Probing deviations from General Relativity with the Euclid spectroscopic survey

We discuss the ability of the planned Euclid mission to detect deviations from General Relativity using its extensive redshift survey of more than 50 Million galaxies. Constraints on the gravity theory are placed measuring the growth rate of structure within 14 redshift bins between z=0.7 and z=2. The growth rate is measured from redshift-space distortions, i.e. the anisotropy of the clustering pattern induced by coherent peculiar motions. This is performed in the overall context of the Euclid spectroscopic survey, which will simultaneously measure the expansion history of the universe, using the power spectrum and its baryonic features as a standard ruler, accounting for the relative degeneracies of expansion and growth parameters. The resulting expected errors on the growth rate in the different redshift bins, expressed through the quantity f\sigma_8, range between 1.3% and 4.4%. We discuss the optimisation of the survey configuration and investigate the important dependence on the growth parameterisation and the assumed cosmological model. We show how a specific parameterisation could actually drive the design towards artificially restricted regions of the parameter space. Finally, in the framework of the popular "\gamma -parameterisation", we show that the Euclid spectroscopic survey alone will already be able to provide substantial evidence (in Bayesian terms) if the growth index differs from the GR value \gamma=0.55 by at least \sim 0.13. This will combine with the comparable inference power provided by the Euclid weak lensing survey, resulting in Euclid's unique ability to provide a decisive test of modified gravity.Comment: 18 pages, 15 figures, accepted by MNRA

LA CULTURA PROFESIONAL DOCENTE. UN ACERCAMIENTO CONCEPTUAL

La cultura profesional docente es lo expresado en el accionar cotidiano de los docentes, directivos y estudiantes, que se mueve entre lo formalmente establecido y su concreción en la práctica. Se establece como prioridad la preparación y superación pedagógica y científica-técnica de sus docentes en la aspiración de convertir al país en una gran universidad, concibiéndola como un proceso permanente y continuo donde la formación docente es entendida como desarrollo profesional, la cual centra su atención en el profesor como sujeto de su desarrollo personal y profesional. En este artículo se presenta un análisis de la categoría cultura profesional docente desde una perspectiva histórico lógica y se pretende socializar con la comunidad científica los resultados obtenidos hasta el momento del proyecto Estrategia Pedagógica para el fomento de la cultura profesional docente en los profesores y estructuras académicas, donde se utilizaron los métodos del nivel teórico y empírico

The impact of HPV type on colposcopy performance in women offered HPV immunisation in a catch-up vaccine programme: a two centre observational study

Objective To determine if HPV immunisation has affected the prevalence of HPV genotypes and colposcopic features of CIN in young women referred for colposcopy. Design A two-centre observational study including vaccinated and unvaccinated women. Setting Colposcopy clinics serving two health regions in Scotland, UK. Population 361 women aged 20-25 years attending colposcopy following an abnormal cervical cytology result at routine cervical screening. Methods Cervical samples were obtained from women for HPV DNA genotyping and mRNA E6/E7 expression of HPV 16,18,31,33 and 45. Demographic data, cytology and histology results and colposcopic features were recorded. Chi squared analysis was conducted to identify associations between vaccine status, HPV genotypes and colposcopic features. Main outcome measures Colposcopic features, HPV genotypes, mRNA expression and cervical histology. Results The prevalence of HPV 16 was significantly lower in the vaccinated (8.6%) compared with the unvaccinated (46.7%) group (p=0.001). The number of cases of cervical intraepithelial neoplasia 2 or more (CIN2+) was significantly lower in vaccinated women (p=0.006).HPV vaccine did not have a statistically significant effect on commonly recognised colposcopic features but there was a slight reduction in the positive predictive value (PPV) of colposcopy for CIN2+ from 74% (unvaccinated) to 66.7% (vaccinated). Conclusions In this group of young women with abnormal cytology referred to colposcopy, HPV vaccination via a catch-up programme reduced the prevalence of CIN2+ and HPV 16 infection. The reduced PPV of colposcopy for the detection of CIN2+ in vaccinated women is at the lower acceptable level of the UK national cervical screening programme guidelines

An integrated methodology for assessing the impact of food matrix and gastrointestinal effects on the biokinetics and cellular toxicity of ingested engineered nanomaterials

