scholarly journals Structural pharmacology of GABAА receptors

2021 ◽  
Vol 15 (4) ◽  
pp. 44-53
Author(s):  
Alexey V. Rossokhin ◽  
Irina N. Sharonova
Keyword(s):  
Electron Microscopy ◽  
Structural Data ◽  
Receptor Activation ◽  
Physiological Effects ◽  
Gamma Aminobutyric Acid ◽  
Inhibitory Neurotransmitter ◽  
Main Target ◽  
Modulatory Sites ◽  
And Function ◽  
The Relationship

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the mammalian central nervous system (CNS), activating the inotropic type A receptors (GABAА receptors) to provide fast inhibition. GABAА receptors are the main target for various groups of drugs that are widely used in the treatment of CNS disorders. This review examines the relationship between the physiological effects of GABAА receptor activation and modulation by various substances (including medicinal compounds), the receptor's structure, and the interaction of these substances with specific modulatory sites. Recent advances in cryogenic electron microscopy have led to fundamental improvements in understanding the detailed organization and function of GABAА receptors. This review is based on both the latest structural data obtained from cryogenic electron microscopy and the results of biochemistry and electrophysiology studies, as well as molecular modelling.

Binding of Tetrahymena dynein to axonemes of Marsilea vestita lacking the outer dynein arm

1985 ◽  
Vol 73 (1) ◽  
pp. 299-310
Author(s):  
J.S. Hyams
Keyword(s):  
Electron Microscopy ◽  
Polyacrylamide Gel Electrophoresis ◽  
Valuable Insight ◽  
Marsilea Vestita ◽  
Thin Section Electron Microscopy ◽  
Section Electron ◽  
And Function ◽  
Relationship Of ◽  
The Relationship ◽  
Insight Into

Axonemes from the heterosporous water fern Marsilea vestita were fixed in the presence of tannic acid and examined by thin-section electron microscopy. Transverse sections revealed the normal 9+2 configuration except for the absence of the outer of the two dynein arms. Both arms were normally preserved in parallel preparations of Chlamydomonas axonemes. Isolated dynein from the ciliated protozoon Tetrahymena bound to Marsilea axonemes at the site normally occupied by the outer arm. Dynein binding was partially reversed by ATP as judged by both electron microscopy and polyacrylamide gel electrophoresis. This system should provide a valuable insight into the biochemistry and function of the inner dynein arm and the relationship of the two arms to motility in more conventionally equipped axonemes.

Individual human genomes frequently contain variants that have epistatic interactions

2020 ◽  
Author(s):  
Henry J Martell ◽  
Darren K Griffin ◽  
Mark N Wass
Keyword(s):  
Genetic Variation ◽  
Structural Data ◽  
Genome Project ◽  
Dimensional Structure ◽  
Protein Interfaces ◽  
Human Genomes ◽  
Synonymous Variant ◽  
And Function ◽  
The Relationship ◽  
Individual Human

AbstractThe availability of thousands of individual genomes provides many opportunities to understand genetic variation and the relationship to phenotype, particularly disease. However, this remains challenging as it is often difficult to identify if a non-synonymous variant alters protein structure and function. Many computational methods have been developed but they typically interpret individual variants in isolation, despite the possibility of variant-variant interactions. Here, we combine the genetic variation data present in the 1000 genome project with protein structural data to identify variant-variant interactions within individual human genomes. We find more than 4,000 combinations of variants that located close in 3D dimensional structure and more than 1,200 in protein-protein interfaces. Many variant combinations include amino acid changes that are compensatory such as maintaining charges or functional groups, thus supporting that these are coevolutionary events. This highlights the need for variant interpretation and precision medicine to consider the gestalt effects of variants.

Electron Microscopy in Cytology

1967 ◽  
Vol 25 ◽  
pp. 1-1
Author(s):  
F. S. Sjöstrand
Keyword(s):  
Electron Microscopy ◽  
Structural Data ◽  
Structure And Function ◽  
Common Type ◽  
Living Systems ◽  
Future Application ◽  
Cell Physiology ◽  
Biochemical Technique ◽  
And Function ◽  
Shed Light

The electron microscope as a tool for recording structural data at the molecular or supramolecular level will be discussed, particularly in connection with the important demonstration by means of electron microscopy of membranes as the most common type of supramolecular structure in cells. Structural analysis as a technique aiming at collecting information that can shed light on the function of living systems has gained tremendously by extending the range of study to molecular and intramolecular dimensions. Correlation of structure and function will be emphasized.Electron microscopy as applied to the analysis of the circuitry of nervous centers will be discussed.The basic problems involved in the application of electron microscopy to biochemical problems where the biochemical technique is used to analyze problems in cell physiology will be illustrated by proper examples.Some important prospects for future application of electron microscopy in Biology will be mentioned.

