ORCID Profile
0000-0001-6956-2843
Current Organisations
University of Cambridge
,
Tampere University
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Publisher: Springer US
Date: 1989
Publisher: Springer Science and Business Media LLC
Date: 1980
DOI: 10.1007/BF00611878
Publisher: Wiley
Date: 29-03-2004
Publisher: Cold Spring Harbor Laboratory
Date: 02-10-2020
DOI: 10.1101/2020.09.30.306795
Abstract: Cancers can vary greatly in their transcriptomes. In contrast to alterations in specific genes or pathways, differences in tumor cell total mRNA content have not been comprehensively assessed. Technical and analytical challenges have impeded examination of total mRNA expression at scale across cancers. To address this, we developed a model for quantifying tumor-specific total mRNA expression (TmS) from bulk sequencing data, which performs transcriptomic deconvolution while adjusting for mixed genomes. We used single-cell RNA sequencing data to demonstrate total mRNA expression as a feature of tumor phenotype. We estimated and validated TmS in 5,015 patients across 15 cancer types identifying significant inter-in idual variability. At a pan-cancer level, high TmS is associated with increased risk of disease progression and death. Cancer type-specific patterns of genetic alterations, intra-tumor genetic heterogeneity, as well as pan-cancer trends in metabolic dysregulation and hypoxia contribute to TmS. Taken together, our results suggest that measuring cell-type specific total mRNA expression offers a broader perspective of tracking cancer transcriptomes, which has important biological and clinical implications.
Publisher: Elsevier BV
Date: 03-2001
DOI: 10.1016/S0042-6989(00)00288-1
Abstract: Photoreceptor noise sets an absolute limit for the accuracy of colour discrimination. We compared colour thresholds in the honeybee (Apis mellifera) with this limit. Bees were trained to discriminate an achromatic stimulus from monochromatic lights of various wavelengths as a function of their intensity. Signal-to-noise ratios were measured by intracellular recordings in the three spectral types of photoreceptor cells. To model thresholds we assumed that discrimination was mediated by opponent mechanisms whose performance was limited by receptor noise. Most of the behavioural thresholds were close to those predicted from receptor signal-to-noise ratios, suggesting that colour discrimination in honeybees is affected by photoreceptor noise. Some of the thresholds were lower than this theoretical limit, which indicates summation of photoreceptor cell signals.
Publisher: Elsevier BV
Date: 12-2008
Publisher: University of Chicago Press
Date: 09-2009
DOI: 10.1086/644683
Publisher: The MIT Press
Date: 07-01-2011
Publisher: Cambridge University Press (CUP)
Date: 06-1979
Publisher: Elsevier BV
Date: 07-2005
Publisher: Public Library of Science (PLoS)
Date: 03-10-2013
Publisher: Elsevier BV
Date: 1994
Publisher: Public Library of Science (PLoS)
Date: 04-05-2007
Publisher: Public Library of Science (PLoS)
Date: 20-03-2007
Publisher: Elsevier BV
Date: 08-1999
DOI: 10.1016/S0042-6989(98)00297-1
Abstract: Recent accounts attribute motion adaptation to a shortening of the delay filter in elementary motion detectors (EMDs). Using computer modelling and recordings from HS neurons in the drone-fly Eristalis tenax, we present evidence that challenges this theory. (i) Previous evidence for a change in the delay filter comes from 'image step' (or 'velocity impulse') experiments. We note a large discrepancy between the temporal frequency tuning predicted from these experiments and the observed tuning of motion sensitive cells. (ii) The results of image step experiments are highly sensitive to the experimental method used. (iii) An apparent motion stimulus reveals a much shorter EMD delay than suggested by previous 'image step' experiments. This short delay agrees with the observed temporal frequency sensitivity of the unadapted cell. (iv) A key prediction of a shortening delay filter is that the temporal frequency optimum of the cell should show a large shift to higher temporal frequencies after motion adaptation. We show little change in the temporal or spatial frequency (and hence velocity) optima following adaptation.
