Hypothalamic and amygdalar cell lines differ markedly in mitochondrial rather than nuclear encoded gene expression

BACKGROUND: Corticotropin-releasing hormone (CRH) plays an important role in regulating the mammalian stress response. Two of the most extensively studied neuronal populations that express CRH are in the hypothalamus and amygdala. Both regions are involved in the stress response, but the amygdala is also involved in mediating response to fear and anxiety. Given that both hypothalamus and amygdala have overlapping functions, but their CRH-expressing neurons may respond differently to a given perturbation, we sought to identify differentially expressed genes between two neuronal cell types, amygdalar AR-5 and hypothalamic IVB cells. Thus, we performed a microarray analysis. Our hypothesis was that we would identify differentially expressed transcription factors, coregulators and chromatin-modifying enzymes. RESULTS: A total of 31,042 genes were analyzed, 10,572 of which were consistently expressed in both cell lines at a 95% confidence level. Of the 10,572 genes, 2,320 genes in AR-5 were expressed at ≥ 2-fold relative to IVBs, 1,104 genes were expressed at ≥2-fold in IVB relative to AR-5 and 7,148 genes were expressed at similar levels between the two cell lines. The greatest difference was in six mitochondrial DNA-encoded genes, which were highly abundant in AR-5 relative to IVB cells. The relative abundance of these genes ranged from 413 to 885-fold according to the microarray results. Differential expression of these genes was verified by RTqPCR. The differentially expressed mitochondrial genes were cytochrome b (MT-CYB), cytochrome c oxidase subunit 1 and 2 (MT-CO1 and MT-CO2) and NADH-ubiquinone oxidoreductase chain 1, 2, and 3 (MT-ND1, MT-ND2, MT-ND3). CONCLUSION: As expected, the array revealed differential expression of transcription factors and coregulators; however the greatest difference between the two cell lines was in genes encoded by the mitochondrial genome. These genes were abundant in AR-5 relative to IVBs. At present, the reason for the marked difference is unclear. The cells may differ in mtDNA copy number, number of mitochondria, or regulation of the mitochondrial genome. The specific functions served by having such different levels of mitochondrial expression have not been determined. It is possible that the greater expression of the mitochondrial genes in the amygdalar cells reflects higher energy requirements than in the hypothalamic cell line

The role of caking in optimising the performance of a concertinaed ceramic filtration membrane

Membrane filtration is a process of separating particles from fluids. Over time, particles are trapped within the membrane structure and on the membrane surface, forming a cake. In this paper, we develop a mathematical model for the transient blocking dynamics in a concertinaed filtration device composed of angled porous membranes and dead-ends. We examine how the inclusion of particles affects the flow dynamics, and we uncover potential inaccuracies in relying on flux–throughput curves to distinguish between caking and internal blocking dynamics. Moreover, we show that optimal filtration performance strongly depends on both the performance metric and the membrane configuration. Finally, to optimise the use of membrane area, we introduce a method for deriving a non-uniform permeance that ensures constant initial cake growth

Understanding how porosity gradients can make a better filter using homogenization theory

Filters whose porosity decreases with depth are often more efficient at removing solute from a fluid than filters with a uniform porosity. We investigate this phenomenon via an extension of homogenization theory that accounts for a macroscale variation in microstructure. In the first stage of the paper, we homogenize the problems of flow through a filter with a near-periodic microstructure and of solute transport owing to advection, diffusion and filter adsorption. In the second stage, we use the computationally efficient homogenized equations to investigate and quantify why porosity gradients can improve filter efficiency. We find that a porosity gradient has a much larger effect on the uniformity of adsorption than it does on the total adsorption. This allows us to understand how a decreasing porosity can lead to a greater filter efficiency, by lowering the risk of localized blocking while maintaining the rate of total contaminant removal

Canonical orbits for rapidly deforming planar microswimmers in shear flow

Classically, the rotation of ellipsoids in shear Stokes flow is captured by Jeffery’s orbits. Here, we demonstrate that Jeffery’s orbits also describe general shape-deforming swimmers moving in the plane of a shear flow, employing only basic properties of Stokes flow and a multiple-scales asymptotic analysis. In doing so, we support the use of these simple models for capturing shape-changing swimmer dynamics in studies of active matter and highlight the ubiquity of ellipsoid-like dynamics in complex systems. This result is robust to weakly confounding effects, such as distant boundaries

