Numerous Mechanisms (numerous + mechanism)

Distribution by Scientific Domains

Selected Abstracts

Na+/H+ exchangers and the regulation of volume

R. T. Alexander
Abstract The regulation of volume is fundamental to life. There exist numerous conditions that can produce perturbations of cell volume. The cell has developed mechanisms to directly counteract these perturbations so as to maintain its physiological volume. Directed influx of the major extracellular cation, sodium, serves to counteract a decreased cell volume through the subsequent osmotically coupled movement of water to the intracellular space. This process, termed regulatory volume increase is often mediated by the ubiquitous sodium/hydrogen ion exchanger, NHE1. Similarly, the maintenance of intravascular volume is essential for the maintenance of blood pressure and consequently the proper perfusion of vital organs. Numerous mechanisms exist to counterbalance alterations in intravascular volume, not the least of which is the renal absorption of sodium filtered at the glomerulus. Two-thirds of filtered sodium and water are absorbed in the renal proximal tubule, a mechanism that intimately involves the apical sodium/hydrogen ion exchanger, NHE3. This isoform is fundamental to the maintenance and regulation of intravascular volume and blood pressure. In this article, the effects of cell volume on the activity of these different isoforms, NHE1 and NHE3, will be described and the consequences of their activity on intracellular and intravascular volume will be explored. [source]

DNA base repair , recognition and initiation of catalysis

Bjørn Dalhus
Abstract Endogenous DNA damage induced by hydrolysis, reactive oxygen species and alkylation modifies DNA bases and the structure of the DNA duplex. Numerous mechanisms have evolved to protect cells from these deleterious effects. Base excision repair is the major pathway for removing base lesions. However, several mechanisms of direct base damage reversal, involving enzymes such as transferases, photolyases and oxidative demethylases, are specialized to remove certain types of photoproducts and alkylated bases. Mismatch excision repair corrects for misincorporation of bases by replicative DNA polymerases. The determination of the 3D structure and visualization of DNA repair proteins and their interactions with damaged DNA have considerably aided our understanding of the molecular basis for DNA base lesion repair and genome stability. Here, we review the structural biochemistry of base lesion recognition and initiation of one-step direct reversal (DR) of damage as well as the multistep pathways of base excision repair (BER), nucleotide incision repair (NIR) and mismatch repair (MMR). [source]

Ecoimmunity: immune tolerance by symmetric co-evolution

Uri Nevo
SUMMARY It is widely accepted that immune tolerance toward "self" is established by central and peripheral adaptations of the immune system. Mechanisms that have been demonstrated to play a role in the induction and maintenance of tolerance include thymic deletion of self-reactive T cells, peripheral T cell anergy and apoptosis, as well as thymic and peripheral induction of regulatory T cells. However, a large body of experimental findings cannot be rationalized solely based on adaptations of the immune system to its environment. Here we propose a new model termed Ecoimmunity, where the immune system and the tissue are viewed as two sides of a continuously active and co-evolving predator,prey system. Ecoimmunity views self-tolerance, not as an equilibrium in which autoimmunity is chronically suppressed, but as a symmetrical balanced conflict between the ability of immune cells to destroy tissue cells by numerous mechanisms, and the capacity of adapted tissue cells to avoid predation. This balance evolves during ontogeny, in parallel to immune adaptations, embryonic tissue cells adapt their phenotype to the corresponding immune activity by developing the ability to escape or modulate damaging local immune responses. This phenotypic plasticity of tissue cells is directed by epigenetic selection of gene expression pattern and cellular phenotype amidst an ongoing immune pressure. Thus, whereas some immune cells prey predominantly on pathogens and infected cells, self-reactive cells continuously prey on incompetent tissue cells that fail to express the adapted phenotype and resist predation. This model uses ecological generalization to reconcile current contradictory observations as well as classical enigmas related to both autoimmunity and to tolerance toward foreign tissues. Finally, it provides empirical predictions and alternative strategies toward clinical challenges. [source]

The role of steroid hormones in the regulation of vasopressin and oxytocin release and mRNA expression in hypothalamo neurohypophysial explants from the rat

