Microscopy, Electron Microscopy, Elemental Analysis, Image Analysis, Digital Photography, And Telepathology Applications In Pharmaceuticals Research

1999 ◽  
Vol 5 (S2) ◽  
pp. 6-7
Author(s):  
G. Argentieri ◽  
P. Grosenstein ◽  
K. Killary
Keyword(s):  
Electron Microscopy ◽  
Image Analysis ◽  
Quality Assurance ◽  
Drug Discovery ◽  
Research And Development ◽  
Light And Electron Microscopy ◽  
Pharmaceutical Research ◽  
Cost Effective ◽  
Wide Range ◽  
Functional Areas

Light and electron microscopy are exceedingly versatile disciplines having many applications in pharmaceutical research. Many corporate and university facilities are organized with a centralized microscopy laboratory that serves the needs of many different investigators. This is also true at the Novartis Pharmaceuticals Corporation in East Hanover, New Jersey. A centralized microscopy laboratory is not only more efficient, but also most cost effective. The microscopy lab at Novartis is designed to meet the needs for a wide range of applications serving all of Research and Development. The lab contains seven functional areas for microscopy applications. A large preparation and processing area, necropsy, microtomy, TEM, SEM, wet and dry dark rooms, and an image analysis suite including telepathology, complete the lab.Microscopy service is widely used in Pathology, Toxicology, Drug Discovery, Technical Research and Development, Production and Quality Assurance, and Compliance. Microscopy services have also been involved in marketing (packaging labels and commercials) for Novartis products.

A Critical and Concise Review of Mass Spectrometry Applied to Imaging in Drug Discovery

2020 ◽  
Vol 25 (9) ◽  
pp. 963-976
Author(s):  
Richard J. A. Goodwin ◽  
Zoltan Takats ◽  
Josephine Bunch
Keyword(s):  
Mass Spectrometry ◽  
Drug Discovery ◽  
Research And Development ◽  
Unmet Need ◽  
Pharmaceutical Research ◽  
Vital Role ◽  
Therapeutic Modalities ◽  
Concise Review ◽  
Program Attrition ◽  
Endogenous Metabolites

During the past decade, mass spectrometry imaging (MSI) has become a robust and versatile methodology to support modern pharmaceutical research and development. The technologies provide data on the biodistribution, metabolism, and delivery of drugs in tissues, while also providing molecular maps of endogenous metabolites, lipids, and proteins. This allows researchers to make both pharmacokinetic and pharmacodynamic measurements at cellular resolution in tissue sections or clinical biopsies. Despite drug imaging within samples now playing a vital role within research and development (R&D) in leading pharmaceutical companies, however, the challenges in turning compounds into medicines continue to evolve as rapidly as the technologies used to discover them. The increasing cost of development of new and emerging therapeutic modalities, along with the associated risks of late-stage program attrition, means there is still an unmet need in our ability to address an increasing array of challenging bioanalytical questions within drug discovery. We require new capabilities and strategies of integrated imaging to provide context for fundamental disease-related biological questions that can also offer insights into specific project challenges. Integrated molecular imaging and advanced image analysis have the opportunity to provide a world-class capability that can be deployed on projects in which we cannot answer the question with our battery of established assays. Therefore, here we will provide an updated concise review of the use of MSI for drug discovery; we will also critically consider what is required to embed MSI into a wider evolving R&D landscape and allow long-lasting impact in the industry.

scholarly journals Novel Approach for Characterizing Ubiquitin E3 Ligase Function

2010 ◽  
Vol 15 (10) ◽  
pp. 1220-1228 ◽  
Author(s):  
Jeffrey G. Marblestone ◽  
K. G. Suresh Kumar ◽  
Michael J. Eddins ◽  
Craig A. Leach ◽  
David E. Sterner ◽  
...  
Keyword(s):  
Drug Discovery ◽  
High Throughput Screening ◽  
E3 Ligase ◽  
Cost Effective ◽  
Ubiquitin Proteasome System ◽  
Dependent Manner ◽  
Ubiquitin Chain ◽  
E3 Ligases ◽  
Effective Manner ◽  
Wide Range

