76 research outputs found

    Assessing membrane material properties from the response of giant unilamellar vesicles to electric fields

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    Knowledge of the material properties of membranes is crucial to understanding cell viability and physiology. A number of methods have been developed to probe membranes in vitro, utilizing the response of minimal biomimetic membrane models to an external perturbation. In this review, we focus on techniques employing giant unilamellar vesicles (GUVs), model membrane systems, often referred to as minimal artificial cells because of the potential they offer to mimick certain cellular features. When exposed to electric fields, GUV deformation, dynamic response and poration can be used to deduce properties such as bending rigidity, pore edge tension, membrane capacitance, surface shear viscosity, excess area and membrane stability. We present a succinct overview of these techniques, which require only simple instrumentation, available in many labs, as well as reasonably facile experimental implementation and analysis

    Characterization of DAG binding to TRPC channels by target-dependent cis–trans isomerization of OptoDArG

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    Azobenzene-based photochromic lipids are valuable probes for the analysis of ion channel–lipid interactions. Rapid photoisomerization of these molecules enables the analysis of lipid gating kinetics and provides information on lipid sensing. Thermal relaxation of the metastable cis conformation to the trans conformation of azobenzene photolipids is rather slow in the dark and may be modified by ligand–protein interactions. Cis photolipid-induced changes in pure lipid membranes as visualized from the morphological response of giant unilamellar vesicles indicated that thermal cis–trans isomerization of both PhoDAG-1 and OptoDArG is essentially slow in the lipid bilayer environment. While the currents activated by cis PhoDAG remained stable upon termination of UV light exposure (dark, UV-OFF), cis OptoDArG-induced TRPC3/6/7 activity displayed a striking isoform-dependent exponential decay. The deactivation kinetics of cis OptoDArG-induced currents in the dark was sensitive to mutations in the L2 lipid coordination site of TRPC channels. We conclude that the binding of cis OptoDArG to TRPC channels promotes transition of cis OptoDArG to the trans conformation. This process is suggested to provide valuable information on DAG–ion channel interactions and may enable highly selective photopharmacological interventions

    Perfluorinated Ligands Induce Meridional Metal Stereochemistry to Generate M8L12, M10L15, and M12L18 Prisms.

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    Meridional (mer) coordination promotes the generation of larger and lower-symmetry prismatic metallosupramolecular structures, in contrast with the facial (fac) coordination common to smaller and higher-symmetry polyhedra. Here, we describe a general route to the selective formation of large metallosupramolecular prisms that contain exclusively mer-coordinated metal vertices. The use of 2-formylpyridine subcomponents that contain perfluorophenylene substituents at their 5-positions resulted in stereoselective formation of the iron(II) complexes from these subcomponents. Only mer vertices were observed, as opposed to the statistical fac/mer mixture otherwise generated. This mer-selective self-assembly could be used to prepare tetragonal (M8L12), pentagonal (M10L15), and hexagonal (M12L18) prisms by taking advantage of the subtle selectivities imposed by the different anilines and counterions employed. The equilibrium between the tetragonal and pentagonal prism followed a linear free-energy relationship, with the ratio between structures correlating with the Hammett σp(+) parameter of the incorporated aniline. The contrasting preferences of the fluorinated and nonfluorinated ligands to generate prisms and tetrahedra, respectively, were quantified energetically, with the destabilization increasing linearly for each "incorrect ligand" incorporated into either structure.This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 642192 and was supported by the UK Engineering and Physical Sciences Research Council (EPSRC). The authors thank Diamond Light Source (UK) for synchrotron beamtime on I19 (MT8464 and MT11397), the Department of Chemistry NMR facility, University of Cambridge, and the EPSRC UK National Mass Spectrometry Facility at Swansea University. M.K. acknowledges the Cambridge Commonwealth, European and International Trust and the Frédéric Fontaine scholarship from Michelin SCA. B.S.P. acknowledges the Herchel Smith Research Fellowship from the University of Cambridge and a Fellowship from Corpus Christi College, Cambridge. D.A.R. acknowledges the Gates Cambridge Trust for Ph.D. funding.This is the final version of the article. It first appeared from the American Chemical Society via https://doi.org/10.1021/jacs.6b0244

    Measurements of KL Branching Fractions and the CP Violation Parameter |eta+-|

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    We present new measurements of the six largest branching fractions of the KL using data collected in 1997 by the KTeV experiment (E832) at Fermilab. The results are B(KL -> pi e nu) = 0.4067 +- 0.0011 B(KL -> pi mu nu) = 0.2701 +- 0.0009 B(KL -> pi+ pi- pi0) = 0.1252 +- 0.0007 B(KL -> pi0 pi0 pi0) = 0.1945 +- 0.0018 B(KL -> pi+ pi-) = (1.975 +- 0.012)E-3, and B(KL -> pi0 pi0) = (0.865 +- 0.010)E-3, where statistical and systematic errors have been summed in quadrature. We also determine the CP violation parameter |eta+-| to be (2.228 +- 0.010)E-3. Several of these results are not in good agreement with averages of previous measurements.Comment: Submitted to Phys. Rev. D; 20 pages, 22 figure

