A method of identifying a bicycle gene involves determining for a candidate gene a series of gene structure-based predictor variables, and applying a bicycle gene classifier including the predictor variables to determine whether the candidate gene is identified as a bicycle gene. The gene structure-based predictor variables can be selected from the following: (i) total gene length (base pair, bp); (ii) total length (bp) of coding exons; (iii) first coding exon length (bp); (iv) last coding exon length (bp); (v) number of internal exons in phase 0); (vi) number of internal exons in phase 1; (vii) number of internal exons in phase 2; and (viii) mean internal exon length (bp).
The present invention is generally directed to novel fluorophores and their use in imaging methods. In one case, the present invention provides a compound according to the structure shown in FIG. 20A. In another case, the present invention provides a method of imaging one or, more cellular structures within one or more cells using a compound of the structure shown in FIG. 20A.
G01N 33/533 - Production of labelled immunochemicals with fluorescent label
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 473/18 - Heterocyclic compounds containing purine ring systems with oxygen, sulfur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
C07D 491/107 - Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
C07D 491/147 - Ortho-condensed systems the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom
C07D 491/22 - Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups , , or in which the condensed system contains four or more hetero rings
A microscope system includes at least one illumination subsystem configured to produce and direct a light sheet toward a specimen region. The illumination subsystem includes a spatial adjustment apparatus configured to operate in a plurality of different modes, each operating mode configured to produce a light sheet having a different spatial status. The microscope system includes at least one detection subsystem arranged to collect fluorescence emitted from the specimen region due to an interaction between a specimen at the specimen region and a light sheet. The at least one detection subsystem includes a plurality of imaging devices, with each imaging device being associated with a different spatial status such that each imaging device is configured to record images of the fluorescence due to an interaction between a specimen at the specimen region and the light sheet of the associated spatial status.
Vectors and methods are described for efficient cloning and integration of a DNA sequence of interest into a genome of a cell. Vectors include a cassette having a nucleotide sequence having a negative selection marker that is a ccdB gene, which is flanked by non-identical attR recombination recognition sequences.
Vectors and methods are described for efficient cloning and integration of a DNA sequence of interest into a genome of a cell. Vectors include a cassette having a nucleotide sequence having a negative selection marker that is a ccdB gene, which is flanked by non-identical attR recombination recognition sequences.
6.
FLUORESCENT SENSORS AND METHODS OF MAKING AND USING
The application discloses a compound having a moiety that is either an affinity tag-containing moiety or a protein-manipulation moiety, a self-labeling protein (SLP) ligand, and a rhodamine dye linking the affinity tag-containing moiety or a protein-manipulation moiety to the SLP ligand. Also disclosed is a complex, which includes the compound and a SLP. Also disclosed is a method that involves contacting the compound and a SLP with a cell, and visualizing fluorescence in the cell or purifying the SLP and associated biological components from the cell.
The present disclosure provides, inter alia, genetically encoded recombinant peptide biosensors comprising analyte-binding framework portions and signaling portions, wherein the signaling portions are present within the framework portions at sites or amino acid positions that undergo a conformational change upon interaction of the framework portion with an analyte.
G01N 33/557 - ImmunoassayBiospecific binding assayMaterials therefor using kinetic measurement, i.e. time rate of progress of an antigen-antibody interaction
C07K 14/195 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria
C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving labelled substances
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
The present invention is generally directed to the synthesis and use of fluorophores. It is more specifically directed to the synthesis and use of deuterated fluorophores. In one case, the present invention provides a compound of the structure shown in FIG. 44.
Tryptophan-containing chemigenetic fluorescent indicators for detecting biologically-relevant analytes are described and are useful for detecting analytes in a living animal.
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving labelled substances
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
12.
CHEMOGENETIC RECEPTORS AND METHODS OF MAKING AND USING
This disclosure describes a number of chemogenetic receptors that bind an ingested substance that reinforces its own ingestion or administration (e.g., an addictive drug) and, upon binding of the molecule, modulate the function of a cell.
A chemigenetic calcium indicator and a method of measuring calcium are provided. The chemigenetic calcium indicator includes a calcium-binding protein domain attached to a ligand binding protein domain. The method of measuring calcium includes administering a chemigenetic calcium indicator to a subject and determining changes in fluorescence, the chemigenetic calcium indicator including a ligand binding protein domain having a calcium-binding protein domain and a dye-ligand conjugate attached thereto.
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving labelled substances
G01N 33/84 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving inorganic compounds or pH
G01N 21/77 - Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
ROS signal upregulates surface CALR and promotes macrophage-HSC interactions, safeguarding the development of stem cells that are stressed or damaged. Described herein are methods of controlling hematopoiesis, e.g., reducing hematopoiesis and/or improving the quality control mechanisms of hematopoiesis, relating to the use or administration of at least one CALR agonist.
A61K 31/00 - Medicinal preparations containing organic active ingredients
A61P 7/00 - Drugs for disorders of the blood or the extracellular fluid
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
This disclosure describes a number of chemogenetic receptors that bind an ingested substance that reinforces its own ingestion or administration (e.g., an addictive drug) and, upon binding of the molecule, modulate the function of a cell.
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61P 25/30 - Drugs for disorders of the nervous system for treating abuse or dependence
Fluorescent stains are described, which enable imaging of cellular structures without the need for genetic manipulation. Unique diaminobenzopyrylium dyes are disclosed, together with their use as live-cell mitochondrial stains.
Methods of imaging biomolecules from a tissue sample are described, including methods for preparing a tissue sample for imaging using expansion microscopy, while achieving ultrahigh effective imaging resolution.
