Circulating microRNAs: next-generation biomarkers for early lung cancer detection

Early diagnosis of lung cancer by low-dose computed tomography is an effective strategy to reduce cancer mortality in high-risk individuals. However, recruitment of at-risk individuals with asymptomatic lung cancer still remains challenging. We developed a minimal invasive serum test, based on the detection of circulating microRNAs, which can identify at-risk individuals with asymptomatic early stage non-small cell lung carcinomas with 80% accuracy

The role of non-coding RNAs in the regulation of stem cells and progenitors in the normal mammary gland and in breast tumors

The outlook on stem cell biology is shifting from a rigid hierarchical to a more flexible model in which the identity and the behavior of adult stem cells (SCs), far from being fixed, are determined by the dynamic integration of cell autonomous and non-autonomous mechanisms. Within this framework, the recent discovery of thousands of non-coding RNAs (ncRNAs) with regulatory function is redefining the landscape of transcriptome regulation, highlighting the interplay of epigenetic, transcriptional and post-transcriptional mechanisms in the specification of cell fate and in the regulation of developmental processes. Furthermore, the expression of ncRNAs is often tissue- or even cell type-specific, emphasizing their involvement in defining space, time and developmental stages in gene regulation. Such a role of ncRNAs has been investigated in embryonic and induced pluripotent stem cells, and in numerous types of adult SCs and progenitors, including those of the breast, which will be the topic of this review. We will focus on ncRNAs with an important role in breast cancer, in particular in mammary cancer stem cells and progenitors, and highlight the ncRNA-based circuitries whose subversion alters a number of the epigenetic, transcriptional and post-transcriptional events that control "stemness" in the physiological setting

Low energy actuation technique of bistable composites for aircraft morphing

Morphing structures for lightweight and energy-efficient aircraft mobile surfaces have been investigated for several years. This paper presents a novel lightweight, passive and low-energy morphing surface concept based on the "lever effect" of a bistable composite plate that can be integrated in aircraft moving surfaces. By using appropriate boundary conditions, it is demonstrated that the magnitude of the activation force on the bistable composite can be tailored to match the differential pressure on the aircraft's airfoil. As a consequence, the bistable laminate can be used as a passive morphing surface. Both numerical simulations and experimental testing are used to prove this concept on a NACA 2412 airfoil structure. The results show that, by choosing proper configuration of constraints, lay-up and aspect ratio of the bistable composite, it is possible to tailor and activate the snap-through mechanism in a passive manner. The proposed concept would save significant weight when compared to an active morphing concept

Microenvironment stimuli HGF and hypoxia differently affected miR-125b and Ets-1 function with opposite effects on the invasiveness of bone metastatic cells : A comparison with breast carcinoma cells

We examined the influence of microenvironment stimuli on molecular events relevant to the biological functions of 1833-bone metastatic clone and the parental MDA-MB231 cells. (i) In both the cell lines, hepatocyte growth factor (HGF) and the osteoblasts\u2019 biological products down regulated nuclear Ets-1-protein level in concomitance with endogenous miR-125b accumulation. In contrast, under hypoxia nuclear Ets-1 was unchanged, notwithstanding the miR-125b increase. (ii) Also, the 1833-cell invasiveness and the expression of Endothelin-1, the target gene of Ets-1/HIF-1, showed opposite patterns under HGF and hypoxia. We clarified the molecular mechanism(s) reproducing the high miR-125b levels with the mimic in 1833 cells. Under hypoxia, the miR-125b mimic maintained a basal level and functional Ets-1 protein, as testified by the elevated cell invasiveness. However, under HGF ectopic miR-125b downregulated Ets-1 protein and cell motility, likely involving an Ets-1-dominant negative form sensible to serum conditions; Ets-1-activity inhibition by HGF implicated HIF-1\u3b1 accumulation, which drugged Ets-1 in the complex bound to the Endothelin-1 promoter. Altogether, 1833-cell exposure to HGF would decrease Endothelin-1 transactivation and protein expression, with the possible impairment of Endothelin-1-dependent induction of E-cadherin, and the reversion towards an invasive phenotype: this was favoured by Ets-1 overexpression, which inhibited HIF-1\u3b1 expression and HIF-1 activity. (iii) In MDA-MB231 cells, HGF strongly and rapidly decreased Ets-1, hampering invasiveness and reducing Ets-1-binding to Endothelin-1 promoter; HIF-1\u3b1 did not form a complex with Ets-1 and Endothelin-1-luciferase activity was unchanged. Overall, depending on the microenvironment conditions and endogenous miR-125b levels, bone-metastatic cells might switch from Ets-1-dependent motility towards colonization/growth, regulated by the balance between Ets-1 and HIF-1

