopy and the amine, carbonyl and hydroxyl groups present in both dyes confirmed promising material that can absorb solar radiation in the visible region (around 380–800 nm) and which finds application in fabricating DSSC. The organic compositions in the mineral dye are studied via the gas chromatography-mass spectrometry and the results justify the observation from the FTIR spectroscopy. The properties observed, via the characterizations techniques used, confirm materials suitable for use as photosensitizers in fabricating DSSC. Keywords: Plant dye, Mineral dye, Photosensitizer, Visible region, DSSC

Increased MTHFR promoter methylation in mothers of Down syndrome individuals

Despite that advanced maternal age at conception represents the major risk factor for the birth of a child with Down syndrome (DS), most of DS babies are born from women aging less than 35 years. Studies performed in peripheral lymphocytes of those women revealed several markers of global genome instability, including an increased frequency of micronuclei, shorter telomeres and impaired global DNA methylation. Furthermore, young mothers of DS individuals (MDS) are at increased risk to develop dementia later in life, suggesting that they might be "biologically older" than mothers of euploid babies of similar age.Mutations in folate pathway genes, and particularly in the methylenetetrahydrofolate reductase (MTHFR) one, have been often associated with maternal risk for a DS birth as well as with risk of dementia in the elderly. Recent studies pointed out that also changes in MTHFR methylation levels can contribute to human disease, but nothing is known about MTHFR methylation in MDS tissues.We investigated MTHFR promoter methylation in DNA extracted from perypheral lymphocytes of 40 MDS and 44 matched control women that coinceived their children before 35 years of age, observing a significantly increased MTHFR promoter methylation in the first group (33.3 ± 8.1% vs. 28.3 ± 5.8%; p = 0.001). In addition, the frequency of micronucleated lymphocytes was available from the women included in the study, was higher in MDS than control mothers (16.1 ± 8.6‰ vs. 10.5 ± 4.3‰ p = 0.0004), and correlated with MTHFR promoter methylation levels (r = 0.33; p = 0.006).Present data suggest that MTHFR epimutations are likely to contribute to the increased genomic instability observed in cells from MDS, and could play a role in the risk of birth of a child with DS as well as in the onset of age related diseases in those women

Association study between the DNMT3A -448A>G polymorphism and risk of Alzheimer's disease in Caucasians of Italian origin

Increasing evidence points to an epigenetic contribution in Alzheimer's disease (AD) pathogenesis. In this regard, variants and polymorphisms of DNA methyltransferase genes (DNMTs) are being investigated for their contribution to cognitive decline and dementia, but results are still scarce or controversial. In the present study we genotyped 710 Caucasian subjects of Italian descent, including 320 late-onset AD (LOAD) patients, 70 individuals with amnestic Mild Cognitive Impairment (MCI), and 320 matched healthy controls, for the presence of a functional DNMT3A -448A>G (rs1550117) polymorphism, searching for association with disease risk. In addition, we searched for correlation between the studied polymorphism and circulating levels of folate, homocysteine (hcy) and vitamin B12, all involved in DNA methylation reactions and available from 189 LOAD patients and 186 matched controls. Both allele and genotype frequencies of rs1550117 were closely similar between MCI, LOAD and control subjects, and no association with dementia or pre-dementia conditions was observed. Plasma hcy levels were significantly higher (p = 0.04) and serum folate levels significantly lower (p = 0.01) in LOAD than in controls, but no difference in circulating folate, hcy or vitamin B12 levels was seen between carriers and non-carriers of the minor DNMT3A -448A allele. Collectively, present results confirmed previous associations of increased hcy and decreased folate with LOAD risk, but do not support an association between the DNMT3A -448A>G polymorphism and AD in our population

Detection of Listeria monocytogenes in foods with a textile organic electrochemical transistor biosensor

Abstract: Foods contaminated by pathogens are responsible for foodborne diseases which have socioeconomic impacts. Many approaches have been extensively investigated to obtain specific and sensitive methods to detect pathogens in food, but they are often not easy to perform and require trained personnel. This work aims to propose a textile organic electrochemical transistor-based (OECT) biosensor to detect L. monocytogenes in food samples. The analyses were performed with culture-based methods, Listeria Precis™ method, PCR, and our textile OECT biosensor which used poly(3,4-ethylenedioxythiophene) (PEDOT):polystyrene sulfonate (PSS) (PEDOT:PSS) for doping the organic channel. Atomic force microscopy (AFM) was used to obtain topographic maps of the gold gate. The electrochemical activity on gate electrodes was measured and related to the concentration of DNA extracted from samples and hybridized to the specific capture probe immobilized onto the gold surface of the gate. This assay reached a limit of detection of 1.05 ng/μL, corresponding to 0.56 pM of L. monocytogenes ATCC 7644, and allowed the specific and rapid detection of L. monocytogenes in the analyzed samples. Keypoints: • Textile organic electrochemical transistors functionalized with a specific DNA probe • AFM topographic and surface potential maps of a functionalized gold gate surface • Comparison between the Listeria monocytogenes Precis™ method and an OECT biosenso

Oxytocin receptor and G-protein polymorphisms in patients with depression and separation anxiety

BACKGROUND: The impact of combined variants of Oxytocin Receptor (OXTR) and G protein β3 subunit genes was investigated in relation to retrospective reports of childhood as well as contemporary adult separation anxiety (SA), based on evidence of a β/γ dimer-mediated signaling for OXTR. METHODS: A case-control association study (225 healthy adults and 188 outpatients with depression) was performed to establish Risk-Combined Genotype (RCG) of the studied variants (OXTR rs53576 and the functional Gβ3 subunit rs5443). Current SA was evaluated by the ASA-27 and retrospective childhood symptoms by the SASI. GG genotype of OXTR rs53576 combined with T-carrier genotype of Gβ3 rs5443 represented the RCG. RESULTS: Compared to non-RCG, those with RCG had significantly higher levels of childhood and adult SA. The RCG was significantly associated with childhood SA threshold score (OR=2.85, 90%CI: 1.08-7.50). Childhood SA was, in turn, strongly associated with a threshold SA score in adulthood (OR=15.58; 95% CI: 4.62-52.59). LIMITATIONS: Although the overall sample size is sizable, comparisons among subgroups with specific combination of alleles are based on relatively small numbers. CONCLUSIONS: Our study indicates that variations in OXTR and Gβ3 genes are specifically associated with presence and severity of SA in childhood and adulthood, but not with depression or anxiety in general. Because there is increasing interest in oxytocin in social behavior, the gene-SA associations identified have potential translational and clinical relevance