Admixture and Genetic Diversity Distribution Patterns of Non-Recombining Lineages of Native American Ancestry in Colombian Populations

Genetic diversity of present American populations results from very complex demographic events involving different types and degrees of admixture. Through the analysis of lineage markers such as mtDNA and Y chromosome it is possible to recover the original Native American haplotypes, which remained identical since the admixture events due to the absence of recombination. However, the decrease in the effective population sizes and the consequent genetic drift effects suffered by these populations during the European colonization resulted in the loss or under-representation of a substantial fraction of the Native American lineages. In this study, we aim to clarify how the diversity and distribution of uniparental lineages vary with the different demographic characteristics (size, degree of isolation) and the different levels of admixture of extant Native groups in Colombia. We present new data resulting from the analyses of mtDNA whole control region, Y chromosome SNP haplogroups and STR haplotypes, and autosomal ancestry informative insertion-deletion polymorphisms in Colombian individuals from different ethnic and linguistic groups. The results demonstrate that populations presenting a high proportion of non-Native American ancestry have preserved nevertheless a substantial diversity of Native American lineages, for both mtDNA and Y chromosome. We suggest that, by maintaining the effective population sizes high, admixture allowed for a decrease in the effects of genetic drift due to Native population size reduction and thus resulting in an effective preservation of the Native American non-recombining lineages.     

Trisomy 8, a Cytogenetic Abnormality in Myelodysplastic Syndromes,Is Constitutional or Not?

Isolated trisomy 8 is not considered presumptive evidence of myelodysplastic syndrome (MDS) in cases without minimal morphological criteria. One reason given is that trisomy 8 (+8) can be found as a constitutional mosaicism (cT8M). We tried to clarify the incidence of cT8M in myeloid neoplasms, specifically in MDS, and the diagnostic value of isolated +8 in MDS. Twenty-two MDS and 10 other myeloid neoplasms carrying +8 were studied. Trisomy 8 was determined in peripheral blood by conventional cytogenetics (CC) and on granulocytes, CD3+ lymphocytes and oral mucosa cells by fluorescence in situ hybridization (FISH). In peripheral blood CC, +8 was seen in 4/32 patients. By FISH, only one patient with chronic myelomonocytic leukemia showed +8 in all cell samples and was interpreted as a cT8M. In our series +8 was acquired in all MDS. Probably, once discarded cT8M by FISH from CD3+ lymphocytes and non-hematological cells, +8 should be considered with enough evidence to MDS.     

Detection of “<Emphasis Type="Italic">Candidatus</Emphasis> Rickettsia sp. strain Argentina”and <Emphasis Type="Italic">Rickettsia bellii</Emphasis> in <Emphasis Type="Italic">Amblyomma</Emphasis> ticks (Acari: Ixodidae) from Northern Argentina

Ixodid ticks were collected from vegetation and from humans, wild and domestic mammals in a rural area in the semi-arid Argentine Chaco in late spring 2006 to evaluate their potential role as vectors of Spotted Fever Group (SFG) rickettsiae. A total of 233 adult ticks, identified as Amblyomma parvum, Amblyomma tigrinum and Amblyomma pseudoconcolor, was examined for Rickettsia spp. We identified an SFG rickettsia of unknown pathogenicity, “Candidatus Rickettsia sp. strain Argentina”, in A. parvum and A. pseudoconcolor by PCR assays targeting gltA, ompA, ompB and 17-kDa outer membrane antigen rickettsial genes. Rickettsia bellii was detected in a host-seeking male of A. tigrinum. Amblyomma parvum is widespread in the study area and is a potential threat to human health.     

Identification of species by multiplex analysis of variable-length sequences

The quest for a universal and efficient method of identifying species has been a longstanding challenge in biology. Here, we show that accurate identification of species in all domains of life can be accomplished by multiplex analysis of variable-length sequences containing multiple insertion/deletion variants. The new method, called SPInDel, is able to discriminate 93.3% of eukaryotic species from 18 taxonomic groups. We also demonstrate that the identification of prokaryotic and viral species with numeric profiles of fragment lengths is generally straightforward. A computational platform is presented to facilitate the planning of projects and includes a large data set with nearly 1800 numeric profiles for species in all domains of life (1556 for eukaryotes, 105 for prokaryotes and 130 for viruses). Finally, a SPInDel profiling kit for discrimination of 10 mammalian species was successfully validated on highly processed food products with species mixtures and proved to be easily adaptable to multiple screening procedures routinely used in molecular biology laboratories. These results suggest that SPInDel is a reliable and cost-effective method for broad-spectrum species identification that is appropriate for use in suboptimal samples and is amenable to different high-throughput genotyping platforms without the need for DNA sequencing.     

A single-point mutation in FGFR2 affects cell cycle and Tgfβ signalling in osteoblasts

Fgf and Tgfβ are key regulators of bone development. It is not known, however, whether there is a relationship between defective Fgf signalling, resulting in a premature cranial suture fusion, and Tgfβ signalling. We used mouse calvaria osteoblasts carrying a mutation (hFGFR2-C278F) associated with Crouzon and Pfeiffer syndromes to investigate effects of this mutation on cell growth and possible mechanisms underlying it. Mutated osteoblasts displayed reduced S-phase, increased apoptosis and increased differentiation. As Tgfβ signalling appeared to be required in an autocrine/paracrine manner for osteoblast proliferation, we tested the hypothesis that reduced growth might be due, at least in part, to an altered balance between FGF and Tgfβ signalling. Tgfβ expression was indeed decreased in mutated osteoblasts, as compared to osteoblasts carrying the wild type hFGFR2. Treatment with Tgfβ, however, neither increased proliferation in mutated osteoblasts, unlike in controls, nor rescued proliferation in control osteoblasts treated with an Erk1/2 inhibitor. Significantly, Erk2, that is important for proliferation, was reduced relatively to Erk1 in mutated cells. Altogether this study suggests that the hFGFR2-C278F mutation affects the osteoblast ability to respond to Tgfβ stimulation via the Erk pathway and that the overall effect of the mutation is a loss of function.     

