229 research outputs found
A translational approach to the genetics of renal disease
No full textDe invloed van genetica op het nefrologisch onderzoek is de afgelopen decennia sterk gegroeid. Toch is van progressieve nierfunctieachteruitgang nauwelijks bekend welke genen het ontstaan en de progressie ervan veroorzaken. De oplossing hiervoor ligt in een translationele aanpak. Zowel verkennende als gerichte genetische studies zoeken naar verbanden tussen een eigenschap van nierziekte en genetische variaties. Het is dus essentieel dat de eigenschappen van nierziekte goed gedefinieerd zijn.
In grote klinische onderzoeken wordt bijvoorbeeld vaak de geschatte nierfunctie gebruikt. Bij niertransplantatiepatiënten blijkt die niet zo betrouwbaar. De grootte van de systematische afwijking wordt bepaald door leeftijd, geslacht, ware nierfunctie en BMI.
Vitamine-D-bindend eiwit in de urine lijkt een goede maat voor verbindweefseling van de ruimte tussen de tubuluscellen, een vergevorderd stadium van veel nierziekten. Normaal wordt dit eiwit, gebonden aan vitamine D, in de tubuluscellen opgenomen, waar het vitamine D geactiveerd wordt. Bij verbindweefseling functioneren de tubuluscellen minder goed en wordt vitamine-D-bindend eiwit niet meer opnomen. Dit mechanisme was overigens geen verklaring voor de prognostische slechte lage vitamine-D-spiegels bij nefrologische patiënten.
Een verkennend onderzoek naar eiwitverlies in de urine identificeerde drie DNA-gebieden bij muizen die hierbij een rol spelen. De ziekteveroorzakende genen zijn nog onbekend. Gericht onderzoek identificeerde zeven genetische variaties in het vitamine-D-metabolisme die vaker voorkomen bij niertransplantaatontvangers dan bij nierdonoren.
Hoewel er nog veel onderzoek nodig is voordat deze genetische ontdekkingen een klinische toepassing krijgen, bieden de resultaten van dit proefschrift een strategie voor betere integratie van genetica en nefrologie.
The influence of genetics on nephrology research has increased in the past decades. Still, the genetic base of progressive renal function loss is hardly known. The solution is a translational approach. Both exploratory and focused genetic studies aim to find associations between a characteristic of renal disease and genetic variation. A precise definition of characteristics of renal disease is therefore essential.
Large-scale clinical trials often rely on estimated renal function. In renal transplant recipients this measure lacks precision. Sources of bias are age, gender, BMI and true renal function.
Vitamin D binding protein is a promising novel marker for fibrosis of the space between tubular cells, a final common pathway for many renal diseases. Normally this protein, bound to vitamin D, is reabsorbed from the glomerular filtrate into tubular cells, where vitamin D is activated. Fibrosis causes tubular dysfunction and inhibits reabsorption of vitamin D binding protein. This mechanism however, did not explain lower vitamin D levels often seen in renal patients, that are associated with worse prognosis.
An exploratory study of urinary albumin loss identified three areas in mouse DNA. The causal genes are still unknown. A focused study identified seven genetic variations in vitamin D metabolism genes that are more prevalent in renal transplant recipients than in kidney donors.
Although much research is required before these genetic discoveries prove their clinical relevance, our results provide a strategy for improved integration of genetics and nephrology.
EUROPEAN SOCIETY FOR VASCULAR SURGERY (ESVS) 2020 CLINICAL PRACTICE GUIDELINES ON THE MANAGEMENT OF ACUTE LIMB ISCHAEMIA - TRANSLATION TO PORTUGUESE
No full textEste documento deve ser referenciado citando também a versão original em Inglês:
Björck M, Earnshaw JJ, Acosta S, Bastos Gonçalves F, Cochennec F, Debus ES, Hinchliffe R, Jongkind V, Koelemay MJW, Menyhei G, Svetlikov AV, Tshomba Y, Van Den Berg JC, Esvs Guidelines Committee, de Borst GJ, Chakfé N, Kakkos SK, Koncar I, Lindholt JS, Tulamo R, Vega de Ceniga M, Vermassen F, Document Reviewers, Boyle JR, Mani K, Azuma N, Choke ETC, Cohnert TU, Fitridge RA, Forbes TL, Hamady MS, Munoz A, Müller-Hülsbeck S, Rai K. Editor's Choice - European Society for Vascular Surgery (ESVS) 2020 Clinical Practice Guidelines on the Management of Acute Limb Ischaemia. Eur J Vasc Endovasc Surg. 2020 Feb;59(2):173-218. Epub 2019 Dec 31. PMID: 31899099. Published by Elsevier B.V. on behalf of European Society for Vascular Surgery. https://doi.org/10.1016/j.ejvs.2019.09.00
Function of a Fly Motion-Sensitive Neuron Matches Eye Movements during Free Flight
No full textSensing is often implicitly assumed to be the passive acquisition of information. However, part of the sensory information is generated actively when animals move. For instance, humans shift their gaze actively in a sequence of saccades towards interesting locations in a scene. Likewise, many insects shift their gaze by saccadic turns of body and head, keeping their gaze fixed between saccades. Here we employ a novel panoramic virtual reality stimulator and show that motion computation in a blowfly visual interneuron is tuned to make efficient use of the characteristic dynamics of retinal image flow. The neuron is able to extract information about the spatial layout of the environment by utilizing intervals of stable vision resulting from the saccadic viewing strategy. The extraction is possible because the retinal image flow evoked by translation, containing information about object distances, is confined to low frequencies. This flow component can be derived from the total optic flow between saccades because the residual intersaccadic head rotations are small and encoded at higher frequencies. Information about the spatial layout of the environment can thus be extracted by the neuron in a computationally parsimonious way. These results on neuronal function based on naturalistic, behaviourally generated optic flow are in stark contrast to conclusions based on conventional visual stimuli that the neuron primarily represents a detector for yaw rotations of the animal.
