Nalorphine: actions at an opiate receptor on frog skeletal muscle fibers

Intracellular microelectrode studies were conducted to investigate the actions of the partial agonist-antagonist nalorphine at an opiate receptor on functional frog skeletal muscle fiber membranes. In high bath concentrations (greater than or equal to 10(-4) M), nalorphine alone produces agonist actions similar to the "full" opiate agonists. These actions were (i) to depress both the sodium and potassium (gNa and gK) conductance increases due to electrical stimulation by a nonspecific local anestheticlike mechanism and (ii) to depress gNa by a specific opiate receptor mediated mechanism. In a much lower bath concentration (1 X 10(-8) M) nalorphine acts to antagonize the specific opiate receptor mediated depression of gNa produced by the "full" agonist meperidine. Thus in this preparation nalorphine, "the partial antagonist," has the same actions as naloxone, which is often considered to be a full antagonist. The quantitative differences observed in the effects of these two opiate antagonists are discussed.     

VANTED: A system for advanced data analysis and visualization in the context of biological networks

Background  

Recent advances with high-throughput methods in life-science research have increased the need for automatized data analysis and visual exploration techniques. Sophisticated bioinformatics tools are essential to deduct biologically meaningful interpretations from the large amount of experimental data, and help to understand biological processes.     

Peculiarities of modifying influence of the factors forming the functional status of the central nervous system on dynamics of the rat higher nervous activity disturbances totally exposed to electron and gamma-radiation at a dose of 100 Gy

The dynamics of using a stabilized motor defensive conditioned reflex of active avoidance in "shuttle-box" in rats after the total influence of high energy electrons and gamma-rays at a dose of 100 Gy and a modifying influence of the two most important factors forming the functional status of the central nervous system: the stage of the conditioned reflex consolidation and typological peculiarities of the higher nervous activity have been investigated. The influence of both types of ionizing radiation has been shown to cause far more profound disturbances of non consolidated conditioned reflexes in comparison with the automatized conditioned reflexes and provoke an inverted picture of disturbances in the animals with opposed peculiarities of the higher nervous activity. The qualitative picture of the dynamics of disturbances that are caused by these types of radiation is identical. In summary, the studied conditions that form the functional status of the central nervous system determine the nature of neuroradiation syndrome to a greater extent than differences in the effectiveness of these types of radiation.     

水稻单核苷酸多态性及其应用现状

单核苷酸多态性（single nucleotide polymorphisms, SNPs）在水稻中数量多,分布密度高,遗传稳定性高。水稻SNPs的发现方法主要有对样本DNA的PCR产物直接测序、从SSR区段检测SNPs和从基因组序列直接搜索等。目前已有多种基因分型技术运用到了水稻SNPs检测,SNPs检测的高度自动化使水稻SNPs基因分型非常方便。单核苷酸多态性在水稻遗传图谱的构建、基因克隆和功能基因组学研究、标记辅助选择育种、遗传资源分类及物种进化等方面的应用具有巨大潜力。     

INTERACTIVE EFFECTS OF CYCLOHEXIMIDE AND PUROMYCIN IN ALTERING BRAIN POLYRIBOSOMES AND NEURAL AND BEHAVIOURAL RESPONSES TO ELECTROSHOCK IN MICE

Abstract— Interactive effects of puromycin and cycloheximide on brain polyribosomes and cortical electrical activity were investigated. The time courses of action of the drugs on these parameters, in comparison to their inhibitory actions on protein synthesis, were also observed. The results indicate that the disruption of brain polyribosomes by cycloheximide was independent of its inhibition of protein synthesis, whereas the two processes were closely linked in the case of puromycin. For both the disruption of polyribosomes and the alteration of electrical activity, the order in which the drugs were administered was critical, with preadministration of cycloheximide having a protective effect. In contrast to the massive effect of cycloheximide on brain polyribosomes, the drug had no such effect on polyribosomes from liver.     

Observation and execution of upper-limb movements as a tool for rehabilitation of motor deficits in paretic stroke patients: protocol of a randomized clinical trial

