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Many gas giant exoplanets orbit so close to their host star that they are heated to high temperatures, causing atmospheric gases to escape. Gas giant atmospheres are mostly hydrogen and helium, which are difficult to observe. Two papers have now observed escaping helium in the near-infrared (see the Perspective by Brogi). Allart et al. observed helium in a Neptune-mass exoplanet and performed detailed simulations of its atmosphere, which put constraints on the escape rate. Nortmann et al. found that helium is escaping a Saturn-mass planet, trailing behind it in its orbit. They combined this with observations of several other exoplanets to show that atmospheres are being lost more quickly by exoplanets that are more strongly heated. Science , this issue p. 1384 , p. 1388 ; see also p. 1360 Helium is observed in the atmosphere of a warm Neptune-mass exoplanet, constraining the atmospheric loss rate. Stellar heating causes atmospheres of close-in exoplanets to expand and escape. These extended atmospheres are difficult to observe because their main spectral signature—neutral hydrogen at ultraviolet wavelengths—is strongly absorbed by interstellar medium. We report the detection of the near-infrared triplet of neutral helium in the transiting warm Neptune-mass exoplanet HAT-P-11b by using ground-based, high-resolution observations. The helium feature is repeatable over two independent transits, with an average absorption depth of 1.08 ± 0.05%. Interpreting absorption spectra with three-dimensional simulations of the planet’s upper atmosphere suggests that it extends beyond 5 planetary radii, with a large-scale height and a helium mass loss rate of ≲3 × 10 5 grams per second. A net blue-shift of the absorption might be explained by high-altitude winds flowing at 3 kilometers per second from day to night-side.

Tregs are able of suppressing tumor-specific effector cells, such as lymphocytes CD8+, CD4+ and Natural Killer cells. Different drugs, especially different schedules of administration, like metronomic chemotherapy (mCHT), seem to be able to increase anticancer immunity, by acting on downregulation of Tregs. Most of the data available regarding the immunomodulating effect of mCHT have been obtained with Cyclophosphamide (CTX). Aim of the present study was to explore the effects of mVRL and mCAPE administration, alone or in combination, on T cells. Observation of 13 metastatic breast cancer patients lasted controlling for 56 days, where Treg frequencies and function, spontaneous anti-tumor T-cell responses were monitored, as well as the clinical outcome. No depletion in Treg absolute numbers, or percentage of T lymphocytes, was observed. Only in 5 patients, a modest and transient depletion of Tregs was observed during the first 14 days of treatment. To better describe the effect on Tregs, we subsequently looked at the variations in Memory, Naïve and Activated Treg subpopulations: we observed a trend in reduction for memory Treg (Treg MEM) and an increase for Treg Naïve (Treg NAIVE) and Treg Activated (Treg ACT) components. We finally analyzed the average trend of Treg in the Treg depleted patients and non-depleted ones, without fiding any significant differences. The trend of the Treg MEM appeared different, showing a reduction during the first 14 days, followed by an increase at the levels before treatment at Day 56 in the group of depleted patients and a progressive substantial reduction in the group of non-depleted patients along the entire course of treatment. Opposed to the data known, treatment with mVRL w/o mCAPE did not show any effect on Tregs.

The evolution of forearc and backarc domains is usually treated separately, as they are separated by a volcanic arc. We analyse their spatial and temporal relationships in the Tyrrhenian subduction system, using seismic profiles and numerical modelling. A volcanic arc, which included the Marsili volcano, was involved in arc-rifting during the Pliocene. This process led to the formation of an oceanic backarc basin (~ 1.8 Ma) to the west of the Marsili volcano. The eastern region corresponded to the forearc domain, floored by serpentinised mantle. Here, a new volcanic arc formed at ~ 1 Ma, marking the onset of the forearc-rifting. This work highlights that fluids and melts induce weakening of the volcanic arc region and drive the arc-rifting that led to the backarc basin formation. Later, the slab rollback causes the trench-ward migration of volcanism that led to the forearc- rifting under the control of fluids released from the downgoing plate.

Nowadays, treatment of metastatic breast cancer (MBC) has been enriched with novel therapeutical strategies. Metronomic chemotherapy (mCHT) is a continuous and frequent administration of chemotherapy at a lower dose and so whit less toxicity. Thus, this strategy could be attractive for elderly MBC patients. Aim of this analysis is to provide insights into mCHT’s activity in a real-life setting of elderly MBC patients. Data of patients ≥ 75 years old included in VICTOR-6 study were analyzed. VICTOR-6 is a multicentre, Italian, retrospective study, which collected data on mCHT in MBC patients treated between 2011 and 2016. A total of 112 patients were included. At the beginning of mCHT, median age was 81 years (75–98) and in 33% of the patients mCHT was the first line choice. Overall Response Rate (ORR) and Disease Control Rate (DCR) were 27.9% and 79.3%, respectively. Median PFS ranged between 7.6 and 9.1 months, OS between 14.1 and 18.5 months. The most relevant toxicity was the hematological one (24.1%); severe toxicity (grade 3–4) ranged from 0.9% for skin toxicity up to 8% for hematologic one. This is a large study about mCHT in elderly MBC patients, providing insights to be further investigated in this subgroup of frail patients.