A voltage indicator includes a polypeptide sequence comprising a voltage-sensitive opsin domain and a capture protein domain arranged and disposed to capture a fluorescent dye ligand. When the fluorescent dye ligand is captured and the voltage indicator is bound to a cell membrane, an increase in voltage across the cell membrane causes an increase in fluorescent emission.
G01R 15/22 - Adaptations providing voltage or current isolation, e.g. for high-voltage or high-current networks using light-emitting devices, e.g. LED, optocouplers
C07K 14/195 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria
C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
This document relates to materials and methods for modulating ligand gated ion channel (LGIC) activity. For example, modified LGICs including at least one LGIC subunit having a modified ligand binding domain (LBD) and/or a modified ion pore domain (IPD) are provided. Also provided are exogenous LGIC ligands that can bind to and activate the modified LGIC, as well as methods of modulating ion transport across the membrane of a cell of a mammal, methods of modulating the excitability of a cell in a mammal, and methods of treating a mammal having a channelopathy.
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
A61K 38/16 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
Disclosed is composition comprising: a first fluorophore moiety, and nanoparticles, wherein the nanoparticles comprise: a first plurality of a first nanoparticle, the first nanoparticle comprising: a first outer surface, a first interior bulk, and a first polymer, wherein the first polymer is covalently bonded to the first fluorophore moiety within the first interior bulk of the first nanoparticle. Also disclosed is a composition comprising: a chelate moiety, and nanoparticles, wherein the nanoparticles comprise: a plurality of a chelate nanoparticle, the chelate nanoparticle comprising: an outer surface, an interior bulk, and a polymer, wherein the polymer is covalently bonded to the chelate moiety within the interior bulk of the chelate nanoparticle. Also disclosed are methods of making such compositions and using such composition for brain mapping and tracing of axonal projections.
Provided are a photoactive fluorophore, a photoactive ligand, and a photoactive complex. The photoactive fluorophore includes a photoactivatable derivative of an azetidine-containing Janelia-Fluor dye. The photoactive ligand includes a photoactive fluorophore and a protein tag. The photoactive complex includes a photoactive ligand conjugated to a protein. Also provided are methods of in vivo labeling with and photoactivation of the photoactive fluorophore, ligand, and complex.
C07D 405/12 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
A microscope system includes at least one illumination subsystem configured to produce and direct a light sheet toward a specimen region. The illumination subsystem includes a spatial adjustment apparatus configured to operate in a plurality of different modes, each operating mode configured to produce a light sheet having a different spatial status. The microscope system includes at least one detection subsystem arranged to collect fluorescence emitted from the specimen region due to an interaction between a specimen at the specimen region and a light sheet. The at least one detection subsystem includes a plurality of imaging devices, with each imaging device being associated with a different spatial status such that each imaging device is configured to record images of the fluorescence due to an interaction between a specimen at the specimen region and the light sheet of the associated spatial status.
bicyclebicyclebicycle bicycle gene. The gene structure-based predictor variables can be selected from the following: (i) total gene length (base pair, bp); (ii) total length (bp) of coding exons; (iii) first coding exon length (bp); (iv) last coding exon length (bp); (v) number of internal exons in phase 0; (vi) number of internal exons in phase 1; (vii) number of internal exons in phase 2; and (viii) mean internal exon length (bp).
C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
41 - Education, entertainment, sporting and cultural services
Goods & Services
Promoting and providing expertise, collaboration, and guidance on diversity, equity, and inclusion within the academic, scientific, research, and medical communities to achieve advances in the integration of equity and inclusion in the fields of biomedical research and related sciences; Providing online information regarding promoting collaboration regarding diversity, equity, and inclusion within the scientific fields of biomedical research and related sciences Educational services, namely, conducting seminars, conferences, workshops, and lectures on diversity, equity and inclusion in the scientific fields of biomedical research and related sciences
The presently-disclosed subject matter includes fluorescent indicators, including bright and targetable red Ca2+ indicators. The presently-disclosed subject matter also includes kits comprising the same as well as methods for using the same to detect a target substance. Fluorescent indicators of the presently-disclosed subject matter include a compound of the formula:
C07F 7/08 - Compounds having one or more C—Si linkages
C07D 405/04 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
G01N 21/78 - Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator producing a change of colour
An optical microscope apparatus includes: a sample interrogation system configured to probe a sample location; and a light collection system configured to collect light output from a sample due to being probed by the sample interrogation system. The light collection system includes: a mirror positioned along an imaging axis that passes through the sample location; and an optical lens system including a plurality of optical lenses arranged along the imaging axis, at least one of the lenses being a multiplet optical lens.
A gripping apparatus includes: a temperature adjusting device held in a substrate wherein the substrate defines an open region; a phase change material held within the open region and thermally coupled with the temperature adjusting device such that a temperature change in the temperature adjusting device causes a temperature change in the phase change material; and a controller connected to the temperature adjusting device and configured to send a signal to the temperature adjusting device to change its temperature and thereby change the temperature of the phase change material that is thermally coupled with the temperature adjusting device. The phase change material is either in a solid state and configured to grip a stick or in a liquid state and the phase change material and configured to loosen its grip on the stick such that the stick is capable of moving through the phase change material.
A method of imaging a sample providing light from a light source, directing the provided light into an extended focus, scanning the extended focus across a wavefront modulating element that modulates amplitudes of the light along the extended focus, providing the modulated light to the sample, detecting light emitted from the sample in response to excitation by the modulated light, and generating an image of the sample based on the detected fluorescence emission light.
G02B 26/08 - Optical devices or arrangements for the control of light using movable or deformable optical elements for controlling the direction of light
31.
