Chemotherapeutic agent 5-fluorouracil increases survival of SOD1 mouse model of ALS

Amyotrophic lateral sclerosis (ALS) is a lethal motor neuron disease with no cure. Currently there are only two ALS drugs approved by the FDA, both with a limited therapeutic effect. In the search for drug candidates for ALS, we studied the effect of known stem cell mobilizing agents (treatment) and antimetabolite 5-fluorouracil (5-FU) (anti-treatment) in SOD1G93A model of ALS. Surprisingly, we found that anti-cancer drug 5-FU increases lifespan, delays the disease onset and improves motor performance in ALS mice. Although we were not able to demonstrate the mechanistic basis of the beneficial 5-FU action in ALS mice, our findings suggest that 5-FU or similar drugs are possible drug candidates for the treatment of motor neuron diseases through drug repurposing

Unravelling the combined use of soil and microbial technologies to optimize cultivation of Halophyte Limonium algarvense (Plumbaginaceae) using saline soils and water

Salt-affected soils have detrimental effects on agriculture and ecosystems. However, these soils can still be used for halophyte (salt-tolerant plants) cultivation using brackish and/or saline water. In this study, we employed soil technologies and mutualistic microorganisms as a sustainable strategy to improve the growth and reproduction of the halophyte Limonium algarvense Erben’s growth and reproduction under saline conditions. A microcosm assay was conducted under controlled greenhouse conditions to cultivate L. algarvense using a saline Fluvisol (FLU) amended—or not—with a Technosol (TEC). Plants were inoculated with the arbuscular mycorrhizal fungus (AMF) Rhizoglomus irregulare and/or a consortium of plant growth-promoting bacteria (PGPB), and they were irrigated with estuarine water. Soil enzyme analysis and physicochemical characterisation of the soils, collected at the beginning and at the end of the assay, were carried out. The physiological status of non-inoculated and inoculated plants was monitored during the assay for 4 months, and AMF root colonisation was evaluated. In FLU, only plants inoculated with the AMF survived. These plants had lower number of leaves, and shoot and root dry biomass than the ones grown in the TEC by the end of the assay. In the TEC, PGPB inoculation led to higher NDVI and PRI values, and AMF inoculation promoted higher reproductive development but not pollen fertility. The findings show that the combined use of soil and microbial technologies can be successfully applied to cultivate L. algarvense, suggesting their generalized use for other Limonium species with economic interest, while contributing to the sustainable use of marginal lands.Federation of European Microbiological Societies (FEMS) (FEMSGO- 2020-203), University of Sevilla (Spain; Plan Propio de Investigación y Tranferencia 2021 Ayuda A1-I.3A1) for grants to support the stays at ISA-ULisboa (Portugal).info:eu-repo/semantics/publishedVersio

The VIMOS-VLT Deep Survey: Evolution in the Halo Occupation Number since z ∼\sim 1

We model the evolution of the mean galaxy occupation of dark-matter halos over the range $0.1<z<1.3$, using the data from the VIMOS-VLT Deep Survey (VVDS). The galaxy projected correlation function $w_p(r_p)$ was computed for a set of luminosity-limited subsamples and fits to its shape were obtained using two variants of Halo Occupation Distribution models. These provide us with a set of best-fitting parameters, from which we obtain the average mass of a halo and average number of galaxies per halo. We find that after accounting for the evolution in luminosity and assuming that we are largely following the same population, the underlying dark matter halo shows a growth in mass with decreasing redshift as expected in a hierarchical structure formation scenario. Using two different HOD models, we see that the halo mass grows by 90% over the redshift interval z=[0.5,1.0]. This is the first time the evolution in halo mass at high redshifts has been obtained from a single data survey and it follows the simple form seen in N-body simulations with $M(z) = M_0 e^{-\beta z}$, and $\beta = 1.3 \pm 0.30$. This provides evidence for a rapid accretion phase of massive halos having a present-day mass $M_0 \sim 10^{13.5} h^{-1} M_\odot$, with a $m > 0.1 M_0$ merger event occuring between redshifts of 0.5 and 1.0. Futhermore, we find that more luminous galaxies are found to occupy more massive halos irrespectively of the redshift. Finally, the average number of galaxies per halo shows little increase from redshift z$\sim$ 1.0 to z$\sim$ 0.5, with a sharp increase by a factor $\sim$3 from z$\sim$ 0.5 to z$\sim$ 0.1, likely due to the dynamical friction of subhalos within their host halos.Comment: 14 pages, 6 figures, 5 tables. MNRAS accepted

