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PubMed2004

Signal transduction inhibitors in cellular function.

Signal transduction pathways mediate cell-cell interactions and integrate signals from the extracellular environment through specific receptors at the cell membrane. They play a pivotal role in regulating cellular growth and differentiation and in mediating many physiological and pathological processes, such as apoptosis, inflammation, and tumor development. The mitogen- activated protein kinases (MAPKs) constitute a cascade of phosphorylation events that transmit extracellular growth signals through membrane-bound Ras to the nucleus of the cell. In this chapter, detailed protocols for analyzing the kinase activities of the key components of the MAPKs pathway MEK1, ERK1, JNK, and p38 MAPK are described. A brief introduction to the chemical inhibitors to the MAPKs pathway is provided in the method section of each kinase assay. Inhibitors of other signaling pathways are summarized in Table 1. The reporter assay of cyclin D1, a key downstream target gene of MAPKs pathway, is also described in detail.

Animals↗

PubMed2006

Marine reserve design: optimal size, habitats, species affinities, diversity, and ocean microclimate.

The design of marine reserves is complex and fraught with uncertainty. However, protection of critical habitat is of paramount importance for reserve design. We present a case study as an example of a reserve design based on fine-scale habitats, the affinities of exploited species to these habitats, adult mobility, and the physical forcing affecting the dynamics of the habitats. These factors and their interaction are integrated in an algorithm that determines the optimal size and location of a marine reserve for a set of 20 exploited species within five different habitats inside a large kelp forest in southern California. The result is a reserve that encompasses approximately 42% of the kelp forest. Our approach differs fundamentally from many other marine reserve siting methods in which goals of area, diversity, or biomass are targeted a priori. Rather, our method was developed to determine how large a reserve must be within a specific area to protect a self-sustaining assemblage of exploited species. The algorithm is applicable across different ecosystems, spatial scales, and for any number of species. The result is a reserve in which habitat value is optimized for a predetermined set of exploited species against the area left open to exploitation. The importance of fine-scale habitat definitions for the exploited species off La Jolla is exemplified by the spatial pattern of habitats and the stability of these habitats within the kelp forest, both of which appear to be determined by ocean microclimate.

California↗

PubMed1993

Treatment of social behavior in autism through the modification of pivotal social skills.

We examined acquisition of individual social communicative behaviors and generalization across other social behaviors in 2 children with autism. The results of a multiple baseline design showed that the children's treated social behaviors improved rapidly and that there were generalized changes in untreated social behaviors. These improvements were accompanied by increases in subjective ratings of the overall appropriateness of the children's social interactions. The results suggest the possibility of identifying pivotal response classes of social communicative behavior that may facilitate the understanding of social behavior in autism as well as improve peer interactions, social integration, and social development.

Adolescent↗

PubMed1979

The theory of social services in disaccumulationist capitalism.

The theory of social services today must be based on a more general theory of the "disaccumulation" of capitalist society. Capitalist society disaccumulates as new productive forces emerge within the framework of the capitalist labor market. These forces are expressed abstractly in new sources of productivity based on information and organization and concretely in a new organization of work. This new organization of work breaks down the old capitalist division between labor and non-labor time and poses instead a more fluid interaction and integration of work and non-work. Capitalist society, however, disaccumulates through social crisis. The reorganization of work is simultaneously expressed as the decay of the labor market. This decay delegitimates social services and creates the present social service crisis. Social services can find their new sources of legitimacy only if social classes can move past the crisis of disaccumulation and find the appropriate new forms of social life based on the emerging non-capitalist organization of work.

Conflict, Psychological↗

PubMed1995

The Internet, World-Wide Web, and Mosaic: an overview.

Technology is revolutionizing education. Global networks, powerful personal computers, and user friendly, graphically oriented software are creating a new infrastructure that promotes rapid, efficient access to information. Images, text, audio, and video can be integrated into interactive multimedia presentations, providing a hierarchy of knowledge that can be traversed by the click of a mouse. The extensive use of images in our arena makes radiologic education a major beneficiary. Because the components (text, images) of educational presentations are stored electronically on a network rather than on the printed page, an individual component can be linked and bundled into as many different presentations as desired. Furthermore, components of information can exist on different computers throughout the world and yet be linked by software into a single presentation.

Computer Communication Networks↗

PubMed1992

Experimental diabetic neuropathy. Effect of ganglioside treatment on axonal transport of cytoskeletal proteins.

