The genetic signature of Neolithic in Greece

The Neolithic is characterized by the transition from a subsistence economy, based on hunting and gathering, to one based on food producing. This important change was paralleled by one of the most significant demographic increase in the recent history of European populations. The earliest Neolithic sites in Europe are located in Greece. However, the debate regarding the colonization route followed by the Middle-eastern farmers is still open. Based on archaeological, archaeobotanical, craniometric and genetic data, two main hypotheses have been proposed. The first implies the maritime colonization of North-eastern Peloponnesus from Crete, whereas the second points to an island hopping route that finally brought migrants to Central Greece. To test these hypotheses using a genetic approach, 206 samples were collected from the two Greek regions proposed as the arrival point of the two routes (Korinthian district and Euboea). Expectations for each hypothesis were compared with empirical observations based on the analysis of 60 SNPs and 26 microsatellite loci of Y-chromosome and mitochondrial DNA hypervariable region I. The analysis of Y-chromosome haplogroups revealed a strong genetic affinity of Euboea with Anatolian and Middle-eastern populations. The inferences of the time since population expansion suggests an earlier usage of agriculture in Euboea. Moreover, the haplogroup J2a-M410, supposed to be associated with the Neolithic transition, was observed at higher frequency and variance in Euboea showing, for both these parameters, a decreasing gradient moving from this area. The time since expansion estimates for J2a-M410 was found to be compatible with the Neolithic and slightly older in Euboea. The analysis of mtDNA resulted less informative. However, a higher genetic affinity of Euboea with Anatolian and Middle-eastern populations was confirmed. These results taken as a whole suggests that the most probable route followed by Neolithic farmers during the colonization of Greece was the island hopping route.

Diagnosis and Fault detection in Electrical Machines and Drives based on Advanced Signal Processing Techniques

In the present thesis, a new methodology of diagnosis based on advanced use of time-frequency technique analysis is presented. More precisely, a new fault index that allows tracking individual fault components in a single frequency band is defined. More in detail, a frequency sliding is applied to the signals being analyzed (currents, voltages, vibration signals), so that each single fault frequency component is shifted into a prefixed single frequency band. Then, the discrete Wavelet Transform is applied to the resulting signal to extract the fault signature in the frequency band that has been chosen. Once the state of the machine has been qualitatively diagnosed, a quantitative evaluation of the fault degree is necessary. For this purpose, a fault index based on the energy calculation of approximation and/or detail signals resulting from wavelet decomposition has been introduced to quantify the fault extend. The main advantages of the developed new method over existing Diagnosis techniques are the following: - Capability of monitoring the fault evolution continuously over time under any transient operating condition; - Speed/slip measurement or estimation is not required; - Higher accuracy in filtering frequency components around the fundamental in case of rotor faults; - Reduction in the likelihood of false indications by avoiding confusion with other fault harmonics (the contribution of the most relevant fault frequency components under speed-varying conditions are clamped in a single frequency band); - Low memory requirement due to low sampling frequency; - Reduction in the latency of time processing (no requirement of repeated sampling operation).

Epigenetic signature in persons with Down Syndrome

Persons affected by Down Syndrome show a heterogeneous phenotype that includes developmental defects and cognitive and haematological disorders. Premature accelerated aging and the consequent development of age associated diseases like Alzheimer Disease (AD) seem to be the cause of higher mortality late in life of DS persons. Down Syndrome is caused by the complete or partial trisomy of chromosome 21, but it is not clear if the molecular alterations of the disease are triggered by the specific functions of a limited number of genes on chromosome 21 or by the disruption of genetic homeostasis due the presence of a trisomic chromosome. As epigenomic studies can help to shed light on this issue, here we used the Infinium HumanMethilation450 BeadChip to analyse blood DNA methylation patterns of 29 persons affected by Down syndrome (DSP), using their healthy siblings (DSS) and mothers (DSM) as controls. In this way we obtained a family-based model that allowed us to monitor possible confounding effects on DNA methylation patterns deriving from genetic and environmental factors. We showed that defects in DNA methylation map in genes involved in developmental, neurological and haematological pathways. These genes are enriched on chromosome 21 but localize also in the rest of the genome, suggesting that the trisomy of specific genes on chromosome 21 induces a cascade of events that engages many genes on other chromosomes and results in a global alteration of genomic function. We also analysed the methylation status of three target regions localized at the promoter (Ribo) and at the 5’ sequences of 18S and 28S regions of the rDNA, identifying differently methylated CpG sites. In conclusion, we identified an epigenetic signature of Down Syndrome in blood cells that sustains a link between developmental defects and disease phenotype, including segmental premature aging.

Antiepileptic drugs and pregnancy. Population based pharmaco-epidemiological study on prescription patterns, pregnancy outcome and foetal health

Aims of the study: To assess the prevalence of Antiepileptic Drug (AED) exposure in pregnant women with or without epilepsy and the comparative risk of terminations of pregnancy (TOPs), spontaneous abortions, stillbirth, major congenital malformations (MCMs) and foetal growth retardation (FGR) following intrauterine AED exposure in the Emilia Romagna region (RER), Northern Italy (4 million inhabitants). Methods: Data were obtained from official regional registries: Certificate of Delivery Assistance, Hospital Discharge Card, reimbursed prescription databases and Registry of Congenital Malformations. We identified all the deliveries, hospitalized abortions and MCMs occurred between January 2009 and December 2011. Results: We identified 145,243 pregnancies: 111,284 deliveries (112,845 live births and 279 stillbirths), 16408 spontaneous abortions and 17551 TOPs. Six hundred and eleven pregnancies (0.42% 95% Cl: 0.39-0.46) were exposed to AEDs. Twenty-one per cent of pregnancies ended in TOP in the AED group vs 12% in the non-exposed (OR:2.24; CI 1.41-3.56). The rate of spontaneous abortions and stillbirth was comparable in the two groups. Three hundred fifty-three babies (0.31%, 95% CI: 0.28-0.35) were exposed to AEDs during the first trimester. The rate of MCMs was 2.3% in the AED group (2.2% in babies exposed to monotherapy and 3.1% in babies exposed to polytherapy) vs 2.0% in the non-exposed. The risk of FGR was 12.7 % in the exposed group compared to 10% in the non-exposed. Discussion and Conclusion: The prevalence of AED exposure in pregnancy in the RER was 0.42%. The rate of MCMs in children exposed to AEDs in utero was almost superimposable to the one of the non-exposed, however polytherapy carried a slightly increased risk . The rate of TOPs was significantly higher in the exposed women. Further studies are needed to clarify whether this high rate reflects a higher rate of MCMs detected prenatally or other more elusive reasons.