scholarly journals Spatial molecular profiling: platforms, applications and analysis tools

2020 ◽  
Author(s):  
Minzhe Zhang ◽  
Thomas Sheffield ◽  
Xiaowei Zhan ◽  
Qiwei Li ◽  
Donghan M Yang ◽  
...  
Keyword(s):  
Spatial Organization ◽  
Spatial Information ◽  
Molecular Profiling ◽  
Tissue Imaging ◽  
Imaging Data ◽  
Tissue Heterogeneity ◽  
Tissue Dissociation ◽  
Recent Developments ◽  
Spatial Locations

Abstract Molecular profiling technologies, such as genome sequencing and proteomics, have transformed biomedical research, but most such technologies require tissue dissociation, which leads to loss of tissue morphology and spatial information. Recent developments in spatial molecular profiling technologies have enabled the comprehensive molecular characterization of cells while keeping their spatial and morphological contexts intact. Molecular profiling data generate deep characterizations of the genetic, transcriptional and proteomic events of cells, while tissue images capture the spatial locations, organizations and interactions of the cells together with their morphology features. These data, together with cell and tissue imaging data, provide unprecedented opportunities to study tissue heterogeneity and cell spatial organization. This review aims to provide an overview of these recent developments in spatial molecular profiling technologies and the corresponding computational methods developed for analyzing such data.

scholarly journals Reconstruction of cell spatial organization based on ligand-receptor mediated self-assembly

2020 ◽  
Author(s):  
Xianwen Ren ◽  
Guojie Zhong ◽  
Qiming Zhang ◽  
Lei Zhang ◽  
Yujie Sun ◽  
...  
Keyword(s):  
Self Assembly ◽  
Spatial Organization ◽  
Spatial Information ◽  
Cell Types ◽  
Cellular Interaction ◽  
Great Promise ◽  
Cellular Interactions ◽  
Tumor Microenvironments ◽  
Tissue Dissociation

AbstractSingle-cell RNA sequencing (scRNA-seq) has revolutionized transcriptomic studies by providing unprecedented cellular and molecular throughputs, but spatial information of individual cells is lost during tissue dissociation. While imaging-based technologies such as in situ sequencing show great promise, technical difficulties currently limit their wide usage. Since cellular spatial organization is inherently encoded by cell identity and can be reconstructed, at least in part, by ligand-receptor interactions, here we present CSOmap, a computational strategy to infer cellular interaction from scRNA-seq. We show that CSOmap can successfully recapitulate the spatial organization of tumor microenvironments for multiple cancers and reveal molecular determinants of cellular interactions. Further, CSOmap readily simulates perturbation of genes or cell types to gain novel biological insights, especially into how immune cells interact in the tumor microenvironment. CSOmap can be widely applicable to interrogate cellular organizations based on scRNA-seq data for various tissues in diverse systems.

Neurochemistry of L-Glutamate Transport in the CNS: A Review of Thirty Years of Progress

2001 ◽  
Vol 66 (9) ◽  
pp. 1315-1340 ◽  
Author(s):  
Vladimir J. Balcar ◽  
Akiko Takamoto ◽  
Yukio Yoneda
Keyword(s):  
Molecular Biology ◽  
Glutamate Transport ◽  
Mammalian Brain ◽  
Activity Data ◽  
System A ◽  
Recent Developments ◽  
The Central Nervous System ◽  
Health And Disease ◽  
Disease Analysis

The review highlights the landmark studies leading from the discovery and initial characterization of the Na+-dependent "high affinity" uptake in the mammalian brain to the cloning of individual transporters and the subsequent expansion of the field into the realm of molecular biology. When the data and hypotheses from 1970's are confronted with the recent developments in the field, we can conclude that the suggestions made nearly thirty years ago were essentially correct: the uptake, mediated by an active transport into neurons and glial cells, serves to control the extracellular concentrations of L-glutamate and prevents the neurotoxicity. The modern techniques of molecular biology may have provided additional data on the nature and location of the transporters but the classical neurochemical approach, using structural analogues of glutamate designed as specific inhibitors or substrates for glutamate transport, has been crucial for the investigations of particular roles that glutamate transport might play in health and disease. Analysis of recent structure/activity data presented in this review has yielded a novel insight into the pharmacological characteristics of L-glutamate transport, suggesting existence of additional heterogeneity in the system, beyond that so far discovered by molecular genetics. More compounds that specifically interact with individual glutamate transporters are urgently needed for more detailed investigations of neurochemical characteristics of glutamatergic transport and its integration into the glutamatergic synapses in the central nervous system. A review with 162 references.

