Clonal human fetal ventral mesencephalic dopaminergic neuron precursors for cell therapy research

A major challenge for further development of drug screening procedures, cell replacement therapies and developmental studies is the identification of expandable human stem cells able to generate the cell types needed. We have previously reported the generation of an immortalized polyclonal neural stem cell (NSC) line derived from the human fetal ventral mesencephalon (hVM1). This line has been biochemically, genetically, immunocytochemically and electrophysiologically characterized to document its usefulness as a model system for the generation of A9 dopaminergic neurons (DAn). Long-term in vivo transplantation studies in parkinsonian rats showed that the grafts do not mature evenly. We reasoned that diverse clones in the hVM1 line might have different abilities to differentiate. In the present study, we have analyzed 9 hVM1 clones selected on the basis of their TH generation potential and, based on the number of v-myc copies, v-myc down-regulation after in vitro differentiation, in vivo cell cycle exit, TH+ neuron generation and expression of a neuronal mature marker (hNSE), we selected two clones for further in vivo PD cell replacement studies. The conclusion is that homogeneity and clonality of characterized NSCs allow transplantation of cells with controlled properties, which should help in the design of long-term in vivo experimentsThis work was supported by grants from the Spanish Ministry of Economy and Competitiveness (formerly Science and Innovation; PLE2009-0101, SAF2010-17167), Comunidad Autónoma Madrid (S2011-BMD-2336), Instituto Salud Carlos III (RETICS TerCel, RD06/0010/0009) and European Union (Excell, NMP4-SL-2008-214706). This work was also supported by an institutional grant from Foundation Ramón Areces to the Center of Molecular Biology Severo Ocho

Taming the terminological tempest in invasion science

\ua9 2024 The Authors. Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society. Standardised terminology in science is important for clarity of interpretation and communication. In invasion science – a dynamic and rapidly evolving discipline – the proliferation of technical terminology has lacked a standardised framework for its development. The result is a convoluted and inconsistent usage of terminology, with various discrepancies in descriptions of damage and interventions. A standardised framework is therefore needed for a clear, universally applicable, and consistent terminology to promote more effective communication across researchers, stakeholders, and policymakers. Inconsistencies in terminology stem from the exponential increase in scientific publications on the patterns and processes of biological invasions authored by experts from various disciplines and countries since the 1990s, as well as publications by legislators and policymakers focusing on practical applications, regulations, and management of resources. Aligning and standardising terminology across stakeholders remains a challenge in invasion science. Here, we review and evaluate the multiple terms used in invasion science (e.g. ‘non-native’, ‘alien’, ‘invasive’ or ‘invader’, ‘exotic’, ‘non-indigenous’, ‘naturalised’, ‘pest’) to propose a more simplified and standardised terminology. The streamlined framework we propose and translate into 28 other languages is based on the terms (i) ‘non-native’, denoting species transported beyond their natural biogeographic range, (ii) ‘established non-native’, i.e. those non-native species that have established self-sustaining populations in their new location(s) in the wild, and (iii) ‘invasive non-native’ – populations of established non-native species that have recently spread or are spreading rapidly in their invaded range actively or passively with or without human mediation. We also highlight the importance of conceptualising ‘spread’ for classifying invasiveness and ‘impact’ for management. Finally, we propose a protocol for classifying populations based on (i) dispersal mechanism, (ii) species origin, (iii) population status, and (iv) impact. Collectively and without introducing new terminology, the framework that we present aims to facilitate effective communication and collaboration in invasion science and management of non-native species

Euclid preparation: VIII. The Complete Calibration of the Colour–Redshift Relation survey: VLT/KMOS observations and data release

The Complete Calibration of the Colour–Redshift Relation survey (C3R2) is a spectroscopic effort involving ESO and Keck facilities designed specifically to empirically calibrate the galaxy colour–redshift relation – P(z|C) to the Euclid depth (iAB = 24.5) and is intimately linked to the success of upcoming Stage IV dark energy missions based on weak lensing cosmology. The aim is to build a spectroscopic calibration sample that is as representative as possible of the galaxies of the Euclid weak lensing sample. In order to minimise the number of spectroscopic observations necessary to fill the gaps in current knowledge of the P(z|C), self-organising map (SOM) representations of the galaxy colour space have been constructed. Here we present the first results of an ESO@VLT Large Programme approved in the context of C3R2, which makes use of the two VLT optical and near-infrared multi-object spectrographs, FORS2 and KMOS. This data release paper focuses on high-quality spectroscopic redshifts of high-redshift galaxies observed with the KMOS spectrograph in the near-infrared H- and K-bands. A total of 424 highly-reliable redshifts are measured in the 1.3 ≤ z ≤ 2.5 range, with total success rates of 60.7% in the H-band and 32.8% in the K-band. The newly determined redshifts fill 55% of high (mainly regions with no spectroscopic measurements) and 35% of lower (regions with low-resolution/low-quality spectroscopic measurements) priority empty SOM grid cells. We measured Hα fluxes in a 1.″2 radius aperture from the spectra of the spectroscopically confirmed galaxies and converted them into star formation rates. In addition, we performed an SED fitting analysis on the same sample in order to derive stellar masses, E(B − V), total magnitudes, and SFRs. We combine the results obtained from the spectra with those derived via SED fitting, and we show that the spectroscopic failures come from either weakly star-forming galaxies (at z   2 galaxies

