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126 records · Page 7Linked to original sources
PubMed2001

The serine/threonine transmembrane receptor ALK2 mediates Müllerian inhibiting substance signaling.

Müllerian inhibiting substance (MIS or anti-Müllerian hormone) is a member of the transforming growth factor-beta family and plays a pivotal role in proper male sexual differentiation. Members of this family signal by the assembly of two related serine/threonine kinase receptors, referred to as type I or type II receptors, and downstream cytoplasmic Smad effector proteins. Although the MIS type II receptor (MISRII) has been identified, the identity of the type I receptor is unclear. Here we report that MIS activates a bone morphogenetic protein-like signaling pathway, which is solely dependent on the presence of the MISRII and bioactive MIS ligand. Among the multiple type I candidates tested, only ALK2 resulted in significant enhancement of the MIS signaling response. Furthermore, dominant-negative and antisense strategies showed that ALK2 is essential for MIS-induced signaling in two independent assays, the cellular Tlx-2 reporter gene assay and the Müllerian duct regression organ culture assay. In contrast, ALK6, the other candidate MIS type I receptor, was not required. Expression analyses revealed that ALK2 is present in all MIS target tissues including the mesenchyme surrounding the epithelial Müllerian duct. Collectively, we conclude that MIS employs a bone morphogenetic protein-like signaling pathway and uses ALK2 as its type I receptor. The use of this ubiquitously expressed type I receptor underscores the role of the MIS ligand and the MIS type II receptor in establishing the specificity of the MIS signaling cascade.

Activin Receptors, Type I↗
PubMed1996

A functional homologue of goosecoid in Drosophila.

We have cloned a Drosophila homologue (D-gsc) of the vertebrate homeobox gene goosecoid (gsc). In the Gsc proteins, the pressure for conservation has been imposed on the homeodomain, the functional domain of the protein: sequence homology is limited to the homeodomain (78% identity) and to a short stretch of 7 aminoacids also found in other homeoproteins such as Engrailed. Despite this weak homology, D-gsc is able to mimic gsc function in a Xenopus assay, as shown by its ability to rescue the axis development of a UV-irradiated embryo. Moreover, our data suggest that the position of insect and vertebrate gsc homologues within a regulatory network has also been conserved: D-gsc expression is controlled by decapentaplegic, orthodenticle, sloppy-paired and tailless whose homologues control gsc expression (for BMP4 and Otx-2), or are expressed at the right time and the right place (for XFKH1/Pintallavis and Tlx) to be interacting with gsc during vertebrate development. However, the pattern of D-gsc expression in ectodermal cells of the nervous system and foregut cannot easily be reconciled with that of vertebrate gsc mesodermal expression, suggesting that its precise developmental function might have diverged. Still, this comparison of domains of expression and functions among Gsc proteins could shed light on a common origin of gut formation and/or on basic cellular processes. The identification of gsc target genes and/or other genes involved in similar developmental processes will allow the definition of the precise phylogenetic relationship among Gsc proteins.

Amino Acid Sequence↗
PubMed2000

The effects of signal salience and caffeine on performance, workload, and stress in an abbreviated vigilance task.

In 2 experiments, a 12-min computerized vigilance task was demonstrated to reproduce the vigilance decrement, high workload (NASA-TLX), and stressful character (Dundee Stress State Questionnaire) of vigilance tasks lasting 30 min or more. In Experiment 1, the abbreviated task was also shown to duplicate the signal salience effect, a major finding associated with long-duration vigilance tasks. Moreover, Experiment 2 showed that performance on the abbreviated task can be enhanced by caffeine - a drug that benefits long-duration tasks. This enhancement effect was limited to performance, however, suggesting that caffeine influences factors that control signal detection but not those that control task-induced stress. The results parallel those obtained with long-duration tasks and support a resource-depletion model of the vigilance decrement. The abbreviated task might be useful in situations in which long-duration tasks are precluded (e.g., performance assessment batteries, neuropsychological testing, and brain imaging).

