The molecular cellular mechanisms of the formation of long-term memory in the snail

Experimental data concerning molecular and cellular mechanisms of the nonassociative and associative forms of learning (sensitization and classical conditioning) in snail Helix lucorum are reviewed. Results of our investigations and data obtained in other laboratories support hypothesis about activation during conditioning of complex metabolic reactions which are specific for each reflex. Integration of different neural signals by single neuron not only activates second messengers system in the neuron but initiates also synthesis of specific (during conditioning) or relatively specific (during sensitization) for definite synaptic inputs protein molecules with short time of half-life (1-3 hours). After weak consolidation effect of conditioning probably coincide with time of half-life of the protein molecules and disappears after catabolism of the molecules. Strong consolidation initiates selfsupport synthesis of the protein molecules and effect of conditioning lasts a long time.     

The descending cortical control of nociceptive signals: the neurochemical mechanisms and pharmacological control

The purpose of the present study was to determine whether electrical cortical stimulation (as a model of descending inhibitory control) could alter the electrophysiological and behavioral signs of a nociceptive response. The inhibitory cortical influence on the neuronal activity produced by nociceptive stimuli (the tooth pulp, C-fibers of afferent somatic nerves, cardiac afferents) was most marked during electrical stimulation the somatosensory (Sn and St) and fronto-orbital cortices. In chronic experiments, somatosensory cortical stimulation delayed the development of the deafferentation pain syndrome and reduced its intensity. The opioid mu-receptor agonists morphine and fentanyl potentiated the inhibitory action of the cortex on evoked neuronal activity. Pentazocine, a kappa-receptor agonist, was less effective. The opioid receptor blocker naloxone eliminated the effect of both cortical stimulation and opioid analgesics. The serotonin receptor blocker methisergide significantly decreased cortical action. Monoamine reuptake inhibitors (amitriptyline, imipramine, fluoxetine) potentiated the effect of cortical stimulation. Adrenergic, dopaminergic cholinergic, and GABA-ergic substances had a little effect. Among nonopioid analgesics, metamyzol and ketorolak only increased moderately descending cortical control.     

The role of neurochemical mechanisms in the pathogenesis of kinetoses and the therapeutic-prophylactic action of drugs]

Experimental and clinical data on the neurochemical and neurohumoral mechanisms underlying the pathogenesis and therapeutic and preventive effects of drugs are generalized. Literature data and the authors' own data concerning drugs used for the prevention and treatment of kinetoses are given. The possible mechanisms of their effect against motion sickness are suggested. New ideas of the means of search for substances possessing vestibuloprotective activity, and the principles of rational pharmacological correction of vestibuloautonomic disorders in motion sickness are discussed.     

The entorhinal cortex-nucleus accumbens pathway and latent inhibition: A behavioral and neurochemical study in rats.

Latent inhibition (LI) refers to the decrease in conditioned response produced by the repeated nonreinforced preexposure to the to-be-conditioned stimulus. Experiment 1 investigated the effects of electrolytic lesions of the entorhinal cortex on LI in a conditioned emotional response procedure. Entorhinal cortex lesions attenuated LI. Experiments 2 and 3 investigated whether this attenuation of LI could result from a modification in nucleus accumbens (NAcc) dopamine (DA) release. Rats with entorhinal cortex lesions displayed normal spontaneous and amphetamine-induced locomotor activity, as well as normal basal and amphetamine-induced release of DA within the NAcc (assessed by microdialysis). Taken together, these results show that entorhinal cortex lesions disrupt LI in a way that is unlikely to be due to an alteration of DA release within the NAcc. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The molecular mechanisms of the instability of the CAG repeat

Expansion of CAG trinucleotide repeats coding for polyglutamine stretches has been identified for seven neurodegenerative diseases including Machado-Joseph disease (MJD). There are many common features shared among these disease such as genetic anticipation i.e. accelerated age at onset in successive generations, which is also a result of intergenerational increase in the size of expanded CAG repeats. To identify elements affecting the intergenerational instability of the CAG repeat, we investigated whether the CGG/GGG polymorphism at the 3' end of the CAG repeat in the MJD1 gene affects intergenerational instability. We suggested that an inter-allelic interaction is involved in the intergenerational instability of the CAG repeat and provide a clue to the molecular mechanisms of the instability of the CAG repeat.     

Correlated ultrastructural and biochemical studies on the mechanisms of secretion of catecholamines

The frequency of dark-cored vesicles is compared with the content in catecholamines in the adrenal medulla and carotid body of normal and reserpine-treated cats. Reserpine produces important diminution in the content of catecholamines but the frequency of the dark-cored vesicles does not parallel this descent. In the carotid body there is no relation between the content in catecholamines and the number of granules. The diameter of the dark cores does not change with the number of secretion vesicles present in normal or treated specimens. It is concluded that there is not partial discharge of the content of the vesicles. An all-or-nothing mechanism of discharge of exocytotic type is proposed.     

