38 results about "Calcium signaling" patented technology

A statistical and functional correlation strategy to identify changes in cellular pathways specifically linked to impaired cognitive function with aging. Analyses using the strategy identified multiple groups of genes expressed in the hippocampi of mammals, where the genes were expressed at different levels for several ages. The aging changes in expression began before mid-life. Many of the genes were involved in specific neuronal and glial pathways with previously unrecognized relationships to aging and / or cognitive decline. The processes identified by the strategy suggest a new hypothesis of brain aging in which initially decreased neuronal activity and / or oxidative metabolism trigger separate but parallel genomic cascades in neurons and glia. In neurons, the cascade results in elevations in calcium signaling and reductions of immediate early gene signaling, biosynthesis, synaptogenesis and neurite remodeling. In contrast, glia undergo increased lipid metabolism and mediate a cycle of demyelination and remyelination that induces antigen presentation, inflammation, oxidative stress and extracellular restructuring. These identified genes and the proteins they encode can be used as novel biomarkers of brain aging and as targets for developing treatment methods against age-related cognitive decline, Alzheimer's Disease and Parkinson's Disease.

In certain aspects, the invention relates to use of PKD2 agonists, such as triptolide and triptolide derivatives, to regulate calcium release. In other aspects, the invention relates to use of PKD2 agonists to treat or aid in the treatment of any condition in which a calcium channel, such as the gene product of PKD 1 and / or PKD2, is mutated; calcium signaling is abnormal; or both, such as polycystic kidney disease.

In accordance with the present invention, it has been discovered that glucose and incretin hormones promote pancreatic islet cell survival via the calcium and cAMP dependent induction, respectively, of the transcription factor CREB. Specifically, a signaling module has been identified which mediates cooperative effects of calcium and cAMP on islet cell gene expression by stimulating the dephosphorylation and nuclear entry of TORC2, a cytoplasmic CREB coactivator. The module comprises a cAMP regulated snf1-like kinase called SIK2 and the calcium regulated phosphatase calcineurin, both of which associate with TORC2 in the cytoplasm. TORC2 is repressed under basal conditions through a phosphorylation dependent interaction with 14-3-3 proteins. cAMP and calcium signals stimulate CREB target gene expression via complementary effects on TORC2 dephosphorylation; cAMP disrupts TORC2-associated activity of SIK2 or related family members, whereas calcium induces TORC2 dephosphorylation via calcineurin. These findings provide a novel mechanism by which CREB activates cellular gene expression, depending on nutrient and energy status, and facilitate development of assays to identify compounds which modulate the role of TORCs. In accordance with the present invention, it has been discovered that fasting and energy-sensing pathways regulate the gluconeogenic program in liver by modulating the nuclear entry of a transcriptional coactivator called Transducer of Regulated CREB Activity 2 (TORC2). Hepatic TORC2 over-expression induces fasting hyperglycemia, whereas knockdown of TORC2 leads to fasting hypoglycemia and silencing of the gluconeogenic program. Since a majority of individuals with Type II diabetes exhibit fasting hyperglycemia due to elevated hepatic gluconeogenesis, compounds that enhance TORC2 phosphorylation will find use as therapeutic agents in this setting.

Compositions and methods related to the amelioration of pancreatitis through the pharmaceutical manipulation of calcium signaling are disclosed. Such compositions and methods may be used to ameliorate symptoms of acute or chronic pancreatitis or to reduce the chance or severity of pancreatitis in an individual at risk of the condition. In other embodiments, disclosed herein are compositions and methods related to the amelioration of viral diseases through the pharmaceutical manipulation of calcium signaling. In further embodiments, disclosed herein are compositions and methods related to the amelioration of Th17-induced diseases through the pharmaceutical manipulation of calcium signaling.

Compositions and methods related to the amelioration of pancreatitis through the pharmaceutical manipulation of calcium signaling are disclosed. Such compositions and methods may be used to ameliorate symptoms of acute or chronic pancreatitis or to reduce the chance or severity of pancreatitis in an individual at risk of the condition. In other embodiments, disclosed herein are compositions and methods related to the amelioration of viral diseases through the pharmaceutical manipulation of calcium signaling. In further embodiments, disclosed herein are compositions and methods related to the amelioration of Th17-induced diseases through the pharmaceutical manipulation of calcium signaling.