The ubiquitin-proteasome system is central to the regulation of numerous cellular events, and dysregulation may lead to disease pathogenesis. E3 ubiquitin ligases typically function in concert with E1 and E2 enzymes to recruit specific substrates, thereby coordinating their ubiquitylation and subsequent proteasomal degradation or cellular activity. E3 ligases have been implicated in a wide range of pathologies, and monitoring their activity in a rapid and cost-effective manner would be advantageous in drug discovery. The relative lack of high-throughput screening (HTS)–compliant E3 ligase assays has significantly hindered the discovery of E3 inhibitors. Herein, the authors describe a novel HTS-compliant E3 ligase assay platform that takes advantage of a ubiquitin binding domain’s inherent affinity for polyubiquitin chains, permitting the analysis of ubiquitin chain formation in an E3 ligase-dependent manner. This assay has been used successfully with members of both the RING and HECT families, demonstrating the platform’s broad utility for analyzing a wide range of E3 ligases. The utility of the assay platform is demonstrated by the identification of inhibitors of the E3 ligase CARP2. As the number of E3 ligases associated with various disease states increases, the ability to quantitate the activity of these enzymes in an expeditious manner becomes imperative in drug discovery.

Applications Of TEM and image analysis in impact-modified thermoplastics

1987 ◽  
Vol 45 ◽  
pp. 514-515
Author(s):  
R.T. Chen
Keyword(s):  
Thin Film ◽  
Electron Microscopy ◽  
Image Analysis ◽  
Cross Sections ◽  
Processing Conditions ◽  
Heavy Atoms ◽  
Thin Sectioning ◽  
Wide Range ◽  
Rubber Particles ◽  
Carbon Coated

Polymers can be blended to produce improved properties appropriate for a wide range of applications. For example, rubbers when added to rigid thermoplastic polymers produce blends with improved impact properties. Generally, the properties of blends are dictated by phase morphology, which can be controlled by processing conditions and chemical composition.This study demonstrates that TEM/image analysis can be used to study deformation of dispersed rubber particles in a matrix and to quantify phase morphologies for process optimization. For TEM, ultrathin specimens were produced by microtomy and stained with heavy atoms to enhance contrast between the different phases. In the present examples, thin film samples were embedded in epoxy and sectioned on a LKB Ultramicrotome. For bulk samples, cryogenic thin sectioning was performed using a Reichert Cryo Ultramicrotome. The thin cross-sections were then vapor stained with OsO4. and carbon coated. Electron microscopy was performed on a JEOL 100CX TEM.

scholarly journals Volume-CLEM: a method for correlative light and electron microscopy in three dimensions

2019 ◽  
Vol 317 (6) ◽  
pp. L778-L784 ◽  
Author(s):  
Jan Hegermann ◽  
Christoph Wrede ◽  
Susanne Fassbender ◽  
Ronja Schliep ◽  
Matthias Ochs ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Light And Electron Microscopy ◽  
Three Dimensional ◽  
Fluorescent Labeling ◽  
Three Dimensions ◽  
Data Sets ◽  
New Approach ◽  
3D Data ◽  
Wide Range ◽  
3D Em

Generation of three-dimensional (3D) data sets from serial sections of tissues imaged by light microscopy (LM) allows identification of rare structures by morphology or fluorescent labeling. Here, we demonstrate a workflow for correlative LM and electron microscopy (EM) from 3D LM to 3D EM, using the same sectioned material for both methods consecutively. The new approach is easy to reproduce in routine EM laboratories and applicable to a wide range of organs and research questions.

scholarly journals Dedicated setup for the photoconversion of fluorescent dyes for functional electron microscopy

