Genome-wide association study of multiple sclerosis confirms a novel locus at 5p13.1

Multiple Sclerosis (MS) is the most common progressive and disabling neurological condition affecting young adults in the world today. From a genetic point of view, MS is a complex disorder resulting from the combination of genetic and non-genetic factors. We aimed to identify previously unidentified loci conducting a new GWAS of Multiple Sclerosis (MS) in a sample of 296 MS cases and 801 controls from the Spanish population. Meta-analysis of our data in combination with previous GWAS was done. A total of 17 GWAS-significant SNPs, corresponding to three different loci were identified:HLA, IL2RA, and 5p13.1. All three have been previously reported as GWAS-significant. We confirmed our observation in 5p13.1 for rs9292777 using two additional independent Spanish samples to make a total of 4912 MS cases and 7498 controls (ORpooled = 0.84; 95%CI: 0.80-0.89; p = 1.36 × 10-9). This SNP differs from the one reported within this locus in a recent GWAS. Although it is unclear whether both signals are tapping the same genetic association, it seems clear that this locus plays an important role in the pathogenesis of MS.     

Endoparasites of fat-tailed mouse opossums (Thylamys: Didelphidae) from northwestern Argentina and southern Bolivia, with the description of a new species of tapeworm

The parasite fauna of 2 species of fat-tailed mouse opossums from northwestern Argentina is herein presented. Five species of helminths were found, i.e., Pterygodermatites kozeki, Hoineffia simplispicula, Oligacanthorhynchus sp., and a new species of tapeworm, Mathevotaenia sanmartini n. sp. (Cyclophyllidea: Anoplocephalidae). The new species is characterized by a calyciform scolex, relatively few testes (32), and a long cirrus sac; it occurs in fat-tailed mouse opossums at localities above 4,000 m. Those characters make it different from 6 species known to occur in marsupials from the New World, and from other species occurring in armadillos and bats. Didelphoxyuris thylamisis, H. simplicispicula, and Oligacanthorhynchus sp. appear to occur in marmosas from the Yungas region. In contrast, both P. kozeki and M. sanmartini n. sp. appear to occur exclusively in the Puna.     

Group-specific primers for DNA-based detection of springtails (Hexapoda: Collembola) within predator gut contents

Group‐specific, degenerate polymerase chain reaction primers for DNA‐based detection of springtails (Hexapoda: Collembola) within predator gut contents have been developed for the first time. Primers were designed from 18S rDNA and amplified fragments of 272 bp and 177 bp from 17 springtail species collected in agricultural habitats. Specificity tests against 41 nontarget species revealed no cross‐reactivity. Group‐specific polymerase chain reaction is advantageous when working in species‐rich habitats and these primers could facilitate studies of trophic links between springtails and generalist arthropod predators worldwide.     

The CAPN10 gene is associated with insulin resistance phenotypes in the Spanish population

Cardiovascular disease is the leading cause of morbidity and mortality in the industrialized world. Familial aggregation of cardiovascular risk factors is a frequent finding, but genetic factors affecting its presentation are still poorly understood. The calpain 10 gene (CAPN10) has been associated with type 2 diabetes (T2DM), a complex metabolic disorder with increased risk of cardiovascular disease. Moreover, the CAPN10 gene has been associated with the presence of metabolic syndrome (MS) in T2DM and in polycystic ovary syndrome (PCOS). In this work, we have analysed whether the polymorphisms UCSNP44, -43, -19 and -63 are related to several cardiovascular risk factors in the context of MS. Molecular analysis of CAPN10 gene was performed in 899 individuals randomly chosen from a cross-sectional population-based epidemiological survey. We have found that CAPN10 gene in our population is mainly associated with two indicators of the presence of insulin resistance: glucose levels two hours after a 75-g oral glucose tolerance test (OGTT) and HOMA values, although cholesterol levels and blood pressure values are also influenced by CAPN10 variants. In addition, the 1221/1121 haplogenotype is under-represented in individuals that fulfil the International Diabetes Federation (IDF) diagnostic criteria for MS. Our results suggest that CAPN10 gene is associated with insulin resistance phenotypes in the Spanish population.     

