Valproic acid determination by liquid chromatography coupled to mass spectrometry (LC–MS/MS) in whole blood for forensic purposes

Valproic acid (VPA) is a well-known drug prescribed as anti-epileptic. It has a narrow therapeutic range and shows great individual differences in pharmacodynamics and pharmacokinetics. Consequently, the therapeutical drug monitoring (TDM) in patient's plasma is of crucial importance. Liquid chromatography coupled to mass spectrometry (LC–MS/MS) has gained importance in TDM applications for its features of sensitivity, selectivity and rapidity. However, in case of VPA, the LC–MS/MS selectivity could be hampered by the lack of a sufficient number of multiple reaction monitoring (MRM) transitions describing the molecule. In fact, the product ion scan of deprotonated molecules of VPA does not produce any ion and thus most LC–MS/MS methods are based on the detection of the unique MRM transition m/z 143➔143. In this way, the advantages of selectivity in LC–MS cannot be effectively exploited. In the present method, stable analyte adducts were exploited for the determination of VPA in blood. An Acquity HSS C18 column and mobile phases consisting of 5-mM ammonium formate and acetonitrile both added 0.1% formic acid were used. Source worked in negative acquisition mode and parameters were optimized to increase the adduct (m/z 189) and dimer (m/z 287) stability, and their fragmentation were used to increase the selectivity of MRM detection. The method has been validated according to the toxicological forensic guidelines and successfully applied to 10 real blood samples. Finally, the present method showed suitable for the rapid LC–MS/MS detection of VPA in whole blood, demonstrating the possibility to increase specificity by exploiting stable in-source adducts. This should be considered of utmost importance in the case of forensic applications

Genome-Wide snp analysis of southern african populations provides new insights into the dispersal of bantu-Speaking groups

The expansion of Bantu-speaking agropastoralist populations had a great impact on the genetic, linguistic, and cultural variation of sub-Saharan Africa. It isgenerally accepted that Bantulanguages originated inanarea around thepresent borderbetweenCameroon and Nigeria approximately 5,000 years ago, from where they spread South and East becoming the largest African linguistic branch. The demic consequences of this event are reflected in the relatively high genetic homogeneity observed acrossmost of sub-Saharan Africapopulations. Inthiswork, weexploredgenome-wide singlenucleotidepolymorphismdata from28populations to characterize the genetic components present in sub-Saharan African populations. Combining novel data from four SouthernAfrican populations withpreviouslypublishedresults,we reject the hypothesis that the" non-Bantu" geneticcomponent reported inSouth-Eastern Africa (Mozambique) reflects extensive gene flow between incoming agriculturalist and resident hunter-gatherer communities.We alternatively suggest that this novel component is the result of demographic dynamics associated with the Bantu dispersal

Complex ancient genetic structure and cultural transitions in Southern African populations

The characterization of the structure of southern African populations has been the subject of numerous genetic, medical, linguistic, archaeological, and anthropological investigations. Current diversity in the subcontinent is the result of complex events of genetic admixture and cultural contact between early inhabitants and migrants that arrived in the region over the last 2000 years. Here, we analyze 1856 individuals from 91 populations, comprising novel and published genotype data, to characterize the genetic ancestry profiles of 631 individuals from 51 southern African populations. Combining both local ancestry and allele frequency based analyses, we identify a tripartite, ancient, Khoesan-related genetic structure. This structure correlates neither with linguistic affiliation nor subsistence strategy, but with geography, revealing the importance of isolation-by-distance dynamics in the area. Fine-mapping of these components in southern African populations reveals admixture and cultural reversion involving several Khoesan groups, and highlights that Bantu speakers and Coloured individuals have different mixtures of these ancient ancestries

Discerning the ancestry of European Americans in genetic association studies

European Americans are often treated as a homogeneous group, but in fact form a structured population due to historical immigration of diverse source populations. Discerning the ancestry of European Americans genotyped in association studies is important in order to prevent false-positive or false-negative associations due to population stratification and to identify genetic variants whose contribution to disease risk differs across European ancestries. Here, we investigate empirical patterns of population structure in European Americans, analyzing 4,198 samples from four genome-wide association studies to show that components roughly corresponding to northwest European, southeast European, and Ashkenazi Jewish ancestry are the main sources of European American population structure. Building on this insight, we constructed a panel of 300 validated markers that are highly informative for distinguishing these ancestries. We demonstrate that this panel of markers can be used to correct for stratification in association studies that do not generate dense genotype data

Persistent homology to analyse 3D faces and assess body weight gain

In this paper, we analyse patterns in face shape variation due to weight gain. We propose the use of persistent homology descriptors to get geometric and topological information about the configuration of anthropometric 3D face landmarks. In this way, evaluating face changes boils down to comparing the descriptors computed on 3D face scans taken at different times. By applying dimensionality reduction techniques to the dissimilarity matrix of descriptors, we get a space in which each face is a point and face shape variations are encoded as trajectories in that space. Our results show that persistent homology is able to identify features which are well related to overweight and may help assessing individual weight trends. The research was carried out in the context of the European project SEMEOTICONS, which developed a multisensory platform which detects and monitors over time facial signs of cardio-metabolic risk

Uniparental markers of contemporary Italian population reveals details on its pre-Roman heritage.

BACKGROUND: According to archaeological records and historical documentation, Italy has been a melting point for populations of different geographical and ethnic matrices. Although Italy has been a favorite subject for numerous population genetic studies, genetic patterns have never been analyzed comprehensively, including uniparental and autosomal markers throughout the country. METHODS/PRINCIPAL FINDINGS: A total of 583 individuals were sampled from across the Italian Peninsula, from ten distant (if homogeneous by language) ethnic communities--and from two linguistic isolates (Ladins, Grecani Salentini). All samples were first typed for the mitochondrial DNA (mtDNA) control region and selected coding region SNPs (mtSNPs). This data was pooled for analysis with 3,778 mtDNA control-region profiles collected from the literature. Secondly, a set of Y-chromosome SNPs and STRs were also analyzed in 479 individuals together with a panel of autosomal ancestry informative markers (AIMs) from 441 samples. The resulting genetic record reveals clines of genetic frequencies laid according to the latitude slant along continental Italy--probably generated by demographical events dating back to the Neolithic. The Ladins showed distinctive, if more recent structure. The Neolithic contribution was estimated for the Y-chromosome as 14.5% and for mtDNA as 10.5%. Y-chromosome data showed larger differentiation between North, Center and South than mtDNA. AIMs detected a minor sub-Saharan component; this is however higher than for other European non-Mediterranean populations. The same signal of sub-Saharan heritage was also evident in uniparental markers. CONCLUSIONS/SIGNIFICANCE: Italy shows patterns of molecular variation mirroring other European countries, although some heterogeneity exists based on different analysis and molecular markers. From North to South, Italy shows clinal patterns that were most likely modulated during Neolithic times