71 research outputs found
HIV Modifies the m6A and m5C Epitranscriptomic Landscape of the Host Cell
The study of RNA modifications, today known as epitranscriptomics, is of growing
interest. The N6-methyladenosine (m6A) and 5-methylcytosine (m5C) RNA modifications
are abundantly present on mRNA molecules, and impact RNA interactions with other
proteins or molecules, thereby affecting cellular processes, such as RNA splicing,
export, stability, and translation. Recently m6A and m5C marks were found to be
present on human immunodeficiency (HIV) transcripts as well and affect viral replication.
Therefore, the discovery of RNA methylation provides a new layer of regulation of
HIV expression and replication, and thus offers novel array of opportunities to inhibit
replication. However, no study has been performed to date to investigate the impact
of HIV replication on the transcript methylation level in the infected cell. We used
a productive HIV infection model, consisting of the CD4+ SupT1 T cell line infected
with a VSV-G pseudotyped HIVeGFP-based vector, to explore the temporal landscape
of m6A and m5C epitranscriptomic marks upon HIV infection, and to compare it to
mock-treated cells. Cells were collected at 12, 24, and 36 h post-infection for mRNA
extraction and FACS analysis. M6A RNA modifications were investigated by methylated
RNA immunoprecipitation followed by high-throughput sequencing (MeRIP-Seq). M5C
RNA modifications were investigated using a bisulfite conversion approach followed by
high-throughput sequencing (BS-Seq). Our data suggest that HIV infection impacted
the methylation landscape of HIV-infected cells, inducing mostly increased methylation
of cellular transcripts upon infection. Indeed, differential methylation (DM) analysis
identified 59 m6A hypermethylated and only 2 hypomethylated transcripts and 14 m5C
hypermethylated transcripts and 7 hypomethylated ones. All data and analyses are also
freely accessible on an interactive web resource (http://sib-pc17.unil.ch/HIVmain.html).
Furthermore, bothm6A andm5Cmethylations were detected on viral transcripts and viral
particle RNA genomes, as previously described, but additional patterns were identified.
This work used differential epitranscriptomic analysis to identify novel players involved in
HIV life cycle, thereby providing innovative opportunities for HIV regulation
Engineers’ abilities influence spatial perspective changing
In this paper we studied the effect of engineering expertise in providing directional judgments. We asked two groups of people, engineers and non-engineers, to observe and memorize five maps, each including a four-point path, for 30 sec. The path was then removed and the participants had to provide two directional judgments: aligned (the imagined perspective on the task was the same as the one just learned), and counter-aligned (the imagined perspective on the task was rotated by 180°). Our results showed that engineers are equally able to perform aligned and counter-aligned directional judgments. The alignment effect due to the distance from the learning perspective was, in fact, shown only by non-engineers. Results are discussed considering engineering both learning expertise and specific predisposition
H.264 sensor aided video encoder for UAV BLOS missions
This paper presents a new low-complexity H.264 encoder, based on x264 implementation, for Unmanned Aerial Vehicles (UAV) applications. The encoder employs a new motion estimation scheme which make use of the global motion information provided by the onboard navigation system. The results are relevant in low frame rate video coding, which is a typical scenario in UAV behind line-of-sight (BLOS) missions
Sluggish response of untrapped electrons and global electrostatic micro-instabilities in a tokamak
Mammotome (®) and EnCor (®): comparison of two systems for stereotactic vacuum-assisted core biopsy in the characterisation of suspicious mammographic microcalcifications alone.
Mutant <i>CTNNB1</i> and histological heterogeneity define metabolic subtypes of hepatoblastoma.
Hepatoblastoma is the most common malignant pediatric liver cancer. Histological evaluation of tumor biopsies is used to distinguish among the different subtypes of hepatoblastoma, with fetal and embryonal representing the two main epithelial components. With frequent <i>CTNNB1</i> mutations, hepatoblastoma is a Wnt/β-catenin-driven malignancy. Considering that Wnt activation has been associated with tumor metabolic reprogramming, we characterized the metabolic profile of cells from hepatoblastoma and compared it to cells from hepatocellular carcinoma. First, we demonstrated that glucose transporter <i>GLUT3</i> is a direct TCF4/β-catenin target gene. RNA sequencing enabled to identify molecular and metabolic features specific to hepatoblastoma and revealed that several glycolytic enzymes are overexpressed in embryonal-like compared to fetal-like tumor cells. This led us to implement successfully three biomarkers to distinguish embryonal from fetal components by immunohistochemistry from a large panel of human hepatoblastoma samples. Functional analyses demonstrated that embryonal-like hepatoblastoma cells are highly glycolytic and sensitive to hexokinase-1 silencing. Altogether, our findings reveal a new, metabolic classification of human hepatoblastoma, with potential future implications for patients' diagnosis and treatment
Rilievi GPR multifrequenza in un sito test controllato in Campania, Italia
In questo report vengono presentati i risultati dell’attività geofisica svolta presso l’area test di Succivo (NA).
