An In Vitro Model of the Glomerular Capillary Wall Using Electrospun Collagen Nanofibres in a Bioartificial Composite Basement Membrane

The filtering unit of the kidney, the glomerulus, contains capillaries whose walls function as a biological sieve, the glomerular filtration barrier. This comprises layers of two specialised cells, glomerular endothelial cells (GEnC) and podocytes, separated by a basement membrane. Glomerular filtration barrier function, and dysfunction in disease, remains incompletely understood, partly due to difficulties in studying the relevant cell types in vitro. We have addressed this by generation of unique conditionally immortalised human GEnC and podocytes. However, because the glomerular filtration barrier functions as a whole, it is necessary to develop three dimensional co-culture models to maximise the benefit of the availability of these cells. Here we have developed the first two tri-layer models of the glomerular capillary wall. The first is based on tissue culture inserts and provides evidence of cell-cell interaction via soluble mediators. In the second model the synthetic support of the tissue culture insert is replaced with a novel composite bioartificial membrane. This consists of a nanofibre membrane containing collagen I, electrospun directly onto a micro-photoelectroformed fine nickel supporting mesh. GEnC and podocytes grew in monolayers on either side of the insert support or the novel membrane to form a tri-layer model recapitulating the human glomerular capillary in vitro. These models will advance the study of both the physiology of normal glomerular filtration and of its disruption in glomerular disease

New Insights into Metabolic Properties of Marine Bacteria Encoding Proteorhodopsins

Proteorhodopsin phototrophy was recently discovered in oceanic surface waters. In an effort to characterize uncultured proteorhodopsin-exploiting bacteria, large-insert bacterial artificial chromosome (BAC) libraries from the Mediterranean Sea and Red Sea were analyzed. Fifty-five BACs carried diverse proteorhodopsin genes, and we confirmed the function of five. We calculate that proteorhodopsin-exploiting bacteria account for 13% of microorganisms in the photic zone. We further show that some proteorhodopsin-containing bacteria possess a retinal biosynthetic pathway and a reverse sulfite reductase operon, employed by prokaryotes oxidizing sulfur compounds. Thus, these novel phototrophs are an unexpectedly large and metabolically diverse component of the marine microbial surface water

Dendritic Spikes Amplify the Synaptic Signal to Enhance Detection of Motion in a Simulation of the Direction-Selective Ganglion Cell

The On-Off direction-selective ganglion cell (DSGC) in mammalian retinas responds most strongly to a stimulus moving in a specific direction. The DSGC initiates spikes in its dendritic tree, which are thought to propagate to the soma with high probability. Both dendritic and somatic spikes in the DSGC display strong directional tuning, whereas somatic PSPs (postsynaptic potentials) are only weakly directional, indicating that spike generation includes marked enhancement of the directional signal. We used a realistic computational model based on anatomical and physiological measurements to determine the source of the enhancement. Our results indicate that the DSGC dendritic tree is partitioned into separate electrotonic regions, each summing its local excitatory and inhibitory synaptic inputs to initiate spikes. Within each local region the local spike threshold nonlinearly amplifies the preferred response over the null response on the basis of PSP amplitude. Using inhibitory conductances previously measured in DSGCs, the simulation results showed that inhibition is only sufficient to prevent spike initiation and cannot affect spike propagation. Therefore, inhibition will only act locally within the dendritic arbor. We identified the role of three mechanisms that generate directional selectivity (DS) in the local dendritic regions. First, a mechanism for DS intrinsic to the dendritic structure of the DSGC enhances DS on the null side of the cell's dendritic tree and weakens it on the preferred side. Second, spatially offset postsynaptic inhibition generates robust DS in the isolated dendritic tips but weak DS near the soma. Third, presynaptic DS is apparently necessary because it is more robust across the dendritic tree. The pre- and postsynaptic mechanisms together can overcome the local intrinsic DS. These local dendritic mechanisms can perform independent nonlinear computations to make a decision, and there could be analogous mechanisms within cortical circuitry

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Starting transient of the flow through an in-vitro model of the vocal folds

