Proceedings of the Royal Society of London Series B-Containing Papers of Abiological Character最新文献

{"title":"The Wellcome lecture, 1988. Muscular dystrophy: a time of hope.","authors":"L M Kunkel","doi":"10.1098/rspb.1989.0032","DOIUrl":"https://doi.org/10.1098/rspb.1989.0032","url":null,"abstract":"<p><p>Duchenne muscular dystrophy (DMD) and its less severe allele Becker muscular dystrophy (BMD) are progressive muscle-wasting disorders of children. DMD is characterized by rapid loss of muscle fibres and the ensuing weakness results in lost mobility and eventual premature death. Despite extensive research for many years, the basic underlying biochemical defect has remained elusive. Here I try to demonstrate how the powerful techniques of molecular genetics can be used to gain a further understanding of this particular disorder and how, in principle, the techniques can be applied to the other 3000 human genetic disorders that are so far uncharacterized. Once the chromosomal map position of DMD was established, the locus that was being disrupted by mutation could be identified and the encoded protein product predicted from the nucleotide sequence of the RNA transcript. This has led to the identification of a previously uncharacterized protein named dystrophin. As the normal function of dystrophin is determined, more accurate clinical diagnosis of DMD and BMD should result and potential approaches to therapy should be designed.</p>","PeriodicalId":54561,"journal":{"name":"Proceedings of the Royal Society of London Series B-Containing Papers of Abiological Character","volume":"237 1286","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"1989-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1098/rspb.1989.0032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13712077","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":"Ion-channel gating mechanisms: model identification and parameter estimation from single channel recordings.","authors":"F G Ball,&nbsp;M S Sansom","doi":"10.1098/rspb.1989.0029","DOIUrl":"https://doi.org/10.1098/rspb.1989.0029","url":null,"abstract":"<p><p>Patch-clamp data may be analysed in terms of Markov process models of channel gating mechanisms. We present a maximum likelihood algorithm for estimation of gating parameters from records where only a single channel is present. Computer simulated data for three different models of agonist receptor gated channels are used to demonstrate the performance of the procedure. Full details of the implementation of the algorithm are given for an example gating mechanism. The effects of omission of brief openings and closings from the single-channel data on parameter estimation are explored. A strategy for discriminating between alternative possible gating models, based upon use of the Schwarz criterion, is described. Omission of brief events is shown not to lead to incorrect model identification, except in extreme circumstances. Finally, the algorithm is extended to include channel gating models exhibiting multiple conductance levels.</p>","PeriodicalId":54561,"journal":{"name":"Proceedings of the Royal Society of London Series B-Containing Papers of Abiological Character","volume":"236 1285","pages":"385-416"},"PeriodicalIF":0.0,"publicationDate":"1989-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1098/rspb.1989.0029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13617429","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":"Mammalian mating systems.","authors":"T H Clutton-Brock","doi":"10.1098/rspb.1989.0027","DOIUrl":"https://doi.org/10.1098/rspb.1989.0027","url":null,"abstract":"<p><p>Male mammals show a diverse array of mating bonds, including obligate monogamy, unimale and group polygyny and promiscuity. These are associated with a wide variety of different forms of mate guarding, including the defence of feeding and mating territories, the defence of female groups and the defence of individual receptive females. Female mating bonds include long-term monogamy, serial monogamy, polyandry and promiscuity. Both male and female mating behaviour varies widely within species. Variation in male mating behaviour is related to the effect of male assistance in rearing young and to the defensibility of females by males. The latter is, in turn, related to female ranging behaviour and to the size and stability of female groups. Much of the variation in mammalian mating bonds and systems of mate guarding can be attributed to differences in these three variables.