Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis

Cancer cells engage in a metabolic program to enhance biosynthesis and support cell proliferation. The regulatory properties of pyruvate kinase M2 (PKM2) influence altered glucose metabolism in cancer. The interaction of PKM2 with phosphotyrosine-containing proteins inhibits enzyme activity and increases the availability of glycolytic metabolites to support cell proliferation. This suggests that high pyruvate kinase activity may suppress tumor growth. We show that expression of PKM1, the pyruvate kinase isoform with high constitutive activity, or exposure to published small-molecule PKM2 activators inhibits the growth of xenograft tumors. Structural studies reveal that small-molecule activators bind PKM2 at the subunit interaction interface, a site that is distinct from that of the endogenous activator fructose-1,6-bisphosphate (FBP). However, unlike FBP, binding of activators to PKM2 promotes a constitutively active enzyme state that is resistant to inhibition by tyrosine-phosphorylated proteins. These data support the notion that small-molecule activation of PKM2 can interfere with anabolic metabolism.National Institutes of Health (U.S.) (NIH grant R01 GM56203)National Institutes of Health (U.S.) (grant NIH 5P01CA120964)Dana-Farber/Harvard Cancer Center (NIH 5P30CA006516)National Institutes of Health (U.S.) (NIH grant R03MH085679)National Human Genome Research Institute (U.S.) (Intramural Research Program)National Institutes of Health (U.S.) (Molecular Libraries Initiative of the NIH Roadmap for Medical Research

GridIMAGE: A Novel Use of Grid Computing to Support Interactive Human and Computer-Assisted Detection Decision Support

This paper describes a Grid-aware image reviewing system (GridIMAGE) that allows practitioners to (a) select images from multiple geographically distributed digital imaging and communication in medicine (DICOM) servers, (b) send those images to a specified group of human readers and computer-assisted detection (CAD) algorithms, and (c) obtain and compare interpretations from human readers and CAD algorithms. The currently implemented system was developed using the National Cancer Institute caGrid infrastructure and is designed to support the identification of lung nodules on thoracic computed tomography. However, the infrastructure is general and can support any type of distributed review. caGrid data and analytical services are used to link DICOM image databases and CAD systems and to interact with human readers. Moreover, the service-oriented and distributed structure of the GridIMAGE framework enables a flexible system, which can be deployed in an institution (linking multiple DICOM servers and CAD algorithms) and in a Grid environment (linking the resources of collaborating research groups). GridIMAGE provides a framework that allows practitioners to obtain interpretations from one or more human readers or CAD algorithms. It also provides a mechanism to allow cooperative imaging groups to systematically perform image interpretation tasks associated with research protocols

Conductive textiles for signal sensing and technical applications

Conductive textiles have found notable applications as electrodes and sensors capable of detecting biosignals like the electrocardiogram (ECG), electrogastrogram (EGG), electroencephalogram (EEG), and electromyogram (EMG), etc; other applications include electromagnetic shielding, supercapacitors, and soft robotics. There are several classes of materials that impart conductivity, including polymers, metals, and non-metals. The most significant materials are Polypyrrole (PPy), Polyaniline (PANI), Poly(3,4-ethylenedioxythiophene) (PEDOT), carbon, and metallic nanoparticles. The processes of making conductive textiles include various deposition methods, polymerization, coating, and printing. The parameters, such as conductivity and electromagnetic shielding, are prerequisites that set the benchmark for the performance of conductive textile materials. This review paper focuses on the raw materials that are used for conductive textiles, various approaches that impart conductivity, the fabrication of conductive materials, testing methods of electrical parameters, and key technical applications, challenges, and future potential

Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis

Cancer cells engage in a metabolic program to enhance biosynthesis and support cell proliferation. The regulatory properties of pyruvate kinase M2 (PKM2) influence altered glucose metabolism in cancer. PKM2 interaction with phosphotyrosine-containing proteins inhibits enzyme activity and increases availability of glycolytic metabolites to support cell proliferation. This suggests that high pyruvate kinase activity may suppress tumor growth. We show that expression of PKM1, the pyruvate kinase isoform with high constitutive activity, or exposure to published small molecule PKM2 activators inhibit growth of xenograft tumors. Structural studies reveal that small molecule activators bind PKM2 at the subunit interaction interface, a site distinct from that of the endogenous activator fructose-1,6-bisphosphate (FBP). However, unlike FBP, binding of activators to PKM2 promotes a constitutively active enzyme state that is resistant to inhibition by tyrosine-phosphorylated proteins. These data support the notion that small molecule activation of PKM2 can interfere with anabolic metabolism

Influence of Spraying Nano-Curcumin and Nano-Glycyrrhizic Acid on Resistance Enhancement and Some Growth Parameters of Soybean (<i>Glycine max</i>) in Response to <i>Tetranychus urticae</i> Infestation and Drought Stress