Publisher: Research Square Platform LLC
Date: 11-06-2021
DOI: 10.21203/RS.3.RS-600171/V1
Abstract: Cancers can vary greatly in their transcriptomes. In contrast to alterations in specific genes or pathways, differences in tumor cell total mRNA content have not been comprehensively assessed. Technical and analytical challenges have impeded examination of total mRNA expression at scale across cancers. To address this, we developed a model for quantifying tumor-specific total mRNA expression (TmS) from bulk sequencing data, which performs transcriptomic deconvolution while adjusting for mixed genomes. We used single-cell RNA sequencing data to demonstrate total mRNA expression as a feature of tumor phenotype. We estimated and validated TmS in 5,015 patients across 15 cancer types identifying significant inter-in idual variability. At a pan-cancer level, high TmS is associated with increased risk of disease progression and death. Cancer type-specific patterns of genetic alterations, intra-tumor genetic heterogeneity, as well as pan-cancer trends in metabolic dysregulation and hypoxia contribute to TmS. Taken together, our results suggest that measuring cell-type specific total mRNA expression offers a broader perspective of tracking cancer transcriptomes, which has important biological and clinical implications.
Publisher: Springer Berlin Heidelberg
Date: 1975
Publisher: Springer Berlin Heidelberg
Date: 1989
Publisher: IOP Publishing
Date: 23-06-2016
Publisher: Springer Berlin Heidelberg
Date: 2000
Publisher: Elsevier BV
Date: 1977
Publisher: Elsevier BV
Date: 2010
DOI: 10.1016/J.CUB.2009.10.079
Abstract: Accurate limb placement helps animals and robots to walk on substrates that are uneven or contain gaps. Visual information is important in controlling limb placement in walking mammals but has received little attention in insects. We investigated whether desert locusts walking along a horizontal ladder use vision to control limb placement. High-speed video analysis showed that locusts targeted their front legs to specific rungs in the absence of any previous contact, suggesting that visual information alone is sufficient for targeting single steps. Comparison between the proportions of missed steps before and after monocular occlusion showed that monocular visual information was used to place the ipsilateral but not the contralateral front leg. Accurate placement also depended upon mechanosensory inputs from the antennae and proprioceptive feedback from the ipsilateral but not the contralateral forelimb. Locusts also compensated for the loss of inputs to one eye by altering their stepping pattern. Changing the rung position after initiation of a step showed that targeting of the front leg depends on visual information acquired before but not during a step. The trajectory was only modified after missing the rung. Our data show that locusts walking in environments where footholds are limited use visual and mechanosensory information to place their front legs.
Publisher: Springer Science and Business Media LLC
Date: 1973
DOI: 10.1007/BF00696346
Publisher: Elsevier BV
Date: 03-1991
DOI: 10.1016/0896-6273(91)90255-X
Abstract: The Shaker gene, responsible for A-type potassium channels in Drosophila muscle, encodes a large family of transcripts capable of generating a variety of kinetically distinct A channels when expressed in oocytes. We describe a distinct class of A channel encoded by the Shaker gene in a novel preparation of dissociated Drosophila photoreceptors. Whole-cell recordings reveal a rapidly inactivating A current that is absent in Shaker mutants and that can be readily isolated in cell-attached patches. Although very similar to their muscle counterparts, the photoreceptor A channels show a striking 40-50 mV negative shift in their voltage-operating range. Two mutations (ShE62 and T(1 Y)W32), which exclude only certain classes of Shaker transcripts, were used to show that photoreceptor A channels are encoded by multiple transcripts distinct from those encoding muscle A channels, while PCR techniques identified four transcripts (ShA1, ShA2, ShG1, and ShG2) in mRNA from dissected retina.
