A chronic implant for recording of cochlear potentials in primates

A new technique for the continuous recording of peripheral bioelectrical activity in the auditory system of primates is described. Because of basic differences in the anatomy of the temporal bone, the approach to the round window of the cochlea is more difficult in most primates than in lower animals. A relatively simple surgical approach, which made possible the placement of an electrode into the perilymph of the inner ear via the well-demarcated horizontal semicircular canal was therefore developed and is described in detail. The bared tip of a Teflon-coated wire was cemented into the canal opening with carboxylate cement, and the wire attached to a permanent electrical connector on the skull. Cochlear microphonic and action potentials of 50 to 100 μV amplitude were thus recorded on a continuing basis at the same time that behavioral studies of primate auditory acuity were conducted.     

The functional morphology of the respiratory system of the Holothyrida (= Tetrastigmata) Acari: Anactinotrichida

The respiratory system of Holothyrus coccinella Gervais (Holothyridae) and Allothyrus australasiae (Womersley) (Allothyridae) were examined. The stigma-peritreme complex is connected to tracheae and ventilated by indirect muscles. The peritreme provides an alternative route for the entry of air into the tracheal system, should a stigma be occluded by debris and retards water vapour transpiration, the mechanisms of which are compared in the two species.     

Genomewide association study for susceptibility genes contributing to familial Parkinson disease

Five genes have been identified that contribute to Mendelian forms of Parkinson disease (PD); however, mutations have been found in fewer than 5% of patients, suggesting that additional genes contribute to disease risk. Unlike previous studies that focused primarily on sporadic PD, we have performed the first genomewide association study (GWAS) in familial PD. Genotyping was performed with the Illumina HumanCNV370Duo array in 857 familial PD cases and 867 controls. A logistic model was employed to test for association under additive and recessive modes of inheritance after adjusting for gender and age. No result met genomewide significance based on a conservative Bonferroni correction. The strongest association result was with SNPs in the GAK/DGKQ region on chromosome 4 (additive model: p = 3.4 × 10⁻⁶; OR = 1.69). Consistent evidence of association was also observed to the chromosomal regions containing SNCA (additive model: p = 5.5 × 10⁻⁵; OR = 1.35) and MAPT (recessive model: p = 2.0 × 10⁻⁵; OR = 0.56). Both of these genes have been implicated previously in PD susceptibility; however, neither was identified in previous GWAS studies of PD. Meta-analysis was performed using data from a previous case–control GWAS, and yielded improved p values for several regions, including GAK/DGKQ (additive model: p = 2.5 × 10⁻⁷) and the MAPT region (recessive model: p = 9.8 × 10⁻⁶; additive model: p = 4.8 × 10⁻⁵). These data suggest the identification of new susceptibility alleles for PD in the GAK/DGKQ region, and also provide further support for the role of SNCA and MAPT in PD susceptibility. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. N. Pankratz and J. B. Wilk are joint first authors.     

An association between the acute phase response and patterns of antigen induced T cell proliferation in juvenile idiopathic arthritis

The aim of this research was to determine whether all memory T cells have the same propensity to migrate to the joint in patients with juvenile idiopathic arthritis. Paired synovial fluid and peripheral blood mononuclear cell proliferative responses to a panel of antigens were measured and the results correlated with a detailed set of laboratory and clinical data from 39 patients with juvenile idiopathic arthritis. Two distinct patterns of proliferative response were found in the majority of patients: a diverse pattern, in which synovial fluid responses were greater than peripheral blood responses for all antigens tested; and a restricted pattern, in which peripheral blood responses to some antigens were more vigorous than those in the synovial fluid compartment. The diverse pattern was generally found in patients with a high acute phase response, whereas patients without elevated acute phase proteins were more likely to demonstrate a restricted pattern. We propose that an association between the synovial fluid T cell repertoire and the acute phase response suggests that proinflammatory cytokines may influence recruitment of memory T cells to an inflammatory site, independent of their antigen specificity. Additionally, increased responses to enteric bacteria and the presence of αEβ7 T cells in synovial fluid may reflect accumulation of gut associated T cells in the synovial compartment, even in the absence of an elevated acute phase response. This is the first report of an association between the acute phase response and the T cell population recruited to an inflammatory site.     

Regulation of Rhodopsin-eGFP Distribution in Transgenic Xenopus Rod Outer Segments by Light

The rod outer segment (OS), comprised of tightly stacked disk membranes packed with rhodopsin, is in a dynamic equilibrium governed by a diurnal rhythm with newly synthesized membrane inserted at the OS base balancing membrane loss from the distal tip via disk shedding. Using transgenic Xenopus and live cell confocal imaging, we found OS axial variation of fluorescence intensity in cells expressing a fluorescently tagged rhodopsin transgene. There was a light synchronized fluctuation in intensity, with higher intensity in disks formed at night and lower intensity for those formed during the day. This fluctuation was absent in constant light or dark conditions. There was also a slow modulation of the overall expression level that was not synchronized with the lighting cycle or between cells in the same retina. The axial variations of other membrane-associated fluorescent proteins, eGFP-containing two geranylgeranyl acceptor sites and eGFP fused to the transmembrane domain of syntaxin, were greatly reduced or not detectable, respectively. In acutely light-adapted rods, an arrestin-eGFP fusion protein also exhibited axial variation. Both the light-sensitive Rho-eGFP and arrestin-eGFP banding were in phase with the previously characterized birefringence banding (Kaplan, Invest. Ophthalmol. Vis. Sci. 21, 395–402 1981). In contrast, endogenous rhodopsin did not exhibit such axial variation. Thus, there is an axial inhomogeneity in membrane composition or structure, detectable by the rhodopsin transgene density distribution and regulated by the light cycle, implying a light-regulated step for disk assembly in the OS. The impact of these results on the use of chimeric proteins with rhodopsin fused to fluorescent proteins at the carboxyl terminus is discussed.