Modeling the functional genomics of autism using human neurons.

Human neural progenitors from a variety of sources present new opportunities to model aspects of human neuropsychiatric disease in vitro. Such in vitro models provide the advantages of a human genetic background combined with rapid and easy manipulation, making them highly useful adjuncts to animal models. Here, we examined whether a human neuronal culture system could be utilized to assess the transcriptional program involved in human neural differentiation and to model some of the molecular features of a neurodevelopmental disorder, such as autism. Primary normal human neuronal progenitors (NHNPs) were differentiated into a post-mitotic neuronal state through addition of specific growth factors and whole-genome gene expression was examined throughout a time course of neuronal differentiation. After 4 weeks of differentiation, a significant number of genes associated with autism spectrum disorders (ASDs) are either induced or repressed. This includes the ASD susceptibility gene neurexin 1, which showed a distinct pattern from neurexin 3 in vitro, and which we validated in vivo in fetal human brain. Using weighted gene co-expression network analysis, we visualized the network structure of transcriptional regulation, demonstrating via this unbiased analysis that a significant number of ASD candidate genes are coordinately regulated during the differentiation process. As NHNPs are genetically tractable and manipulable, they can be used to study both the effects of mutations in multiple ASD candidate genes on neuronal differentiation and gene expression in combination with the effects of potential therapeutic molecules. These data also provide a step towards better understanding of the signaling pathways disrupted in ASD

AdS_7/CFT_6, Gauss-Bonnet Gravity, and Viscosity Bound

We study the relation between the causality and the positivity of energy bounds in Gauss-Bonnet gravity in AdS_7 background and find a precise agreement. Requiring the group velocity of metastable states to be bounded by the speed of light places a bound on the value of Gauss-Bonnet coupling. To find the positivity of energy constraints we compute the parameters which determine the angular distribution of the energy flux in terms of three independent coefficients specifying the three-point function of the stress-energy tensor. We then relate the latter to the Weyl anomaly of the six-dimensional CFT and compute the anomaly holographically. The resulting upper bound on the Gauss-Bonnet coupling coincides with that from causality and results in a new bound on viscosity/entropy ratio.Comment: 21 page, harvmac; v2: reference adde

Causality constraints in AdS/CFT from conformal collider physics and Gauss-Bonnet gravity

We explore the relation between positivity of the energy constraints in conformal field theories and causality in their dual gravity description. Our discussion involves CFTs with different central charges whose description, in the gravity side, requires the inclusion of quadratic curvature corrections. It is enough, indeed, to consider the Gauss-Bonnet term. We find that both sides of the AdS/CFT correspondence impose a restriction on the Gauss-Bonnet coupling. In the case of 6d supersymmetric CFTs, we show the full matching of these restrictions. We perform this computation in two ways. First by considering a thermal setup in a black hole background. Second by scrutinizing the scattering of gravitons with a shock wave in AdS. The different helicities provide the corresponding lower and upper bounds. We generalize these results to arbitrary higher dimensions and comment on some hints and puzzles they prompt regarding the possible existence of higher dimensional CFTs and the extent to which the AdS/CFT correspondence would be valid for them.Comment: 31 pages, 5 figures; v2: typos fixed, cosmetic amendments and references adde

Holographic GB gravity in arbitrary dimensions

We study the properties of the holographic CFT dual to Gauss-Bonnet gravity in general $D \ge 5$ dimensions. We establish the AdS/CFT dictionary and in particular relate the couplings of the gravitational theory to the universal couplings arising in correlators of the stress tensor of the dual CFT. This allows us to examine constraints on the gravitational couplings by demanding consistency of the CFT. In particular, one can demand positive energy fluxes in scattering processes or the causal propagation of fluctuations. We also examine the holographic hydrodynamics, commenting on the shear viscosity as well as the relaxation time. The latter allows us to consider causality constraints arising from the second-order truncated theory of hydrodynamics.Comment: 48 pages, 9 figures. v2: New discussion on free fields in subsection 3.3 and new appendix B on conformal tensor fields. Added comments on the relation between the central charge appearing in the two-point function and the "central charge" characterizing the entropy density in the discussion. References adde

Holographic studies of quasi-topological gravity

Quasi-topological gravity is a new gravitational theory including curvature-cubed interactions and for which exact black hole solutions were constructed. In a holographic framework, classical quasi-topological gravity can be thought to be dual to the large $N_c$ limit of some non-supersymmetric but conformal gauge theory. We establish various elements of the AdS/CFT dictionary for this duality. This allows us to infer physical constraints on the couplings in the gravitational theory. Further we use holography to investigate hydrodynamic aspects of the dual gauge theory. In particular, we find that the minimum value of the shear-viscosity-to-entropy-density ratio for this model is $\eta/s \simeq 0.4140/(4\pi)$.Comment: 45 pages, 6 figures. v2: References adde