Neuropathological sequelae of traumatic brain injury: relationship to neurochemical and biomechanical mechanisms

Brain injury is the leading cause of death among individuals under the age of 45 years in the United States and Europe. Recently, the neuropathologic classification of posttraumatic brain damage has provided insight into the specific mechanisms underlying traumatically induced neuronal damage and death. Studies regarding the biomechanics of brain trauma have also provided great insight into the pathophysiologic mechanisms underlying specific patterns of posttraumatic cellular death. Based upon recent clinical evaluations and biomechanical studies, laboratory models of human brain injury have been developed that faithfully reproduce a number of important features of clinical brain trauma. Biomechanical models have been used to study both the acute sequelae of brain injury and the role of neurochemical alterations in contributing to the development of secondary or delayed cellular death and damage. This report reviews and integrates the laboratory investigations linking experimental models of brain injury to clinical diagnosis and treatment.     

Simplifying the molecular mechanisms of human papillomavirus

Human papillomaviruses are a common human pathogen responsible for diseases varying in severity from warts to cervical cancer. This article examines the functions of the viral gene products and how they interact with cellular factors to replicate themselves and cause disease.     

Biochemical and molecular mechanisms regulating apoptosis

In eukaryotes, the regulation of tissue cell numbers is a critical homeostatic objective that is achieved through tight control of apoptosis, mitosis and differentiation. While much is known about the genetic regulation of cell growth and differentiation, the molecular basis of apoptosis is less well understood. Genes involved in both cell proliferation and apoptosis reflect the role of some stimuli in both of these processes, the cell response depending on the overall cellular milieu. Recent research has given fascinating insights into the complex genetic and molecular mechanisms regulating apoptosis. A picture is emerging of the initiation in certain cells, after an apoptotic trigger, of sequential gene expression and specific signal transduction cascades that guide cells along the cell death pathway. Changes in gene expression precede the better known biochemical and morphological changes of apoptosis. It seems possible that, as a result of increased understanding of the cellular events preceding cell death, apoptosis may become more amenable to manipulation by appropriate drug- and gene-based therapies.     

On the molecular characteristics, compositional properties, and structural-functional mechanisms of maltodextrins: a review

Compositional, physicochemical, and structural properties of maltodextrins and the most important advances that have been made are critically reviewed. Individual topics focuses on the maltodextrin production, carbohydrate composition, and dextrose equivalent determination, factors that alter the polysaccharide properties, the molecular arrangement, the mechanisms and complex physicochemical changes of maltodextrins such as water interaction (hygroscopicity, precipitation, turbidity, bound and free water) and the role of molecular interactions for a network formation. Of particular importance is the information concerning the network structure of maltodextrins gels (degree of crystallinity, crystallite size, aggregation) and the involvement of linear and branched chains for the network formation. Rheological properties have become a desirable tool to predict and understand their structural and functional properties, in single and in mixed systems with other macromolecules. These advances are assessed together with the structural development of food products and processes. Their main food applications, particular advantages, recent commercial directions, and modifications together with potential problems are also discussed. As food ingredients, maltodextrins are a valuable production tool, but still with considerable promises. Nevertheless, a more detailed knowledge of the properties of maltodextrins is necessary in order for their use to be considered as sufficiently effective and desirable in a number of known food applications and for novel development purposes.     

Cellular and molecular mechanisms of tumor invasion

This review summarizes data on cellular and molecular mechanisms underlying phenotypical characteristics of tumor cells that determine their ability for invasion. These mechanisms include dysregulation of adhesive interactions of tumor cells with each other and with extracellular matrix, protease production, locomotion reactions of tumor cells, and induction of angiogenesis in tumor. Data on structure and functions of transmembrane adhesion molecules and their ligands, molecular composition of adhesion structures (intercellular and focal contacts), and role of adhesion molecules as transducers of intracellular signals are considered. Alterations of expression of adhesion molecules and cytoplasmic proteins in adhesion structures and hyperphosphorylation of these molecules by oncogene products are described as a precondition of invasion activity of tumor cells. The contact interaction between circulating tumor cells and vascular endothelium is considered as the important stage of the metastatic process. Secretion of proteases by tumor cells and regulation of their activity by specific stromal inhibitors are described. Function of motogens in the acquisition by a tumor cell of locomotor phenotype facilitating invasion and impairments of topographic reactions of cells playing an important role in the invasion are considered. Attention is given to mechanisms of neoangiogenesis in the tumor providing additional ways for dissemination of tumor cells.     