Publisher: Springer Science and Business Media LLC
Date: 18-04-2016
DOI: 10.1038/NPHYS3715
Publisher: Springer Science and Business Media LLC
Date: 13-06-2022
DOI: 10.1038/S41587-022-01342-X
Abstract: Single-cell RNA sequencing studies have suggested that total mRNA content correlates with tumor phenotypes. Technical and analytical challenges, however, have so far impeded at-scale pan-cancer examination of total mRNA content. Here we present a method to quantify tumor-specific total mRNA expression (TmS) from bulk sequencing data, taking into account tumor transcript proportion, purity and ploidy, which are estimated through transcriptomic/genomic deconvolution. We estimate and validate TmS in 6,590 patient tumors across 15 cancer types, identifying significant inter-tumor variability. Across cancers, high TmS is associated with increased risk of disease progression and death. TmS is influenced by cancer-specific patterns of gene alteration and intra-tumor genetic heterogeneity as well as by pan-cancer trends in metabolic dysregulation. Taken together, our results indicate that measuring cell-type-specific total mRNA expression in tumor cells predicts tumor phenotypes and clinical outcomes.
Publisher: Springer Science and Business Media LLC
Date: 06-1973
DOI: 10.1007/BF01352157
Publisher: Wiley
Date: 19-12-2007
DOI: 10.1111/J.1475-1313.1992.TB00281.X
Abstract: When the pupil is opened to increase sensitivity there is a loss of image sharpness due to aberrations. This trade-off between sensitivity and sharpness is analysed theoretically by calculating the information capacity of the retinal image. The analysis uses optical measurements of image sharpness made at different pupil diameters. At each luminance there is a pupil diameter that maximizes information capacity. This optimum is close to the diameter adopted under normal viewing conditions. The optimum is broad, consequently the system tolerates inaccurate adjustment. The benefits of correctly adjusting the pupil are evaluated. At low light levels the advantage is 68%, at intermediate levels it falls to around 20% but under daylight conditions it increases to 52%. These advantages suggest that the primary function of the pupillary light reflex is to maximize acuity over a wide range of luminances.
Publisher: The Royal Society
Date: 04-2017
Abstract: Voltage-dependent conductances in many spiking neurons are tuned to reduce action potential energy consumption, so improving the energy efficiency of spike coding. However, the contribution of voltage-dependent conductances to the energy efficiency of analogue coding, by graded potentials in dendrites and non-spiking neurons, remains unclear. We investigate the contribution of voltage-dependent conductances to the energy efficiency of analogue coding by modelling blowfly R1-6 photoreceptor membrane. Two voltage-dependent delayed rectifier K + conductances (DRs) shape the membrane's voltage response and contribute to light adaptation. They make two types of energy saving. By reducing membrane resistance upon depolarization they convert the cheap, low bandwidth membrane needed in dim light to the expensive high bandwidth membrane needed in bright light. This investment of energy in bandwidth according to functional requirements can halve daily energy consumption. Second, DRs produce negative feedback that reduces membrane impedance and increases bandwidth. This negative feedback allows an active membrane with DRs to consume at least 30% less energy than a passive membrane with the same capacitance and bandwidth. Voltage-dependent conductances in other non-spiking neurons, and in dendrites, might be organized to make similar savings.
Publisher: Elsevier BV
Date: 11-2000
DOI: 10.1016/S0896-6273(00)00136-7
Abstract: In many species, including humans, exposure to high image velocities induces motion adaptation, but the neural mechanisms are unclear. We have isolated two mechanisms that act on directionally selective motion-sensitive neurons in the fly's visual system. Both are driven strongly by movement and weakly, if at all, by flicker. The first mechanism, a subtractive process, is directional and is only activated by stimuli that excite the neuron. The second, a reduction in contrast gain, is strongly recruited by motion in any direction, even if the adapting stimulus does not excite the cell. These mechanisms are well designed to operate effectively within the context of motion coding. They can prevent saturation at susceptible nonlinear stages in processing, cope with rapid changes in direction, and preserve fine structure within receptive fields.