Precise timing in fly motion vision is mediated by fast components of combined graded and spike signals
No full textBeckers U, Egelhaaf M, Kurtz R. Precise timing in fly motion vision is mediated by fast components of combined graded and spike signals. Neuroscience. 2009;160(3):639-650.Firing of an individual neuron is determined by the activity of its presynaptic input ensemble. In this study we analyzed how presynaptic signals with different dynamics interact to control postsynaptic activity. In the blowfly's visual system we simultaneously recorded in vivo from an identified motion-sensitive neuron and from elements of the presynaptic ensemble. The presynaptic cells themselves are mutually electrically coupled and convey both graded and spike signals to their common postsynaptic target. We elicited spikes in the postsynaptic neuron by voltage-clamping one of the presynaptic neurons to various holding potentials and then analyzed the time course of the holding current. Current transients in the clamped presynaptic cell were found to coincide with postsynaptic spikes. The current transients were highly variable in amplitude and occasionally absent during postsynaptic spiking. These characteristics indicate that the current transients in the voltage-clamped neuron result from spikes in electrically coupled co-members of the presynaptic ensemble. Our results suggest that electrical coupling among presynaptic neurons mediates synchronization of spikes within the cell ensemble. Moreover, our findings demonstrate that the graded response component of the presynaptic cells effectively controls the postsynaptic firing rate on a coarse scale while the precise timing of the postsynaptic spikes is a consequence of spikes superimposed on the graded signals of the presynaptic neurons
Synaptic transfer of dynamic motion information between identified neurons in the visual system of the blowfly
No full textWarzecha A-K, Kurtz R, Egelhaaf M. Synaptic transfer of dynamic motion information between identified neurons in the visual system of the blowfly. Neuroscience. 2003;119(4):1103-1112.Synaptic transmission is usually studied in vitro with electrical stimulation replacing the natural input of the system. In contrast, we analyzed in vivo transfer of visual motion information from graded-potential presynaptic to spiking postsynaptic neurons in the fly. Motion in the null direction leads to hyperpolarization of the presynaptic neuron but does not much influence the postsynaptic cell, because its firing rate is already low during rest, giving only little scope for further reductions. In contrast, preferred-direction motion leads to presynaptic depolarizations and increases the postsynaptic spike rate. Signal transfer to the postsynaptic cell is linear and reliable for presynaptic graded membrane potential fluctuations of up to approximately 10 Hz. This frequency range covers the dynamic range of velocities that is encoded with a high gain by visual motion-sensitive neurons. Hence, information about preferred-direction motion is transmitted largely undistorted ensuring a consistent dependency of neuronal signals on stimulus parameters, such as motion velocity. Postsynaptic spikes are often elicited by rapid presynaptic spike-like depolarizations which superimpose the graded membrane potential. Although the timing of most of these spike-like depolarizations is set by noise and not by the motion stimulus, it is preserved at the synapse with millisecond precision. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved
Shock behaviour of a phenolic resin
No full textPhenolic resins are used in many aspects of everyday life, e.g. as the matrix material for carbon fibre laminates used in the aerospace industry. Consequently detailed knowledge of this material, especially while under shock loading, is extremely useful for the design of components that could be subjected to impact during their lifespan. The shock Hugoniot equation of state for phenolic resin (Durite SC-1008), with initial density of 1.18 gcm −3 have been determined using the plate-impact technique with in situ manganin stress gauges. The Hugoniot equation in the shock velocity-particle velocity plane was found to be non-linear in nature with the following equation: Us = 2.14 + 3.79up - 1.68up2. Further, the Hugoniot in the pressure-volume plane was observed to largely follow the hydrostatic curve. Lateral gauge measurements were also obtained. An ANSYS Autodyn TM 2D model was used to investigate the lateral stress behaviour of the SC-1008. A comparison of the Hugoniot elastic limit calculated from the shear strength and measured sound speeds gave reasonable agreement with a value of 0.66 ± 0.35 GPa obtained.Journal of Materials Scienc
Time-resolved FRET fluorescence spectroscopy of visible fluorescent protein pairs
No full textFörster resonance energy transfer (FRET) is a powerful method for obtaining information about small-scale lengths between biomacromolecules. Visible fluorescent proteins (VFPs) are widely used as spectrally different FRET pairs, where one VFP acts as a donor and another VFP as an acceptor. The VFPs are usually fused to the proteins of interest, and this fusion product is genetically encoded in cells. FRET between VFPs can be determined by analysis of either the fluorescence decay properties of the donor molecule or the rise time of acceptor fluorescence. Time-resolved fluorescence spectroscopy is the technique of choice to perform these measurements. FRET can be measured not only in solution, but also in living cells by the technique of fluorescence lifetime imaging microscopy (FLIM), where fluorescence lifetimes are determined with the spatial resolution of an optical microscope. Here we focus attention on time-resolved fluorescence spectroscopy of purified, selected VFPs (both single VFPs and FRET pairs of VFPs) in cuvette-type experiments. For quantitative interpretation of FRET-FLIM experiments in cellular systems, details of the molecular fluorescence are needed that can be obtained from experiments with isolated VFPs. For analysis of the time-resolved fluorescence experiments of VFPs, we have utilised the maximum entropy method procedure to obtain a distribution of fluorescence lifetimes. Distributed lifetime patterns turn out to have diagnostic value, for instance, in observing populations of VFP pairs that are FRET-inactive
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