14 research outputs found
‘Albania: €1’ or the story of ‘big policies, small outcomes’: how Albania constructs and engages its diaspora
Since the fall of the communist regime in the early 1990s, Albania has experienced one of the most significant emigrations in the world as a share of its population. By 2010 almost half of its resident population was estimated to be living abroad – primarily in neighbouring Greece and Italy, but also in the UK and North America. This chapter discusses the emergence and establishment of the Albanian diaspora, its temporal and geographical diversity, and not least its involvement with Albania itself. Albania’s policymaking and key institutions are considered, with a focus on matters of citizenship; voting rights; the debate on migration and development; and not least the complex ways in which kin-state minority policies – related to ethnic Albanians living in Kosovo, Montenegro, southern Serbia, Macedonia and Greece – are interwoven with Albania’s emigration policies
Gene profiling of the erythro- and megakaryoblastic leukaemias induced by the Graffi murine retrovirus
<p>Abstract</p> <p>Background</p> <p>Acute erythro- and megakaryoblastic leukaemias are associated with very poor prognoses and the mechanism of blastic transformation is insufficiently elucidated. The murine Graffi leukaemia retrovirus induces erythro- and megakaryoblastic leukaemias when inoculated into NFS mice and represents a good model to study these leukaemias.</p> <p>Methods</p> <p>To expand our understanding of genes specific to these leukaemias, we compared gene expression profiles, measured by microarray and RT-PCR, of all leukaemia types induced by this virus.</p> <p>Results</p> <p>The transcriptome level changes, present between the different leukaemias, led to the identification of specific cancerous signatures. We reported numerous genes that may be potential oncogenes, may have a function related to erythropoiesis or megakaryopoiesis or have a poorly elucidated physiological role. The expression pattern of these genes has been further tested by RT-PCR in different samples, in a Friend erythroleukaemic model and in human leukaemic cell lines.</p> <p>We also screened the megakaryoblastic leukaemias for viral integrations and identified genes targeted by these integrations and potentially implicated in the onset of the disease.</p> <p>Conclusions</p> <p>Taken as a whole, the data obtained from this global gene profiling experiment have provided a detailed characterization of Graffi virus induced erythro- and megakaryoblastic leukaemias with many genes reported specific to the transcriptome of these leukaemias for the first time.</p
Characterization of transcriptional networks in blood stem and progenitor cells using high-throughput single-cell gene expression analysis
Cellular decision-making is mediated by a complex interplay of external stimuli with the intracellular environment, in particular transcription factor regulatory networks. Here we have determined the expression of a network of 18 key haematopoietic transcription factors in 597 single primary blood stem and progenitor cells isolated from mouse bone marrow. We demonstrate that different stem/progenitor populations are characterized by distinctive transcription factor expression states, and through comprehensive bioinformatic analysis reveal positively and negatively correlated transcription factor pairings, including previously unrecognized relationships between Gata2, Gfi1 and Gfi1b. Validation using transcriptional and transgenic assays confirmed direct regulatory interactions consistent with a regulatory triad in immature blood stem cells, where Gata2 may function to modulate cross-inhibition between Gfi1 and Gfi1b. Single-cell expression profiling therefore identifies network states and allows reconstruction of network hierarchies involved in controlling stem cell fate choices, and provides a blueprint for studying both normal development and human disease
Jorgucat_IT and Urban Regeneration
Proposal and depiction of small design interventions in the village of Jorgucat aimed at promoting sustainable economies, bringing back the young people to the villagem by creating opportunities, encouraging social relationships, and better infrastructure creations
Polymorphisms of the insulin receptor and the insulin receptor substrates genes in polycystic ovary syndrome: A Mendelian randomization meta-analysis
Polycystic ovary syndrome (PCOS) is a heterogeneous condition with unknown aetiology which is considered to be the most common endocrine disorder in women of reproductive age. In this work we investigated the association of insulin receptor (INSR) and insulin receptor substrates (IRSs) polymorphisms with the risk of developing PCOS. The meta-analysis of eleven studies (889 cases, 1303 controls) yielded a significant association for IRS-1 Gly972Arg (G972R) polymorphism concerning the GR vs. GG genotype (OR: 1.77, 95% Cl: 1.28, 2.45), with no between-studies heterogeneity. Concerning INSR His1058 C/T, the meta-analysis of eight studies (795 cases, 576 controls) found no significant evidence for association with PCOS (OR for the TT + CT vs. CC comparison equal to 1.28 with 95% Cl: 0.88, 1.85) and a moderate between studies variability (I-2 = 44.6%). No evidence for publication bias was found in these meta-analyses. Following a multivariate Mendelian randomization approach, the overall OR was unaffected but the overall mean difference of fasting insulin levels between carriers of GR and RR genotypes in controls was significant (2.18, 95% Cl: 0.36, 4.01). These results suggest that IRS-1 Gly972Arg polymorphism is significantly associated with the risk of developing PCOS and that this association is primarily mediated by increasing the levels of fasting insulin. The particular polymorphism is located in a region nearby two phosphorylation sites that interact physically with INSR and PI 3-kinase and there is enough evidence from the literature suggesting that the Arg972 variant is associated with decreased PI 3-kinase activity and impaired insulin-stimulated signaling
FLVCR is necessary for erythroid maturation, may contribute to platelet maturation, but is dispensable for normal hematopoietic stem cell function
Gain-of-function mutation of GATA-2 in acute myeloid transformation of chronic myeloid leukemia
Acquisition of additional genetic and/or epigenetic abnormalities other than the BCR/ABL fusion gene is believed to cause disease progression in chronic myeloid leukemia (CML) from chronic phase to blast crisis (BC). To gain insights into the underlying mechanisms of progression to BC, we screened DNA samples from CML patients during blast transformation for mutations in a number of transcription factor genes that are critical for myeloid–lymphoid development. In 85 cases of CML blast transformation, we identified two new mutations in the coding region of GATA-2, a negative regulator of hematopoietic stem/progenitor cell differentiation. A L359V substitution within zinc finger domain (ZF) 2 of GATA-2 was found in eight cases with myelomonoblastic features, whereas an in-frame deletion of 6 aa (Δ341–346) spanning the C-terminal border of ZF1 was detected in one patient at myeloid BC with eosinophilia. Further studies indicated that L359V not only increased transactivation activity of GATA-2 but also enhanced its inhibitory effects on the activity of PU.1, a major regulator of myelopoiesis. Consistent with the myelomonoblastic features of CML transformation with the GATA-2 L359V mutant, transduction of the GATA-2 L359V mutant into HL-60 cells or BCR/ABL-harboring murine cells disturbed myelomonocytic differentiation/proliferation in vitro and in vivo, respectively. These data strongly suggest that GATA-2 mutations may play a role in acute myeloid transformation in a subset of CML patients