Publisher: IOP Publishing
Date: 24-02-2016
Publisher: Springer Science and Business Media LLC
Date: 1976
DOI: 10.1007/BF00606466
Publisher: Elsevier BV
Date: 04-2010
DOI: 10.1016/J.CUB.2010.01.064
Abstract: Animal locomotion often depends upon stabilization reflexes that use sensory feedback to maintain trajectories and orientation. Such stabilizing reflexes are critically important for the blowfly, whose aerodynamic instability permits outstanding maneuverability but increases the demands placed on flight control. Flies use several sensory systems to drive reflex responses, and recent studies have provided access to the circuitry responsible for combining and employing these sensory inputs. We report that lobula plate VS neurons combine inputs from two optical sensors, the ocelli and the compound eyes. Both systems deliver essential information on in-flight rotations, but our neuronal recordings reveal that the ocelli encode this information in three axes, whereas the compound eyes encode in nine. The difference in dimensionality is reconciled by tuning each VS neuron to the ocellar axis closest to its compound eye axis. We suggest that this simple projection combines the speed of the ocelli with the accuracy of the compound eyes without compromising either. Our findings also support the suggestion that the coordinates of sensory information processing are aligned with axes controlling the natural modes of the fly's flight to improve the efficiency with which sensory signals are transformed into appropriate motor commands.
Publisher: Elsevier BV
Date: 09-2000
Publisher: Springer Berlin Heidelberg
Date: 2001
Publisher: SAGE Publications
Date: 10-2001
DOI: 10.1097/00004647-200110000-00001
Abstract: Anatomic and physiologic data are used to analyze the energy expenditure on different components of excitatory signaling in the grey matter of rodent brain. Action potentials and postsynaptic effects of glutamate are predicted to consume much of the energy (47% and 34%, respectively), with the resting potential consuming a smaller amount (13%), and glutamate recycling using only 3%. Energy usage depends strongly on action potential rate—an increase in activity of 1 action potential/cortical neuron/s will raise oxygen consumption by 145 mL/100 g grey matter/h. The energy expended on signaling is a large fraction of the total energy used by the brain this favors the use of energy efficient neural codes and wiring patterns. Our estimates of energy usage predict the use of distributed codes, with ≤15% of neurons simultaneously active, to reduce energy consumption and allow greater computing power from a fixed number of neurons. Functional magnetic resonance imaging signals are likely to be dominated by changes in energy usage associated with synaptic currents and action potential propagation.
Publisher: The MIT Press
Date: 07-01-2011
DOI: 10.7551/MITPRESS/9780262014120.001.0001
Abstract: Work as fundamental to life, explored at different levels of organization from the perspectives of a variety of biological and nonbiological disciplines. The work performed by living systems ranges from photosynthesis to prodigious feats of computation and organization. This multidisciplinary volume explores the relationships between work and the study of work across many different levels of organization. By addressing how work gets done, and why, from the perspectives of a range of disciplines, including cell and evolutionary biology, neuroscience, psychology, electrical and computer engineering, and design, the volume sets out to establish an integrative approach to the study of work.Chapters introduce the biological work of producing energy in the cell establish inherent tradeoffs between energy and information in neural systems relate principles of integrated circuit manufacture to work in biological systems explore the work of photosynthesis investigate how work shapes organisms' evolutionary niches consider the human work of design describe the effects of job satisfaction and dissatisfaction on work-life balance and address the effects of environmental challenges (stress) on how humans and animals do work. Finally, editors and contributors draw these studies together and point to future developments. ContributorsAlan Blackwell, Gillian Brown, Christina De La Rocha, Kevin Laland, Simon Laughlin, Robert Levin, Michael Lightner, Steven Maier, Joseph Rosse, Stacy Saturay
Publisher: Frontiers Media SA
Date: 2010
Publisher: Springer US
Date: 1984
Publisher: Elsevier BV
Date: 04-2018
Publisher: MIT Press - Journals
Date: 06-2002
DOI: 10.1162/089976602753712963
Abstract: We investigate the energy efficiency of signaling mechanisms that transfer information by means of discrete stochastic events, such as the opening or closing of an ion channel. Using a simple model for the generation of graded electrical signals by sodium and potassium channels, we find optimum numbers of channels that maximize energy efficiency. The optima depend on several factors: the relative magnitudes of the signaling cost (current flow through channels), the fixed cost of maintaining the system, the reliability of the input, additional sources of noise, and the relative costs of upstream and downstream mechanisms. We also analyze how the statistics of input signals influence energy efficiency. We find that energy-efficient signal ensembles favor a bimodal distribution of channel activations and contain only a very small fraction of large inputs when energy is scarce. We conclude that when energy use is a significant constraint, trade-offs between information transfer and energy can strongly influence the number of signaling molecules and synapses used by neurons and the manner in which these mechanisms represent information.
