Metabolic scaling and twin placentas.

OBJECTIVE: Do monochorionic (MC) and/or dichorionic (DC) twins show allometric scaling between placental and birth weight (PW, BW)? METHODS: We extracted BW, PW, gestational age (GA) and cord insertion type from 52 MC to 310 DC twins to calculate ß. DC twins were analyzed as summed and as individuals if placentas were separate. RESULTS: Mean ß for MC (0.78 ± 0.02), DC summed (0.78 ± 0.02), and DC with separate placentas (0.77 ± 0.03 and 0.76 ± 0.04) all non-significant. GA, summed BWs, total PW, BW discordance, and cord insertion sites did not differ between twin types or with ß. CONCLUSION: MC and DC twins show allometric scaling similar to singletons.

Figure/Ground Segmentation via a Haptic Glance: Attributing Initial Finger Contacts to Objects or Their Supporting Surfaces.

The current study addresses the well-known "figure/ground" problem in human perception, a fundamental topic that has received surprisingly little attention from touch scientists to date. Our approach is grounded in, and directly guided by, current knowledge concerning the nature of haptic processing. Given inherent figure/ground ambiguity in natural scenes and limited sensory inputs from first contact (a "haptic glance"), we consider first whether people are even capable of differentiating figure from ground (Experiments 1 and 2). Participants were required to estimate the strength of their subjective impression that they were feeling an object (i.e., figure) as opposed to just the supporting structure (i.e., ground). Second, we propose a tripartite factor classification scheme to further assess the influence of kinetic, geometric (Experiments 1 and 2), and material (Experiment 2) factors on haptic figure/ground segmentation, complemented by more open-ended subjective responses obtained at the end of the experiment. Collectively, the results indicate that under certain conditions it is possible to segment figure from ground via a single haptic glance with a reasonable degree of certainty, and that all three factor classes influence the estimated likelihood that brief, spatially distributed fingertip contacts represent contact with an object and/or its background supporting structure.

Tactile and Haptic Illusions.

This paper surveys the research literature on robust tactile and haptic illusions. The illusions are organized into two categories. The first category relates to objects and their properties, and is further differentiated in terms of haptic processing of material versus geometric object properties. The second category relates to haptic space, and is further differentiated in terms of the observer's own body versus external space. The illusions are initially described and where possible addressed in terms of their functional properties and/or underlying neural processes. The significance of these illusions for the design of tactile and haptic displays is also discussed. We conclude by briefly considering a number of important general themes that have emerged in the materials surveyed.

Haptic Classification of Facial Identity in 2D Displays: Configural versus Feature-Based Processing.

Participants learned through feedback to haptically classify the identity of upright versus inverted versus scrambled faces depicted in simple 2D raised-line displays. We investigated whether identity classification would make use of a configural face representation, as is evidenced for vision and 3D haptic facial displays. Upright and scrambled faces produced equivalent accuracy, and both were identified more accurately than inverted faces. The mean magnitude of the haptic inversion effect for 2D facial identity was a sizable 26 percent, indicating that the upright orientation was ¿privileged¿ in the haptic representations of facial identity in these 2D displays, as with other facial modalities. However, given the effect of scrambling, we conclude that configural processing was not employed; rather, only local information about the features was used, the features being treated as oriented objects within a body-centered frame of reference. The results indicate a fundamental difference between haptic identification of 2D facial depictions and 3D faces, paralleling a corresponding difference in recognition of nonface objects.

Haptic perception: a tutorial.

This tutorial focuses on the sense of touch within the context of a fully active human observer. It is intended for graduate students and researchers outside the discipline who seek an introduction to the rapidly evolving field of human haptics. The tutorial begins with a review of peripheral sensory receptors in skin, muscles, tendons, and joints. We then describe an extensive body of research on "what" and "where" channels, the former dealing with haptic perception of objects, surfaces, and their properties, and the latter with perception of spatial layout on the skin and in external space relative to the perceiver. We conclude with a brief discussion of other significant issues in the field, including vision-touch interactions, affective touch, neural plasticity, and applications.

Haptic Processing of Facial Expressions of Emotion in 2D Raised-Line Drawings.

Participants haptically (vs. visually) classified universal facial expressions of emotion (FEEs) depicted in simple 2D raised-line displays. Experiments 1 and 2 established that haptic classification was well above chance; face-inversion effects further indicated that the upright orientation was privileged. Experiment 2 added a third condition in which the normal configuration of the upright features was spatially scrambled. Results confirmed that configural processing played a critical role, since upright FEEs were classified more accurately and confidently than either scrambled or inverted FEEs, which did not differ. Because accuracy in both scrambled and inverted conditions was above chance, feature processing also played a role, as confirmed by commonalities across confusions for upright, inverted, and scrambled faces. Experiment 3 required participants to visually and haptically assign emotional valence (positive/negative) and magnitude to upright and inverted 2-D FEE displays. While emotional magnitude could be assigned using either modality, haptic presentation led to more variable valence judgments. We also documented a new face-inversion effect for emotional valence visually, but not haptically. These results suggest emotions can be interpreted from 2-D displays presented haptically as well as visually; however, emotional impact is judged more reliably by vision than by touch. Potential applications of this work are also considered.