An exact theory of voiced sound production can be useless. An exact numerical calculation is, in fact, a detailed experiment, which does not by itself provide any insight. For example a detailed numerical simulation cannot be used to obtain data compression or real-time sound synthesis. By contrast the most simple models available such as source/filter models are already quite versatile tools. As the available computational power increases we would like to use more complex models. Physical modeling is a guide to generate models with a limited number of parameters with limited ranges of plausible values, determined from physiological data. A physical model should have a reasonable balance in the degree of sophistication used to describe the various elements such as: mechanical system, flow, articulation, and so on. The aim of our long-term research is to test the most simple fluid dynamic theories by means of accurate in vitro experiments, providing the specialist with a range of models rather than a specific model. Our research program was triggered by request of colleagues from the Institute for Perception Research anxious to evaluate the relevance of the work of Teager [1,2]. Based on our earlier experience on natural gastransport systems and on musical acoustics we started by a literature study [3]. We certainly agree with Teager that a more systematic description of the flow can be useful. However, some of his research proposals are highly disputable. For example, it may be fascinating to place a hot wire in our mouth and observe the complex flow signal obtained during phonation. However, we will never be able to relate such data to any quantitative theory because we have no information about the flow channel geometry nor on the position of the hot wire. This makes in vivo experiments with hot wires rather frustrating. As fluid dynamicists we were much more impressed by simple in vitro experiments with fixed geometry [4,5] or oscillating models [6,7]. Based on the difficulties that we had already encountered in oscillating valves models [8], we decided to focus on fixed rigid geometries. We decided to introduce an unsteadiness of the flow by driving the model with a valve as we had done earlier for the organ pipe [9,10] . As we knew how difficult quantitative measurements are, we started by considering a smoothly converging two-dimensional flow channel with a sharp-edged termination. Steady and unsteady flow measurements were carried out in this geometry to check the calibrations of our pressure gauges and of our hot wires. (Even steady wall pressure measurements should always be checked because of potential problems with pressure holes.) While the sharp edged geometry is not physiologically relevant it allows detailed two-dimensional point vortex simulation because we know that vortex shedding occurs at the sharp edges and is described by a Kutta condition [11]. We actually are still working on this reference geometry. It is rather obvious that the glottis is smoothly shaped and that we should therefore develop a theory describing the flow through lip-like channels. A first step in this direction was carried out by Belfroid [12] followed by Pelorson etal. [13-15]. Using this set-up we now produced quite realistic flow pulses as shown in Figure 3-1. In the present chapter we give an informal description of the results we have obtained until now. More precise information both concerning the theory and the experiments is found in the papers previously quoted. We focus on the glottis. The interesting subject of the aeroacoustics of the vocal tract is not considered. A discussion of literature available on this subject is given in our earlier paper [3] and the recent review of Davies etal. [16]

Enduring Influence of Elizabethan Ophthalmic Texts of the 1580s: Bailey, Grassus, and Guillemeau

Three English ophthalmic texts of the 1580s were frequently republished: 1) Walter Bailey’s A Briefe Treatise Touching the Preseruation of the Eie Sight, 2) The Method of Phisicke, an adaptation of the medieval treatise of Benevenutus Grassus, and 3) A Worthy Treatise of the Eyes, a translation of Jacques Guillemeau’s treatise. Their history is intertwined through composite publications, some of which lacked clear attribution. At least 21 editions incorporated these texts. Although not previously realized, major elements of all 3 works are found in Two Treatises Concerning the Preseruation of Eie-sight, first published in 1616. To preserve eyesight, Bailey recommended eyebright (Euphrasia officinalis), fennel (Fæniculum vulgare), and a moderate lifestyle incorporating wine. In the works of Grassus and Guillemeau, cataracts were believed to lie anterior to the ‘crystalline humor,’ and were treated by the ‘art of the needle,’ or couching. Links are found between Grassus, Guillemeau, and eighteenth century glaucoma concepts. Although one of his students has traditionally received credit, it was English oculist John Thomas Woolhouse who first combined the early concepts and used the term glaucoma to describe the palpably hard eye in the early eighteenth century. The three primary ophthalmic texts of 1580s England influenced ophthalmic thought for over a century

Jet formation and jet velocity fluctuations in a flue organ pipe

\u3cp\u3eFlow visualization of the initial transient in a small recorderlike flue organ pipe is presented and the various stages of the jet formation are related to measurements of the acoustic response of the pipe. An initial acoustic signal, due to the unsteady volume flow of the jet, appears before the forming jet reaches the labium. This signal can easily be modeled using a low-frequency approximation. The initial trajectory of the jet makes a curve towards the exterior of the pipe. Under certain conditions, the jet may even, at first, miss the labium. This effect is related to the steepness of the pressure rise in the foot of the pipe. The initial impact of the jet with the labium appears to be a crucial factor in the triggering of the transient. Moving the labium towards the exterior of the pipe, using a steep pressure rise or putting ears around the mouth increase the chance that the jet will hit the labium. This initial impact is followed by an impulsive vortex shedding at the labium and subsequently a high-frequency varicoselike oscillation is observed on the jet. This oscillation is also observed without labium. After about three periods of the fundamental mode of the pipe, turbulence appears therefore destroying these coherent structures. Whereas the time dependency of the jet velocity dominates the first stage of the starting transient, the jet velocity fluctuations during steady-state result in a non-negligible damping. This loss mechanism is, for the fundamental mode of our experimental organ pipe, of the same order of magnitude as the radiation or visco-thermal damping.\u3c/p\u3