Non-redundant Components Research Articles

Towards full employment: using RNAi to find roles for the redundant

Cancer is a genetic disease that ultimately results from the failure of cells to respond correctly to diverse signals. Signal transduction and signal integration are highly complex, requiring the combinatorial interaction of multiple genes. Classical genetics in model organisms including Caenorhabditis elegans has been of immense use in identifying nonredundant components of conserved signalling pathways. However, it is likely that there is much functional redundancy in the informational processing machinery of metazoan cells; we therefore need to develop methods for uncovering such redundant functions in model organisms if we are to use them to understand complex gene interactions and oncogene cooperation. RNAi may provide a powerful tool to probe redundancy in informational networks. In this review, I set out some of the progress made so far by classical genetics in understanding redundancy in gene networks, and outline how RNAi may allow us to approach this problem more systematically in C. elegans. In particular, I discuss the use of genome-wide RNAi screens in C. elegans to identify synthetic lethal interactions and compare this with synthetic lethal interaction analysis in Saccharomyces cerevisiae.

Early auditory–visual interactions in human cortex during nonredundant target identification

A common finding of behavioral studies is that objects characterized by redundant multisensory cues are identified more rapidly than the same objects presented in either unimodal condition. In a previous electrophysiological study in humans, we have described a network of crossmodal interactions that could be associated with this facilitation effect [M.H. Giard, F. Peronnet, J. Cogn. Neurosci. 11(5) (1999) 473–490]. Here, we sought to determine whether the recognition of objects characterized by nonredundant bimodal components may still induce crossmodal neural interactions. Subjects had to identify three objects defined either by auditory or visual features alone, or by the combination of nonredundant auditory and visual features. As expected, behavioral measures showed no sign of facilitation in bimodal processing. Yet, event-related potential analysis revealed the existence of early (<200 ms latency) crossmodal activities in sensory-specific and nonspecific cortical areas, that were partly dependent on the sensory dominance of the subjects to perform the task. Comparative analysis of the interaction patterns involved in redundant and nonredundant cue processing provides evidence for the robustness of the principle of crossmodal neural synergy that applies whatever the stimulus content (redundant or nonredundant information), and for the high flexibility of the neural networks of integration that are sensitive both to the nature of the perceptual task and to the sensory skill of the individual in that particular task.

X-LINKED AGAMMAGLOBULINEMIA

B-lymphocyte development is essential for production of functional antibody and humoral immune responses. The mechanisms that regulate this process are complex and tightly regulated. Defects in nonredundant components of this pathway lead to a clinical and immunologic syndrome of congenital agammaglobulinemia with absence of B-cell development. X-linked agammaglobulinemia (XLA) was the first of these conditions to be described and is the most common cause of congenital agammaglobulinemia. In 1993, abnormalities in the Bruton's tyrosine kinase (BTK) gene were shown to be the cause of XLA. A considerable amount of research has since been dedicated to understanding the genetic basis and molecular pathogenesis of the disease.

B-1 and B-2 cell-derived immunoglobulin M antibodies are nonredundant components of the protective response to influenza virus infection.

We have studied the role of secreted immunoglobulin (Ig)M in protection from infection with influenza virus and delineated the relative contributions of B-1 versus B-2 cell-derived IgM in this process. Mice deficient in secreted IgM but capable of expressing surface IgM and secreting other Ig classes show significantly reduced virus clearance and survival rates compared with wild-type controls. Irradiation chimeras in which only either B-1 or B-2 cells lack the ability to secrete IgM show mortality rates similar to those of mice in which neither B-1 nor B-2 cells secrete IgM. Dependence on both sources of IgM for survival is partially explained by findings in allotype chimeras that broadly cross-reactive B-1 cell-derived natural IgM is present before infection, whereas virus strain-specific, B-2 cell-derived IgM appears only after infection. Furthermore, lack of IgM secreted from one or both sources significantly impairs the antiviral IgG response. Reconstitution of chimeras lacking B-1 cell-derived IgM only with IgM-containing serum from noninfected mice improved both survival rates and serum levels of virus-specific IgG. Thus, virus-induced IgM must be secreted in the presence of natural IgM for efficient induction of specific IgG and for immune protection, identifying B-1 and B-2 cell-derived IgM antibodies as nonredundant components of the antiviral response.

Quality of life in psychiatry: a systematic contribution to construct validation and the development of the integrative assessment tool "modular system for quality of life".

