The morphological basis of proestrus endometrial bleeding in canines

Endometrial bleeding during proestrus is a well-known phenomenon in the bitch. However, the exact events on the cellular level have not been studied. In the present investigation, immunohistochemical methods and transmission electron microscopy were employed to obtain more information about this cyclic event in canines. Long, stretched blood vessels were seen in H&E stained sections during proestrus. These vessels showed mitotic activity, as evidenced by Ki67 immunostaining. Although the endothelial lining and basement membrane of endometrial blood vessels seemed continuous, as indicated by immunohistochemical staining for laminin and Von Willebrand factor, transmission electron microscopy showed an extreme thinning and even interruption of the vascular wall in endometrial venules. Platelets were frequently seen in those areas, and also detected by immunohistochemistry. Interestingly, all endometrial capillaries examined by electron microscopy had an intact wall. We therefore postulate the endometrial venules to be the blood vessels that are mainly responsible for proestrus endometrial bleeding, rather than subepithelial capillaries.     

The peripheral morphological basis of tactile sensibility in the beak of geese

Cell and Tissue Research - The distribution, form variability and organization of two types of encapsulated mechanoreceptors, the Grandry and the Herbst corpuscles, were studied in the beak of...     

Modeling of T-lymphocyte extravasation into a lymph node: The connection between the morphological basis of the process and the clonal selection theory

A model of the process of T-lymphocyte extravasation into a lymph node via the high endothelial venules in the course of the immune response has been developed. The histological structure and the morphometric parameters of the lymph node and its venules, as well as the presence of adhesion molecules on the endothelial cells and the speed of T-lymphocyte movement, were taken into account in the model and compared to the basic postulates of the clonal selection theory of immune surveillance. The inability of the venules of the lymph node to provide the passage of a sufficient number of T lymphocytes has been demonstrated; thus, the concept of immune surveillance formulated within the existing immunological theory has been proven inadequate. This finding points to the need for revision of the widely accepted concepts of the emergence of T-lymphocyte specificity and the very foundations of the clonal selection theory.     

An elaboration of the evolutionary morphological basis for the systematics of the Plathelminthes

Compared with Hennig's phylogenetical systematics which has as its aim the retracing of genealogical relations between taxonomic groups, evolutionary morphological systematics is equally justified. Classifications of basic plans, morphological types, and morphofunctional systems of organisms serve as the foundation of evolutionary morphological systems. They are constructed on the basis of thorough understanding and further iteration of morphological transformation in phylogenetical branches based on the constructional pecularities of the morphofunctional systems. The evolutionary morphological approach in systematics is important especially for elaborating macrosystems dealing with vastly divergant groups where it is impossible to trace their real genealogy. The general principles of evolutionary morphological systematics are considered. A variant of the classification system of the Plathelminthes is suggested.     

The morphological basis of fluid balance in the interstitium of the juxtaglomerular apparatus

Summary The morphological basis of fluid balance in the interstitium of the juxtaglomerular apparatus (JGA) was reevaluated in rats, mice and Tupaia. Three ultrastructural features in the region of the vascular pole of the renal corpuscle are described that may be important for the fluid balance in this region: (1) podocyte foot processes in the parietal layer of Bowman's capsule, (2) endothelial fenestrations in the wall of the incoming afferent arteriole, both facing Goormaghtigh and epithelioid cells, and (3) the mesangial type lining of the glomerular stalk. With respect to the relevant pressure gradients, this morphology may provide the basis of bulk-fluid flow directed to the interstitium of the JGA including the Goormaghtigh cell field. Thus, the fluid balance in the lacis area and, consequently, the tubulo-glomerular feedback mechanism, probably does not solely depend upon the reabsorptive transport of the macula densa. Similar considerations may be valid for the humoral control of renin secretion from juxtaglomerular epithelioid cells.These studies were supported by the German Research Foundation within the SFB 90 Cardiovasculäres System     

The morphological basis of intracellular measurements in the cockroach tactile spine neuron

Summary The femoral tactile spine of the cockroach (Periplaneta americana) contains a single sensory neuron, which adapts rapidly and completely to step deformations of the spine. Techniques for stable intracellular recording from the tactile spine neuron have recently been established, allowing electrophysiological investigation of mechanotransduction and adaptation in this sensory neuron. However, intracellular recordings from the neuron produce a wide range of action potential heights and thresholds, raising the possibility that some penetrations are in adjacent, but closely coupled supporting glial cells. This problem is exacerbated because the cell cannot be visualized during penetration.Systematic measurements of action potential heights and thresholds were made in tactile spine cells, together with identification of some penetrated cells by intracellular injection of Lucifer Yellow. All stained cells were clearly sensory neurons, although their action potentials amplitudes varied from 9 mV to 80 mV. Smaller action potentials were broader than larger action potentials, and the changes in height and shape could be explained by a simple cable conduction model using measured morphological and electrical parameters. The model could also account for the observed relationship between action potential height and threshold.These results indicate that reliable recording from the tactile spine neuron is possible, but that variability in the positions of the penetration or the spike initiating zone cause an apparently wide range of electrophysiological measurements.     

