Genomic diversity and population structure analysis reveal few genetic differences among Ethiopian indigenous sheep populations

African sheep, like other domestic sheep, are domesticated from the Asiatic mouflon (Ovis orientalis). They entered the continent through the North and the Horn of Africa regions following maritime and terrestrial trading routes. Ethiopia is one of the main entry points of various plant and animal domesticates into Africa. It is characterised by diverse agro-ecologies, ancient human ethnic diversity and the presence of indigenous sheep breeds/populations of unprecedented morphological diversity (e.g. tail types). Here, we investigate the genome diversity and population structure of 146 unrelated animals from 11 Ethiopian indigenous sheep populations. DNA was extracted from ear tissue punches and genotyped with the Illumina Ovine 50K SNP BeadChip assay. Sheep populations from The Caribbean, Europe, Middle East and China as well as from western, northern and southern Africa were included to clarify the genetic history of origin, introduction and dispersal of the species into Ethiopia. Principal component analysis (PCA), clearly separated all Ethiopian sheep from the other populations. Population structure and phylogenetic (neighbour-joining tree) analysis subdivided the Ethiopian indigenous sheep into three genetic clusters corresponding to their tail morphology (rump fat-tailed, short fat-tailed and long fat/thin-tailed population). It supports a common genetic ancestry for populations of each tail type in the country. Genetic distances among the Ethiopian populations were positively correlated with geographic distances (Mantel test, P < 0.001, r = 0.465) and the highest genetic diversity was recorded in the fat-tailed (short, rump and/or long fat-tailed) close to the Bab-el-Mandeb strait. However, despite their distinct morphology and separate geographic distribution, little genetic differentiation between Ethiopian populations are observed. This is most likely a consequence of their ancient and modern intermixing following their introduction into the country

Autologous tooth graft after endodontical treated used for socket preservation: A multicenter clinical study.

The aim of the study was to evaluate the tooth extracted use as autologous tooth graft after endodontic root canal therapies used for socket preservation. To this purpose, the Tooth Transformer shredding and decontamination machine has been used. The graft obtained in this way, was inserted at the time of the extraction or at a second surgery altogether with the chosen regenerative therapy. This clinical trial enrolled patients with post-estractive defects requiring the restoration bone dimension and shape in the maxillary and mandibular zone. In addition, 98 patients with 119 extraction sockets were enrolled across 10 standardized centers. An innovative preparation method, using the dedicated automated device Tooth Transformer, able to transform autologous teeth in suitable grafting material, has been used. The extracted tooth was cleaned and treated using a Tooth Transformer and made a socket preservation. Thirteen Biopsies were realized to analyze the histologic outcomes at the average time of four months to demonstrate that the autologous tooth graft made from root after endodontic therapy should be used in human bone regeneration as graft for dental implant placement

Trayectorias laborales de jóvenes trabajadores de la actividad vitivinícola : departamento Maipú, Mendoza

La presente investigación tuvo como eje los vínculos entre educación y trabajo en la vitivinicultura mendocina desde 1990 . El objetivo general fue comprender los procesos de incorporación de jóvenes de ambos sexos al mundo del trabajo y su vínculo con las estrategias de formación y los esquemas de percepción en el mercado vitivinícola mendocino desde los 90. Se analizaron e identificaron los tipos de trayectorias educativas, laborales y transiciones existentes en los jóvenes. También los condicionantes de género que operan desde la perspectiva de las mujeres jóvenes. Se buscó comprender las formas que adquieren, cómo se manifiestan y varían las perspectivas acerca del trabajo, de las exigencias laborales y las condiciones del mercado de trabajo a lo largo de las trayectorias educativas y laborales y cuáles son los principales elementos constitutivos de las trayectorias de inserción, qué factores están asociados a sus variaciones y cómo se vinculan con las expectativas y estrategias de formación de inserción laboral.Fil: Martín, María Eugenia. CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas) - Universidad Nacional de CuyoFil: Zamarbide, Gabriela. Universidad Nacional de Cuy

Tracking Zebu Introgression in Mediterranean Cattle Breeds

A recent work investigating genetic origin, admixture and population history of primitive European cattle highlighted, by using genome-wide single nucleotide polymorphisms, zebu gene flow in the Balkan and Italian Podolic cattle populations. Haemoglobin protein polymorphism analysis in Italian breeds highlighted the presence of zebuine markers in both Italian Podolic and Alpine Grey cattle. Based on the above evidences, we here specifically look for genomic regions of zebuine ancestry in a different dataset of 50K genotypes from Mediterranean breeds including 29 Marismena (Spain); 30 Bazadaise and 30 Gasconne (France); 24 Alpine Grey, 97 Piemontese, 51 Chianina, 5 Marchigiana, 121 Romagnola, 24 Podolica, 24 Modenese, 30 Reggiana, 30 Cinisara and 30 Modicana (Italy); 24 Guelmoise (Algeria); 24 Cika (Slovenia), 43 Illyrian Mountain Bu\u161a (Albania). Additional taurine and zebuine breeds from previously published studies are also included in the analyses. Special emphasis in genetic analyses is also given to the identification of genomic regions potentially associated with a phenotypic trait observed in several taurine breeds as well as in some zebuine breeds, characterized by calves having a fawn coat at birth, while turning to various shades of grey in adult animals. The obtained results contribute to a better characterization of history and genetic structure of Mediterranean cattle breeds

Novel SMAC-mimetics synergistically stimulate melanoma cell death in combination with TRAIL and Bortezomib

