"Weber's law" for position: unconfounding the role of separation and eccentricity

Bisection thresholds are approximately proportional to the separation/eccentricity of the targets. This "Weber's law" for position has been invoked over the past century. It is the separation of the reference targets, or their eccentricity which determines the threshold? In previous studies separation and eccentricity are confounded. In the present report we have pitted separation against eccentricity. Bisection thresholds were measured for stimuli presented on an isoeccentric arc, so that separation could be varied while holding the eccentricity of the test lines constant. We used a 5-fold range of separations from 2-10 deg. In this regime, the present results provide strong evidence against Weber's law. When separation is varied but eccentricity held constant, there is no Weber's law. Rather the thresholds are approximately constant. Our results suggest that the judgement of the separation of widely separated objects is similar to a distance measurement using a ruler on the cortex, in that the error of measurement is independent of the separation between objects. The results imply that when we attempt to gauge the distance between widely separated objects it is unlikely that we do so on the basis of the outputs of large spatial filters; rather it appears that we make such judgements by estimating the cortical distance which separates the targets of interest.     

Genetic testing for hearing loss: different motivations for the same outcome

Autism is a complex genetic disorder. Chromosome 15 is of particular interest in this disorder, because of previous reports of individuals with autism with chromosomal abnormalities in the 15q11-q13 region. Transmission disequilibrium between polymorphisms in this region and autism has been also been reported in some, but not all studies. Recently, a novel maternally expressed gene, ATP10C, was characterized and mapped to the chromosome 15q11-q13 region, 200 kb distal to UBE3A. It encodes a putative aminophospholipid translocase likely to be involved in the asymmetric distribution of proteins in the cell membrane. Preferential maternal expression has been demonstrated in fibroblasts and brain. Because of its physical location and imprinting pattern, ATP10C was considered to be a candidate gene for chromosome 15-associated autism. In an effort to find the genes responsible for autism in this chromosomal region, 1.5 kb of the 5' flanking region, as well as the coding and splicing regions of ATP10C, were screened for sequence variants. Several polymorphic markers including five nonsynonymous SNPs were identified. To investigate transmission disequilibrium between ATP10C and autism, a family-based association study was conducted for 14 markers in 115 autism trios. No significant transmission disequilibrium was found, suggesting ATP10C is unlikely to contribute strongly to susceptibility to autism in these families. However, due to limited power to detect genes of modest effect, the possible functional role of the nonsynonymous SNPs and the functional implications of the SNPs identified from 5' flanking region and intron 2 splicing region may be evaluated in further studies.     

Role of the alveolar macrophage in host defense and immunity to Legionella micdadei pneumonia in the guinea pig

Guinea pigs develop a lethal pneumonia after intratracheal infection with Legionella micdadei, and the lung displays pathological changes similar to those observed in humans. To investigate the role of the resident alveolar macrophage in the pathogenesis of L. micdadei pneumonia, guinea pig alveolar macrophages obtained by bronchoalveolar lavage were cultured in vitro and infected with L. micdadei. In the absence of opsonins L. micdadei was phagocytized by, and multiplied within, alveolar macrophages with greater than a 100-fold increase in cell-associated colony forming units over 20 h. L. micdadei opsonized with complement or antibody multiplied within alveolar macrophages at the same rate as unopsonized bacteria. Guinea pigs which were treated with antimicrobials after infection with L. micdadei and recovered from the pneumonia were immune to challenge with an otherwise lethal inoculum of L. micdadei. However, the growth curve of both unopsonized and opsonized L. micdadei in the alveolar macrophages from immune animals was essentially identical to that in macrophages from susceptible animals. Thus, the resident alveolar macrophage is not capable of limiting the growth of Legionella. Rather, the alveolar macrophages appear to be the primary site of Legionella multiplication within the lung. Although alveolar macrophages may participate in other aspects of pulmonary immunity to the legionellae, these data indicate that the alveolar macrophage alone does not act as an effector cell in cell-mediated immunity to Legionella.     

Mutations in the retinal guanylate cyclase (RETGC-1) gene in dominant cone-rod dystrophy

The dominant cone-rod dystrophy gene CORD6 has previously been mapped to within an 8 cM interval on chromosome 17p12-p13. The retinal- specific guanylate cyclase gene (RETGC-1), which maps to within this genetic interval and previously was implicated in Leber's congenital amaurosis, was screened for mutations within this family and in a panel of small families and individuals with various cone and cone- rod dystrophy phenotypes. A missense mutation (E837D) was identified in affected members of the CORD6 family, as well as a second missense mutation (R838C) in three other families with dominant cone-rod dystrophy. RETGC-1 is only the fourth gene to be implicated in cone-rod dystrophy and this is the first report of dominant mutations in this gene.      