Hot Jupiter WASP-18b: a too-close encounter 'Hot Jupiter' extrasolar planets are thought to have formed at some distance from their host stars and to have migrated inwards at a later date. These planets provide new perspectives on the evolution of planetary systems, and the discovery of WASP-18b, the closest-orbiting and most extreme hot Jupiter yet, provides a glimpse of what may be a planet nearing the end of its life. With a close orbit, high mass (ten times that of Jupiter), and brief (0.94-day) orbital period, WASP-18b has the strongest tidal interaction of any known star–planet system. We appear to be seeing WASP-18b in a rare and short-lived state as it spirals towards its host star, destined to be destroyed within the host star's lifetime. Alternatively, the tidal dissipation this system — and perhaps other hot Jupiters — must be much weaker than that in our Solar System. 'Hot Jupiters' abound in lists of known extrasolar planets. Those closest to their parent stars have strong tidal interactions, leading to the suggestion that systems such as OGLE-TR-56 could be used as tests of tidal dissipation theory. Here, the discovery of planet WASP-18b is reported, with an orbital period of 0.94 days and a tidal interaction an order of magnitude stronger than that of OGLE-TR-56b. Either WASP-18 is in a rare, short-lived state, or the tidal dissipation in this system must be weaker than in the Solar System. The ‘hot Jupiters’ that abound in lists of known extrasolar planets are thought to have formed far from their host stars, but migrate inwards through interactions with the proto-planetary disk from which they were born 1 , 2 , or by an alternative mechanism such as planet–planet scattering 3 . The hot Jupiters closest to their parent stars, at orbital distances of only ∼0.02 astronomical units, have strong tidal interactions 4 , 5 , and systems such as OGLE-TR-56 have been suggested as tests of tidal dissipation theory 6 , 7 . Here we report the discovery of planet WASP-18b with an orbital period of 0.94 days and a mass of ten Jupiter masses (10  M Jup ), resulting in a tidal interaction an order of magnitude stronger than that of planet OGLE-TR-56b. Under the assumption that the tidal-dissipation parameter Q of the host star is of the order of 10 6 , as measured for Solar System bodies and binary stars and as often applied to extrasolar planets, WASP-18b will be spiralling inwards on a timescale less than a thousandth that of the lifetime of its host star. Therefore either WASP-18 is in a rare, exceptionally short-lived state, or the tidal dissipation in this system (and possibly other hot-Jupiter systems) must be much weaker than in the Solar System.

We report the discovery of a transiting planet with an orbital period of 3.05 days orbiting the star TYC 7247-587-1. The star, WASP-41, is a moderately bright G8 V V star ( V = 11.6 V = 11.6 ) with a metallicity close to solar ([Fe/H] = -0.08 ± 0.09 [ Fe / H ] = - 0.08 ± 0.09 ). The star shows evidence of moderate chromospheric activity, both from emission in the cores of the Ca iiH and K ines and photometric variability with a period of 18.4 days and an amplitude of about 1%. We use a new method to show quantitatively that this periodic signal has a low false-alarm probability. The rotation period of the star implies a gyrochronological age for WASP-41 of 1.8 Gyr with an error of about 15%. We have used a combined analysis of the available photometric and spectroscopic data to derive the mass and radius of the planet (0.92 ± 0.06 M Jup 0.92 ± 0.06     M Jup ,1.20 ± 0.06 R Jup 1.20 ± 0.06     R Jup ). Further observations of WASP-41 can be used to explore the connections between the properties of hot Jupiter planets and the level of chromospheric activity in their host stars.

Tregs are able of suppressing tumor-specific effector cells, such as lymphocytes CD8+, CD4+ and Natural Killer cells. Different drugs, especially different schedules of administration, like metronomic chemotherapy (mCHT), seem to be able to increase anticancer immunity, by acting on downregulation of Tregs. Most of the data available regarding the immunomodulating effect of mCHT have been obtained with Cyclophosphamide (CTX). Aim of the present study was to explore the effects of mVRL and mCAPE administration, alone or in combination, on T cells. Observation of 13 metastatic breast cancer patients lasted controlling for 56 days, where Treg frequencies and function, spontaneous anti-tumor T-cell responses were monitored, as well as the clinical outcome. No depletion in Treg absolute numbers, or percentage of T lymphocytes, was observed. Only in 5 patients, a modest and transient depletion of Tregs was observed during the first 14 days of treatment. To better describe the effect on Tregs, we subsequently looked at the variations in Memory, Naïve and Activated Treg subpopulations: we observed a trend in reduction for memory Treg (Treg MEM) and an increase for Treg Naïve (Treg NAIVE) and Treg Activated (Treg ACT) components. We finally analyzed the average trend of Treg in the Treg depleted patients and non-depleted ones, without fiding any significant differences. The trend of the Treg MEM appeared different, showing a reduction during the first 14 days, followed by an increase at the levels before treatment at Day 56 in the group of depleted patients and a progressive substantial reduction in the group of non-depleted patients along the entire course of treatment. Opposed to the data known, treatment with mVRL w/o mCAPE did not show any effect on Tregs.

