Cerebrospinal fluid and the early brain development of autism

Abstract Background There is currently a renaissance of interest in the many functions of cerebrospinal fluid (CSF). Altered flow of CSF, for example, has been shown to impair the clearance of pathogenic inflammatory proteins involved in neurodegenerative diseases, such as amyloid-β. In addition, the role of CSF in the newly discovered lymphatic system of the brain has become a prominently researched area in clinical neuroscience, as CSF serves as a conduit between the central nervous system and immune system. Main body This article will review the importance of CSF in regulating normal brain development and function, from the prenatal period throughout the lifespan, and highlight recent research that CSF abnormalities in autism spectrum disorder (ASD) are present in infancy, are detectable by conventional structural MRI, and could serve as an early indicator of altered neurodevelopment. Conclusion The identification of early CSF abnormalities in children with ASD, along with emerging knowledge of the underlying pathogenic mechanisms, has the potential to serve as early stratification biomarkers that separate children with ASD into biological subtypes that share a common pathophysiology. Such subtypes could help parse the phenotypic heterogeneity of ASD and map on to targeted, biologically based treatments

Generalized Rosenfeld scalings for tracer diffusivities in not-so-simple fluids: Mixtures and soft particles

Rosenfeld [Phys. Rev. A 15, 2545 (1977)] noticed that casting transport coefficients of simple monatomic, equilibrium fluids in specific dimensionless forms makes them approximately single-valued functions of excess entropy. This has predictive value because, while the transport coefficients of dense fluids are difficult to estimate from first principles, excess entropy can often be accurately predicted from liquid-state theory. Here, we use molecular simulations to investigate whether Rosenfeld's observation is a special case of a more general scaling law relating mobility of particles in mixtures to excess entropy. Specifically, we study tracer diffusivities, static structure, and thermodynamic properties of a variety of one- and two-component model fluid systems with either additive or non-additive interactions of the hard-sphere or Gaussian-core form. The results of the simulations demonstrate that the effects of mixture concentration and composition, particle-size asymmetry and additivity, and strength of the interparticle interactions in these fluids are consistent with an empirical scaling law relating the excess entropy to a new dimensionless (generalized Rosenfeld) form of tracer diffusivity, which we introduce here. The dimensionless form of the tracer diffusivity follows from knowledge of the intermolecular potential and the transport / thermodynamic behavior of fluids in the dilute limit. The generalized Rosenfeld scaling requires less information, and provides more accurate predictions, than either Enskog theory or scalings based on the pair-correlation contribution to the excess entropy. As we show, however, it also suffers from some limitations, especially for systems that exhibit significant decoupling of individual component tracer diffusivities.Comment: 15 pages, 10 figure

Nuclear fusion during yeast mating occurs by a three-step pathway

In Saccharomyces cerevisiae, mating culminates in nuclear fusion to produce a diploid zygote. Two models for nuclear fusion have been proposed: a one-step model in which the outer and inner nuclear membranes and the spindle pole bodies (SPBs) fuse simultaneously and a three-step model in which the three events occur separately. To differentiate between these models, we used electron tomography and time-lapse light microscopy of early stage wild-type zygotes. We observe two distinct SPBs in ∼80% of zygotes that contain fused nuclei, whereas we only see fused or partially fused SPBs in zygotes in which the site of nuclear envelope (NE) fusion is already dilated. This demonstrates that SPB fusion occurs after NE fusion. Time-lapse microscopy of zygotes containing fluorescent protein tags that localize to either the NE lumen or the nucleoplasm demonstrates that outer membrane fusion precedes inner membrane fusion. We conclude that nuclear fusion occurs by a three-step pathway

Carrier capture dynamics of single InGaAs/GaAs quantum-dot layers

Using 800nm, 25-fs pulses from a mode locked Ti:Al2O3 laser, we have measured the ultrafast optical reflectivity of MBE-grown, single-layer In0.4Ga0.6As/GaAs quantum-dot (QD) samples. The QDs are formed via two-stage Stranski-Krastanov growth: following initial InGaAs deposition at a relatively low temperature, self assembly of the QDs occurs during a subsequent higher temperature anneal. The capture times for free carriers excited in the surrounding GaAs (barrier layer) are as short as 140fs, indicating capture efficiencies for the InGaAs quantum layer approaching 1. The capture rates are positively correlated with initial InGaAs thickness and annealing temperature. With increasing excited carrier density, the capture rate decreases; this slowing of the dynamics is attributed to Pauli state blocking within the InGaAs quantum layer

Isothiourea-catalysed regioselective acylative kinetic resolution of axially chiral biaryl diols

The research leading to these results has received funding from the ERC under the European Union's Seventh Framework Programme (FP7/2007-2013)/E.R.C. grant agreement n° 279850. The Chinese Scholarship Scheme and University of St Andrews are thanked for a CSC Scholarship (S.Q.). A.D.S. thanks the Royal Society for a Wolfson Research Merit Award.An operationally‐simple isothiourea‐catalyzed acylative kinetic resolution of unprotected 1,1′‐biaryl‐2,2′‐diol derivatives has been developed to allow access to axially chiral compounds in highly enantioenriched form (s values up to 190). Investigation of the reaction scope and limitations provided three key observations: i) the diol motif of the substrate was essential for good conversion and high s values; ii) the use of an α,α‐disubstituted mixed anhydride (2,2‐diphenylacetic pivalic anhydride) was critical to minimize diacylation and give high selectivity; iii) the presence of substituents in the 3,3′‐positions of the diol hindered effective acylation. This final observation was exploited for the highly regioselective acylative kinetic resolution of unsymmetrical biaryl diol substrates bearing a single 3‐substituent. Based on the key observations identified, acylation transition state models have been proposed to explain the atropselectivity of this kinetic resolution.PostprintPeer reviewe