Studies on Leukemogenic and Sarcomagenic Viruses

1970 ◽  
Vol 28 ◽  
pp. 156-157
Author(s):  
Leon Dmochowski
Keyword(s):  
Electron Microscopy ◽  
Electron Microscope ◽  
Morphological Properties ◽  
Mode Of Development ◽  
Relationship Of ◽  
The Relationship

Electron microscopy has proved to be an invaluable discipline in studies on the relationship of viruses to the origin of leukemia, sarcoma, and other types of tumors in animals and man. The successful cell-free transmission of leukemia and sarcoma in mice, rats, hamsters, and cats, interpreted as due to a virus or viruses, was proved to be due to a virus on the basis of electron microscope studies. These studies demonstrated that all the types of neoplasia in animals of the species examined are produced by a virus of certain characteristic morphological properties similar, if not identical, in the mode of development in all types of neoplasia in animals, as shown in Fig. 1.

A SEM/TEM examination of a ceramic membrane

1986 ◽  
Vol 44 ◽  
pp. 682-683
Author(s):  
C.E. Voegele-Kliewer ◽  
A.D. McMaster ◽  
G.W. Dirks
Keyword(s):  
Electron Microscopy ◽  
Gas Separation ◽  
Ceramic Membrane ◽  
Hydrogen Iodide ◽  
Separation Processes ◽  
Corning Glass ◽  
Gas Transport Properties ◽  
Porous Microstructure ◽  
Microscopy Techniques ◽  
The Relationship

Materials other than polymers, e.g. ceramic silicates, are currently being investigated for gas separation processes. The permeation characteristics of one such material, Vycor (Corning Glass #1370), have been reported for the separation of hydrogen from hydrogen iodide. This paper will describe the electron microscopy techniques applied to reveal the porous microstructure of a Vycor membrane. The application of these techniques has led to an increased understanding in the relationship between the substructure and the gas transport properties of this material.

Use of human autoantibodies and immunoelectron microscopy to study structure and function of the nucleolus and nuclear bodies

1992 ◽  
Vol 50 (1) ◽  
pp. 506-507
Author(s):  
Robert L. Ochs
Keyword(s):  
Electron Microscopy ◽  
Structure And Function ◽  
Nuclear Bodies ◽  
Nuclear Interior ◽  
Coiled Bodies ◽  
Interchromatin Granules ◽  
And Function ◽  
Conventional Electron Microscopy ◽  
Perichromatin Granules ◽  
Perichromatin Fibrils

By conventional electron microscopy, the formed elements of the nuclear interior include the nucleolus, chromatin, interchromatin granules, perichromatin granules, perichromatin fibrils, and various types of nuclear bodies (Figs. 1a-c). Of these structures, all have been reasonably well characterized structurally and functionally except for nuclear bodies. The most common types of nuclear bodies are simple nuclear bodies and coiled bodies (Figs. 1a,c). Since nuclear bodies are small in size (0.2-1.0 μm in diameter) and infrequent in number, they are often overlooked or simply not observed in any random thin section. The rat liver hepatocyte in Fig. 1b is a case in point. Historically, nuclear bodies are more prominent in hyperactive cells, they often occur in proximity to nucleoli (Fig. 1c), and sometimes they are observed to “bud off” from the nucleolar surface.

Profile Imaging of Silicon Surface Reconstructions

1985 ◽  
Vol 43 ◽  
pp. 262-263
Author(s):  
O.L. Krivanek ◽  
G.J. Wood
Keyword(s):  
Electron Microscopy ◽  
Surface Structure ◽  
Structure Determination ◽  
Silicon Surface ◽  
Good Resolution ◽  
Surface Reconstructions ◽  
Bulk Structure ◽  
Point To Point ◽  
The Relationship

Electron microscopy at 0.2nm point-to-point resolution, 10-10 torr specimei region vacuum and facilities for in-situ specimen cleaning presents intere; ing possibilities for surface structure determination. Three methods for examining the surfaces are available: reflection (REM), transmission (TEM) and profile imaging. Profile imaging is particularly useful because it giv good resolution perpendicular as well as parallel to the surface, and can therefore be used to determine the relationship between the surface and the bulk structure.