</p>","PeriodicalId":54561,"journal":{"name":"Proceedings of the Royal Society of London Series B-Containing Papers of Abiological Character","volume":"236 1285","pages":"339-72"},"PeriodicalIF":0.0,"publicationDate":"1989-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1098/rspb.1989.0027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13710697","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":"Ocular vergence under natural conditions. I. Continuous changes of target distance along the median plane.","authors":"C J Erkelens,&nbsp;J Van der Steen,&nbsp;R M Steinman,&nbsp;H Collewijn","doi":"10.1098/rspb.1989.0030","DOIUrl":"https://doi.org/10.1098/rspb.1989.0030","url":null,"abstract":"<p><p>Horizontal binocular eye movements of four subjects were recorded with the scleral sensor coil--revolving magnetic field technique while they fixated a natural target, whose distance was varied in a normally illuminated room. The distance of the target relative to the head of the subject was changed in three ways: (a) the target was moved manually by the experimenter; (b) the target was moved manually by the subject; (c) the target remained stationary while the subject moved his upper torso towards and away from the target. The rate of change of target distance was varied systematically in four levels, ranging from 'slow' to 'very fast', corresponding to changes in target vergence from about 10 degrees s-1 to about 100 degrees s-1. The dynamics of ocular vergence with regard to delay and speed were, under all three conditions, considerably better than could be expected from the literature on ocular vergence induced by disparity and/or blur. When 'very fast' changes in the distance of the target were made, subjects achieved maximum vergence speeds of up to about 100 degrees s-1. Delays of these fast vergence responses were generally smaller than 125 ms. Negative delays, i.e. ocular vergence leading the change in target distance, were observed. The eyes led the target (i.e. predicted target motion) by about 90 ms on average, when the subject used his hand to move the target. Vergence tracking was almost perfect when changes in distance were produced by moving the upper torso. In this condition, the eye led the target by about 5 ms. In the 'slow' and 'medium' conditions (stimulus speeds about 10-40 degrees s-1) tracking was accurate to within 1-2 degrees, irrespective of the way in which the target was moved. In the 'fast' and 'very fast' conditions (stimulus speeds about 40-100 degrees s-1), the accuracy of vergence tracking was better for self-induced than for experimenter-induced target displacements, and accuracy was best during voluntary movements of the upper torso. In the last case, ocular vergence speed was within about 10% of the rate of change of the vergence angle formed by the eyes and the stationary target. The dynamics of convergent and divergent vergence responses varied considerably. These variations were idiosyncratic. They were consistent within, but not between, subjects. Ocular vergence associated with attempted fixation of an imagined target, changing distance in darkness, could only be made by two of the four subjects.(ABSTRACT TRUNCATED AT 400 WORDS)</p>","PeriodicalId":54561,"journal":{"name":"Proceedings of the Royal Society of London Series B-Containing Papers of Abiological Character","volume":"236 1285","pages":"417-40"},"PeriodicalIF":0.0,"publicationDate":"1989-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1098/rspb.1989.0030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13710699","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":"Role of excitatory amino acid receptors in synaptic transmission in area CA1 of rat hippocampus.","authors":"S N Davies,&nbsp;G L Collingridge","doi":"10.1098/rspb.1989.0028","DOIUrl":"https://doi.org/10.1098/rspb.1989.0028","url":null,"abstract":"<p><p>The new antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), which blocks responses to kainate and quisqualate, has been used in conjunction with D-2-amino-5-phosphonovalerate (APV), which blocks selectively responses to N-methyl-D-aspartate (NMDA), to determine the role of excitatory amino acid receptors in synaptic transmission. An excitatory postsynaptic potential (EPSP)-inhibitory postsynaptic potential (IPSP) sequence was evoked in CA1 neurons by stimulation of the Schaffer collateral-commissural pathway in rat hippocampal slices. CNQX (10 microM) substantially reduced the EPSP without having any effect on input resistance or membrane potential. The IPSP was also reduced provided that the stimulating electrode was place approximately 1 mm from the recording electrode. The EPSP that remained in the presence of CNQX had characteristics of an NMDA receptor-mediated potential; it had a slow timecourse, summated at high frequencies, was blocked reversibly by APV, increased greatly in size in Mg2+-free medium, and showed an anomalous voltage dependence in Mg2+-containing medium. In the presence of CNQX, an APV-sensitive polysynaptic GABAergic IPSP could be evoked, indicating that NMDA receptors can mediate suprathreshold EPSPS in inhibitory interneurons. It is suggested that either NMDA or non-NMDA receptors can, under different circumstances, mediate the synaptic excitation of pyramidal neurons and inhibitory interneurons in area CA1 of the hippocampus.