abCDEuropa: guida al wiki dei CDE italiani

Il wiki dei CDE italiani è uno strumento pensato e creato specificamente per l’uso online poiché ha una struttura reticolare di rimandi incrociati invece di un’esposizione lineare. Questa breve guida non intende quindi riproporre il wiki dei CDE, che è uno strumento dinamico in continua evoluzione e aggiornamento, bensì fornire in una pluralità di supporti oltre al web - carta, libro elettronico - indicazioni generali e sintetiche sui principali contenuti del wiki

Prune-1 drives polarization of tumor-associated macrophages (TAMs) within the lung metastatic niche in triple-negative breast cancer

M2-tumor-associated macrophages (M2-TAMs) in the tumor microenvironment represent a prognostic indicator for poor outcome in triple-negative breast cancer (TNBC). Here we show that Prune-1 overexpression in human TNBC patients has positive correlation to lung metastasis and infiltrating M2-TAMs. Thus, we demonstrate that Prune-1 promotes lung metastasis in a genetically engineered mouse model of metastatic TNBC augmenting M2-polarization of TAMs within the tumor microenvironment. Thus, this occurs through TGF-β enhancement, IL-17F secretion, and extracellular vesicle protein content modulation. We also find murine inactivating gene variants in human TNBC patient cohorts that are involved in activation of the innate immune response, cell adhesion, apoptotic pathways, and DNA repair. Altogether, we indicate that the overexpression of Prune-1, IL-10, COL4A1, ILR1, and PDGFB, together with inactivating mutations of PDE9A, CD244, Sirpb1b, SV140, Iqca1, and PIP5K1B genes, might represent a route of metastatic lung dissemination that need future prognostic validations

Detection of Human Papillomaviruses in the Nasopharynx of Breastfed Infants: New Findings and Meta-Analysis

Vertical transmission of human papillomaviruses (HPVs) from mother to infant is known to occur during labor, delivery or breastfeeding. Infection with mucosal HPV 6 and 11 may cause recurrent respiratory papillomatosis in children, which is a rare and severe respiratory disease. The cutaneous HPV genotypes have also been described to be transmitted from mother to newborn through skin-to-skin contacts and during breastfeeding. To investigate the perinatal transmission of alpha and beta HPVs we collected nasopharyngeal specimens from 0–12-months-old infants born by vaginal delivery and breastfed at the time of sample collection. The mucosal and cutaneous HPVs were searched by nested PCR using the MY09/11-MGPs and CP65/70-CP66/69 primer sets, respectively, and genotypes identified by direct sequencing analysis. Fourteen out of 113 (12.4%) samples tested positive for HPV and sequence analysis allowed us to identify eight beta genotypes (HPV 5b, 20, 25, 100, 107, 124, 152 and RTRX7). Moreover, we performed a comprehensive review of published studies on the prevalence of mucosal and cutaneous HPVs among 5126 newborns and observed that 10% and 53% were positive for alpha and beta HPVs, respectively. In all studies there was an inverse correlation between the rate of alpha HPV positivity and age, while a significant positive trend was observed in beta HPV detection and age with the highest rate among children older than 12 months (Χ2 test for trend of 10.6, p < 0.001). Further studies are needed to confirm the hypothesis that beta HPVs are transmitted to breastfeeding infants through shedding of viruses in the breast milk or on the external breast epithelium

CAG repeat expansion in the Huntington's disease gene shapes linear and circular RNAs biogenesis.

Alternative splicing (AS) appears to be altered in Huntington's disease (HD), but its significance for early, pre-symptomatic disease stages has not been inspected. Here, taking advantage of Htt CAG knock-in mouse in vitro and in vivo models, we demonstrate a correlation between Htt CAG repeat length and increased aberrant linear AS, specifically affecting neural progenitors and, in vivo, the striatum prior to overt behavioral phenotypes stages. Remarkably, a significant proportion (36%) of the aberrantly spliced isoforms are not-functional and meant to non-sense mediated decay (NMD). The expanded Htt CAG repeats further reflect on a previously neglected, global impairment of back-splicing, leading to decreased circular RNAs production in neural progenitors. Integrative transcriptomic analyses unveil a network of transcriptionally altered micro-RNAs and RNA-binding proteins (Celf, hnRNPs, Ptbp, Srsf, Upf1, Ythd2) which might influence the AS machinery, primarily in neural cells. We suggest that this unbalanced expression of linear and circular RNAs might alter neural fitness, contributing to HD pathogenesis

Related to Fig 1.

