Synaptophysin Is Required for Synaptobrevin Retrieval during Synaptic Vesicle Endocytosis

The integral synaptic vesicle (SV) protein synaptophysin forms approximately 10% of total SV protein content, but has no known function in SV physiology. Synaptobrevin (sybII) is another abundant integral SV protein with an essential role in SV exocytosis. Synaptophysin and sybII form a complex in nerve terminals, suggesting this interaction may have a key role in presynaptic function. To determine how synaptophysin controls sybII traffic in nerve terminals, we used a combination of optical imaging techniques in cultures derived from synaptophysin knockout mice. We show that synaptophysin is specifically required for the retrieval of the pH-sensitive fluorescent reporter sybII-pHluorin from the plasma membrane during endocytosis. The retrieval of other SV protein cargo reporters still occurred, however their recapture proceeded with slower kinetics. This slowing of SV retrieval kinetics in the absence of synaptophysin did not impact on global SV turnover. These results identify a specific and selective requirement for synaptophysin in the retrieval of sybII during SV endocytosis and suggest that their interaction may act as an adjustable regulator of SV retrieval efficiency

Uniaxial and biaxial soft deformations of nematic elastomers

We give a geometric interpretation of the soft elastic deformation modes of nematic elastomers, with explicit examples, for both uniaxial and biaxial nematic order. We show the importance of body rotations in this non-classical elasticity and how the invariance under rotations of the reference and target states gives soft elasticity (the Golubovic and Lubensky theorem). The role of rotations makes the Polar Decomposition Theorem vital for decomposing general deformations into body rotations and symmetric strains. The role of the square roots of tensors is discussed in this context and that of finding explicit forms for soft deformations (the approach of Olmsted).Comment: 10 pages, 10 figures, RevTex, AmsTe

Icosahedral metallacarborane/carborane species derived from 1,1′-bis(o-carborane)

We thank ORSAS (GS) and the EPSRC (DE and DMcK supported by project EP/E02971X/1, WYM supported by project EP/I031545/1) for funding.Examples of singly-metallated derivatives of 1,1[prime or minute]-bis(o-carborane) have been prepared and spectroscopically and structurally characterised. Metallation of [7-(1[prime or minute]-1[prime or minute],2[prime or minute]-closo-C2B10H11)-7,8-nido-C2B9H10]2- with a {Ru(p-cymene)}2+ fragment affords both the unisomerised species [1-(1[prime or minute]-1[prime or minute],2[prime or minute]-closo-C2B10H11)-3-(p-cymene)-3,1,2-closo-RuC2B9H10] (2) and the isomerised [8-(1[prime or minute]-1[prime or minute],2[prime or minute]-closo-C2B10H11)-2-(p-cymene)-2,1,8-closo-RuC2B9H10] (3), and 2 is easily transformed into 3 with mild heating. Metallation with a preformed {CoCp}2+ fragment also affords a 3,1,2-MC2B9-1[prime or minute],2[prime or minute]-C2B10 product [1-(1[prime or minute]-1[prime or minute],2[prime or minute]-closo-C2B10H11)-3-Cp-3,1,2-closo-CoC2B9H10] (4), but if CoCl2/NaCp is used followed by oxidation the result is the 2,1,8-CoC2B9-1[prime or minute],2[prime or minute]-C2B10 species [8-(1[prime or minute]-1[prime or minute],2[prime or minute]-closo-C2B10H11)-2-Cp-2,1,8-closo-CoC2B9H10] (5). Compound 4 does not convert into 5 in refluxing toluene, but does do so if it is reduced and then reoxidised, perhaps highlighting the importance of the basicity of the metal fragment in the isomerisation of metallacarboranes. A computational study of 1,1[prime or minute]-bis(o-carborane) is in excellent agreement with a recently-determined precise crystallographic study and establishes that the {1[prime or minute],2[prime or minute]-closo-C2B10H11} fragment is electron-withdrawing compared to H.Publisher PDFPeer reviewe

Accommodation lags are higher in myopia than in emmetropia:Measurement methods and metrics matter

