Sensitivity of BALB/c and WR strain mice to the immunodepressive action of cyclophosphamide and thiophosphamide

Experiments were made on BALB/cJ YSto and WR/Y mice to study the immunosuppressant action of cyclophosphamide (CP) and thiophosphamide (thiotepa) in vivo. WR mice were found to be significantly more sensitive to the immunosuppressant action of thiotepa than BALB/c mice and to have similar sensitivity to the action of CP. BALB/c mice appeared highly resistant to the action of both the drugs. Based on the data obtained and those reported in the literature a possible parallelism is suggested between the mutagenic and immunosuppressant action of CP and thiotepa.     

Behavioral fingerprints predict insecticide and anthelmintic mode of action

Novel invertebrate‐killing compounds are required in agriculture and medicine to overcome resistance to existing treatments. Because insecticides and anthelmintics are discovered in phenotypic screens, a crucial step in the discovery process is determining the mode of action of hits. Visible whole‐organism symptoms are combined with molecular and physiological data to determine mode of action. However, manual symptomology is laborious and requires symptoms that are strong enough to see by eye. Here, we use high‐throughput imaging and quantitative phenotyping to measure Caenorhabditis elegans behavioral responses to compounds and train a classifier that predicts mode of action with an accuracy of 88% for a set of ten common modes of action. We also classify compounds within each mode of action to discover substructure that is not captured in broad mode‐of‐action labels. High‐throughput imaging and automated phenotyping could therefore accelerate mode‐of‐action discovery in invertebrate‐targeting compound development and help to refine mode‐of‐action categories.     

Receptor potentials and action potentials in Drosera tentacles

Summary Voltage fluctuations identified as receptor potentials can be detected with electrodes applied to the mucilage surrounding the head of a tentacle of Drosera intermedia if the head is stimulated by contact with a live insect, by the touch of a clean, inert object, or by application of salt solutions. Associated with a low receptor potential are action potentials, which occur at a frequency dependent on the magnitude of the receptor potential. These action potentials can be detected with electrodes applied to any region of the stalk of the tentacle. Inflection of the lower stalk follows the occurrence of action potentials. Inflection is minute for isolated action potentials but large and rapid when several occur within a brief interval.The apparent amplitude of action potentials recorded from the stalk is independent of receptor potential amplitude, but that of action potentials recorded from the mucilage commonly decreases as the receptor potential deviates from the baseline and increases as it returns. It is suggested that variation of apparent amplitude of the action potentials may result from postulated variation in the resistance of receptor membranes.     

Ritual and the Constitution of Social Structure

The constitution and reproduction of structure through the action orientations of social actors remains a basic question in the social sciences. Most sociological theories have stressed a purposive-rational model of action in the constitution of structure. These models of action have not been able to account for either the external constraints of structure or for its internal obligatory nature. This paper argues that a theory of ritual action is able to explain both the external and the internal obligatory nature of social structure.     

胰岛素信号转导障碍与胰岛素抵抗的形成

胰岛素生理作用的发挥,起始于胰岛素与其受体的结合,并由此引起细胞内一系列信号转导,最终到达各效应器产生各种生理效应。胰岛素信号转导在胰岛素生理作用的发挥中起着至关重要的作用。胰岛素信号转导减弱或受阻,使得胰岛素生理作用减弱,导致胰岛素抵抗形成。本文综述了胰岛素信号转导失调在胰岛素抵抗形成中的作用。     

Species differences in ligand specificity of auxin-controlled elongation and auxin transport: comparing Zea and Vigna

