Emotion recognition deficits in pediatric anxiety disorders: implications for amygdala research

INTRODUCTION: Anxiety disorders in adults involve aberrant processing of emotional information that is hypothesized to reflect perturbations in the amygdala. This study examines the relationship between face-emotion recognition and anxiety in a sample of children and adolescents participating in a brain-imaging study of amygdala structure and function. METHODS: This study recruited 15 children and adolescents with ongoing anxiety disorders and 11 psychiatrically healthy comparisons group-matched on age, gender, and IQ. Face-emotion recognition was assessed using the Diagnostic Analysis of Nonverbal Accuracy Scale (DANVA). RESULTS: Children and adolescents with anxiety disorders exhibited significantly poorer performance on the face-emotion recognition task compared to healthy controls (z = 2.2; p < 0.05). This difference was found only for expressions posed by adults but not children. Discussion: Reduced accuracy on a face-emotion recognition test is consistent with perturbed amygdala function in pediatric anxiety disorders. CONCLUSION: As this study was conducted in a sample undergoing a neuroimaging investigation of amygdala integrity, future analyses will examine associations among amygdala function, clinical anxiety, and face-recognition abilities.     

Quercetin,an Over-the-Counter Supplement,Causes Neuroblastoma-like Elevation of Plasma Homovanillic Acid

A 22-month-old boy, who regularly consumed the oral dietary supplement, quercetin, was suspected erroneously of having a catecholamine-producing tumor, based on elevated serum and urine levels of the dopamine metabolite, homovanillic acid (HVA). Subsequent studies of healthy adult volunteers showed that significant elevations in plasma HVA are a consequence of quercetin ingestion.     

Further evidence that chick eyes use the sign of blur in spectacle lens compensation

Young animals compensate for defocus imposed by positive or negative spectacle lenses by adjusting the elongation rate of their vitreous chambers, thus matching the length of the eye with the focal length of the eye's optics combined with the spectacle lenses. The ability to compensate for either negative or positive lenses could rely on the ability to distinguish between myopic and hyperopic blur, or it could rely on the fact that positive lenses would bring nearby objects into focus, thereby reducing the amount of blur, whereas negative lenses would not. This study asks whether eyes emmetropize using the magnitude of blur or the sign of blur as a directional cue. We fitted chick eyes with positive lenses while imposing a substantial amount of blur, either (a) by having them wear lenses only when restrained in the center of a cylinder, the walls of which were beyond their far-point or (b) by having them wear mild diffusers over positive lenses. We found good refractive compensation in both situations in a large number of birds. Furthermore, we found that mild diffusers worn on top of positive lenses differentially affected the two ocular components of refractive compensation: there was less choroidal thickening, but more inhibition of ocular elongation, compared to wearing positive lenses alone. These findings argue both that the eye can discern the sign of the blur and that choroidal and ocular-elongation components of the refractive compensation do not respond identically to visual inputs.     

Potency of myopic defocus in spectacle lens compensation

PURPOSE: Previous studies have shown that chick eyes compensate for positive or negative lenses worn for brief periods if the chicks are in darkness the remainder of the time. This study was undertaken to determine whether chicks can compensate for brief periods of lens wear if given unrestricted vision the remainder of the time. Previous studies have also shown that chick eyes alternately wearing positive and negative lenses for brief periods compensate for the positive lenses. The current study sought to determine whether brief periods of positive lens wear can outweigh daylong wearing of negative lenses. METHODS: Chicks wore +6 D or +10 D lenses for between 8 and 60 min/d, in two to six periods and wore either no lenses or negative lenses for the remainder of the 12-hour daylight period. Refraction and ultrasound biometry were performed before and after the 3-day-long experiments. RESULTS: Wearing positive lenses for as little as 12 min/d (six periods of 2 minutes) with unrestricted vision the remainder of the time caused eyes to become hyperopic and reduced the rate of ocular elongation. These effects also occurred when the scene viewed was beyond the far point of the lens-wearing eye and thus was myopically blurred. Even when chicks wore negative lenses for the entire day except for 8 minutes of wearing positive lenses, the eyes compensated for the positive lenses, as though the negative lenses had not been worn. When chicks wore binocular negative lenses for the entire day except for 8 minutes of wearing a positive lens on one eye and a plano lens on the other, the eye wearing the positive lens became less myopic than the eye wearing the plano lens. CONCLUSIONS: Brief periods of myopic defocus imposed by positive lenses prevent myopia caused by daylong wearing of negative lenses. This implies that periods of myopic and hyperopic defocus do not add linearly. If children are like chicks and if the hyperopic defocus of long daily periods of reading predisposes a child to myopia, regular, brief interruptions of reading might have use as a prophylaxis against progression of myopia.     

