158 research outputs found
Zn-containing double complex salts formed by Keggin type polyoxotungstates: Synthesis and crystal structure
© 2017, Pleiades Publishing, Ltd. Novel double complex salts, [Zn(DMF) 6 ] 2 [SiW 12 O 40 ] · 2H 2 O (I) and [Zn(H 2 O) 2 (DMF) 4 ][Zn(DMF) 6 ] 2 [PW 12 O 40 ] 2 · 6DMF (II) (DMF = N,N-dimethylformamide), were prepared by the reaction of Zn 2+ and heteropoly acids H x [EW 12 O 40 ] · xH 2 O (E = P, X = 3, E = Si, X = 4) in DMF. Compounds I and II were studied by X-ray diffraction (СIF files CCDC nos. 1497570 (I) and 1497571 (II)) and IR spectroscopy
Extensive characterization of NF-κB binding uncovers non-canonical motifs and advances the interpretation of genetic functional traits
Background
Genetic studies have provided ample evidence of the influence of non-coding DNA polymorphisms on trait variance, particularly those occurring within transcription factor binding sites. Protein binding microarrays and other platforms that can map these sites with great precision have enhanced our understanding of how a single nucleotide polymorphism can alter binding potential within an in vitro setting, allowing for greater predictive capability of its effect on a transcription factor binding site.
Results
We have used protein binding microarrays and electrophoretic mobility shift assay-sequencing (EMSA-Seq), a deep sequencing based method we developed to analyze nine distinct human NF-κB dimers. This family of transcription factors is one of the most extensively studied, but our understanding of its DNA binding preferences has been limited to the originally described consensus motif, GGRRNNYYCC. We highlight differences between NF-κB family members and also put under the spotlight non-canonical motifs that have so far received little attention. We utilize our data to interpret the binding of transcription factors between individuals across 1,405 genomic regions laden with single nucleotide polymorphisms. We also associated binding correlations made using our data with risk alleles of disease and demonstrate its utility as a tool for functional studies of single nucleotide polymorphisms in regulatory regions.
Conclusions
NF-κB dimers bind specifically to non-canonical motifs and these can be found within genomic regions in which a canonical motif is not evident. Binding affinity data generated with these different motifs can be used in conjunction with data from chromatin immunoprecipitation-sequencing (ChIP-Seq) to enable allele-specific analyses of expression and transcription factor-DNA interactions on a genome-wide scale.Wellcome Trust (London, England) (grant 075491/Z/04)European Commission (Seventh Framework Programme FP7/2007-2013: Model-In (222008))European Commission (Seventh Framework Programme FP7 ITN Network INTEGER (214902))Medical Research Council (Canada) (MRC project grant G0700818
Complexes of non-lacunary Keggin- and Dawson-type polyoxometalates with Pb(ii): formation of 1D coordination polymers with different bonding modes
© The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.A new coordination polymer based on Keggin-type [SiW12O40]4- and Pb2+ ions, {Pb2(μ2-DMF)2(DMF)8(SiW12O40)} (1a), was prepared by a reaction between H4[SiW12O40] and Pb(NO3)2 in N,N-dimethylformamide (DMF). Varying the crystallization conditions, a complex with a slightly different coordination mode of the {Pb2} unit and solvate composition, {Pb2(μ2-DMF)2(DMF)8(SiW12O40)}·DMF (1b), can be obtained. The complex containing Well-Dawson polyoxoanions, {(Pb(μ2-DMF)3(DMF)6)(Pb(DMF)5)(P2W18O62)}·0.5DMF·1.3H2O (2), was prepared by a similar strategy
IRF5 promotes influenza-induced inflammatory responses in human iPSC-derived myeloid cells and murine models.
