An analysis of the unconfined compression of articular cartilage

Analytical solutions have been obtained for the internal deformation and fluid-flow fields and the externally observable creep, stress relaxation, and constant strain-rate behaviors which occur during the unconfined compression of a cylindrical specimen of a fluid-filled, porous, elastic solid, such as articular cartilage, between smooth, impermeable plates. Instantaneously, the "biphasic" continuum deforms without change in volume and behaves like an incompressible elastic solid of the same shear modulus. Radial fluid flow then allows the internal fluid pressure to equilibrate with the external environment. The equilibrium response is controlled by the Young's modulus and Poisson's ratio of the solid matrix.     

The nuclear matrix from cells of different origin. Evidence for a common set of matrix proteins

We compared the protein composition of the nuclear matrix isolated from several murine embryonal carcinoma cells and mature tissues by two-dimensional gel electrophoresis. Two nuclear matrix fractions were investigated: the "peripheral" nuclear matrix (matrix proteins that remain insoluble after reduction), and the "internal" nuclear matrix (matrix proteins released by reduction). The two subfractions have completely different protein compositions. Although numerous differences in nuclear matrix protein composition among different cell types were observed, a limited set of polypeptides common to all mouse cell types was identified. A majority of these common proteins was also present in cells from other mammalian species (i.e. rat and human). For this set of proteins, we coin the term "minimal matrix." As expected, lamin B, known to be expressed throughout differentiation, is part of the common set of peripheral nuclear matrix proteins. Lamins A and C are not because these proteins were absent from undifferentiated embryonal carcinoma cells. Since these common nuclear matrix proteins occur in all mammalian nuclear matrices analyzed so far, it is likely that they have a basic role in nuclear organization and function.     

Renal epithelial fluid secretion and cyst growth: the role of cyclic AMP

Transepithelial fluid secretion has been postulated to account for the accumulation of fluid within hereditary and acquired renal cysts, but no such mechanism has been demonstrated in human kidney epithelium. It is shown here that transepithelial fluid secretion was stimulated by prostaglandin E1 (PGE1), forskolin, 8-Br-cyclic AMP, and 1-methyl-3-isobutylxanthine in polarized monolayers of established renal cell lines (MDCK and rat glomerular epithelial cells) and in monolayer cultures derived from the cyst walls of human autosomal dominant polycystic kidney disease and from epithelial cells of normal human renal cortex. Treatment with cyclic AMP agonists caused the same cells, when dispersed within a gel matrix of type I collagen (Vitrogen), to proliferate and form spherical fluid-filled monolayered cysts. Our findings suggest that increased intracellular cyclic AMP levels may have a critical role in the formation and expansion of hereditary and acquired renal cysts.     

Teaching the interrelationship between stress, emotions, and cardiovascular risk using a classic paper by Walter Cannon

Classroom discussion of the classic article by Walter B. Cannon in 1914, entitled "The emergency function of the adrenal medulla in pain and the major emotions," is an excellent tool to teach graduate students the interaction between stress, emotions, and cardiovascular function. Using this article, we are able to review important early research by Dr. Cannon, including discussion of his scientific methods and results and how they hold true today. This article outlines how this classic paper is used to allow students to explore basics principles of cardiovascular control during stress. The teaching points that are presented illustrate how students can be directed to understand the interrelationship between chronic stress and cardiovascular disease.     

Among the Peoples of the Agreste of Pernambuco

Anthropology, despite its historic role in both creating and dismantling the American racial worldview, seems barely visible in contemporary scholarly and public discussions of "race." The authors argue that race should once again be central to anthropological inquiry, that cultural and physical anthropologists must jointly develop and publicly disseminate a unified, uniquely anthropological perspective. They suggest ways to proceed and identify internal barriers that must be overcome before the anthropological voice can be heard.     

The developments between gametogenesis and fertilization: ovulation and female sperm storage in Drosophila melanogaster

In animals with internal fertilization, ovulation and female sperm storage are essential steps in reproduction. While these events are often required for successful fertilization, they remain poorly understood at the developmental and molecular levels in many species. Ovulation involves the regulated release of oocytes from the ovary. Female sperm storage consists of the movement of sperm into, maintenance within, and release from specific regions of the female reproductive tract. Both ovulation and sperm storage elicit important changes in gametes: in oocytes, ovulation can trigger changes in the egg envelopes and the resumption of meiosis; for sperm, storage is a step in their transition from being "movers" to "fertilizers." Ovulation and sperm storage both consist of timed and directed cell movements within a morphologically and chemically complex environment (the female reproductive tract), culminating with gamete fusion. We review the processes of ovulation and sperm storage for Drosophila melanogaster, whose requirements for gamete maturation and sperm storage as well as powerful molecular genetics make it an excellent model organism for study of these processes. Within the female D. melanogaster, both processes are triggered by male factors during and after mating, including sperm and seminal fluid proteins. Therefore, an interplay of male and female factors coordinates the gametes for fertilization.     