The essential role of stimulus temporal patterning in enabling perceptual learning

Little is known about how temporal stimulus factors influence perceptual learning. Here we demonstrate an essential role of stimulus temporal patterning in enabling perceptual learning by showing that 'unlearnable' contrast and motion-direction discrimination (resulting from random interleaving of stimuli) can be readily learned when stimuli are practiced in a fixed temporal pattern. This temporal patterning does not facilitate learning by reducing stimulus uncertainty; further, learning enabled by temporal patterning can later generalize to randomly presented stimuli.     

Induction of IgE antibodies to antigen isolated from tobacco leaves and from cigarette smoke condensate.

Neonatal California White rabbits were sensitized with a glycoprotein purified from cured Virginia Bright tobacco leaves. Their serums, but not serums from normal rabbits, were demonstrated by passive cutaneous anaphylaxis technique to contain heat-labile, homocytophilic antibodies to this antigen and to similar material purified from cigarette smoke condensate. Serums containing IgE antibodies to tobacco antigen would not be demonstrated to contain hemagglutinating antibodies to this antigen. These experiments demonstrate that antigen capable of triggering specific IgE-mediated release of inflammatory mediators is present in cigarette smoke. It can be hypothesized that IgE-mediated responses to antigen in cigarette smoke are causally related to the development of vascular injury and of myocardial arrhythmia in hypersensitive smokers.     

Characterization of Mycobacterium montefiorense sp. nov., a novel pathogenic Mycobacterium from moray eels that is related to Mycobacterium triplex

The characterization of a novel Mycobacterium sp. isolated from granulomatous skin lesions of moray eels is reported. Analysis of the hsp65 gene, small-subunit rRNA gene, rRNA spacer region, and phenotypic characteristics demonstrate that this organism is distinct from its closest genetic match, Mycobacterium triplex, and it has been named M. montefiorense sp. nov.     

Inhibition of experimental autoimmune encephalomyelitis in Lewis rats by nasal administration of encephalitogenic MBP peptides: synergistic effects of MBP 68-86 and 87-99

Induction of mucosal tolerance by inhalation of soluble peptides with defined T cell epitopes is receiving much attention as a means of specifically down-regulating pathogenic T cell reactivities in autoimmune and allergic disorders. Experimental autoimmune encephalomyelitis (EAE) induced in the Lewis rat by immunization with myelin basic protein (MBP) and Freund's adjuvant (CFA) is mediated by CD4+ T cells specific for the MBP amino acid sequences 68-86 and 87-99. To further define the principles of nasal tolerance induction, we generated three different MBP peptides (MBP 68-86, 87-99 and the non- encephalitogenic peptide 110-128), and evaluated whether their nasal administration on day -11, -10, -9, -8 and -7 prior to immunization with guinea pig MBP (gp-MBP) + CFA confers protection to Lewis rat EAE. Protection was achieved with the encephalitogenic peptides MBP 68-86 and 87-99, MBP 68-86 being more potent, but not with MBP 110-128. Neither MBP 68-86 nor 87-99 at doses used conferred complete protection to gp-MBP-induced EAE. In contrast, nasal administration of a mixture of MBP 68-86 and 87-99 completely blocked gp-MBP-induced EAE even at lower dosage compared to that being used for individual peptides. Rats tolerized with MBP 68-86 + 87-99 nasally showed decreased T cell responses to MBP reflected by lymphocyte proliferation and IFN-gamma ELISPOT assays. Rats tolerized with MBP 68-86 + 87-99 also had abrogated MBP-reactive IFN-gamma and tumor necrosis factor-alpha mRNA expression in lymph node cells compared to rats receiving MBP 110-128 nasally, while similar low levels of MBP-reactive transforming growth factor-beta and IL-4 mRNA expressing cells were observed in the two groups. Nasal administration of MBP 68-86 + 87-99 only slightly inhibited guinea pig spinal cord homogenate-induced EAE, and passive transfer of spleen mononuclear cells from MBP 68-86 + 87-99-tolerized rats did not protect naive rats from EAE. Finally, we show that nasal administration of MBP 68-86 + 87-99 can reverse ongoing EAE induced with gp-MBP, although higher doses are required compared to the dosage needed for prevention. In conclusion, nasal administration of encephalitogenic MBP peptides can induce antigen-specific T cell tolerance and confer incomplete protection to gp-MBP-induced EAE, and MBP 68-86 and 87-99 have synergistic effects. Non-regulatory mechanisms are proposed to be responsible for tolerance development after nasal peptide administration.