Background Engineered nanomaterials (ENMs) are increasingly added to foods to improve their quality, sensory appeal, safety and shelf-life. Human exposure to these ingested ENMs (iENMS) is inevitable, yet little is known of their hazards. To assess potential hazards, efficient in vitro methodologies are needed to evaluate particle biokinetics and toxicity. These methodologies must account for interactions and transformations of iENMs in foods (food matrix effect) and in the gastrointestinal tract (GIT) that are likely to determine nano-biointeractions. Here we report the development and application of an integrated methodology consisting of three interconnected stages: 1) assessment of iENM-food interactions (food matrix effect) using model foods; 2) assessment of gastrointestinal transformations of the nano-enabled model foods using a three-stage GIT simulator; 3) assessment of iENMs biokinetics and cellular toxicity after exposure to simulated GIT conditions using a triculture cell model. As a case study, a model food (corn oil-in-water emulsion) was infused with Fe2O3 (Iron(III) oxide or ferric oxide) ENMs and processed using this three-stage integrated platform to study the impact of food matrix and GIT effects on nanoparticle biokinetics and cytotoxicity . Methods A corn oil in phosphate buffer emulsion was prepared using a high speed blender and high pressure homogenizer. Iron oxide ENM was dispersed in water by sonication and combined with the food model. The resulting nano-enabled food was passed through a three stage (mouth, stomach and small intestine) GIT simulator. Size distributions of nano-enabled food model and digestae at each stage were analyzed by DLS and laser diffraction. TEM and confocal imaging were used to assess morphology of digestae at each phase. Dissolution of Fe2O3 ENM along the GIT was assessed by ICP-MS analysis of supernatants and pellets following centrifugation of digestae. An in vitro transwell triculture epithelial model was used to assess biokinetics and toxicity of ingested Fe2O3 ENM. Translocation of Fe2O3 ENM was determined by ICP-MS analysis of cell lysates and basolateral compartment fluid over time. Results It was demonstrated that the interactions of iENMs with food and GIT components influenced nanoparticle fate and transport, biokinetics and toxicological profile. Large differences in particle size, charge, and morphology were observed in the model food with and without Fe2O3 and among digestae from different stages of the simulated GIT (mouth, stomach, and small intestine). Immunoflorescence and TEM imaging of the cell culture model revealed markers and morphology of small intestinal epithelium including enterocytes, goblet cells and M cells. Fe2O3 was not toxic at concentrations tested in the digesta. In biokinetics studies, translocation of Fe2O3 after 4 h was \u3c1% and ~2% for digesta with and without serum, respectively, suggesting that use of serum proteins alters iENMs biokinetics and raises concerns about commonly-used approaches that neglect iENM – food-GIT interactions or dilute digestae in serum-containing media. Conclusions We present a simple integrated methodology for studying the biokinetics and toxicology of iENMs, which takes into consideration nanoparticle-food-GIT interactions. The importance of food matrix and GIT effects on biointeractions was demonstrated, as well as the incorporation of these critical factors into a cellular toxicity screening model. Standardized food models still need to be developed and used to assess the effect of the food matrix effects on the fate and bioactivity of iENMs since commercial foods vary considerably in their compositions and structures

Disentangling molecular and clinical stratification patterns in beta-galactosidase deficiency

INTRODUCTION: This study aims to define the phenotypic and molecular spectrum of the two clinical forms of β-galactosidase (β-GAL) deficiency, GM1-gangliosidosis and mucopolysaccharidosis IVB (Morquio disease type B, MPSIVB). METHODS: Clinical and genetic data of 52 probands, 47 patients with GM1-gangliosidosis and 5 patients with MPSIVB were analysed. RESULTS: The clinical presentations in patients with GM1-gangliosidosis are consistent with a phenotypic continuum ranging from a severe antenatal form with hydrops fetalis to an adult form with an extrapyramidal syndrome. Molecular studies evidenced 47 variants located throughout the sequence of the GLB1 gene, in all exons except 7, 11 and 12. Eighteen novel variants (15 substitutions and 3 deletions) were identified. Several variants were linked specifically to early-onset GM1-gangliosidosis, late-onset GM1-gangliosidosis or MPSIVB phenotypes. This integrative molecular and clinical stratification suggests a variant-driven patient assignment to a given clinical and severity group. CONCLUSION: This study reports one of the largest series of b-GAL deficiency with an integrative patient stratification combining molecular and clinical features. This work contributes to expand the community knowledge regarding the molecular and clinical landscapes of b-GAL deficiency for a better patient management

Spatial Extent of Charge Repulsion Regulates Assembly Pathways for Lysozyme Amyloid Fibrils

