73 research outputs found

    Mitochondrial phylogeography and demographic history of the Vicuña: implications for conservation

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    The vicuña (Vicugna vicugna; Miller, 1924) is a conservation success story, having recovered from near extinction in the 1960s to current population levels estimated at 275 000. However, lack of information about its demographic history and genetic diversity has limited both our understanding of its recovery and the development of science-based conservation measures. To examine the evolution and recent demographic history of the vicuña across its current range and to assess its genetic variation and population structure, we sequenced mitochondrial DNA from the control region (CR) for 261 individuals from 29 populations across Peru, Chile and Argentina. Our results suggest that populations currently designated as Vicugna vicugna vicugna and Vicugna vicugna mensalis comprise separate mitochondrial lineages. The current population distribution appears to be the result of a recent demographic expansion associated with the last major glacial event of the Pleistocene in the northern (18 to 22°S) dry Andes 14–12 000 years ago and the establishment of an extremely arid belt known as the 'Dry Diagonal' to 29°S. Within the Dry Diagonal, small populations of V. v. vicugna appear to have survived showing the genetic signature of demographic isolation, whereas to the north V. v. mensalis populations underwent a rapid demographic expansion before recent anthropogenic impacts

    Barriers and facilitators to implementing community outreach work, and inter-professional collaboration with regional partners

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    Abstract : Objective. Community outreach workers support individuals in accessing the health and community services they require through various forms of proximity approaches. Even though community outreach has been available in the province of Quebec (Canada) for the past 40 years, it is still difficult to implement and sustain, especially with families of young children. The aim of this study was to document barriers and facilitators to implementing community outreach practices, and to describe how such workers collaborate with sectoral (e.g. health care) and inter-sectoral (e.g. municipalities, community organizations, schools) partners. Methodology. We performed a content analysis on 55 scientific and grey literature documents, and transcriptions of 24 individual interviews and 3 focus groups with stakeholders including parents, community outreach workers, health care employees, and inter-sectoral partners. Results. This study reveals four categories of barriers and facilitators to the implementation of community outreach work (i.e. organizational factors, nature of the work and worker-related factors, family-related factors, external factors). With regards to collaboration, community outreach workers deal with various partners. Good inter-professional collaboration is achieved through positive interactions and communication, shared or co-developed activities for the families, co-intervention with families, and strategies to enhance role awareness and inter-sectoral meetings. Conclusion. Results highlighted that many factors interact and can either influence, positively or negatively, the opportunity to implement community outreach work. The collaborative practices identified may help to maximize facilitators and overcome barriers. Advocacy and a better understanding of how to integrate community outreach work within health services while maintaining the workers’ flexibility are needed to sustain this practice

    Domain Swapping and Different Oligomeric States for the Complex Between Calmodulin and the Calmodulin-Binding Domain of Calcineurin A

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    BACKGROUND: Calmodulin (CaM) is a ubiquitously expressed calcium sensor that engages in regulatory interactions with a large number of cellular proteins. Previously, a unique mode of CaM target recognition has been observed in the crystal structure of a complex between CaM and the CaM-binding domain of calcineurin A. METHODOLOGY/PRINCIPAL FINDINGS: We have solved a high-resolution crystal structure of a complex between CaM and the CaM-binding domain of calcineurin A in a novel crystal form, which shows a dimeric assembly of calmodulin, as observed before in the crystal state. We note that the conformation of CaM in this complex is very similar to that of unliganded CaM, and a detailed analysis revels that the CaM-binding motif in calcineurin A is of a novel '1-11' type. However, using small-angle X-ray scattering (SAXS), we show that the complex is fully monomeric in solution, and a structure of a canonically collapsed CaM-peptide complex can easily be fitted into the SAXS data. This result is also supported by size exclusion chromatography, where the addition of the ligand peptide decreases the apparent size of CaM. In addition, we studied the energetics of binding by isothermal titration calorimetry and found them to closely resemble those observed previously for ligand peptides from CaM-dependent kinases. CONCLUSIONS/SIGNIFICANCE: Our results implicate that CaM can also form a complex with the CaM-binding domain of calcineurin in a 1 ratio 1 stoichiometry, in addition to the previously observed 2 ratio 2 arrangement in the crystal state. At the structural level, going from 2 ratio 2 association to two 1 ratio 1 complexes will require domain swapping in CaM, accompanied by the characteristic bending of the central linker helix between the two lobes of CaM

    Identification of a Danish breast/ovarian cancer family double heterozygote for BRCA1 and BRCA2 mutations

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    Mutations in the two breast cancer susceptibility genes BRCA1 and BRCA2 are associated with increased risk of breast and ovarian cancer. Patients with mutations in both genes are rarely reported and often involve Ashkenazi founder mutations. Here we report the first identification of a Danish breast and ovarian cancer family heterozygote for mutations in the BRCA1 and BRCA2 genes. The BRCA1 nucleotide 5215G > A/c.5096G > A mutation results in the missense mutation Arg1699Gln, while the BRCA2 nucleotide 859 + 4A > G/c.631 + 4A > G is novel. Exon trapping experiments and reverse transcriptase (RT)–PCR analysis revealed that the BRCA2 mutation results in skipping of exon 7, thereby introducing a frameshift and a premature stop codon. We therefore classify the mutation as disease causing. Since the BRCA1 Arg1699Gln mutation is also suggested to be disease-causing, we consider this family double heterozygote for BRCA1 and BRCA2 mutations

