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Basic Mechanisms (basic + mechanism)
Selected AbstractsStatus epilepticus in infants and young children: Basic mechanisms, clinical evaluation, prognosis and treatmentACTA NEUROLOGICA SCANDINAVICA, Issue 2007T. Nagai No abstract is available for this article. [source] Basic mechanisms of high-risk human papillomavirus-induced carcinogenesis: Roles of E6 and E7 proteinsCANCER SCIENCE, Issue 10 2007Mako Narisawa-Saito Human papillomaviruses (HPV) are believed to be the primary causal agents for development of pre-neoplastic and malignant lesions of the uterine cervix, and high-risk types such as type 16 and 18 are associated with more than 90% of all cervical carcinomas. The E6 and E7 genes of HPV are thought to play causative roles, since E6 promotes the degradation of p53 through its interaction with E6AP, an E3 ubiquitin ligase, whereas E7 binds to the retinoblastoma protein (pRb) and disrupts its complex formation with E2F transcription factors. Although prophylactic vaccines have become available, it is still necessary to clarify the mechanisms of HPV-induced carcinogenesis because of the widespread nature of HPV infection. Approximately 493 000 new cases of cervical cancer are diagnosed each year with approximately 274 000 mortalities due to invasive cervical cancer. In the present article, the mechanisms of HPV16 E6- and E7-induced multistep carcinogenesis and recently identified functions of these onco-proteins are reviewed. (Cancer Sci 2007; 98: 1505,1511) [source] 3252: Basic mechanisms and factors influencing the neurovascular coupling in the eyeACTA OPHTHALMOLOGICA, Issue 2010G GARHOFER Neuro-vascular coupling is a basic physiological mechanism in the eye that allows for adapting retinal and optic nerve head blood flow to changing metabolic demands, induced by an increase in neural activity. Despite many efforts, the mechanisms that leads to this coupling process are largely unknown. Among others, nitric oxide seems to play an important role in the vasodilatory answer. It has been shown that the unspecific blockade of nitric-oxide syntheses leads to a pronounced reduction of flicker induced vasodilatation in healthy subjects. This indicates that nitric oxide plays an important role in this signaling cascade. Additionally, there is evidence that astrocytes act as a mediator between ganglion cells and blood vessels in the retina. This hypothesis is strengthened by the observation that the presence and distribution of retinal astrocytes correlates with the presence and distribution of retinal blood vessels. This talk will summarize the concept of neuro-vascular coupling in the eye and give an overview about our current understanding of the mechanisms and factors involved in this process. [source] Replication fork block protein, Fob1, acts as an rDNA region specific recombinator in S. cerevisiaeGENES TO CELLS, Issue 2 2002Katsuki Johzuka Background: The analysis of homologous recombination in the tandemly repeating rDNA array of Saccharomyces cerevisiae should provide useful information about the stability of not only the rDNA repeat but also the abundant repeated sequences on higher eukaryotic genomes. However, the data obtained so far are not yet conclusive, due to the absence of a reliable assay for detecting products of recombination in the rDNA array. Results: We developed an assay method to detect the products of unequal sister-chromatid recombination (marker-duplication products) in yeast rDNA. This assay, together with the circular rDNA detection assay, was used for the analysis. Marker-duplication occurred throughout the rDNA cluster, preferentially between nearby repeat units. The FOB1 and RAD52 genes were required for both types of recombinant formation. FOB1 showed a gene dosage effect on not only the amounts of both recombinants, but also on the copy number of the repeat. However, unlike the RAD52 gene, the FOB1 gene was not involved in homologous recombination in a non-rDNA locus. In addition, the marker-duplication products were drastically decreased in the mre11 mutant. Conclusion: Our data demonstrate that FOB1 - and RAD52 -dependent homologous recombination cause the gain and loss of a few copies of the rDNA unit, and this must be a basic mechanism responsible for amplification and reduction of the rDNA copy number. In addition, FOB1 may also play a role in the copy number regulation of rDNA tandem repeats. [source] Identifications of expressed sequence tags from Pacific threadfin (Polydactylus sexfilis) skeletal muscle cDNA libraryAQUACULTURE RESEARCH, Issue 4 2010Shizu Watanabe Abstract Pacific threadfin (Polydactylus sexfilis), locally known as Moi, is a desirable fish for aquaculture and recreational fishing. To understand the basic mechanism of muscle formation and its impacts on flesh quality, we established a cDNA library using mRNA of the skeletal muscle tissue from fingerlings. The library size was 1.1 × 108 plaque forming units mg,1 and the percentage of recombinant clones was >81%. A pilot sequencing project from 181 clones identified 129 useful expressed sequence tags (ESTs), of which 90 ESTs exhibited significant homology to known genes and 39 ESTs have low homologies to unknown genes by blast algorithm. The most abundant EST from the pilot sequence data is nikotinamide riboside kinase 2 (59 times), followed by 60S ribosomal protein L24 (12 times) and ribosomal protein L8 (5 times). Fourteen novel genes were retrieved from the sequenced clones and subjected to gene ontology annotation. Four mRNA sequences were identified as significant regulators of transcription, including Not2p, Tsc22 domain family 2, LIM domain binding factor 3 and mesenchyme homeobox 2. These results suggest that the muscle cDNA library is an useful source for identifying EST sequences of Pacific threadfin. [source] The