The physiology of vasopressin release and the pathogenesis of impaired water excretion in adrenal,thyroid, and edematous disorders.

Osmotic control for vasopressin release has been recognized for several years. Further understanding of factors affecting the sensitivity and threshold of ADH release has been advanced by the technological development of a sensitive radioimmunoassay. Evidence suggesting that ADH secretion is also mediated by nonosmotic stimuli involving a separate anatomic pathway from the hypothalamic osmoreceptor has been well documented. Experimental results suggest that the parasympathetic afferent pathways from both "high" and "low" pressure receptors constitute the most important nonosmotic pathways for ADH release. Factors such as hypoxia, altered hemodynamic states, alpha- and beta-adrenergic stimuli, nicotine, adrenal insufficiency, and advanced hypothyroidism are likely examples which activate this nonosmotic pathway. Clarification of the exact interrelationship between the osmotic and nonosmotic release of ADH needs further examination, particularly in the area of central neurotransmitters. However, available information allows for the proposal of a model of this interaction and its clinical implications which may explain many cases of "reset osmostat." Recent available data also provide support for ADH playing a role in the maintenance of blood pressure under certain circumstances. Like other potent vasoconstrictors, preliminary evidence suggests that ADH requires transcellular calcium influx for its vascular effects. Adrenal, thyroid, and edematous disorders have all been shown to be associated with abnormal water excretion. The results of recent studies indicate that these abnormal physiological states have impaired water excretion as a result of both nonosmolar factors stimulating ADH release and intrarenal factors, including diminished glomerular filtration rate or increased proximal tubule reabsorption which lead to decreased distal fluid delivery to the diluting segment of the nephron. Verney''s original studies demonstrating the osmoreceptor regulation of ADH release remain a milestone in renal physiology. In the past decade, considerable new information about nonosmotic regulation of ADH has led to further understanding of renal water regulation in health and disease; nevertheless, many of these answers have only stimulated the imagination to ponder even more questions.     

A re-evaluation of Melanospora Gorda and similar Pyrenomycetes, with a revision of the British species

A re-evaluation of Melanospora Corda and similar genera is presented, based mainly on new data obtained by SEM examination of the ascospores. Eight genera are accepted: Melanospora (nine British species, including M. longisetosa P. Cannon & D. Hawksw.), Persiciospora P. Cannon & D. Hawksw. (including P. moreaui P. Cannon & D. Hawsksw. and P. masonii (Kirschst.) P. Cannon & D. Hawksw.), Phaeostoma (one species), Scopinella (four species; two in the British Isles), Sphaerodes (six species, including S. beatonii (D. Hawksw.) P. Cannon & D. Hawksw., 5. compressa (Udagawa & Cain) P. Cannon & D. Hawksw., S.fimicola (Hansen) P. Cannon & D. Hawksw., S. perplexa (D. Hawksw.) P. Cannon & D. Hawksw., S. retispora (Udagawa & Cain) P. Cannon & D. Hawksw., 5. retispora var. inferior (Udagawa & Cain) P. Cannon & D. Hawksw.; two in the British Isles), Sphaeronaemella (one species, not known in Britain), Syspastospora P. Cannon & D. Hawksw. (one species, S. parasitica (Tul.) P. Cannon & D. Hawksw.) and Viennotidea P. Cannon & D. Hawksw. (four species, including V.fmicola (Marchal) P. Cannon & D. Hawksw., V. humicola (Samson & W. Gams) P. Cannon & D. Hawksw., V. spermosphaerici (Malloch) P. Cannon & D. Hawksw., and V. raphani (Malloch) P. Cannon & D. Hawksw.; one in the British Isles).     

Stromules-like protrusions of the membrane environment of plastids in the root cells

The results of visualization of the stromules-like protrusions of the membrane environment of plastids in the root cells with the help of an electronic microscope are submitted. The cases of occurrence of long narrow protrusion of the external membrane with more short protrusion of the internal membrane of plastid environment inside it are discussed. The possible role of cytoskeleton and plastoskeleton in formation, accordingly, of "external" and "internal" protrusions is considered. The conclusion that the structure and functions of stromules in plant cells should be considered in unity with the structure and functions of the endoplasmic reticulum internal space is made.     