Recognition of Influenza A virus (IAV) by the innate immune system triggers pathways that restrict viral replication, activates innate immune cells, and regulates adaptive immunity. However, excessive innate immune activation can exaggerate disease. The pathways promoting excessive activation are incompletely understood, with limited experimental models to investigate mechanisms driving influenza-induced inflammation in humans. Interferon regulatory factor (IRF5) is a transcription factor that plays important roles in induction of cytokines after viral sensing. In an in vivo model of IAV infection, IRF5 deficiency reduced IAV-driven immune pathology and associated inflammatory cytokine production, specifically reducing cytokine-producing myeloid cell populations in Irf5-/- mice, but not impacting type 1 IFN production or virus replication. Using cytometry by time-of-flight (CyTOF), we identified that human lung IRF5 expression was highest in cells of the myeloid lineage. To investigate the role of IRF5 in mediating human inflammatory responses by myeloid cells to IAV, we employed human induced pluripotent stem cells (hIPSCs) with biallelic mutations in IRF5, demonstrating for the first time iPS-derived dendritic cells (iPS-DCs) with biallelic mutations can be used to investigate regulation of human virus-induced immune responses. Using this technology, we reveal that IRF5 deficiency in human DCs, or macrophages, corresponded with reduced virus-induced inflammatory cytokine production, with IRF5 acting downstream of TLR7 and, possibly, RIG-I after viral sensing. Thus, IRF5 acts as a regulator of myeloid cell inflammatory cytokine production during IAV infection in mice and humans, and drives immune-mediated viral pathogenesis independently of type 1 IFN and virus replication.ImportanceThe inflammatory response to Influenza A virus (IAV) participates in infection control but contributes to disease severity. After viral detection intracellular pathways are activated, initiating cytokine production, but these pathways are incompletely understood. We show that interferon regulatory factor 5 (IRF5) mediates IAV-induced inflammation and, in mice, drives pathology. This was independent of antiviral type 1 IFN and virus replication, implying that IRF5 could be specifically targeted to treat influenza-induced inflammation. We show for the first time that human iPSC technology can be exploited in genetic studies of virus-induced immune responses. Using this technology, we deleted IRF5 in human myeloid cells. These IRF5-deficient cells exhibited impaired influenza-induced cytokine production and revealed that IRF5 acts downstream of Toll-like receptor 7 and possibly retinoic acid-inducible gene-I. Our data demonstrate the importance of IRF5 in influenza-induced inflammation, suggesting genetic variation in the IRF5 gene may influence host susceptibility to viral diseases.This work was supported by The Wellcome Trust. This work was funded by a Wellcome 641 Trust Senior Research Fellowship to Ian Humphreys (207503/Z/17/Z); Medical Research 642 Council, United Kingdom (MR/L018942/1 and MRC Human Immunology Unit Core); 643 Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences 644 (CIFMS), China (grant number: 2018-I2M-2-002). The Wellcome Trust Sanger Institute was 645 the source of the Kolf2 human induced pluripotent cell line which was generated under the 646 Human Induced Pluripotent Stem Cell Initiative funded by a grant from the Wellcome Trust Downloaded from http://jvi.asm.org/ on March 2, 2020 at CAMBRIDGE UNIV27 and Medical Research Council, supported 647 by the Wellcome Trust (WT098051) and the 648 NIHR/Wellcome Trust Clinical Research Facility, and Life Science Technologies 649 Corporation provided Cytotune for reprogramming. We thank the Wellcome Trust Sanger Institute Gene editing pipeline for generation of IRF5-/- 650 iPSCs and the Mass spectrometry 651 Facility at the Weatherall Institute of Molecular Medicine for help with CyTOF experiments
ВЛИЯНИЕ СОСТАВА ТОРФОБРИКЕТОВ НА ФОРМИРОВАНИЕ РАССАДЫ ОГУРЦА В ИНТЕНСИВНОЙ СВЕТОКУЛЬТУРЕ
