ANK, a Host Cytoplasmic Receptor for the Tobacco mosaic virus Cell-to-Cell Movement Protein, Facilitates Intercellular Transport through Plasmodesmata

Plasmodesma (PD) is a channel structure that spans the cell wall and provides symplastic connection between adjacent cells. Various macromolecules are known to be transported through PD in a highly regulated manner, and plant viruses utilize their movement proteins (MPs) to gate the PD to spread cell-to-cell. The mechanism by which MP modifies PD to enable intercelluar traffic remains obscure, due to the lack of knowledge about the host factors that mediate the process. Here, we describe the functional interaction between Tobacco mosaic virus (TMV) MP and a plant factor, an ankyrin repeat containing protein (ANK), during the viral cell-to-cell movement. We utilized a reverse genetics approach to gain insight into the possible involvement of ANK in viral movement. To this end, ANK overexpressor and suppressor lines were generated, and the movement of MP was tested. MP movement was facilitated in the ANK-overexpressing plants, and reduced in the ANK-suppressing plants, demonstrating that ANK is a host factor that facilitates MP cell-to-cell movement. Also, the TMV local infection was largely delayed in the ANK-suppressing lines, while enhanced in the ANK-overexpressing lines, showing that ANK is crucially involved in the infection process. Importantly, MP interacted with ANK at PD. Finally, simultaneous expression of MP and ANK markedly decreased the PD levels of callose, β-1,3-glucan, which is known to act as a molecular sphincter for PD. Thus, the MP-ANK interaction results in the downregulation of callose and increased cell-to-cell movement of the viral protein. These findings suggest that ANK represents a host cellular receptor exploited by MP to aid viral movement by gating PD through relaxation of their callose sphincters

Single Cell and Combinatorial Analyses of Chromatin Accessibility

The study of chromatin accessibility and DNA methylation have been fundamentally important to the understanding of gene regulation and disease. I developed methyl-ATAC-seq to query the relationship between DNA methylation and accessibility at transposase-hypersensitive chromatin, and to characterize sites of methylation-dependent accessibility in human colorectal tumor cells. Furthermore, I have performed single-cell combinatorial indexing assay for transposase accessible chromatin using sequencing (sci-ATAC-seq) to characterize the changes in cellular heterogeneity and chromatin accessibility in the cortices of Ts65Dn Down syndrome model mice. Using sci-ATAC-seq I identified 26 distinct cell-types in the cortex; I found broad changes in cell-type distribution of varying severity, including a substantial increase in abundance of several classes of interneurons corresponding to a decrease in excitatory neuron abundance. These efforts provide novel tools for analyzing chromatin states and a high-resolution assay of cellular changes that accompany Down syndrome

Single-cell chromatin accessibility and lipid profiling reveals SCD1-dependent metabolic shift in adipocytes induced by bariatric surgery.

Obesity promotes type 2 diabetes and cardiometabolic pathologies. Vertical sleeve gastrectomy (VSG) is used to treat obesity resulting in long-term weight loss and health improvements that precede weight loss; however, the mechanisms underlying the immediate benefits remain incompletely understood. Because adipose plays a crucial role in energy homeostasis and utilization, we hypothesized that VSG exerts its influences, in part, by modulating adipose functional states. We applied single-cell ATAC sequencing and lipid profiling to inguinal and epididymal adipose depots from mice that received sham surgery or VSG. We observed depot-specific cellular composition and chromatin accessibility patterns that were altered by VSG. Specifically, accessibility at Scd1, a fatty acid desaturase, was substantially reduced after VSG in mature adipocytes of inguinal but not epididymal depots. This was accompanied by reduced accumulation of SCD1-produced unsaturated fatty acids. Given these findings and reports that reductions in Scd1 attenuate obesity and insulin resistance our results suggest VSG exerts its beneficial effects through an inguinal depot-specific reduction of SCD1 activity

Recycling of Waste Aluminum Production in the Ceramic Industry

Сформулированные принципы оценки минерализаторов по их термореологическим свойствам позволили выбрать, проверить и рекомендовать ряд перспективных отходов алюминиевой промышленности, содержащих комплекс низковязких минерализаторов. Данные отходы повышают эксплуатационные характеристики керамических материалов в интервале вязкости минерализующего компонента =(0,6-5) Па·с. Установленная способность минерализатора ускорять процессы полиморфных превращений кварца использована при получении облицовочных керамических материалов из кремнеземистых техногенных продуктов путем создания каркасно-армированной структуры материала.Formulated principles for evaluation mineralizers of their thermorheological properties it possible to select, test and recommend a number of promising aluminum industry waste containing low-viscosity complex mineralizers. These wastes increase the performance of ceramic materials in the viscosity of the mineralizers component = (0,6-5) Pa s. The installed capacity of mineralizing components accelerate the processes of polymorphic transformations of quartz used in obtaining materials from ceramic tiles siliceous man-made products through the establishment of reinforced frame structure of the material