The aim of the present study is to contribute to an ongoing validation process of the Quality of Life (QoL) construct in the clinical field by investigating its internal structure. Eight (inter)nationally validated questionnaires have been analyzed by an integrative approach in a multicenter study. Data has been collected in a mentally healthy (n = 479), a depressed (n = 171) and a schizophrenic (n = 139) sample. Apart from conventional psychometric criteria a similarity structure analysis (SSA) within a facet analytic methodology has been applied. A dimensional structure of the resulting integrative questionnaire "Modular System for Quality of Life" (MSQoL) could be generated that consists of one "G-factor" (life in general) and six specific dimensions (physical health, vitality, psychosocial relationships, material resources, affect, leisure time). This basic structure represents a core module measured by 47 items which is sufficiently valid for all three samples. The empirical structures of healthy, depressed and schizophrenic samples fulfill the first law of attitude and share a common variance of 95%. In addition, there are four specific modules (demography, family, partnership, profession). No specific modules could be identified for the psychopathological subgroups. The conclusion can be drawn that QoL is construed very similar by all three investigated populations which is the base for searching for quantitative differences and profiles. The MSQoL integrates the non-redundant components of eight QoL-instruments, is psychometrically able to assess the basic structure and can be completed within a cumulative research design by items specific for a particular setting.

Causal reasoning and the diagnostic process.

Causal reasoning as a way to make a diagnosis seems convincing. Modern medicine depends on the search for causes of disease and it seems fair to assert that such knowledge is employed in diagnosis. Causal reasoning as it has been presented neglects to some extent the conception of multifactorial disease causes. The purpose of this paper is to analyze aspects of causation relevant for discussing causal reasoning in a diagnostic context. The analysis will discuss different conceptions of causal reasoning in medical diagnosis, discriminating primarily between narrow causal diagnosis and more thorough causal explanation. The theory of causes as non-redundant factors in effective causal complexes is used as an analytical background. Causal explanations are performed according to different causal models. Such models of diagnosis are assumptions concerning structure and mechanisms, which cannot be directly or immediately observed. Conceptions and results of causal search strategies differ, according to the focus of the searcher. Causal reasoning is also seen in diagnosis in a more extensive meaning: the pin-pointing of factors responsible for the condition of the patient at any time during the course of disease. Causal reasoning and diagnosis go well in hand, especially if both concepts are widened. The theory of causes as non-redundant components in effective causal complexes, modulated by what is referred to as the stop problem and causal fields, is valuable for explaining the many aspects of causal reasoning in medical diagnosis.

Androgyny and sex role measurement: A personal construct approach.

Recent research into sex roles has been heavily influenced by androgyny theory, and by the development of the Bern Sex-Role Inventory (BSRI; Bern, 1974). Psychological androgyny is the combination, in one individual, of both culturally defined masculine and feminine personality traits. The Sex-Rep, a new instrument for assessing sex role which is aimed at rectifying certain problems associated with the BSRI, was then described. The Sex-Rep, the BSRI (Bern, 19 34), the Texas Social Behavior Inventory (TSBI; Spence & Stapp, 1974), the Beck Depression Inventory (BDI, Beck, 1967), and a self-concept thermometer, were given to 100 male and 108 female undergraduates. Results indicated that the BSRI and the Sex-Rep are both valid sex-role instruments, insofar as they both discriminate between males and females. They tend to measure nonredundant components of sex role as indicated by a lack of overlap between their sex-role classifications. The present study did not find any support for the balance model of androgyny which suggests that high masculinity and high femininity interact by balancing each other to produce a healthier, more behaviorally flexible individual. BSRI masculinity (M) was strongly related to adjustment in both sexes, but BSRI femininity (F) had little impact. This relationship between BSRI M and adjustment was described as probably resulting from measurement artifact since (&) only socially desirable traits are included on the BSRI, (b) removing self-esteem effects from the BSRI M scale enhanced its ability to discriminate between the sexes, (c) Sex-Rep masculinity was not related to adjustment for women, and its linkage to adjustment for men was less strong than BSRI M, (d) women rated their feminine constructs as more desirable than their masculine constructs, and (e) there were no actual self-esteem differences between males and females. Thus, findings from the BSRI regarding the relationship between sex role and adjustment must be called into question. Furthermore, since there is little overlap between genderrelated personal construals and social stereotypes, it is important to discover the effects of personal gender identity on personality and behavior.