The spreadsheets (n = 5) report the total description of the alternative splicing (AS) events observed in 1. the striatum (STR), 2. the cortex (CTX) and 3. liver. All data are calculated comparing Htt CAG expanded genotypes (Q80, Q92, Q111, Q140, Q175) to Q20 control (see methods). The GO terms and pathways enrichment for 4. AS events in the STR and 5. Skipped exon (SE) events in the STR are presented. (XLSX)</p

<i>Htt</i> CAG length correlation with linear alternative splicing events in KI mouse models.

The bar graphs report the total number of differential AS events in the striatum (upper row, light blue), cortex (mid row, green) and liver (bottom, purple row) from mouse KI models of HD, presenting 6 different Htt CAG repeat lengths (Q20, Q80, Q92, Q111, Q140 and Q175) and 3 time points (2, 6, and 10 months). The inclusion level is calculated in comparison to Q20 controls and the positive or negative values are plotted in the graph. The number of events is reported for each genotype and time point (different Y-axis values are presented). Source data by Langfelder P. et al (2016) [28]. Further details can be found in the Methods section and S1 Table. The Pearson’s correlation (R2) between differential AS and Htt CAG expansion is plotted in each graph. Standard deviations and trend lines are presented. (TIFF)</p

Related to Fig 2.

The spreadsheets (n = 10) report the total description of the alternative splicing (AS) events observed in 1. The mouse embryonic stem cells (ESC), 2. The mouse neuronal progenitors (NPC). All data are calculated comparing Htt CAG expanded genotypes (Q50, Q92, Q111) to Q20 control (see methods). The total list of transcriptionally dysregulated genes (DEG) is presented for the NPC comparisons of 3. Q20 versus Q50, 4. Q20 versus Q92, 5. Q20 versus Q111. The list of GO terms and pathways enrichments for 6. the total AS events and 7. the skipped exon (SE) events detected between NPC Q20 versus Q111 comparison is presented. The list of GO terms and pathways associated to DEG for the 3 NPC comparisons of 8. Q20 versus Q50, 9. Q20 versus Q92, 10. Q20 versus Q111 is accessible. Highlighted in yellow pathways and terms related to RNA binding proteins (RBPs) and RNA modifications. (XLSX)</p

Differentially expressed genes presenting AS events in the striatum tissue of KI mouse models.

The bar graph presents the number of differentially expressed genes (DEG) which also are characterized by at least one significant AS event in the striatum of KI animal models of HD. Logarithmic fold change (LogFC) of their expression compared to Q20 control is reported in the y-axis. Transcripts are filtered based on significant p-value (p-value (TIFF)</p

Neuronal differentiation impact on small RNAs.

A) The coloured bar graphs report the number of small RNAs (>1 count/sample, see also Methods) comparing ESC and NPC conditions. Series of 4 Htt CAG expansion alleles (Q20, Q50, Q92 and Q111) are presented. Different classes of small RNAs are examined. Abbreviations as follows: microRNAs (miRNAs), Mitochondrial transfer RNAs (Mt-tRNAs), processed pseudogenes, ribosomal RNAs (rRNAs), small nucleolar RNAs (snoRNAs), small nuclear RNAs (snRNAs) small Cajal body-specific RNAs (scaRNAs), To be Experimentally Confirmed (TEC), transcribed processed pseudogenes. B) The heatmap presents the number of expressed (> 1 count per million, CPM) small RNAs among heterozygous Htt CAG knock-in HttQ20, HttQ50, HttQ92 and HttQ111 (Q20, Q50, Q92, Q111), comparing ESC and NPC lines. Different classes of small RNAs are examined. Abbreviations as in GENCODE transcript biotypes [86]. Color code bar (upper right) reports the number of expressed small RNAs in each condition. C) The bar chart shows the number of small RNAs differentially expressed between Htt Q111 versus Q20 genotypes. The comparison is presented for pluripotent (ESC) and neural committed progenitors (NPC). The number of small RNAs increasing (Increasing in Q111—upper part of the plot), and decreasing their expression in Q111 versus Q20 (Decreasing in Q111—lower part of the plot) is depicted. (TIFF)</p