nervous system and gastrointestinal functionDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 2 2008Muhammad A. Altaf Abstract The enteric nervous system is an integrative brain with collection of neurons in the gastrointestinal tract which is capable of functioning independently of the central nervous system (CNS). The enteric nervous system modulates motility, secretions, microcirculation, immune and inflammatory responses of the gastrointestinal tract. Dysphagia, feeding intolerance, gastroesophageal reflux, abdominal pain, and constipation are few of the medical problems frequently encountered in children with developmental disabilities. Alteration in bowel motility have been described in most of these disorders and can results from a primary defect in the enteric neurons or central modulation. The development and physiology of the enteric nervous system is discussed along with the basic mechanisms involved in controlling various functions of the gastrointestinal tract. The intestinal motility, neurogastric reflexes, and brain perception of visceral hyperalgesia are also discussed. This will help better understand the pathophysiology of these disorders in children with developmental disabilities. © 2008 Wiley-Liss, Inc. Dev Disabil Res Rev 2008;14:87,95. [source] Mechanistic hypotheses for nonsynaptic epileptiform activity induction and its transition from the interictal to ictal state,Computational simulationEPILEPSIA, Issue 11 2008Antônio-Carlos G. De Almeida Summary Purpose:, The aim of this work is to study, by means of computational simulations, the induction and sustaining of nonsynaptic epileptiform activity. Methods:, The computational model consists of a network of cellular bodies of neurons and glial cells connected to a three-dimensional (3D) network of juxtaposed extracellular compartments. The extracellular electrodiffusion calculation was used to simulate the extracellular potential. Each cellular body was represented in terms of the transmembrane ionic transports (Na+/K+ pumps, ionic channels, and cotransport mechanisms), the intercellular electrodiffusion through gap-junctions, and the neuronal interaction by electric field and the variation of cellular volume. Results:, The computational model allows simulating the nonsynaptic epileptiform activity and the extracellular potential captured the main feature of the experimental measurements. The simulations of the concomitant ionic fluxes and concentrations can be used to propose the basic mechanisms involved in the induction and sustaining of the activities. Discussion:, The simulations suggest: The bursting induction is mediated by the Cl, Nernst potential overcoming the transmembrane potential in response to the extracellular [K+] increase. The burst onset is characterized by a critical point defined by the instant when the Na+ influx through its permeable ionic channels overcomes the Na+/K+ pump electrogenic current. The burst finalization is defined by another critical point, when the electrogenic current of the Na+/K+ pump overcomes its influx through the channels. [source] Complexity of resilient network optimisation,EUROPEAN TRANSACTIONS ON TELECOMMUNICATIONS, Issue 7 2009Mateusz, otkiewicz Path restoration (PR) is one of the basic mechanisms for securing telecommunication networks against failures. In the paper, we discuss the complexity of certain variants of a multi-commodity flow network optimisation problem in directed graphs related to state-independent path restoration mechanisms. We demonstrate that most variants of the considered problem are -hard. Depending on the variant, we show how the problem can be reduced either from the partition problem or from the problem of finding an arc-disjoint pair of paths that connect two distinct pairs of nodes. We also demonstrate that at the same time the considered problem is difficult to approximate. The complexity results of the paper are important as they can help to devise proper algorithms for resilient network design tools. Copyright © 2009 John Wiley & Sons, Ltd. [source] ORIGINAL ARTICLE: Probability of emergence of antimalarial resistance in different stages of the parasite life cycleEVOLUTIONARY APPLICATIONS (ELECTRONIC), Issue 1 2009Wirichada Pongtavornpinyo Abstract Understanding the evolution of drug resistance in malaria is a central area of study at the intersection of evolution and medicine. Antimalarial drug resistance is a major threat to malaria control and directly related to trends in malaria attributable mortality. Artemisinin combination therapies (ACT) are now recommended worldwide as first line treatment for uncomplicated malaria, and losing them to resistance would be a disaster for malaria control. Understanding the emergence and spread of antimalarial drug resistance in the context of different scenarios of antimalarial drug use is essential for the development of strategies protecting ACTs. In this study, we review the basic mechanisms of resistance emergence and describe several simple equations that can be used to estimate the probabilities of de novo resistance mutations at three stages of the parasite life cycle: sporozoite, hepatic merozoite and asexual blood stages; we discuss the factors that affect parasite survival in a single host in the context of different levels of antimalarial drug use, immunity and parasitaemia. We show that in the absence of drug effects, and despite very different parasite numbers, the probability of resistance emerging at each stage is very low and similar in all stages (for example per-infection probability of 10,10,10,9 if the per-parasite chance of mutation is 10,10 per asexual division). However, under the selective pressure provided by antimalarial treatment and particularly in the presence of hyperparasitaemia, the probability of resistance emerging in the blood stage of the