How large are departures from lithostatic pressure? Constraints from host-inclusion elasticity

Minerals trapped as inclusions within other host minerals will develop non-lithostatic pressures during both prograde and retrograde metamorphism because of the differences between the thermo-elastic properties of the host and inclusion phases. There is only a single possible path in P-T space, the entrapment isomeke, along which no residual pressure would be developed in a host/inclusion system; non-lithostatic pressures are developed in inclusions as a result of the external pressure and temperature deviating from the isomeke that passes through the entrapment conditions. With modern equation of state and elasticity data for minerals now available it is possible to perform precise calculations of the isomekes for mineral pairs. These show that isomeke lines are not straight lines in P-T space at metamorphic conditions. We show that silicate inclusions in silicate hosts tend to have flat isomekes, with small values of dP/dT(isomeke), because of the small range of thermal expansion coefficients of silicate minerals. As a consequence, the general behaviour under decompression is for soft silicate inclusions in stiffer hosts to develop excess pressures, whereas a stiff silicate inclusion in a softer matrix will experience lower pressures than lithostatic pressure. The opposite effects occur for compression after entrapment on the prograde path. The excess pressures in inclusions, including allowance for mutual elastic relaxation of the host and inclusion, are most easily calculated by using the isomeke as a basis. Analysis of the simplest possible model of a host-inclusion system indicates that deviations from lithostatic pressure in excess of 1 GPa can be readily produced in quartz inclusions within garnets in metamorphic rocks. For softer host minerals such as feldspars the pressure deviations are smaller, because of greater elastic relaxation of the host. The maximum pressure deviation from lithostatic pressure in the host phase around the inclusion is one-third of the pressure deviation in the inclusion. Routines for performing these calculations have been added to the EosFit7c software package

Reversal of contractility as a signature of self-organization in cytoskeletal bundles.

Funder: FP7 People: Marie-Curie Actions; FundRef: http://dx.doi.org/10.13039/100011264; Grant(s): PCIG12-GA-2012-334053Bundles of cytoskeletal filaments and molecular motors generate motion in living cells, and have internal structures ranging from very organized to apparently disordered. The mechanisms powering the disordered structures are debated, and existing models predominantly predict that they are contractile. We reexamine this prediction through a theoretical treatment of the interplay between three well-characterized internal dynamical processes in cytoskeletal bundles: filament assembly and disassembly, the attachement-detachment dynamics of motors and that of crosslinking proteins. The resulting self-organization is easily understood in terms of motor and crosslink localization, and allows for an extensive control of the active bundle mechanics, including reversals of the filaments' apparent velocities and the possibility of generating extension instead of contraction. This reversal mirrors some recent experimental observations, and provides a robust criterion to experimentally elucidate the underpinnings of both actomyosin activity and the dynamics of microtubule/motor assemblies in vitro as well as in diverse intracellular structures ranging from contractile bundles to the mitotic spindle

Getting the whole picture: High content screening using three-dimensional cellular model systems and whole animal assays

Phenotypic or High Content Screening (HCS) is becoming more widely used for primary screening campaigns in drug discovery. Currently the vast majority of HCS campaigns are using cell lines grown in well-established monolayer cultures (2D tissue culture). There is widespread recognition that the more biologically relevant 3D tissue culture technologies such as spheroids and organoids and even whole animal assays will eventually be run as primary HCS. Upgrading the IT infrastructure to cope with the increase in data volumes requires investments in hardware (and software) and this will be manageable. However, the main bottleneck for the effective adoption and use of 3D tissue culture and whole animal assays in HCS is anticipated to be the development of software for the analysis of 3D images. In this review we summarize the current state of the available software and how they may be applied to analyzing 3D images obtained from a HCS campaign