Abnormalities in axonal transport of proteins are thought to play an important role in the pathogenesis of diabetic neuropathy. Gangliosides exert a positive action on numerous alterations in biochemistry and physiology of diabetic nerves. This study was undertaken to assess the effects of exogenous gangliosides on the axonal transport of structural proteins such as actin and tubulin in the sensory fibers of short-term (9-wk) and long-term (6-mo) diabetic rats. Adult Sprague-Dawley rats were made diabetic with a single injection of 70 mg/kg streptozocin i.p. Subgroups were injected daily with either highly purified ganglioside mixture (10 mg/kg i.p.) or saline for 1 mo, beginning either 2 or 17 wk after streptozocin injection. Age-matched rats were used as controls. Axonal transport was studied by the pulse-labeling technique. Three weeks after labeling, sciatic nerves were dissected out and processed for sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography. In diabetic rats of both experimental designs, the transport rate of tubulin and actin was decreased by approximately 30% compared with control rats. Ganglioside treatment counteracted such alterations in both 9-wk and 6-mo diabetic rats. These data suggest a pharmacological effect that could be correlated with molecular interactions between integral membrane glycolipids and cytoskeletal elements.

Actins↗

PubMed2004

Enhancement of prosthetics and orthotics learning and teaching through e-Learning technology and methodology.

A Write-Once Publish-Everywhere model was used to create and deliver on-line clinical training and education for undergraduate prosthetics and orthotics students. This project consisted of three phases: developing multimedia learning and teaching tools, integrating these tools into the curriculum (combination of e-Learning and live practical sessions), and evaluating the outcomes. Video-based multimedia contents were captured and integrated with graphic, audio and text into a PowerPoint presentation software format. The web-based content was integrated into the WebCT platform for course management. Questionnaires were used to obtain student feedback on this e-Learning approach. Results were compared within the prosthetics and orthotics (P&O) programme, with other Health Sciences programmes, and overall with the University. P&O student responses were significantly higher than other groups for career relevance and problem solving. Qualitative feedback indicated that students appreciated the easy access, integrated and interactive approach of the text materials, concise PowerPoint presentation, demonstration video and the on-line case discussion via the WebCT platform. Educators appreciated the ability easily to maintain contents and publish the modules across multiple media without recreating the contents.

Adult↗

PubMed2006

Global public health issues.

The context of the conference presentation that gave rise to this article was the importance of veterinarians becoming more engaged in the public-health challenges of today. During the presentation, I sought to point out some of the pressing reasons why. Of particular concern to me are the missed opportunities to help influence human health and well-being as private veterinary practitioners in addition to public-practice veterinarians. Key elements: Public health, the protection and improvement of community health by organized community effort; the global community, the entire world; social responsibility, being, as members of society, morally and legally responsible for the welfare of human beings; terrorism, the systematic use of terror (fear), especially as a means of coercion (it is always local!); system integration, the interaction of interdependent groups to form a unified whole.

Animal Welfare↗

PubMed2004

Different costimulatory and growth factor requirements for CD4+ and CD8+ T cell-mediated rejection.

Costimulatory signals and growth factor signals play a key role in commanding T cell activation and T cell effector function. However, how costimulatory signals and growth factor signals interact and integrate into the activation program of CD4(+) and CD8(+) T cells during the allograft response remains poorly defined. In the present study we found that either CD4- or CD8-deficient mice can vigorously reject the skin allografts. Blocking rapamycin-sensitive growth factor signals produced long term skin allograft survival in CD4-deficient mice (mean survival time, >120 days), but not in CD8-deficient mice (mean survival time, 20 days). Analysis of CFSE-labeled cells proliferating in the allogeneic hosts revealed that clonal expansion of CD4(+) T cells in vivo was more resistant to growth factor blockade than that of CD8(+) T cells. However, blockade or genetic absence of CD28/CD154 costimulatory molecules rendered CD4(+) T cell-mediated rejection sensitive to rapamycin, and long term skin allograft survival can be readily induced by rapamycin in the absence of CD28/CD154 signals (>100 days). Furthermore, blocking OX40 costimulation induced long term skin allograft survival in CD4-deficient mice and CD8-deficient mice when both CD28 and CD154 were transiently blocked. We conclude that CD4(+) and CD8(+) T cells exhibit distinct sensitivity to growth factor blockade in transplant rejection, and CD28/CD154-independent rejection is sensitive to rapamycin and appears to be supported by OX40 costimulation.

