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PubMed2004

Sequential phases of cortical specification involve Neurogenin-dependent and -independent pathways.

Neocortical projection neurons, which segregate into six cortical layers according to their birthdate, have diverse morphologies, axonal projections and molecular profiles, yet they share a common cortical regional identity and glutamatergic neurotransmission phenotype. Here we demonstrate that distinct genetic programs operate at different stages of corticogenesis to specify the properties shared by all neocortical neurons. Ngn1 and Ngn2 are required to specify the cortical (regional), glutamatergic (neurotransmitter) and laminar (temporal) characters of early-born (lower-layer) neurons, while simultaneously repressing an alternative subcortical, GABAergic neuronal phenotype. Subsequently, later-born (upper-layer) cortical neurons are specified in an Ngn-independent manner, requiring instead the synergistic activities of Pax6 and Tlx, which also control a binary choice between cortical/glutamatergic and subcortical/GABAergic fates. Our study thus reveals an unanticipated heterogeneity in the genetic mechanisms specifying the identity of neocortical projection neurons.

Animals↗
PubMed2001

14-3-3 proteins; bringing new definitions to scaffolding.

The 14-3-3 proteins are a part of an emerging family of proteins and protein domains that bind to serine/threonine-phosphorylated residues in a context specific manner, analogous to the Src homology 2 (SH2) and phospho-tyrosine binding (PTB) domains. 14-3-3 proteins bind and regulate key proteins involved in various physiological processes such as intracellular signaling (e.g. Raf, MLK, MEKK, PI-3 kinase, IRS-1), cell cycling (e.g. Cdc25, Wee1, CDK2, centrosome), apoptosis (e.g. BAD, ASK-1) and transcription regulation (e.g. FKHRL1, DAF-16, p53, TAZ, TLX-2, histone deacetylase). In contrast to SH2 and PTB domains, which serve mainly to mediate protein-protein interactions, 14-3-3 proteins in many cases alter the function of the target protein, thus allowing them to serve as direct regulators of their targets. This review focuses on the various mechanisms employed by the 14-3-3 proteins in the regulation of their diverse targets, the structural basis for 14-3-3-target protein interaction with emphasis on the role of 14-3-3 dimerization in target protein binding and regulation and provides an insight on 14-3-3 regulation itself.

14-3-3 Proteins↗
PubMed2006

Comparison of spatio-temporal, metabolic, and psychometric responses in recreational and highly trained swimmers during and after a 400-m freestyle swim.

Spatio-temporal, metabolic and psychometric responses during and after a 400-m freestyle swim trial were investigated for gender and skill-level effects. Thirty-four men and women, 18 national and international competitors and 16 recreational swimmers, were compared. Mean speed, stroke rate (SR), and stroke length (SL) were obtained from video recordings. Peak heart rate (HR) and the lactate value (Hla) were determined, as were the recovery kinetics, i.e., the recovery time index (RTI) for heart rate and %Hla (r) for the lactate values. Well-being was assessed with the Profile of Mood States questionnaire (POMS). Subjective workload was assessed with the NASA-TLX questionnaire. The experts showed less variation in their swim speed than the recreational swimmers. The male experts showed greater SL and the female experts showed greater SL and SR. No significant difference was noted between the experts and recreational swimmers for peaks of HR and Hla, POMS (157.3 +/- 15.1 vs. 163.1 +/- 21.5), or subjective workload (32.4 +/- 6.7 vs. 31.6 +/- 6.1). The experts exhibited higher RTI (- 38.5 +/- 5.5 % vs. - 31.1 +/- 5.4 %) and %Hla (r) (8.6 +/- 7.18 % vs. 1.65 +/- 8.2 %). They also showed an improvement of 7.8 +/- 2.6 % for men and 6.02 +/- 1.6 % for women between the performance time for the trial and the best competitive time of the season. Last, our results suggest that the 400-m freestyle trial is a valid field test to evaluate the maximal aerobic speed (MAS) of swimmers with different training status. The systemic analysis herein described can be used to set the end-of-season target time for expert competitors. Attention should focus on SL, race management, and the physiological recovery for training prescription.

Adult↗
PubMed2003

Dispersal of NK homeobox gene clusters in amphioxus and humans.