Adolescent↗
PubMed1998

Context effects in subjective mental workload ratings.

The impact of performance context on subjective mental workload ratings was assessed with the Subjective Workload Assessment Technique (SWAT) and the NASA Task Load Index (TLX). In Experiment 1, a strong context effect was demonstrated. A low range of task difficulty produced considerably higher ratings on a common set of difficulty levels than did a high range of task difficulty. In Experiment 2, increasing the participants' range of experiences during practice eliminated the context effect. We recommend that methods for standardizing context, such as providing experience with the complete difficulty range, be developed for subjective mental workload evaluations. Actual or potential applications of this research include providing methodologies for controlling context effects in practical assessments of mental workload to increase the validity of subjective measures.

Adult↗
PubMed2003

The vigilance decrement reflects limitations in effortful attention, not mindlessness.

Robertson, Manly, Andrade, Baddeley, and Yiend (1997) proposed that the decline in performance efficiency over time in vigilance tasks (the vigilance decrement) is characterized by "mindlessness" or a withdrawal of attentional effort from the monitoring assignment. We assessed that proposal using measures of perceived mental workload (NASA-TLX) and stress (Dundee Stress State Questionnaire). Two types of vigilance task were employed: a traditional version, wherein observers made button-press responses to signify detection of rarely occurring critical signals, and a modified version, developed by Robertson et al. to promote mindlessness via routinization, wherein button-press responses acknowledged frequently occurring neutral stimulus events and response withholding signified critical signal detection. The vigilance decrement was observed in both tasks, and both tasks generated equally elevated levels of workload and stress, the latter including cognitions relating to performance adequacy. Vigilance performance seems better characterized by effortful attention (mindfulness) than by mindlessness. Actual or potential applications of this research include procedures to reduce the information-processing demand imposed by vigilance tasks and the stress associated with such tasks.

Adult↗
PubMed2004

Effects of the periodic administration of odor or vibration on a 3-hr. vigilance task.

The present study examined performance during 3 hr. of simulated sentry duty with and without the intermittent administration of low-level sensory stimuli (odor or vibration). For odor and control conditions, target-detection latency increased steadily over the course of the 3-hr. session. Administration of a tactile stimulus reduced the increase in detection latency compared to that found in odor and control conditions. For all conditions, there were no significant differences in target-detection frequency, shot accuracy, or friend-foe discrimination. Across all conditions, restlessness (motor activity) increased significantly the first hour and remained elevated for the rest of the session. Subjective measures of workload (NASA-TLX) indicated that the 3-hr. task rated high on physical demand, mental demand, frustration, and overall workload. These findings suggest that the intermittent delivery of a clearly detectable tactile stimulus can reduce reaction-time decrements that occur as time on task increases.

Arousal↗
PubMed1994

Recurrent abortions and lymphocyte transfusions.

Normal pregnancies depend on successful implantation of the placenta in the uterus. The trophoblast which forms the ultimate interface between the fetal and maternal tissue seems to lack the foreign (allo) antigens (namely HLA/TLX) required to induce immunological rejection reactions in the mother. It was previously believed that the trophoblast expressed paternal allo antigens and that successful pregnancies were dependent on so called 'kind' (non-cytotoxic or non-complement binding) blocking antibodies in order to protect the fetal unit from maternal cytotoxic T-cells and -antibodies. Blocking antibodies attached to paternal antigens on the trophoblast were assumed to prevent maternal cytotoxic T cell and cytotoxic antibodies from recognising the trophoblast as foreign tissue. On this assumption it was reasoned that transfusions of paternal HLA-expressing lymphocytes would increase maternal antipaternal HLA (TLX) blocking antibodies and thus be beneficial to women who experienced multiple miscarriages. There is, however, no scientific evidence for a specific immune response after lymphocyte transfusions that fulfil this function. Immunological tests, as for example mixed lymphocyte culture (MLC), on peripheral blood lymphocytes do not seem to reflect the local immune state in the uterus, either in the pregnant or the non-pregnant state. Since the trophoblast forms the ultimate interface between fetal and maternal tissue, its structure, secretions, and interaction with the decidua must be of definite importance for implantation of the blastocyst and growth of the embryo.