Formation of large protein fibrils with a characteristic cross β-sheet architecture is the key indicator for a wide variety of systemic and neurodegenerative amyloid diseases. Recent experiments have strongly implicated oligomeric intermediates, transiently formed during fibril assembly, as critical contributors to cellular toxicity in amyloid diseases. At the same time, amyloid fibril assembly can proceed along different assembly pathways that might or might not involve such oligomeric intermediates. Elucidating the mechanisms that determine whether fibril formation proceeds along non-oligomeric or oligomeric pathways, therefore, is important not just for understanding amyloid fibril assembly at the molecular level but also for developing new targets for intervening with fibril formation. We have investigated fibril formation by hen egg white lysozyme, an enzyme for which human variants underlie non-neuropathic amyloidosis. Using a combination of static and dynamic light scattering, atomic force microscopy and circular dichroism, we find that amyloidogenic lysozyme monomers switch between three different assembly pathways: from monomeric to oligomeric fibril assembly and, eventually, disordered precipitation as the ionic strength of the solution increases. Fibril assembly only occurred under conditions of net repulsion among the amyloidogenic monomers while net attraction caused precipitation. The transition from monomeric to oligomeric fibril assembly, in turn, occurred as salt-mediated charge screening reduced repulsion among individual charged residues on the same monomer. We suggest a model of amyloid fibril formation in which repulsive charge interactions are a prerequisite for ordered fibril assembly. Furthermore, the spatial extent of non-specific charge screening selects between monomeric and oligomeric assembly pathways by affecting which subset of denatured states can form suitable intermolecular bonds and by altering the energetic and entropic requirements for the initial intermediates emerging along the monomeric vs. oligomeric assembly path

Genetic population structure of Anopheles gambiae in Equatorial Guinea

BACKGROUND: Patterns of genetic structure among mosquito vector populations in islands have received particular attention as these are considered potentially suitable sites for experimental trials on transgenic-based malaria control strategies. In this study, levels of genetic differentiation have been estimated between populations of Anopheles gambiae s.s. from the islands of Bioko and Annobón, and from continental Equatorial Guinea (EG) and Gabon. METHODS: Genotyping of 11 microsatellite loci located in chromosome 3 was performed in three island samples (two in Bioko and one in Annobón) and three mainland samples (two in EG and one in Gabon). Four samples belonged to the M molecular form and two to the S-form. Microsatellite data was used to estimate genetic diversity parameters, perform demographic equilibrium tests and analyse population differentiation. RESULTS: High levels of genetic differentiation were found between the more geographically remote island of Annobón and the continent, contrasting with the shallow differentiation between Bioko island, closest to mainland, and continental localities. In Bioko, differentiation between M and S forms was higher than that observed between island and mainland samples of the same molecular form. CONCLUSION: The observed patterns of population structure seem to be governed by the presence of both physical (the ocean) and biological (the M-S form discontinuity) barriers to gene flow. The significant degree of genetic isolation between M and S forms detected by microsatellite loci located outside the "genomic islands" of speciation identified in A. gambiae s.s. further supports the hypothesis of on-going incipient speciation within this species. The implications of these findings regarding vector control strategies are discussed

Old stones' song: Use-wear experiments and analysis of the Oldowan quartz and quartzite assemblage from Kanjera South (Kenya)

Evidence of Oldowan tools by w2.6 million years ago (Ma) may signal a major adaptive shift in hominin evolution. While tool-dependent butchery of large mammals was important by at least 2.0 Ma, the use of artifacts for tasks other than faunal processing has been difficult to diagnose. Here we report on use-wear analysis ofw2.0 Ma quartz and quartzite artifacts from Kanjera South, Kenya. A use-wear framework that links processing of specific materials and tool motions to their resultant use-wear patterns was developed. A blind test was then carried out to assess and improve the efficacy of this experimental use-wear framework, which was then applied to the analysis of 62 Oldowan artifacts from Kanjera South. Usewear on a total of 23 artifact edges was attributed to the processing of specific materials. Use-wear on seven edges (30%) was attributed to animal tissue processing,corroborating zooarchaeological evidence for butchery at the site. Use-wear on 16 edges (70%)was attributed to the processing of plant tissues, including wood, grit-covered plant tissues that we interpret asunderground storage organs (USOs), and stems of grass or sedges. These results expand our knowledge of the suite of behaviours carried out in the vicinity of Kanjera South to include the processing of materials that would be ‘invisible’ using standard archaeological methods. Wood cutting and scraping may represent the production and/or maintenance of wooden tools. Use-wear related to USO processing extends the archaeological evidence for hominin acquisition and consumption of this resource by over 1.5 Ma. Cutting of grasses, sedges or reeds may be related to a subsistence task (e.g., grass seed harvesting, cutting out papyrus culm for consumption) and/or a non-subsistence related task (e.g., production of ‘twine,’ simple carrying devices, or bedding). These results highlight the adaptive significance of lithic technology for hominins at Kanjera