Abstract: Milling with ultraviolet excitation (MUVE) realizes high-throughput multiplex imaging of large three-dimensional samples. The instrumentation may comprise a UV-source attachment, precision stage attachment, and/or a blade assembly, and the instrumentation may overcome several constraints inherent to current state-of-the-art three-dimensional microscopy. MUVE offers throughput that is orders of magnitude faster than other technology by collecting a two-dimensional array of pixels simultaneously. The proposed instrumentation also utilizes serial ablation and provides the opportunity for true whole-organ imaging at microscopic resolution.

Abstract: Milling with ultraviolet excitation (MUVE) realizes high-throughput multiplex imaging of large three-dimensional samples. The instrumentation may comprise a UV-source attachment, precision stage attachment, and/or a blade assembly, and the instrumentation may overcome several constraints inherent to current state-of-the-art three-dimensional microscopy. MUVE offers throughput that is orders of magnitude faster than other technology by collecting a two-dimensional array of pixels simultaneously. The proposed instrumentation also utilizes serial ablation and provides the opportunity for true whole-organ imaging at microscopic resolution.

Abstract: Imaging systems and methods, referred to herein as surface ablation lathe tomography (SALT), may be capable of providing whole organ tomography to provide 3D imaging. The system may provide a UV source that excites a sample, and a camera may capture imaging of fluorescent emission cause by the excitation. The tissue sample may be treated or stained with an imaging agent, such as fluorescent markers with fluorescently-tagged antibodies. The sample may also be infused with and/or embedded in paraffin wax. The tissue sample embedded in paraffin may be placed on a rotating mechanism that rotates, while the UV source excites a desired region and the camera captures imaging of a thin surface layer or shell of the sample. The system may also provide an ablation mechanism, such as a microtome blade or lathe, to ablate surface of the sample during rotation to allow imaging of subsequent layers of the sample.

Abstract: In some embodiments, the present disclosure pertains to a method for retrieving at least one molecular recognition element in a fixed tissue. In some embodiments the method comprises preparing a solution comprising at least one aldehyde-scavenging agent. In some embodiments, the method comprises contacting the fixed tissue with the solution. In some embodiments, the tissue is fixed with an aldehyde-based cross-linking agent. In some embodiments, a reaction of the aldehyde-scavenging agent with the aldehydes comprising the cross-linking agent retrieves the at least one molecular recognition element. In some embodiments, the at least one molecular recognition element comprises of amino acids, peptides, proteins, nucleic acids, carbohydrates, lipids, or a combination thereof.

Abstract: Imaging systems and methods, referred to herein as surface ablation lathe tomography (SALT), may be capable of providing whole organ tomography to provide 3D imaging. The system may provide a UV source that excites a sample, and a camera may capture imaging of fluorescent emission cause by the excitation. The tissue sample may be treated or stained with an imaging agent, such as fluorescent markers with fluorescently-tagged antibodies. The sample may also be infused with and/or embedded in paraffin wax. The tissue sample embedded in paraffin may be placed on a rotating mechanism that rotates, while the UV source excites a desired region and the camera captures imaging of a thin surface layer or shell of the sample. The system may also provide an ablation mechanism, such as a microtome blade or lathe, to ablate surface of the sample during rotation to allow imaging of subsequent layers of the sample.

Abstract: In some embodiments, the present disclosure pertains to a method for retrieving at least one molecular recognition element in a fixed tissue. In some embodiments the method comprises preparing a solution comprising at least one aldehyde-scavenging agent. In some embodiments, the method comprises contacting the fixed tissue with the solution. In some embodiments, the tissue is fixed with an aldehyde-based cross-linking agent. In some embodiments, a reaction of the aldehyde-scavenging agent with the aldehydes comprising the cross-linking agent retrieves the at least one molecular recognition element. In some embodiments, the at least one molecular recognition element comprises of amino acids, peptides, proteins, nucleic acids, carbohydrates, lipids, or a combination thereof.

Abstract: In some embodiments, the present disclosure pertains to a method for retrieving at least one molecular recognition element in a fixed tissue. In some embodiments the method comprises preparing a solution comprising at least one aldehyde-scavenging agent. In some embodiments, the method comprises contacting the fixed tissue with the solution. In some embodiments, the tissue is fixed with an aldehyde-based cross-linking agent. In some embodiments, a reaction of the aldehyde-scavenging agent with the aldehydes comprising the cross-linking agent retrieves the at least one molecular recognition element. In some embodiments, the at least one molecular recognition element comprises of amino acids, peptides, proteins, nucleic acids, carbohydrates, lipids, or a combination thereof.

Abstract: In some embodiments, the present disclosure pertains to a method for retrieving at least one molecular recognition element in a fixed tissue. In some embodiments the method comprises preparing a solution comprising at least one aldehyde-scavenging agent. In some embodiments, the method comprises contacting the fixed tissue with the solution. In some embodiments, the tissue is fixed with an aldehyde-based cross-linking agent. In some embodiments, a reaction of the aldehyde-scavenging agent with the aldehydes comprising the cross-linking agent retrieves the at least one molecular recognition t. In some embodiments, the at least one rolecular recognition element comprises of amino acids, peptides, proteins, nucleic acids, carbohydrates, lipids, or a combination thereof.