The Drosophila melanogaster genome has six physically clustered NK-related homeobox genes in just 180 kb. Here we show that the NK homeobox gene cluster was an ancient feature of bilaterian animal genomes, but has been secondarily split in chordate ancestry. The NK homeobox gene clusters of amphioxus and vertebrates are each split and dispersed at two equivalent intergenic positions. From the ancestral NK gene cluster, only the Tlx-Lbx and NK3-NK4 linkages have been retained in chordates. This evolutionary pattern is in marked contrast to the Hox and ParaHox gene clusters, which are compact in amphioxus and vertebrates, but have been disrupted in Drosophila.

Amino Acid Sequence↗
PubMed2000

Evolution of Antp-class genes and differential expression of Hydra Hox/paraHox genes in anterior patterning.

The conservation of developmental functions exerted by Antp-class homeoproteins in protostomes and deuterostomes suggested that homologs with related functions are present in diploblastic animals. Our phylogenetic analyses showed that Antp-class homeodomains belong either to non-Hox or to Hox/paraHox families. Among the 13 non-Hox families, 9 have diploblastic homologs, Msx, Emx, Barx, Evx, Tlx, NK-2, and Prh/Hex, Not, and Dlx, reported here. Among the Hox/paraHox, poriferan sequences were not found, and the cnidarian sequences formed at least five distinct cnox families. Two are significantly related to the paraHox Gsx (cnox-2) and the mox (cnox-5) sequences, whereas three display some relatedness to the Hox paralog groups 1 (cnox-1), 9/10 (cnox-3) and the paraHox cdx (cnox-4). Intermediate Hox/paraHox genes (PG 3 to 8 and lox) did not have clear cnidarian counterparts. In Hydra, cnox-1, cnox-2, and cnox-3 were not found chromosomally linked within a 150-kb range and displayed specific expression patterns in the adult head. During regeneration, cnox-1 was expressed as an early gene whatever the polarity, whereas cnox-2 was up-regulated later during head but not foot regeneration. Finally, cnox-3 expression was reestablished in the adult head once it was fully formed. These results suggest that the Hydra genes related to anterior Hox/paraHox genes are involved at different stages of apical differentiation. However, the positional information defining the oral/aboral axis in Hydra cannot be correlated strictly to that characterizing the anterior-posterior axis in vertebrates or arthropods.

Amino Acid Sequence↗
PubMed2002

Age differences in perceived workload across a short vigil.

The main objective of this research was to investigate age differences in the perceived workload associated with the performance of a demanding, high event rate, vigilance task. Younger participants (n=26) aged 16 to 35 years (M=27.8) and older participants (n=24) aged 45 to 65 years (M=52.2) completed perceived workload scales (NASA-TLX) following a brief practice session (pretest) on the vigilance task, and then again following a test session (posttest) lasting nine minutes. In relation to the vigilance task, a statistically significant performance decrement was identified, but there was no evidence that performance differed according to age in respect to that decrement. However, a dissociation was found in relation to the perceived workload ratings: while no age differences were found in vigilance performance, the workload ratings revealed older participants to perceive a significantly greater increase in workload from pretest to posttest. These findings are considered theoretically in relation to the demands placed upon attentional resources, and their implications for both laboratory-based vigilance research, and workplace systems monitoring situations, are discussed.

Adolescent↗
PubMed2003

Multimodal feedback: an assessment of performance and mental workload.

Multimodal interfaces offer great potential to humanize interactions with computers by employing a multitude of perceptual channels. This paper reports on a novel multimodal interface using auditory, haptic and visual feedback in a direct manipulation task to establish new recommendations for multimodal feedback, in particular uni-, bi- and trimodal feedback. A close examination of combinations of uni-, bi- and trimodal feedback is necessary to determine which enhances performance without increasing workload. Thirty-two participants were asked to complete a task consisting of a series of 'drag-and-drops' while the type of feedback was manipulated. Each participant was exposed to three unimodal feedback conditions, three bimodal feedback conditions and one trimodal feedback condition that used auditory, visual and haptic feedback alone, and in combination. Performance under the different conditions was assessed with measures of trial completion time, target highlight time and a self-reported workload assessment captured by the NASA Task Load Index (NASA-TLX). The findings suggest that certain types of bimodal feedback can enhance performance while lowering self-perceived mental demand.

Adult↗
PubMed1996

Effects of control order, augmented feedback, input device and practice on tracking performance and perceived workload.