Celia D. Sladek
Vasopressin and oxytocin release from the neural lobe, and the vasopressin and oxytocin mRNA contents of the supraoptic and paraventricular nuclei are increased by hypertonicity of the extracellular fluid. The factors regulating these parameters can be conveniently studied in perifused explants of the hypothalamo-neurohypophysial system that include the supraoptic nucleus (but not the paraventricular nucleus) with its axonal projections to the neural lobe. Vasopressin and oxytocin release and the mRNA content of these explants respond appropriately to increases in the osmolality of the perifusate. This requires synaptic input from the region of the organum vasculosum of the lamina terminalis. Glutamate is a likely candidate for transmitting osmotic information from the organum vasculosum of the lamina terminalis to the magnocellular neurones, because agonists for excitatory amino acid receptors stimulate vasopressin and oxytocin release, and because increased vasopressin release and mRNA content induced in hypothalamo-neurohypophysial explants by a ramp increase in osmolality are blocked by antagonists of both NMDA (N -methyl-D-aspartate) and non-NMDA glutamate receptors. Osmotically stimulated vasopressin release is also blocked by testosterone, dihydrotestosterone, oestradiol and corticosterone. Both oestrogen and dihydrotestosterone block NMDA stimulation of vasopressin release, and in preliminary studies oestradiol blocked AMPA stimulation of vasopressin release. Thus, steroid inhibition of osmotically stimulated vasopressin secretion may reflect inhibition of mechanisms mediated by excitatory amino acids. Recent studies have demonstrated numerous mechanisms by which steroid hormones may impact upon neuronal function. Therefore, additional work is warranted to understand these effects of the steroid hormones on vasopressin and oxytocin secretion and to elucidate the potential contribution of these mechanisms to regulation of hormone release in vivo. [source]

Exploring the link between microorganisms and oral cancer: A systematic review of the literature

Samuel J. Hooper PhD
Abstract The majority of cases of oral cancer have been related to tobacco use and heavy alcohol consumption. However, the incidence of oral cavity carcinoma appears to be increasing in many parts of the world in a manner that it is difficult to explain with traditional risk factors alone. Meanwhile, interest in the possible relationships between microorganisms and the different stages of cancer development has been rising and numerous mechanisms by which bacteria and yeast may initiate or promote carcinogenesis are currently under investigation. In particular, a persuasive body of evidence suggests a possible etiological role involving the metabolism and production of carcinogenic products, such as acetaldehyde. Other suggested mechanisms include the induction of chronic inflammation and direct interference with eukaryotic cell cycle and signaling pathways. This review aims to summarize the known associations between microbial infection and cancer and draw attention to how they may relate to oral carcinoma. © 2009 Wiley Periodicals, Inc. Head Neck, 2009 [source]

Wnt/frizzled family members mediate olfactory sensory neuron axon extension

Diego J. Rodriguez-Gil
Abstract A comprehensive model has yet to emerge, but it seems likely that numerous mechanisms contribute to the specificity of olfactory sensory neuron (OSN) axon innervation of the olfactory bulb. Elsewhere in the nervous system the Wnt/Fz family has been implicated in patterning of anterior-posterior axes, cell type specification, cell proliferation, and axon guidance. Because of our work describing cadherin-catenin family member expression in the primary olfactory pathway, and because mechanisms of Wnt-Fz interactions can depend in part on catenins, we were encouraged to explore Wnt-Fz expression and function in OSN axon extension. Here, we show that OSNs express Fz-1, Fz-3, and Wnt-5a, whereas olfactory ensheathing cells (OECs) express Wnt-4. Fz-7 is also expressed in the olfactory nerve by cells that delineate large axon fascicles, but are negative for OEC markers. Fz-1 showed a developmental downregulation. However, in adults it is expressed at different levels across the olfactory epithelium and in restricted glomeruli across the olfactory bulb, suggesting an important role in the formation and maintenance of OSN connections to the olfactory bulb. Reporter TOPGAL mice demonstrated that some OECs located in the inner olfactory nerve layer can respond to Wnt ligands. Of further interest, we show here with in vitro assays that Wnt-5a increases OSN axon outgrowth and alters growth cone morphology. Our data point to a key role for Wnt/Fz molecules in the development of the mouse olfactory system, providing complementary mechanisms required for OSN axon extension and coalescence. J. Comp. Neurol. 511:301,317, 2008. © 2008 Wiley-Liss, Inc. [source]