Publisher: Cambridge University Press
Date: 15-05-2000
Publisher: The Optical Society
Date: 02-2001
Abstract: Although a great deal of experimental evidence supports the notion of a Reichardt correlator as a mechanism for biological motion detection, the correlator does not signal true image velocity. This study examines the accuracy with which realistic Reichardt correlators can provide velocity estimates in an organism's natural visual environment. The predictable statistics of natural images imply a consistent correspondence between mean correlator response and velocity, allowing the otherwise ambiguous Reichardt correlator to act as a practical velocity estimator. Analysis and simulations suggest that processes commonly found in visual systems, such as prefiltering, response compression, integration, and adaptation, improve the reliability of velocity estimation and expand the range of velocities coded. Experimental recordings confirm our predictions of correlator response to broadband images.
Publisher: Elsevier BV
Date: 11-1987
Publisher: Springer Science and Business Media LLC
Date: 1978
DOI: 10.1007/BF00657606
Publisher: Springer Science and Business Media LLC
Date: 1975
DOI: 10.1007/BF00613963
Publisher: Springer Science and Business Media LLC
Date: 07-1987
DOI: 10.1038/328292A0
Publisher: Elsevier BV
Date: 12-2002
DOI: 10.1016/S0960-9822(02)01345-3
Abstract: Gap junctions have been shown to electrically couple cone photoreceptors: coupling blurs the image coded by cones, but this loss is offset by a decrease in noise. Electrical coupling thus improves the resolution of signals distributed across groups of cells.
Publisher: Springer Science and Business Media LLC
Date: 04-1978
DOI: 10.1007/BF00219782
Publisher: Springer Science and Business Media LLC
Date: 1976
DOI: 10.1007/BF00606539
Publisher: Elsevier BV
Date: 02-2010
Publisher: Elsevier BV
Date: 2000
DOI: 10.1016/S0042-6989(99)00171-6
Abstract: White noise techniques are used to compare the two photoreceptor sub-types in blowfly retina, the short visual fibres (R1-6) that code achromatic contrast, and the long visual fibres (R7 and R8) that together code wavelength distribution and polarisation plane. Measurements of signal and noise spectra and contrast gain, taken across a broad intensity range, permit a detailed comparison of coding efficiency under natural conditions of illumination. As a function of excitation (effective photons per photoreceptor per second h upsilon/rec per s), adaptive changes in the long and short visual fibres are similar, suggesting that post-rhodopsin their phototransduction cascades are identical. Under identical natural daylight conditions (photons per cm2 per second h upsilon/cm2 per s) short visual fibres catch more photons, thus operating with a higher signal to noise ratio and faster response, to consistently outperform the long visual fibres. Long visual fibres compensate for their poor quantum catch by having a higher absolute gain (mV/h upsilon) which at low light intensities enables them to achieve a level of contrast gain (mV/unit contrast) similar to the short visual fibres. Differences in signal to noise ratios are related to known differences in photoreceptor structure and synaptic frequency among visual interneurons. The principles of matching sensitivity and synapse number to quantum catch described here could explain analogous differences between chromatic and achromatic pathways in mammalian and hibian retinas.
Publisher: Frontiers Media SA
Date: 2010
Publisher: Wiley
Date: 20-07-2001
Abstract: Neural coding in the retina and lamina of fly compound eyes is amenable to detailed anatomical, physiological and theoretical analysis. This approach shows how identified cell signalling systems are optimized to maximize the transmission of information. Optimization reveals three familiar constraints, noise, saturation and bandwidth, and shows how coding can minimize their effects. Experiments reveal a fourth constraint, metabolic cost, whose properties favour the distribution of information among multiple pathways. The advantages of distributed codes will be offset by increasing complexity and the build up of noise. The optimization of coding in fly retina suggests that both noise and complexity will be reduced by matching each step in the system's operations to the input signal, and to the logical requirements of the network's ultimate function, pattern processing. This line of argument suggests tightly organized networks, laid out that information flows freely and independently, yet patterned so that the necessary contacts and transactions are made quickly and efficiently.