Cell surface expression of single chain antibodies with applications to imaging of gene expression in vivo

Imaging of gene expression in vivo has many potential uses for biomedical research and drug discovery, ranging from the study of gene regulation and cancer to the non-invasive assessment of gene therapies. To streamline the development of imaging marker gene technologies for nuclear medicine, we propose a new approach to the design of reporter/probe pairs wherein the reporter is a cell surface-expressed single chain antibody variable fragment that has been raised against a low molecular weight imaging probe with optimized pharmacokinetic properties. Proof of concept of the approach was achieved using a single chain antibody variable fragment that binds with high affinity to fluorescein and an imaging probe consisting of fluorescein isothiocyanate coupled to the chelator diethylene triamine penta-acetic acid labeled with the gamma-emitter ¹¹¹In. We demonstrate specific high-affinity binding of this probe to the cell surface-expressed reporter in vitro and assess the in vivo biodistribution of the probe both in wild-type mice and in mice harboring tumor xenografts expressing the reporter. Specific uptake of the probe by, and in vivo imaging of, tumors expressing the reporter are shown. Since ScFvs with high affinities can be raised to almost any protein or small molecule, the proposed methodology may offer a new flexibility in the design of imaging tracer/reporter pairs wherein both probe pharmacokinetics and binding affinities can be readily optimized.     

Adenovirus-mediated expression of human prorelaxin promotes the invasive potential of canine mammary cancer cells

This study reports the characterization of a recombinant adenoviral vector containing a tetracycline-regulatable promoter, driving the bicistronic expression of the human H2 preprorelaxin (hH2) cDNA and enhanced green fluorescent protein, via an internal ribosomal entry site. An hH2 ELISA was used to measure the secreted levels of recombinant hH2 in transfected canine (CF33.Mt) and human (MDA-MB-435) mammary cancer cell lines over a 6-d period; secreted peptide peaked on d 2 and 4 for the canine and human cell types, respectively. An unprocessed hH2 immunoreactive form of approximately 18 kDa was identified by Western blotting analysis and confirmed by mass spectrometry, suggesting that prorelaxin remains unprocessed in these cell types. The biological activity of the adenovirally expressed human prorelaxin was measured in the established human monocytic cell line THP-1 cAMP ELISA and in an in vitro Transwell cell migration system. Exogenous recombinant hH2 and adenovirally-mediated delivery of prorelaxin to CF33.Mt cells conferred a significant migratory action in the cells, compared with controls. Cell proliferation assays were performed to discount the possibility that the effect of relaxin was mitogenic. Thus, we have demonstrated that prorelaxin has the ability to facilitate cell migration processes exclusive of its ability to stimulate cell proliferation. In validating this adenovirus-based system, we have created a potential tool for further exploration of the physiology of relaxin in mammalian systems.     

Shank–cortactin interactions control actin dynamics to maintain flexibility of neuronal spines and synapses

The family of Shank scaffolding molecules (comprising Shank1, 2 and 3) are core components of the postsynaptic density (PSD) in neuronal synapses. Shanks link surface receptors to other scaffolding molecules within the PSD, as well as to the actin cytoskeleton. However, determining the function of Shank proteins in neurons has been complicated because the different Shank isoforms share a very high degree of sequence and domain homology. Therefore, to control Shank content while minimizing potential compensatory effects, a miRNA‐based knockdown strategy was developed to reduce the expression of all synaptically targeted Shank isoforms simultaneously in rat hippocampal neurons. Using this approach, a strong (>75%) reduction in total Shank protein levels was achieved at individual dendritic spines, prompting an approximately 40% decrease in mushroom spine density. Furthermore, Shank knockdown reduced spine actin levels and increased sensitivity to the actin depolymerizing agent Latrunculin A. A SHANK2 mutant lacking the proline‐rich cortactin‐binding motif (SHANK2‐ΔPRO) was unable to rescue these defects. Furthermore, Shank knockdown reduced cortactin levels in spines and increased the mobility of spine cortactin as measured by single‐molecule tracking photoactivated localization microscopy, suggesting that Shank proteins recruit and stabilize cortactin at the synapse. Furthermore, it was found that Shank knockdown significantly reduced spontaneous remodelling of synapse morphology that could not be rescued by the SHANK2‐ΔPRO mutant. It was concluded that Shank proteins are key intermediates between the synapse and the spine interior that, via cortactin, permit the actin cytoskeleton to dynamically regulate synapse morphology and function.