    Инфекционная составляющая и иммунопатология при хронических воспалительных заболеваниях слизистой оболочки гастродуоденальной области

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    Выявлено коинфицирование слизистой оболочки желудочно−кишечного тракта Helicobacter pylori и вирусами группы герпеса у больных хроническим гастритом, язвенной болезнью желудка и двенадцатиперстной кишки. Проведена оценка общих и специфических иммунных реакций организма на указанные инфекционные агенты. Обнаруженные изменения в клеточном и гуморальном звене иммунитета могут свидетельствовать об обусловленном ими системном иммунопатологическом процессе.Co−infection of the gastrointestinal mucosa with Helicobacter pylori and herpes viruses in patients with chronic gastritis, gastric and duodenal ulcer was revealed. General and specific immune reactions of the organism to the above agents were evaluated. The revealed changes in the cellular and humoral immunity can suggest systemic immunopathological process

    A method to assess the clinical significance of unclassified variants in the BRCA1 and BRCA2 genes based on cancer family history

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    Introduction Unclassified variants (UVs) in the BRCA1/BRCA2 genes are a frequent problem in counseling breast cancer and/or ovarian cancer families. Information about cancer family history is usually available, but has rarely been used to evaluate UVs. The aim of the present study was to identify which is the best combination of clinical parameters that can predict whether a UV is deleterious, to be used for the classification of UVs. Methods We developed logistic regression models with the best combination of clinical features that distinguished a positive control of BRCA pathogenic variants (115 families) from a negative control population of BRCA variants initially classified as UVs and later considered neutral (38 families). Results The models included a combination of BRCAPRO scores, Myriad scores, number of ovarian cancers in the family, the age at diagnosis, and the number of persons with ovarian tumors and/ or breast tumors. The areas under the receiver operating characteristic curves were respectively 0.935 and 0.836 for the BRCA1 and BRCA2 models. For each model, the minimum receiver operating characteristic distance (respectively 90% and 78% specificity for BRCA1 and BRCA2) was chosen as the cutoff value to predict which UVs are deleterious from a study population of 12 UVs, present in 59 Dutch families. The p. S1655F, p. R1699W, and p. R1699Q variants in BRCA1 and the p. Y2660D, p. R2784Q, and p. R3052W variants in BRCA2 are classified as deleterious according to our models. The predictions of the p. L246V variant in BRCA1 and of the p. Y42C, p. E462G, p. R2888C, and p. R3052Q variants in BRCA2 are in agreement with published information of them being neutral. The p. R2784W variant in BRCA2 remains uncertain. Conclusions The present study shows that these developed models are useful to classify UVs in clinical genetic practic

    Intra-Genomic Ribosomal RNA Polymorphism and Morphological Variation in Elphidium macellum Suggests Inter-Specific Hybridization in Foraminifera

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    Elphidium macellum is a benthic foraminifer commonly found in the Patagonian fjords. To test whether its highly variable morphotypes are ecophenotypes or different genotypes, we analysed 70 sequences of the SSU rRNA gene from 25 specimens. Unexpectedly, we identified 11 distinct ribotypes, with up to 5 ribotypes co-occurring within the same specimen. The ribotypes differ by varying blocks of sequence located at the end of stem-loop motifs in the three expansion segments specific to foraminifera. These changes, distinct from typical SNPs and indels, directly affect the structure of the expansion segments. Their mosaic distribution suggests that ribotypes originated by recombination of two or more clusters of ribosomal genes. We propose that this expansion segment polymorphism (ESP) could originate from hybridization of morphologically different populations of Patagonian Elphidium. We speculate that the complex geological history of Patagonia enhanced divergence of coastal foraminiferal species and contributed to increasing genetic and morphological variation

    Phylogeography of the Patagonian otter Lontra provocax: adaptive divergence to marine habitat or signature of southern glacial refugia?

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    <p>Abstract</p> <p>Background</p> <p>A number of studies have described the extension of ice cover in western Patagonia during the Last Glacial Maximum, providing evidence of a complete cover of terrestrial habitat from 41°S to 56°S and two main refugia, one in south-eastern Tierra del Fuego and the other north of the Chiloé Island. However, recent evidence of high genetic diversity in Patagonian river species suggests the existence of aquatic refugia in this region. Here, we further test this hypothesis based on phylogeographic inferences from a semi-aquatic species that is a top predator of river and marine fauna, the huillín or Southern river otter (<it>Lontra provocax</it>).</p> <p>Results</p> <p>We examined mtDNA sequences of the control region, ND5 and Cytochrome-b (2151 bp in total) in 75 samples of <it>L. provocax </it>from 21 locations in river and marine habitats. Phylogenetic analysis illustrates two main divergent clades for <it>L. provocax </it>in continental freshwater habitat. A highly diverse clade was represented by haplotypes from the marine habitat of the Southern Fjords and Channels (SFC) region (43°38' to 53°08'S), whereas only one of these haplotypes was paraphyletic and associated with northern river haplotypes.</p> <p>Conclusions</p> <p>Our data support the hypothesis of the persistence of <it>L. provocax </it>in western Patagonia, south of the ice sheet limit, during last glacial maximum (41°S latitude). This limit also corresponds to a strong environmental change, which might have spurred <it>L. provocax </it>differentiation between the two environments.</p
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