Publisher: Elsevier BV
Date: 06-1996
DOI: 10.1016/0042-6989(95)00242-1
Abstract: This study demonstrates how phototransduction cascades and membranes tune photoreceptor response dynamics to image quality, and eliminate noise introduced in cell signalling. Intracellular recordings from intact retina confirm that the light-adapted photoreceptors of the crane fly Tipula paludosa (Diptera Tipulidae) have a slow response, appropriate for their visual ecology. To provide a slow response, the phototransduction cascade's impulse response fails to narrow with light-adaptation, despite reductions in the timescales of latency and quantum bumps. The photoreceptor membrane acts as a passive RC-filter, because light induced depolarization inactivates voltage-gated potassium currents. The frequency response of the membrane equals the cascade's and, as a result, the membrane is a matched filter that suppresses photon shot noise. This type of broad-band filter, matched to the predictable dynamics of preceding processes to remove noise, could be widely employed in vision and in many other chains of cellular communication.
Publisher: Elsevier BV
Date: 1995
DOI: 10.1016/0166-2236(95)93945-T
Abstract: That particular membrane conductances are selected for expression to enable the efficient coding of biologically relevant signals is illustrated by recent work on insect photoreceptors. These studies exploit the richness of insect vision and the accessibility of insect photoreceptors to cellular analysis in both intact animal and isolated cell preparations. The distribution of voltage-gated conductances among photoreceptors of different species correlates with visual ecology. Delayed-rectifier K+ channels are found in the rapidly responding photoreceptors of fast-flying flies. The conductance's activation range and dynamics match light-induced signals, and enable a rapid response by reducing the membrane time constant. Slow-moving flies have slowly responding photoreceptors that lack the delayed rectifier, but express an inactivating K+ conductance that is metabolically less demanding. Complementing these findings, locust photoreceptor membranes are modulated diurnally. The delayed rectifier is exhibited during the day and the inactivating K+ current is exhibited at night. Insect photoreceptors also demonstrate the lification of signals by voltage-gated Na+ channels. In drone-bee photoreceptors, voltage-gated Na+ channels combine with K+ channels to enhance the small transient signals produced by the image of a queen bee passing over the retina. This subthreshold lifier operates most effectively over the range of light intensities at which drones pursue queens.
Publisher: The MIT Press
Date: 07-01-2011
Publisher: The MIT Press
Date: 07-01-2011
Publisher: Elsevier BV
Date: 06-2005
DOI: 10.1016/J.CUB.2005.05.056
Abstract: The action potential (AP) is transmitted by the concerted action of voltage-gated ion channels. Thermodynamic fluctuations in channel proteins produce probabilistic gating behavior, causing channel noise. Miniaturizing signaling systems increases susceptibility to noise, and with many cortical, cerebellar, and peripheral axons <0.5 mum diameter [1, 2 and 3], channel noise could be significant [4 and 5]. Using biophysical theory and stochastic simulations, we investigated channel-noise limits in unmyelinated axons. Axons of diameter below 0.1 microm become inoperable because single, spontaneously opening Na channels generate spontaneous AP at rates that disrupt communication. This limiting diameter is relatively insensitive to variations in biophysical parameters (e.g., channel properties and density, membrane conductance and leak) and will apply to most spiking axons. We demonstrate that the essential molecular machinery can, in theory, fit into 0.06 microm diameter axons. However, a comprehensive survey of anatomical data shows a lower limit for AP-conducting axons of 0.08-0.1 microm diameter. Thus, molecular fluctuations constrain the wiring density of brains. Fluctuations have implications for epilepsy and neuropathic pain because changes in channel kinetics or axonal properties can change the rate at which channel noise generates spontaneous activity.
Publisher: Public Library of Science (PLoS)
Date: 23-01-2014
Publisher: Public Library of Science (PLoS)
Date: 07-2010
Publisher: Springer Science and Business Media LLC
Date: 1974
DOI: 10.1007/BF00694708
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Matti Nykter.