Disclosed are methods of identifying an agent that modulates an NFAT regulator protein. One such method comprises contacting at least one test agent with a recombinant cell comprising at least one NFAT regulator protein or fragment or derivative thereof, assessing the effect of the test agent on an activity, interaction, expression, or binding to the NFAT regulator protein or fragment or derivative thereof, and identifying the test agent that has an effect on an activity, interaction, expression, or binding to the NFAT regulator protein or fragment or derivative thereof, whereby the identified test agent is characterized as an agent that modulates an NFAT regulator protein. Methods of identifying an agent that modulates intracellular calcium, methods to screen for an agent that modulates NFAT regulator function, methods to diagnose unexplained immunodeficiency in a subject, and methods for identifying an agent for treating or preventing a disease or disorder associated with a NFAT regulator protein or calcium signaling are also disclosed.

The invention provides an antibody or fragment thereof that binds to human tumor-associated calcium signal transducer 2 (Trop-2) protein, and an application of the antibody or fragment thereof to prevention or treatment of diseases. The antibody or the fragment thereof can be effectively combined with the human Trop-2 protein, has internalization activity, is enhanced in internalization activity after ADC drug labeling, and is not lower than a control antibody in in-vivo drug effect and safety of a mouse model.

Described herein are therapeutic strategies (methods and compositions) useful for treating conditions in which cilia are affected and which manifest with cysts and / or fibrosis, such as conditions in which the kidney, pancreas, liver and / or spleen are affected and contain cysts. Particular embodiments described herein are therapeutic strategies in which PC-2 agonists, particularly agonists (calcium channel agonists) that target PC-2 directly and / or selectively, are administered to individuals with mutations in PKD1, in order to alter the course of polycystic kidney disease, particularly ADPKD. In specific embodiments, the invention relates to use of PC-2 agonists triptolide and triptolide derivatives to regulate calcium release. In other aspects, the invention relates to use of PC-2 agonists to treat or aid in the treatment of any condition in which a calcium channel, such as the gene product of PKD1 and / or PKD2, is mutated; calcium signaling is abnormal; or both.

The present invention relates to compositions and methods useful for detecting and / or measuring, e.g., intracellular signaling in vivo. More particularly, compositions and methods are provided, which include transgenic animals, that are useful in mapping and examining, e.g., calcium fluctuations in vivo between and within populations of cells in real time. Methods for screening for candidate compounds that effect, e.g., intracellular calcium signaling are also provided.

The invention relates to a Ca<2+> signal transduction saline-alkali modifier and a mixture ratio of raw materials. The Ca<2+> signal transduction saline-alkali modifier is specially used for modifying chloride saline-alkali lands, sulfate saline-alkali lands and carbonate saline-alkali lands. The related technology comprises the steps of selection of raw materials, crushing, sieving, weighing, mixing, stirring and subpackaging of finished products. The mixture ratio of raw materials is as follows: 0.1 to 0.2 percent of calcium signaling molecules, 1 to 2 percent of paclobutrazol, 0.5 to 5 percent of high molecular polymers, 6 to 40 percent of humic acid, 10 to 30 percent of phosphogypsum, 10 to 70 percent of zeolite powder (between 60 and 80 meshes), 25 to 30 percent of calcium superphosphate, 20 to 40 percent of fermented cow manure, 5 to 10 percent of nitrogen phosphorus potassium, 1 to 2 percent of ferrous sulfate and proper amount of vermiculite. The Ca<2+> signal transduction saline-alkali modifier aims to improve the utilization rate and the economic value of the chloride saline-alkali lands, the sulfate saline-alkali lands and the carbonate saline-alkali lands.

The present invention includes compositions and methods for neuroprotection by modulating intracellular calcium concentrations by administering an effective amount of an N-acylethanolamine to a subject.

Disclosed are methods of identifying an agent that modulates an NFAT regulator protein. One such method comprises contacting at least one test agent with a recombinant cell comprising at least one NFAT regulator protein or fragment or derivative thereof, assessing the effect of the test agent on an activity, interaction, expression, or binding to the NFAT regulator protein or fragment or derivative thereof, and identifying the test agent that has an effect on an activity, interaction, expression, or binding to the NFAT regulator protein or fragment or derivative thereof, whereby the identified test agent is characterized as an agent that modulates an NFAT regulator protein. Methods of identifying an agent that modulates intracellular calcium, methods to screen for an agent that modulates NFAT regulator function, methods to diagnose unexplained immunodeficiency in a subject, and methods for identifying an agent for treating or preventing a disease or disorder associated with a NFAT regulator protein or calcium signaling are also disclosed.