The structural basis for the regulation of tissue transglutaminase by calcium ions.

The role of calcium ions in the regulation of tissue transglutaminase is investigated by experimental approaches and computer modeling. A three-dimensional model of the transglutaminase is computed by homology building on crystallized human factor XIII and is used to interpret structural and functional results. The molecule is a prolate ellipsoid (6.2 x 4.2 x 11 nm) and comprises four domains, assembled pairwise into N-terminal and C-terminal regions. The active site is hidden in a cleft between these regions and is inaccessible to macromolecular substrates in the calcium-free form. Protein dynamics simulation indicates that these regions move apart upon addition of calcium ions, revealing the active site for catalysis. The protein dimensions are consistent with results obtained with small-angle neutron and X-ray scattering. The gyration radius of the protein (3 nm) increases in the presence of calcium ions (3.9 nm), but it is virtually unaffected in the presence of GTP, suggesting that only calcium ions can promote major structural changes in the native protein. Proteolysis of an exposed loop connecting the N-terminal and C-terminal regions is linearly correlated with enzyme inactivation and prevents the calcium-induced conformational changes.     

The structural basis of allosteric regulation in proteins

Allosteric regulation of protein function occurs when the regulatory trigger, such as the binding of a small-molecule effector or inhibitor, takes place some distance from the protein’s, or protein complex’s, active site. This distance can be a few Å, or tens of Å. Many proteins are regulated in this way and exhibit a variety of allosteric mechanisms. Here we review how analyses of experimentally determined models of protein 3D structures, using either X-ray crystallography or NMR spectroscopy, have revealed some of the mechanisms involved.     

The physiological basis of intracrine stem cell regulation

Intracrine peptides and proteins participate in the regulation of adult and pleuripotential embryonic-like stem cells. Included among these factors are VEGF, dynorphin, the readthrough form of acetylcholinesterase, Oct3/4, Pdx-1, Pax-6, and high-mobility group protein B1, among others. In some cases, the establishment of intracrine feedback loops can be shown to be relevant to this regulation, consistent with previously proposed principles of intracrine action. Here the role of intracrines in stem cell regulation is reviewed, with particular attention to the intracrine regulation of cardiac stem cells. The reprogramming of cells to restore the pleuripotent phenotype and the possible role of stem/progenitor cells in neoplasia are also discussed.     

The Rac-RhoGDI complex and the structural basis for the regulation of Rho proteins by RhoGDI

Rho family-specific guanine nucleotide dissociation inhibitors (RhoGDIs) decrease the rate of nucleotide dissociation and release Rho proteins such as RhoA, Rac and Cdc42 from membranes, forming tight complexes that shuttle between cytosol and membrane compartments. We have solved the crystal structure of a complex between the RhoGDI homolog LyGDI and GDP-bound Rac2, which are abundant in leukocytes, representing the cytosolic, resting pool of Rho species to be activated by extracellular signals. The N-terminal domain of LyGDI (LyN), which has been reported to be flexible in isolated RhoGDIs, becomes ordered upon complex formation and contributes more than 60% to the interface area. The structure is consistent with the C-terminus of Rac2 binding to a hydrophobic cavity previously proposed as isoprenyl binding site. An inner segment of LyN forms a helical hairpin that contacts mainly the switch regions of Rac2. The architecture of the complex interface suggests a mechanism for the inhibition of guanine nucleotide dissociation that is based on the stabilization of the magnesium (Mg2+) ion in the nucleotide binding pocket.     

The basis for spinal manipulation: Chiropractic perspective of indications and theory

It is reasonable to think that patients responding to spinal manipulation (SM), a mechanically based therapy, would have mechanical derangement of the spine as a critical causal component in the mechanism of their condition. Consequently, SM practitioners routinely assess intervertebral motion, and treat patients on the basis of those assessments. In chiropractic practice, the vertebral subluxation has been the historical raison d'etre for SM. Vertebral subluxation is a biomechanical spine derangement thought to produce clinically significant effects by disturbing neurological function. This paper reviews the putative mechanical features of the subluxation and three theories that form the foundation for much of chiropractic practice. It concludes with discussion of subluxation as an indicator for SM therapy, particularly from the perspective that subluxation may be one contributory cause of ill-health within a "web of causation".     

翻译后修饰——p53功能调节的分子基础

p53的稳定与活化是细胞应对癌基因激活或DNA损伤等刺激的关键早期事件。可逆的翻译后修饰可严密调控p53的总蛋白质水平和反式激活能力,对维持正常的细胞生长、抑制细胞的早期癌变及肿瘤的发生至关重要。最新研究发现,除了磷酸化、泛素化和乙酰化修饰外,p53还能发生多个位点的甲基化、类泛素化和糖基化等修饰。这些翻译后修饰之间彼此联系,构成一个复杂的调控网络,对p53的稳定及其功能产生深远影响。