The plant hormone auxin affects cell elongation in both roots and shoots. In roots, the predominant action of auxin is to inhibit cell elongation while in shoots auxin, at normal physiological levels, stimulates elongation. The question of whether the primary receptor for auxin is the same in roots and shoots has not been resolved. In addition to its action on cell elongation in roots and shoots, auxin is transported in a polar fashion in both organs. Although auxin transport is well characterized in both roots and shoots, there is relatively little information on the connection, if any, between auxin transport and its action on elongation. In particular, it is not clear whether the protein mediating polar auxin movement is separate from the protein mediating auxin action on cell elongation or whether these two processes might be mediated by one and the same receptor. We examined the identity of the auxin growth receptor in roots and shoots by comparing the response of roots and shoots of the grass Zea mays L. and the legume Vigna mungo L. to indole-3-acetic acid, 2-naphthoxyacetic acid, 4,6-dichloroindoleacetic acid, and 4,7-dichloroindoleacetic acid. We also studied whether or not a single protein might mediate both auxin transport and auxin action by comparing the polar transport of indole-3-acetic acid and 2-naphthoxyacetic acid through segments from Vigna hypocotyls and maize coleoptiles. For all of the assays performed (root elongation, shoot elongation, and polar transport) the action and transport of the auxin derivatives was much greater in the dicots than in the grass species. The preservation of ligand specificity between roots and shoots and the parallels in ligand specificity between auxin transport and auxin action on growth are consistent with the hypothesis that the auxin receptor is the same in roots and shoots and that this protein may mediate auxin efflux as well as auxin action in both organ types.     

Experimental study of the interaction of nonsteroidal anti-inflammatory agents--voltaren and acetylsalicylic acid--with beta-adrenoblockers

It has been demonstrated in rat experiments that the beta-adrenoblockers propranolol and pindolol differ in the influence on the therapeutic and toxic effects of voltaren and acetylsalicylic acid. Propranolol has an analgetic action of its own, reducing the analgetic and antiinflammatory effects of voltaren and acetylsalicylic acid. It potentiates the antipyretic effect of voltaren and ulcerogenic action of both nonsteroidal antiinflammatory drugs. Pindolol exerts both analgetic and antiinflammatory action and does not affect the antipyretic effect of voltaren and ulcerogenic action of nonsteroidal antiinflammatory drugs. The difference in the action of the beta-adrenoblockers under study is likely to be linked with the characteristics of their pharmacological action spectrum.     

The Genesis and Transmission of Epidermal Potentials of Newt Embryonic Cells in Vivo and in Vitro

The genesis and transmission of action potentials in epidermal cells of a newt ( Cynops pyrrhogaster ) embryo were investigated quantitatively in vivo during development and in vitro in the absence of nerve cells. Typical action potentials, composed of a fast spike followed by a slow action potential, can be recorded from any of the epidermal cells from Stage 24/25 to 35/36. The potential is graded with current intensity, and only the slow component induces transmission to other epidermal cells. The fast spike is found in all epidermal cells from Stage 24/25 to Stage 50; it is abolished by Stage 52. The slow potential disappears at Stage 38 just before or after hatching. The cultured epithelioid explants (epithelioid aggregate) and cultured monolayer cells taken from the presumptive epidermal tissue of the ectoderm of the pregastrula, indicate that sequential changes in the genesis of the dual action potentials are similar to those of the intact embryo. In monolayer cell culture devoid of nerve cells, the epidermal cells, also generate a two-step action potential. Such two-step potentials are characteristic of both ciliated and non-ciliated epidermal cells and occur even during mitotic activity. In contrast, cultured neural plate cells isolated from the neurula generate typical spike-like action potentials.     

Separation of the action potential into a Na-channel spike and a K- channel spike by tetrodotoxin and by tetraethylammonium ion in squid giant axons internally perfused with dilute Na-salt solutions

Squid giant axons internally perfused with a 30 mM NaF solution and bathed in a 100 mM CaCl2 solution, which are known to produce long lasting action potentials in response to pulses of outward current, were investigated. The effects of tetrodotoxin (TTX) and of tetraethylammonium ion (TEA+) on such action potentials were studied. The results are summarized as follows: (a) An addition of 1--3 microM TTX to the external solution altered but did not block the action potentials; it increased the height of the action potential by approximately 15 mV, and it decreased the membrane conductance as the peak of excitation by about two-thirds. (b) Voltage-clamp experiments performed with both NaCl and TTX in the external CaCl2 solution revealed that the TTX-insensitive action potential does not involve a rise in gNa, whereas the experiments performed without TTX showed that the action potential is accompanied by a large rise in gNa. (c) Internally applied TEA+ was shown to selectively block the TTX- insensitive action potential, but it did not block the other component of the action potential, which is accompanied by a rise in gNa, and which is selectively suppressed by TTX. (d) The addition of a small amount of KCl to the external CaCl2 solution containing TTX greatly increased both the maximum peak inward current under voltage clamp and the maximum slope conductance. Furthermore, it was shown that K+ applied on both sides of the axon plays a dominant role in producing the membrane potential in the active state in the presence of TTX, even though a large amount of Ca2+ is presented in the bathing medium. These observations have led me to conclude that the sodium channel is responsible for the production of the TTX-sensitive component of the action potential under the ionic conditions of these experiments, and the potassium channel for the TTX-insensitive component of the action potential.     