The present invention provides reagents and methods for identifying inhibitors of the L-type Ca2+ channel β3 protein, which has been demonstrated to be involved in calcium signaling, insulin secretion, and glucose homeostasis. The invention also provides therapeutics and methods for treating a subject with one or more of diabetes, insulin resistance, impaired insulin secretion, and impaired glucose homeostasis, involving the use of inhibitors of an L-type Ca2+ channel β3 subunit to provide a benefit to the subject.

The disclosure relates in some aspects to imaging agents, and in particular, imaging agents for sensing of calcium signaling. According to some embodiments of the disclosure, contrast agents for magnetic resonance imaging and related technologies are provided, and methods of making and using the contrast agents.

The present invention relates to compositions and methods useful for detecting and / or measuring, e.g., intracellular signaling in vivo. More particularly, compositions and methods are provided, which include transgenic animals, that are useful in mapping and examining, e.g., calcium fluctuations in vivo between and within populations of cells in real time. Methods for screening for candidate compounds that effect, e.g., intracellular calcium signaling are also provided.

The invention discloses a back-portable visual in-vivo calcium imaging device, and belongs to the technical field of in-vivo calcium imaging. The device includes a device body, a spine holder and fixing screws; the device body includes a track pulley system, four universal wheels and a spine holder base, the track pulley system is composed of two mutually perpendicular metal rods, wherein the twomutually perpendicular metal rods include a horizontal track and a longitudinal track, and the bottom end of the longitudinal track is provided with a microscope fixing platform; and the spine holderis connected to the spine holder base of the device main body through the four fixing screws, and is located at the inner lower part of the device main body. According to the mouse back-portable in-vivo calcium imaging device provided by the invention, a mouse spine can be fixed and is not easy to move, the mouse spine can be combined with the device main body carrying an ultramicroscope, and thedevice has the advantages of clever design, a simple and reasonable structure, stable clamping, good flexibility, convenient use, and strong compatibility, and can make calcium signal recording methods more abundant.

IgA receptors, including a polymeric immunoglobulin receptor (pIgR) and a FcαR, have been found on smooth muscle cells, synovial fibroblast cells and on both synovial and endothelial cells in synovial tissues from patients with arthritis. Incubation of smooth muscle cells or tissue with pIgA increases cytosolic calcium and alters the contractile state. Incubation of synovial cells with IgA modulates the inflammatory responses of these cells. The invention relates to methods of modulating calcium signalling and / or contractility of mesenchymal cells, as well as modulating (preferably inhibiting) the inflammatory responses of mesenchymal cells, methods of treating inflammatory conditions (such as asthma and arthritis), methods of drug delivery to mesenchymal cells and methods of detecting conditions associated with IgA receptors on mesenchymal cells.

The invention relates to the technical field of genetic engineering, and particularly relates to a peanut glutamyl t-RNA reductase, and further relates to applications of the peanut glutamyl t-RNA reductase in regulating the expression of chlorophyll and calmodulin. The peanut glutamyl t-RNA reductase has the beneficial effects that the functions of the peanut glutamyl t-RNA reductass are identified, namely, the peanut glutamyl t-RNA reductase has the actions of regulating the expression of chlorophyll and calmodulin, thus clearing the action relationship of reductase and calcium signals and establishing a theory basis for later research.

The present invention relates to use of miR-18b for prevention, treatment, or diagnosis of muscle diseases or neuromuscular diseases, and specifically it was confirmed that, in a muscle disease by gene mutations model, gene mutations reduce miR-18b expression, cause dysregulation of miR-18b signaling pathways, and thus induce calcium signaling, cell differentiation inhibition, and apoptosis. Therefore, miR-18b of the present invention may be used as a target factor for diagnosing and treating muscle diseases caused by gene mutations such as ALS and DMD.

The disclosure relates in some aspects to imaging agents, and in particular, imaging agents for sensing of calcium signaling. According to some embodiments of the disclosure, contrast agents for magnetic resonance imaging and related technologies are provided, and methods of making and using the contrast agents.

The invention discloses a method for increasing tropane alkaloid content in belladonna hairy roots by using a calcium signal inhibitor, which is characterized in that extracellular Ca < 2 + > concentration is reduced by using a Ca < 2 + > specific chelating agent, or a Ca < 2 + > / CaM signal pathway in the belladonna hairy roots is inhibited by using a cell membrane Ca < 2 + > channel inhibitor or an intracellular Ca < 2 + > receptor calmodulin inhibitor, so that the content of tropane alkaloid in the belladonna hairy roots is increased. Therefore, the expression of related genes PMT, TRI, CYP80F1, H6H and ArAT4 in the synthetic route of the tropane alkaloids is induced, and the synthesis and accumulation of the tropane alkaloids hyoscyamine, anisodamine or scopolamine are promoted.