Purpose: To determine whether accommodative errors in emmetropes and myopes are systematically different, and the effect of using different instruments and metrics. Methods: Seventy-six adults aged 18–27 years comprising 24 emmetropes (spherical equivalent refraction of the dominant eye +0.04 ± 0.03 D) and 52 myopes (−2.73 ± 0.22 D) were included. Accommodation responses were measured with a Grand Seiko WAM-5500 and a Hartmann–Shack Complete Ophthalmic Analysis System aberrometer, using pupil plane (Zernike and Seidel refraction) and retinal image plane (neural sharpness—NS; and visual Strehl ratio for modulation transfer function—VSMTF) metrics at 40, 33 and 25 cm. Accommodation stimuli were presented to the corrected dominant eye, and responses, referenced to the corneal plane, were determined in the fellow eye. Linear mixed-effects models were used to determine influence of the refractive group, the measurement method, accommodation stimulus, age, race, parental myopia, gender and binocular measures of heterophoria, accommodative convergence/accommodation and convergence accommodation/convergence ratios. Results: Lags of accommodation were affected significantly by the measurement method (p < 0.001), the refractive group (p = 0.003), near heterophoria (p = 0.002) and accommodative stimulus (p < 0.05), with significant interactions between some of these variables. Overall, emmetropes had smaller lags of accommodation than myopes with respective means ± standard errors of 0.31 ± 0.08 D and 0.61 ± 0.06 D (p = 0.003). Lags were largest for the Grand Seiko and Zernike defocus, intermediate for NS and VSMTF, and least for Seidel defocus. Conclusions: The mean lag of accommodation in emmetropes is approximately equal to the previously reported depth of focus. Myopes had larger (double) lags than emmetropes. Differences between methods and instruments could be as great as 0.50 D, and this must be considered when comparing studies and outcomes. Accommodative lag increased with the accommodation stimulus, but only for methods using a fixed small pupil diameter.</p

Endurance training provokes Arrhythmogenic Right Ventricular Cardiomyopathy phenotype in heterozygous Desmoglein 2 mutants:Alleviation by preload reduction

Desmoglein-2 mutations are detected in 5–10% of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Endurance training accelerates the development of the ARVC phenotype, leading to earlier arrhythmic events. Homozygous Dsg2 mutant mice develop a severe ARVC-like phenotype. The phenotype of heterozygous mutant (Dsg2mt/wt) or haploinsufficient (Dsg20/wt) mice is still not well understood. To assess the effects of age and endurance swim training, we studied cardiac morphology and function in sedentary one-year-old Dsg2mt/wt and Dsg20/wt mice and in young Dsg2mt/wt mice exposed to endurance swim training. Cardiac structure was only occasionally affected in aged Dsg20/wt and Dsg2mt/wt mice manifesting as small fibrotic foci and displacement of Connexin 43. Endurance swim training increased the right ventricular (RV) diameter and decreased RV function in Dsg2mt/wt mice but not in wild types. Dsg2mt/wt hearts showed increased ventricular activation times and pacing-induced ventricular arrhythmia without obvious fibrosis or inflammation. Preload-reducing therapy during training prevented RV enlargement and alleviated the electrophysiological phenotype. Taken together, endurance swim training induced features of ARVC in young adult Dsg2mt/wt mice. Prolonged ventricular activation times in the hearts of trained Dsg2mt/wt mice are therefore a potential mechanism for increased arrhythmia risk. Preload-reducing therapy prevented training-induced ARVC phenotype pointing to beneficial treatment options in human patients

A Semi-Distributed Electric Demand-Side Management System with PV Generation for Self-Consumption Enhancement

This paper presents the operation of an Electrical Demand-Side Management (EDSM) system in a real solar house. The use of EDSM is one of the most important action lines to improve the grid electrical efficiency. The combination between the EDSM and the PV generation performs a new control level in the local electric behavior and allows new energy possibilities. The solar house used as test-bed for the EDSM system owns a PV generator, a lead-acid battery storage system and a grid connection. The electrical appliances are controllable from an embedded computer. The EDSM is implemented by a control system which schedules the tasks commanded by the user. By using the control system, we define the house energy policy and improve the energy behavior with regard to a selected energy criterion, self-consumption. The EDSM system favors self-consumption with regard to a standard user behavior and reduces the energy load from the grid