Haptic recognition of static and dynamic expressions of emotion in the live face.

If humans can detect the wealth of tactile and haptic information potentially available in live facial expressions of emotion (FEEs), they should be capable of haptically recognizing the six universal expressions of emotion (anger, disgust, fear, happiness, sadness, and surprise) at levels well above chance. We tested this hypothesis in the experiments reported here. With minimal training, subjects' overall mean accuracy was 51% for static FEEs (Experiment 1) and 74% for dynamic FEEs (Experiment 2). All FEEs except static fear were successfully recognized above the chance level of 16.7%. Complementing these findings, overall confidence and information transmission were higher for dynamic than for corresponding static faces. Our performance measures (accuracy and confidence ratings, plus response latency in Experiment 2 only) confirmed that happiness, sadness, and surprise were all highly recognizable, and anger, disgust, and fear less so.

CD20-induced B cell death can bypass mitochondria and caspase activation.

The apoptotic pathway activated by chimeric anti-CD20 monoclonal antibodies (rituximab, IDEC.C2B8) was analyzed using the Burkitt lymphoma cell line Ramos. Crosslinking of CD20 (CD20XL) induced apoptosis in Ramos cells, which involved loss of mitochondrial membrane potential (Deltapsi(m)), the release of cytochrome-c (cyt-c), and activation of caspases-9 and -3. Nevertheless, several lines of evidence showed that the apoptotic outcome did not depend on these events. First, under circumstances where Ramos cells display resistance to either CD95- or B cell receptor (BCR)-induced apoptosis, CD20XL-induced apoptosis was not affected, pointing to a distinct pathway. Second, the broad-spectrum caspase inhibitor zVAD-fmk prevented processing of caspase-9, -3 and PARP as well as DNA fragmentation, but did not block apoptosis as measured by annexin V staining, cell size and membrane integrity. Lastly, Bcl-2 overexpression blocked cyt-c release and the decrease in Deltapsi(m), and completely prevented CD95- or BCR-mediated apoptosis; however, it did not affect CD20XL-induced cell death. We conclude that although CD20XL can initiate the mitochondrial apoptosis pathway, CD20-induced apoptosis does not necessarily require active caspases and cannot be blocked by Bcl-2. Since most chemotherapeutic drugs require the activation of caspases to exert their cytotoxicity, these findings provide an important rationale for the use of CD20 mAbs in chemoresistant malignancies.

Tolerization of dendritic cells by T(S) cells: the crucial role of inhibitory receptors ILT3 and ILT4.

Immunoglobulin-like transcript 3 (ILT3) and ILT4 belong to a family of inhibitory receptors expressed by human monocytes and dendritic cells. We show here that CD8+CD28(-) alloantigen-specific T suppressor (TS) cells induce the up-regulation of ILT3 and ILT4 on monocytes and dendritic cells, rendering these antigen-presenting cells (APCs) tolerogenic. Tolerogenic APCs show reduced expression of costimulatory molecules and induce antigen-specific unresponsiveness in CD4+ T helper cells. Studies of human heart transplant recipients showed that rejection-free patients have circulating TS cells, which induce the up-regulation of ILT3 and ILT4 in donor APCs. These findings demonstrate an important mechanism of immune regulation.

fMRI-derived cortical maps for haptic shape, texture, and hardness.

We used functional magnetic resonance imaging (fMRI) to investigate the neural substrates involved in haptic processing of texture, shape, and hardness. Subjects performed haptic classification tasks on a set of 27 silicone objects having parametrically defined shape, texture, and hardness. The objects were ellipsoids of revolution in which the ratio of the long to the short axis was varied, producing three different shapes. Three surface textures and three hardness levels were used. In three separate experiments, the same subjects classified each object along the three levels of one of the object properties (shape, texture, or hardness). Texture, shape, and hardness processing led to contralateral activation in the postcentral gyrus (PCG). A common region located within relatively posterior portions of the PCG was observed during shape and texture identification whereas a separate and more anterior region was activated during the hardness identification task. The hardness identification task also produced bilateral activation within the parietal operculum.

Expression and function of TRAF-3 splice-variant isoforms in human lymphoma cell lines.

