The functional vascular anatomy of the swine for research

Vascular ◽  
2021 ◽  
pp. 170853812199650
Author(s):  
Joseph Edwards ◽  
Hossam Abdou ◽  
Neerav Patel ◽  
Marta J Madurska ◽  
Kelly Poe ◽  
...  

Objectives Swine ( Sus Scrofa) are utilized broadly in research settings, given similarities to human vessel size and function; however, there are some important differences for clinicians to understand in order to interpret and perform translational research. This review article uses angiograms acquired in the course of a translational research program to present a description of the functional anatomy of the swine. Methods Digital subtraction angiography and computed tomography angiography were obtained throughout the course of multiple studies utilizing power injection with iodinated contrast. Subtracted two-dimensional images and three-dimensional multiplanar reformations were utilized post image acquisition to create maximal intensity projections and three-dimensional renderings of using open-source software (OsiriX). These imaging data are presented along with vessel measurements for reference. Results An atlas highlighting swine vascular anatomy, with an emphasis on inter-species differences that may influence how studies are conducted and interpreted, was compiled. Conclusions Swine are utilized in broad-reaching fields for preclinical research. While many similarities between human and swine vasculature exist, there are important differences to consider when conducting and interpreting research. This review article highlights these differences and presents accompanying images to inform clinicians gaining experience in swine research.

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1694
Author(s):  
Jhalak Dholakia ◽  
Carly Scalise ◽  
Rebecca C. Arend

Gynecologic malignancies are increasing in incidence, with a plateau in clinical outcomes necessitating novel treatment options. Immunotherapy and modulation of the tumor microenvironment are rapidly developing fields of interest in gynecologic oncology translational research; examples include the PD-1 (programmed cell death 1) and CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) axes and the Wnt pathway. However, clinical successes with these agents have been modest and lag behind immunotherapy successes in other malignancies. A thorough contextualization of preclinical models utilized in gynecologic oncology immunotherapy research is necessary in order to effectively and efficiently develop translational medicine. These include murine models, in vitro assays, and three-dimensional human-tissue-based systems. Here, we provide a comprehensive review of preclinical models for immunotherapy in gynecologic malignancies, including benefits and limitations of each, in order to inform study design and translational research models. Improved model design and implementation will optimize preclinical research efficiency and increase the translational value to positive findings, facilitating novel treatments that improve patient outcomes.


2018 ◽  
Vol 314 (6) ◽  
pp. F1145-F1153 ◽  
Author(s):  
Olumide Ogunlade ◽  
John J. Connell ◽  
Jennifer L. Huang ◽  
Edward Zhang ◽  
Mark F. Lythgoe ◽  
...  

Noninvasive imaging of the kidney vasculature in preclinical murine models is important for the assessment of renal development, studying diseases and evaluating new therapies but is challenging to achieve using existing imaging modalities. Photoacoustic imaging is a promising new technique that is particularly well suited to visualizing the vasculature and could provide an alternative to existing preclinical imaging methods for studying renal vascular anatomy and function. To investigate this, an all-optical Fabry-Perot-based photoacoustic scanner was used to image the abdominal region of mice. High-resolution three-dimensional, noninvasive, label-free photoacoustic images of the mouse kidney and renal vasculature were acquired in vivo. The scanner was also used to visualize and quantify differences in the vascular architecture of the kidney in vivo due to polycystic kidney disease. This study suggests that photoacoustic imaging could be utilized as a novel preclinical imaging tool for studying the biology of renal disease.


Author(s):  
M. Boublik ◽  
W. Hellmann ◽  
F. Jenkins

The present knowledge of the three-dimensional structure of ribosomes is far too limited to enable a complete understanding of the various roles which ribosomes play in protein biosynthesis. The spatial arrangement of proteins and ribonuclec acids in ribosomes can be analysed in many ways. Determination of binding sites for individual proteins on ribonuclec acid and locations of the mutual positions of proteins on the ribosome using labeling with fluorescent dyes, cross-linking reagents, neutron-diffraction or antibodies against ribosomal proteins seem to be most successful approaches. Structure and function of ribosomes can be correlated be depleting the complete ribosomes of some proteins to the functionally inactive core and by subsequent partial reconstitution in order to regain active ribosomal particles.


Author(s):  
Peter Sterling

The synaptic connections in cat retina that link photoreceptors to ganglion cells have been analyzed quantitatively. Our approach has been to prepare serial, ultrathin sections and photograph en montage at low magnification (˜2000X) in the electron microscope. Six series, 100-300 sections long, have been prepared over the last decade. They derive from different cats but always from the same region of retina, about one degree from the center of the visual axis. The material has been analyzed by reconstructing adjacent neurons in each array and then identifying systematically the synaptic connections between arrays. Most reconstructions were done manually by tracing the outlines of processes in successive sections onto acetate sheets aligned on a cartoonist's jig. The tracings were then digitized, stacked by computer, and printed with the hidden lines removed. The results have provided rather than the usual one-dimensional account of pathways, a three-dimensional account of circuits. From this has emerged insight into the functional architecture.


