An EBC/Plasma miRNA Signature Discriminates Lung Adenocarcinomas From Pleural Mesothelioma and Healthy Controls

Background: Despite significant improvement in screening programs for cancers of the respiratory district, especially in at-risk subjects, early disease detection is still a major issue. In this scenario, new molecular and non-invasive biomarkers are needed to improve early disease diagnosis. Methods: We profiled the miRNome in exhaled breath condensate (EBC) and plasma samples from fourteen patients affected by lung AdCa, nine healthy subjects. miRNA signatures were then analyzed in another neoplasia of the respiratory district, i.e. pleural mesothelioma (n = 23) and subjects previously exposed to asbestos were used as controls for this cohort (n = 19). Selected miRNAs were analyzed in purified pulmonary neoplastic or normal epithelial and stromal cell subpopulation from AdCa patients. Finally, the plasmatic miRNA signature was analyzed in a publicly available cohort of NSCLC patients for data validation and in silico analysis was performed with predicted miRNA targets using the multiMiR tool and STRING database. Results: miR-597-5p and miR-1260a are significantly over-expressed in EBC from lung AdCa and are associated with AdCa. Similarly, miR-1260a is also up-regulated in the plasma of AdCa patients together with miR-518f-3p and correlates with presence of lung cancer, whereas let-7f-5p is under-expressed. Analysis of these circulating miRNAs in pleural mesothelioma cases confirmed that up-regulation of miR-518f-3p, -597-5p and -1260a, is specific for lung AdCa. Lastly, quantification of the miRNAs in laser-assisted microdissected lung tissues revealed that miR-518f-3p, 597-5p and miR-1260a are predominantly expressed in tumor epithelial cells. Validation analysis confirmed miR-518f-3p as a possible circulating biomarker of NSCLC. In silico analysis of the potentially modulated biological processes by these three miRNAs, shows that tumor bioenergetics are the most affected pathways. Conclusions: Overall, our data suggest a 3-miRNAs signature as a non-invasive and accurate biomarker of lung AdCa. This approach could supplement the current screening approaches for early lung cancer diagnosis

A genetic history of the pre-contact Caribbean

Humans settled the Caribbean about 6,000 years ago, and ceramic use and intensified agriculture mark a shift from the Archaic to the Ceramic Age at around 2,500 years ago1,2,3. Here we report genome-wide data from 174 ancient individuals from The Bahamas, Haiti and the Dominican Republic (collectively, Hispaniola), Puerto Rico, Curaçao and Venezuela, which we co-analysed with 89 previously published ancient individuals. Stone-tool-using Caribbean people, who first entered the Caribbean during the Archaic Age, derive from a deeply divergent population that is closest to Central and northern South American individuals; contrary to previous work4, we find no support for ancestry contributed by a population related to North American individuals. Archaic-related lineages were >98% replaced by a genetically homogeneous ceramic-using population related to speakers of languages in the Arawak family from northeast South America; these people moved through the Lesser Antilles and into the Greater Antilles at least 1,700 years ago, introducing ancestry that is still present. Ancient Caribbean people avoided close kin unions despite limited mate pools that reflect small effective population sizes, which we estimate to be a minimum of 500–1,500 and a maximum of 1,530–8,150 individuals on the combined islands of Puerto Rico and Hispaniola in the dozens of generations before the individuals who we analysed lived. Census sizes are unlikely to be more than tenfold larger than effective population sizes, so previous pan-Caribbean estimates of hundreds of thousands of people are too large5,6. Confirming a small and interconnected Ceramic Age population7, we detect 19 pairs of cross-island cousins, close relatives buried around 75 km apart in Hispaniola and low genetic differentiation across islands. Genetic continuity across transitions in pottery styles reveals that cultural changes during the Ceramic Age were not driven by migration of genetically differentiated groups from the mainland, but instead reflected interactions within an interconnected Caribbean world1,8.This work was supported by a grant from the National Geographic Society to M. Pateman to facilitate analysis of skeletal material from The Bahamas and by a grant from the Italian ‘Ministry of Foreign Affairs and International Cooperation’ (Italian archaeological, anthropological and ethnological missions abroad, DGPSP Ufficio VI). D.R. was funded by NSF HOMINID grant BCS-1032255, NIH (NIGMS) grant GM100233, the Paul Allen Foundation, the John Templeton Foundation grant 61220 and the Howard Hughes Medical Institute.Peer reviewe

Efficacia di un training di regolazione delle emozioni in un gruppo di studenti universitari.

