P. Novick, P. Brennwald, N. Walworth, A. Kabcenell, M. Garrett, M. Moya, D. Roberts, H. Müller, B. Govindan, R. Bowser
{"title":"The cycle of SEC4 function in vesicular transport.","authors":"P. Novick, P. Brennwald, N. Walworth, A. Kabcenell, M. Garrett, M. Moya, D. Roberts, H. Müller, B. Govindan, R. Bowser","doi":"10.1002/9780470514450.ch14","DOIUrl":"https://doi.org/10.1002/9780470514450.ch14","url":null,"abstract":"Sec4 is a Ras-like GTP-binding protein required for exocytosis in yeast. Unlike Ras, it is the ability of Sec4 to cycle between the GTP- and GDP-bound forms rather than the absolute levels of the GTP-bound form that is critical for function. This cycle may be coupled to an observed cycle of Sec4 localization within the cell. Sec4 binds to secretory vesicles which then fuse with the plasma membrane in exocytosis. Sec4 can recycle from the plasma membrane through a soluble pool to rebind to a new round of vesicles. We have found an activity in yeast (Saccharomyces cerevisiae) comparable to that of the GDP dissociation inhibitor protein isolated from mammalian cells that releases GDP-bound Sec4 from membranes. DSS4-1, a dominant suppressor of the sec4-8 temperature-sensitive mutation, encodes a nucleotide exchange protein. The cycle of Sec4 may function to allow the assembly and subsequent disassembly of a set of proteins necessary for exocytosis. Candidates for members of this set of proteins are encoded by sec genes which show strong genetic interactions with sec4-8. Two of these (SEC8 and SEC15) encode large proteins which form a complex that is peripherally associated with the plasma membrane.","PeriodicalId":10218,"journal":{"name":"Ciba Foundation symposium","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2007-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87690359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Experimental studies of ongoing conscious experience.","authors":"J. Singer","doi":"10.1002/9780470514412.CH6","DOIUrl":"https://doi.org/10.1002/9780470514412.CH6","url":null,"abstract":"A research programme designed to find ways of applying a variety of methods in psychological science to studying the seemingly ephemeral phenomena of the human stream of consciousness and its manifestations in daydreams, interior monologues, imagery and related private experiences is described. Approaches include psychometric studies to establish normative information on daydreaming and experimental studies using signal-detection paradigms to capture the ongoing stream of thought. Recent experiments involve thought-sampling methods for identifying the determinants of the content of the stream of thought in adolescents or the ways in which self-beliefs and emotions are manifested in a group of cocaine and heroin abusers. Children's pretend play is studied as a possible forerunner of adult consciousness. It is proposed that the human condition involves a continuing tension between processing information generated from the physical and social milieu and the continuous operation of centrally generated material from long-term memory in the form of reminiscences, wishes, current concerns, expectancies and fantasies. This concept has implications for personality variation, affective arousal and adaptive behaviour.","PeriodicalId":10218,"journal":{"name":"Ciba Foundation symposium","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2007-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83787428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Programming by early nutrition in man.","authors":"A. Lucas","doi":"10.1002/9780470514047.CH4","DOIUrl":"https://doi.org/10.1002/9780470514047.CH4","url":null,"abstract":"Whether early diet influences long-term health or achievement is a key question in nutrition. Such long-term consequences would invoke the concept of 'programming'--a more general process whereby a stimulus or insult at a critical period of development has lasting or lifelong significance. Data from small mammals and primates show that early nutrition may have potentially important long-term effects, for example on blood lipids, plasma insulin, obesity, atherosclerosis, behaviour and learning. Corresponding studies in man have been largely retrospective and difficult to interpret. The preterm infant is however an important model for human research because formal random assignment to early diet is practical. A large prospective randomized multicentre study has been undertaken on 926 preterm infants to test the hypothesis that early diet influences long-term outcome. Diets included human milk, standard formula and nutrient-enriched preterm formula. The diet consumed for on average the first month post partum had a major impact on subsequent developmental attainment, growth and allergic status in early childhood. That such a brief period of dietary manipulation has lasting significance implies that the neonatal period is critical for nutrition after preterm birth. These data may have broader implications for human nutrition.","PeriodicalId":10218,"journal":{"name":"Ciba Foundation symposium","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2007-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87096397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The relationship between erythromycin consumption and resistance in Finland. Finnish Study Group for Antimicrobial Resistance.","authors":"P. Huovinen, H. Seppălä, J. Kataja, T. Klaukka","doi":"10.1002/9780470515358.CH3","DOIUrl":"https://doi.org/10.1002/9780470515358.CH3","url":null,"abstract":"Because the discovery of new antimicrobial agents cannot be expected in the near future, we will have to manage with the antimicrobials currently available at least for the next decade or two. Therefore, attempts to prevent development of antimicrobial resistance are of major importance. The relationship of local antimicrobial consumption and antimicrobial resistance has been shown in many hospital studies but not in the community, even though this is where most antibiotics are used. At the beginning of 1990s, erythromycin resistance in group