<Emphasis Type="Italic">PTPN22</Emphasis> 1858C>T (R620W) functional polymorphism and human longevity

The PTPN22 gene, located on chromosome 1p13, encoding lymphoid protein tyrosine phosphatase (LYP), plays a crucial role in the negative control of T lymphocyte activation. Since the age-related change in T-cell signal transduction may be one of the most important causes of cell-mediated immune response decline with ageing, we performed a population-based association study to test whether the PTPN22 1858C>T (R620W) functional polymorphism affects the ability to survive to old age and to reach even exceptional life expectancy. 892 unrelated healthy individuals (age range 8–106 years, 403 males and 489 females) from central Italy were studied. For both gender, the frequency of PTPN22*T1858 carriers does not differ significantly in nona/centenarians and in octogenarians respect to young group. Allele and genotype frequencies of age groups were compared to those reported in previously published studied carried out on control individuals with Italic ancestry (N = 1393), further confirming results obtained from our sample population. Overall, our study suggests that PTPN22*T1858 allele is not negatively selected at oldest ages and we speculate that its increased ability to protect individuals against development of infectious diseases may counteract its deleterious effect on immune system leading to autoimmunity.     

Species boundaries and phylogeography of the "Euscorpius carpathicus complex" (Scorpiones: Euscorpiidae) in Italy

Euscorpius tergestinus (C.L. Koch, 1837), Euscorpius concinnus (C.L. Koch, 1837) and Euscorpius sicanus (C.L. Koch, 1837), three presumed closely related species belonging to the "carpathicus group", occur in the Italian peninsula with a largely parapatric distribution and some zones of range overlap. These areas of sympatry represent interesting opportunities to investigate species boundaries in natural populations. Here we report on a study exploring genetic variation in sympatric populations of the three species from central Tuscany. Additional collecting sites, from different localities across Italy, were also included in the analysis in order to explore the phylogeographic structure of the group. Species boundaries and evolutionary relationships were examined by sequence comparison of mitochondrial 16S rRNA and nuclear ITS-1 rRNA gene fragments. DNA sequence data show no evidence of genetic introgression between different evolutionary lineages from the area of range overlap, suggesting the absence of either past or ongoing inter-specific gene flow. It is therefore probable that reproductive barriers exist, preventing gene pools from amalgamating. Furthermore, our results support the recent morphological distinction of E. tergestinus, as traditionally classified, into two different species: E. tergestinus and E. concinnus. Both mitochondrial and nuclear sequence data clearly indicate that the two taxa represent well-supported and deeply divergent lineages. Euscorpius sicanus seems to represent a monophyletic taxon, but the high genetic variability observed within this taxon calls for future investigation. The present distribution patterns across the Italian peninsula were mainly interpreted as the consequence of climatic oscillations.     

Contribution of individual disulfide bonds to the oxidative folding of ribonuclease A

The eight cysteine residues of ribonuclease A form four disulfide bonds in the native protein. We have analyzed the folding of three double RNase A mutants (C65A/C72A, C58A/C110A, and C26A/C84A, lacking the C65-C72, C58-C110, and C26-C84 disulfide bonds, respectively) and two single mutants (C110A and C26A), in which a single cysteine is replaced with an alanine and the paired cysteine is present in the reduced form. The folding of these mutants was carried out in the presence of oxidized and reduced glutathione, which constitute the main redox agents present within the ER. The use of mass spectrometry in the analysis of the folding processes allowed us (i) to follow the formation of intermediates and thus the pathway of folding of the RNase A mutants, (ii) to quantitate the intermediates that formed, and (iii) to compare the rates of formation of intermediates. By comparison of the folding kinetics of the mutants with that of wild-type RNase A, the contribution of each disulfide bond to the folding process has been evaluated. In particular, we have found that the folding of the C65A/C72A mutant occurs on the same time scale as that of the wild-type protein, thus suggesting that the removal of the C65-C72 disulfide bond has no effect on the kinetics of RNase A folding. Conversely, the C58A/C110A and C26A/C84A mutants fold much more slowly than the wild-type protein. The removal of the C58-C110 and C26-C84 disulfide bonds has a dramatic effect on the kinetics of RNase A folding. Results described in this paper provide specific information about conformational folding events in the regions involving the mutated cysteine residues, thus contributing to a better understanding of the complex mechanism of oxidative folding.     

Identification of Polymorphisms in the Rabbit Growth Hormone Receptor (GHR) Gene and Association with Finishing Weight in a Commercial Meat Rabbit Line

A shortcut to identify DNA markers associated with economic traits is to use a candidate gene approach that is still useful in livestock species in which molecular tools and resources are not advanced or not well developed. Mutations in the growth hormone receptor (GHR) gene associated with production traits have been already described in several livestock species. For this reason GHR could be an interesting candidate gene in the rabbit. In this study we re-sequenced all exons and non-coding regions of the rabbit GHR gene in a panel of 10 different rabbits and identified 10 single nucleotide polymorphisms (SNPs). One of them (g.63453192C>G or c.106C>G), located in exon 3 was a missense mutation (p.L36V) substituting an amino acid in a highly conserved position across all mammals. This mutation was genotyped in 297 performance tested rabbits of a meat male line and association analysis showed that the investigated SNP was associated with weight at 70 days (P < 0.05). The most frequent genotype (GG) was in animals with higher weight at this age, suggesting that the high directional selection pressure toward this trait since the constitution of the genotyped line might have contributed to shape allele frequencies at this polymorphic site.     

Early childhood arts education in the United States: A special issue of Arts Education Policy Review

ABSTRACT

In this introduction to Early Childhood Arts Education in the United States, a special issue of Arts Education Policy Review, the editors provide a platform for stakeholders' increased awareness and understandings of the need to ensure children's rights to arts education. They summarize the five articles comprising this issue, and invite stakeholders to consider example action steps to apply content from this Issue to arts interactions with young children.     

New aryldithiolethione derivatives as potent histone deacetylase inhibitors

A series of dithiolethione derivatives was synthesized and the in vitro HDAC inhibitory activity was tested. The most active compounds, 1 and 2, exhibited an IC₅₀ in nM range with a strong hyperacetylation of histone H4 in A549 cells. The HDAC inhibitory activity comparable to that of SAHA and the inhibition of A549 cell proliferation suggest that these compounds are worthy of further studies as potential anticancer agents.