scholarly journals Molecular Modeling of Histamine Receptors—Recent Advances in Drug Discovery

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1778
Author(s):  
Pakhuri Mehta ◽  
Przemysław Miszta ◽  
Sławomir Filipek
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Molecular Modeling ◽  
Molecular Targets ◽  
Histamine Receptors ◽  
Experimental Characterization ◽  
Complex Disorders ◽  
Theoretical Investigations ◽  
Recent Developments

The recent developments of fast reliable docking, virtual screening and other algorithms gave rise to discovery of many novel ligands of histamine receptors that could be used for treatment of allergic inflammatory disorders, central nervous system pathologies, pain, cancer and obesity. Furthermore, the pharmacological profiles of ligands clearly indicate that these receptors may be considered as targets not only for selective but also for multi-target drugs that could be used for treatment of complex disorders such as Alzheimer’s disease. Therefore, analysis of protein-ligand recognition in the binding site of histamine receptors and also other molecular targets has become a valuable tool in drug design toolkit. This review covers the period 2014–2020 in the field of theoretical investigations of histamine receptors mostly based on molecular modeling as well as the experimental characterization of novel ligands of these receptors.

scholarly journals Ultrasonic Time-of-Flight Computed Tomography for Investigation of Batch Crystallisation Processes

Sensors ◽  
2021 ◽  
Vol 21 (2) ◽  
pp. 639
Author(s):  
Panagiotis Koulountzios ◽  
Tomasz Rymarczyk ◽  
Manuchehr Soleimani
Keyword(s):  
Spatial Information ◽  
Injection Rate ◽  
Ultrasound Tomography ◽  
Measurement Systems ◽  
Process Dynamics ◽  
Tomography System ◽  
Ultrasonic Time ◽  
Crystallisation Process ◽  
Liquid Suspensions

Crystallisation is a crucial step in many industrial processes. Many sensors are being investigated for monitoring such processes to enhance the efficiency of them. Ultrasound techniques have been used for particle sizing characterization of liquid suspensions, in crystallisation process. An ultrasound tomography system with an array of ultrasound sensors can provide spatial information inside the process when compared to single-measurement systems. In this study, the batch crystallisation experiments have been conducted in a lab-scale reactor in calcium carbonate crystallisation. Real-time ultrasound tomographic imaging is done via a contactless ultrasound tomography sensor array. The effect of the injection rate and the stirring speed was considered as two control parameters in these crystallisation functions. Transmission mode ultrasound tomography comprises 32 piezoelectric transducers with central frequency of 40 kHz has been used. The process-based experimental investigation shows the capability of the proposed ultrasound tomography system for crystallisation process monitoring. Information on process dynamics, as well as process malfunction, can be obtained via the ultrasound tomography system.

scholarly journals Genome-wide binding potential and regulatory activity of the glucocorticoid receptor’s monomeric and dimeric forms

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Thomas A. Johnson ◽  
Ville Paakinaho ◽  
Sohyoung Kim ◽  
Gordon L. Hager ◽  
Diego M. Presman
Keyword(s):  
Receptor Binding ◽  
Site Response ◽  
Physiological Role ◽  
Binding Potential ◽  
Open Chromatin ◽  
Imaging Data ◽  
Response Elements ◽  
Genome Wide ◽  
Genomic Studies

AbstractA widely regarded model for glucocorticoid receptor (GR) action postulates that dimeric binding to DNA regulates unfavorable metabolic pathways while monomeric receptor binding promotes repressive gene responses related to its anti-inflammatory effects. This model has been built upon the characterization of the GRdim mutant, reported to be incapable of DNA binding and dimerization. Although quantitative live-cell imaging data shows GRdim as mostly dimeric, genomic studies based on recovery of enriched half-site response elements suggest monomeric engagement on DNA. Here, we perform genome-wide studies on GRdim and a constitutively monomeric mutant. Our results show that impairing dimerization affects binding even to open chromatin. We also find that GRdim does not exclusively bind half-response elements. Our results do not support a physiological role for monomeric GR and are consistent with a common mode of receptor binding via higher order structures that drives both the activating and repressive actions of glucocorticoids.