Animals↗

PubMed2001

Problem-based learning in medical education: the Singapore hybrid.

INTRODUCTION: Problem-based learning (PBL) is an innovative educational strategy to enhance student-centred, interactive and integrated learning through intensive small group tutorials. PBL is problem-first learning in which a commonly encountered medical problem serves as the primary focus of and stimulus for learning. Several adaptations have evolved since its implementation at McMaster University in 1969. In 1999, the Singapore medical school implemented PBL as a key feature within its new hybrid curriculum. METHODS: The review will focus on the educational implications and impact of the present curriculum reform with emphasis on the implementation of PBL within the new hybrid medical curriculum. RESULTS: Our early experience in implementing PBL resembles those of several other "traditional" medical schools, namely, a generally favourable and positive response from staff and students mixed with varying degree of anxiety to change. CONCLUSION: Appropriate training and changing the mindsets of staff and students, strong leadership from the Dean and a deep commitment by all concerned are essential to ensure the successful implementation of PBL within a "traditional" medical school. PBL will enhance the quality of medical education and the educational preparation of our students to meet the challenges of future medical practice.

Education, Medical↗

PubMed2001

[Molecular epidemiology and cancer prevention].

Environmental factors act in concert with individual susceptibility to cause most human cancers. The modulation of these environmental factors by host susceptibility has rarely been evaluated. Recently, the molecular epidemiology of human cancer has been extended to a study clarifying individual variation and gene-environmental interactions by integrating molecular biology, in vitro and in vivo laboratory models, biochemistry and epidemiology to infer individual cancer risk. This article briefly reviews genetic polymorphisms frequently used in molecular epidemiological studies and shows, as an example, a possible association between the genetic polymorphisms of CYP17 genes and prostate cancer risk.

Androgens↗

PubMed2002

TMJ fractures in children: importance of functional activation of muscles in preventing mandibular asymmetries and facial maldevelopment.

Normal development of the mandible as well as some portions of the upper jaw and face are related to good function of the masticatory apparatus: the integrity and interaction of bony and soft-tissue structures may be highly disturbed by injury of the TM joints and result in facial and occlusal disharmonies. When the neuromuscular system is in harmony, the mandibular muscles collectively exert their effect on both position and movement of the jaw and the loading of forces on the TM joints is optimal and balanced. Unfortunately, TMJ fractures may alter completely this balance with loss of the support to the mandible against the temporal component and loss of the functional effect of the lateral pterygoid muscle on the mandible. Disturbances in the harmonious interplay of the masticatory muscles may result in facial alteration and asymmetries. If not treated, the dysplastic patterns of growth continues and worsens during the years.

Cephalometry↗

PubMed2002

Integrative biological modelling in silico.

In silico models of biological systems provide a powerful tool for integrative analysis of physiological function. Using the computational models of the heart as examples, we discuss three types of integration: structural integration implies integration across physical scales of biological organization from protein molecule to whole organ; functional integration of interacting physiological processes such as signalling, metabolism, excitation and contraction; and the synthesis of experimental observation with physicochemical and mathematical principles.

Animals↗

PubMed2000

Signal transduction by xenobiotics in fish.

Signal transduction by xenobiotics in fish has recently gained much attention. The better known transduction mechanisms are those elicited by organochlorines, organophosphates, carbamates and heavy metals. Organochlorines specifically bind to the membrane bound ouabain sensitive Na+-K+-ATPase affecting neural transmission while the organophosphates and carbamates bind specifically to the membrane bound enzyme acetylcholinesterase again affecting neural transmission. Since the nervous system is one of the important integrative and interactive physiological systems in animals, hypofunction of the nervous system leads to secondary effects in the endocrine system including thyroidal, gonadal, interrenal, pituitary and hypothalamic functions. Even low levels of xenobiotics are efficient enough to bring about remarkable changes in the functional physiology of the non target animals. Heavy metals such as cadmium or mercury belonging to the same group II B in the periodic table probably have a similar mechanism of action. Avidity of these metals to SH-radicals allow them to bind indiscriminately to SH groups in proteins. One pathway of interaction by inorganic mercury with the membrane bound ouabain sensitive Na+-K+-ATPase has been clearly established in fish liver and ovary. Binding of inorganic mercury to the membrane bound enzyme is through sulfhydryl group which inactivates the sodium pump leading to accumulation of the cation in the cytosol. The inorganic mercury is next conjugated by the cytosolar nucleophile, glutathione, and is transported to the nucleus where dissociation occurs and the free metal binds to the metal regulatory element to initiate gene expression. The inducible proteins are 3beta-hydroxysteroid dehydrogenase in the oocyte and metallothionein and C-reactive protein in the liver. The present review deals with the role of xenobiotic as a stress factor.

