Natural killer cell lymphoma shares strikingly similar molecular features with a group of non-hepatosplenic γδ T-cell lymphoma and is highly sensitive to a novel aurora kinase A inhibitor in vitro.

Natural killer (NK) cell lymphomas/leukemias are rare neoplasms with an aggressive clinical behavior. The majority of the cases belong to extranodal NK/T-cell lymphoma, nasal type (ENKTL) in the current WHO classification scheme. Gene-expression profiling (GEP) of 21 ENKTL and NK-cell lymphoma/leukemia patients, 17 NK- and T-cell lines and 5 indolent NK-cell large-granular-lymphocytic proliferation was performed and compared with 125 peripheral T-cell lymphoma (PTCL) patients previously studied. The molecular classifier derived for ENKTL patients was comprised of 84 transcripts with the majority of them contributed by the neoplastic NK cells. The classifier also identified a set of γδ-PTCLs both in the ENKTL cases as well as in cases initially classified as PTCL-not otherwise specified. These γδ-PTCLs expressed transcripts associated with the T-cell receptor (TCR)/CD3 complex, suggesting T cell rather than NK-cell lineage. They were very similar to NK-cell tumors by GEP, but were distinct from cytotoxic (αß)-PTCL and hepatosplenic T-cell lymphoma, indicating derivation from an ontogenically and functionally distinct subset of γδ T cells. They showed distinct expression of Vγ9, Vδ2 transcripts and were positive for TCRγ, but negative for TCRß by immunohistochemistry. Targeted inhibition of two oncogenic pathways (AURKA and NOTCH-1) by small-molecular inhibitors induced significant growth arrest in NK-cell lines, thus providing a rationale for clinical trials of these inhibitors in NK-cell malignancies.

Reading disability and chromosome 6p21.3: evaluation of MOG as a candidate gene.

Linkage analysis has localized a gene influencing specific reading disability (dyslexia) to 6p21.3. The myelin oligodendrocyte glycoprotein (MOG) gene, which maps to this region, was selected as a candidate. Myelin oligodendrocyte glycoprotein is a membrane protein, a member of the immunoglobin superfamily, that is found on the outermost lamellae of mature myelin. Although the exact function of this protein is unknown, its presence in the central nervous system and the hypothesized relationship between dyslexia and temporal processing rate as well as a suggested relationship with intelligence made this gene a candidate for dyslexia. Analysis of the coding exons and adjacent splice sites in a subset of 22 children with dyslexia from 10 sibships found a missense mutation in exon 4 in 2 of the sibships. This change from the published sequence also occurred in 86 of 96 random controls, making it considerably less frequent in this small sample of individuals with dyslexia. Subsequent typing of this single nucleotide polymorphism (SNP) in 74 nuclear families in which at least one child had reading disability showed no significant difference in frequency from the controls, however. Sib-pair linkage analysis with these families did not show significant linkage with the SNP nor with a separate polymorphic dinucleotide repeat marker in the MOG gene (MOG31/32), but association analysis identified two alleles of MOG31/32 that were associated with reading disability phenotypes with a low level of significance. Thus, although alleles in the MOG gene may be in linkage disequilibrium with a locus that contributes to reading disability, it is unlikely that the MOG gene itself is involved.

Genomewide search and genetic localization of a second gene associated with autosomal dominant branchio-oto-renal syndrome: clinical and genetic implications.

Branchio-oto-renal (BOR) syndrome is characterized by ear malformations, cervical fistulas, hearing loss, and renal anomalies. It is an autosomal dominant disorder with variable clinical manifestations. The most common features of BOR syndrome are branchial, hearing, and renal anomalies. However, many affected subjects have been observed with branchial-cleft anomalies and hearing loss but without renal anomalies, a condition called "branchio-otic" (BO) syndrome. It is logical to question whether the BOR and BO syndromes are allelic or whether they represent distinct genetic entities. We identified a very large extended family whose members had branchial and hearing anomalies associated with commissural lip pits that segregated in an autosomal dominant fashion. Using a genomewide search strategy, we identified genetic linkage, with a maximum LOD score of 4.81 at recombination fraction 0, between the BO phenotype and polymorphic marker D1S2757 in the genetic region of chromosome 1q31. This is the first report of linkage for a second gene associated with BOR syndrome. The findings have important clinical implications and will provide insight into the genetic basis of BOR syndrome.

The face typicality-recognizability relationship: encoding or retrieval locus?

