T Cell Leukemia/Lymphoma 1A is essential for mouse epidermal keratinocytes proliferation promoted by insulin-like growth factor 1

T Cell Leukemia/Lymphoma 1A is expressed during B-cell differentiation and, when overexpressed, acts as an oncogene in mouse (Tcl1a) and human (TCL1A) B-cell chronic lymphocytic leukemia (B-CLL) and T-cell prolymphocytic leukemia (T-PLL). Furthermore, in the murine system Tcl1a is expressed in the ovary, testis and in pre-implantation embryos, where it plays an important role in blastomere proliferation and in embryonic stem cell (ESC) proliferation and self-renewal. We have also observed that Tcl1-/-adult mice exhibit alopecia and deep ulcerations. This finding has led us to investigate the role of TCL1 in mouse skin and hair follicles. We have found that TCL1 is expressed in the proliferative structure (i.e.The secondary hair germ) and in the stem cell niche (i.e.The bulge) of the hair follicle during regeneration phase and it is constitutively expressed in the basal layer of epidermis where it is required for the correct proliferative-differentiation program of the keratinocytes (KCs). Taking advantage of the murine models we have generated, including the Tcl1-/-and the K14-TCL1 transgenic mouse, we have analysed the function of TCL1 in mouse KCs and the molecular pathways involved. We provide evidence that in the epidermal compartment TCL1 has a role in the regulation of KC proliferation, differentiation, and apoptosis. In particular, the colony-forming efficiency (CFE) and the insulin-like growth factor 1 (IGF1)-induced proliferation are dramatically impaired, while apoptosis is increased, in KCs from Tcl1-/-mice when compared to WT. Moreover, the expression of differentiation markers such as cytokeratin 6 (KRT6), filaggrin (FLG) and involucrin (IVL) are profoundly altered in mutant mice (Tcl1-/-). Importantly, by over-expressing TCL1A in basal KCs of the K14-TCL1 transgenic mouse model, we observed a significant rescue of cell proliferation, differentiation and apoptosis of the mutant phenotype. Finally, we found TCL1 to act, at least in part, via increasing phospho-ERK1/2 and decreasing phospho-P38 MAPK. Hence, our data demonstrate that regulated levels of Tcl1a are necessary for the correct proliferation and differentiation of the interfollicular KC

The Hybrid Integrated Circuit of the ALICE Inner Tracking System upgrade

The upgrade of the Inner Tracking System scheduled during the second long shutdown is an important milestone of the ALICE upgrade and it will provide a high improvement of its performances. In this contribution the smallest operator unit of the detector, the Hybrid Integrated Circuits, is presented

Inhaler technique knowledge and skills before and after an educational program in obstructive respiratory disease patients: A real-life pilot study

Patients present poor knowledge and skills about their respiratory disease and inhaler device. We aimed to: (1) evaluate COPD and asthmatic patients' ability to manage inhaled drugs (2) identify differences among devices and (3) correlate clinical data with patient ability.Patients (n=134) admitted for pulmonary rehabilitation (PR) were given an ad-hoc questionnaire covering 0% as the worst and 100% the best value of global ability (indicating the sum of knowledge and skills in managing inhaled drugs) at baseline (T0) and discharge (T1). Educational program was provided during PR. Setting of rehabilitation, age, sex, diagnosis, spirometry, CIRS score, level of autonomy to use medications, if naïve about PR, educational level, and number/type of prescribed inhaled drugs were recorded.Most patients used 1 drug while 37% used 2 drugs. DPIs were the main device prescribed. At baseline, patients' mean level of knowledge and skills were 73% and 58%, respectively. There was a significant difference in level of skills (p=0.046) among device families, DPIs resulting worst and pMDIs best. Global ability, skills and knowledge improved after educational support (p0.001) but did not reach the optimal level, 88%, 87% and 89%, respectively. Baseline global ability was positively correlated to female gender, younger age, previous PR access, outpatient status, higher education level and GOLD D class.At hospital admission, global ability was not optimal. Education may improve this, irrespective of the type of device used, in particular in male, elderly, naïve to PR, low educational level patients

High promiscuity among females of the invasive pest species Drosophila suzukii

Drosophila suzukii (Matsumura, 1931), the spotted-wing drosophila, is a highly invasive fruit fly that spread from Southern Asia across most regions of Asia and, in the last 15 years, has invaded Europe and the Americas. It is an economically important pest of small fruits such as berries and stone fruits. Drosophila suzukii speciated by adapt ing to cooler, mountainous, and forest environments. In temperate regions, it evolved seasonal polyphenism traits which enhanced its survival during stressful winter population bottlenecks. Consequently, in these temperate regions, the populations undergo seasonal reproductive dynamics. Despite its economic importance, no data are available on the behavioural reproductive strategies of this fly. The presence of polyandry, for example, has not been determined despite the important role it might play in the reproductive dynamics of populations. We explored the presence of poly andry in an established population in Trentino, a region in northern Italy. In this area, D. suzukii overcomes the winter bottleneck and undergoes a seasonal reproductive fluctuation. We observed a high remating frequency in females during the late spring demographic explosion that led to the abundant summer population. The presence of a high degree of polyandry and shared paternity associated with the post-winter population increase raises the question of the possible evolutionary adaptive role of this reproductive behaviour in D. suzuki

Antideuterons as a Signature of Supersymmetric Dark Matter

Once the energy spectrum of the secondary component is well understood, measurements of the antiproton cosmic-ray flux at the Earth will be a powerful way to indirectly probe for the existence of supersymmetric relics in the galactic halo. Unfortunately, it is still spoilt by considerable theoretical uncertainties. As shown in this work, searches for low-energy antideuterons appear in the mean time as a plausible alternative, worth being explored. Above a few GeV/n, a dozen spallation antideuterons should be collected by the future AMS experiment on board ISSA. For energies less than about 3 GeV/n, the antideuteron spallation component becomes negligible and may be supplanted by a potential supersymmetric signal. If a few low-energy antideuterons are discovered, this should be seriously taken as a clue for the existence of massive neutralinos in the Milky Way.Comment: 16 pages, 9 figure

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