Cancer genes hypermethylated in human embryonic stem cells

Developmental genes are silenced in embryonic stem cells by a bivalent histone-based chromatin mark. It has been proposed that this mark also confers a predisposition to aberrant DNA promoter hypermethylation of tumor suppressor genes (TSGs) in cancer. We report here that silencing of a significant proportion of these TSGs in human embryonic and adult stem cells is associated with promoter DNA hypermethylation. Our results indicate a role for DNA methylation in the control of gene expression in human stem cells and suggest that, for genes repressed by promoter hypermethylation in stem cells in vivo, the aberrant process in cancer could be understood as a defect in establishing an unmethylated promoter during differentiation, rather than as an anomalous process of de novo hypermethylation.     

New Pd(II) and Pt(II) complexes with N,S-chelated pyrazolonate ligands: molecular and supramolecular structure and preliminary study of their in vitro antitumoral activity

New Pd(II) and Pt(II) complexes [ML2] (HL=a substituted 2,5-dihydro-5-oxo-1H-pyrazolone-1-carbothioamide) have been synthesized by reacting K2MCl4 (M=Pd, Pt) or Pd(OAc)2 with beta-ketoester thiosemicarbazones. The structures of seven of these complexes were determined by X-ray diffraction. Although all exhibit a distorted square-planar coordination with trans- or (in one case) cis-[MN2S2] kernels, their supramolecular arrangements vary widely from isolated molecules to 3D-networks. The in vitro antitumoral assays performed with two HL ligands and their metal complexes showed significant cytostatic activity for the latter, with the most active [ML2] derivative (a palladium complex) being about sixteen times more active than cis-DDP against the cisplatinum-resistant cell line A2780cisR.     

Detection of Alpha and Gamma-Proteobacteria in <Emphasis Type="Italic">Amblyomma triste</Emphasis> (Acari: Ixodidae) from Uruguay

Amblyomma triste is the most prevalent tick species reported in human tick bites in Uruguay and has been found to be infected with Rickettsia parkeri, but no other microorganisms have been reported from this tick. A sample of 254 adults of A. triste was collected by flagging on vegetation in suburban areas in southern Uruguay. Pools of five ticks were assembled and a screening for the DNA from the resulting 51 pools was realized by PCR assays using primers for amplifying a fragment of 16S rRNA gene for members of Anaplasmataceae. Seventeen pools were positive (33%) and the sequenciation of the gene fragment amplified revealed the presence of a putative new Alpha-Proteobacterium (denominated Atri-uru). The phylogenetic analysis showed that this microorganism is closely related to the symbiont of I. ricinus denominated ‘Candidatus Midichloria mitochondrii’ and other associated organisms. This rickettsial symbiont of ticks is included in a recent new clade proposed for the Alpha subclass of the Proteobacteria. The discovery of this bacterium in A. triste is the first evidence of this group of Rickettsiales detected in the Genus Amblyomma, and the first record in South America. Also, in two of 17 positive samples a Gamma-Proteobacterium related to Francisella-like organisms was detected.     

DNA hybridization biosensors using polylysine modified SPCEs

Two electrochemical DNA hybridization biosensors (genosensors) for the detection of a 30-mer sequence unique to severe acute respiratory syndrome (SARS) virus are described in this work. Both genosensors rely on the hybridization of the oligonucleotide target with its complementary probe, which is immobilized on positively charged polylysine modified screen-printed carbon electrodes (SPCEs), through electrostatic interactions. In one design, a biotinylated target is used and the detection of the hybridization reaction is monitored using alkaline phosphatase labeled streptavidin (S-AP). This enzyme catalyzes the hydrolysis of the substrate 3-indoxyl phosphate (3-IP) to indigo, which is then solubilized to indigo carmine and detected by means of cyclic voltammetry (CV). In the other design, the target is labeled using an Au(I) complex, sodium aurothiomalate, and the duplex formation is detected by measuring, for first time, the current generated by the hydrogen evolution catalyzed by the gold label. Using 30 min of hybridization time, a detection limit of 8 pM is calculated for the enzymatic genosensor. Although this good sensitivity cannot be reached with the metal label (0.5 nM), the use of this label allows a considerable decrease of the analysis time. Both genosensors do not require the modification of the oligonucleotide probe and using stringent experimental conditions (60 min of hybridization time and 50% formamide in the hybridization buffer) can discriminate between a complementary oligonucleotide and an oligonucleotide with a three-base mismatch.