</p>","PeriodicalId":54561,"journal":{"name":"Proceedings of the Royal Society of London Series B-Containing Papers of Abiological Character","volume":"236 1285","pages":"373-84"},"PeriodicalIF":0.0,"publicationDate":"1989-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1098/rspb.1989.0028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13710698","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":"Ocular vergence under natural conditions. II. Gaze shifts between real targets differing in distance and direction.","authors":"C J Erkelens,&nbsp;R M Steinman,&nbsp;H Collewijn","doi":"10.1098/rspb.1989.0031","DOIUrl":"https://doi.org/10.1098/rspb.1989.0031","url":null,"abstract":"<p><p>Horizontal binocular eye movements of three subjects were recorded with the scleral sensor coil--revolving magnetic field technique during voluntary shifts of gaze between pairs of stationary, real, continuously visible targets. The target pairs were located either along the median plane (requiring symmetrical vergence), or on either side of the median plane (requiring asymmetrical vergence). Symmetrical vergence was primarily smooth, but it was often assisted by small, disjunctive saccades. Peak vergence speeds were very high; they increased from about 50 degrees s-1 for vergence changes of 5 degrees to between 150 and 200 degrees s-1 for vergence changes of 34 degrees. Differences between convergence and divergence were idiosyncratic. Asymmetrical vergence, requiring a vergence of 11 degrees combined with a version of 45 degrees, was largely saccadic. Unequal saccades mediated virtually all (95%) of the vergence required in the divergent direction, whereas 75% of the vergence required in the convergent direction was mediated by unequal saccades, with the remaining convergence mediated by smooth vergence, following completion of the saccades. Peak divergence speeds during these saccades were very high (180 degrees s-1 for a change of vergence of 11 degrees); much faster than the smooth, symmetrical vergence change of comparable size (14 degrees). Peak convergent saccadic speeds were about 20% lower. This difference in peak speed was caused by an initial, transient divergence, observed at the beginning of all horizontal saccades. The waveform of disjunctive saccades did not have the same shape as the waveform of conjugate saccades of similar size. The smaller saccade of the disjunctive pair was stretched out in time so as to have the same duration as its larger, companion saccade. These results permitted the conclusion that the subsystems controlling saccades and vergence are not independent. Vergence responses were relatively slow and incomplete with monocular viewing, which excluded disparity as a cue. Monocularly stimulated vergence decreased as a function of the increasing presbyopia of our three subjects. Subjects were able to generate some vergence in darkness towards previously seen and remembered targets. Such responses, however, were slow, irregular and evanescent. In conclusion, vergence shifts between targets, which provided all natural cues to distance, were fast and accurate; they appeared adequate to provide effective binocular vision under natural conditions. This result could not have been expected on the basis of previous observations, all of which had been made with severely reduced cues to depth.(ABSTRACT TRUNCATED AT 400 WORDS)</p>","PeriodicalId":54561,"journal":{"name":"Proceedings of the Royal Society of London Series B-Containing Papers of Abiological Character","volume":"236 1285","pages":"441-65"},"PeriodicalIF":0.0,"publicationDate":"1989-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1098/rspb.1989.0031","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13711284","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":"Steps in the development of chemical and electrical synapses by pairs of identified leech neurons in culture.","authors":"Y Liu,&nbsp;J Nicholls","doi":"10.1098/rspb.1989.0023","DOIUrl":"https://doi.org/10.1098/rspb.1989.0023","url":null,"abstract":"<p><p>Experiments have been made to follow the development of chemical and electrical transmission between pairs of leech neurons in culture. 