Genetically encoded calcium indicators (GECIs) and methods of making and using
A microscope directs light through an excitation objective to generate a lattice light sheet (LLS) within a sample. A detection objective collects signal light from the sample in response to the LLS and images the collected light onto a detector. Second and third light beams are imaged onto focal planes of the excitation objective and detection objective, respectively. One or more wavefront detectors determine wavefronts of light emitted from the sample and through the excitation objective in response to the imaged second light beam and emitted from the sample through the detection objective in response to the imaged third light beam. A wavefront of the first light beam is modified to reduce a sample-induced aberration of the LLS within the sample, and a wavefront of the signal light emitted from the sample is modified to reduce a sample-induced aberration of the signal light at the detector.
Provided herein are a voltage indicator and a method of measuring voltage. The voltage indicator includes a membrane-localized voltage-sensitive protein coupled to a capture protein. The method of measuring voltage includes administering a voltage indicator including a membrane-localized voltage-sensitive protein coupled to a capture protein, and determining changes in fluorescence of a small-molecule fluorescent dye captured by the capture protein.
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving labelled substances
C07K 14/195 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria
C07K 14/215 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria from Halobacteriaceae (F)
C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
C07K 14/46 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates
C07K 14/465 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from birds
The Board of Trustees of the Leland Stanford Junior University (USA)
University of York (United Kingdom)
Howard Hughes Medical Institute (USA)
Inventor
Jonikas, Martin C.
Meyer, Moritz
He, Shan
Itakura, Alan
Chen Wong, Vivian
Mackinder, Luke Colin Martin
Yu, Zhiheng
Matthies, Doreen
Chou, Hui-Ting
Abstract
Described herein are chimeric polypeptides that include one or more Rubisco-binding motifs (RBMs) and a heterologous polypeptide. Additional aspects of the present disclosure provide genetically altered plants having a chimeric polypeptide including one or more Rubisco-binding motifs (RBMs) and a heterologous polypeptide. Further aspects of the present disclosure relate to genetically altered plants having a stabilized polypeptide including two or more RBMs and one or both of an algal Rubisco-binding membrane protein (RBMP) and a Rubisco small subunit (SSU) protein. Other aspects of the present disclosure relate to methods of making such chimeric polypeptides and plants, as well as cultivating these genetically altered plants.
A sample is imaged using light-sheet imaging. The light-sheet imaging includes generating light, forming one or more light sheets from the light at one or more positions within the sample along respective illumination directions that are parallel with an illumination axis, and recording images of fluorescence emitted along a detection direction from the sample due to the optical interaction between the one or more light sheets and the sample. One or more properties relating to the light-sheet imaging are measured; the one or more measured properties are analyzed; and one or more operating parameters associated with the light-sheet imaging are adjusted based on the analysis of the one or more measured properties.
Disclosed herein include engineered opioid biosensors, and related compositions, vectors, cells, and systems. Also disclosed include methods that provide opioid biosensors with sensitivity and selectivity suitable for continuous opioid monitoring as well as the use of the opioid biosensors for detecting one or more specific opioids. The opioid biosensors, which are capable of undergoing a detectable conformational change upon binding to an opioid, can each comprise a first periplasmic binding protein (PBP) domain and a second PBP domain connected to the first PBP domain, wherein at least one of the first PBP domain and the second PBP domain comprises one or more mutations.
G01N 33/542 - ImmunoassayBiospecific binding assayMaterials therefor with immune complex formed in liquid phase with steric inhibition or signal modification, e.g. fluorescent quenching
C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
G01N 33/94 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving narcotics
Disclosed herein include engineered opioid biosensors, and related compositions, vectors, cells, and systems. Also disclosed include methods that provide opioid biosensors with sensitivity and selectivity suitable for continuous opioid monitoring as well as the use of the opioid biosensors for detecting one or more specific opioids. The opioid biosensors, which are capable of undergoing a detectable conformational change upon binding to an opioid, can each comprise a first periplasmic binding protein (PBP) domain and a second PBP domain connected to the first PBP domain, wherein at least one of the first PBP domain and the second PBP domain comprises one or more mutations.
The present disclosure provides, inter alia, genetically encoded recombinant peptide biosensors comprising analyte-binding framework portions and signaling portions, wherein the signaling portions are present within the framework portions at sites or amino acid positions that undergo a conformational change upon interaction of the framework portion with an analyte.
G01N 33/557 - ImmunoassayBiospecific binding assayMaterials therefor using kinetic measurement, i.e. time rate of progress of an antigen-antibody interaction
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving labelled substances
C07K 14/195 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria
C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
43.
MODIFIED LIGAND-GATED ION CHANNELS AND METHODS OF USE
This document relates to materials and methods for controlling ligand gated ion channel (LGIC) activity. For example, modified LGICs including at least one LGIC subunit having a modified ligand binding domain (LBD) and/or a modified ion pore domain (IPD) are provided. Also provided are exogenous LGIC ligands that can bind to and activate the modified LGIC, as well as methods of modulating ion transport across the membrane of a cell of a mammal, methods of modulating the excitability of a cell in a mammal, and methods of treating a mammal having a channelopathy.
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
C12N 15/00 - Mutation or genetic engineeringDNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purificationUse of hosts therefor
This document relates to materials and methods for controlling ligand gated ion channel (LGIC) activity. For example, modified LGICs including at least one LGIC subunit having a modified ligand binding domain (LBD) and/or a modified ion pore domain (IPD) are provided. Also provided are exogenous LGIC ligands that can bind to and activate the modified LGIC, as well as methods of modulating ion transport across the membrane of a cell of a mammal, methods of modulating the excitability of a cell in a mammal, and methods of treating a mammal having a channelopathy.