2019 ◽  
Author(s):  
Katharine L. Dobson ◽  
Carmel L. Howe ◽  
Yuri Nishimura ◽  
Vincenzo Marra
Keyword(s):  
Electron Microscopy ◽  
Fluorescent Dyes ◽  
Lucifer Yellow ◽  
Light And Electron Microscopy ◽  
Region Of Interest ◽  
Cost Effective ◽  
Cortical Slice ◽  
Time Required ◽  
And Function ◽  
Established Technique

AbstractHere, we describe a cost-effective setup for targeted photoconversion of fluorescent signals into electron dense ones. This approach has offered invaluable insights in the morphology and function of fine neuronal structures. The technique relies on the localized oxidation of diaminobenzidine (DAB) mediated by excited fluorophores. This paper includes a detailed description of how to build a simple photoconversion setup that can increase reliability and throughput of this well-established technique. The system described here, is particularly well-suited for thick neuronal tissue, where light penetration and oxygen diffusion may be limiting DAB oxidation. To demonstrate the system, we use Correlative Light and Electron Microscopy (CLEM) to visualize functionally-labelled individual synaptic vesicles released onto an identified layer 5 neuron in an acute cortical slice. The setup significantly simplifies the photoconversion workflow, increasing the depth of photoillumination, improving the targeting of the region of interest and reducing the time required to process each individual samples. We have tested this setup extensively for the photoconversion of FM 1-43FX and Lucifer Yellow both excited at 473 nm. In principle, the system can be adapted to any dye or nanoparticle able to oxidize DAB when excited by a specific light wavelength.

Fine structure of the giant cells induced by Meloidogyne javanica in lima bean

1984 ◽  
Vol 62 (3) ◽  
pp. 429-436 ◽  
Author(s):  
F. Fattah ◽  
J. M. Webster
Keyword(s):  
Electron Microscopy ◽  
Fine Structure ◽  
Light And Electron Microscopy ◽  
Lima Bean ◽  
Meloidogyne Javanica ◽  
Giant Cells ◽  
Egg Laying ◽  
Phaseolus Lunatus ◽  
Wide Range

Giant cells associated with egg-laying females of Meloidogyne javanica in lima bean, Phaseolus lunatus cv. L-136, were examined by light and electron microscopy. These giant cells have characteristics that are typical of nematode-induced giant cells in a wide range of hosts, but they differ in that they (i) are less closely associated with xylem vessels, (ii) contain a very large number of plastids which are devoid of starch grains, and (iii) contain several different forms of cytoplasmic crystals. One form of the crystal is associated with a large number of "spiny" vesicles. The possible role of these features, especially the crystals, in the giant cell response of lima bean is discussed.

Seeing the Forest for the Trees: Selective Staining and Contrast Enhancement Methods for Biological Electron Microscopy

2001 ◽  
Vol 7 (S2) ◽  
pp. 766-767
Author(s):  
M. H. Ellisman
Keyword(s):  
Electron Microscopy ◽  
Electron Tomography ◽  
Light And Electron Microscopy ◽  
Fluorescent Compound ◽  
Selective Staining ◽  
3 Dimensional ◽  
Cellular Processes ◽  
Wide Range ◽  
Invaluable Tool ◽  
Versatile Technique

Electron tomography has proven to be an invaluable tool for studying the 3-dimensional organization of a wide range of structures, from large cellular processes down to individual macromolecular complexes. An important requirement for electron tomography of thick specimens is the need for selective staining to delineate the structure of interest from other cellular constituents. of particular usefulness in this regard is the method of fluorescence photooxidation, whereby the reactive oxygen generated by a fluorescent compound is used to oxidize diaminobenzidine into a reaction product that can then be visualized with the electron microscope. The main advantages of this method are that not only does it allow for excellent correlated light and electron microscopy, but also the relatively small size of the oxidizing agent used allows for excellent 3-D labeling with high resolution.This method has proven to be a particularly versatile technique.

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