Obtaining high-quality seedlings is an essential condition for growing vegetables in modern cultivation facilities of protected ground. The influence of the composition and properties of peat briquettes on the growth and development of hybrid F1 of cucumber Zozulya seedlings, indicators of plant leaves photosynthetic activity, their net productivity in cultivation under controlled conditions of intensive light culture were investigated. It is shown how the change in the composition of peat briquettes affects their hydrophysical properties: volume, density, moisture absorbing capacity, etc., which is reflected in the state of cucumber seedlings. Thus, for the grown cucumber seedlings, peat briquettes had more favorable hydrophysical properties, which included, in addition to neutralized peat, Cambrian clay, separately or in combination with straw in the amount of 10% of the peat volume, or with sapropel. The moisture absorbing capacity in the considered peat briquettes was optimal for growing plants in conditions of intensive light culture and ranged from 617 to 774%. Optimization of the hydrophysical properties of peat briquettes was positively reflected in the photosynthetic activity of the leaves. The photosynthetic potential increased by 20-29%, the leaf surface area – by 19-40%; net productivity of plants photosynthesis – by 0.6-3.2 g/m2 per day, which eventually led to the formation of plants with a higher biomass – by 10-48%. An increase in the content of straw in the peat briquette to 20% led to a decrease in the moisture absorbing capacity of the peat briquette, which contributed to a certain deterioration in the physiological state of plants and, as a consequence, to a tendency towards to reduce the mass of plant seedlings.Получение качественной рассады является неотъемлемым условием при выращивании овощных культур в современных культивационных сооружениях защищенного грунта. Исследовано влияние состава и свойств торфобрикетов на рост и развитие рассады гибрида F1 огурца Зозуля, показатели фотосинтетической активности листьев растений, их нетто-продуктивность при культивировании в регулируемых условиях интенсивной светокультуры. Показано, как изменение состава торфобрикетов влияет на их гидрофизические свойства: объем, плотность, водопоглощающую способность и др., что отражается на состоянии рассады огурца. Так, для выращиваемой рассады огурца более благоприятными гидрофизическими свойствами обладали торфобрикеты, в состав которых кроме нейтрализованного торфа входили кембрийская глина, отдельно или в сочетании с соломой в количестве 10% от объема торфа, или с сапропелем. Влагопоглощающая способность в рассматриваемых торфобрикетах была оптимальной для выращивания растений в условиях интенсивной светокультуры и находилась в диапазоне от 617 до 774%. Оптимизация гидрофизических свойств торфобрикетов, положительным образом отражалась на показателях фотосинтетической деятельности листьев. Фотосинтетический потенциал увеличивался на 20-29%, площадь листовой поверхности листьев возрастала на 19-40%; чистая продуктивность фотосинтеза растений – на 0,6-3,2 г/м2 сутки, что в конечном итоге приводило к формированию растений с более высокой биомассой – на 10- 48%. Увеличение содержания соломы в торфобрикете до 20% приводило к снижению влагопоглощающей способности торфобрикета, что способствовало некоторому ухудшению физиологического состояния растений и, как следствие, проявлению тенденции к снижению массы рассады растений
Identification of a Novel β-Cell Glucokinase (GCK) Promoter Mutation (−71G>C) That Modulates GCK Gene Expression Through Loss of Allele-Specific Sp1 Binding Causing Mild Fasting Hyperglycemia in Humans
OBJECTIVE: Inactivating mutations in glucokinase (GCK) cause mild fasting hyperglycemia. Identification of a GCK mutation has implications for treatment and prognosis; therefore, it is important to identify these individuals. A significant number of patients have a phenotype suggesting a defect in glucokinase but no abnormality of GCK. We hypothesized that the GCK beta-cell promoter region, which currently is not routinely screened, could contain pathogenic mutations; therefore, we sequenced this region in 60 such probands. RESEARCH DESIGN AND METHODS: The beta-cell GCK promoter was sequenced in patient DNA. The effect of the identified novel mutation on GCK promoter activity was assessed using a luciferase reporter gene expression system. Electrophoretic mobility shift assays (EMSAs) were used to determine the impact of the mutation on Sp1 binding. RESULTS: A novel -71G>C mutation was identified in a nonconserved region of the human promoter sequence in six apparently unrelated probands. Family testing established cosegregation with fasting hyperglycemia (> or = 5.5 mmol/l) in 39 affected individuals. Haplotype analysis in the