Scopo del lavoro è verificare la risposta di antenne GPR (Ground Penetration Radar) a diversa frequenza (100 MHz – 270 MHz) in terreni di natura piroclastica dove sono stati interrati oggetti di varia natura (fusti metallici, muretti in tufo e tubi in PVC) e a diverse profondità (1m - 2m - 3m).
Conoscendo la stratigrafia di massima del sottosuolo e la disposizione degli oggetti sepolti, sono stati ottenuti radargrammi 2D la cui analisi ed interpretazione hanno permesso di definire la risposta delle antenne GPR in termini di risoluzione e profondità.
L’attività ha permesso di conseguire importanti informazioni sulla scelta della frequenza di utilizzo delle antenne GPR in terreni piroclastici e sulla risposta che tale tecnica fornisce nell’identificazione di oggetti sepolti .Tali informazioni risultano essenziali qualora venga usata la tecnica GPR per rilevare la presenza di oggetti sepolti (metallici e non) a varie profondità
Convergent roles of ATF3 and CSL in chromatin control of cancer-associated fibroblast activation.
Cancer-associated fibroblasts (CAFs) are important for tumor initiation and promotion. CSL, a transcriptional repressor and Notch mediator, suppresses CAF activation. Like CSL, ATF3, a stress-responsive transcriptional repressor, is down-modulated in skin cancer stromal cells, and Atf3 knockout mice develop aggressive chemically induced skin tumors with enhanced CAF activation. Even at low basal levels, ATF3 converges with CSL in global chromatin control, binding to few genomic sites at a large distance from target genes. Consistent with this mode of regulation, deletion of one such site 2 Mb upstream of IL6 induces expression of the gene. Observed changes are of translational significance, as bromodomain and extra-terminal (BET) inhibitors, unlinking activated chromatin from basic transcription, counteract the effects of ATF3 or CSL loss on global gene expression and suppress CAF tumor-promoting properties in an in vivo model of squamous cancer-stromal cell expansion. Thus, ATF3 converges with CSL in negative control of CAF activation with epigenetic changes amenable to cancer- and stroma-focused intervention
The consensus molecular subtypes of colorectal cancer
Colorectal cancer (CRC) is a frequently lethal disease with heterogeneous outcomes and drug responses. To resolve inconsistencies among the reported gene expression-based CRC classifications and facilitate clinical translation, we formed an international consortium dedicated to large-scale data sharing and analytics across expert groups. We show marked interconnectivity between six independent classification systems coalescing into four consensus molecular subtypes (CMSs) with distinguishing features: CMS1 (microsatellite instability immune, 14%), hypermutated, microsatellite unstable and strong immune activation; CMS2 (canonical, 37%), epithelial, marked WNT and MYC signaling activation; CMS3 (metabolic, 13%), epithelial and evident metabolic dysregulation; and CMS4 (mesenchymal, 23%), prominent transforming growth factor-beta activation, stromal invasion and angiogenesis. Samples with mixed features (13%) possibly represent a transition phenotype or intratumoral heterogeneity. We consider the CMS groups the most robust classification system currently available for CRC-with clear biological interpretability-and the basis for future clinical stratification and subtype-based targeted interventions
RIP4 inhibits STAT3 signaling to sustain lung adenocarcinoma differentiation.
Loss of epithelial differentiation and extracellular matrix (ECM) remodeling are known to facilitate cancer progression and are associated with poor prognosis in patients with lung cancer. We have identified Receptor-interacting serine/threonine protein kinase 4 (RIP4) as a regulator of tumor differentiation in lung adenocarcinoma (AC). Bioinformatics analyses of human lung AC samples showed that poorly differentiated tumors express low levels of RIP4, whereas high levels are associated with better overall survival. In vitro, lung tumor cells expressing reduced RIP4 levels showed enhanced activation of STAT3 signaling and had a greater ability to invade through collagen. In contrast, overexpression of RIP4 inhibited STAT3 activation, which abrogated interleukin-6-dependent induction of lysyl oxidase, a collagen cross-linking enzyme. In an autochthonous mouse model of lung AC initiated by Kras(G12D) expression with loss of p53, Rip4 knockdown tumors progressed to a poorly differentiated state marked by an increase in Hmga2, reduced Ttf1, and enrichment of genes regulating extracellular remodeling and Jak-Stat signaling. Tail vein injections of cells overexpressing Rip4 showed a reduced potential to invade and form tumors, which was restored by co-expression of Stat3. Altogether, our work has identified that loss of RIP4 enhances STAT3 signaling in lung cancer cells, promoting the expression of ECM remodeling genes and cancer dedifferentiation
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