A streptococci increased rapidly in Finland. The geographical variations found led to a nationwide study of the possible relation between local erythromycin consumption and variations in erythromycin resistance in the community. Erythromycin resistance was found to be significantly (P = 0.006) linked to local consumption of erythromycin. In further experiments, we found that a new erythromycin resistance phenotype belonging to the T4 serotype was spread over the whole country; 83% of the erythromycin-resistant isolates were of this new phenotype in 1994. In 1991, recommendations were given to reduce use of erythromycin in Finland. Following these recommendations, macrolide consumption decreased by 40% from 1991-1994. Studies are now in progress to evaluate the effect of this reduction on erythromycin resistance of group A streptococci.","PeriodicalId":10218,"journal":{"name":"Ciba Foundation symposium","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2007-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74550591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Antibody catalysis of carbon-carbon bond formation.","authors":"D. Hilvert","doi":"10.1002/9780470514108.CH12","DOIUrl":"https://doi.org/10.1002/9780470514108.CH12","url":null,"abstract":"We have used rationally designed transition state analogues to generate antibodies that catalyse two important carbon-carbon bond forming reactions: a bimolecular Diels-Alder cycloaddition and a unimolecular Claisen rearrangement. Our tailored immunoglobulin catalysts (abzymes) exhibit all the properties of naturally occurring enzymes, including substantial rate accelerations, substrate specificity, and high regio- and stereoselectivity. As first generation abzymes are generally inferior to naturally occurring enzymes, we are also employing classical genetic selection strategies to augment their chemical efficiency. We have expressed the antibody that catalyses the Claisen rearrangement of chorismate in yeast cells that lack natural chorismate mutase activity. Improved versions of the abzyme will be identified, following random mutagenesis, by their ability to repair this metabolic defect. The development and study of highly efficient catalytic antibodies promises to advance our understanding of how enzymes work and evolve, how protein function correlates with structure, and how entirely new enzymic activities can be created for use in research, industry and medicine.","PeriodicalId":10218,"journal":{"name":"Ciba Foundation symposium","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2007-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78925510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Detrusor-external sphincter dyssynergia.","authors":"M. Chancellor, S. Kaplan, J. Blaivas","doi":"10.1002/9780470513941.CH11","DOIUrl":"https://doi.org/10.1002/9780470513941.CH11","url":null,"abstract":"Detrusor-external sphincter dyssynergia (DESD) is characterized by involuntary contractions of the external urethral sphincter during an involuntary detrusor contraction. It is caused by neurological lesions between the brainstem (pontine micturition centre) and the sacral spinal cord (sacral micturition centre). These include traumatic spinal cord injury, multiple sclerosis, myelodysplasia and other forms of transverse myelitis. There are three main types of DESD. In Type 1 there is a concomitant increase in both detrusor pressure and sphincter EMG activity. At the peak of the detrusor contraction the sphincter suddenly relaxes and unobstructed voiding occurs. Type 2 DESD is characterized by sporadic contractions of the external urethral sphincter throughout the detrusor contraction. In Type 3 DESD there is a crescendo-decrescendo pattern of sphincter contraction which results in urethral obstruction throughout the entire detrusor contraction. In patients with sufficient manual dexterity the most reasonable treatment option is to abolish the involuntary detrusor contractions (to ensure continence) and then to institute intermittent self-catheterization (in order to empty the bladder). The bladder may be paralysed pharmacologically or may be surgically converted to a low pressure urinary reservoir by the technique of augmentation enterocystoplasty. In quadriplegic men, transurethral external sphincterotomy may be performed and the incontinence managed with an external urinary appliance. Without proper treatment over 50% of men with DESD develop serious urological complications within about five years. In women these complications are much less common.","PeriodicalId":10218,"journal":{"name":"Ciba Foundation symposium","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2007-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80723266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Intercellular calcium waves mediated by inositol trisphosphate.","authors":"Michael J. Sanderson","doi":"10.1002/9780470514696.CH10","DOIUrl":"https://doi.org/10.1002/9780470514696.CH10","url":null,"abstract":"Intercellular calcium waves occur in diverse cells. Those that are induced by mechanical stimulation have been extensively investigated in epithelial and glial cells. Mechanical stimulation of an individual cell initiates an increase in the intracellular free calcium concentration, [Ca2+]i, that spreads across the cell. At the cell border this intracellular Ca2+ wave is arrested but, after a brief delay, similar Ca2+ waves occur in adjacent cells. The repetition of this process results in the propagation of an intercellular Ca2+ wave through a limited number of cells. The propagation of intercellular Ca2+ waves correlates with the presence of functional gap junctions and occurs in the absence of extracellular Ca2+ or following the microinjection of inositol 1,4,5-trisphosphate (InsP3). The propagation of intercellular Ca2+ waves is inhibited by heparin (an InsP3 receptor antagonist) and by U73122 (a phospholipase C inhibitor) or when intracellular Ca2+ stores are depleted with thapsigargin. These characteristics suggest that mechanical stimulation initiates InsP3 production and