Prolonged cultivation of hippocampal neural precursor cells shifts their differentiation potential and selects for aneuploid cells

Neural precursor cells (NPCs) are lineage-restricted neural stem cells with limited self-renewal, giving rise to a broad range of neural cell types such as neurons, astrocytes, and oligodendrocytes. Despite this developmental potential, the differentiation capacity of NPCs has been controversially discussed concerning the trespassing lineage boundaries, for instance resulting in hematopoietic competence. Assessing their in vitro plasticity, we isolated nestin+/Sox2+, NPCs from the adult murine hippocampus. In vitro-expanded adult NPCs were able to form neurospheres, self-renew, and differentiate into neuronal, astrocytic, and oligodendrocytic cells. Although NPCs cultivated in early passage efficiently gave rise to neuronal cells in a directed differentiation assay, extensively cultivated NPCs revealed reduced potential for ectodermal differentiation. We further observed successful differentiation of long-term cultured NPCs into osteogenic and adipogenic cell types, suggesting that NPCs underwent a fate switch during culture. NPCs cultivated for more than 12 passages were aneuploid (abnormal chromosome numbers such as 70 chromosomes). Furthermore, they showed growth factor-independent proliferation, a hallmark of tumorigenic transformation. In conclusion, our findings substantiate the lineage restriction of NPCs from adult mammalian hippocampus. Prolonged cultivation results, however, in enhanced differentiation potential, which may be attributed to transformation events leading to aneuploid cells.

Estimation of Gaussian process regression model using probability distance measures

A new class of parameter estimation algorithms is introduced for Gaussian process regression (GPR) models. It is shown that the integration of the GPR model with probability distance measures of (i) the integrated square error and (ii) Kullback–Leibler (K–L) divergence are analytically tractable. An efficient coordinate descent algorithm is proposed to iteratively estimate the kernel width using golden section search which includes a fast gradient descent algorithm as an inner loop to estimate the noise variance. Numerical examples are included to demonstrate the effectiveness of the new identification approaches.

The equivalent-weights particle filter in a high-dimensional system

In general, particle filters need large numbers of model runs in order to avoid filter degeneracy in high-dimensional systems. The recently proposed, fully nonlinear equivalent-weights particle filter overcomes this requirement by replacing the standard model transition density with two different proposal transition densities. The first proposal density is used to relax all particles towards the high-probability regions of state space as defined by the observations. The crucial second proposal density is then used to ensure that the majority of particles have equivalent weights at observation time. Here, the performance of the scheme in a high, 65 500 dimensional, simplified ocean model is explored. The success of the equivalent-weights particle filter in matching the true model state is shown using the mean of just 32 particles in twin experiments. It is of particular significance that this remains true even as the number and spatial variability of the observations are changed. The results from rank histograms are less easy to interpret and can be influenced considerably by the parameter values used. This article also explores the sensitivity of the performance of the scheme to the chosen parameter values and the effect of using different model error parameters in the truth compared with the ensemble model runs.

Food geographies I: relational foodscapes and the busy-ness of being more-than-food

The study of foodscapes has spread throughout geography at the same time as food scholarship has spearheaded post-disciplinary research. This report argues that geographers have taken to post-disciplinarity to explore the ways that food is ‘more-than-food’ through analyses of the visceral nature of eating and politics and the vital (re)materializations of food’s cultural geographies. Visceral food geographies illuminate what I call the ‘contingent relationalities’ of food in the critical evaluation of the indeterminate, situated politics of ‘feeling food’ and those of the embodied collectivities of obesity. Questions remain, however, about how a visceral framework might be deployed for broader critiques within foodscapes and the study of human geography. The study of food’s vital materialisms opens up investigation into the practices of the ‘makings’ of meat, food waste and eating networks. Analysis of affect, embodiment and cultural practices is central to these theorizations and suggests consideration of the multiple materialisms of food, space and eating. There is, I contend, in the more radical, ‘post-relational’ approaches to food, the need for a note of caution. Exuberant claims for the ontological, vital agency of food should be tempered by, or at least run parallel to, critical questions of the real politik of political and practical agency in light of recent struggles over austerity, food poverty and food justice.

Syntactic complexity in the comprehension of wh-questions and relative clauses in typical language development and autism

This study investigates effects of syntactic complexity operationalised in terms of movement, intervention and (NP) feature similarity in the development of A’ dependencies in 4-, 6-, and 8-year old typically developing (TD) French children and children with Autism Spectrum Disorders (ASD). Children completed an off-line comprehension task testing eight syntactic structures classified in four levels of complexity: Level 0: No Movement; Level 1: Movement without (configurational) Intervention; Level 2: Movement with Intervention from an element which is maximally different or featurally ‘disjoint’ (mismatched in both lexical NP restriction and number); Level 3: Movement with Intervention from an element similar in one feature or featurally ‘intersecting’ (matched in lexical NP restriction, mismatched in number). The results show that syntactic complexity affects TD children across the three age groups, but also indicate developmental differences between these groups. Movement affected all three groups in a similar way, but intervention effects in intersection cases were stronger in younger than older children, with NP feature similarity affecting only 4-year olds. Complexity effects created by the similarity in lexical restriction of an intervener thus appear to be overcome early in development, arguably thanks to other differences of this intervener (which was mismatched in number). Children with ASD performed less well than the TD children although they were matched on non-verbal reasoning. Overall, syntactic complexity affected their performance in a similar way as in their TD controls, but their performance correlated with non-verbal abilities rather than age, suggesting that their grammatical development does not follow the smooth relation to age that is found in TD children.