Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockade

Adenosine is a neuromodulator that operates via the most abundant inhibitory adenosine A1 receptors (A1Rs) and the less abundant, but widespread, facilitatory A2ARs. It is commonly assumed that A1Rs play a key role in neuroprotection since they decrease glutamate release and hyperpolarize neurons. In fact, A1R activation at the onset of neuronal injury attenuates brain damage, whereas its blockade exacerbates damage in adult animals. However, there is a down-regulation of central A1Rs in chronic noxious situations. In contrast, A2ARs are up-regulated in noxious brain conditions and their blockade confers robust brain neuroprotection in adult animals. The brain neuroprotective effect of A2AR antagonists is maintained in chronic noxious brain conditions without observable peripheral effects, thus justifying the interest of A2AR antagonists as novel protective agents in neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease, ischemic brain damage and epilepsy. The greater interest of A2AR blockade compared to A1R activation does not mean that A1R activation is irrelevant for a neuroprotective strategy. In fact, it is proposed that coupling A2AR antagonists with strategies aimed at bursting the levels of extracellular adenosine (by inhibiting adenosine kinase) to activate A1Rs might constitute the more robust brain neuroprotective strategy based on the adenosine neuromodulatory system. This strategy should be useful in adult animals and especially in the elderly (where brain pathologies are prevalent) but is not valid for fetus or newborns where the impact of adenosine receptors on brain damage is different

HORuS transmission spectroscopy of 55 Cnc e

The High Optical Resolution Spectrograph (HORuS) is a new high-resolution echelle spectrograph available on the 10.4-m Gran Telescopio Canarias (GTC). We report on the first HORuS observations of a transit of the super-Earth planet 55 Cnc e. We investigate the presence of Na i and Hα in its transmission spectrum and explore the capabilities of HORuS for planetary transmission spectroscopy. Our methodology leads to residuals in the difference spectrum between the in-transit and out-of-transit spectra for the Na i doublet lines of (3.4 ± 0.4) × 10-4, which sets an upper limit to the detection of line absorption from the planetary atmosphere that is one order of magnitude more stringent that those reported in the literature. We demonstrate that we are able to reach the photon-noise limit in the residual spectra using HORuS to a degree that we would be able to easily detect giant planets with larger atmospheres. In addition, we modelled the structure, chemistry, and transmission spectrum of 55 Cnc e using state-of-the-art open source tools.With funding from the Spanish government through the "María de Maeztu Unit of Excellence" accreditation (MDM-2017-0737

Adverse prognostic impact of complex karyotype (≥3 cytogenetic alterations) in adult T-cell acute lymphoblastic leukemia (T-ALL)

Altres ajuts: Asociación Española Contra el Cáncer (AECC GC16173697BIGA); Fondo Europeo de Desarrollo Regional (FEDER "A way to make Europe"); European Social Fund (ESF "Investing in your future"); CERCA; Fundació "La Caixa".The potential prognostic value of conventional karyotyping in adult T-cell acute lymphoblastic leukemia (T-ALL) remains an open question. We hypothesized that a modified cytogenetic classification, based on the number and type of cytogenetic abnormalities, would allow the identification of high-risk adult T-ALL patients. Complex karyotype defined by the presence of ≥3 cytogenetic alterations identified T-ALL patients with poor prognosis in this study. Karyotypes with ≥3 abnormalities accounted for 16 % (22/139) of all evaluable karyotypes, corresponding to the largest poor prognosis cytogenetic subgroup of T-ALL identified so far. Patients carrying karyotypes with ≥3 cytogenetic alterations showed a significantly inferior response to therapy, and a poor outcome in terms of event-free survival (EFS), overall survival (OS) and cumulative incidence of relapse (CIR), independently of other baseline characteristics and the end-induction minimal residual disease (MRD) level. Additional molecular analyses of patients carrying ≥3 cytogenetic alterations showed a unique molecular profile that could contribute to understand the underlying molecular mechanisms of resistance and to evaluate novel targeted therapies (e.g. IL7R directed) with potential impact on outcome of adult T-ALL patients

ANTARES and IceCube Combined Search for Neutrino Point-like and Extended Sources in the Southern Sky

A search for point-like and extended sources of cosmic neutrinos using data collected by the ANTARES and IceCube neutrino telescopes is presented. The data set consists of all the track-like and shower-like events pointing in the direction of the Southern Sky included in the nine-year ANTARES point-source analysis, combined with the throughgoing track-like events used in the seven-year IceCube point-source search. The advantageous field of view of ANTARES and the large size of IceCube are exploited to improve the sensitivity in the Southern Sky by a factor of ∼2 compared to both individual analyses. In this work, the Southern Sky is scanned for possible excesses of spatial clustering, and the positions of preselected candidate sources are investigated. In addition, special focus is given to the region around the Galactic Center, whereby a dedicated search at the location of SgrA∗ is performed, and to the location of the supernova remnant RXJ 1713.7-3946. No significant evidence for cosmic neutrino sources is found, and upper limits on the flux from the various searches are presented

ANTARES and IceCube Combined Search for Neutrino Point-like and Extended Sources in the Southern Sky

A search for point-like and extended sources of cosmic neutrinos using data collected by the ANTARES and IceCube neutrino telescopes is presented. The data set consists of all the track-like and shower-like events pointing in the direction of the Southern Sky included in the nine-year ANTARES point-source analysis, combined with the throughgoing track-like events used in the seven-year IceCube point-source search. The advantageous field of view of ANTARES and the large size of IceCube are exploited to improve the sensitivity in the Southern Sky by a factor of ∼2 compared to both individual analyses. In this work, the Southern Sky is scanned for possible excesses of spatial clustering, and the positions of preselected candidate sources are investigated. In addition, special focus is given to the region around the Galactic Center, whereby a dedicated search at the location of SgrA∗ is performed, and to the location of the supernova remnant RXJ 1713.7-3946. No significant evidence for cosmic neutrino sources is found, and upper limits on the flux from the various searches are presented