Recycling of Waste Aluminum Production in the Ceramic Industry

Сформулированные принципы оценки минерализаторов по их термореологическим свойствам позволили выбрать, проверить и рекомендовать ряд перспективных отходов алюминиевой промышленности, содержащих комплекс низковязких минерализаторов. Данные отходы повышают эксплуатационные характеристики керамических материалов в интервале вязкости минерализующего компонента =(0,6-5) Па·с. Установленная способность минерализатора ускорять процессы полиморфных превращений кварца использована при получении облицовочных керамических материалов из кремнеземистых техногенных продуктов путем создания каркасно-армированной структуры материала.Formulated principles for evaluation mineralizers of their thermorheological properties it possible to select, test and recommend a number of promising aluminum industry waste containing low-viscosity complex mineralizers. These wastes increase the performance of ceramic materials in the viscosity of the mineralizers component = (0,6-5) Pa s. The installed capacity of mineralizing components accelerate the processes of polymorphic transformations of quartz used in obtaining materials from ceramic tiles siliceous man-made products through the establishment of reinforced frame structure of the material

Construction Composites Based on Man-Made Mineral Fillers

В настоящее время отсутствует системный подход к процессам получения облицовочных керамических материалов на базе природного и техногенного сырья, базирующегося на установлении критериев формирования структуры, прогнозирования и направленного регулирования состава керамических материалов и технологических процессов их получения. В статье представлены результаты исследований по оптимизации зернового состава кремнеземистых техногенных продуктов для получения облицовочных керамических материалов с направленно регулируемыми эксплуатационными свойствами. Описана модель облицовочного керамического композиционного материала на базе наполнителя из зерен кварца. Выявлен оптимальный зерновой состав кремнеземистых отходов для регулирования плотности упаковки керамических масс на стадии подготовки сырья, формования и обжига.At the same time there is no systematic approach to processes of producing facing materials on the base of natural and industrial waste materials that would rely on setting the criteria for forming the structure, forecasting and directed adjusting of ceramic material composition and process flow sheets of their production. The work contains the results of study on improving the grain distribution of high-silica technogenic products for obtaining facing ceramic materials with forecastable operating properties. The study presents a model of facing composite material on the base of quartz grain fill. The optimal grain distribution of high-silica wastes was detected with the purpose of adjusting the packing density of ceramic materials at the stage of feed preparation, moulding and baking

Construction Composites Based on Man-Made Mineral Fillers

В настоящее время отсутствует системный подход к процессам получения облицовочных керамических материалов на базе природного и техногенного сырья, базирующегося на установлении критериев формирования структуры, прогнозирования и направленного регулирования состава керамических материалов и технологических процессов их получения. В статье представлены результаты исследований по оптимизации зернового состава кремнеземистых техногенных продуктов для получения облицовочных керамических материалов с направленно регулируемыми эксплуатационными свойствами. Описана модель облицовочного керамического композиционного материала на базе наполнителя из зерен кварца. Выявлен оптимальный зерновой состав кремнеземистых отходов для регулирования плотности упаковки керамических масс на стадии подготовки сырья, формования и обжига.At the same time there is no systematic approach to processes of producing facing materials on the base of natural and industrial waste materials that would rely on setting the criteria for forming the structure, forecasting and directed adjusting of ceramic material composition and process flow sheets of their production. The work contains the results of study on improving the grain distribution of high-silica technogenic products for obtaining facing ceramic materials with forecastable operating properties. The study presents a model of facing composite material on the base of quartz grain fill. The optimal grain distribution of high-silica wastes was detected with the purpose of adjusting the packing density of ceramic materials at the stage of feed preparation, moulding and baking

Potent in vivo lung cancer Wnt signaling inhibition via cyclodextrin-LGK974 inclusion complexes

Activation of the Wnt signaling pathway promotes lung cancer progression and contributes to poor patient prognosis. The porcupine inhibitor LGK974, a novel orally bioavailable cancer therapeutic in Phase I clinical trials, induces potent Wnt signaling inhibition and leads to suppressed growth and progression of multiple types of cancers. The clinical use of LGK974, however, is limited in part due to its low solubility and high toxicity in tissues that rely on Wnt signaling for normal homeostasis. Here, we report the use of host-guest chemistry to enhance the solubility and bioavailability of LGK974 in mice through complexation with cyclodextrins (CD). We assessed the effects of these complexes to inhibit Wnt signaling in lung adenocarcinomas that are typically driven by overactive Wnt signaling. 2D ‘H NMR confirmed host-guest complexation of CDs with LGK974. CD:LGK974 complexes significantly decreased the expression of Wnt target genes in lung cancer organoids and in lung cancer allografts in mice. Further, CD:LGK974 complexes increased the bioavailability upon oral administration in mice compared to free LGK974. In a mouse lung cancer allograft model, CD:LGK974 complexes induced potent Wnt signaling inhibition with reduced intestinal toxicity compared to treatment with free drug. Collectively, the development of these complexes enables safer and repeated oral or parenteral administration of Wnt signaling inhibitors, which hold promise for the treatment of multiple types of malignancies