TRAF-3 gene products are signaling adaptor molecules required for lymphocytes to mediate T-dependent antibody responses in vivo. Previous work identified 8 splice-variant TRAF-3 mRNA species by RT-PCR that have the potential to encode novel isoforms, seven of which induce NF-kappaB activation when over-expressed in 293 cells. Here, their expression was characterized by RNAse protection assay, which showed the T cell line Jurkat D1.1 and the B cell lines BJAB, Daudi, and Raji each expressed mRNA encoding TRAF-3 splice-variants in approximately the same rank order (from highest to lowest); TRAF-3 Delta103aa, Delta83aa, full-length, Delta25aa, Delta52aa, Delta56aa, Delta27aa, and Delta221aa mRNA. The TRAF-3 Delta130aa mRNA was not detectable in any of the cell lines examined. The functional effect of over-expressing each TRAF-3 splice-variant on NF-kappaB activation was studied in the TRAF-5-responsive B cell line, BJAB. Of the seven TRAF-3 splice-variant isoforms that induce NF-kappaB activation in 293 cells, only TRAF-3 Delta27aa, Delta103aa, or Delta130aa induce NF-kappaB activation in BJAB cells. Together, these data indicate that a number of TRAF-3 splice-variant mRNAs are expressed and function in B and T lymphoma lines, which suggests that certain TRAF-3 splice-variant isoforms may participate in mediating the known functions of the TRAF-3 gene in lymphocytes.

Pregnancy weight gain and postpartum loss: avoiding obesity while optimizing the growth and development of the fetus.

Weight gain during pregnancy may contribute to obesity development. Concerns about possible adverse effects of pregnancy weight gain on later maternal weight and on labor and delivery must be rigorously evaluated in light of possible benefits for fetal growth and development. Birth-weight rises with increased pregnancy weight gain, and perinatal and neonatal mortality fall as birthweight increases in both preterm and term infants. The lowest mortality is observed at 3500 to 4500 g in infants of white women. Although often thought to be at high risk, infants termed "macrosomic" include infants of the lowest mortality rate. Thus, restricting weight gain may be detrimental to the baby. Weight gain that is optimal for the mother and the baby differs according to the mother's prepregnancy weight. Pregnancy weight gain exceeding current recommendations is associated with increases in maternal fat gain, pregnancy complications, and delivery problems and should be discouraged. Postpartum weight loss is essential to prevent permanent weight increase. Smoking cessation during pregnancy, reduced postpartum physical activity, and other lifestyle changes can contribute to increased postpartum weight. Health care providers can help to reduce obesity risk by regularly monitoring women's weight; promoting appropriate prepregnancy weight, pregnancy weight gain, and postpartum weight less; and explicitly encouraging maintenance of an active postpartum lifestyle.

Induction of xenoreactive CD4+ T-cell anergy by suppressor CD8+CD28- T cells.

BACKGROUND: The underlying mechanism of immune suppression mediated by regulatory T cells is not completely understood. In previous studies we have shown that antigen-specific human T suppressor cells (Ts) can be generated in vitro by multiple rounds of stimulation with allogeneic, xenogeneic, or antigen-pulsed autologous antigen-presenting cells (APC). Human Ts express the CD8+CD28- phenotype and require specific recognition of MHC class I/peptide complexes on the surface of APC to block proliferation of T helper cells (Th). The aim of the present study was to explore the activation requirements of Ts as well as the nature of Th unresponsiveness to xenogeneic (swine) antigens induced by Ts. METHODS AND RESULTS: We investigated whether specific antigenic stimulation of Ts is required for their ability to inhibit early activation of xenoreactive Th (up-regulation of CD40 ligand). Flow cytometry studies indicated that Ts function required specific recognition of MHC class I on the surface of the stimulating APC. However, neither proliferation nor protein synthesis was required for the ability of Ts to inhibit Th. Ts drastically reduced the capacity of xenoreactive Th cells to produce interleukin (IL)-2 in response to the specific APC, without affecting their surface expression of IL-2 receptor. The suppressor effect that Ts exerted on Th proliferation could not be circumvented by CD40 ligation on the surface of the APC but could be reversed by the addition of exogenous IL-2. CONCLUSION: These data indicate that Ts induce anergy of xenoreactive human Th cells upon specific recognition of MHC class I antigens. Hence, Ts may prevent the activation of T cell-mediated immune responses against xenogeneic transplants.

TRAF-3 interacts with p62 nucleoporin, a component of the nuclear pore central plug that binds classical NLS-containing import complexes.