Abstract: The present invention is directed to novel treatment of controlling hippocampal neural circuit hyperexcitability occurring in a neurological disease or disorder associated with epileptogenesis in a subject in need of such treatment, comprising the step of contacting the hippocampus in said subject with a compound effective to restore excitatory/inhibitor balance thereby controlling the neural circuit hyperexcitability. Further provided is a method of treating a neurological disease or disorder associated with epileptogenesis in a subject in need of such treatment, comprising the step of administering an amount of an adenosine A1 receptor agonist pharmacologically effective to block epileptogenetic activities without blocking excitatory synaptic transmission.

Abstract: Provided herein are methods, compounds, mixtures and formulations of antigen retrieval agent useful in retrieving antigens and improving the detection of amino acids, peptides and proteins or epitopes thereon in a tissue fixed with aldehyde-based cross-linking agents. Contacting the fixed tissue with a solution of the aldehyde scavenging agent causes reactivity with the aldehyde moieties to retrieve antigens and improve detection of the amino acids, peptides and proteins or epitopes. Also provided are kits comprising the antigen retrieval agent and, optionally, components for staining or detecting the proteins or the antigens or epitopes and instructions for using the kit. Further provided is a method for identifying an antigen retrieval agent. A fixed protein is contacted with an agent to be tested and heated in solution therewith. Detection of protein peaks via mass spectrometry indicates the tested agent is an antigen retrieval agent.

Abstract: This document relates to methods and materials for detecting mutations that can be linked to dementia. For example, methods and materials for detecting one or more mutations within PGRN nucleic acid are provided. This document also provides methods and materials for detecting the level of progranulin expression. In addition, this document relates to methods and materials for treating mammals having a neurodegenerative disorder (e.g., dementia). For example, methods and materials for increasing PGRN polypeptide levels in mammals are provided, as are methods and materials for identifying agents that can be used to increase PGRN polypeptide levels in mammals.

Abstract: Provided herein are methods, compounds, mixtures and formulations of antigen retrieval agent useful in retrieving antigens and improving the detection of amino acids, peptides and proteins or epitopes thereon in a tissue fixed with aldehyde-based cross-linking agents. Contacting the fixed tissue with a solution of the aldehyde scavenging agent causes reactivity with the aldehyde moieties to retrieve antigens and improve detection of the amino acids, peptides and proteins or epitopes. Also provided are kits comprising the antigen retrieval agent and, optionally, components for staining or detecting the proteins or the antigens or epitopes and instructions for using the kit. Further provided is a method for identifying an antigen retrieval agent. A fixed protein is contacted with an agent to be tested and heated in solution therewith. Detection of protein peaks via mass spectrometry indicates the tested agent is an antigen retrieval agent.

Abstract: The present invention is directed to novel treatment of controlling hippocampal neural circuit hyperexcitability occurring in a neurological disease or disorder associated with epileptogenesis in a subject in need of such treatment, comprising the step of contacting the hippocampus in said subject with a compound effective to restore excitatory/inhibitor balance thereby controlling the neural circuit hyperexcitability. Further provided is a method of treating a neurological disease or disorder associated with epileptogenesis in a subject in need of such treatment, comprising the step of administering an amount of an adenosine A1 receptor agonist pharmacologically effective to block epileptogenetic activities without blocking excitatory synaptic transmission.

Abstract: This document relates to methods and materials for detecting mutations that can be linked to dementia. For example, methods and materials for detecting one or more mutations within PGRN nucleic acid are provided. This document also provides methods and materials for detecting the level of progranulin expression. In addition, this document relates to methods and materials for treating mammals having a neurodegenerative disorder (e.g., dementia). For example, methods and materials for increasing PGRN polypeptide levels in mammals are provided, as are methods and materials for identifying agents that can be used to increase PGRN polypeptide levels in mammals.

Abstract: This document relates to methods and materials for detecting mutations that can be linked to dementia. For example, methods and materials for detecting one or more mutations within PGRN nucleic acid are provided. This document also provides methods and materials for detecting the level of progranulin expression. In addition, this document relates to methods and materials for treating mammals having a neurodegenerative disorder (e.g., dementia). For example, methods and materials for increasing PGRN polypeptide levels in mammals are provided, as are methods and materials for identifying agents that can be used to increase PGRN polypeptide levels in mammals.

Abstract: This document relates to methods and materials for detecting mutations that can be linked to dementia. For example, methods and materials for detecting one or more mutations within PGRN nucleic acid are provided. This document also provides methods and materials for detecting the level of progranulin expression. In addition, this document relates to methods and materials for treating mammals having a neurodegenerative disorder (e.g., dementia). For example, methods and materials for increasing PGRN polypeptide levels in mammals are provided, as are methods and materials for identifying agents that can be used to increase PGRN polypeptide levels in mammals.

Abstract: This document relates to methods and materials involved in detecting mutations linked to dementia (e.g., frontotemporal lobar degeneration). For example, methods and materials for determining whether or not a mammal is homozygous for a mutant T allele of rs5848 are provided. This document also relates to methods and materials involved in treating mammals having or being susceptible to developing neurodegenerative disorders (e.g., frontotemporal lobar degeneration). For example, methods and materials for inhibiting the ability of miRNA to suppress GRN polypeptide expression in mammals are provided.