1. The cell bodies of identified neurons were isolated from the CNS by suction after mild enzyme treatment, together with a length of the initial segment (or 'stump'). The neurons tested were Retzius cells (R), annulus erector motoneurons (AE), Anterior pagoda cells (AP) and pressure sensory cells (P). Pairs of cells were placed together in various configurations, with different sites on their surfaces making contact. 2. When pairs of Retzius cells were apposed with their stumps touching, serotonergic, chemically mediated synaptic transmission became apparent before electrical transmission. By 2.5 h impulses in either of the two Retzius cells produced hyperpolarizing inhibitory potentials in the other. These potentials were reversed by raised intracellular Cl and showed clear facilitation. The strength of chemical transmission between Retzius cells increased over the next 72 h. 3. After chemical transmission had been established, weak non-rectifying electrical transmission became apparent between Retzius cells at about 24-72 h. By 4 days coupling became stronger and tended to obscure chemically evoked synaptic potentials. 4. When pairs of Retzius cells were aligned in culture with the tip of one cell stump touching the soma of the other, chemical transmission also developed rapidly. Transmission was, however, in one direction, from stump to soma. At later stages non-rectifying electrical coupling developed as with stump-stump configuration. With the cell bodies of two Retzius cells apposed, electrical coupling developed after several days, before chemical transmission could be observed. 5. When Retzius and P cells were cultured with their stumps in contact, inhibitory chemical synaptic transmission developed within 24 h. Transmission was always in one direction, from Retzius to P cell. Electrical coupling of Retzius and P cells never occurred whatever the spatial relations of the cells to one another. 6. Annulus erector motoneurons, which contain ACh and a peptide resembling FMRFamide, first developed electrical coupling when the two stumps were in contact and then, later, bi-directional chemical transmission. Anterior Pagoda pairs placed stump-to-stump showed electrical connections. 7. Electronmicrographs revealed the presence of synaptic structures within 24 h after Retzius-Retzius, Retzius-P or AE-AE stumps were apposed. 8. The specificity of connections between cultured cells was similar to that observed in earlier experiments.(ABSTRACT TRUNCATED AT 400 WORDS)</p>","PeriodicalId":54561,"journal":{"name":"Proceedings of the Royal Society of London Series B-Containing Papers of Abiological Character","volume":"236 1284","pages":"253-68"},"PeriodicalIF":0.0,"publicationDate":"1989-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1098/rspb.1989.0023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13711156","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":"Pertussis in England and Wales: an investigation of transmission dynamics and control by mass vaccination.","authors":"B T Grenfell,&nbsp;R M Anderson","doi":"10.1098/rspb.1989.0022","DOIUrl":"https://doi.org/10.1098/rspb.1989.0022","url":null,"abstract":"<p><p>The epidemiology of pertussis and its prospects for control by mass vaccination in England and Wales are investigated by analyses of longitudinal records on incidence and vaccine uptake, and horizontal data on age-stratified case reports. Mathematical models of the transmission dynamics of the infection that incorporate loss of natural and vaccine-induced immunity plus variable vaccine efficacy are developed, and their predictions compared with observed trends. Analyses of case reports reveal that the individual force of infection is age dependent, with peak transmission in the 5- to 10-year-old age class. A model incorporating this age dependency, along with partial vaccine efficacy and loss of vaccine-induced immunity, generates predicted patterns that best mirror observed trends since mass vaccination was inaugurated in 1957 in England and Wales. Model projections accurately mirror the failure of mass vaccination to increase the inter-epidemic period of the infection (three years) over that pertaining before control. The analysis suggests that this is due to the impact of partial vaccine efficacy. Projected trends do not accurately reflect the low levels of pertussis incidence reported between epidemics in the periods of high vaccine uptake. This is thought to arise from a combination of factors, including loss of natural and vaccine induced