parasite can be approximately five orders of magnitude higher than in the absence of drugs. Detailed models built upon these basic methods should allow us to assess the relative probabilities of resistance emergence in the different phases of the parasite life cycle. [source] Neurotoxins in the Neurobiology of PainHEADACHE, Issue 2003Stephen D. Silberstein MD Migraine is a common, chronic, incapacitating, neurovascular disorder that affects an estimated 12% of the population. Understanding the basic mechanisms of pain is important when treating patients with chronic pain disorders. Pain, an unpleasant sensory and emotional experience, is usually triggered by stimulation of peripheral nerves and often associated with actual or potential tissue damage. Peripheral nerve fibers transmit pain signals from the periphery toward the spinal cord or brain stem. The different diameter pain fibers (A and C) vary in the speed of conduction and the type of pain transmitted (eg, sharp versus dull). When stimulated, peripheral pain fibers carrying sensory input from the body enter at different layers of the dorsal horn, which is then propagated toward the thalamus via the spinothalamic tract within the spinal cord. Conversely, sensory input from the face does not enter the spinal cord but enters the brain stem via the trigeminal nerve. This review describes in detail the neurobiological mechanisms and pathways for pain sensation, with a focus on migraine pain. [source] Application of nonlinear time,scaling for robust controller design of reaction systemsINTERNATIONAL JOURNAL OF ROBUST AND NONLINEAR CONTROL, Issue 1 2002P. Moya Abstract Even though the basic mechanisms of operation of reaction systems are relatively simple the dynamical models obtained from first principles are complex and contain highly uncertain terms. To develop reliable model-based controllers it is therefore necessary to simplify the system dynamics preserving the features which are essential for control. Towards this end, co-ordinate transformations identifying the states which are dependent/independent of the reactions and flows have been reported in the literature. This has allowed, for instance, the design of observers which are insensitive to the (usually unknown) reaction functions. The main contribution of this paper is to show the utility of nonlinear state-dependent time-scaling to simplify the system dynamics, and consequently the controller design. In particular, we show that with time-scaling and an input transformation we can reveal the existence of attractive invariant manifolds, which allows us to reduce the dimension of the system. As an application we study the well-known fourth order baker's yeast fed-batch fermentation process model, whose essential dynamics is captured by a planar system perturbed by an exponentially decaying term. We then exploit this particular structure to design, with reduced control authority, a nonlinear asymptotically stabilizing control law which is robust with respect to the reaction function. Copyright © 2001 John Wiley & Sons, Ltd. [source] Organizational culture in nursing schools in Turkey: faculty members' perspectivesINTERNATIONAL NURSING REVIEW, Issue 3 2009F. Kantek rn Background:, Among the benefits of examining an organization's culture are the opportunity to understand the basic mechanisms of the institutional and structural procedures, to determine the need for change and to ensure the development and satisfaction of the faculty members. Aim:, To determine the perceptions of faculty members of organizational culture at nursing schools in Turkey and to examine different perceptions in relation to demographic variables. Method:, The study was conducted with 180 faculty members from seven nursing schools in state universities located in different geographical regions of Turkey that granted permission for the study. All faculty members in these schools with at least 1 year of institutional experience were included in the research. No sampling was required. A demographic information form and an organizational culture scale were used as data collection materials. The organizational culture scale contains 30 items and resolves the organizational culture in three dimensions. The minimum score obtained was 1 and the maximum was 5. Findings:, The mean score for faculty members' in total scale was 3.40 (SD = 0.68), while it was 3.26 (SD = 0.77) for the management style dimension, 3.39 (SD = 0.73) for the organizational commitment/relations dimension and 3.68 (SD = 0.73) for the student-oriented dimension. There was no statistical difference between the perception of organizational culture and work experience at the institution, marital status or educational status, but there were differences in age, number of years in the profession and academic titles. Conclusion:, It was found that strong perceptions have been established in nursing schools in regard to student-oriented practices, and that groups consisting of senior academic personnel and experienced academicians are considered to be better at perceiving the importance of the organizational culture. The administrators are recommended to promote policies to enhance the participation in decision-making processes and regularly monitor the cultural changes in the organization. [source] History of science , sporesJOURNAL OF APPLIED MICROBIOLOGY, Issue 3 2006Lewis B Perry Memorial Lecture 200 Abstract Bacterial endospores were first studied 130 years ago by Cohn in 1876 and independently by Koch in the same year. Although spore dormancy and resistance have been much studied since then, questions still remain concerning the basic mechanisms and the kinetics of heat inactivation in particular. Likewise, the extreme dormancy and longevity of spores was recognized early on and later greatly extended but still evade complete