The Gulf of Patti and its onshore sector represent one of the most seismically active regions of the Italian Peninsula. Over the period 1984–2014, about 1800 earthquakes with small-to-moderate magnitude and a maximum hypocentral depth of 40 km occurred in this area. Historical catalogues reveal that the same area was affected by several strong earthquakes such as the Mw = 6.1 event in April 1978 and the Mw = 6.2 one in March 1786 which have caused severe damages in the surrounding localities. The main seismotectonic feature affecting this area is represented by a NNW–SSE trending right-lateral strike-slip fault system called “Aeolian–Tindari–Letojanni” (ATLFS) which has been interpreted as a lithospheric transfer zone extending from the Aeolian Islands to the Ionian coast of Sicily. Although the large-scale role of the ATLFS is widely accepted, several issues about its structural architecture (i.e. distribution, attitude and slip of fault segments) and the active deformation pattern are poorly constrained, particularly in the offshore. An integrated analysis of field structural geology with marine geophysical and seismological data has allowed to better understand the structural fabric of the ATLFS which, in the study area, is expressed by two major NW–SE trending, en-echelon arranged fault segments. Minor NNE–SSW oriented extensional structures mainly occur in the overlap region between major faults, forming a dilatational stepover. Most faults display evidence of active deformation and appear to control the main morphobathymetric features. This aspect, together with diffused continental slope instability, must be considered for the revaluation of the seismic and geomorphological hazard of this sector of southern Tyrrhenian Sea.

The miR-483-3p is upregulated in several tumors, including liver tumors, where it inhibits TP53-dependent apoptosis by targeting the pro-apoptotic gene BBC3 /PUMA. The transcriptional regulation of the miR-483-3p could be driven by the β-catenin/USF1 complex, independently from its host gene IGF2, and we previously demonstrated that in HepG2 hepatoblastoma cells carrying wild-type TP53 the upregulation of the miR-483-3p overcomes the antitumoral effects of the tumor-suppressor miR-145-5p by a mechanism involving cellular glucose availability. Here we demonstrate that in HepG2 cells, the molecular link between glucose concentration and miR-483-3p expression entails the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT), which stabilizes the transcriptional complex at the miR-483 promoter. HepG2 cells showed reduced miR-483-3p expression and increased susceptibility to 5-fluorouracil (5-FU)-induced apoptosis in presence of the inhibitor of glycolysis 2-deoxy- d -glucose (2-DG). However, i n vivo experiments showed that HepG2 cells with higher miR-483-3p expression were selected during tumor progression regardless of 5-FU treatment. Furthermore, treatment with 2-DG alone did not significantly reduce HepG2 xenograft load in immunodeficient mice. In conclusion, we show that in HepG2 cells glucose uptake increases the expression of the oncogenic miR-483-3p through the OGT pathway. This suggests that depletion of the miR-483-3p may be a valuable therapeutic approach in liver cancer patients, but the use of inhibitors of glycolysis to achieve this purpose could accelerate the selection of resistant neoplastic cell clones.

Deregulation of the miR-15a/16-1 cluster has a key role in the pathogenesis of chronic lymphocytic leukemia (CLL), a clinically heterogeneous disease with indolent and aggressive forms. The miR-15a/16-1 locus is located at 13q14, the most frequently deleted region in CLL. Starting from functional investigations of a rare SNP upstream the miR cluster, we identified a novel allele-specific mechanism that exploits a cryptic activator region to recruit the RNA polymerase III for miR-15a/16-1 transcription. This regulation of the miR-15a/16- locus is independent of the DLEU2 host gene, which is often transcribed monoallellically by RPII. We found that normally one allele of miR-15a/16-1 is transcribed by RNAPII, the other one by RNAPIII. In our subset of CLL patients harboring 13q14 deletions, exclusive RNA polymerase III (RPIII)-driven transcription of the miR-15a/16-1 was the consequence of loss of the RPII-regulated allele and correlated with high expression of the poor prognostic marker ZAP70 ( P =0.019). Thus, our findings point to a novel biological process, characterized by double allele-specific transcriptional regulation of the miR-15a/16-1 locus by alternative mechanisms. Differential usage of these mechanisms may distinguish at onset aggressive from indolent forms of CLL. This provides a basis for the clinical heterogeneity of the CLL patients carrying 13q14 deletions.