Virtual interfaces to advanced human-machine systems will present operators with a variety of perceptual-motor challenges. To inform the virtual interface design processes, the present experiments examined the effects of track order, level of knowledge of performance, type of control device, and the extent of practice on tracking performance and associated mental workload. Tracking was assessed by root mean square error. Subjective workload was measured using both the NASA Task Load Index (TLX) and the Subjective Workload Assessment Technique (SWAT). Results indicated non-linear effects, where tracking error and subjective workload both increased non-proportionally with track order. Trackball use resulted in more accurate performance and was judged to be of lower subjective workload than input using a mouse. Augmented knowledge of performance had little effect on either performance or workload. There was a number of interactions affecting performance that were replicated in perceived workload. Over acquisition trials, second-order tracking exhibited continuous improvement. This capability was retained even after a 30-day rest interval. Decrease a workload followed performance improvement in both initial acquisition and subsequent retention phases. The two subjective workload scales were essentially equivalent in terms of their sensitivity to task manipulations. These results support the direct association between workload and performance and confirms the use of workload in helping to evaluate the influence of diverse task-related demands. The implications for the design of virtual interfaces to real-world systems are examined in the light of these findings.

Adult↗
PubMed1993

Sex differences in vigilance performance and perceived workload.

Female and male subjects monitored the repetitive presentation of a pair of lines for occasional changes in height (spatial task) or duration (temporal task). Perceptual sensitivity for critical signals favored men in the spatial task, whereas no sex differences in signal detectability existed in the temporal task. Measurements of perceived workload using the NASA-TLX scale mirrored these performance effects. Women tended to rate the overall workload associated with the spatial task to be greater in comparison with men. In addition, women found the spatial task to be significantly more frustrating, mentally demanding, and effortful than men did and rated their own performance lower than their male counterparts did. In contrast, no sex-linked differences in perceived workload were noted in regard to the temporal task. The results support the suggestion by Dittmar, Warm, and Dember (1987) that sex differences in sustained attention are task specific.

Adolescent↗
PubMed2001

Heavy mining vehicle controls and skidding accidents.

This paper examines various control locations in heavy mining vehicles. Three trucks have been tested on a skid pad in both clockwise and anticlockwise directions. The skid lengths were measured after each trial. The primary focus of the study was the positioning of various controls and their relevance to various skid lengths. Some additional measures such as NASA-TLX scales were also used to make subjective evaluations. The results are presented in this paper. The findings clearly indicate the relevance of control locations to actual skid lengths. The poorly located controls resulted in greater skid lengths. This is an important finding as skid lengths are related to greater reaction times in a skidding situation and hence greater risk of accidents on relevant trucks. Such accidents can incur large repair bills for damaged equipment whereas more importantly, jeopardizing the life and safety of heavy mining vehicle drivers.

Accidents, Occupational↗
PubMed1986

Inhibitors of complement-mediated cytotoxicity in normal and secondary aborter sera.

Sera from patients with secondary (2 degrees) spontaneous abortions contain complement-dependent cytotoxic (CDC) antibodies with specificity for paternal lymphocytes. These lymphocytotoxins are not anti-HLA (human lymphocyte antigen) as shown by their polyspecificity on HLA select cell panels and by their removal following absorption with HLA-negative trophoblast membranes. They are predominantly IgG and have been designated as trophoblast-lymphocyte cross-reactive (TLX) antibodies. Normal and homologous 2 degrees aborter sera contain a CDC inhibitor that does not bind to paternal cells and must be present when complement is added to antibody. The inhibitor does not manifest anticomplement effects and appears to be species specific. Inhibitory capacity is increased by heating (56 degrees C for 30 min) and by absorption with heparin. When chromatographed on G-200 Sephadex, inhibitor appears in the void volume, suggesting a molecular weight of more than 250,000. It can be isolated from diethylaminoethyl cellulose into an euglobulin fraction that does not contain IgG, but does contain IgM, though no studies indicate the inhibitor to be IgM. We suggest that the inhibitor is under the control of a regulator molecule, probably an inhibitor-of-inhibitor, and that in 2 degrees aborter sera the equilibrium is unbalanced between antibody, inhibitor, and regulator.

Abortion, Habitual↗
PubMed1986

Immunotherapy of primary immunological aborters: rationale for the use of pooled cryopreserved purified normal peripheral blood mononuclear cells.