Differences in Na and Ca Spikes As Examined by Application of Tetrodotoxin, Procaine, and Manganese Ions

The effects of tetrodotoxin, procaine, and manganese ions were examined on the Ca spike of the barnacle muscle fiber injected with Ca-binding agent as well as on the action potential of the ventricular muscle fiber of the frog heart. Although tetrodotoxin and procaine very effectively suppress the "Na spike" of other tissues, no suppressing effects are found on "Ca spike" of the barnacle fiber, while the initiation of the Ca spike is competitively inhibited by manganese ions. The initial rate of rise of the ventricular action potential is suppressed by tetrodotoxin and procaine but the plateau phase of the action potential is little affected. In contrast the suppressing effect of manganese ions is mainly on the plateau phase. The results suggest that the plateau phase of the ventricular action potential is related to the conductance increase in the membrane to Ca ions even though Na conductance change may also contribute to the plateau.     

The theory of functional systems and purposeful behavior

The role of probability forecasting in the purposive behavior under conditions of subjective uncertainty is considered in terms of the theory of functional systems. Participation of the probability forecasting in the afferent synthesis, goal formation, formation of the acceptor of action result and action program, and, finally, in the action program actualization is substantiated. The model of behavior under conditions of subjective uncertainty is advanced. It includes all the classical elements of the model of behavioral act developed by P.K. Anokhin. In order to take into account the probability aspects of behavior, the role of probability forecasting is emphasized at every stage of the system functioning. In addition to the classical elements, two novel components are introduced. These are the "memory buffer" (results of searching reactions) and the apparatus of probability decisions about changes in the action program. By the memory buffer an apparatus is meant, which gathers and stores the information about the results of many behavioral acts performed during the actualization of the action program. This information is used in the process of making a probability decision as whether to alter or not the action program after each specific behavioral act. Such an approach integrates the probability forecasting and the theory of functional systems. The theory becomes universal, i.e., applicable not only to deterministic but also to probabilistic environments.     

Electrical signals in higher plants: Mechanisms of generation and propagation

Local stimulation induces generation and propagation of electric signals in higher plants. Noninvasive stimulus induces an action potential and damaging influences lead to the variation potential. The mechanism of the generation of an action potential is rather complex in nature and is associated with both activation of ion channels (Ca²⁺, Cl^–, and K⁺) and transient change in the activity of the plasma membrane H⁺-ATPase. Generation of the variation potential, the duration of which is considerably longer than that of the action potential, is based on transient inactivation of the electrogenic pump; however, passive ion fluxes also contribute to such process, which causes qualitative similarity of the mechanisms of action potential and variation potential generation. Propagation of electrical signals mainly occurs in conducting bundles; thus, transfer of an action potential is associated with vascular parenchyma and sieve elements, while the variation potential is connected to the xylem vessels. The mechanism of the distribution the action potential is similar to nerve impulse transmission, while generation of the variation potential is induced by transfer of a chemical substance, whose propagation is accelerated by a hydraulic wave.     

Toxicity of para-aminobenzhydrazide and its influence on nucleic acid biosynthesis in cultures of normal and tumor cells

We have investigated cytotoxic action of p-aminobenzhydrazide and its influence on biosynthesis of nucleic acids in cultures of intact cells, tumor cells and intact cells stimulated by phytohemagglutinin. p-Aminobenzhydrazide is considered as a representative of hydrazine's derivatives (in particular, of hydrazine sulphate). We compare its action with that of a typical cytotoxic agent such as iododeoxyuridine. We have found that p-aminobenzhydrazide influences biosynthesis of nucleic acids in the same way as iododeoxyuridine. However it acts toxically on tumor cells though it is not toxic for intact cells so that its action is different as compared to that of cytotoxic agents. Specific toxic action of aminobenzhydrazide on tumor cells may be due to the enhancement of antitumor activity substances of this compound and absence of such enhancement of side toxic effects.     