understanding. Evidence has accumulated for the involvement of specific spore components such as calcium, dipicolinic acid, small acid soluble proteins in the core and peptidoglycan in the cortex. Involvement of physical factors too, such as the relative dehydration of the core, maybe in a high-viscosity state or even in a glassy state, has added to appreciation of the multicomponent nature of dormancy and resistance. Spore-former morphology formed the basis for early classification systems of sporeformers from about 1880 and consolidated in the mid-1900s, well prior to the use of modern genetic procedures. With respect to sporulation, groundbreaking sequence studies in the 1950s provided the basis for later elucidation of the genetic control widely relevant to many cell differentiation mechanisms. With respect to the breaking of dormancy (activation and germination), the elucidation of mechanisms began in the 1940s following the observations of Hills at Porton who identified specific amino acid and riboside ,germinants', and laid the basis for the later genetic analyses, the identification of germinant receptor genes and the elucidation of key germination reactions. The nonexponential nature of germination kinetics has thwarted the development of practical Tyndallization-like processing. So inactivation by heat remains the premier method of spore control, the basis of a huge worldwide industry, and still relying on the basic kinetics of inactivation of Clostridium botulinum spores, and the reasoning regarding safety first evolved by Bigelow et al. in 1920 and Esty and Meyer in 1922. ,Newer' processes such as treatment with ionizing radiation (first proposed in 1905) and high hydrostatic pressure (first proposed in 1899) may be introduced if consumer resistance and some remaining technical barriers could be overcome. [source] New light on the biology and developmental potential of haematopoietic stem cells and progenitor cellsJOURNAL OF INTERNAL MEDICINE, Issue 4 2009M. Sigvardsson Abstract. Even though stem cells have been identified in several tissues, one of the best understood somatic stem cells is the bone marrow residing haematopoietic stem cell (HSC). These cells are able to generate all types of blood cells found in the periphery over the lifetime of an animal, making them one of the most profound examples of tissue-restricted stem cells. HSC therapy also represents one of the absolutely most successful cell-based therapies applied both in the treatment of haematological disorders and cancer. However, to fully explore the clinical potential of HSCs we need to understand the molecular regulation of cell maturation and lineage commitment. The extensive research effort invested in this area has resulted in a rapid development of the understanding of the relationship between different blood cell lineages and increased understanding for how a balanced composition of blood cells can be generated. In this review, several of the basic features of HSCs, as well as their multipotent and lineage-restricted offspring, are addressed, providing a current view of the haematopoietic development tree. Some of the basic mechanisms believed to be involved in lineage restriction events including activities of permissive and instructive external signals are also discussed, besides transcription factor networks and epigenetic alterations to provide an up-to-date view of early haematopoiesis. [source] Dynamics of particles suspended in a yield stress fluid flowing in a pipeAICHE JOURNAL, Issue 5 2008Othmane Merkak Abstract This study seeks to understand the basic mechanisms governing the dynamics of a solid particle in a Poiseuille flow field of a viscoplastic fluid. An experimental set-up to create flows with a prescribed flow rate and enable the particles to be visualized in three dimensions was designed and validated. The absence of slip at the interfaces between flows and particles was characterized. The Reynolds numbers are low, gravity effects negligible and plastic effects significant. The ratio of pipe diameter to particle diameter is 8. The dynamics of a particle in a velocity field depends strongly on its position in the sheared wall zone or in the moving rigid zone. The effect of rigid and sheared zones on particle behavior was examined. Changes in particle translation and rotation velocities were quantified. © 2008 American Institute of Chemical Engineers AIChE J, 2008 [source] Biological agents in the treatment of Crohn's diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2002R. Caprilli SUMMARY The main aim of the management of Crohn's disease is to reduce inflammation. Current approaches with corticosteroids, immunosuppressive agents, mesalazine and antibiotics have limited therapeutic benefit for many patients. Considerable progress has been made with regard to our knowledge of the basic mechanisms of the disease, which is associated with immunological imbalance characterized by an excess of pro-inflammatory cytokines. Recent advances in bio-technology have led to the development of many new therapeutic agents, so-called biological agents, which selectively target single key processes involved in the pathogenesis of the disease. A growing number of biological agents are under investigation in both randomized controlled trials and uncontrolled studies. The aim of this review is to provide the clinician with an insight into the randomized controlled trials published in the literature on the use of biological agents in the treatment of Crohn's disease. [source] Differential requirements for interleukin (IL)-4 and IL-13 in protein contact dermatitis induced by AnisakisALLERGY, Issue 9 2009N. Nieuwenhuizen Background:, Exposure to antigens of the fish parasite Anisakis is associated with the development of protein contact dermatitis in seafood-processing workers. Understanding