Abortion, Habitual↗
PubMed1997

Factors influencing mental workload indexes.

Several findings of the author's own mental workload research are reviewed. Especially, factors, except task demand, influencing mental workload indexes are discussed. First, an experiment using the National Aeronautics and Space Administration Task Load Index (NASA TLX) is reviewed and the effects of a prior task load on a subsequent subjective workload are described. In a physiological measures section, the low reliability of the heart rate variability (HRV) parameters when the subjects' respiration pattern are highly irregular, and the existence of low sweat respondent, although perspiration seems to be sensitive to the workload, are indicated. Furthermore, results of the task specific physiological responses and of a HRV parameter affected by the individual characteristics, like type A behavior pattern, are shown. Discrepancy between autonomic nervous system activity measures may be solvable by introducing a new concept of autonomic space (synergism of sympathetic and parasympathetic nervous system). Finally, the need for strategies of data management concerning the individual differences is emphasized.

Autonomic Nervous System↗
PubMed2001

Dendritic growth induced by BMP-7 requires Smad1 and proteasome activity.

Bone morphogenetic proteins (BMPs) induce dendritic growth in cultured sympathetic neurons; however, the signaling pathways that mediate this dendrite-promoting activity have not been previously characterized. Here we report studies of the signaling events that regulate the growth of these afferent processes. We find that Smad1 is expressed in sympathetic neurons and that BMPs rapidly induce its phosphorylation and translocation from the cytoplasm to the nucleus. Furthermore, a dominant negative form of Smad1 inhibits BMP-7-induced dendritic growth, suggesting a requirement for Smad1 activation in this biological activity of BMP-7. A physical interaction between Smad1 and components involved in the proteasome-mediated degradation system was detected with a yeast two-hybrid screen, thereby prompting an examination of the effects of proteasome inhibitors on dendritic growth. Lactacystin and ALLN (N-acetyl-Leu-Leu-norleucinal) selectively blocked BMP-7-induced dendritic growth without adversely affecting either cell viability or axonal growth. Moreover, studies of transfected P19 cells suggest that the proteasome inhibitors directly block the effects of Smad1 on the transcriptional activity of the Tlx-2 promoter. These data indicate that BMP-induced dendritic growth requires Smad1 activation and involves proteasome-mediated degradation events.

Acetylcysteine↗
PubMed1992

Flow cytometric quantitation of the expression of membrane cofactor protein as a marker for the human sperm acrosome reaction.

A mAb (TRA-2-10, IgG1) to an embryonal carcinoma cell line (2102ep) that recognizes an antigen termed membrane cofactor protein (CD 46, TLX antigen) binds to human sperm after chemical induction of acrosomal loss by Ca2+ ionophore. An indirect immunofluorescence assay was developed in which sperm membrane cofactor protein was detected by flow cytometry on acrosome-reacted living human sperm. The expression of the membrane cofactor protein antigen on acrosome-reacted sperm may represent a marker that can be used in a rapid, quantitative, and reproducible flow cytometric assay for the evaluation of human sperm acrosomal loss.

Acrosome↗
PubMedDate not supplied

Immunobiomarkers in alloimmune recurrent spontaneous abortion. A reappraisal.

The Class I gene expression and regulation will be in the near future a main topic for studies in the reproductive immunology. Unfortunately at present this finding do not provide yet available markers for the diagnostic work-up of recurrent abortions. In addition also the study of HLA frequencies in individuals affected by recurrent abortions is not providing a clear marker to be utilized for clinical purposes. Also the TLX antigen system is submitted to several critiques: the antigens have yet to be characterized biochemically. Furthermore the blocking activity is not always detected in the serum of women with normal pregnancy, as shown in the mixed lymphocyte reaction (MLR). The Authors conclude, on the bases of the biologic evidence, that more effective immunobiomarkers are needed to detect a possible pathologic allogenic recognition in recurrent aborters.