BACKGROUND: XIAP (X-linked inhibitor of apoptosis protein) is an anti-apoptotic protein exerting its activity by binding and suppressing caspases. As XIAP is overexpressed in several tumours, in which it apparently contributes to chemoresistance, and because its activity in vivo is antagonised by second mitochondria-derived activator of caspase (SMAC)/direct inhibitor of apoptosis-binding protein with low pI, small molecules mimicking SMAC (so called SMAC-mimetics) can potentially overcome tumour resistance by promoting apoptosis. METHODS: Three homodimeric compounds were synthesised tethering a monomeric SMAC-mimetic with different linkers and their affinity binding for the baculoviral inhibitor repeats domains of XIAP measured by fluorescent polarisation assay. The apoptotic activity of these molecules, alone or in combination with tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and/or Bortezomib, was tested in melanoma cell lines by MTT viability assays and western blot analysis of activated caspases. RESULTS: We show that in melanoma cell lines, which are typically resistant to chemotherapeutic agents, XIAP knock-down sensitises cells to TRAIL treatment in vitro, also favouring the accumulation of cleaved caspase-8. We also describe a new series of 4-substituted azabicyclo[5.3.0] alkane monomeric and dimeric SMAC-mimetics that target various members of the IAP family and powerfully synergise at submicromolar concentrations with TRAIL in inducing cell death. Finally, we show that the simultaneous administration of newly developed SMAC-mimetics with Bortezomib potently triggers apoptosis in a melanoma cell line resistant to the combined effect of SMAC-mimetics and TRAIL. CONCLUSION: Hence, the newly developed SMAC-mimetics effectively synergise with TRAIL and Bortezomib in inducing cell death. These findings warrant further preclinical studies in vivo to verify the anticancer effectiveness of the combination of these agents

The sub-seasonal to seasonal prediction (S2S) project database

A database containing sub-seasonal to seasonal forecasts from 11 operational centres is available to the research community and will help advance our understanding of the sub-seasonal to seasonal time range. Demands are growing rapidly in the operational prediction and applications communities for forecasts that fill the gap between medium-range weather and long-range or seasonal forecasts. Based on the potential for improved forecast skill at the sub-seasonal to seasonal time range, a sub-seasonal prediction (S2S) research project has been established by the World Weather Research Program/World Climate Research Program. A main deliverable of this project is the establishment of an extensive database, containing sub-seasonal (up to 60 days) forecasts, 3-weeks behind real-time, and reforecasts from 11 operational centers, modelled in part on the THORPEX Interactive Grand Global Ensemble (TIGGE) database for medium range forecasts (up to 15 days). The S2S database, available to the research community since May 2015, represents an important tool to advance our understanding of the sub-seasonal to seasonal time range that has been considered for a long time as a “desert of predictability”. In particular, this database will help identify common successes and shortcomings in the model simulation and prediction of sources of sub-seasonal to seasonal predictability. For instance, a preliminary study suggests that the S2S models underestimate significantly the amplitude of the Madden Julian Oscillation (MJO) teleconnections over the Euro-Atlantic sector. The S2S database represents also an important tool for case studies of extreme events. For instance, a multi-model combination of S2S models displays higher probability of a landfall over Vanuatu islands 2 to 3 weeks before tropical cyclone Pam devastated the islands in March 2015

Reversible Keap1 inhibitors are preferential pharmacological tools to modulate cellular mitophagy

Mitophagy orchestrates the autophagic degradation of dysfunctional mitochondria preventing their pathological accumulation and contributing to cellular homeostasis. We previously identified a novel chemical tool (hereafter referred to as PMI), which drives mitochondria into autophagy without collapsing their membrane potential (ΔΨm). PMI is an inhibitor of the protein-protein interaction (PPI) between the transcription factor Nrf2 and its negative regulator, Keap1 and is able to up-regulate the expression of autophagy-associated proteins, including p62/SQSTM1. Here we show that PMI promotes mitochondrial respiration, leading to a superoxide-dependent activation of mitophagy. Structurally distinct Keap1-Nrf2 PPI inhibitors promote mitochondrial turnover, while covalent Keap1 modifiers, including sulforaphane (SFN) and dimethyl fumarate (DMF), are unable to induce a similar response. Additionally, we demonstrate that SFN reverses the effects of PMI in co-treated cells by reducing the accumulation of p62 in mitochondria and subsequently limiting their autophagic degradation. This study highlights the unique features of Keap1-Nrf2 PPI inhibitors as inducers of mitophagy and their potential as pharmacological agents for the treatment of pathological conditions characterized by impaired mitochondrial quality control

Contribution of ultrarare variants in mTOR pathway genes to sporadic focal epilepsies

Objective: We investigated the contribution to sporadic focal epilepsies (FE) of ultrarare variants in genes coding for the components of complexes regulating mechanistic Target Of Rapamycin (mTOR)complex 1 (mTORC1). Methods: We collected genetic data of 121 Italian isolated FE cases and 512 controls by Whole Exome Sequencing (WES) and single-molecule Molecular Inversion Probes (smMIPs) targeting 10 genes of the GATOR1, GATOR2, and TSC complexes. We collapsed \u201cqualifying\u201d variants (ultrarare and predicted to be deleterious or loss of function) across the examined genes and sought to identify their enrichment in cases compared to controls. Results: We found eight qualifying variants in cases and nine in controls, demonstrating enrichment in FE patients (P&nbsp;=&nbsp;0.006; exact unconditional test, one-tailed). Pathogenic variants were identified in DEPDC5 and TSC2, both major genes for Mendelian FE syndromes. Interpretation: Our findings support the contribution of ultrarare variants in genes in the mTOR pathway complexes GATOR and TSC to the risk of sporadic FE and a shared genetic basis between rare and common epilepsies. The identification of a monogenic etiology in isolated cases, most typically encountered in clinical practice, may offer to a broader community of patients the perspective of precision therapies directed by the underlying genetic cause