immunity, biases in case reporting (where reporting efficiency is positively associated with the incidence of pertussis), and seasonal variations in transmission. Model predictions suggest that the vaccination of 88% of each birth cohort before the age of 1 year will eliminate bacterial transmission, provided the vaccine confers lifelong protection against infection. If vaccine-induced immunity is significantly less than lifelong (or if vaccination fails to protect all its recipients) repeated cohort immunization is predicted to be necessary to eliminate transmission. Future research needs are discussed, and emphasis is placed on the need for more refined data on vaccine efficacy, the duration of natural and vaccine-induced immunity and the incidence of clinical pertussis and subclinical infections (perhaps by the development of reliable serological tests). Future mathematical models will need especially to incorporate seasonality in transmission.</p>","PeriodicalId":54561,"journal":{"name":"Proceedings of the Royal Society of London Series B-Containing Papers of Abiological Character","volume":"236 1284","pages":"213-52"},"PeriodicalIF":0.0,"publicationDate":"1989-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1098/rspb.1989.0022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13711155","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":"Equivalence of aggregated Markov models of ion-channel gating.","authors":"P Kienker","doi":"10.1098/rspb.1989.0024","DOIUrl":"https://doi.org/10.1098/rspb.1989.0024","url":null,"abstract":"<p><p>One cannot always distinguish different Markov models of ion-channel kinetics solely on the basis of steady-state kinetic data. If two generator (or transition) matrices are related by a similarity transformation that does not combine states with different conductances, then the models described by these generator matrices have the same observable steady-state statistics. This result suggests a procedure for expressing the model in a unique form, and sometimes reducing the number of parameters in a model. I apply the similarity transformation procedure to a number of simple models. When a model specifies the dependence of the rates of transition on an experimentally variable parameter such as the concentration of a ligand or the membrane potential, the class of equivalent models may be further restricted, but a model is not always uniquely determined even under these conditions. Voltage-step experiments produce non-stationary data that can also be used to distinguish models.</p>","PeriodicalId":54561,"journal":{"name":"Proceedings of the Royal Society of London Series B-Containing Papers of Abiological Character","volume":"236 1284","pages":"269-309"},"PeriodicalIF":0.0,"publicationDate":"1989-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1098/rspb.1989.0024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13616641","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":"Automated site-directed drug design: a general algorithm for knowledge acquisition about hydrogen-bonding regions at protein surfaces.","authors":"D J Danziger,&nbsp;P M Dean","doi":"10.1098/rspb.1989.0015","DOIUrl":"https://doi.org/10.1098/rspb.1989.0015","url":null,"abstract":"<p><p>This is the first of four papers that begin to explore the possibility of automated site-directed drug design. A general outline is given of the logical steps involved in approaching the problem. The starting point is the process of knowledge acquisition about the site. An algorithm is described here for the construction of a map of hydrogen-bonding regions at protein surfaces directly from the Brookhaven Protein Data Bank coordinates. Hydrogen-bonding atoms are located, intramolecular bonds are searched for, hydrogen-bonding atoms at the surface are found and hydrogen-bonding regions are computed at the accessible surface. A grid is placed within each region discovered and the probability of hydrogen bonding at each grid point is computed. The output of the program is a map of hydrogen-bonding regions displayed within a user-defined window. This information can be used as part of a knowledge base for the automatic construction of novel ligands to fit specified binding sites.</p>","PeriodicalId":54561,"journal":{"name":"Proceedings of the Royal Society of London Series B-Containing Papers of Abiological Character","volume":"236 1283","pages":"101-13"},"PeriodicalIF":0.0,"publicationDate":"1989-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1098/rspb.1989.0015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13709226","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}