The evolutionary young miR-1290 favors mitotic exit and differentiation of human neural progenitors through altering the cell cycle proteins.

Regulation of cellular proliferation and differentiation during brain development results from processes requiring several regulatory networks to function in synchrony. MicroRNAs are part of this regulatory system. Although many microRNAs are evolutionarily conserved, recent evolution of such regulatory molecules can enable the acquisition of new means of attaining specialized functions. Here we identify and report the novel expression and functions of a human and higher primate-specific microRNA, miR-1290, in neurons. Using human fetal-derived neural progenitors, SH-SY5Y neuroblastoma cell line and H9-ESC-derived neural progenitors (H9-NPC), we found miR-1290 to be upregulated during neuronal differentiation, using microarray, northern blotting and qRT-PCR. We then conducted knockdown and overexpression experiments to look at the functional consequences of perturbed miR-1290 levels. Knockdown of miR-1290 inhibited differentiation and induced proliferation in differentiated neurons; correspondingly, miR-1290 overexpression in progenitors led to a slowing down of the cell cycle and differentiation to neuronal phenotypes. Consequently, we identified that crucial cell cycle proteins were aberrantly changed in expression level. Therefore, we conclude that miR-1290 is required for maintaining neurons in a differentiated state

Col-Graph: Towards Writable and Scalable Linked Open Data

International audienceLinked Open Data faces severe issues of scalability, availability and data quality. these issues are observed by data consumers performing federated queries; SPARQL endpoints do not respond and results can be wrong or out-of-date. If a data consumer finds an error, how can she fix it? This raises the issue of the writability of Linked Data. In this paper, we devise aan extension of the federation of Linked Data to data consumers. A data consumer can make partial copies of different datasets and make them available through a SPARQL endpoint. A data consumer can update her local copy and share updates with data providers and consumers. Update sharing improves general data quality, and replicated data creates opportunities for federated query engines to improve availability. However, when updates occur in an uncontrolled way, consistency issues arise. In this paper, we define fragments as SPARQL CONSTRUCT queries and propose a correction criterion to maintain these fragments incrementally without reevaluating the query. We define a coordination free protocol based on the counting of triples derivations and provenance. We analyze the theoretical complexity of the protocol in time, space and traffic. Experimental results suggest the scalability of our approach

A Link Between Methylglyoxal and Heart Failure During HIV-1 Infection

Early-onset heart failure (HF) continues to be a major cause of morbidity and mortality in people living with human immunodeficiency virus type one (HIV-1) infection (PLWH), yet the molecular causes for this remain poorly understood. Herein NOD.Cg- PrkdcscidIl2rgtm1Wjl/SzJ humanized mice (Hu-mice), plasma from PLWH, and autopsied cardiac tissues from deceased HIV seropositive individuals were used to assess if there is a link between the glycolysis byproduct methylglyoxal (MG) and HF in the setting of HIV-1 infection. At five weeks post HIV infection, Hu-mice developed grade III-IV diastolic dysfunction (DD) with an associated two-fold increase in plasma MG. At sixteen-seventeen weeks post infection, cardiac ejection fraction and fractional shortening also declined by 26 and 35%, and plasma MG increased to four-fold higher than uninfected controls. Histopathological and biochemical analyses of cardiac tissues from Hu-mice 17 weeks post-infection affirmed MG increase with a concomitant decrease in expression of the MG-degrading enzyme glyoxalase-1 (Glo1). The endothelial cell marker CD31 was found to be lower, and coronary microvascular leakage and myocardial fibrosis were prominent. Increasing expression of Glo1 in Hu-mice five weeks post-infection using a single dose of an engineered AAV2/9 (1.7 × 1012 virion particles/kg), attenuated the increases in plasma and cardiac MG levels. Increasing Glo1 also blunted microvascular leakage, fibrosis, and HF seen at sixteen weeks post-infection, without changes in plasma viral loads. In plasma fromvirally suppressed PLWH,MG was also 3.7-fold higher. In autopsied cardiac tissues from seropositive, HIV individuals with low viral log, MG was 4.2-fold higher and Glo1 was 50% lower compared to uninfected controls. These data show for the first time a causal link between accumulation of MG and HF in the setting of HIV infection

Methylome-wide Analysis of Chronic HIV Infection Reveals Five-Year Increase in Biological Age and Epigenetic Targeting of HLA

HIV-infected individuals are living longer on antiretro-viral therapy, but many patients display signs that in some ways resemble premature aging. To investigate and quantify the impact of chronic HIV infection on aging, we report a global analysis of the whole-blood DNA methylomes of 137 HIV+ individuals under sustained therapy along with 44 matched HIV- individuals. First,we develop and validate epigenetic models of aging that are independent of blood cell composition. Using these models, we find that both chronic and recent HIV infection lead to an average aging advancement of 4.9 years, increasing expected mortality risk by 19%. In addition, sustained infection results in global deregulation of the methylome across \u3e80,000 CpGs and specific hypomethylation of the region encoding the human leukocyte antigen locus (HLA).We find that decreased HLA methylation is predictive of lower CD4/CD8T cell ratio, linking molecular aging, epigenetic regulation, and disease progression

DAW: Duplicate-AWare Federated Query Processing over the Web of Data

Abstract. Over the last years the Web of Data has developed into a large compendium of interlinked data sets from multiple domains. Due to the decentralised architecture of this compendium, several of these datasets contain duplicated data. Yet, so far, only little attention has been paid to the effect of duplicated data on federated querying. This work presents DAW, a novel duplicate-aware approach to feder-ated querying over the Web of Data. DAW is based on a combination of min-wise independent permutations and compact data summaries. It can be directly combined with existing federated query engines in or-der to achieve the same query recall values while querying fewer data sources. We extend three well-known federated query processing engines – DARQ, SPLENDID, and FedX – with DAW and compare our exten-sions with the original approaches. The comparison shows that DAW can greatly reduce the number of queries sent to the endpoints, while keeping high query recall values. Therefore, it can significantly improve the performance of federated query processing engines. Moreover, DAW provides a source selection mechanism that maximises the query recall, when the query processing is limited to a subset of the sources