Using a crossover recognition memory testing paradigm, we tested whether the effects on face recognition of the memorability component of face typicality (Vokey & Read, 1992, 1995) are due primarily to the encoding process occurring during study or to the retrieval process occurring at test. At study, faces were either veridical in form or at moderate (Experiment 1) or extreme (Experiment 2) levels of caricature. The variable of degree of facial caricature at study was crossed with the degree of caricature at test. The primary contribution of increased memorability to increased hit rate was through increased distinctiveness at study. Increased distinctiveness at test contributed to substantial reductions in the false alarm rate, too. Signal detection analyses confirmed that the mirror effects obtained were primarily stimulus/memory-based, rather than decision-based. Contrary to the conclusion of Vokey and Read (1992), we found that increments in face memorability produced increments in face recognition that were due at least as much to enhanced encoding of studied faces as they were to increased rejection of distractor faces.

EYA1 nonsense mutation in a Japanese branchio-oto-renal syndrome family.

Advances in molecular genetics have recently revealed that mutations in the EYA1 gene are responsible for branchio-oto-renal (BOR) syndrome in European and other populations. This is the first report confirming that an EYA1 gene mutation is also disease-causing in an Asian population. We have described one Japanese BOR syndrome family showing a novel mutation in exon 7 of the EYA1 gene. There was extensive variation of clinical phenotypes within this family. When the physician is confronted with a BOR family showing a wide variation in clinical expression, molecular genetic testing helps to achieve accurate diagnosis.

The perception of face gender: the role of stimulus structure in recognition and classification.

The perception of face gender was examined in the context of extending "face space" models of human face representations to include the perceptual categories defined by male and female faces. We collected data on the recognizability, gender classifiability (reaction time to classify a face as male/female), attractiveness, and masculinity/femininity of individual male and female faces. Factor analyses applied separately to the data for male and female faces yielded the following results. First, for both male and female faces, the recognizability and gender classifiability of faces were independent--a result inconsistent with the hypothesis that both recognizability and gender classifiability depend on a face's "distance" from the subcategory gender prototype. Instead, caricatured aspects of gender (femininity/masculinity ratings) related to the gender classifiability of the faces. Second, facial attractiveness related inversely to face recognizability for male, but not for female, faces--a result that resolves inconsistencies in previous studies. Third, attractiveness and femininity for female faces were nearly equivalent, but attractiveness and masculinity for male faces were not equivalent. Finally, we applied principal component analysis to the pixel-coded face images with the aim of extracting measures related to the gender classifiability and recognizability of individual faces. We incorporated these model-derived measures into the factor analysis with the human rating and performance measures. This combined analysis indicated that face recognizability is related to the distinctiveness of a face with respect to its gender subcategory prototype. Additionally, the gender classifiability of faces related to at least one caricatured aspect of face gender.

Facial aging, attractiveness, and distinctiveness.

A standard facial caricature algorithm has been applied to a three-dimensional (3-D) representation of human heads, those of Caucasian male and female young adults. Observers viewed unfamiliar faces at four levels of caricature--anticaricature, veridical, moderate caricature, and extreme caricature--and made ratings of attractiveness and distinctiveness (experiment 1) or learned to identify them (experiment 2). There were linear increases in perceived distinctiveness and linear decreases in perceived attractiveness as the degree of facial caricature (Euclidean distance from the average face in 3-D-grounded face space) increased. Observers learned to identify faces presented at either level of positive caricature more efficiently than they did with either uncaricatured or anticaricatured faces. Using the same faces, 3-D representation, and caricature levels, O'Toole, Vetter, Volz, and Salter (1997, Perception 26 719-732) had shown a linear increase in judgments of face age as a function of degree of caricature. Here it is concluded that older-appearing faces are less attractive, but more distinctive and memorable than younger-appearing faces, those closer to the average face.

Branchio-oto-renal syndrome: identification of novel mutations, molecular characterization, mutation distribution, and prospects for genetic testing.

The branchio-oto-renal syndrome (BOR) is an autosomal dominant disorder characterized by branchial clefts, preauricular sinuses, hearing loss, and renal anomalies. The BOR gene, EYA1, on chromosome 8q13 has recently been cloned and mutations have been identified. In this study, we have analyzed the sites of mutations in the EYA1 gene in BOR patients to determine the spectrum of mutations. We have identified two missense mutations and have compared all the mutations reported to date in the EYA1 gene. In total, 20 mutations have been described, the majority of which are clustered in the carboxy-terminal region of the gene. The clinical features of the BOR individuals have also been compared to determine if the nature of the mutation correlates with the type and severity of the clinical symptoms. Most of the mutations arose de novo and, other than the clustering in carboxy-terminal exons 9-16, no mutation hot spots have been identified. These results provide the basis for molecular genetic testing that will help in the clinical evaluation and genetic counseling of members of BOR families.

Models of behaviors when detecting displacements of joints.