Connecting stellar mass and star-formation rate to dark matter halo mass out to z ~ 2

We have constructed an extended halo model (EHM) which relates the total stellar mass and star-formation rate (SFR) to halo mass (M_h). An empirical relation between the distribution functions of total stellar mass of galaxies and host halo mass, tuned to match the spatial density of galaxies over 0<z<2 and the clustering properties at z~0, is extended to include two different scenarios describing the variation of SFR on M_h. We also present new measurements of the redshift evolution of the average SFR for star-forming galaxies of different stellar mass up to z=2, using data from the Herschel Multi-tiered Extragalactic Survey (HerMES) for infrared-bright galaxies. Combining the EHM with the halo accretion histories from numerical simulations, we trace the stellar mass growth and star-formation history in halos spanning a range of masses. We find that: (1) The intensity of the star-forming activity in halos in the probed mass range has steadily decreased from z~2 to 0; (2) At a given epoch, halos in the mass range between a few times 10^{11} M_Sun and a few times 10^{12} M_Sun are the most efficient at hosting star formation; (3) The peak of SFR density shifts to lower mass halos over time; (4) Galaxies that are forming stars most actively at z~2 evolve into quiescent galaxies in today's group environments, strongly supporting previous claims that the most powerful starbursts at z~2 are progenitors of today's elliptical galaxies.Comment: 15 pages, 12 figures, accepted for publication in MNRA

Cognitive impairment induced by delta9-tetrahydrocannabinol occurs through heteromers between cannabinoid CB1 and serotonin 5-HT2A receptors

Delta-9-tetrahydrocannabinol (THC), the main psychoactive compound of marijuana, induces numerous undesirable effects, including memory impairments, anxiety, and dependence. Conversely, THC also has potentially therapeutic effects, including analgesia, muscle relaxation, and neuroprotection. However, the mechanisms that dissociate these responses are still not known. Using mice lacking the serotonin receptor 5-HT2A, we revealed that the analgesic and amnesic effects of THC are independent of each other: while amnesia induced by THC disappears in the mutant mice, THC can still promote analgesia in these animals. In subsequent molecular studies, we showed that in specific brain regions involved in memory formation, the receptors for THC and the 5-HT2A receptors work together by physically interacting with each other. Experimentally interfering with this interaction prevented the memory deficits induced by THC, but not its analgesic properties. Our results highlight a novel mechanism by which the beneficial analgesic properties of THC can be dissociated from its cognitive side effects

The CAMELS project: Cosmology and Astrophysics with MachinE Learning Simulations

We present the Cosmology and Astrophysics with MachinE Learning Simulations --CAMELS-- project. CAMELS is a suite of 4,233 cosmological simulations of $(25~h^{-1}{\rm Mpc})^3$ volume each: 2,184 state-of-the-art (magneto-)hydrodynamic simulations run with the AREPO and GIZMO codes, employing the same baryonic subgrid physics as the IllustrisTNG and SIMBA simulations, and 2,049 N-body simulations. The goal of the CAMELS project is to provide theory predictions for different observables as a function of cosmology and astrophysics, and it is the largest suite of cosmological (magneto-)hydrodynamic simulations designed to train machine learning algorithms. CAMELS contains thousands of different cosmological and astrophysical models by way of varying $\Omega_m$, $\sigma_8$, and four parameters controlling stellar and AGN feedback, following the evolution of more than 100 billion particles and fluid elements over a combined volume of $(400~h^{-1}{\rm Mpc})^3$. We describe the simulations in detail and characterize the large range of conditions represented in terms of the matter power spectrum, cosmic star formation rate density, galaxy stellar mass function, halo baryon fractions, and several galaxy scaling relations. We show that the IllustrisTNG and SIMBA suites produce roughly similar distributions of galaxy properties over the full parameter space but significantly different halo baryon fractions and baryonic effects on the matter power spectrum. This emphasizes the need for marginalizing over baryonic effects to extract the maximum amount of information from cosmological surveys. We illustrate the unique potential of CAMELS using several machine learning applications, including non-linear interpolation, parameter estimation, symbolic regression, data generation with Generative Adversarial Networks (GANs), dimensionality reduction, and anomaly detection.Comment: 33 pages, 18 figures, CAMELS webpage at https://www.camel-simulations.or