U.K. family and four of the Slovakian families demonstrated that the mutation had arisen independently. The mutation maps to a potential transcriptional activator binding site for Sp1. Reporter assays demonstrated that the mutation reduces promoter activity by up to fourfold. EMSAs demonstrated a dramatic reduction in Sp1 binding to the promoter sequence corresponding to the mutant allele. CONCLUSIONS: A novel beta-cell GCK promoter mutation was identified that significantly reduces gene expression in vitro through loss of regulation by Sp1. To ensure correct diagnosis of potential GCK-MODY (maturity-onset diabetes of the young) cases, analysis of the beta-cell GCK promoter should be included
АГРОТЕХНОЛОГИИ МАЛООБЪЕМНОЙ И БЕССУБСТРАТНОЙ ИНТЕНСИВНОЙ СВЕТОКУЛЬТУРЫ ОГУРЦА
Technology of intense light-culture has been developed to grow different crops under controlled environmental conditions with the use of specialized vegetation apparatus (VSU). In the specialized vegetation apparatus, designed to grow plants of cucumber, tomato and leafy crops, the formation of optimal light condition is constructively made with application of separate powerful lamps that have the same or different spectral quality irradiance, providing the high illuminance, 60-90 W/m2 PAR on cultivated plants. The vertical vegetation apparatus were used to develop technology of intense light-culture in cucumber. Three modifications of vertical vegetation apparatus differing in soil blocks and the way of nutrient supply to root habitation area were elaborated to grow the plants of cucumber. The development of cucumber plants in three apparatus modifications was carried out by one stem, where the growth was limited by the sizes of apparatus to 1.8 meter. The result of development of small-volume and non-soil technology of intense lightculture in cucumber was presented in the article. This technology provides high productivity of plant being grown and reduces the ecological problems related to waste treatment. The application of technology of intense light-culture in cucumber assists the plants to realize a biological potential and to reach the highest productivity. The observed plant products are of high quality without pesticides and other harmful contaminants. The nitrate content in young fruits was significantly lower the threshold allowable concentration (TAC). The basic principles of intense technology of light-culture can be used for economically profitable enterprises for production of raw material needs for pharmaceutical and perfumery industries, and to produce vitamin products in small volumes for kindergardens, hospitals, schools and private housekeeping.В статье представлены результаты разработки малообъемной и бессубстратной технологий интенсивной светокультуры растений огурца, позволяющие при высокой продуктивности значительно сократить длительность вегетационного периода по сравнению с тепличными технологиями светокультуры (досветкой). Для выращивания растений огурца разработаны три модификации автономных вегетационных установок (ВСУ) – «вертикальных» ВСУ, различающихся оригинальными конструкциями почвенного блока. Выращивание растений в таких ВСУ практически исключает возможность развития массовых заболеваний растений, передаваемых через общие системы культивирования. Световые блоки вертикальных ВСУ состоят из 3 ламп Днат 400 или ДРИ 400. Используются следующие режимы облучения растений: в фазе рассады включается первая лампа, по мере роста растений и сбора зеленцов последовательно включаются первая и вторая, вторая и третья и только третья лампы. Создаваемые уровни облученности выращиваемых растений ~ 60-90 Вт/м2 ФАР обеспечивают высокую продуктивность растений огурца в вертикальных ВСУ ~ 25-30 кг/ВСУ при длительности выращивания 75-80 суток. Применение в разработанных технологиях органоминеральных субстратов, имеющих близкое к оптимальному соотношение воздушной, водной и твердой фаз – агрофита, верхового торфа или коковита, представляющих собой экологически безопасные органические удобрения, обеспечивает значительное снижение уровня загрязнения окружающей среды. Для питания растений разработана тонкослойная нереверсивная система, обеспечивающая хорошие условия аэрации питательного раствора. Периодичность и нормы полива регулируются автоматически и зависят от фазы роста растений, температуры и влажности окружающей среды. Разработанные малообъемные и бессубстратные технологии интенсивной светокультуры растений огурца обеспечивают раскрытие биопотенциала культивируемых растений, практического достижения их максимальной продуктивности. Полученная овощная продукция отличается высоким качеством: отсутствием загрязнения пестицидами и другими вредными примесями. Содержание нитратов в зеленцах огурца значительно ниже норм ПДК. Основные положения интенсивных технологий светокультуры могут быть использованы для экономически рентабельного производства сырья для фармацевтической и парфюмерной промышленности, а также для выращивания витаминной продукции в небольших объемах в детских садах, больницах, школах и частных домовладениях