Alterations in the mechanical properties of the human chondrocyte pericellular matrix with osteoarthritis

In articular cartilage, chondrocytes are surrounded by a pericellular matrix (PCM), which together with the chondrocyte have been termed the "chondron." While the precise function of the PCM is not know there has been considerable speculation that it plays a role in regulating the biomechanical environment of the chondrocyte. In this study, we measured the Young's modulus of the PCM from normal and osteoarthritic cartilage using the micropipette aspiration technique, coupled with a newly developed axisymmetric elastic layered half-space model of the experimental configuration. Viable, intact chondrons were extracted from human articular cartilage using a new microaspiration-based isolation technique. In normal cartilage, the Young's modulus of the PCM was similar in chondrons isolated from the surface zone (68.9 +/- 18.9 kPa) as compared to the middle and deep layers (62.0 +/- 30.5 kPa). However, the mean Young's modulus of the PCM (pooled for the two zones) was significantly decreased in osteoarthritic cartilage (66.5 +/- 23.3 kPa versus 41.3 +/- 21.1 kPa, p < 0.001). In combination with previous theoretical models of cell-matrix interactions in cartilage, these findings suggest that the PCM has an important influence on the stress-strain environment of the chondrocyte that potentially varies with depth from the cartilage surface. Furthermore, the significant loss of PCM stiffness that was observed in osteoarthritic cartilage may affect the magnitude and distribution of biomechanical signals perceived by the chondrocytes.     

Molecular bases of evolution

The general notions of the theory of evolution are listed. The unity of the "engineering principles" of the living nature is emphasized. The generalists and specialists species are discussed. The estimation of their evolution rates must be different if it is expressed by the number of species or by the morphological changes. The principles of "protein engineering" of the organisms and the role of metals in protein evolution are discussed. It is suggested that in the presence of ions of transition metals and zinc the Fox's proteinoids can possess more specific forms of enzymatic activity. In the evolution of language the horizontal transfer plays a much more important role than in the biological evolution. However in this case also the initial basis of the language remains. The random drift is considered and it is shown that in concordance with the neutralist theory there are no grounds to replace the calculation of the rates of mutational changes per time unity by the calculation per generation. The molecular drive is the main source of the evolutionary novelties. The drive is connected with drift. The synonymic mutations and the mutations in non-functional DNA are evolutionary important. The future mathematical theory of evolution must be based on the theory of Markov's chains with the stochastic matrix changing along the chain and containing the set of the non-diagonal members equal to zero. The results obtained in the theory of ontogeny are presented. The evolution of species is the evolution of ontogenies, the formation of the molecular theory of evolution can be possible only on the basis of the molecular theory of ontogeny. The internal causes of extinction of species reduce the accumulation of neutral and pseudo-neutral mutations.     

Ommaya 囊在神经外科治疗中的研究进展

Ommaya囊是巴基斯坦神经外科医师Ommaya发明的脑室引流工具,包括一个扁平状的储液器与一根引流管相接而成,其最初设计目的是在治疗真菌性脑膜炎时进行侧脑室内持续给药,因此又称为"储药囊"。Ommaya囊的引流管也可以置入患者四脑室、疆池、囊腔与脑池。其对颅脑肿瘤、脑室出血、脑膜炎等疾病的治疗、中枢神经系统感染与脑脊液药理学、细胞学的实验研究等方面也有重要意义。     

Legumain/asparaginyl endopeptidase controls extracellular matrix remodeling through the degradation of fibronectin in mouse renal proximal tubular cells

Legumain/asparaginyl endopeptidase (EC 3.4.22.34) is a novel cysteine protease that is abundantly expressed in the late endosomes and lysosomes of renal proximal tubular cells. Recently, emerging evidence has indicated that legumain might play an important role in control of extracellular matrix turnover in various pathological conditions such as tumor growth/metastasis and progression of atherosclerosis. We initially found that purified legumain can directly degrade fibronectin, one of the main components of the extracellular matrix, in vitro. Therefore, we examined the effect of legumain on fibronectin degradation in cultured mouse renal proximal tubular cells. Fibronectin processing can be inhibited by chloroquine, an inhibitor of lysosomal degradation, and can be enhanced by the overexpression of legumain, indicating that fibronectin degradation occurs in the presence of legumain in lysosomes from renal proximal tubular cells. Furthermore, in legumain-deficient mice, unilateral ureteral obstruction (UUO)-induced renal interstitial protein accumulation of fibronectin and renal interstitial fibrosis were markedly enhanced. These findings indicate that legumain might have an important role in extracellular matrix remodeling via the degradation of fibronectin in renal proximal tubular cells.     