Managing the Edentulous Mandible using Recent Technological Developments: A Case Study

2013 ◽  
Vol 2 (2) ◽  
pp. 50-54
Author(s):  
Ashok Sethi ◽  
Thomas Kaus ◽  
Naresh Sharma ◽  
Peter Sochor
Keyword(s):  
Computed Tomography ◽  
Spatial Information ◽  
Imaging Techniques ◽  
Accurate Information ◽  
Imaging Data ◽  
Surgical Guide ◽  
Prosthetic Reconstruction ◽  
Anterior Teeth ◽  
Edentulous Mandible ◽  
Cad Cam

Safe clinical practice in implant dentistry requires an accurate investigation of the availability of bone for implant placement and the avoidance of critical anatomical structures. Modern imaging techniques using computed tomography (CT) and cone beam computed tomography (CBCT) provide the clinician with the required information. The imaging thus obtained provides accurate representation of the height, width and length of the available bone.1 In addition, whenever adequate radiation dose is used, accurate information about the bone density in Hounsfield units can be obtained. Important spatial information regarding the orientation of the ridges and the relationship to the proposed prosthetic reconstruction can be obtained with the aid of radiopaque templates during the acquisition of CT scan data. Modern software also provides the facility to decide interactively upon the positioning of the implants and is able to relate this to a stereolithographic model constructed from the imaging data. A surgical guide for the accurate positioning of the implants can be constructed. The construction of screw retained prostheses is fraught with difficulties regarding the accuracy of the construction. Accurate fit of the prosthesis is difficult to obtain due to the inherent errors in impression taking, component discrepancies, investing and casting inaccuracies.2,3 CAD/CAM technology eliminates the inaccuracies involved with the investing and casting of superstructures. Clinical Case This case describes the management of an 84 year old female patient, who had recently lost her remaining mandibular anterior teeth. This resulted in the patient's inability to wear conventional dentures in the mandible.

The Membrane Skeleton of Pseudomicrothorax

1991 ◽  
Vol 100 (4) ◽  
pp. 707-715 ◽  
Author(s):  
IRM HUTTENLAUCH ◽  
ROBERT K. PECK
Keyword(s):  
Spatial Organization ◽  
Membrane Skeleton ◽  
Basal Bodies ◽  
Structural Elements ◽  
Or Groups ◽  
Positive Immunoreactivity ◽  
Cortical Membranes ◽  
Cytoskeletal Elements

The membrane skeleton, or epiplasm, is part of the structurally complex ciliate cortex. It is thought to have skeletal functions concerning the spatial organization of cortical elements such as the basal bodies. Here we report the biochemical and immunological characterization of some components of the purified epiplasm of Pseudomicrothorax dubius. The epiplasm proteins consist of two quantitatively major groups of proteins, one of 76–80x103Mr, the other of 11–13x103Mr, which appear to be the principal structural elements of the epiplasm, and a series of minor components of 62–18x103Mr. Based upon lectin labeling and glycosidase treatment, some of the latter have been identified as glycoproteins. Using affinity-purified antibodies specific for individual glycoproteins or groups of glycoproteins, we were able to localize them in situ by immunoelectron microscopical methods. This in situ localization demonstrates that the glycosylated epitopes, unlike the glycoresidues of membrane proteins, are distributed throughout the entire epiplasmic layer rather than being restricted to regions adjacent to the cortical membranes. Thus, these proteins represent glycosylated, cytoskeletal elements. At least one of these glycoproteins (Mr 62x103) shows positive immunoreactivity with a monoclonal antibody (Pruss anti-IFA) recognizing most intermediate filament (IF) proteins, indicating that IF proteins might be present in protozoan cytoskeletons.

