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At least 91 records · Page 5

State of the mitral valve in rabbits with hypokinesia

In hypokinesia, edema of all the layers of the mitral value was observed, which resulted in morphological changes of the cellular and noncellular components. An increase in ratio of elastic and collagenic fibers in the value was also observed along with and changes in their structural and staining properties. The observed changes can limit valve mobility and can result in manifestations of cardiac valve insufficiency, which is found clinically.

Strelkovska, V. Y.↗

Sympathetic preganglionic efferent and afferent neurons mediated by the greater splanchnic nerve in rabbit

As a part of the study of the vestibular-autonomic pathways involved in motion sickness, the location and the morphology of preganglionic sympathetic neurons (PSNs) projecting via the greater splanchnic nerve were examined. Retrograde labeling of neurons was obtained by application of horseradish peroxidase to the cut end of the greater splanchnic nerve. Labeled PSNs were found, ipsilaterally, within the T1 to T11 spinal cord segments, with the highest density of neurons in T6. Most PSNs were located within the intermediolateral column, but a significant portion also occurred within the lateral funiculus, the intercalated region, and the central autonomic area; the proportion of labeling between the four regions depended on the spinal cord segment.

Torigoe, Yasuhiro↗

Rapid Sample Insertion/Extraction Systems for Gamma Irradiation

The Rapid Sample Insertion/Extraction System for Gamma Irradiation, otherwise known as the "rabbit" system, was a four-week long project which included many different aspects; from coding an Arduino to building PVC piping to 3-D printing the "rabbit" capsules. The "rabbit" system is a system of PVC piping that allows a quick and efficient transfer of materials into/out of one of the irradiation chambers in the Gamma Irradiation Facility (GIF) with the use of a 3-D printed "rabbit." This "rabbit" encapsulates material to be irradiated and carries it from a position outside of the irradiation chamber to the basket inside of the chamber. The main purpose of this system is to save time and provide more exact data without any delays that normally occur when a person has to enter the chamber, retrieve data, and then analyze the data. This system should take measurements and retrieve the data instantaneously. The way in which the "rabbit" is sent through the PVC piping is with an advanced bi-directional, high-throughput pneumatic system, or a shop vacuum cleaner. When the vacuum is set to blow or suck then the "rabbit" will be pulled through the PVC piping to its intended destination and will hit sensors along the sides of the tubing when it reaches the end of the piping. These sensors tell the Arduino that the "rabbit" is finished moving throughout the tubing and stops a timer. Another timer is used to see how long the "rabbit" is being irradiated so when the "rabbit" reaches the sensors in the basket in the irradiation chamber another timer is started and it ends when the sensors no longer detect the "rabbit," which means that it has begun its journey back to the starting point.

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗

Additively Manufactured Pressure Limiting Irradiation Capsule for the High Flux Isotope Reactor

The Advanced Materials and Manufacturing Technologies (AMMT) program previously demonstrated an additively manufactured (AM) irradiation capsule (commonly referred to as a “rabbit”) from 316H stainless steel (SS) for insertion into the High Flux Isotope Reactor (HFIR) at Oak Ridge National Laboratory (ORNL)1. This report details efforts to design and fabricate an AM pressure limiting structure (PLS) into one of the end caps of a rabbit capsule and qualify it for insertion into HFIR. The PLS includes a thin cylindrical rupture wall, a shield, and internal supports to facilitate printing and ensure mechanical integrity. Its overall dimensions are 9-mm tall and 10-mm in diameter— equivalent to about one-fourth of the size of a AAA battery. The PLS maintains safe internal operating pressures for a rabbit capsule while in the reactor. Although this application is specific to HFIR, the approach lends itself to further applications in industrial, aeronautical, advanced space and power generation environments. Several PLS rabbits capsules have been successfully designed, fabricated, pressure tested, and qualified for future insertion into the HFIR for irradiation and post-irradiation evaluation.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗

Rapid and robust antibody Fab fragment crystallization utilizing edge-to-edge beta-sheet packing

Antibody therapeutics are one of the most important classes of drugs. Antibody structures have become an integral part of predicting the behavior of potential therapeutics, either directly or as the basis of modeling. Structures of Fab:antigen complexes have even greater value. While the crystallization and structure determination of Fabs is easy relative to many other protein classes, especially membrane proteins, broad screening and optimization of crystalline hits is still necessary. Through a comprehensive review of rabbit Fab crystal contacts and their incompatibility with human Fabs, we identified a small secondary structural element from the rabbit light chain constant domain potentially responsible for hindering the crystallization of human Fabs. Upon replacing the human kappa constant domain FG loop (HQGLSSP) with the two residue shorter rabbit loop (QGTTS), we dramatically improved the crystallization of human Fabs and Fab:antigen complexes. Our design, which we call “Crystal Kappa”, enables rapid crystallization of human fabs and fab complexes in a broad range of conditions, with less material in smaller screens or from dilute solutions.