The TRAF-3 gene encodes a number of splice-variant isoforms that function as adapter molecules in NF-kappaB signaling, in part by associating with the cytoplasmic tails of CD40 or other TNF-receptor (TNF-R) family members. To identify downstream molecules in TRAF-3 signaling, a yeast two-hybrid library was screened with a full-length TRAF-3 construct. Nine independent TRAF-3 interacting clones encoded fragments of p62 Nucleoporin (p62), a 522 amino acid (aa) component of the nuclear pore central plug, that is known to bind karyopherin-beta/classical-NLS import factor complexes. The interaction of p62 with TRAF-3 was specific, since p62 failed to interact with TRAF-2, -4, -5, or -6. Deletional analysis in yeast revealed that the p62:TRAF-3 interaction is mediated by a p62 carboxy (C)-terminal coiled-coil domain and TRAF-3's fifth zinc (Zn) finger and coiled-coil domain. In human 293 T cells, recombinant TRAF-3 or p62 specifically co-immunoprecipitates the other species. In addition, endogenous p62 co-precipitates over-expressed TRAF-3. The functional effects of over-expressing a TRAF-3 binding fragment, p62(aa 336-522) were studied on NF-kappaB-dependent, or control STAT1-dependent reporter activity in 293 T cells, either resting or after stimulation by CD40 or IFN-gamma, respectively. Over-expression of p62(aa 336-522) induces NF-kappaB activation in resting cells and augments CD40-induced NF-kappaB activation, but has no effect on control STAT1 reporter activity, either at baseline or after IFN-gamma induction. The finding that TRAF-3 binds p62, suggests that TRAF-3 may serve as an adapter molecule at the nuclear membrane, in addition to its known adapter function at the plasma membrane.

The material-weight illusion revisited.

Experiment 1 documents modality effects on the material-weight illusion for a low-mass object set (58.5 g). These modality effects indicate that the material-weight illusion is principally a haptically derived phenomenon: Haptically accessed material cues were both sufficient and necessary for full-strength illusions, whereas visually accessed material cues were only sufficient to generate moderate-strength illusions. In contrast, when a high-mass object set (357 g) was presented under the same modality conditions, no illusions were generated. The mass-dependent characteristic of this illusion is considered to be a consequence of differing grip forces. Experiment 2 demonstrates that the enforcement of a firm grip abolishes the low-mass material-weight illusion. Experiment 3 documents that a firm grip also diminishes perceptual differentiation of actual mass differences. Several possible explanations of the consequences of increasing grip force are considered.

T suppressor lymphocytes inhibit NF-kappa B-mediated transcription of CD86 gene in APC.

CD8+CD28- human T suppressor cells (Ts) act on APC, inhibiting their ability to elicit Th activation and proliferation. This effect is due to inhibition of the CD40 pathway which normally leads to CD80 and CD86 up-regulation. To determine whether Ts inhibit expression of B7 molecules by blocking transcription, we cloned and characterized the CD86 promoter. Mutational analysis revealed that Ts inhibit transcription driven by the CD86 promoter. The NF-kappa B binding site, at -612 of the CD86 promoter, is essential for Th-induced transcription. In cultures containing Th and Ts, Ts inhibit Th-induced NF-kappa B activation in APC. Together, these findings indicate that Ts inhibition of NF-kappa B activation in APC is a means by which they regulate the activation and proliferation of Th.

TRAF-3 mRNA splice-deletion variants encode isoforms that induce NF-kappaB activation.

Although TRAF-3 gene products are required for signaling in T-B cell collaboration, full-length TRAF-3 appears to lack signaling function in transient transfection assays that measure NF-kappaB activation. However, the TRAF-3 gene also encodes at least three mRNA splice-deletion variants that predict protein isoforms (delta25aa, delta52aa and delta56aa) with altered zinc (Zn) finger domains and unknown functional capacities. To determine whether TRAF-3 splice-deletion variants may transmit activating receptor signals to the nucleus, cDNAs for five additional splice-variant isoforms (delta27aa, delta83aa, delta103aa, delta130aa and delta221aa) were cloned from a TRAF-3+ lymphoma and the expression and function of each of the eight TRAF-3 splice-deletion variants was analyzed. Among the splice-deletion variants, TRAF-3 delta130 mRNA is expressed by tonsillar B cells and by each of a panel of B and T cell lines. TRAF-3 delta221 protein is expressed by tonsillar B cells and by each of the lymphocytic lines. The functional effect of over-expressing each TRAF-3 splice-deletion variant on NF-kappaB activation was studied in 293 T cells. Seven of the TRAF-3 splice-deletion variants, such as TRAF-3 delta130, induce substantial NF-kappaB-driven luciferase activity (80-500 fold). In contrast, TRAF-3 delta221 (in which the complete Zn finger domain is absent) fails to induce NF-kappaB activation. Although full-length TRAF-3 alone is inactive, it augments the functional effects of the seven activating TRAF-3 splice-deletion variants (1.4-5 fold). These data indicate that alterations of the Zn finger domains render the TRAF-3 splice-deletion variants capable of inducing NF-kappaB activation and that full-length TRAF-3 augments their signaling.