Abstract 23: Characterization of MitoTimer, a Novel Tool for Monitoring Mitochondrial Turnover

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Christine A Thornton ◽  
Allen M Andres ◽  
Genaro Hernandez ◽  
Jon Sin ◽  
Roberta Gottlieb
Keyword(s):  
Protein Import ◽  
Spatial Information ◽  
Fluorescent Protein ◽  
Mitochondrial Dynamics ◽  
Inducible Promoter ◽  
Subcellular Fractionation ◽  
Fluorescent Reporter ◽  
Hek 293 ◽  
Mitochondrial Turnover

Fluorescent Timer, or DsRed1-E5, is a mutant of the red fluorescent protein, dsRed, developed by Terskikh and colleagues. Its fluorescence shifts over time from green to red as the protein matures. This molecular clock gives temporal and spatial information on protein turnover. To visualize mitochondrial turnover, we targeted Timer to the mitochondrial matrix with a mitochondrial targeting sequence (coined “MitoTimer”) and cloned it into a tetracycline-inducible promoter construct to regulate its expression. Here we report characterization of this novel fluorescent reporter for mitochondrial dynamics. Tet-On HEK 293 cells were transfected with pTRE-tight-MitoTimer and induced production with doxycycline. Mitochondrial distribution was demonstrated by fluorescence microscopy and verified by subcellular fractionation and western blot analysis. Doxycycline addition for as little as 1hr was sufficient to label mitochondria. MitoTimer was detected as early as 4hr following doxycycline addition, and persisted in mitochondria for at least 72hr. The color-specific conformation of MitoTimer was stable after fixation with 4% paraformaldehyde. MitoTimer matured to red fluorescence within 48hr, at which time a second pulse of doxycycline induced expression of green (immature) MitoTimer which was selectively incorporated into a subset of mitochondria actively engaged in protein import. The extent of new protein incorporation during a second pulse was increased under conditions of mito-biogenesis and reduced if mitochondrial membrane potential was dissipated. We conclude that MitoTimer can be used to monitor mitophagy and biogenesis.

Characterization of Geometrical and Temporal Properties of Large-scale Motions in Turbulent Flows

2021 ◽  
Author(s):  
Christina Tsai ◽  
Kuang-Ting Wu
Keyword(s):  
Turbulent Flow ◽  
Turbulent Flows ◽  
Coherent Structures ◽  
Large Scale ◽  
Streamwise Velocity ◽  
Turbulent Structures ◽  
Temporal Properties ◽  
Turbulent Statistics ◽  
Spatial Locations

<p>It is demonstrated that turbulent boundary layers are populated by a hierarchy of recurrent structures, normally referred to as the coherent structures. Thus, it is desirable to gain a better understanding of the spatial-temporal characteristics of coherent structures and their impact on fluid particles. Furthermore, the ejection and sweep events play an important role in turbulent statistics. Therefore, this study focuses on the characterizations of flow particles under the influence of the above-mentioned two structures.</p><div><span>With regard to the geometry of turbulent structures, </span><span>Meinhart & Adrian (1995) </span>first highlighted the existence of large and irregularly shaped regions of uniform streamwise momentum zone (hereafter referred to as a uniform momentum zone, or UMZs), regions of relatively similar streamwise velocity with coherence in the streamwise and wall-normal directions.  <span>Subsequently, </span><span>de Silva et al. (2017) </span><span>provided a detection criterion that had previously been utilized to locate the uniform momentum zones (UMZ) and demonstrated the application of this criterion to estimate the spatial locations of the edges that demarcates UMZs.</span></div><div> </div><div>In this study, detection of the existence of UMZs is a pre-process of identifying the coherent structures. After the edges of UMZs are determined, the identification procedure of ejection and sweep events from turbulent flow DNS data should be defined. As such, an integrated criterion of distinguishing ejection and sweep events is proposed. Based on the integrated criterion, the statistical characterizations of coherent structures from available turbulent flow data such as event durations, event maximum heights, and wall-normal and streamwise lengths can be presented.</div>

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