ЭКОНОМИЧЕСКАЯ ЭФФЕКТИВНОСТЬ ИСПОЛЬЗОВАНИЯ В ТЕХНОЛОГИЯХ МАЛООБЪЕМНОЙ ИНТЕНСИВНОЙ СВЕТОКУЛЬТУРЫ ПИТАТЕЛЬНЫХ РАСТВОРОВ НА ОСНОВЕ ПРОМЫШЛЕННО ВЫПУСКАЕМЫХ УДОБРЕНИЙ
In conditions of maintenance of environment parameters for plant growth, the use of nutrient solutions prepared with non-deficient fertilizers is an effective method of reducing the cost of vegetable production. The article examines economic prospects of the use of technologies of small-volume (0,15 — 0,3 l./per plant) the intensity of light-culture of plants in nutrient solutions, prepared on the basis of industrially produced fertilizers ‘Rastvorin A’, ‘Akvarin’, ‘Agricola’ and ‘Kemira Lux’, which are recommended for leafy crops. ‘Knop’ solution as one of the most effective for intensive technologies of the light-culture of leafy crops was used as a control. The object of study was a lettuce, cultivar ‘Tayphun’ and parsley cultivar ‘Bogatyr’. Plants were grown under different levels of light irradiance. Light during the growing period for both species was for 12 hours, the temperature was maintained at 20-22C° in the day and 18-20C° at night, air humidity between 60-65%. The duration of the vegetation period is 25 days. As a result of the study, it was shown that the productivity of lettuce cultivar ‘Typhun’ and parsley cultivar ‘Bogatyr’ that were grown on nutrient solutions ‘Agricola’ and ‘Rastvorin’ was very high. The content of nitrates for all cases was not extended more than the MCL. The highest productivity in the range of irradiance between 60 and 40 watts has been observed in lettuce plants of cultivar ‘Typhoon’, grown under light-culture system with the use of nutrient solutions ‘Akvarin’ and ‘Agricola’. Thus, the study carried out has showed that nutrient solutions ‘Akvarin’, ‘Agricola’ and ‘Rastvorin’ can be recommended for cultivation of leafy crops under condition of changeable light irradiation.В условиях поддержания комфортных для выращивания растений параметров окружающей среды, использование питательных растворов, приготовленных из недорогих недефицитных удобрений, является эффективным методом снижения затрат на производство единицы овощной продукции. Целью данного исследования являлось определение перспективности использования в условиях интенсивных малообъемных технологий (0,15-0,3 л/растение) светокультуры питательных растворов, приготовленных на основе широко распространенных промышленно выпускаемых удобрений; исследование экономической эффективности применения выбранных составов питательных растворов для выращивания салата сорта Тайфун и петрушки сорта Богатырь в светоустановках (ВСУ) в условиях различных уровней облученности. В статье проанализирована перспективность использования питательных растворов, приготовленных на основе промышленно выпускаемых удобрений, рекомендованных для выращивания зеленных культур: Растворин марки А, Акварин, Агрикола и Кемира Люкс. В качестве контрольного раствора использовался раствор Кнопа – один из самых эффективных при использовании в технологиях интенсивной светокультуры зеленных растений. Проведенные исследования выявили наибольшую перспективность для выращивания растений салата питательных растворов на основе Растворина и Акварина, а для растений петрушки – питательных растворов на основе Кнопа и Агриколы. При выращивании растений салата сорта Тайфун при пониженной облученности установлено, что наибольшую продуктивность в диапазоне облученности от 60 до 40 Вт ФАР показали растения, выращиваемые в ВСУ с использованием питательных растворов, приготовленных на основе смесей Акварин и Агрикола. Таким образом, в результате исследований показано, что питательные растворы Акварин, Агрикола и Растворин могут быть рекомендованы для выращивания зеленной продукции в условиях изменяющихся уровней облученности растений
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