59 BASIC BIOLOGICAL SCIENCES↗

Localization of the human 64kD autoantigen D1 to myofibrils in a subset of extraocular muscle fibers

PURPOSE. To evaluate the tissue-specific expression pattern of the 64kD human autoantigen D1, a tropomodulin-related protein that may be involved in thyroid-associated ophthalmopathy. METHODS. Recombinant 64kD human autoantigen D1 was generated in a bacterial expression system and used to immunize rabbits. Specific antibodies were affinity-purified and used for Western blots on normal and hyperthyroid rat and rabbit tissue, and immunofluorescence localization on cryosections of rat tissue. RESULTS. Anti-64kD human autoantigen D1 antibodies recognize specifically a approximately 70kD polypeptide in western blots of extraocular muscle, sternothyroid muscle, and smooth muscle. Immunofluorescence staining demonstrates that the 64kD human autoantigen D1 localizes to myofibrils in slow fibers from rat extraocular and sternothyroid muscle. The level of this protein is not altered in extraocular muscles from hyperthyroid rabbits. CONCLUSIONS. The 64kD human autoantigen D1 is expressed in slow fibers of extraocular and sternothyroid muscles as a component of myofibrils, and is not upregulated in conditions of hyperthyroidism.

Proteins/genetics/immunology/metabolism↗

Cross-reactive sarbecovirus antibodies induced by mosaic RBD nanoparticles

Broad immune responses are needed to mitigate viral evolution and escape. To induce antibodies against conserved receptor-binding domain (RBD) regions of SARS-like betacoronavirus (sarbecovirus) spike proteins that recognize SARS-CoV-2 variants of concern and zoonotic sarbecoviruses, we developed mosaic-8b RBD nanoparticles presenting eight sarbecovirus RBDs arranged randomly on a 60-mer nanoparticle. Mosaic-8b immunizations protected animals from challenges from viruses whose RBDs were matched or mismatched to those on nanoparticles. Here, we describe neutralizing mAbs isolated from mosaic-8b-immunized rabbits, some on par with Pemgarda, the only currently FDA-approved therapeutic mAb. Deep mutational scanning, in vitro selection of spike resistance mutations, and single-particle cryo-electron microscopy structures of spike–antibody complexes demonstrated targeting of conserved RBD epitopes. Rabbit mAbs included critical D-gene segment RBD-recognizing features in common with human anti-RBD mAbs, despite rabbit genomes lacking an equivalent human D-gene segment, thus demonstrating that the immune systems of humans and other mammals can utilize different antibody gene segments to arrive at similar modes of antigen recognition. These results suggest that animal models can be used to elicit anti-RBD mAbs with similar properties to those raised in humans, which can then be humanized for therapeutic use, and that mosaic RBD nanoparticle immunization coupled with multiplexed screening represents an efficient way to generate and select broadly cross-reactive therapeutic pan-sarbecovirus and pan-SARS-CoV-2 variant mAbs.

Science & Technology - Other Topics↗

Changes in sulfhydryl groups of honeybee glyceraldehyde phosphate dehydrogenase associated with generation of the intermediate plateau in its saturation kinetics

Honeybee and rabbit muscle GPDH were studied to obtain information at the chemical level regarding anomolous saturation kinetics of the honeybee enzyme. Results demonstrate that the enzyme's sulfhydryl groups are implicated in the process. Measured by DTNB titration, native honeybee GPDH has one less active SH than the native rabbit muscle enzyme and displays changes in overall sulfhydryl reactivity after preincubation with G-3-P or G-3-P plus NAD+. The total DTNB reactive sulfhydryls of rabbit muscle GPDH are not changed by preincubation with NAD+ or G-3-P; honeybee GPDH, under certain conductions of preincubation with these ligands, shows a decrease of two total DTNB reactive SH groups. This difference has been confirmed by an independent experiment in which the two enzymes were carboxymethylated with C-14 bromoacetic acid.

Gelb, W. G.↗