ABSTRACT: BACKGROUND: Evidence exist that motor observation activates the same cortical motor areas that are involved in the performance of the observed actions. The so called "mirror neuron system" has been proposed to be responsible for this phenomenon. We employ this neural system and its capability to re-enact stored motor representations as a tool for rehabilitating motor control. In our new neurorehabilitative schema (videotherapy) we combine observation of daily actions with concomitant physical training of the observed actions focusing on the upper limbs. Following a pilot study in chronic patients in an ambulatory setting, we currently designed a new multicenter clinical study dedicated to patients in the sub-acute state after stroke using a home-based self-induced training. Within our protocol we assess 1) the capability of action observation to elicit rehabilitational effects in the motor system, and 2) the capacity of this schema to be performed by patients without assistance from a physiotherapist. The results of this study would be of high health and economical relevance. Methods/ Design A controlled, randomized, multicenter, paralleled, 6 month follow-up study will be conducted on three groups of patients: one group will be given the experimental treatment whereas the other two will participate in a control treatment. All patients will undergo their usual rehabilitative treatment beside participation in the study. The experimental condition consists in the observation and immediate imitation of common daily hand and arm actions. The two parallel control groups are a placebo group and a group receiving usual rehabilitation without any trial-related treatment. Trial randomization is provided via external data management. The primary efficacy endpoint is the improvement of the experimental group in a standardized motor function test (Wolf Motor Function Test) relative to control groups. Further assessments refer to subjective and qualitative rehabilitational scores. This study has been reviewed and approved by the ethics committee of Aachen University. DISCUSSION: This therapy provides an extension of therapeutic procedures for recovery after stroke and emphasizes the importance of action perception in neurorehabilitation The results of the study could become implemented into the wide physiotherapeutic practice, for example as an ad on and individualized therapy.     

Assessment of socio-economic ramifications

Implementation of remedial measures for contaminated sediments may well have to contend with the not in my backyard (NIMBY) syndrome. These are situations characterized by high levels of distrust which include transference of these feelings to the assessment techniques used to select the measures. Hence, there is an underlying contextual issue relating to the perceived legitimacy of the process through which decisions are made as the ramifications become apparent. The experiences of agencies searching for satisfactory solutions to such problems need to be more widely known.Moreover, remedial measures for contaminated sediments are but one portion of a set needed to rehabilitate degraded aquatic ecosystems. Recent collaborative work to outline feasible strategies for ecosystem rehabilitation in the Great Lakes is outlined. Such strategies are scientifically feasible, socio-economically defensible, and the institutions to address the problems are available. However, strategies need to be tailored to the circumstances of selected near-shore areas. For two such areas, analyses of societal arrangements have been directed to identifying the relevant actor system composed of government agencies and non-governmental groups, and assessing the alternatives to regulatory management. Various collaborative processes to facilitate rehabilitative management are noted, but the contextual issue remains pre-eminantly important.     

Separation technologies for glycomics

Progress in genome projects has provided us with fundamentals on genetic information; however, the functions of a large number of genes remain to be elucidated. To understand the in vivo functions of eukaryotic genes, it is essential to grasp the features of their post-translational modifications. Among them, protein glycosylation is a central issue to be discussed, considering the predominant roles of glycoproteins in cell-cell and cell-substratum recognition events in multicellular organisms. In this context, it is necessary to establish a core strategy for analyzing glycosylated proteins under the concept of the "glycome" [Trends Glycosci. Glycotechnol. 12 (2000) 1]. Though the term glycome should be defined, in analogy to the genome and proteome, as "a whole set of glycans produced in a single organism", here we propose a glycome project specifically focusing on glycoproteins. Principal objectives in the project are to identify: (1) which genes encode glycoproteins (i.e. genome information); (2) which sites among potential glycosylation sites are actually glycosylated (i.e. glycosylation site information); (3) what are the structures of glycans (i.e. structural information); and (4) what are the effects (functions) of glycosylation (functional information). For these purposes, two affinity technologies have been introduced. One is named the "glyco-catch method" to identify genes encoding glycoproteins [Proteomics 1 (2001) 295], and the other is the recently reinforced "frontal affinity chromatography" [J. Chromatogr. A 890 (2000) 261]. By the former method, genes that encode glycoproteins as well as glycosylation sites are systematically identified by the efficient combination of conventional lectin-affinity chromatography and contemporary in silico database searching. The following three actions have been devised for rapid and systematic characterization of glycans: (1) mass spectrometry to acquire exact mass information; (2) 2-D/3-D mapping to obtain refined chemical information; and (3) reinforced frontal affinity chromatography to determine affinity constants (K(a)-values) for a set of lectins. Pyridylaminated glycans are used throughout the characterization processes. In this review, the concept and strategy of glycomic approaches are described referring to the on-going glycome project focused on the nematode Caenorhabditis elegans.     

Cellulose: To depolymerize… or not to?