Author(s):  
M. Boublik ◽  
N. Robakis ◽  
J.S. Wall

The three-dimensional structure and function of biological supramolecular complexes are, in general, determined and stabilized by conformation and interactions of their macromolecular components. In the case of ribosomes, it has been suggested that one of the functions of ribosomal RNAs is to act as a scaffold maintaining the shape of the ribosomal subunits. In order to investigate this question, we have conducted a comparative TEM and STEM study of the structure of the small 30S subunit of E. coli and its 16S RNA.The conventional electron microscopic imaging of nucleic acids is performed by spreading them in the presence of protein or detergent; the particles are contrasted by electron dense solution (uranyl acetate) or by shadowing with metal (tungsten). By using the STEM on freeze-dried specimens we have avoided the shearing forces of the spreading, and minimized both the collapse of rRNA due to air drying and the loss of resolution due to staining or shadowing. Figure 1, is a conventional (TEM) electron micrograph of 30S E. coli subunits contrasted with uranyl acetate.


Author(s):  
G. Jacobs ◽  
F. Theunissen

In order to understand how the algorithms underlying neural computation are implemented within any neural system, it is necessary to understand details of the anatomy, physiology and global organization of the neurons from which the system is constructed. Information is represented in neural systems by patterns of activity that vary in both their spatial extent and in the time domain. One of the great challenges to microscopists is to devise methods for imaging these patterns of activity and to correlate them with the underlying neuroanatomy and physiology. We have addressed this problem by using a combination of three dimensional reconstruction techniques, quantitative analysis and computer visualization techniques to build a probabilistic atlas of a neural map in an insect sensory system. The principal goal of this study was to derive a quantitative representation of the map, based on a uniform sample of afferents that was of sufficient size to allow statistically meaningful analyses of the relationships between structure and function.


The review article discusses the possibilities of using fractal mathematical analysis to solve scientific and applied problems of modern biology and medicine. The authors show that only such an approach, related to the section of nonlinear mechanics, allows quantifying the chaotic component of the structure and function of living systems, that is a priori important additional information and expands, in particular, the possibilities of diagnostics, differential diagnosis and prediction of the course of physiological and pathological processes. A number of examples demonstrate the specific advantages of using fractal analysis for these purposes. The conclusion can be made that the expanded use of fractal analysis methods in the research work of medical and biological specialists is promising.


2018 ◽  
Vol 16 (1) ◽  
pp. 49-55 ◽  
Author(s):  
J. Stenzel ◽  
C. Rühlmann ◽  
T. Lindner ◽  
S. Polei ◽  
S. Teipel ◽  
...  

Background: Positron-emission-tomography (PET) using 18F labeled florbetaben allows noninvasive in vivo-assessment of amyloid-beta (Aβ), a pathological hallmark of Alzheimer’s disease (AD). In preclinical research, [<sup>18</sup>F]-florbetaben-PET has already been used to test the amyloid-lowering potential of new drugs, both in humans and in transgenic models of cerebral amyloidosis. The aim of this study was to characterize the spatial pattern of cerebral uptake of [<sup>18</sup>F]-florbetaben in the APPswe/ PS1dE9 mouse model of AD in comparison to histologically determined number and size of cerebral Aβ plaques. Methods: Both, APPswe/PS1dE9 and wild type mice at an age of 12 months were investigated by smallanimal PET/CT after intravenous injection of [<sup>18</sup>F]-florbetaben. High-resolution magnetic resonance imaging data were used for quantification of the PET data by volume of interest analysis. The standardized uptake values (SUVs) of [<sup>18</sup>F]-florbetaben in vivo as well as post mortem cerebral Aβ plaque load in cortex, hippocampus and cerebellum were analyzed. Results: Visual inspection and SUVs revealed an increased cerebral uptake of [<sup>18</sup>F]-florbetaben in APPswe/ PS1dE9 mice compared with wild type mice especially in the cortex, the hippocampus and the cerebellum. However, SUV ratios (SUVRs) relative to cerebellum revealed only significant differences in the hippocampus between the APPswe/PS1dE9 and wild type mice but not in cortex; this differential effect may reflect the lower plaque area in the cortex than in the hippocampus as found in the histological analysis. Conclusion: The findings suggest that histopathological characteristics of Aβ plaque size and spatial distribution can be depicted in vivo using [<sup>18</sup>F]-florbetaben in the APPswe/PS1dE9 mouse model.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
M. Asada-Utsugi ◽  
K. Uemura ◽  
M. Kubota ◽  
Y. Noda ◽  
Y. Tashiro ◽  
...  

AbstractN-cadherin is a homophilic cell adhesion molecule that stabilizes excitatory synapses, by connecting pre- and post-synaptic termini. Upon NMDA receptor (NMDAR) activation by glutamate, membrane-proximal domains of N-cadherin are cleaved serially by a-disintegrin-and-metalloprotease 10 (ADAM10) and then presenilin 1(PS1, catalytic subunit of the γ-secretase complex). To assess the physiological significance of the initial N-cadherin cleavage, we engineer the mouse genome to create a knock-in allele with tandem missense mutations in the mouse N-cadherin/Cadherin-2 gene (Cdh2R714G, I715D, or GD) that confers resistance on proteolysis by ADAM10 (GD mice). GD mice showed a better performance in the radial maze test, with significantly less revisiting errors after intervals of 30 and 300 s than WT, and a tendency for enhanced freezing in fear conditioning. Interestingly, GD mice reveal higher complexity in the tufts of thorny excrescence in the CA3 region of the hippocampus. Fine morphometry with serial section transmission electron microscopy (ssTEM) and three-dimensional (3D) reconstruction reveals significantly higher synaptic density, significantly smaller PSD area, and normal dendritic spine volume in GD mice. This knock-in mouse has provided in vivo evidence that ADAM10-mediated cleavage is a critical step in N-cadherin shedding and degradation and involved in the structure and function of glutamatergic synapses, which affect the memory function.


Sign in / Sign up

Export Citation Format

Share Document