Euclid preparation: VII. Forecast validation for Euclid cosmological probes

Aims: The Euclid space telescope will measure the shapes and redshifts of galaxies to reconstruct the expansion history of the Universe and the growth of cosmic structures. The estimation of the expected performance of the experiment, in terms of predicted constraints on cosmological parameters, has so far relied on various individual methodologies and numerical implementations, which were developed for different observational probes and for the combination thereof. In this paper we present validated forecasts, which combine both theoretical and observational ingredients for different cosmological probes. This work is presented to provide the community with reliable numerical codes and methods for Euclid cosmological forecasts. / Methods: We describe in detail the methods adopted for Fisher matrix forecasts, which were applied to galaxy clustering, weak lensing, and the combination thereof. We estimated the required accuracy for Euclid forecasts and outline a methodology for their development. We then compare and improve different numerical implementations, reaching uncertainties on the errors of cosmological parameters that are less than the required precision in all cases. Furthermore, we provide details on the validated implementations, some of which are made publicly available, in different programming languages, together with a reference training-set of input and output matrices for a set of specific models. These can be used by the reader to validate their own implementations if required. / Results: We present new cosmological forecasts for Euclid. We find that results depend on the specific cosmological model and remaining freedom in each setting, for example flat or non-flat spatial cosmologies, or different cuts at non-linear scales. The numerical implementations are now reliable for these settings. We present the results for an optimistic and a pessimistic choice for these types of settings. We demonstrate that the impact of cross-correlations is particularly relevant for models beyond a cosmological constant and may allow us to increase the dark energy figure of merit by at least a factor of three

MAPK pathway activation in pilocytic astrocytoma

Pilocytic astrocytoma (PA) is the most common tumor of the pediatric central nervous system (CNS). A body of research over recent years has demonstrated a key role for mitogen-activated protein kinase (MAPK) pathway signaling in the development and behavior of PAs. Several mechanisms lead to activation of this pathway in PA, mostly in a mutually exclusive manner, with constitutive BRAF kinase activation subsequent to gene fusion being the most frequent. The high specificity of this fusion to PA when compared with other CNS tumors has diagnostic utility. In addition, the frequency of alteration of this key pathway provides an opportunity for molecularly targeted therapy in this tumor. Here, we review the current knowledge on mechanisms of MAPK activation in PA and some of the downstream consequences of this activation, which are now starting to be elucidated both in vitro and in vivo, as well as clinical considerations and possible future directions

Euclid preparation: V. Predicted yield of redshift 7<z<9 quasars from the wide survey

We provide predictions of the yield of 7 < z < 9 quasars from the Euclid wide survey, updating the calculation presented in the Euclid Red Book in several ways. We account for revisions to the Euclid near-infrared filter wavelengths; we adopt steeper rates of decline of the quasar luminosity function (QLF; Φ) with redshift, Φ ∝ 10k(z−6) , k = −0.72, and a further steeper rate of decline, k = −0.92; we use better models of the contaminating populations (MLT dwarfs and compact early-type galaxies); and we make use of an improved Bayesian selection method, compared to the colour cuts used for the Red Book calculation, allowing the identification of fainter quasars, down to JAB ∼ 23. Quasars at z > 8 may be selected from Euclid OY JH photometry alone, but selection over the redshift interval 7 < z < 8 is greatly improved by the addition of z-band data from, e.g., Pan-STARRS and LSST. We calculate predicted quasar yields for the assumed values of the rate of decline of the QLF beyond z = 6. If the decline of the QLF accelerates beyond z = 6, with k = −0.92, Euclid should nevertheless find over 100 quasars with 7.0 < z < 7.5, and ∼ 25 quasars beyond the current record of z = 7.5, including ∼ 8 beyond z = 8.0. The first Euclid quasars at z > 7.5 should be found in the DR1 data release, expected in 2024. It will be possible to determine the bright-end slope of the QLF, 7 < z < 8, M1450 < −25, using 8 m class telescopes to confirm candidates, but follow-up with JWST or E-ELT will be required to measure the faint-end slope. Contamination of the candidate lists is predicted to be modest even at JAB ∼ 23. The precision with which k can be determined over 7 < z < 8 depends on the value of k, but assuming k = −0.72 it can be measured to a 1σ uncertainty of 0.07