This report describes two models of human behavior when detecting displacements of joints that allow one to compare and integrate findings from different proprioception tests in a quantitative way. Results from various tests have led to different and often conflicting conclusions about proprioceptive behaviors and their underlying neural mechanisms. However, it has been impossible to compare data and conclusions in any meaningful way due to lack of a suitable analytical framework to accommodate important differences in procedures used in the various tests. These models can provide one such framework. The models, developed using data from proprioception tests reported in the literature, describe how the amplitude and velocity of joint excursions, and the subject bias expressed as false alarm rate, affect the detectability of displacements of joints. Two models were needed to represent observed behaviors: one based on velocity signals alone (the velocity model) and the other based on both velocity and positional signals (the displacement-velocity model). To simulate the detection-decision process subjects used to determine whether a joint was displaced, we adapted strategies from signal detection theory. The models characterized reported behaviors from disparate proprioception tests remarkably well, requiring only 3 degrees of freedom in the velocity case, and 4 in the displacement-velocity case.

An 'other-race effect' for categorizing faces by sex.

It is well-known that people recognize faces of their own race more accurately than faces of other races-a phenomenon often referred to as the 'other-race effect'. Using brief presentations of faces, we show a similar effect for the task of discriminating the sex of a face. Specifically, Caucasian observers discriminated male and female Caucasian faces more accurately/efficiently than did Oriental observers, and Oriental observers discriminated male and female Japanese faces more accurately/efficiently than did Caucasian observers. This result indicates that, under suboptimal viewing conditions, the identification of even the most salient of facial characteristics-face sex-is impaired for other-race faces. This finding suggests, also, that the nature and diversity of our experience with faces may affect not only the quality of the face representation for later access by recognition processes, but also the efficiency of a perceptual discrimination process. Intriguingly, too, we found that female observers, for both races tested, were considerably more accurate at the sex classification task than were male observers.

A metric for assessing acuity in positioning joints and limbs.

In this paper, we present a method for assessing the exactness of sensing and setting the positions of joints and limbs, using a measure we call target resolution. Target resolution, derived from information theory but ultimately based on variance, estimates the fewest number of discrete, equally spaced targets required within a range to provide the maximum possible information transfer from any target set. We argue that target resolution provides better insight into the exactness of position sense than does the usual measure of accuracy based on mean or constant error. Studies have shown that measures of mean error in setting or indicating positions of joints or limbs exhibit lability; they drift and show considerable sensitivity to factors such as previous positions of the limb and learning. We derive the equation for calculating target resolution and give example resolutions for several joints we have tested. Target resolution often gives a quite different impression of proprioceptive exactness than do measures of accuracy based on mean error.

Structural aspects of face recognition and the other-race effect.

The other-race effect was examined in a series of experiments and simulations that looked at the relationships among observer ratings of typicality, familiarity, attractiveness, memorability, and the performance variables of d' and criterion. Experiment 1 replicated the other-race effect with our Caucasian and Japanese stimuli for both Caucasian and Asian observers. In Experiment 2, we collected ratings from Caucasian observers on the faces used in the recognition task. A Varimax-rotated principal components analysis on the rating and performance data for the Caucasian faces replicated Vokey and Read's (1992) finding that typicality is composed of two orthogonal components, dissociable via their independent relationships to: (1) attractiveness and familiarity ratings and (2) memorability ratings. For Japanese faces, however, we found that typicality was related only to memorability. Where performance measures were concerned, two additional principal components dominated by criterion and by d' emerged for Caucasian faces. For the Japanese faces, however, the performance measures of d' and criterion merged into a single component that represented a second component of typicality, one orthogonal to the memorability-dominated component. A measure of face representation quality extracted from an autoassociative neural network trained with a majority of Caucasian faces and a minority of Japanese faces was incorporated into the principal components analysis. For both Caucasian and Japanese faces, the neural network measure related both to memorability ratings and to human accuracy measures. Combined, the human data and simulation results indicate that the memorability component of typicality may be related to small, local, distinctive features, whereas the attractiveness/familiarity component may be more related to the global, shape-based properties of the face.

Memory for faces: testing method, encoding strategy, and confidence.

Signal detection theory predicts a square root 2 recognition memory performance advantage for the two-alternative forced choice (2AFC) procedure over the yes-no (YN) procedure. In auditory psychophysics this advantage has been related to greater demands on memory in the YN task. The present experiment tested this prediction by assessing face-recognition accuracy and confidence in 72 college student subjects. Testing method (2AFC or YN) and encoding instructions (standard, overall gestalt, or distinctive feature scan) were varied, the latter in an effort to vary trace strength to see whether stronger traces would yield a lesser 2AFC advantage. A 1-week retention test revealed an overall 2AFC advantage of 1.61 and superiority of gestalt and feature-scan instructions over standard ones. While confidence and accuracy were related both within and across subjects, 2AFC subjects were significantly more confident than YN ones. Intriguingly, more efficient encodings resulted in a greater, rather than a lesser 2AFC advantage.