Modern nanotechnology has been credited as one of the most significant inventions of the 21st century. Many agricultural disciplines have been affected by nanotechnology in agriculture. Pest control based on natural compounds needs to be enhanced, and enhancing plant growth under climate change conditions, with increasing periods of drought in many countries, is a very vital aim. Thus, the effect of curcumin nanoparticles (Cu-NPs) and glycyrrhizic acid nanoparticles (GA-NPs) as a foliar application under water deficit on natural infestation with the two-spotted spider mite Tetranychus urticae, plant growth and yield, anatomical and chemical parameters were investigated during this study. The obtained results revealed that drought stress over the two studied seasons significantly increased the population of T. urticae and decreased all morphological and yield characteristics. The application of three mM GA-NPs reduced the mite population average by 39% while using the same concentration of Cu-NPs caused a 33.9% reduction percentage under drought stress. Using 1 mM GA-NPs gave the highest averages of plant height, number of branches, and leaves/plant fresh and dry weight. Moreover, the number of pods, 100 seed weight and seed yield (kg/ha) increased significantly as a result of spraying with GA-NPs under water deficit. From the results, water deficit decreased the values of the leaf and stem anatomical parameters. Treatment with Cu-NPs or GA-NPs under drought stress increased the thickness of mid-vein, xylem, and phloem tissues. Likewise, such treatment increased stem diameter due mainly to the increase in the thickness of cortex, phloem, and xylem tissues compared with the control. Spraying plants with GA-NPs at 1 mM increased the percentages of nitrogen, phosphor, and potassium in seeds in addition to total chlorophyll. Moreover, glutamate, aspartate, leucine, arginine, Lysine, glycine, tyrosine, tryptophan, and methionine concentrations did not differ significantly (p > 0.05) in response to all the studied levels of Cu-NPs or GA-NPs either under normal irrigation or drought condition. In light of these findings, researchers and producers should apply and test both Cu-NPs and GA-NP as nano-fertilizer natural sources on economically viable crops

Central memory CD8+ T cells become CD69+ tissue-residents during viral skin infection independent of CD62L-mediated lymph node surveillance.

Memory CD8+ T cells in the circulation rapidly infiltrate non-lymphoid tissues following infection and provide protective immunity in an antigen-specific manner. However, the subsequent fate of memory CD8+ T cells after entering non-lymphoid tissues such as the skin during a secondary infection is largely unknown. Furthermore, because expression of CD62L is often used to identify the central memory (TCM) CD8+ T cell subset, uncoupling the physical requirement for CD62L-mediated lymph node homing versus other functional attributes of TCM CD8+ T cells remains unresolved. Here, we show that in contrast to naïve CD8+ T cells, memory CD8+ T cells traffic into the skin independent of CD62L-mediated lymph node re-activation and provide robust protective immunity against Vaccinia virus (VacV) infection. TCM, but not effector memory (TEM), CD8+ T cells differentiated into functional CD69+/CD103- tissue residents following viral clearance, which was also dependent on local recognition of antigen in the skin microenvironment. Finally, we found that memory CD8+ T cells expressed granzyme B after trafficking into the skin and utilized cytolysis to provide protective immunity against VacV infection. Collectively, these findings demonstrate that TCM CD8+ T cells become cytolytic following rapid infiltration of the skin to protect against viral infection and subsequently differentiate into functional CD69+ tissue-residents

Salinity and Fertility Status of Irrigated soils in District Nankana Sahib, Punjab Pakistan

The soil is the basic medium for growth of plant as it supplies essential nutrients and water required for plant processes. The productivity of crop is highly dependent upon fertility and salinity of soil. Current study was carried out to explore and analyze the soils of Tehsil Nankana Sahib (Nankana, Shahkot, Sangilla) for its salinity, sodicity and fertility status at union council level from 2018-2021. A total 2030 soil samples were collected from three Tehsils of District Nankana Sahib, Punjab, Pakistan. The results indicated that the soil salinity status about 33.9% (690 samples) soils were non-saline, 23.6% (480 samples) saline sodic, 28.5% (580 samples) sodic and only 13.8% (280 samples) were saline. Maximum problematic soil was found in tehsil Nankana Sahib while minimum in Sangilla. As for the soil fertility status of District Nankana Sahib is concerned, 60.1% soils were poor in organic matter (OM) that was observed in 1220 samples, and 39.1% medium range organic matter was observed from the 794 samples while 7.8% from the only 160 samples that were approaching the adequate range. The available phosphorus in soils was found poor among 26.1% (530 samples), 56.1% medium (1140 samples) and the adequate range of available phosphorus was 17.7% (360 samples).    Full Tex