that intercellular Ca2+ waves are propagated through the movement of InsP3 through gap junctions. Mathematical modelling supports the idea that diffusion of InsP3 is a viable hypothesis for the generation of intercellular Ca2+ waves. The ability of cells to display changes in [Ca2+]i that are independent of neighbouring cells (i.e., asynchronous Ca2+ oscillations) and the low diffusion constant of Ca2+ suggest that Ca2+ itself is not a major messenger moving between cells to propagate Ca2+ waves.","PeriodicalId":10218,"journal":{"name":"Ciba Foundation symposium","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2007-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90273945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Religious aspects of human genetic information.","authors":"Rihito Kimura, Rihito Kimura","doi":"10.1002/9780470513903.CH11","DOIUrl":"https://doi.org/10.1002/9780470513903.CH11","url":null,"abstract":"To obtain human genetic information with the intention of treating and curing severe genetic disease would be considered to be a positive personal decision of a moral agent in various religious contexts. According to some religious teachings human suffering should not be regarded merely as a negative element of life; however, the scientific achievement of obtaining genetic information should surely increase the possibility of hope for the eventual cure of genetically determined diseases. The elimination of human suffering and tragedy in severe genetically determined illness, on the criterion of the benefit of the patient, is permitted by various contemporary religious teachings, according to an analysis of publications by the World Council of Churches and the Vatican and sources from Jewish, Islamic and Buddhist teachings.","PeriodicalId":10218,"journal":{"name":"Ciba Foundation symposium","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2007-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89213963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Experimental myopia in tree shrews.","authors":"T. Norton","doi":"10.1002/9780470514023.CH11","DOIUrl":"https://doi.org/10.1002/9780470514023.CH11","url":null,"abstract":"When deprived of form vision during postnatal development, tree shrews reliably develop an axial myopia characterized by elongation of the vitreous chamber, zonular dysplasia and a slight reduction in lens weight and thickness. Corneal flattening has been observed in animals visually deprived by eyelid suture but is absent in animals visually deprived with an opaque goggle. The sensitive period for myopia development starts about 15 days after the eyes open and sensitivity remains high for about 3-4 weeks thereafter. Recovery from experimental myopia can occur in tree shrews that are visually deprived using goggles for a short period. Blockade of action potentials from ganglion cells in deprived eyes by intravitreal injections of tetrodotoxin (TTX) does not prevent the development of myopia, suggesting that local retinoscleral mechanisms can contribute to experimental myopia in this species. Open eyes receiving intravitreal injections of either saline or TTX have shorter vitreous chambers than control eyes, suggesting that puncturing the globe reduces forces within the eye that contribute to its expansion. Animals treated intraperitoneally with lathyritic agents to block collagen cross-linking for three weeks during a 75-day period of monocular visual deprivation develop a very large myopia in the visually deprived eye that is accompanied by a large vitreous chamber elongation and marked thinning of the posterior sclera. The results from studies in tree shrews are consistent with the suggestion that an internally driven expansion acts in concert with ocular growth to increase the axial length of the eye, helping to move the eye from hyperopia toward emmetropia. The resistance of the sclera and/or choroid to this expansion may be affected by activity within the retina. Increased retinal activity associated with achieving a clear image on the retina may result in increased resistance to expansion, helping to hold the retina at the focal plane. Recovery may occur by a slowing of axial expansion while the optical surfaces proceed toward adult values.","PeriodicalId":10218,"journal":{"name":"Ciba Foundation symposium","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2007-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76931107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Rules for the production of sensory cells.","authors":"J. Lewis","doi":"10.1002/9780470514122.CH3","DOIUrl":"https://doi.org/10.1002/9780470514122.CH3","url":null,"abstract":"During development and regeneration, cells divide, move, change their internal state, respond to environmental signals and die according to rules specified by their genome. These rules of cell behaviour are fundamental to any explanation of how sensory tissues are generated or repaired. An attempt is made to summarize and compare the rules underlying the development of four different sensory tissues: mammalian retina, avian auditory epithelium, mechanosensory bristle fields in Drosophila and, very briefly, Drosophila retina. There are parallels in cell lineage, in the timing of developmental decisions, in the postponement of the choice of differentiated state until the final cell division cycle, in the role of short-range lateral inhibition, and in the involvement of genes such as Notch and achaete/scute. These similarities may reflect the conservation of some basic mechanisms of sensory development that originated early in the evolution of multicellular animals. If so, studies in Drosophila, with its advantages for molecular genetics, may give important clues to the mechanisms of sensory development and regeneration in vertebrates.","PeriodicalId":10218,"journal":{"name":"Ciba Foundation symposium","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2007-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79280138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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