the basic mechanisms controlling allergic sensitization through the skin is critical for designing therapies that will prevent the progression of allergic disease. Objective:, To investigate the roles of interleukin (IL)-4, IL-13 and the IL-4R, in both local skin pathology and systemic sensitization following epicutaneous exposure to Anisakis proteins. Methods:, BALB/c wild-type (WT) mice and mice deficient in IL-4, IL-13 or IL-4 and IL-13, as well as mice with cell-specific impairment of IL-4R, expression, were sensitized to Anisakis antigen by repeated epicutaneous application of Anisakis extract. Following this sensitization, skin pathology was recorded and systemic responses were investigated. Intravenous challenge with Anisakis extract was performed to test for the development of biologically relevant systemic sensitization. Results:, In WT mice, epicutaneous sensitization with Anisakis larval antigens induced localized inflammation, epidermal hyperplasia, production of TH2 cytokines, antigen-specific IgE and IgG1. Intravenous challenge of sensitized mice resulted in anaphylactic shock. Interestingly, IL-13 deficient mice failed to develop epidermal hyperplasia and inflammation, whilst anaphylaxis was reduced only in strains deficient either in IL-4 only, or deficient in IL-4 and IL-13 concurrently, as well as in mice deficient in IL-4R, or with impaired IL-4R, expression on CD4+ T cells. Conclusions:, Interleukin-13 plays a central role in protein contact dermatitis associated with repeated epicutaneous exposure to Anisakis extract, whereas IL-4 drives systemic sensitization and resultant anaphylactic shock. [source] The ozone paradox: Ozone is a strong oxidant as well as a medical drugMEDICINAL RESEARCH REVIEWS, Issue 4 2009Velio Bocci Abstract After five decades characterized by empiricism and several pitfalls, some of the basic mechanisms of action of ozone in pulmonary toxicology and in medicine have been clarified. The present knowledge allows to understand the prolonged inhalation of ozone can be very deleterious first for the lungs and successively for the whole organism. On the other hand, a small ozone dose well calibrated against the potent antioxidant capacity of blood can trigger several useful biochemical mechanisms and reactivate the antioxidant system. In detail, firstly ex vivo and second during the infusion of ozonated blood into the donor, the ozone therapy approach involves blood cells and the endothelium, which by transferring the ozone messengers to billions of cells will generate a therapeutic effect. Thus, in spite of a common prejudice, single ozone doses can be therapeutically used in selected human diseases without any toxicity or side effects. Moreover, the versatility and amplitude of beneficial effect of ozone applications have become evident in orthopedics, cutaneous, and mucosal infections as well as in dentistry. © 2009 Wiley Periodicals, Inc. Med Res Rev [source] Lateral magnocellular nucleus of the anterior neostriatum (LMAN) in the zebra finch: Neuronal connectivity and the emergence of sex differences in cell morphologyMICROSCOPY RESEARCH AND TECHNIQUE, Issue 6 2001Barbara E. Nixdorf-Bergweiler Abstract The song system of birds provides a model system to study basic mechanisms of neuronal plasticity and development underlying learned behavior. Song learning and production involve discrete sets of interconnected nuclei in the avian brain. One of these nuclei, the lateral magnocellular nucleus of the anterior neostriatum (LMAN), is the output of the so-called anterior forebrain pathway known to be essential for learning and maintenance of song, both processes depending on auditory feedback. In zebra finches, only males sing and this sexually dimorphic behavior is mirrored by sexual dimorphism in neuronal structure that develops during ontogeny. Female zebra finches are not able to sing and nuclei of the song system are strongly reduced in size or even lacking, when compared to male brains. Only LMAN can be delineated as easily in females as in males. Since female zebra finches, despite being unable to sing, recognize song just as males do and form a memory for song (model acquisition) early in life, LMAN is a putative candidate for song acquisition in both sexes. Therefore, development of LMAN was studied at the cellular and ultrastructural level in both male and female zebra finches. Regressive development of dendritic spines, enlargement of neuronal cell body and nuclei size, as well as changes at the nucleolar level are events all occurring exclusively in males, when song learning progresses. The decline in synapse number and the augmentation in synaptic contact length at synapses in LMAN in males are indicative for synaptic plasticity, whereas in females synapse number and synaptic contact length remain unchanged. Microsc. Res. Tech. 54:335,353, 2001. © 2001 Wiley-Liss, Inc. [source] The pathophysiology of tremorMUSCLE AND NERVE, Issue 6 2001Günther Deuschl MD Abstract Tremor is defined as rhythmic oscillatory activity of body parts. Four physiological basic mechanisms for such oscillatory activity have been described: mechanical oscillations; oscillations based on reflexes; oscillations due to central neuronal pacemakers; and oscillations because of disturbed feedforward or feedback loops. New methodological approaches with animal models, positron emission tomography, and mathematical analysis of electromyographic and electroencephalographic signals have provided new insights into the mechanisms underlying specific forms of tremor. Physiological tremor is due to mechanical and central components. Psychogenic tremor is considered to depend on a clonus mechanism and is thus believed to be mediated by reflex mechanisms. Symptomatic palatal tremor is most likely due to rhythmic activity of the inferior olive, and there is much evidence