The invention discloses a high-throughput method for judging human sperm quality by detecting a calcium signal, and belongs to the technical field of medicine. On the basis of a population sperm sample physiological environment, [Ca < 2 + >] i change high-throughput microplate reader detection under stimulation of various physiological factors is performed on the same sample, the regulation condition of [Ca < 2 + >] i by each physiological factor on a big data clinical sample size is taken as a research object, and corresponding physiological stimulation in each process of functional regulation and control of sperms before gamete fertilization is selected, and whether each sperm sample is normal is observed in each aspect in the fertilization preparation process or not.

The invention discloses a zebrafish model for in vivo screening of islet β-cell function-promoting drugs. The zebrafish model for in vivo screening of pancreatic islet β-cell function-promoting drugs has the coding sequence of the ins gene on the gene BAC_CH211_69I14 replaced with a fluorescent protein sequence , and the fluorescent signals were specifically expressed in islet β cells, which could indicate changes in the calcium ion signal of islet β cells in vivo. The present invention creates the first animal model that can indicate the function of pancreatic islet beta cells in vivo. The transgenic zebrafish line of the present invention can observe the changes of calcium signals in islet beta cells in real time in vivo, and intuitively and accurately report islet beta cells Functional status. Using this transgenic zebrafish line, the functional characteristics of islet β cells can be analyzed conveniently, automatically and with high throughput at the in vivo level, so as to achieve high-throughput screening of drugs that promote islet β cell function, which is of great practical significance and wide range. application prospects.

The present invention describes a calcium-binding myristoylated protein with homology to calcineurin B which interacts preferentially with presenilin 2 protein. Also, the present invention relates to methods that alter protein-protein interaction of the calcium-binding myristoylated protein with presenilin 2 thereby reducing deleterious effects of the protein-protein interaction, such as apoptosis. The present invention further relates to introducing and expressing a mutant presenilin 2 protein or mutant calcium-binding myristoylated protein to modulate cell functions relating to calcium signaling and apoptosis.

The present invention provides reagents and methods for identifying inhibitors of the L-type Ca2+ channel β3 protein, which has been demonstrated to be involved in calcium signaling, insulin secretion, and glucose homeostasis. The invention also provides therapeutics and methods for treating a subject with one or more of diabetes, insulin resistance, impaired insulin secretion, and impaired glucose homeostasis, involving the use of inhibitors of an L-type Ca2+ channel β3 subunit to provide a benefit to the subject.

The present invention features methods that allow for diagnosing a risk for a patient or subject developing an Autism Spectrum Disorder, for identifying potentially therapeutic anti-ASD agents, and methods for treatment monitoring as specified in the independent claims.

The invention relates to the field of biological medicine, and in particular, relates to an application of an FRT cell strain in preparation of a preparation or a kit for screening a Chrm3 regulator.FRT cells endogenously express Chrm3 in mRNA and protein levels; an FRT cell model capable of stably co-expressing ANO1 and YFP-H148Q / I152L is successfully constructed; the cell model can sensitivelydetect the intracellular calcium concentration, the slope value of fluorescence change and the concentration of the Chrm3 regulator form a dose-dependent relationship, and the cell model can be used for screening the Chrm3 regulator; the Z' factor value of the model is 0.678, and the requirement of high-throughput screening is met. The cell model realizes high-throughput screening of the Chrm3 regulator by sensitively detecting a calcium signal, and can also be applied to screening of other GPCR targets related to the calcium ion signal.

The invention discloses application of phytosulfokine-alpha to improvement on plant resistance to botrytis cinerea and application of the phytosulfokine-alpha to preparation of a preparation for improving the plant resistance to the botrytis cinerea. The preparation prepared by using the phytosulfokine-alpha as a main active component can significantly enhance the plant resistance to the botrytis cinerea through induction of a calcium signal path in a plant so as to reduce the economic losses caused by botrytis cinerea infection. Application of the preparation provided by the invention to control plant botrytis cinerea is simple and easy and relatively low in cost; growth of botrytis cinerea on leaves and disease spread can be significantly delayed and inhibited, so that the plant resistance to the botrytis cinerea is greatly improved.