Scanning tunneling microscopy (STM) of DNA and RNA

1989 ◽  
Vol 47 ◽  
pp. 34-35
Author(s):  
Patricia G. Arscott ◽  
Gil Lee ◽  
Victor A. Bloomfield ◽  
D. Fennell Evans
Keyword(s):  
Molecular Structures ◽  
Inorganic Materials ◽  
Resolving Power ◽  
Scanning Tunneling ◽  
Tunneling Microscopy ◽  
Form And Function ◽  
Dna And Rna ◽  
Calf Thymus ◽  
And Function ◽  
The Relationship

STM is one of the most promising techniques available for visualizing the fine details of biomolecular structure. It has been used to map the surface topography of inorganic materials in atomic dimensions, and thus has the resolving power not only to determine the conformation of small molecules but to distinguish site-specific features within a molecule. That level of detail is of critical importance in understanding the relationship between form and function in biological systems. The size, shape, and accessibility of molecular structures can be determined much more accurately by STM than by electron microscopy since no staining, shadowing or labeling with heavy metals is required, and there is no exposure to damaging radiation by electrons. Crystallography and most other physical techniques do not give information about individual molecules.We have obtained striking images of DNA and RNA, using calf thymus DNA and two synthetic polynucleotides, poly(dG-me5dC)·poly(dG-me5dC) and poly(rA)·poly(rU).

Crystal Structures of Fragments D and Double-D from Fibrinogen and Fibrin

1999 ◽  
Vol 82 (08) ◽  
pp. 271-276 ◽  
Author(s):  
Glen Spraggon ◽  
Stephen Everse ◽  
Russell Doolittle
Keyword(s):  
Electron Microscopy ◽  
High Resolution ◽  
Crystal Structures ◽  
Structure And Function ◽  
X Ray ◽  
Long Period ◽  
And Function

IntroductionAfter a long period of anticipation,1 the last two years have witnessed the first high-resolution x-ray structures of fragments from fibrinogen and fibrin.2-7 The results confirmed many aspects of fibrinogen structure and function that had previously been inferred from electron microscopy and biochemistry and revealed some unexpected features. Several matters have remained stubbornly unsettled, however, and much more work remains to be done. Here, we review several of the most significant findings that have accompanied the new x-ray structures and discuss some of the problems of the fibrinogen-fibrin conversion that remain unresolved. * Abbreviations: GPR—Gly-Pro-Arg-derivatives; GPRPam—Gly-Pro-Arg-Pro-amide; GHRPam—Gly-His-Arg-Pro-amide

Physicianship and the Rebirth of Medical Education

2018 ◽  
Author(s):  
J. Donald Boudreau ◽  
Eric Cassell ◽  
Abraham Fuks
Keyword(s):  
Medical Education ◽  
Educational Process ◽  
Medical Attention ◽  
Patient Centeredness ◽  
Goals Of Medicine ◽  
The Subject ◽  
Definition Of ◽  
And Function ◽  
William Osler ◽  
The Relationship

This book reimagines medical education and reconstructs its design. It originates from a reappraisal of the goals of medicine and the nature of the relationship between doctor and patient. The educational blueprint outlined is called the “Physicianship Curriculum” and rests on two linchpins. First is a new definition of sickness: Patients know themselves to be ill when they cannot pursue their purposes and goals in life because of impairments in functioning. This perspective represents a bulwark against medical attention shifting from patients to diseases. The curriculum teaches about patients as functional persons, from their anatomy to their social selves, starting in the first days of the educational program and continuing throughout. Their teaching also rests on the rock-solid grounding of medicine in the sciences and scientific understandings of disease and function. The illness definition and knowledge base together create a foundation for authentic patient-centeredness. Second, the training of physicians depends on and culminates in development of a unique professional identity. This is grounded in the historical evolution of the profession, reaching back to Hippocrates. It leads to reformulation of the educational process as clinical apprenticeships and moral mentorships. “Rebirth” in the title suggests that critical ingredients of medical education have previously been articulated. The book argues that the apprenticeship model, as experienced, enriched, taught, and exemplified by William Osler, constitutes a time-honored foundation. Osler’s “natural method of teaching the subject of medicine” is a precursor to the Physicianship Curriculum.

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