Abortion, Habitual↗
PubMed1986

Characterization of the human trophoblast-leukocyte antigenic molecules defined by a monoclonal antibody.

The murine monoclonal antibody H316 recognizes cell surface glycoproteins shared in expression by human trophoblast and peripheral blood leukocytes. It is also strongly expressed by many human tumor cell types, including choriocarcinoma and teratocarcinoma. The H316 antigenic determinant from these different cell types is carried on two wheat germ agglutinin-reactive glycoproteins of approximately 65,000 and 55,000 m.w. The antigenicity is not dependent on N-linked glycosylation. Biochemical fractionation procedures suggest that the molecules are related to each other, are not associated through intermolecular disulfide bonds, but do exhibit intramolecular disulfide interactions. These glycoproteins demonstrate m.w. heterogeneity between different cell lines and individual trophoblast membrane preparations. Such properties suggest that H316 molecules may be representative of TLX antigens (trophoblast-leukocyte common antigens), which have been suggested to influence maternofetal immunogenetic interactions.

Antibodies, Monoclonal↗
PubMed1986

Clinical value of research in chronic spontaneous abortion.

We have focused on comparisons of abnormal with normal pregnancies. Humoral and cellular aspects were studied in 50 couples with unexplained consecutive pregnancy failures and compared with 15 fertile couples. The results show that spontaneous aborters generally fall into two groups: Primary spontaneous aborters are those women who, by the same husband, never have carried a pregnancy beyond 20 weeks; secondary spontaneous aborters have had, by the same husband, either a normal pregnancy or a pregnancy failure beyond the 20th week. Primary spontaneous aborting couples tend to share a significantly greater number of HLA antigens than do secondary aborters or normally fertile mates. Secondary spontaneous aborters manifest cytotoxic non-HLA-dependent antibody to husbands' lymphocytes in complement-dependent assays; these are antibodies to trophoblast-lymphocyte cross-reactive (TLX) antigens. Secondary but not primary aborters have complement-independent antibody-dependent cell-mediated cytotoxicity reactions to their husbands' lymphocytes. Both exhibit diminished mixed lymphocyte culture reactions between mating partners if the tests are done in autologous plasma; only primary aborters show poor reactions if the assays are done in control sera. Immunotherapy with nonhusband lymphocytes in more than 20 primary spontaneous aborters has resulted in greater than 90% successful subsequent pregnancies. Leukocyte immunotherapy has not been useful for secondary aborters, but two of three women have had normal pregnancies following daily subcutaneous injections of heparin. The clinical relevance of these findings will be discussed.

Abortion, Habitual↗
PubMed1986

Immunological and genetic factors influencing pregnancy and development.

Hypotheses concerning reproductive competence focus on immunological and genetic mechanisms. The immunological hypothesis involves arguments that an immune response is necessary for implantation (or at least increased reproductive capacity), the antibody response to the placental antigens is composed of "blocking" antibodies, immunosuppressive factors are produced during pregnancy, and HLA antigen sharing in humans having chronic spontaneous abortions (CSA) causes a decreased immune response. The most potent antigen on the placenta is a class I molecule different from the classical transplantation antigens: Pa in the rat and TLX in the human. The genetic hypothesis states that CSA may be due to the presence of major histocompatibility complex (MHC)-linked, recessive lethal genes in the fetus and that the sharing of HLA antigens is just a marker for this segment of chromosome. Recessive lethal genes linked to the MHC exist in mice and rats and possibly in humans. They could act by themselves to cause fetal loss, or they could act epistatically with nonMHC lethal genes. This type of interaction occurs in the rat between the MHC-linked grc and Tal or Hre. Recent work in our laboratory has shown that the grc also increases susceptibility to the development of cancer following the feeding of a chemical carcinogen. This unique finding presents a new and powerful approach to exploring the relationship between embryogenesis and carcinogenesis.