Patients with recurrent spontaneous abortions have been successfully treated in many centers with third-party immunization directed to a putative TLX antigen system. This immunotherapy requires the screening of a large number of donors to match the patients' red blood cell (RBC) phenotype and has the potential risks associated with transfusions from 30 to 50 donors. Our modified approach to third-party immunization is to use irradiated frozen-stored purified lymphocytes pooled from five normal donors. Mononuclear cells from normal donors are obtained in a cell separator. After sedimentation and Ficoll-Hypaque separation, the cells are stored in liquid N2. The RBC depletion of the final preparation is of the order of 5 to 6 logs, theoretically decreasing the need for RBC phenotyping except for the Rh system. Using a highly sensitive fluorescence-activated cell sorter technique and an ADCC assay, we found that ABH, Rh, Fya Fyb, Jka Jkb, MNS, and Kell antigens are either not expressed by cryopreserved human mononuclear cells, or, if so, they are below the level of detection of these highly sensitive assays. We conclude that the use of pooled frozen mononuclear cells is an adequate alternative for immunotherapy. It decreases the transfusion risks associated with exposure to a large number of donors and the need for RBC phenotyping, making this modality of treatment more accessible.

ABO Blood-Group System↗
PubMed1986

Distribution of Trop 3 and 4 antigens as defined by monoclonal antibodies raised against a human choriocarcinoma cell line.

The reactivities of Trop 3 and 4 monoclonal antibodies (MAbs) were studied on human term and 7-week extraembryonic membranes, adult tissues, and cell lines. Trop 3 MAb reacted with cells of chorionic villi, decidua, amniotic epithelium, and basal plate trophoblast. Trop 4 MAb reacted only with syncytiotrophoblast. On epithelium, Trop 3 MAb bound to stratified and glandular epithelium, but Trop 4 MAb reactivity was limited to basal keratinocytes. On peripheral blood mononuclear cells, Trop 3 MAb reacted with the majority of cells and Trop 4 MAb with the totality. Most cell lines were positive with both MAbs. However, one chemically induced MHC mutant was negative and another decreased its expression of Trop 3 antigen. Our results suggest Trop 3 MAb might recognize a monomorphic determinant of TLX antigens and Trop 4 is involved in cell proliferation or in cell-to-cell interaction.

Antibodies, Monoclonal↗
PubMedDate not supplied

Immunological role for seminal plasma in insemination and pregnancy.

Insemination confronts the female with paternally derived alloantigens and represents an immunological challenge preceding fertilization and implantation. Current evidence suggests a role for seminal plasma in regulating maternal immunity for insemination and pregnancy. In vitro seminal plasma has been shown to suppress T- and B-cell proliferation, neutrophil and macrophage phagocytic activity, as well as killer cell activity. Seminal plasma interacts with complement components C1 and C3 and contains factors that specifically bind the Fc region of IgG. These in vitro findings suggest possible seminal plasma-suppressive effects on female alloimmune responses after insemination. Seminal plasma also contains allotypic TLX antigens that could prime mothers prior to fertilization. Such priming effects for pregnancy acceptance are supported by improved implantation rates in controlled clinical trials using timed vaginal exposure to semen during in vitro fertilization or gamete intrafallopian transfer treatment cycles.

Female↗
PubMed1997

Human cytotrophoblastic cells absorb the NK blocking activity of monoclonal BA11.

PROBLEM: R80K is a polymorphic alloantigeneic protein present on human placental trophoblast and on paternal B lymphocytes and monocytes. This protein, unlike the former candidate TLX antigen, stimulates a protective maternal immune response in vivo. A murine monoclonal BA11 antibody, directed against R80K, prevents abortion in three murine pregnancy-failure models and inhibits human and murine NK activity. We attempted to define the target of BA11 in the human NK assay system. METHODS: A CELISA method was used to detect R80K antigen on the surface of different cells using the BA11 antibody. The effect, on human peripheral blood NK activity against K562, by BA11 before and after absorption by different cells, including the K562 target, was determined. RESULTS: R80K was detected on term placental syncytio and cytotrophoblast and on BeWo cells, by CELISA. BA11 suppressed NK lysis of K562 cell sin a dose-dependent manner. Absorption of the BA11 by BeWo and by cytotrophoblastic cells significantly decreased the NK-inhibitory activity. There was minimal absorption by K562 and BA11-pretreateed K562 cells remained susceptible to NK lysis. By contrast, BA11-pretreated peripheral blood cells lost all NK activity. CONCLUSIONS: The inhibition of NK killing of K562 cells by BA11 is more complex than simple masking of a trophoblast cell-associated molecule in K562 necessary for recognition in NK cells.