Euclid preparation: V. Predicted yield of redshift 7 < z < 9 quasars from the wide survey

We provide predictions of the yield of 7 8 may be selected from Euclid OY JH photometry alone, but selection over the redshift interval 7 7.5 should be found in the DR1 data release, expected in 2024. It will be possible to determine the bright-end slope of the QLF, 7 < z < 8, M1450 < −25, using 8 m class telescopes to confirm candidates, but follow-up with JWST or E-ELT will be required to measure the faint-end slope. Contamination of the candidate lists is predicted to be modest even at JAB ∼ 23. The precision with which k can be determined over 7 < z < 8 depends on the value of k, but assuming k = −0.72 it can be measured to a 1σ uncertainty of 0.07

Euclid preparation: X. The Euclid photometric-redshift challenge

Forthcoming large photometric surveys for cosmology require precise and accurate photometric redshift (photo-z) measurements for the success of their main science objectives. However, to date, no method has been able to produce photo-zs at the required accuracy using only the broad-band photometry that those surveys will provide. An assessment of the strengths and weaknesses of current methods is a crucial step in the eventual development of an approach to meet this challenge. We report on the performance of 13 photometric redshift code single value redshift estimates and redshift probability distributions (PDZs) on a common set of data, focusing particularly on the 0.2−2.6 redshift range that the Euclid mission will probe. We designed a challenge using emulated Euclid data drawn from three photometric surveys of the COSMOS field. The data was divided into two samples: one calibration sample for which photometry and redshifts were provided to the participants; and the validation sample, containing only the photometry to ensure a blinded test of the methods. Participants were invited to provide a redshift single value estimate and a PDZ for each source in the validation sample, along with a rejection flag that indicates the sources they consider unfit for use in cosmological analyses. The performance of each method was assessed through a set of informative metrics, using cross-matched spectroscopic and highlyaccurate photometric redshifts as the ground truth. We show that the rejection criteria set by participants are efficient in removing strong outliers, that is to say sources for which the photo-z deviates by more than 0.15(1 + z) from the spectroscopic-redshift (spec-z). We also show that, while all methods are able to provide reliable single value estimates, several machine-learning methods do not manage to produce useful PDZs. We find that no machine-learning method provides good results in the regions of galaxy color-space that are sparsely populated by spectroscopic-redshifts, for example z > 1. However they generally perform better than template-fitting methods at low redshift (z < 0.7), indicating that template-fitting methods do not use all of the information contained in the photometry. We introduce metrics that quantify both photo-z precision and completeness of the samples (post-rejection), since both contribute to the final figure of merit of the science goals of the survey (e.g., cosmic shear from Euclid). Template-fitting methods provide the best results in these metrics, but we show that a combination of template-fitting results and machine-learning results with rejection criteria can outperform any individual method. On this basis, we argue that further work in identifying how to best select between machine-learning and template-fitting approaches for each individual galaxy should be pursued as a priority

Euclid preparation XXVIII. Forecasts for ten different higher-order weak lensing statistics

Recent cosmic shear studies have shown that higher-order statistics (HOS) developed by independent teams now outperform standard two-point estimators in terms of statistical precision thanks to their sensitivity to the non-Gaussian features of large-scale structure. The aim of the Higher-Order Weak Lensing Statistics (HOWLS) project is to assess, compare, and combine the constraining power of ten different HOS on a common set of Euclid-like mocks, derived from N-body simulations. In this first paper of the HOWLS series, we computed the nontomographic (Ωm, σ8) Fisher information for the one-point probability distribution function, peak counts, Minkowski functionals, Betti numbers, persistent homology Betti numbers and heatmap, and scattering transform coefficients, and we compare them to the shear and convergence two-point correlation functions in the absence of any systematic bias. We also include forecasts for three implementations of higher-order moments, but these cannot be robustly interpreted as the Gaussian likelihood assumption breaks down for these statistics. Taken individually, we find that each HOS outperforms the two-point statistics by a factor of around two in the precision of the forecasts with some variations across statistics and cosmological parameters. When combining all the HOS, this increases to a 4.5 times improvement, highlighting the immense potential of HOS for cosmic shear cosmological analyses with Euclid. The data used in this analysis are publicly released with the paper