Modelling the Genetic Risk in Age-Related Macular Degeneration

Late-stage age-related macular degeneration (AMD) is a common sight-threatening disease of the central retina affecting approximately 1 in 30 Caucasians. Besides age and smoking, genetic variants from several gene loci have reproducibly been associated with this condition and likely explain a large proportion of disease. Here, we developed a genetic risk score (GRS) for AMD based on 13 risk variants from eight gene loci. The model exhibited good discriminative accuracy, area-under-curve (AUC) of the receiver-operating characteristic of 0.820, which was confirmed in a cross-validation approach. Noteworthy, younger AMD patients aged below 75 had a significantly higher mean GRS (1.87, 95% CI: 1.69–2.05) than patients aged 75 and above (1.45, 95% CI: 1.36–1.54). Based on five equally sized GRS intervals, we present a risk classification with a relative AMD risk of 64.0 (95% CI: 14.11–1131.96) for individuals in the highest category (GRS 3.44–5.18, 0.5% of the general population) compared to subjects with the most common genetic background (GRS −0.05–1.70, 40.2% of general population). The highest GRS category identifies AMD patients with a sensitivity of 7.9% and a specificity of 99.9% when compared to the four lower categories. Modeling a general population around 85 years of age, 87.4% of individuals in the highest GRS category would be expected to develop AMD by that age. In contrast, only 2.2% of individuals in the two lowest GRS categories which represent almost 50% of the general population are expected to manifest AMD. Our findings underscore the large proportion of AMD cases explained by genetics particularly for younger AMD patients. The five-category risk classification could be useful for therapeutic stratification or for diagnostic testing purposes once preventive treatment is available

Dark energy survey year-1 results: galaxy mock catalogues for BAO

CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFINEP - FINANCIADORA DE ESTUDOS E PROJETOSFAPERJ - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DO RIO DE JANEIROMCTIC - MINISTÉRIO DA CIÊNCIA, TECNOLOGIA, INOVAÇÕES E COMUNICAÇÕESMock catalogues are a crucial tool in the analysis of galaxy surveys data, both for the accurate computation of covariance matrices, and for the optimization of analysis methodology and validation of data sets. In this paper, we present a set of 1800 galaxy mock catalogues designed to match the Dark Energy Survey Year-1 BAO sample (Crocce et al. 2017) in abundance, observational volume, redshift distribution and uncertainty, and redshift-dependent clustering. The simulated samples were built upon HALOGEN (Avila et al. 2015) halo catalogues, based on a 2LPTdensity field with an empirical halo bias, For each of them, a light-cone is constructed by the superposition of snapshots in the redshift range 0.45 < z < 1.4. Uncertainties introduced by so-called photometric redshifts estimators were modelled with a double-skewed-Gaussian curve fitted to the data. We populate haloes with galaxies by introducing a hybrid halo occupation distribution-halo abundance matching model with two free parameters. These are adjusted to achieve a galaxy bias evolution b(z(ph)) that matches the data at the 1 sigma level in the range 0.6 < z(ph) < 1.0. We further analyse the galaxy mock catalogues and compare their clustering to the data using the angular correlation function w(theta), the comoving transverse separation clustering xi(mu < 0.8)(S-perpendicular to) and the angular power spectrum C-l, finding them in agreement. This is the first large set of three-dimensional {RA,Dec.,z} galaxy mock catalogues able to simultaneously accurately reproduce the photometric redshift uncertainties and the galaxy clustering.479194110CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFINEP - FINANCIADORA DE ESTUDOS E PROJETOSFAPERJ - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DO RIO DE JANEIROMCTIC - MINISTÉRIO DA CIÊNCIA, TECNOLOGIA, INOVAÇÕES E COMUNICAÇÕESCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFINEP - FINANCIADORA DE ESTUDOS E PROJETOSFAPERJ - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DO RIO DE JANEIROMCTIC - MINISTÉRIO DA CIÊNCIA, TECNOLOGIA, INOVAÇÕES E COMUNICAÇÕES465376/2014-2Sem informaçãoSem informaçãoSem informaçãoSem informaçãoAgências de fomento estrangeiras apoiaram essa pesquisa, mais informações acesse artig

Cell-Autonomous Requirement for Rx Function in the Mammalian Retina and Posterior Pituitary

Rx is a paired-like homeobox gene that is required for vertebrate eye formation. Mice lacking Rx function do not develop eyes or the posterior pituitary. To determine whether Rx is required cell autonomously in these tissues, we generated embryonic chimeras consisting of wild type and Rx−/− cells. We found that in the eye, Rx-deficient cells cannot participate in the formation of the neuroretina, retina pigment epithelium and the distal part of the optic stalk. In addition, in the ventral forebrain, Rx function is required cell autonomously for the formation of the posterior pituitary. Interestingly, Rx−/− and wild type cells segregate before the morphogenesis of these two tissues begins. Our observations suggest that Rx function is not only required for the morphogenesis of the retina and posterior pituitary, but also prior to morphogenesis, for the sorting out of cells to form distinct fields of retinal/pituitary cells