that essential tremor is also generated within the olivocerebellar circuits. Orthostatic tremor is likely to originate in hitherto unidentified brainstem nuclei. Rest tremor of Parkinson's disease is probably generated in the basal ganglia loop, and dystonic tremor may also originate within the basal ganglia. Cerebellar tremor is at least in part caused by a disturbance of the cerebellar feedforward control of voluntary movements, and Holmes' tremor is due to the combination of the mechanisms producing parkinsonian and cerebellar tremor. Neuropathic tremor is believed to be caused by abnormally functioning reflex pathways and a wide variety of causes underlies toxic and drug-induced tremors. The understanding of the pathophysiology of tremor has made significant progress but many hypotheses are not yet based on sufficient data. Modern neurology needs to develop and test such hypotheses, because this is the only way to develop rational medical and surgical therapies. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 716,735, 2001 [source] Proteomic profiling of animal models mimicking skeletal muscle disordersPROTEOMICS - CLINICAL APPLICATIONS, Issue 9 2007Philip Doran Abstract Over the last few decades of biomedical research, animal models of neuromuscular diseases have been widely used for determining pathological mechanisms and for testing new therapeutic strategies. With the emergence of high-throughput proteomics technology, the identification of novel protein factors involved in disease processes has been decisively improved. This review outlines the usefulness of the proteomic profiling of animal disease models for the discovery of new reliable biomarkers, for the optimization of diagnostic procedures and the development of new treatment options for skeletal muscle disorders. Since inbred animal strains show genetically much less interindividual differences as compared to human patients, considerably lower experimental repeats are capable of producing meaningful proteomic data. Thus, animal model proteomics can be conveniently employed for both studying basic mechanisms of molecular pathogenesis and the effects of drugs, genetic modifications or cell-based therapies on disease progression. Based on the results from comparative animal proteomics, a more informed decision on the design of clinical proteomics studies could be reached. Since no one animal model represents a perfect pathobiochemical replica of all of the symptoms seen in complex human disorders, the proteomic screening of novel animal models can also be employed for swift and enhanced protein biochemical phenotyping. [source] Functional significance of stimulatory GTP-binding protein in hippocampus is associated with kindling-elicited epileptogenesisPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 2 2000Hiroto Iwasa MD Abstract In order to evaluate the involvement of the stimulatory G-protein (Gs)-related transduction system in the basic mechanisms of epilepsy, we examine the expression levels of Gs, mRNA and specific GTP-binding ability in the hippocampus of amygdaloid-kindled rats at various seizure stages. Northern blot analysis showed a significant increase in the Gs, mRNA expression level in the bilateral hippocampus at 24 h after the last generalized seizure. The [3H]-GTP-binding assay with isoproterenol (IPN), a ,-receptor agonist, revealed a remarkable increase of Bmax values in the sham-operated control and partially kindled groups. However, the IPN-induced increase of Bmax values was abolished on both sides of the hippocampus at 24 h after and at 4 weeks after the last generalized seizure in fully kindled rats. These data suggest that alteration in the Gs function and ,-adrenergic receptor-Gs coupling might be implicated in the neurobiological basis of the induction mechanisms of the generalization of seizures and the mechanisms of the maintenance of enduring epileptogenesis. Conversely, the Gs -related transduction system might have a lesser impact on the acquisition process of epileptogenesis. [source] Conserved neurochemical pathways involved in hypothalamic control of energy homeostasisTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 3 2007Paul M. Forlano Abstract The melanocortin system, which includes ,-melanocyte-stimulating hormone (,-MSH) and its endogenous antagonist, agouti-related protein (AgRP), is fundamental for the central control of energy homeostasis in mammals. Recent studies have demonstrated that many neuropeptides involved in the control of ingestive behavior and energy expenditure, including melanocortins, are also expressed and functional in teleost fishes. To test the hypothesis that the underlying neural pathways involved in energy homeostasis are conserved throughout vertebrate evolution, the neuroanatomical distribution of ,-MSH in relation to AgRP was mapped in a teleost (zebrafish, Danio rerio) by double-label immunocytochemistry. Zebrafish ,-MSH- and AgRP-immunoreactive (ir) cells are found in discrete populations in the ventral periventricular hypothalamus, the proposed arcuate homologue in teleosts. Major ascending projections are similar for both peptides, and dense ir-fibers innervate preoptic and ventral telencephalic nuclei homologous to paraventricular, lateral septal, and amygdala nuclei in mammals. Furthermore, ,-MSH and AgRP-ir somata and fibers are pronounced at 5 days post fertilization when yolk reserves are depleted and larvae begin to feed actively, which supports the functional significance of these peptides for feeding behavior. The conservation of melanocortin peptide function and projection pathways further support zebrafish as an excellent genetic model system to investigate basic mechanisms involved in the central regulation of energy homeostasis. J. Comp. Neurol. 