INFN What Next: Ultra-relativistic Heavy-Ion Collisions

This document was prepared by the community that is active in Italy, within INFN (Istituto Nazionale di Fisica Nucleare), in the field of ultra-relativistic heavy-ion collisions. The experimental study of the phase diagram of strongly-interacting matter and of the Quark-Gluon Plasma (QGP) deconfined state will proceed, in the next 10-15 years, along two directions: the high-energy regime at RHIC and at the LHC, and the low-energy regime at FAIR, NICA, SPS and RHIC. The Italian community is strongly involved in the present and future programme of the ALICE experiment, the upgrade of which will open, in the 2020s, a new phase of high-precision characterisation of the QGP properties at the LHC. As a complement of this main activity, there is a growing interest in a possible future experiment at the SPS, which would target the search for the onset of deconfinement using dimuon measurements. On a longer timescale, the community looks with interest at the ongoing studies and discussions on a possible fixed-target programme using the LHC ion beams and on the Future Circular Collider.Comment: 99 pages, 56 figure

Measurement of the angular correlation between the two gamma rays emitted in the radioactive decays of a 60^{60}Co source with two NaI(Tl) scintillator

We implemented a didactic experiment to study the angular correlation between the two gamma rays emitted in typical $^{60}$Co radioactive decays. We used two NaI(Tl) scintillators, already available in our laboratory, and a low-activity $^{60}$Co source. The detectors were mounted on two rails, with the source at their center. The first rail was fixed, while the second could be rotated around the source. We performed several measurements by changing the angle between the two scintillators in the range from $90^\circ$ to $180^\circ$. Dedicated background runs were also performed, removing the source from the experimental setup. We found that the signal rate increases with the angular separation between the two scintillators, with small discrepancies from the theoretical expectations.Comment: 15 pages, 12 figure

A serum circulating miRNA diagnostic test to identify asymptomatic high-risk individuals with early stage lung cancer

Lung cancer is the first cause of cancer mortality worldwide, and its early detection is currently the main available strategy to improve disease prognosis. While early diagnosis can be successfully achieved through tomography-based population screenings in high-risk individuals, simple methodologies are needed for effective cancer prevention programs. We developed a test, based on the detection of 34 microRNAs (miRNAs) from serum, that could identify patients with early stage non-small cell lung carcinomas (NSCLCs) in a population of asymptomatic high-risk individuals with 80% accuracy. The signature could assign disease probability accurately either in asymptomatic or symptomatic patients, is able to distinguish between benign and malignant lesions, and to capture the onset of the malignant disease in individual patients over time. Thus, our test displays a number of features of clinical relevance that project its utility in programs for the early detection of NSCLC

Degradation dynamics of micrornas revealed by a novel pulse-chase approach

The regulation of miRNAs is critical to the definition of cell identity and behavior in normal physiology and disease. To date, the dynamics of miRNA degradation and the mechanisms involved in remain largely obscure, in particular, in higher organisms. Here, we developed a pulse-chase approach based on metabolic RNA labeling to calculate miRNA decay rates at genome-wide scale in mammalian cells. Our analysis revealed heterogeneous miRNA half-lives, with many species behaving as stable molecules (T1/2 > 24 h), while others, including passenger miRNAs and a number (25/129) of guide miRNAs, are quickly turned over (T1/2 = 4-14 h). Decay rates were coupled with other features, including genomic organization, transcription rates, structural heterogeneity (isomiRs), and target abundance, measured through quantitative experimental approaches. This comprehensive analysis highlighted functional mechanisms that mediate miRNA degradation, as well as the importance of decay dynamics in the regulation of the miRNA pool under both steady-state conditions and during cell transitions