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
C12N 15/00 - Mutation or genetic engineeringDNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purificationUse of hosts therefor
The present invention is generally directed to the synthesis and use of fluorophores. It is more specifically directed to the synthesis and use of deuterated fluorophores. In one case, the present invention provides a compound of the structure shown in FIG. 44.
The present invention is generally directed to novel fluorophores and their use in imaging methods. In one case, the present invention provides a compound according to the structure shown in FIG. 20A. In another case, the present invention provides a method of imaging one or more cellular structures within one or more cells using a compound of the structure shown in FIG. 20A.
C07D 491/147 - Ortho-condensed systems the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom
C07D 491/107 - Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 491/22 - Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups , , or in which the condensed system contains four or more hetero rings
C07D 473/18 - Heterocyclic compounds containing purine ring systems with oxygen, sulfur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
Disclosed is composition comprising: a first fluorophore moiety, and nanoparticles, wherein the nanoparticles comprise: a first plurality of a first nanoparticle, the first nanoparticle comprising: a first outer surface, a first interior bulk, and a first polymer, wherein the first polymer is covalently bonded to the first fluorophore moiety within the first interior bulk of the first nanoparticle. Also disclosed is a composition comprising: a chelate moiety, and nanoparticles, wherein the nanoparticles comprise: a plurality of a chelate nanoparticle, the chelate nanoparticle comprising: an outer surface, an interior bulk, and a polymer, wherein the polymer is covalently bonded to the chelate moiety within the interior bulk of the chelate nanoparticle. Also disclosed are methods of making such compositions and using such composition for brain mapping and tracing of axonal projections.
C09K 11/04 - Luminescent, e.g. electroluminescent, chemiluminescent, materials containing natural or artificial radioactive elements or unspecified radioactive elements
This document provides methods and materials for modulating one or more properties of transporter proteins. For example, inverted transporter polypeptides including a leader sequence fused to a transporter protein, and methods of using one or more inverted transporter polypeptides to modulate (e.g., stimulate or inhibit) the excitability of one or more cells (e.g., neurons and myocytes) are provided.
Reversibly switchable fluorescent protein-based indicators are disclosed, and can be used as neuronal activity markers. The disclosed reversibly switchable fluorescent protein-based indicators exhibit faster or slower photoswitching the presence or absence of calcium, and depending on the wavelength of light stimulus employed.
This document relates to materials and methods for modulating ligand gated ion channel (LGIC) activity. For example, modified LGICs including at least one LGIC subunit having a modified ligand binding domain (LBD) and/or a modified ion pore domain (IPD) are provided. Also provided are exogenous LGIC ligands that can bind to and activate the modified LGIC, as well as methods of modulating ion transport across the membrane of a cell of a mammal, methods of modulating the excitability of a cell in a mammal, and methods of treating a mammal having a channelopathy.
C07F 9/6568 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus atoms as the only ring hetero atoms
C07D 409/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
C07D 413/10 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 491/147 - Ortho-condensed systems the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom
An optical microscope apparatus includes: a sample interrogation system configured to probe a sample location; and a light collection system configured to collect light output from a sample due to being probed by the sample interrogation system. The light collection system includes: a mirror positioned along an imaging axis that passes through the sample location; and an optical lens system including a plurality of optical lenses arranged along the imaging axis, at least one of the lenses being a multiplet optical lens.
An optical microscope apparatus includes: a sample interrogation system configured to probe a sample location; and a light collection system configured to collect light output from a sample due to being probed by the sample interrogation system. The light collection system includes: a mirror positioned along an imaging axis that passes through the sample location; and an optical lens system including a plurality of optical lenses arranged along the imaging axis, at least one of the lenses being a multiplet optical lens.
A method of imaging a sample providing light from a light source, directing the provided light into an extended focus, scanning the extended focus across a wavefront modulating element that modulates amplitudes of the light along the extended focus, providing the modulated light to the sample, detecting light emitted from the sample in response to excitation by the modulated light, and generating an image of the sample based on the detected fluorescence emission light.
G02B 21/16 - Microscopes adapted for ultraviolet illumination
G02B 26/08 - Optical devices or arrangements for the control of light using movable or deformable optical elements for controlling the direction of light
G02B 26/12 - Scanning systems using multifaceted mirrors
The presently-disclosed subject matter includes fluorescent compounds of the following formula:
The presently-disclosed subject matter includes fluorescent compounds of the following formula:
The presently-disclosed subject matter includes fluorescent compounds of the following formula:
The compounds can be used as probes, dyes, tags, and the like. The presently-disclosed subject matter also includes kits comprising the same as well as methods for using the same to detect a target substance.
The presently-disclosed subject matter includes fluorescent indicators, including bright and targetable red Ca2+ indicators. The presently-disclosed subject matter also includes kits comprising the same as well as methods for using the same to detect a target substance. Fluorescent indicators of the presently-disclosed subject matter include a compound of the formula:
C07F 7/08 - Compounds having one or more C—Si linkages
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 405/04 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
G01N 21/78 - Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator producing a change of colour
59.
Video-rate volumetric functional imaging of the brain at synaptic resolution
A scanning microscope includes a light source for generating a light beam having a wavelength, λ, and beam-forming optics configured for receiving the light beam and generating a quasi-Bessel excitation beam that is directed into a sample. The quasi-Bessel beam has a lateral FWHM and an axial FWHM that is greater than ten times the lateral FWHM, and the beam-forming optics include an excitation objective having an axis oriented in a first direction. The microscope includes beam scanning optics configured for scanning the quasi-Bessel beam in one or more directions that are substantially perpendicular to the first direction, and a detector configured for detecting signal light received from positions within the sample that are illuminated by the quasi-Bessel beam. The signal light is generated in response to an interaction of the excitation beam with the sample, and the signal light is imaged, at least in part, by the excitation objective, onto the detector.