Optimising the flow through a concertinaed filtration membrane

Membrane filtration is a vital industrial process, with applications including air purification and blood filtration. In this paper, we study the optimal design for a concertinaed filtration membrane composed of angled porous membranes and dead-ends. We examine how the filter performance depends on the angle, position, thickness, and permeance of the membrane, through a combination of numerical and asymptotic approaches, the latter in the limit of a slightly angled membrane. We find that, for a membrane of fixed angle and physical properties, there can exist multiple membrane positions that maximise the flux for an applied pressure difference. More generally, we show that while the maximal flux achievable depends on the membrane thickness and permeance, the optimal membrane configuration is always in one of two setups: centred and diagonal across the full domain; or angled and in the corner of the domain.Comment: 24 pages, 10 figure

Adaptive backstepping controller design of quadrotor biplane for payload delivery

Performance of the UAVs for a particular application can be enhanced by hybrid design, where take-off, hover, and landing happen like rotary-wing UAVs, and flies like fixed-wing UAVs. A backstepping controller and an adaptive backstepping controller are designed for trajectory tracking and payload delivery in a medical emergency or medical substance delivery like vaccine delivery in the presence of wind gust. Simulation results show that the backstepping controller effectively tracks the trajectory during the entire flight envelope, including take-off, hovering, the transition phase, level flight mode, and landing. A comparison between Backstepping, Integral Terminal Sliding Mode (ITSMC) and Adaptive Backstepping controllers for payload delivery show that the adaptive backstepping controller effectively tracks the altitude and attitude. ITSMC is capable of tracking the desired trajectory for a change in the mass but has sluggish response. The backstepping controller generates a steady-state error in altitude during the mass change in biplane-quadrotor.The publication of this article was funded by Qatar National Library.Scopu

The effect of weak inertia in rotating high-aspect-ratio vessel bioreactors

One method to grow artificial body tissue is to place a porous scaffold seeded with cells, known as a tissue construct, into a rotating bioreactor filled with a nutrient-rich fluid. The flow within the bioreactor is affected by the movement of the construct relative to the bioreactor which, in turn, is affected by the hydrodynamical and gravitational forces the construct experiences. The construct motion is thus coupled to the flow within the bioreactor. Over the timescale of a few hours, the construct appears to move in a periodic orbit but, over tens of hours, the construct drifts from periodicity. In the biological literature, this effect is often attributed to the change in density of the construct that occurs via tissue growth. In this paper, we show that weak inertia can cause the construct to drift from its periodic orbit over the same timescale as tissue growth. We consider the coupled flow and construct motion problem within a rotating high-aspect- ratio vessel bioreactor. Using an asymptotic analysis, we investigate the case where the Reynolds number is large but the geometry of the bioreactor yields a small reduced Reynolds number, resulting in a weak inertial effect. In particular, to accurately couple the bioreactor and porous flow regions, we extend the nested boundary layer analysis of Dalwadi et al. (J. Fluid Mech. vol. 798, pp. 88–139, 2016) to include moving walls and the thin region between the porous construct and the bioreactor wall. This allows us to derive a closed system of nonlinear ordinary differential equations for the construct trajectory, from which we show that neglecting inertia results in periodic orbits; we solve the inertia-free problem analytically, calculating the periodic orbits in terms of the system parameters. Using a multiple-scale analysis, we then systematically derive a simpler system of nonlinear ordinary differential equations that describe the long-time drift of the construct due to the effect of weak inertia. We investigate the bifurcations of the construct trajectory behaviour, and the limit cycles that appear when the construct is less dense than the surrounding fluid and the rotation rate is large enough. Thus, we are able to predict when the tissue construct will drift towards a stable limit cycle within the bioreactor and when it will drift out until it hits the bioreactor edg

A homogenised model for flow, transport and sorption in a heterogeneous porous medium

A major challenge in flow through porous media is to better understand the link between microstructure and macroscale flow and transport. For idealised microstructures, the mathematical framework of homogenisation theory can be used for this purpose. Here, we consider a two-dimensional microstructure comprising an array of obstacles of smooth but arbitrary shape, the size and spacing of which can vary along the length of the porous medium. We use homogenisation via the method of multiple scales to systematically upscale a novel problem involving cells of varying area to obtain effective continuum equations for macroscale flow and transport. The equations are characterised by the local porosity, a local anisotropic flow permeability, an effective local anisotropic solute diffusivity, and an effective local adsorption rate. These macroscale properties depend nontrivially on the two degrees of microstructural geometric freedom in our problem: obstacle size, and obstacle spacing. We exploit this dependence to construct and compare scenarios where the same porosity profile results from different combinations of obstacle size and spacing. We focus on a simple example geometry comprising circular obstacles on a rectangular lattice, for which we numerically determine the macroscale permeability and effective diffusivity. We investigate scenarios where the porosity is spatially uniform but the permeability and diffusivity are not. Our results may be useful in the design of filters, or for studying the impact of deformation on transport in soft porous media

Choroba Mikulicza-Radeckiego z zapaleniem przysadki — nowe zaburzenie związane z IgG4