La regolazione emotiva (RE) è fondamentale per il benessere psicofisico degli studenti universitari che spesso si trovano a fronteggiare situazioni stressanti e stimoli del tutto nuovi. In letteratura sono pochi gli studi che verifichino gli effetti di training specifici sulla RE con studenti universitari. L’obiettivo di questo studio è quello di misurare l’efficacia di un un training di RE volto ad incrementare l’utilizzo della strategia di rivalutazione cognitiva e a ridurre l’utilizzo della soppressione espressiva, strategie di regolazione emotiva associate in letteratura rispettivamente ad outcome psicosociali positivi e negativi. L’obiettivo secondario, invece, è quello di misurare la sua efficacia nel ridurre i sintomi legati ad ansia, depressione e insonnia. I punteggi dei questionari somministrati al pre e al post assessment sono analizzati confrontando il gruppo sperimentale di studenti universitari (n = 18) con un gruppo di controllo (n = 16). I risultati evidenziano che il gruppo dei partecipanti al training di RE riportano punteggi significativamente più bassi al post training nella scala di soppressione espressiva rispetto ai controlli. Si registrano punteggi significativamente più bassi anche per i sintomi di ansia, seppure al pari dei controlli. Non emergono altri risultati significativi. Questo studio pilota presenta interessanti risultati preliminari di efficacia, evidenziando la necessità di replicare lo studio in un campione più ampio per la sua potenziale applicazione a livello clinico e subclinico.Emotion Regulation (ER) plays a critical role in individual psychological and physical well-being, especially in college students who mismanage school-related stress and new stimuli. Only a few studies have attempted to determine the effectiveness of emotion regulation training with both adults and college students. The first aim of this study is to evaluate the effectiveness of ER training program in increasing the use of cognitive reappraisal and in decreasing the use of expressive suppression, two ER strategies respectively related to adaptive and maladaptive psychosocial outcomes. The secondary purpose is to examine the effect of the ER training on the reduction of anxiety, depression and insomnia symptoms. The mean scores of pre-and post-assessment were analyzed by comparing the experimental group of students (N = 18) with a control group (N = 16) and controlling for gender. Students who received ER training reported significant lower post-training scores on expressive suppression than controls. Significant lower post training symptoms of anxiety were observed, although scores did not differ between groups. No significant results emerged for the other investigated issues. This pilot study provided preliminary results on the ER training effectiveness, thus highlighting its potential clinical and subclinical application. It is recommended to replicate the study in a larger sample size using more sophisticated methods

Plasmonic and Conductive Structures of TCO Films with Embedded Cu Nanoparticles

Cu nanoparticles were produced by using solid-state dewetting (dry) of a 1.3 nm Cu layer or laser ablation of a Cu solid target (wet) in acetone and methanol. The morphology and chemical composition of the nanoparticles were investigated as a function of the synthesis methods and their key parameters of the annealing temperature (200–500 °C) and the liquid environment during the ablation. Cu nanoparticles were then embedded in transparent conductive oxide (TCO) films as aluminum-doped zinc oxide (AZO) or zirconium-doped indium oxide (IZrO); the TCObott/Cu nanoparticle/TCOtop structures were synthesized with all combinations of AZO and IZrO as the top and bottom layers. The goal was to achieve a plasmonic and conductive structure for photovoltaic applications via a comparison of the involved methods and all fabricated structures. In particular, solid-state dewetting produced faceted or spherical (depending on the annealing temperature) nanoparticles with an average size below 150 nm while laser ablation produced spherical nanoparticles below 250 nm. Dry and wet plasmonic conductive structures as a function of the TCOs employed and the temperature of annealing could reach a sheet resistance of 86 Ω/sq. The energy band-gap Egap, absorbance, transmittance, and reflectance of the plasmonic conductive structures were investigated in the UV–vis–NIR range. They showed a dependence on the sequence of the top and bottom TCO, with best transmittances of 89.4% for the dry plasmonic conductive structure and 84.7% for the wet plasmonic conductive structure. The latter showed a higher diffused transmittance of between 10–20% in the visible range

Deregulation of miRNAs-cMYC circuits is a key event in refractory celiac disease type-2 lymphomagenesis

A percentage of celiac disease (CD) patients develop refractory type-2 disease (RCD2), a condition associated with increased risk of enteropathy-associated T-cell-lymphoma (EATL) and without therapeutic option. Therefore, we profiled the miRNome in series of peripheral T-cell lymphomas (PTCLs), CD, RCD1 or 2 and in the murine interleukin-15 (IL15)-transgenic (TG) model of RCD. The transcriptome was analyzed in 18 intestinal T-cell lymphomas (ITLs). Bioinformatics pipelines provided significant microRNA (miRNA) lists and predicted targets that were confirmed in a second set of patients. Our data show that ITLs have a unique miRNA profile with respect to other PTCLs. The c-MYC regulated miR-17/92 cluster distinguishes monomorphic epitheliotropic ITL (MEITL) from EATL and prognosticates EATL outcome. These miRNAs are decreased in IL15-TG mice upon Janus kinase (JAK) inhibition. The random forest algorithm identified a signature of 38 classifier miRNAs, among which, the miR-200 and miR-192/215 families were progressively lost in RCD2 and ITL-CD, whereas miR-17/92 and C19MC miRNAs were up-regulated. Accordingly, SMAD3, MDM2, c-Myc and activated-STAT3 were increased in RCD2 and EATL tissues while JAK inhibition in IL15-TG mice restored their levels to baseline. Our data suggest that miRNAs circuit supports activation of STAT3 and c-Myc oncogenic signaling in RCD2, thus contributing to lymphomagenesis. This novel understanding might pave the way to personalized medicine approaches for RCD and EATL