A61B 1/00 - Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopesIlluminating arrangements therefor
THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY (USA)
UNIVERSITY OF YORK (United Kingdom)
HOWARD HUGHES MEDICAL INSTITUTE (USA)
Inventor
Jonikas, Martin C.
Meyer, Moritz
He, Shan
Itakura, Alan
Chen Wong, Vivian
Mackinder, Luke Colin Martin
Yu, Zhiheng
Matthies, Doreen
Chou, Hui-Ting
Abstract
Described herein are chimeric polypeptides that include one or more Rubisco-binding motifs (RBMs) and a heterologous polypeptide. Additional aspects of the present disclosure provide genetically altered plants having a chimeric polypeptide including one or more Rubisco-binding motifs (RBMs) and a heterologous polypeptide. Further aspects of the present disclosure relate to genetically altered plants having a stabilized polypeptide including two or more RBMs and one or both of an algal Rubisco-binding membrane protein (RBMP) and a Rubisco small subunit (SSU) protein. Other aspects of the present disclosure relate to methods of making such chimeric polypeptides and plants, as well as cultivating these genetically altered plants.
The present disclosure provides, inter alia, genetically encoded recombinant peptide biosensors comprising analyte-binding framework portions and signaling portions, wherein the signaling portions are present within the framework portions at sites or amino acid positions that undergo a conformational change upon interaction of the framework portion with an analyte.
G01N 33/557 - ImmunoassayBiospecific binding assayMaterials therefor using kinetic measurement, i.e. time rate of progress of an antigen-antibody interaction
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving labelled substances
C07K 14/195 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria
C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
62.
Modified ligand-gated ion channels and methods of use
This document relates to materials and methods for controlling ligand gated ion channel (LGIC) activity. For example, modified LGICs including at least one LGIC subunit having a modified ligand binding domain (LBD) and/or a modified ion pore domain (IPD) are provided. Also provided are exogenous LGIC ligands that can bind to and activate the modified LGIC, as well as methods of modulating ion transport across the membrane of a cell of a mammal, methods of modulating the excitability of a cell in a mammal, and methods of treating a mammal having a channelopathy.
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
C12N 15/00 - Mutation or genetic engineeringDNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purificationUse of hosts therefor
A voltage indicator includes a polypeptide sequence comprising a voltage-sensitive opsin domain and a capture protein domain arranged and disposed to capture a fluorescent dye ligand. When the fluorescent dye ligand is captured and the voltage indicator is bound to a cell membrane, an increase in voltage across the cell membrane causes an increase in fluorescent emission.
G01R 15/22 - Adaptations providing voltage or current isolation, e.g. for high-voltage or high-current networks using light-emitting devices, e.g. LED, optocouplers
G01R 19/00 - Arrangements for measuring currents or voltages or for indicating presence or sign thereof
C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
Provided herein are methods of recovering single nuclei from a tissue sample comprising chopping or dounce homogenizing the tissue sample in a nuclear extraction buffer at 4° C. to produce a tissue homogenate; centrifuging the tissue homogenate to produce a nuclear pellet; resuspending the nuclear pellet in a nuclear resuspension buffer comprising bovine serum albumin, RNase inhibitor, and salts to produce a resuspension; and filtering the resuspension through a strainer, wherein the single nuclei are present in a supernatant passed through the strainer. The invention also provides a method of single cell sequencing comprising extracting nuclei from a population of cells under conditions that preserve a portion of the outer nuclear envelope and rough endoplasmic reticulum; sorting single nuclei into separate reaction vessels; extracting RNA from the single nuclei; generating a cDNA library, whereby gene expression data from single cells are obtained. The tissue sample may be fresh or frozen.
C40B 50/18 - Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creationParticular methods of cleavage from the solid support using a particular method of attachment to the solid support
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
A chemigenetic calcium indicator and a method of measuring calcium are provided. The chemigenetic calcium indicator includes a calcium-binding protein domain attached to a ligand binding protein domain. The method of measuring calcium includes administering a chemigenetic calcium indicator to a subject and determining changes in fluorescence, the chemigenetic calcium indicator including a ligand binding protein domain having a calcium-binding protein domain and a dye-ligand conjugate attached thereto.
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving labelled substances
G01N 33/84 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving inorganic compounds or pH
G01N 21/77 - Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
A scanning microscope includes a light source for generating a light beam having a wavelength, λ, and beam-forming optics configured for receiving the light beam and generating a quasi-Bessel excitation beam that is directed into a sample. The quasi-Bessel beam has a lateral FWHM and an axial FWHM that is greater than ten times the lateral FWHM, and the beam-forming optics include an excitation objective having an axis oriented in a first direction. The microscope includes beam scanning optics configured for scanning the quasi-Bessel beam in one or more directions that are substantially perpendicular to the first direction, and a detector configured for detecting signal light received from positions within the sample that are illuminated by the quasi-Bessel beam. The signal light is generated in response to an interaction of the excitation beam with the sample, and the signal light is imaged, at least in part, by the excitation objective, onto the detector.
A61B 1/00 - Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopesIlluminating arrangements therefor
67.