Determination of substrate preferences of tench, Tinca tinca (L.), under controlled experimental conditions

The substrate preference of tench Tinca tinca (L.), 33 2‐year‐old individuals, mean size 10 ± 0.36 cm total length, was determined using four different substrates (concrete, artificial vegetation, sand and mud) in a 26 m long maquette. The species showed a high preference (100%) for the mud. Six more trials were performed combining the substrates by pairs (concrete–vegetation, concrete–mud, concrete–sand, mud–vegetation, mud–sand, sand–vegetation). Selection order was: mud (100% of the individuals when compared with concrete and sand and 98.26 ± 2.68% when compared with artificial vegetation), artificial vegetation (100% of the individuals when compared with concrete and 99.81 ± 0.76% when compared with sand), sand (98.29 ± 3.66% when compared with concrete) and concrete.     

Low prevalence of hepatitis C virus infection in Amerindians from Western Venezuela

Previous studies have not found hepatitis C virus (HCV) infection in Amerindians from Western Venezuela. A survey of 254 Bari and Yukpa natives aged 10-60 years (mean +/- SD age = 35 +/- 5.4 years) from four communities, two Bari and two Yukpa, in this area were studied to assess the prevalence of antibodies to HCV (anti-HCV) and HCV RNA among these indigenous populations. Serum samples were examined initially for anti-HCV by a four generation enzyme-linked immunosorbent assay (ELISA). Reactive samples were then tested using a third generation recombinant immunoblot assay (RIBA-3). Viral RNA was investigated in all immunoblot-reactive samples by a nested polymerase chain reaction (PCR) method. Six (2.3%) of 254 natives were positive by ELISA, one (2.2%) of these reactive samples were positive by RIBA, and four (1.5%) were indeterminate. Only two (0.8%) were positive by PCR, corresponding to 1 (2.1%) of 47 inhabitants of a Yukpa community and to 1 (2.2%) of 45 subjects of a Bari community. Iatrogenic is thought to play a role in acquisition of the infection. The findings indicate a HCV focus of low endemicity and are compatible with a low degree of exposures of the natives to the virus. Studies are necessary to assess the risk factors for infection in these Amerindians.     

Histamine improves antigen uptake and cross-presentation by dendritic cells

Previous studies have shown that histamine is able to modulate the function of dendritic cells (DCs). Histamine seems to be required for the normal differentiation of DCs. Moreover, it is capable of stimulating the chemotaxis of immature DCs and of promoting the differentiation of T CD4+ cells into a Th2 profile. In this study, we analyzed whether histamine was able to modulate endocytosis and cross-presentation mediated by immature DCs. Our results show that both functions are stimulated by histamine. Endocytosis of soluble HRP and FITC-OVA and cross-presentation of soluble OVA were markedly increased by histamine. Interestingly, stimulation of endocytosis and cross-presentation appeared to be mediated through different histamine receptors. In fact, the enhancement of endocytosis was prevented by the histamine2 receptor (H2R) antagonist cimetidine, whereas the stimulation of cross-presentation was prevented by the H3R/H4R antagonist thioperamide. Of note, contrasting with the observations made with soluble Ags, we found that histamine did not increase either the uptake of OVA-attached to latex beads, or the cross-presentation of OVA immobilized on latex beads. This suggests that the ability of histamine to increase endocytosis and cross-presentation is dependent on the Ag form and/or the mechanisms through which the Ag is internalized by DCs. Our results support that histamine may favor cross-presentation of soluble allergens by DCs enabling the activation of allergen-specific T CD8+ cells, which appears to play an important role in the development of allergic responses in the airway.     

Hyperthermia-Induced Seizures Modify the GABA<Subscript>A</Subscript> and Benzodiazepine Receptor Binding in Immature Rat Brain

Effects of hyperthermia-induced seizures (HS) on GABA_A and benzodiazepine (BDZ) receptor binding in immature rat brain were evaluated using in vitro autoradiography. HS were induced in 10-days-old rats by a regulated stream of moderately heated air directed 50 cm above the animals. Rats were killed 30 min, 24 h or 20 days after HS and their brains were used for in vitro autoradiography experiments to determine GABA_A and BDZ receptor binding. GABA_A binding was significantly enhanced in all brain areas evaluated 30 min after HS, an effect that endures 24 h and 20 days after seizures. Concerning BDZ receptor binding, a significant increase was detected in entorhinal and perirhinal cortices and decreased in basolateral amygdala 30 min following HS. One day after HS, animals demonstrated enhanced BDZ binding in the cingulate, frontal, posterior parietal, entorhinal, temporal and perirhinal cortices; striatum, accumbens, substantia nigra pars compacta and amygdala nuclei. Twenty days after HS enhanced BDZ binding was restricted in the cingulated, frontal, anterior and posterior parietal cortices, as well as in substantia nigra pars reticulata, whereas decreased values were found in accumbens nucleus and substantia nigra pars compacta. Our data indicate differential effects of HS in GABA_A and BDZ binding in immature brain. HS-induced GABA_A and BDZ changes are different from those previously described in experimental models of temporal lobe epilepsy in adult animals.