505:235,248, 2007. © 2007 Wiley-Liss, Inc. [source] Clinical Implications of Advances in the Basic Science of Liver Repair and RegenerationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2009S. J. Karp Recent advances in our understanding of the basic mechanisms that control liver regeneration and repair will produce the next generation of therapies for human liver disease. Insights gained from large-scale genetic analysis are producing a new framework within which to plan interventions. Identification of specific molecules that drive regeneration will increase the options for live-donor liver transplantation, and help treat patients with small-for-size syndrome or large tumors who would otherwise have inadequate residual mass after resection. In a complementary fashion, breakthroughs in the ability to manipulate various cell types to adopt the hepatocyte or cholangiocyte phenotype promise to revolutionize therapy for acute liver failure and metabolic liver disease. Finally, elucidating the complex interactions of liver cells with each other and various matrix components during the response to injury is essential for fabricating a liver replacement device. This focused review will discuss how a variety of important scientific advances are likely to impact the treatment of specific types of liver disease. [source] ANAESTHESIA AND ANALGESIA: CONTRIBUTION TO SURGERY, PRESENT AND FUTUREANZ JOURNAL OF SURGERY, Issue 7 2008Edward Shipton Anaesthetists provide comprehensive perioperative medical care to patients undergoing surgical and diagnostic procedures, including postoperative intensive care when needed. They are involved in the management of perioperative acute pain as well as chronic pain. This manuscript considers some of the recent advances in modern anaesthesia and their contribution to surgery, from the basic mechanisms of action, to the delivery systems for general and regional anaesthesia, to the use of new drugs and new methods of monitoring. It assesses the resulting progress in acute and chronic pain services and looks at patient safety and risk management. It speculates on directions that may shape its future contributions to the management of the patient undergoing surgery. [source] Predictability of early stages of primary succession in post-mining landscapes of Lower Lusatia, GermanyAPPLIED VEGETATION SCIENCE, Issue 1 2001Gerhard Wiegleb Abstract. The predictability of early primary succession in post-mining landscapes of eastern Germany was studied at sites 5,70 yr following dumping. This chronosequence was investigated using indirect ordination methods. The position of the vegetation types in the ordination diagram was found not to infer any temporal sequence. Independent observations show that the change of vegetation type is slow and does not necessarily occur among types adjacent in the ordination diagram. Furthermore, direct ordination revealed that environmental parameters such as pH, the levels of available phosphate and organic carbon as well as the age of the study sites do not significantly account for the variance. Instead, attention needs to be paid to the influence of spatial aspects and also what recultivation measures have been carried out. A detailed account of the vegetation dynamics of individual sample plots showed - depending on the respective vegetation type - divergence, convergence, and fluctuation at the smallest spatial scale. While the species richness of the sample plots remained more or less constant after initial colonization, mean vegetation cover continuously increases with age, although some sites still remain free of vegetation after as long as 70 yr. No general trend in dominant life forms was indicated. A conceptual model of early succession mechanisms is outlined and five basic mechanisms are identified (i.e. site availability, site suitability, availability of diaspores, strategies of colonizing species and biotic interactions). Their respective importance in three different stages of early succession is estimated and compared. The predictability of vegetation dynamics at each stage is rated differently. [source] Helioseismology program for Solar Dynamics ObservatoryASTRONOMISCHE NACHRICHTEN, Issue 3-4 2007A. G. Kosovichev Abstract An overview of the science investigation program for the Helioseismic and Magnetic Imager (HMI) of the Solar Dynamics Observatory (SDO) space mission scheduled for launch in 2008 is presented. The HMI investigation encompasses three primary objectives of the Living With a Star Program:.rst, to determine how and why the Sun varies; second, to improve our understanding of how the Sun drives global change and space weather; and third, to determine to what extent predictions of space weather and global change can be made and to prototype predictive techniques. Helioseismology provides unique tools to study the basic mechanisms of the Sun's magnetic activity and variability. It plays a crucial role in all HMI investigations, which include convection-zone dynamics and the solar dynamo; origin and evolution of sunspots, active regions and complexes of activity; sources and drivers of solar activity and disturbances; links between the internal processes and dynamics of the corona and heliosphere; and precursors of solar disturbances for space-weather forecasts. We describe new unique opportunities for helioseismology studies with HMI data, in combination with data from the other SDO instruments, Atmospheric Imaging Assembly (AIA) and Extreme-ultraviolet Variability Experiment (EVE), and also from various space and ground-based observatories. The complete HMI science investigation and data analysis plan is available at http://hmi.stanford.edu. (© 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Bärtierchen und die Kunst des Überlebens.BIOLOGIE IN UNSERER ZEIT (BIUZ), Issue 4 2010Von Biodiversität bis Biotechnologie Abstract Viele kleine Tiere sind häufigen