Methods and compositions for micro-electron diffraction
A sample preparation method includes disposing a microcrystal on an electrically conductive grid, coating the microcrystal with an electrically conductive material to yield a coated microcrystal, milling the coated microcrystal with a first ion beam to yield a milled microcrystal, and polishing the milled microcrystal with a second ion beam to yield a polished microcrystal. A length of a side of the milled microcrystal is between about 250 nm and about 500 nm, and a length of the corresponding side of the polished microcrystal is between about 150 nm and about 250 nm. Assessing the crystal structure of the polished microcrystal includes rotating the polished microcrystal while accelerating electrons toward the polished microcrystal, diffracting the electrons from the polished microcrystal to yield a multiplicity of diffraction patterns, and assessing, from the multiplicity of diffraction patterns, the crystal structure of the polished microcrystal.
G01N 23/20058 - Measuring diffraction of electrons, e.g. low energy electron diffraction [LEED] method or reflection high energy electron diffraction [RHEED] method
G01N 23/20008 - Constructional details of analysers, e.g. characterised by X-ray source, detector or optical systemAccessories thereforPreparing specimens therefor
G01N 23/2251 - Investigating or analysing materials by the use of wave or particle radiation, e.g. X-rays or neutrons, not covered by groups , or by measuring secondary emission from the material using electron or ion microprobes using incident electron beams, e.g. scanning electron microscopy [SEM]
A gripping apparatus includes: a temperature adjusting device held in a substrate wherein the substrate defines an open region; a phase change material held within the open region and thermally coupled with the temperature adjusting device such that a temperature change in the temperature adjusting device causes a temperature change in the phase change material; and a controller connected to the temperature adjusting device and configured to send a signal to the temperature adjusting device to change its temperature and thereby change the temperature of the phase change material that is thermally coupled with the temperature adjusting device. The phase change material is either in a solid state and configured to grip a stick or in a liquid state and the phase change material and configured to loosen its grip on the stick such that the stick is capable of moving through the phase change material.
Provided herein are a voltage indicator and a method of measuring voltage. The voltage indicator includes a membrane-localized voltage-sensitive protein coupled to a capture protein. The method of measuring voltage includes administering a voltage indicator including a membrane-localized voltage-sensitive protein coupled to a capture protein, and determining changes in fluorescence of a small-molecule fluorescent dye captured by the capture protein.
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving labelled substances
C07K 14/195 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria
C07K 14/215 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria from Halobacteriaceae (F)
C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
C07K 14/46 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates
C07K 14/465 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from birds
This document relates to materials and methods for controlling ligand gated ion channel (LGIC) activity. For example, modified LGICs including at least one LGIC subunit having a modified ligand binding domain (LBD) and/or a modified ion pore domain (IPD) are provided. Also provided are exogenous LGIC ligands that can bind to and activate the modified LGIC, as well as methods of modulating ion transport across the membrane of a cell of a mammal, methods of modulating the excitability of a cell in a mammal, and methods of treating a mammal having a channelopathy.
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
C12N 15/00 - Mutation or genetic engineeringDNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purificationUse of hosts therefor
The present disclosure provides, inter alia, genetically encoded recombinant peptide biosensors comprising analyte-binding framework portions and signaling portions, wherein the signaling portions are present within the framework portions at sites or amino acid positions that undergo a conformational change upon interaction of the framework portion with an analyte.
G01N 33/557 - ImmunoassayBiospecific binding assayMaterials therefor using kinetic measurement, i.e. time rate of progress of an antigen-antibody interaction
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving labelled substances
C07K 14/195 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria
C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
72.
INVERTED TRANSPORTER POLYPEPTIDES AND METHODS OF USING
This document provides methods and materials for modulating one or more properties of transporter proteins. For example, inverted transporter polypeptides including a leader sequence fused to a transporter protein, and methods of using one or more inverted transporter polypeptides to modulate (e.g., stimulate or inhibit) the excitability of one or more cells (e.g., neurons and myocytes) are provided.
The present invention is generally directed to the synthesis and use of fluorophores. It is more specifically directed to the synthesis and use of deuterated fluorophores. In one case, the present invention provides a compound of the structure shown in FIG. 44.
A61K 31/352 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. cannabinols, methantheline
A microscopy system includes a gas cluster beam system configured for generating a beam of gas clusters directed toward a sample to irradiate a sample and mill away successive surface layers from the sample, a scanning electron microscope system configured for irradiating the successive surface layers of the sample with an electron beam and for imaging the successive surface layers of the sample in response to the irradiation of the surface layer, and a processor configured for generating a three dimensional image of the sample based on the imaging of the successive layers of the sample.
H01J 37/26 - Electron or ion microscopesElectron- or ion-diffraction tubes
G01N 23/2251 - Investigating or analysing materials by the use of wave or particle radiation, e.g. X-rays or neutrons, not covered by groups , or by measuring secondary emission from the material using electron or ion microprobes using incident electron beams, e.g. scanning electron microscopy [SEM]
Labeled probes, and methods of use thereof, comprise a Cas polypeptide conjugated to gRNA that is specific for target nucleic acid sequences, including genomic DNA sequences. The probes and methods can be used to label nucleic acid sequences without global DNA denaturation.
C12Q 1/683 - Hybridisation assays for detection of mutation or polymorphism involving restriction enzymes, e.g. restriction fragment length polymorphism [RFLP]
C12Q 1/6804 - Nucleic acid analysis using immunogens
C07H 21/04 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
A microscopy system includes a gas cluster beam system configured for generating a beam of gas clusters directed toward a sample to irradiate a sample and mill away successive surface layers from the sample, a scanning electron microscope system configured for irradiating the successive surface layers of the sample with an electron beam and for imaging the successive surface layers of the sample in response to the irradiation of the surface layer, and a processor configured for generating a three dimensional image of the sample based on the imaging of the successive layers of the sample.