Oxidation of the primary OH groups in cellulose is a pivotal reaction both at lab and industrial scale, leading to the value-added products, i.e. oxidized cellulose which have tremendous applications in medicine, pharmacy and hi-tech industry. Moreover, the introduction of carboxyl moieties creates prerequisites for further cellulose functionalization through covalent attachment or electrostatic interactions, being an essential achievement designed to boost the area of cellulose-based nanomaterials fabrication. Various methods for the cellulose oxidation have been developed in the course of time, aiming the selective conversion of the OH groups. These methods use: nitrogen dioxide in chloroform, alkali metal nitrites and nitrates, strong acids alone or in combination with permanganates or sodium nitrite, ozone, and sodium periodate or lead (IV) tetraacetate. In the case of the last two reagents, cellulose dialdehydes derivatives are formed, which are further oxidized by sodium chlorite or hydrogen peroxide to form dicarboxyl groups. A major improvement in the cellulose oxidation was represented by the introduction of the stable nitroxyl radicals, such as 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO). However, a major impediment for the researchers working in this area is related with the severe depolymerisation occurred during the TEMPO-mediated conversion of CH₂OH into COOH groups. On the other hand, the cellulose depolymerisation represent the key step, in the general effort of searching for alternative strategies to develop new renewable, carbon-neutral energy sources. In this connection, exploiting the biomass feed stocks to produce biofuel and other low molecular organic compounds, involves a high amount of research to improve the overall reaction conditions, limit the energy consumption, and to use benign reagents. This work is therefore focused on the parallelism between these two apparently antagonist processes involving cellulose, building a necessary bridge between them, thinking how the reported drawbacks of the TEMPO-mediated oxidation of cellulose are heading towards to the biomass valorisation, presenting why the apparently undesired side reactions could be turned into beneficial processes if they are correlated with the existing achievements of particular significance in the field of cellulose conversion into small organic compounds, aiming the general goal of pursuing for alternatives to replace the petroleum-based products in human life.     

Improving fluorescence-based assays for the in vitro analysis of cell adhesion and migration

Cell adhesion and cell migration are two primary cellular phenomena to be approached in vitro in order to allow for the effective dissection of the individual events and the unravelling of their underlying molecular mechanisms. The use of assays dedicated to the analysis of cell adhesion and migration in vitro also affords an efficient way of conducting larger basic and applied research screenings of the conditions affecting these processes and are potentially exploitable in the context of routine tests in the biological and medical fields. Therefore, there is a substantial interest in devicing more rationale such assays and major contributions in this direction have been provided by the advent of procedures based on fluorescent cell tagging. In this article we describe three fluorescence-based model assays for the qualitative and quantitative assessment of cell adhesion and cell locomotion in static and dynamic conditions. The assays are easily performed, accurate and reproducible, and can be automatized for high-throughput screenings of cell behavior in vitro. Performance of the assays involves the use of certain dedicated disposable accessories, which are commercially available, and a few instruments that, due to their versatility, can be regarded as constituents of a more generic laboratory setup.     

Mechanism of prolactin action

Most experimental information regarding the mechanism of action of prolactin in its diverse array of target tissues has been discovered using mammary tissues. Evidence has recently been presented that suggests that prolactin may be "internalized" into its target cells and have intracellular actions. Accordingly, it has been reported that prolactin stimulates RNA synthesis in isolated nuclei from mammary tissues; and by immunoflorescent studies, prolactin has been located within its target cells. It has been further suggested from additional experimental studies that the primary action of prolactin may involve its initial interaction with fixed plasma membrane receptor sites. Subsequent actions of prolactin may involve the following: a) an increased intracellular concentration of potassium and a reduced level of sodium, b) an increased level of cGMP and a reduced level of cAMP, c) an enhanced rate of prostaglandin biosyntheesis mediated by a stimulation of phospholipase A2 activity, and d) a stimulation of polyamine synthesis. It has also been shown that the actions of prolactin require calcium ions in the extracellular environment. Laboratory studies have thus indicated that the actions of prolactin may be carried out by a number of processes; but a single, primary action of this hormone that accounts for all of its actions has not yet been proven.     

High performance liquid chromatography of nucleotides. Major methods and their development

The separation of mono- and oligonucleotides possibilities by means of high performance ion-exchange, reversed-phase, so-called "ion-pair" and adsorption chromatography are studied. The influence of the eluent composition (solvent, salt) and pH on the retention, selectivity and resolution in reversed-phase and ion-exchange chromatography is investigated. The model of the hydrophobic-pair ion-exchange mechanism of ion-pair chromatography is considered. The conditions for analysis and preparative isolation of a desired component are optimized for selectivity, resolution and throughput. The methods for prediction of the optimal gradient elution program reasonable resolution at the desired retention time and for choosing the guard-column packing material are proposed. A design of the gradient for system and the version of slurry packing method for HPLC prolonged life-time columns are improved. The automatized analytical technique for determination of the oligonucleotide monomeric composition with two coupled microcolumns is described, that involves enzymatic digestion of an oligonucleotide followed by ion-exchange separation of the hydrolysate.     