Animals↗

PubMed2003

New functions of an old protein: the eukaryotic porin or voltage dependent anion selective channel (VDAC).

Mitochondrial porin or VDAC (Voltage Dependent Anion selective Channels) was identified for the first time in 1976, on the basis of the evolutionary similarity between the gram negative and mitochondrial outer membranes. Since this achievement VDAC has been extensively investigated: its functional features have been sharply defined upon reconstitution in artificial membranes and its sequence has been determined in many genomes. Unfortunately the tertiary structure has not yet been solved, mainly because it proved to be very difficult to get suitable crystals. Despite this established knowledge, in the last few years this protein has attracted renewed interest. There are two main reasons for this interest: the discovery, in most eukaryotes, of a family of genes encoding VDAC isoforms and the claims of VDAC involvement in the intrinsic pathway of apoptosis and in particular in the mechanism of cytochrome c release from mitochondria. We can affirm that nowadays the eukaryotic porin (or VDAC) is studied in a more general cellular contest, looking at the interactions and integration with other molecules, since VDAC is in a crucial position in the cell, forming the main interface between the mitochondrial and the cellular metabolisms. In this minireview we will briefly focus our attention onto the following topics: 1) recent advances about the structure of VDAC; 2) the VDAC-related multigene families; 3) the presence, targeting and function of VDAC in various cell membranes.

Animals↗

PubMed2003

[Epidemiology and social determinants of health inequalities].

BACKGROUND: The general approach of social epidemiology is based on the observation of a strong social stratification of health outcomes within populations: a similar stratification of factors associated with health must therefore also exist according to social status. To explain social differences in health, the natural approach for epidemiologists is to consider an imbalanced distribution of established risk factors according to the social position of individuals. As this approach has largely failed, two main other research areas were recently explored: (i) identification of "new" social risk factors; (ii) research of possible mechanisms of social differences in health. METHODS AND RESULTS: Identification of social risk factors: early events and life course, occupational factors, social relationships (social networks and support, discrimination, neighborhood characteristics), health care. Research of possible mechanisms of social differences in health in the context of specific theoretical frameworks: the materialist model, the psychosocial model and the eco-social model integrating the interaction between individuals'characteristics and their environment. COMPLEX METHODOLOGICAL PROBLEMS: definition and measurement of variables characterizing the social situation of individuals; quantification of social inequalities at population level. Observational methods must often rely on very long-lasting cohorts, and imply statistical methods that account for longitudinal data or are able to manage simultaneously individual and contextual data.

Cohort Studies↗

PubMedDate not supplied

[On the reactions of the human nervous system to complex-frequency optical stimulation].

A computerized system for precise stimulation and analysis of electroencephalographic (EEG) reactions to two simultaneously presented frequencies of sine-wave light (one constant, 13 Hz, and the other varying from 1 to 6 Hz and vice versa) was used to study the mechanisms of human brain reactivity to complex rhythmical stimulation. The frequencies were generated by computer and presented to the subjects by three different ways: as a result of their simple summation (additively), as a product of their multiplication (multiplicatively, amplitude modulation of constant frequency by the varying frequency), or by separate presentation to different eyes. The dynamics of electroencephalograms for different types of stimulation were compared. Under all three experimental conditions, the dynamics of EEG spectra has demonstrated the same general pattern of resonance activation, which was similar to that observed for the presented signals in the case of their amplitude modulation. Significant positive shifts in the functional state of subjects were observed as a result of stimulation. The results obtained show the leading role of the processes of amplitude modulation in the interaction of integrative, adaptive, and trace mechanisms of the brain functioning during human perception of complex rhythmical stimuli.

Brain↗

PubMed2005

[A state of immune system in patients with acute stroke].

Over the last years the data on the changes of immunological parameters in traumatic and pathological lesions of brain hemispheres has been obtained by neuroimmunology, a science investigating mechanisms, principles, regularities as well as interaction and integration of immune and nervous systems. However many aspects of the field remain unclear and need further study. In this context parameters of immune system in patients with acute stroke have been examined. These parameters proved to correlate with the disease severity suggesting that the main parameters of cell and humoral patterns of immune system depend on the structural and functional state of brain hemispheres.

Aged↗