  Introduction: We present a case of Mikulicz’s Disease with hypophysitis. This is a rare clinical association as part of the group of IgG4- related diseases, a group of disorders which can have multiorgan involvement. Methods: A 55-year-old male patient was diagnosed with Mikulicz’s disease. He was treated with oral steroids for six months with complete resolution. After two years the patient presented with fatigue, generalised weakness, and weight loss of 11 kg over six months. On evaluation he was found to have panhypopituitarism. MRI pituitary revealed homogeneously enlarged, well enhancing pituitary with thickening of the stalk. Serum IgG4 levels were significantly elevated. The patient was treated with methyl prednisolone pulse therapy followed by oral steroids for three months. He developed diabetes insipidus after starting steroid therapy. There was a significant resolution in the enlargement of the pituitary and stalk thickening at three months. Results: The clinical, biochemical, and radiological findings of hypophysitis associated with Mikulicz’s disease are presented with a brief review of literature. Conclusions: IgG4-related diseases are rare and have recently been recognised as a cause of hypophysitis. They can have multiorgan involvement. A high index of suspicion is required for clinching this rare diagnosis, which can be confirmed by measurement of serum levels of IgG4. Steroid therapy can reverse the inflammatory changes in IgG4 hypophysitis. (Endokrynol Pol 2016; 67 (6): 622–626)    Wstęp: W pracy przedstawiono przypadek choroby Mikulicza-Radeckiego z zapaleniem przysadki. Jest to rzadko występujące połączenie zaburzeń należących do grupy chorób związanych z IgG4, które mogą obejmować wiele narządów. Metody: U mężczyzny w wieku 55 lat rozpoznano chorobę Mikulicza-Radeckiego. Stosowano doustne steroidy przez 6 miesięcy, uzyskując całkowite ustąpienie choroby. Po 2 latach chory zaczął odczuwać zmęczenie i ogólne osłabienie, a ponadto w ciągu 6 miesięcy schudł 11 kg. Badanie wykazało wielohormonalną niedoczynność przysadki. Badanie rezonansu magnetycznego przysadki uwidoczniło równomiernie powiększoną, ulegającą wzmocnieniu po podaniu kontrastu, z pogrubioną szypułą. Stężenie IgG4 w surowicy było istotnie podwyższone. U pacjenta zastosowano najpierw terapię pulsacyjną metylprednizolonem, a następnie 3-miesięczne leczenie steroidami podawanymi doustnie. Po rozpoczęciu leczenia steroidami u chorego rozwinęła się moczówka prosta. Po 3 miesiącach nastąpiło istotne zmniejszenie powiększonej przysadki i pogrubionej szypuły. Wyniki: Przedstawiono kliniczne, biochemiczne i radiologiczne objawy niedoczynności przysadki związanej z chorobą Mikulicza-Radeckiego oraz krótki przegląd literatury. Wnioski: Choroby związane z IgG4 występują rzadko. W ostatnim czasie wykazano, że mogą powodują one niedoczynność przysadki. Mogą one obejmować wiele narządów. Rozpoznanie tej rzadkiej choroby można potwierdzić, oznaczając stężenie IgG4 w surowicy. Można potwierdzić diagnozę, mierząc stężenie IgG4 w surowicy. Leczenie steroidami może spowodować ustąpienie zmian zapalnych z niedoczynności przysadki związanej z IgG4. (Endokrynol Pol 2016; 67 (6): 622–626)

A multiscale method to calculate filter blockage

Filters that act by adsorbing contaminant onto their pore walls will experience a decrease in porosity over time, and may eventually block. As adsorption will generally be greater towards the entrance of a filter, where the concentration of contaminant particles is higher, these effects can also result in a spatially varying porosity. We investigate this dynamic process using an extension of homogenization theory that accounts for a macroscale variation in microstructure. We formulate and homogenize the coupled problems of flow through a filter with a near-periodic time-dependent microstructure, solute transport due to advection, diffusion and filter adsorption, and filter structure evolution due to the adsorption of contaminant. We use the homogenized equations to investigate how the contaminant removal and filter lifespan depend on the initial porosity distribution for a unidirectional flow. We confirm a conjecture made by Dalwadi et al. (Proc. R. Soc. Lond. A, vol. 471 (2182), 2015, 20150464) that filters with an initially negative porosity gradient have a longer lifespan and remove more contaminant than filters with an initially constant porosity, or worse, an initially positive porosity gradient. In addition, we determine which initial porosity distributions result in a filter that will block everywhere at once by exploiting an asymptotic reduction of the homogenized equations. We show that these filters remove more contaminant than other filters with the same initial average porosity, but that filters which block everywhere at once are limited by how large their initial average porosity can be