Radiation resistance of motor-defensive conditioned reflexes in rats at different stages of the formation and stabilization of a temporary connection

Disturbances were studied of the motor defensive conditioned reflexes in rats radiated in a dose of 100 Gy at different stages of formation and stabilization of temporary connection. In comparison with consolidated (automatized) conditioned reflexes of active avoidance, early stages of formation and stabilization of the temporary connection are characterized by a relatively low resistance against extreme factors and by deepest disturbances of reproduction in radiated animals. The most probable mechanisms of these disturbances are connected with pathological changes of the nervous processes balance towards an increase of excitability and weakening of internal inhibition. Yet a direct radiation influence on the mechanisms of temporary connection reproduction at the second stage of its consolidation cannot be excluded. The role is shown of the emotional reactivity in the above-described processes.     

In Vitro and In Vivo Neuronal Electrotaxis: A Potential Mechanism for Restoration?

Electrical brain stimulation used to treat a variety of neurological and psychiatric diseases is entering a new period. The technique is well established and the potential complications are well known and generally manageable. Recent studies demonstrated that electrical fields (EFs) can enhance neuroplasticity-related processes. EFs applied in the physiological range induce migration of different neural cell types from different species in vitro. There are some evidences that also the speed and directedness of cell migration are enhanced by EFs. However, it is still unclear how electrical signals from the extracellular space are translated into intracellular actions resulting in the so-called electrotaxis phenomenon. Here, we aim to provide a comprehensive review of the data on responses of cells to electrical stimulation and the relation to functional recovery.     

Coherent analysis of the electrical activity of the rabbit brain during the formation of a motor polarization dominant

By the method of spectral-coherent analysis the dynamics was studied of successive changes in the structure the rabbit brain electrical activity coherent relations in the process of formation of motor polarization dominant created by DC anode action on the sensorimotor cortical region. It has been shown that at earlier stages, when the motor "dominant" reaction is absent, there appears an interhemispheric asymmetry in Coh spectra of electrical activity of the sensorimotor cortex and of the thalamus VPL. On the contrary, interhemispheric asymmetry in Coh spectra of electrical activity of the sensorimotor cortex and dorsal hippocampus CA3 field appears only at the stage when the motor "dominant" reaction is recorded. Asymmetry in alpha- and beta-frequencies ranges in biopotentials Coh spectra of the studied regions coinciding with the motor "dominant" reaction realization is connected with processes of movement organization.     

Proteins of Excitable Membranes

Excitable membranes have the special ability of changing rapidly and reversibly their permeability to ions, thereby controlling the ion movements that carry the electric currents propagating nerve impulses. Acetylcholine (ACh) is the specific signal which is released by excitation and is recognized by a specific protein, the ACh-receptor; it induces a conformational change, triggering off a sequence of reactions resulting in increased permeability. The hydrolysis of ACh by ACh-esterase restores the barrier to ions. The enzymes hydrolyzing and forming ACh and the receptor protein are present in the various types of excitable membranes. Properties of the two proteins directly associated with electrical activity, receptor and esterase, will be described in this and subsequent lectures. ACh-esterase has been shown to be located within the excitable membranes. Potent enzyme inhibitors block electrical activity demonstrating the essential role in this function. The enzyme has been recently crystallized and some protein properties will be described. The monocellular electroplax preparation offers a uniquely favorable material for analyzing the properties of the ACh-receptor and its relation to function. The essential role of the receptor in electrical activity has been demonstrated with specific receptor inhibitors. Recent data show the basically similar role of ACh in the axonal and junctional membranes; the differences of electrical events and pharmacological actions are due to variations of shape, structural organization, and environment.     

Drugs that interact with cardiac electro-mechanics: old and new targets for treatment

The concept of mechano-electrical feedback was derived from the observation that a short stretch applied to the beating heart can invoke an electrical response in the form of an afterdepolarization or a premature ventricular beat. More recent work has identified stretch-activated channels whose specific inhibition might help to treat atrial fibrillation in the near future. But the interaction between electrical and mechanical function of the heart is a continuum from short-term (within milliseconds) to long-term (within weeks or months) effects. The long-term effects of pressure overload have been well-described on the molecular and cellular level, and substances that interact with these processes are used in clinical routine in the care of patients with cardiac hypertrophy and heart failure. These treatments help to prevent lethal arrhythmias (sudden death) and potentially atrial fibrillation. The intermediate interaction between mechanical and electrical function of the heart is less well-understood. Several recently identified regulatory mechanisms may provide novel antiarrhythmic targets associated with the "intermediate" response of the myocardium to stretch.