Ethylmalonic encephalopathy is caused by mutations in ETHE1, a gene encoding a mitochondrial matrix protein

Ethylmalonic encephalopathy (EE) is a devastating infantile metabolic disorder affecting the brain, gastrointestinal tract, and peripheral vessels. High levels of ethylmalonic acid are detected in the body fluids, and cytochrome c oxidase activity is decreased in skeletal muscle. By use of a combination of homozygosity mapping, integration of physical and functional genomic data sets, and mutational screening, we identified GenBank D83198 as the gene responsible for EE. We also demonstrated that the D83198 protein product is targeted to mitochondria and internalized into the matrix after energy-dependent cleavage of a short leader peptide. The gene had previously been known as "HSCO" (for hepatoma subtracted clone one). However, given its role in EE, the name of the gene has been changed to "ETHE1." The severe consequences of its malfunctioning indicate an important role of the ETHE1 gene product in mitochondrial homeostasis and energy metabolism.     

Interfacial barriers to gas transport: probing solid-gas interfaces at the atomistic level

ABSTRACT

An understanding of interfacial barriers underpinning fluid transport in nanoporous membranes is critical for the design of efficient next generation membranes, to harness their potential for industrial scale separations. Such barriers include the contribution of external and internal interfacial barriers, and strongly depend on smoothness of the pore surface, pore size, shape, tortuosity, structural defects such as pore blockage and thermodynamic state of the fluid. We review recent progress in the transport of a fluid through nanoporous membrane materials such as zeolites and carbon nanotubes, which hold promise for industrial significance, but their application is subject to strong interfacial barriers. The contribution of interfacial barriers to the overall transport in these membrane materials is found to be particularly significant when the pore surface is uniform as well as at low temperatures and pressures. Further, such barriers that arise from internal defects such as grain boundaries are found to be remarkable and detrimental to separation kinetics. The internal interfacial barriers are found to be significant, and are enhanced when a dense medium such as a polymer is present at the interface, suggesting that interfacial barriers can play a key role in mixed matrix membranes and is an important area requiring further attention.     

Value of renal biopsy in acute intrinsic renal failure.

Eighty-four patients presented with acute renal failure and features suggesting a diagnosis of intrinsic renal disease other than "acute reversible renal failure." Renal biopsy proved valuable in establishing the diagnosis, in indicating the reversibility of the lesion, and in helping to decide on treatment.     

Finite Element Modeling Predictions of Region-specific Cell-matrix Mechanics in the Meniscus

The knee meniscus exhibits significant spatial variations in biochemical composition and cell morphology that reflect distinct phenotypes of cells located in the radial inner and outer regions. Associated with these cell phenotypes is a spatially heterogeneous microstructure and mechanical environment with the innermost regions experiencing higher fluid pressures and lower tensile strains than the outer regions. It is presently unknown, however, how meniscus tissue mechanics correlate with the local micromechanical environment of cells. In this study, theoretical models were developed to study mechanics of inner and outer meniscus cells with varying geometries. The results for an applied biaxial strain predict significant regional differences in the cellular mechanical environment with evidence of tensile strains along the collagen fiber direction of ~0.07 for the rounded inner cells, as compared to levels of 0.02–0.04 for the elongated outer meniscus cells. The results demonstrate an important mechanical role of extracellular matrix anisotropy and cell morphology in regulating the region-specific micromechanics of meniscus cells, that may further play a role in modulating cellular responses to mechanical stimuli.     

Phenotypic modulation of endothelial cells by transforming growth factor-beta depends upon the composition and organization of the extracellular matrix

Transforming growth factor beta (TGF-beta) is angiogenic in vivo. In vitro, endothelial cell proliferation is inhibited by TGF-beta. We have correlated this inhibitory effect with an increase in cellular fibronectin synthesis and deposition in a two-dimensional culture system using specific matrix coatings. The inhibitory effect was mimicked by addition of soluble fibronectin to cultures. In contrast, TGF-beta was found to elicit the formation of tube-like structures (mimicking angiogenesis) when microvascular endothelial cells were grown in three-dimensional collagen gels. In this culture system TGF-beta elicited rapid extensive formation of complex, branching, tube-like structures, while cell proliferation was not inhibited. These data confirm and support the hypothesis that TGF-beta is angiogenic and may exert some of its effects through modulation of matrix synthesis and are consistent with the hypothesis that the organization of the extracellular environment influences cellular responses to this "panregulin."     

Role of matrix metalloproteinases in development of diabetic nephropathy

This review considers molecular mechanisms that underlie disorders in the structure and metabolism of renal extracellular matrix in diabetic nephropathy. The contribution of the increased synthesis of renal extracellular matrix proteins in the accumulation of renal mesangial matrix is considered, and the important role of the degradation system of the extracellular matrix proteins in the development of fibrosis is also shown. Data on changes in mRNA expression for the matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) in various forms of diabetic nephropathy are presented. A correlation is established between changes in the balance of MMP proteolytic activity and TIMP activity and the accumulation of extracellular matrix.