Veränderungen des Mikroklimas ausgesetzt, die ihr Überleben direkt beeinflussen. Solche Veränderungen, wie die De- und Rehydrierung oder das Gefrieren und Wiederauftauen, können mehrmals regelmäßig im Tagesverlauf auftreten oder auch nur gelegentlich im Abstand von Wochen oder Monaten. Als Tönnchen sind Bärtierchen in der Lage, einen langen Zeitraum zu überdauern. Mit zunehmender Zeit in Anhydrobiose nehmen jedoch DNA-Schäden zu, daher kann davon ausgegangen werden, dass aufgrund zellulärer Schädigungen kein unbegrenztes Überdauern möglich ist. Bislang sind die zugrundeliegenden Mechanismen noch weitgehend unklar. Für die Biotechnologie sind Bärtierchen daher ein lohnendes Forschungsfeld, denn für eine Langzeitkonservierung biologischer Materialien gibt es zahlreiche Anwendungsmöglichkeiten. From Biodiversity to Biotechnology: Water bears and the art of survival Many small organisms are frequently exposed to microclimate changes, which directly affect their survival. Such changes, for example dehydration and rehydration or freezing and thawing, can occur several times during a day or at intervals of weeks or months. As a tun, water bears are able to survive long periods of time, however, with increasing time in the anhydrobiotic state DNA damage increases. Therefore, we assume that unlimited survival is not possible, due to cellular damage. Currently the basic mechanisms of this phenomenon are to a large extent unknown. Water bears are an interesting field of research in biotechnology, as many applications for long-term preservation of biological material can be envisaged. [source] Posturographic description of the regaining of postural stability following strokeCLINICAL PHYSIOLOGY AND FUNCTIONAL IMAGING, Issue 1 2005Henrik Rogind Summary Background:, Failing balance and increased liability to falling are common complaints among hemiplegic subjects. During rehabilitation much effort is put into regaining postural stability. Purpose:, To describe the regaining of postural stability during rehabilitation for the first year following stroke in hemiplegic patients Materials and methods:, Twenty-six patients were included within 5 days of suffering a stroke resulting from a CT-verified clearly defined thromboembolic lesion, localized in the vascular bed of middle cerebral artery on either side. Posturographic evaluation of sway was performed on a commercially available force plate system (Balance Master Pro®). Measured parameters included per cent maximum stability (PMS), per cent ankle strategy (AST), and average angular velocity (AVE). An additional parameter was derived by calculating the slope (SLP) of the linear relationship between stability and ankle strategy. SLP reflects the predisposition of the stroke patient to keep using ankle strategy when faced with increasingly difficult balance tasks. The presence of familiarization to the measurement method was examined by including a preliminary measurement not otherwise included in the analysis of changes during the first year of follow-up. The temporal evolvement of sway was described by measuring sway parameters 1, 2, 4, 8 and 52 weeks following stroke. The proportions of the variation in sway caused by measurement error and between patients were compared. Results:, All parameters improved over time, as demonstrated by significant improvements from each of week 1, 2, 4 and 8 to week 52. There was evidence of familiarisation for PMS, AST and AVE, but not for SLP. Estimation of variance components showed that between patient variation accounts for between two-thirds and four-fifths of the total variation. A considerable part of this variation was caused by individual differences in the temporal improvement of sway over time. Patients considered the evaluation of postural sway demanding and time consuming resulting in a relatively large loss to follow-up: 15 patients completed the 8-week visit while seven completed the 1 year visit. Conclusion:, Postural stability increases for the first year following stroke. There is evidence of familiarization towards the measurements process for the traditional posturographic parameters PMS, AST and AVE, but not for the derived parameter SLP, which might make the latter a candidate for a sway parameter reflecting basic mechanisms of upholding upright stance in hemiplegic patients. The estimated variance components stress the considerable between-patient variation and question the ability of the force plate method to monitor individual sway performance of such patients during the rehabilitation process. [source] Inflammatory Process and Molecular Targets for Antiinflammatory NutraceuticalsCOMPREHENSIVE REVIEWS IN FOOD SCIENCE AND FOOD SAFETY, Issue 4 2004M.-T. Huang ABSTRACT Intense interest in nutraceuticals and their potential benefits has created the need to review the existing scientific information on their effect in preventing and managing inflammation that accompanies most chronic diseases. This article reviews the basic mechanisms of inflammation and the potential of 9 nutraceuticals to be effective as chronic disease preventive agents. Furthermore, the article emphasizes studies in which nutraceuticals are shown to be effective in preventing inflammation and mentions other molecular targets that can be of use in the future. The effects of the following nutraceuticals: ,-tocopherol, ascorbic acid, curcumin, resveratrol, (-)-epigallocatechin gallate, theaflavin, genistein, omega-3 fatty acids, and lycopene on reactive oxygen species scavenging ability, as well as proinflammatory targets, such as tumor necrosis factor , interleukin-1, interleukin-1,, nuclear factor kappa B, cellular and adhesion molecules, cyclooxygenase-2, inducible nitric oxide synthase, 5-lipoxygenase (5-LOX), phospholipase A2, reactive oxygen species generating enzymes are discussed. [source] | |||||||||||||||||||||||||