Irinotecan+5-fluorouracil with concomitant pre-operative radiotherapy in locally advanced non-resectable rectal cancer: a phase I/II study

In the UK, 10% of patients diagnosed with rectal cancer have inoperable disease at presentation. This study ascertained whether the resectability rate of inoperable locally advanced rectal cancer was improved by administration of intravenous irinotecan, 5-fluorouracil (5-FU) and pelvic radiotherapy. During phase I of the trial (n=12), the dose of irinotecan was escalated in three-patient cohorts from 50 mg m−2 to 60 mg m−2 to 70 mg m−2 to identify the maximum tolerated dose (60 mg m−2). In phase II, 31 patients with non-resectable disease received 45 Gy radiotherapy and 5-FU infusions (200 mg m−2 per day) for 5 weeks. Irinotecan (60 mg m−2) was given on days 1, 8, 15 and 22. After treatment, patients were operated on if possible. Thirty patients completed the protocol, 28 underwent surgery. Before surgery, MRI restaging of 24 patients showed that 19 (79%) had a reduction in tumour stage after treatment (seven complete clinical response and 12 partial). Of 27 patients followed up after surgery, 22 (81%) had clear circumferential resection margins. Disease-free and overall survival estimates at 3 years were 65 and 90%, respectively. The regimen was well tolerated. Irinotecan, 5-FU and radiotherapy results in tumour downgrading, allowing resection of previously inoperable tumour with acceptable toxicity

Search for the Higgs boson in events with missing transverse energy and b quark jets produced in proton-antiproton collisions at s**(1/2)=1.96 TeV

We search for the standard model Higgs boson produced in association with an electroweak vector boson in events with no identified charged leptons, large imbalance in transverse momentum, and two jets where at least one contains a secondary vertex consistent with the decay of b hadrons. We use ~1 fb-1 integrated luminosity of proton-antiproton collisions at s**(1/2)=1.96 TeV recorded by the CDF II experiment at the Tevatron. We find 268 (16) single (double) b-tagged candidate events, where 248 +/- 43 (14.4 +/- 2.7) are expected from standard model background processes. We place 95% confidence level upper limits on the Higgs boson production cross section for several Higgs boson masses ranging from 110 GeV/c2 to 140 GeV/c2. For a mass of 115 GeV/c2 the observed (expected) limit is 20.4 (14.2) times the standard model prediction.Comment: 8 pages, 2 figures, submitted to Phys. Rev. Let

Measurement of the Helicity Fractions of W Bosons from Top Quark Decays Using Fully Reconstructed top-antitop Events with CDF II

We present a measurement of the fractions F_0 and F_+ of longitudinally polarized and right-handed W bosons in top quark decays using data collected with the CDF II detector. The data set used in the analysis corresponds to an integrated luminosity of approximately 318 pb -1. We select ttbar candidate events with one lepton, at least four jets, and missing transverse energy. Our helicity measurement uses the decay angle theta*, which is defined as the angle between the momentum of the charged lepton in the W boson rest frame and the W momentum in the top quark rest frame. The cos(theta*) distribution in the data is determined by full kinematic reconstruction of the ttbar candidates. We find F_0 = 0.85 +0.15 -0.22 (stat) +- 0.06 (syst) and F_+ = 0.05 +0.11 -0.05 (stat) +- 0.03 (syst), which is consistent with the standard model prediction. We set an upper limit on the fraction of right-handed W bosons of F_+ < 0.26 at the 95% confidence level.Comment: 11 pages, 2 figures, submitted to Phys. Rev.