Abortion, Spontaneous↗
PubMed1981

Human extra-embryonic membranes: role of trophoblast in normal and abnormal pregnancies.

The human embryo is encased in extra-embryonic membranes which are covered with trophoblast throughout pregnancy. Bits and pieces of trophoblast break away from the placenta and are swept into the mother's circulation to lodge in her lungs without causing evidence of inflammation or rejection. This is in part due to an absence of histocompatibility antigens from trophoblast membranes, but it may also be due to a structural glycoprotein which is capable of inhibiting allogeneic recognition and rejection reactions. Another glycoprotein of the trophoblast is shared with lymphocytes, and serological studies have shown this to be polymorphic. Evidence has also been accumulated that this genetically determined cell membrane component is associated with the major histocompatibility complex, and that maternal recognition of this may be necessary to produce blocking factors that protect trophoblast from maternal rejection. Women who lack these factors during pregnancy tend to abort, and some of these patients also share several HLA antigens with their husbands. In an effort to produce blocking factors artificially, four aborting women were immunized with trophoblast-lymphocyte cross-reactive antigens, and this has resulted in normal pregnancies and the delivery of healthy babies at term. This finding suggests that genetical diversity of HLA is associated with TLX antigens, thus providing a mechanism whereby HLA not only generates but is also responsible for the perpetuation of diversity in human populations.

Abortion, Spontaneous↗
PubMed1997

[Immunopathology of early abortion: current status].

We reviewed the bibliography concerning the roles involved in the immunological mechanism related to the etiology of miscarriage, pointing out the main theories specially related to the Major Histocompatibility Complex and TLX antigen all together are beginners of the antiidiotype reaction in order to avoid having a miscarriage. It is mentioned that the blocking antibodies, suppressor cells and interleukines arrest the citotoxic immune mechanism against the fetal allograft. The new therapeutic approach is mentioned.

Abortion, Habitual↗
PubMed1996

[Immunology of early pregnancy. II. Decidua and trophoblast relationship].

Immunological competent cells and their cytokines exert a potent influence on both the placental function and the fetus. The different fetal and placental cells and in the same way modify cytokines production by the immunological system. The further characteristic of decidual lymphocytes subpopulations and their role in the regulation of embryonic development has been presented. The interactions between cytokines and growth factors derived from both decidua and trophoblast have been reviewed. The role of HLA-G, TLX and expressed cell differentiation antigens (complement system suppression) in the early pregnancy protection as well as trophoblast invasion inhibition have been discussed. The potential role of these factors in the early pregnancy loss has been considered.

Antigens, Differentiation↗
PubMed2026

Tailless terminates the neural stem cell temporal cascade in both the optic lobe and central brain.

Temporal patterning is an evolutionarily conserved mechanism to produce neuronal and glial diversity from common cells of origin during neurodevelopment. This process is controlled by a series of temporal transcription factors that are transiently expressed and drive the sequential production of specific progeny subtypes. Intermediate neural progenitors (INPs) and optic lobe neural stem cells (OL NSCs) share striking similarities in temporal factor expression despite divergent cells of origin. Tailless (Tll) is a terminal temporal factor in the visual system in OL NSCs. Its expression coincides with the termination of neurogenesis and onset of gliogenesis. Here, we report that Tll also acts as a terminal factor in Drosophila INPs, demonstrating functional conservation. Tll expression is activated by the preceding temporal factor Scarecrow, and represses odd-paired and hamlet. tll also plays a partial role in promoting gliogenesis in gliogenic NSCs. We performed genome-wide binding analysis of Tll in the OL NSCs and INPs by Targeted DamID, revealing both conserved and divergent targets, reflecting differences in regulatory outcomes. We show that temporal patterning mechanisms are conserved between different brain regions, whilst facilitating lineage-specific outputs.

Animals↗