    Realization of reproductive function in patients with polycystic ovary syndrome

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    The aim of the study – present a clinical case of the realization of reproductive function in a patient with PCOS against the background of conservative treatmentЦель исследования – представление клинического случая реализации репродуктивной функции у пациентки с СПЯ на фоне консервативного лечения

    Случай успешного хирургического лечения разрыва гигантской аневризмы инфраренального отдела аорты у пациентки старческого возраста

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    Today, abdominal aortic aneurysm surgery is a fairly well-studied area of medicine. Nevertheless, some questions remain rather debatable. No clear criteria for giant aneurysms have been developed so far. The available foreign and domestic literature reports about 40 cases of surgical treatment of giant abdominal aortic aneurysms, 16 of which are cases of aneurysm rupture. Open surgery remains the method of choice in the treatment of giant aneurysms due to the pronounced technical difficulties of endovascular intervention. The authors present a case of successful surgical treatment of a giant aneurysm rupture in an elderly patient. The peculiarity of this patient's condition is the occurrence of aneurysm rupture after hospital admission. The patient refused surgical treatment for two years after aneurysm detection. On examination after admission, multispiral computed tomography revealed an aneurysm size of 101 mm. On the eve of surgery, pain syndrome in the left abdomen and tachycardia appeared. Aneurysm rupture was suspected and the patient was urgently admitted to the operating room. The surgery was performed under the conditions of machine reinfusion of autoblood. The patient underwent abdominal aortic aneurysm resection with linear prosthesis and retroperitoneal hematoma removal. The postoperative period had no peculiarities. On the 10th day after the operation the patient was discharged in satisfactory condition to the outpatient treatment. This clinical case demonstrates the possibility of successful surgical treatment of giant aneurysm rupture in elderly patients.Сегодня хирургия аневризмы брюшного отдела является достаточно хорошо изученным разделом медицины. Тем не менее некоторые вопросы остаются довольно дискутабельными. До сих пор не выработано четких критериев гигантских аневризм. В доступной зарубежной и отечественной литературе сообщается о 40 случаях хирургического лечения гигантских аневризм брюшного отдела аорты, 16 из которых – в состоянии разрыва аневризмы. Методом выбора при лечении гигантских аневризм остается открытая операция в связи с выраженными техническими трудностями эндоваскулярного вмешательства. В статье авторы приводят случай успешного хирургического лечения разрыва гигантской аневризмы пациентки старческого возраста. Особенностью течения состояния данной пациентки является возникновение разрыва аневризмы после поступления в стационар. Пациентка в течение двух лет после обнаружения аневризмы отказывалась от оперативного лечения. При обследовании после поступления в стационар по данным мультиспиральной компьютерной томографии размер аневризмы достигал 101 мм. Накануне операции появились болевой синдром в левых отделах живота, тахикардия. Был заподозрен разрыв аневризмы, пациентка экстренно подана в операционную. Операция проводилась в условиях аппаратной реинфузии аутокрови. Больной выполнены резекция аневризмы брюшного отдела аорты с линейным протезированием и удаление забрюшинной гематомы. Течение послеоперационного периода проходило без особенностей. На 10-е сутки после операции пациентка в удовлетворительном состоянии выписана на амбулаторный этап лечения. Данный клинический случай свидетельствует о возможности успешного хирургического лечения разрыва гигантской аневризмы у пациентов старческой возрастной группы

    Reading tea leaves worldwide: Decoupled drivers of initial litter decomposition mass‐loss rate and stabilization

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    The breakdown of plant material fuels soil functioning and biodiversity. Currently, process understanding of global decomposition patterns and the drivers of such patterns are hampered by the lack of coherent large-scale datasets. We buried 36,000 individual litterbags (tea bags) worldwide and found an overall negative correlation between initial mass-loss rates and stabilization factors of plant-derived carbon, using the Tea Bag Index (TBI). The stabilization factor quantifies the degree to which easy-to-degrade components accumulate during early-stage decomposition (e.g. by environmental limitations). However, agriculture and an interaction between moisture and temperature led to a decoupling between initial mass-loss rates and stabilization, notably in colder locations. Using TBI improved mass-loss estimates of natural litter compared to models that ignored stabilization. Ignoring the transformation of dead plant material to more recalcitrant substances during early-stage decomposition, and the environmental control of this transformation, could overestimate carbon losses during early decomposition in carbon cycle models

    Reading tea leaves worldwide: decoupled drivers of initial litter decomposition mass‐loss rate and stabilization

    Get PDF
    The breakdown of plant material fuels soil functioning and biodiversity. Currently, process understanding of global decomposition patterns and the drivers of such patterns are hampered by the lack of coherent large‐scale datasets. We buried 36,000 individual litterbags (tea bags) worldwide and found an overall negative correlation between initial mass‐loss rates and stabilization factors of plant‐derived carbon, using the Tea Bag Index (TBI). The stabilization factor quantifies the degree to which easy‐to‐degrade components accumulate during early‐stage decomposition (e.g. by environmental limitations). However, agriculture and an interaction between moisture and temperature led to a decoupling between initial mass‐loss rates and stabilization, notably in colder locations. Using TBI improved mass‐loss estimates of natural litter compared to models that ignored stabilization. Ignoring the transformation of dead plant material to more recalcitrant substances during early‐stage decomposition, and the environmental control of this transformation, could overestimate carbon losses during early decomposition in carbon cycle models
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