A sample is imaged using light-sheet imaging. The light-sheet imaging includes generating light, forming one or more light sheets from the light at one or more positions within the sample along respective illumination directions that are parallel with an illumination axis, and recording images of fluorescence emitted along a detection direction from the sample due to the optical interaction between the one or more light sheets and the sample. One or more properties relating to the light-sheet imaging are measured; the one or more measured properties are analyzed; and one or more operating parameters associated with the light-sheet imaging are adjusted based on the analysis of the one or more measured properties.
A chemigenetic calcium indicator and a method of measuring calcium are provided. The chemigenetic calcium indicator includes a calcium-binding protein domain attached to a ligand binding protein domain. The method of measuring calcium includes administering a chemigenetic calcium indicator to a subject and determining changes in fluorescence, the chemigenetic calcium indicator including a ligand binding protein domain having a calcium-binding protein domain and a dye-ligand conjugate attached thereto.
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving labelled substances
An apparatus includes a light source configured for generating a coherent light beam having a wavelength, λ, a light detector, and beam-forming optics configured for receiving the generated light beam and for generating a plurality of substantially parallel Bessel-like beams directed into a sample in a first direction. Each of the Bessel-like beams has a fixed phase relative to the other Bessel-like beams. Imaging optics are configured for receiving light from a position within the sample that is illuminated by the Bessel-like beams and for imaging the received light onto the detector. The imaging optics include a detection objective having an axis oriented in a second direction that is non-parallel to the first direction, where the detector is configured for detecting light received by the imaging optics. A processor configured to generate an image of the sample based on the detected light.
This document relates to materials and methods for modulating ligand gated ion channel (LGIC) activity. For example, modified LGICs including at least one LGIC subunit having a modified ligand binding domain (LBD) and/or a modified ion pore domain (IPD) are provided. Also provided are exogenous LGIC ligands that can bind to and activate the modified LGIC, as well as methods of modulating ion transport across the membrane of a cell of a mammal, methods of modulating the excitability of a cell in a mammal, and methods of treating a mammal having a channelopathy.
Genetically encoded calcium indicator (GECI) polypeptides and the nucleic acid molecules encoding such polypeptides are provided. In addition, methods of using such nucleic acids and polypeptides in methods of screening for agonists or antagonists of G-protein coupled receptor (GPCR) or ion channels and methods of monitoring neural activity also are provided.
C07H 21/04 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
Genetically encoded calcium indicator (GECI) polypeptides and the nucleic acid molecules encoding such polypeptides are provided. In addition, methods of using such nucleic acids and polypeptides in methods of screening for agonists or antagonists of G-protein coupled receptor (GPCR) or ion channels and methods of monitoring neural activity also are provided.
This document relates to materials and methods for modulating ligand gated ion channel (LGIC) activity. For example, modified LGICs including at least one LGIC subunit having a modified ligand binding domain (LBD) and/or a modified ion pore domain (IPD) are provided. Also provided are exogenous LGIC ligands that can bind to and activate the modified LGIC, as well as methods of modulating ion transport across the membrane of a cell of a mammal, methods of modulating the excitability of a cell in a mammal, and methods of treating a mammal having a channelopathy.
C12N 15/62 - DNA sequences coding for fusion proteins
A61K 31/439 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
A61K 31/551 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogens as ring hetero atoms, e.g. clozapine, dilazep
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
A microscope directs light through an excitation objective having an axis oriented in a first direction, to generate a lattice light sheet (LLS) within a sample. A detection objective oriented in a direction substantially perpendicular to the first direction collects signal light emitted from the sample in response to the LLS within the sample and images the collected light onto a detector. A second light beam is imaged onto a focal plane of the excitation objective, a third light beam is imaged onto a focal plane of the detection objective. One or more wavefront detectors determine a wavefront of light emitted from the sample and through the excitation objective in response to the second light beam being imaged onto the focal plane of the excitation objective and determine a wavefront of light emitted from the sample through the detection objective in response to the third light beam being imaged onto the focal plane of the detection objective. A first wavefront modulating element modifies a wavefront of the first light beam from to reduce a sample-induced aberration of the LLS within the sample, and a second wavefront modulating element modifies a wavefront of the signal light emitted in response to the LLS to reduce a sample-induced aberration of the signal light at the detector.
A microscope directs light through an excitation objective to generate a lattice light sheet (LLS) within a sample. A detection objective collects signal light from the sample in response to the LLS and images the collected light onto a detector. Second and third light beams are imaged onto focal planes of the excitation objective and detection objective, respectively. One or more wavefront detectors determine wavefronts of light emitted from the sample and through the excitation objective in response to the imaged second light beam and emitted from the sample through the detection objective in response to the imaged third light beam. A wavefront of the first light beam is modified to reduce a sample-induced aberration of the LLS within the sample, and a wavefront of the signal light emitted from the sample is modified to reduce a sample-induced aberration of the signal light at the detector.
The presently-disclosed subject matter includes azetidine-substituted fluorescent compounds, where the compounds may be used as probes, dyes, tags, and the like. The presently-disclosed subject matter also includes kits comprising the same as well as methods for using the same to detect a target substance.
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
C07D 405/04 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 473/18 - Heterocyclic compounds containing purine ring systems with oxygen, sulfur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
C07D 205/06 - Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
A61K 31/397 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having four-membered rings, e.g. azetidine
A61K 31/438 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring being spiro-condensed with carbocyclic or heterocyclic ring systems
A61K 31/473 - QuinolinesIsoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
A61K 31/536 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and at least one oxygen as the ring hetero atoms, e.g. 1,2-oxazines ortho- or peri-condensed with carbocyclic ring systems
A61K 31/498 - Pyrazines or piperazines ortho- or peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
A61K 31/095 - Sulfur, selenium or tellurium compounds, e.g. thiols
G01N 33/52 - Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper
A microscope system including: a source of light; a sample objective configured for focusing the light at a focal plane within a sample; a remote focus unit configured for changing a position of the focal plane along an axis perpendicular to the focal plane; one or more optical element configured for directing the focused light to a location within the focal plane; and a detector configured for detecting light emitted from the focal plane within the sample; wherein the one or more optical element is located after the remote focus unit along a beam path of the light from the source to the sample objective, such that the changing the position of the focal plane along the axis is performed before the directing the focused light to the location within the focal plane.
