Translational outcomes in a full gene deletion of ubiquitin protein ligase E3A rat model of Angelman syndrome.

Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by developmental delay, impaired communication, motor deficits and ataxia, intellectual disabilities, microcephaly, and seizures. The genetic cause of AS is the loss of expression of UBE3A (ubiquitin protein ligase E6-AP) in the brain, typically due to a deletion of the maternal 15q11-q13 region. Previous studies have been performed using a mouse model with a deletion of a single exon of Ube3a. Since three splice variants of Ube3a exist, this has led to a lack of consistent reports and the theory that perhaps not all mouse studies were assessing the effects of an absence of all functional UBE3A. Herein, we report the generation and functional characterization of a novel model of Angelman syndrome by deleting the entire Ube3a gene in the rat. We validated that this resulted in the first comprehensive gene deletion rodent model. Ultrasonic vocalizations from newborn Ube3am-/p+ were reduced in the maternal inherited deletion group with no observable change in the Ube3am+/p- paternal transmission cohort. We also discovered Ube3am-/p+ exhibited delayed reflex development, motor deficits in rearing and fine motor skills, aberrant social communication, and impaired touchscreen learning and memory in young adults. These behavioral deficits were large in effect size and easily apparent in the larger rodent species. Low social communication was detected using a playback task that is unique to rats. Structural imaging illustrated decreased brain volume in Ube3am-/p+ and a variety of intriguing neuroanatomical phenotypes while Ube3am+/p- did not exhibit altered neuroanatomy. Our report identifies, for the first time, unique AS relevant functional phenotypes and anatomical markers as preclinical outcomes to test various strategies for gene and molecular therapies in AS

The importance of parameter choice in modelling dynamics of the eye lens

The lens provides refractive power to the eye and is capable of altering ocular focus in response to visual demand. This capacity diminishes with age. Current biomedical technologies, which seek to design an implant lens capable of replicating the function of the biological lens, are unable as yet to provide such an implant with the requisite optical quality or ability to change the focussing power of the eye. This is because the mechanism of altering focus, termed accommodation, is not fully understood and seemingly conflicting theories require experimental support which is difficult to obtain from the living eye. This investigation presents finite element models of the eye lens based on data from human lenses aged 16 and 35 years that consider the influence of various modelling parameters, including material properties, a wide range of angles of force application and capsular thickness. Results from axisymmetric models show that the anterior and posterior zonules may have a greater impact on shape change than the equatorial zonule and that choice of capsular thickness values can influence the results from modelled simulations

Resonant Thermoelectric Nanophotonics

Photodetectors are typically based either on photocurrent generation from electron–hole pairs in semiconductor structures or on bolometry for wavelengths that are below bandgap absorption. In both cases, resonant plasmonic and nanophotonic structures have been successfully used to enhance performance. Here, we show subwavelength thermoelectric nanostructures designed for resonant spectrally selective absorption, which creates large localized temperature gradients even with unfocused, spatially uniform illumination to generate a thermoelectric voltage. We show that such structures are tunable and are capable of wavelength-specific detection, with an input power responsivity of up to 38 V W^(–1), referenced to incident illumination, and bandwidth of nearly 3 kHz. This is obtained by combining resonant absorption and thermoelectric junctions within a single suspended membrane nanostructure, yielding a bandgap-independent photodetection mechanism. We report results for both bismuth telluride/antimony telluride and chromel/alumel structures as examples of a potentially broader class of resonant nanophotonic thermoelectric materials for optoelectronic applications such as non-bandgap-limited hyperspectral and broadband photodetectors

Challenges in the association of human single nucleotide polymorphism mentions with unique database identifiers

Thomas PE, Klinger R, Furlong LI, Hofmann-Apitius M, Friedrich CM. Challenges in the association of human single nucleotide polymorphism mentions with unique database identifiers. BMC Bioinformatics. 2011;12(Suppl 4): S4