BBLN-1 is essential for intermediate filament organization and apical membrane morphology

Epithelial tubes are essential components of metazoan organ systems that control the flow of fluids and the exchange of materials between body compartments and the outside environment. The size and shape of the central lumen confer important characteristics to tubular organs and need to be carefully controlled. Here, we identify the small coiled-coil protein BBLN-1 as a regulator of lumen morphology in the C. elegans intestine. Loss of BBLN-1 causes the formation of bubble-shaped invaginations of the apical membrane into the cytoplasm of intestinal cells and abnormal aggregation of the subapical intermediate filament (IF) network. BBLN-1 interacts with IF proteins and localizes to the IF network in an IF-dependent manner. The appearance of invaginations is a result of the abnormal IF aggregation, indicating a direct role for the IF network in maintaining lumen homeostasis. Finally, we identify bublin (BBLN) as the mammalian ortholog of BBLN-1. When expressed in the C. elegans intestine, BBLN recapitulates the localization pattern of BBLN-1 and can compensate for the loss of BBLN-1 in early larvae. In mouse intestinal organoids, BBLN localizes subapically, together with the IF protein keratin 8. Our results therefore may have implications for understanding the role of IFs in regulating epithelial tube morphology in mammals

Проектирование автоматизированной системы управления установки предварительного сбора воды

Объектом исследования является УПСВ. Цель работы – разработка автоматизированной системы управления УПСВ с использованием ПЛК, на основе выбранной SCADA-системы. В данном проекте была разработана система контроля и управления технологическим процессом на базе промышленных контроллеров Siemens SIMATIC S7-300 с применением SCADA-системы SIMATIC WinCC. Разработанная система может быть применена в системах контроля, управления и сбора данных на различных промышленных предприятиях.The object of the study is the UWWR. The aim of the work is the development of an automated control system for the UPSV using PLC, based on the selected SCADA system. In this project, a system for monitoring and controlling the process was developed on the basis of Siemens SIMATIC S7-300 industrial controllers using the SIMATIC WinCC SCADA system. The developed system can be applied in the systems of control, management and data collection at various industrial enterprises

PV self-consumption optimization with storage and Active DSM for the residential sector

With the rising prices of the retail electricity and the decreasing cost of the PV technology, grid parity with commercial electricity will soon become a reality in Europe. This fact, together with less attractive PV feed-in-tariffs in the near future and incentives to promote self-consumption suggest, that new operation modes for the PV Distributed Generation should be explored; differently from the traditional approach which is only based on maximizing the exported electricity to the grid. The smart metering is experiencing a growth in Europe and the United States but the possibilities of its use are still uncertain, in our system we propose their use to manage the storage and to allow the user to know their electrical power and energy balances. The ADSM has many benefits studied previously but also it has important challenges, in this paper we can observe and ADSM implementation example where we propose a solution to these challenges. In this paper we study the effects of the Active Demand-Side Management (ADSM) and storage systems in the amount of consumed local electrical energy. It has been developed on a prototype of a self-sufficient solar house called “MagicBox” equipped with grid connection, PV generation, lead–acid batteries, controllable appliances and smart metering. We carried out simulations for long-time experiments (yearly studies) and real measures for short and mid-time experiments (daily and weekly studies). Results show the relationship between the electricity flows and the storage capacity, which is not linear and becomes an important design criterion

Neural network controller for active demand side management with PV energy in the residential sector

In this paper, we describe the development of a control system for Demand-Side Management in the residential sector with Distributed Generation. The electrical system under study incorporates local PV energy generation, an electricity storage system, connection to the grid and a home automation system. The distributed control system is composed of two modules: a scheduler and a coordinator, both implemented with neural networks. The control system enhances the local energy performance, scheduling the tasks demanded by the user and maximizing the use of local generation