Antimicrobial resistance in staphylococci. Epidemiology, molecular mechanisms, and clinical relevance

Staphylococcal infections continue to pose important clinical problems in children and adults. Antibiotic resistance among the staphylococci has rendered therapy of these infections a therapeutic challenge. Despite early, uniform susceptibility to penicillin, staphylococci acquired a gene elaborating beta-lactamase that rendered penicillin inactive and that is borne by nearly all clinical isolates. "Penicillinase-resistant beta-lactams," such as methicillin, were introduced in the early 1960s, but resistance to them has become an increasing concern. The mechanism of the so-called "methicillin resistance" is complex. Moreover, once confined to the ecology of hospitals and other institutions, a recent increase in community-acquired methicillin-resistant S. aureus infections has been observed. Glycopeptides, until now the only uniformly reliable therapeutic modality, have been increasingly used for therapy of staphylococcal infections. The recent recognition of clinical isolates with reduced susceptibility to glycopeptides is of concern.     

The mechanisms of formation and prevention of channel segregation during alloy solidification

Conditions for the formation of macroscopic segregation channels have been examined in the ammonium chloride-water and lead-tin systems, using base chilled molds. Such channels develop when the rejected solute is less dense than the solvent and are therefore a result of density inversion, but slow (≺5 rpm) rates of mold rotation, about axes inclined to the vertical by 20 deg to 30 deg, throughout the time of solidification, effectively prevent the formation or propagation of these channels. Artificially created channels or those momentarily blocked fail to continue and are overgrown, but channels can be initiated by drawing liquid upward from close to the growth front in fine capillaries. Examination of these effects leads to the conclusion that channels originate at the growth front, rather than within the dendritic array, and that their formation is necessarily preceded by a liquid perturbation from the less dense boundary layer into the supernatant, quiescent bulk liquid. Intermittent ‘solute fingers’ are then fed by dendritic entrainment to produce stable convective plumes and concomitant channels. It is considered that the effects of mold precession are primarily caused by translation of bulk liquid across the dendritic growth front, shearing off convective perturbations from the boundary layer before they have time to develop. The nature of the liquid movements is discussed and shown to be a function of the mold dimensions. The inclination of the gravitational vector within the solid-liquid, dendritic array is considered to be of secondary importance to the formation or prevention of channels. This paper is based on a presentation made at the symposium “Fluid Flow at Solid-Liquid Interfaces” held at the fall meeting of the TMS-AIME in Philadelphia, PA on October 5, 1983 under the TMS-AIME Solidification Committee.     

Metabolic encephalopathy as a complication of renal failure: mechanisms and mediators

Among patients with end-stage renal disease, nervous system dysfunction remains a major cause of disability. Patients with chronic renal failure who have not yet received dialysis may develop symptoms ranging from mild sensorial clouding to delirium and coma. Dialysis itself is associated with at least three distinct disorders of the CNS: dialysis disequilibrium syndrome; dialysis dementia; and progressive intellectual dysfunction. Peripheral neuropathy is also a major cause of disability in uremic subjects. It is believed that aluminum contributes to the pathogenesis of dialysis dementia. Biochemically, brain calcium is elevated in patients with renal failure, probably because of actions of parathyroid hormone on the brain. The diagnosis of dialysis disequilibrium syndrome, intellectual dysfunction, dialysis dementia, and uremic neuropathy can be made by the characteristic clinical pictures of these syndromes and the exclusion of other causes of nervous system dysfunction.     

The molecular mechanisms of actin-based intracellular motility by Listeria monocytogenes

A rapid, sensitive method was developed for the quantification of the R- and S-enantiomers of ketoprofen and their acyl glucuronide conjugates in the plasma and dialysate of hemodialysis-dependent anephric patients. Unconjugated R- and S-ketoprofen plasma concentrations were determined directly by liquid chromatography using a S,S-Whelk-O1 chiral stationary phase. R- and S-Ketoprofen glucuronide for use as standard were resolved using a C18 reversed-phase HPLC column with a mobile phase containing the ion-pair reagent tetrabutylammonium hydrogen sulfate. Plasma glucuronides, however, could not be directly quantified due to matrix interference. Therefore, the glucuronides were isolated using reversed-phase HPLC and quantified after alkaline hydrolysis using the S,S-Whelk-O1 chiral stationary phase column.     

Polarity of epithelial cells of the liver. Cellular and molecular mechanisms, and pathologic changes

Smooth muscle contraction is primarily regulated not only by changes in cytosolic Ca2+ concentrations ([Ca2+]i) but also by changes in the force/[Ca2+]i ratio. The use of membrane-permeabilization technique facilitated demonstration of an increase in the level of force at constant [Ca2+]i (Ca2+ sensitization). It was clarified that Rho-associated kinase (Rho-kinase) is a novel mediator of Ca2+ sensitization of the smooth muscle contraction, by introducing the recombinant catalytic domain of Rho-kinase into the cytosol of vascular smooth muscle permeabilized with beta-escin. This review article focuses on novel mechanisms, by which activation of receptor-coupled G-protein(s) increases Ca2+ sensitivity of the contractile apparatus in smooth muscle: Rho-kinase and protein kinase C.