The present invention is generally directed to novel fluorophores and their use in imaging methods. In one case, the present invention provides a compound according to the structure shown in FIG. 20A. In another case, the present invention provides a method of imaging one or more cellular structures within one or more cells using a compound of the structure shown in FIG. 20A.
C07D 491/147 - Ortho-condensed systems the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom
C07D 491/107 - Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 491/22 - Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups , , or in which the condensed system contains four or more hetero rings
C07D 473/18 - Heterocyclic compounds containing purine ring systems with oxygen, sulfur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
The present disclosure provides, inter alia, genetically encoded recombinant peptide biosensors comprising analyte-binding framework portions and signaling portions, wherein the signaling portions are present within the framework portions at sites or amino acid positions that undergo a conformational change upon interaction of the framework portion with an analyte.
G01N 33/557 - ImmunoassayBiospecific binding assayMaterials therefor using kinetic measurement, i.e. time rate of progress of an antigen-antibody interaction
C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
C07K 14/195 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving labelled substances
93.
Sample analysis, presence determination of a target sequence
The present invention provides a combination of genomic and computational technologies to provide rapid, portable sample analysis for sequencing or identifying a target sequence involving generating probes for use in analyzing a sample which may comprise a target sequence.
C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving virus or bacteriophage
C12Q 1/6816 - Hybridisation assays characterised by the detection means
C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
C07H 21/04 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
Techniques are described for imaging a sample where the techniques include acquiring a raster scan image of the sample, providing light from a light source, directing the light into a plurality of different light beam paths at different times, providing light in each of the plurality of light beam paths through an objective lens to the sample, and providing light in each of the plurality of beams to different locations within the sample. Fluorescence emission light from the sample is detected in response to excitation by light in each of the plurality of light beam paths, where the detected fluorescence emission light corresponds to low coherence projections of the sample, and an image of the sample is generated based on the detected fluorescence emission light and based on the raster scan image.
Techniques are described for imaging a sample where the techniques include acquiring a raster scan image of the sample, providing light from a light source, directing the light into a plurality of different light beam paths at different times, providing light in each of the plurality of light beam paths through an objective lens to the sample, and providing light in each of the plurality of beams to different locations within the sample. Fluorescence emission light from the sample is detected in response to excitation by light in each of the plurality of light beam paths, where the detected fluorescence emission light corresponds to fluorescence intensity projections of the sample with low mutual coherence, and an image of the sample is generated based on the detected fluorescence emission light and based on the raster scan image.
Genetically encoded calcium indicator (GECI) polypeptides and the nucleic acid molecules encoding such polypeptides are provided. In addition, methods of using such nucleic acids and polypeptides in methods of screening for agonists or antagonists of G-protein coupled receptor (GPCR) or ion channels and methods of monitoring neural activity also are provided.
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
C07K 14/00 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof
An apparatus includes a magnetic apparatus that defines an actuation volume that is large enough to accommodate a sample, the magnetic apparatus including a magnet that is configured to create a magnetic field having a magnitude B in the sample when supplied with a DC current; at least one biological construct within the sample, the biological construct configured to change its status in response to a change in a property; and at least one magnetocaloric actuator coupled with the biological construct. A change in a characteristic in the actuation volume causes the property of the magnetocaloric actuator to change, which causes a change in the status of the biological construct.
G01R 33/3815 - Systems for generation, homogenisation or stabilisation of the main or gradient magnetic field using electromagnets with superconducting coils, e.g. power supply therefor
A61B 5/055 - Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fieldsMeasuring using microwaves or radio waves involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
G01R 33/56 - Image enhancement or correction, e.g. subtraction or averaging techniques
An imaging apparatus for imaging a sample includes a magnetic apparatus that defines a sample volume that is large enough to accommodate the sample to be imaged, and one or more magnetically manipulatable materials within the sample. The magnetic apparatus includes a magnet that is configured to create a magnetic field having a magnitude B in the sample Each magnetically manipulatable material is a material that exhibits a transition between a first magnetic state and a second magnetic state in response to a change in a property associated with the sample while the magnetic field having the magnitude B is maintained in the sample.
A61B 5/055 - Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fieldsMeasuring using microwaves or radio waves involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
An apparatus includes a magnetic apparatus that defines an actuation volume that is large enough to accommodate a sample, the magnetic apparatus including a magnet that is configured to create a magnetic field having a magnitude B in the sample when supplied with a DC current; at least one biological construct within the sample, the biological construct configured to change its status in response to a change in a property; and at least one magnetocaloric actuator coupled with the biological construct. A change in a characteristic in the actuation volume causes the property of the magnetocaloric actuator to change, which causes a change in the status of the biological construct.
The presently-disclosed subject matter includes azetidine-substituted fluorescent compounds, where the compounds may be used as probes, dyes, tags, and the like. The presently-disclosed subject matter also includes kits comprising the same as well as methods for using the same to detect a target substance.
G01N 33/52 - Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving labelled substances
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 473/18 - Heterocyclic compounds containing purine ring systems with oxygen, sulfur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
C07D 405/04 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07F 7/08 - Compounds having one or more C—Si linkages
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
C07D 205/06 - Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