Absorption↗
PubMed1992

[Immunologic factors in habitual abortion].

Recent advances in immunology have discovered two immunological factors in part of the patients with habitual first-trimester abortions. Antibody formation against the major histocompatibility antigens (HLA = human leukocyte antigen) which can be demonstrated during normal pregnancy is often not detectable in these patients, sometimes presumably because of compatibility in the HLA antigens between mother and fetus. In a high percentage of these patients immunotherapy by subcutaneous leukocyte injections can lead to antibody formation and successful pregnancy. As another immunological factor, a genetic variant of the complement-inactivating leukocyte differentiation antigen CD46 (= TLX antigen, = membrane cofactor protein) could be identified, which can be seen more frequently in patients with habitual abortions as compared to healthy controls. Both factors seem just to contribute to a predisposition for early-pregnancy abortions rather than to be an absolute barrier, as they can also be seen in normal pregnancy and successful carriages can also occur without any therapy in early-pregnancy aborters with an immunological background.

Abortion, Habitual↗
PubMed2006

The evaluation of a pulmonary display to detect adverse respiratory events using high resolution human simulator.

OBJECTIVE: Authors developed a picture-graphics display for pulmonary function to present typical respiratory data used in perioperative and intensive care environments. The display utilizes color, shape and emergent alerting to highlight abnormal pulmonary physiology. The display serves as an adjunct to traditional operating room displays and monitors. DESIGN: To evaluate the prototype, nineteen clinician volunteers each managed four adverse respiratory events and one normal event using a high-resolution patient simulator which included the new displays (intervention subjects) and traditional displays (control subjects). Between-group comparisons included (i) time to diagnosis and treatment for each adverse respiratory event; (ii) the number of unnecessary treatments during the normal scenario; and (iii) self-reported workload estimates while managing study events. MEASUREMENTS: Two expert anesthesiologists reviewed video-taped transcriptions of the volunteers to determine time to treat and time to diagnosis. Time values were then compared between groups using a Mann-Whitney-U Test. Estimated workload for both groups was assessed using the NASA-TLX and compared between groups using an ANOVA. P-values < 0.05 were considered significant. RESULTS: Clinician volunteers detected and treated obstructed endotracheal tubes and intrinsic PEEP problems faster with graphical rather than conventional displays (p < 0.05). During the normal scenario simulation, 3 clinicians using the graphical display, and 5 clinicians using the conventional display gave unnecessary treatments. Clinician-volunteers reported significantly lower subjective workloads using the graphical display for the obstructed endotracheal tube scenario (p < 0.001) and the intrinsic PEEP scenario (p < 0.03). CONCLUSION: Authors conclude that the graphical pulmonary display may serve as a useful adjunct to traditional displays in identifying adverse respiratory events.

Attitude of Health Personnel↗
PubMed1995

Effects of jet engine noise and performance feedback on perceived workload in a monitoring task.

This study examined the effects of exposure to intermittent jet aircraft noise (70 dBA or 95 dBA maximum intensity) and knowledge of results concerning signal detections (hit-KR) on performance efficiency and perceived workload in a 40-min visual vigilance task. The noise featured a Doppler-like quality in which planes seemed to approach from the monitor's left and recede to the right. Perceptual sensitivity (d') was poorer in the context of noise than in quiet but only in the presence of hit-KR. The lack of noise-related performance differences in the absence of hit-KR most likely reflected a "floor effect" rather than some special relation between noise and feedback. When compared to subjects performing in quiet, those who operated in noise were less able to profit from hit-KR, a result that may reflect the effects of noise on information processing. In addition to its negative effects on signal detectability, noise elevated the perceived workload, as measured by the NASA-TLX. This effect was robust; it was independent of the presence of hit-KR, even though hit-KR generally lowered the overall level of perceived workload. The results provide the initial experimental demonstration that perceived workload is a sensitive measure of the effects of aircraft noise in monitoring tasks.

Adolescent↗