Black Holes in Quasi-topological Gravity

We construct a new gravitational action which includes cubic curvature interactions and which provides a useful toy model for the holographic study of a three parameter family of four- and higher-dimensional CFT's. We also investigate the black hole solutions of this new gravity theory. Further we examine the equations of motion of quasi-topological gravity. While the full equations in a general background are fourth-order in derivatives, we show that the linearized equations describing gravitons propagating in the AdS vacua match precisely the second-order equations of Einstein gravity.Comment: 33 pages, 4 figures; two references adde

The impact of proxy selection strategies on a millennium-long ensemble of hydroclimatic records in Monsoon Asia

Large-scale palaeoclimate reconstructions can be very sensitive to the proxy records they are based on, and hence to the criteria used to select proxy records. Data selection rarely follows objective criteria that are applicable to all types of proxies, including both low- and high-resolution records. Thus, there is a need for a uniform and transparent approach to assess the suitability of input proxy data for a reconstruction. Here, we develop classification criteria that are applicable to multiple proxy types and evaluate different selection strategies using a network of 62 millennium-long terrestrial hydroclimate proxy records from Monsoon Asia. Our results reveal that robust evidence for a coherent climate signal and high dating accuracy are important criteria for benchmarking the suitability of each proxy record. We determine these criteria by reviewing the literature for each record (rather than screening against instrumental data). We show that the proposed selection approach can yield a network with a stronger common signal. By evaluating the uncertainty and centennial variability of composite reconstructions, from differently selected subsets of the proxy network, it appears beneficial to use suitable proxies stemming from different archives, as well as having a dense network of proxy sites. We suggest that future large-scale palaeoclimate reconstructions might be improved by evaluating proxy networks according to the universal categories presented here and, if indicated, removing less suitable records. This will strengthen the climate signal in the final reconstruction, allowing more precise inferences about past climate variability and more robust comparisons with climate model simulations

Apparent diffusion coefficient restriction in the white matter: going beyond acute brain territorial ischemia

BACKGROUND: Reduction of apparent diffusion coefficient (ADC) values in white matter is not always ischaemic in nature. METHODS: We retrospectively analysed our MRI records featuring reduced ADC values in the centrum semiovale without grey matter involvement or significant vasogenic oedema. RESULTS: Several conditions showed the aforementioned MR findings: moose-horn lesions on coronal images in X-linked Charcot-Marie-Tooth disease; small fronto-parietal lesions in Menkes disease; marked signal abnormalities in the myelinised regions in the acute neonatal form of maple syrup urine disease; strip-like involvement of the corpus callosum in glutaric aciduria type 1; persistent periventricular parieto-occipital abnormalities in phenylketonuria; diffuse signal abnormalities with necrotic evolution in global cerebral anoxia or after heroin vapour inhalation; almost completely reversible symmetric fronto-parietal lesions in methotrexate neurotoxicity; chain-like lesions in watershed ischaemia; splenium involvement that normalises in reversible splenial lesions or leads to gliosis in diffuse axonal injury. CONCLUSION: Neuroradiologists must be familiar with these features, thereby preventing misdiagnosis and inappropriate management

Comments on Holographic Entanglement Entropy and RG Flows

Using holographic entanglement entropy for strip geometry, we construct a candidate for a c-function in arbitrary dimensions. For holographic theories dual to Einstein gravity, this c-function is shown to decrease monotonically along RG flows. A sufficient condition required for this monotonic flow is that the stress tensor of the matter fields driving the holographic RG flow must satisfy the null energy condition over the holographic surface used to calculate the entanglement entropy. In the case where the bulk theory is described by Gauss-Bonnet gravity, the latter condition alone is not sufficient to establish the monotonic flow of the c-function. We also observe that for certain holographic RG flows, the entanglement entropy undergoes a 'phase transition' as the size of the system grows and as a result, evolution of the c-function may exhibit a discontinuous drop.Comment: References adde

Obesity and nutrition behaviours in Western and Palestinian outpatients with severe mental illness

Extent: 7p.Background: While people with severe mental illness have been found to be more overweight and obese in Western nations, it is unknown to what extent this occurs in Middle Eastern nations and which eating behaviours contribute to obesity in Middle Eastern nations. Method: A total of 665 responses were obtained from patients with serious mental illness attending out-patient clinics in Western developed countries (Germany, UK and Australia; n = 518) and Palestine (n = 147). Patients were evaluated by ICD-10 clinical diagnosis, anthropometric measurements and completed a self-report measure of frequencies of consuming different food items and reasons for eating. Nutritional habits were compared against a Western normative group. Results: More participants from Palestine were overweight or obese (62%) compared to Western countries (47%). In the Western sample, obese patients reported consuming more low-fat products (OR 2.54, 95% CI 1.02-6.33) but also greater eating due to negative emotions (OR 1.84, 95% CI 1.31-2.60) than patients with a healthy body-mass index. In contrast, obese patients from Palestine reported increased consumption of unhealthy snacks (OR 3.73 95% CI 1.16-12.00). Conclusion: Patients with mental illness have poorer nutritional habits than the general population, particularly in Western nations. Separate interventions to improve nutritional habits and reduce obesity are warranted between Western nations and Palestine.David Jakabek, Frances Quirk, Martin Driessen, Yousef Aljeesh and Bernhard T Baun