Regulating and disturbing effects of alpha-tocopherol on lipid bilayers

Using the high resolution 1H-NMR spectroscopy and spin-probes the influence of alpha-tocopherol on lipid bilayer microviscosity has been studied. It has been established that alpha-tocopherol shows the cholesterol-like action on the physical state of lipid bilayer: alpha-tocopherol increase microviscosity of unsaturated bilayers and decrease microviscosity of saturated bilayers. The character of alpha-tocopherol action is determined by the fatty acidic lipid composition but does not depend on the polar group structure of phospholipid molecule as cholesterol-like action of alpha-tocopherol is found itself in liposomes prepared both from phosphatidylcholine and phosphatidylethanolamine. Analog of alpha-tocopherol without phytol chain 2,2,5,7,8-penthamethyl-6-oxychroman does not show the cholesterol-like action as it is not able to disorder the saturated bilayers.     

Growth inhibitory effect of antibiotic tetaine on yeast and mycelial forms of Candida albicans

The mycelial (M) form of Candida albicans is more sensitive to the action of the antibiotic tetaine than the yeast (Y) form. Tetaine, at low concentrations about 1 microgram/ml also inhibits Y-M transition. It causes severe deformation of cells, agglutination and inhibits septum formation in the yeast forms. Tetaine action is reversed by dipeptides in both forms and by tripeptides in M form. N-acetyl glucosamine is a powerful antagonist of tetaine action on both morphological forms. Tetaine action on mycelial forms is slightly antagonised by N-acetyl mannosamine and very powerfully by glutamine.     

Actions,Action Sequences and Habits: Evidence That Goal-Directed and Habitual Action Control Are Hierarchically Organized

Behavioral evidence suggests that instrumental conditioning is governed by two forms of action control: a goal-directed and a habit learning process. Model-based reinforcement learning (RL) has been argued to underlie the goal-directed process; however, the way in which it interacts with habits and the structure of the habitual process has remained unclear. According to a flat architecture, the habitual process corresponds to model-free RL, and its interaction with the goal-directed process is coordinated by an external arbitration mechanism. Alternatively, the interaction between these systems has recently been argued to be hierarchical, such that the formation of action sequences underlies habit learning and a goal-directed process selects between goal-directed actions and habitual sequences of actions to reach the goal. Here we used a two-stage decision-making task to test predictions from these accounts. The hierarchical account predicts that, because they are tied to each other as an action sequence, selecting a habitual action in the first stage will be followed by a habitual action in the second stage, whereas the flat account predicts that the statuses of the first and second stage actions are independent of each other. We found, based on subjects'' choices and reaction times, that human subjects combined single actions to build action sequences and that the formation of such action sequences was sufficient to explain habitual actions. Furthermore, based on Bayesian model comparison, a family of hierarchical RL models, assuming a hierarchical interaction between habit and goal-directed processes, provided a better fit of the subjects'' behavior than a family of flat models. Although these findings do not rule out all possible model-free accounts of instrumental conditioning, they do show such accounts are not necessary to explain habitual actions and provide a new basis for understanding how goal-directed and habitual action control interact.     

Effect of phenylephrine on pyruvate dehydrogenase activity in rat hepatocytes and its interaction with insulin and glucagon

In isolated rat hepatocytes phenylephrine promotes a rapid increase in the amount of pyruvate dehydrogenase present in its active form (PDHa). This action is mediated by alpha 1-adrenergic receptors and is not observed in Ca2+-depleted hepatocytes. It is mimicked by the Ca2+ ionophore A23187. No changes in metabolites known to affect PDH activity are measured 3 min after addition of phenylephrine. Glucagon also increases PDHa, its action is additive to that of phenylephrine. The action of phenylephrine on PDHa could be explained by an increase in mitochondrial free Ca2+.     

Insulin Action in Rats Is Influenced by Amount and Composition of Dietary Fat

The chronic influence of dietary fat composition on obesity and insulin action is not well understood. We examined the effect of amount (20% vs 60% of total calories) and type (saturated vs polyunsaturated) of fat on insulin action and body composition in mature male rats. Six months of feeding a high fat (HF) diet led to obesity and impaired insulin action (determined by a euglycemic-hyperinsulinemic clamp), neither of which were reversed by a subsequent 6 months of feeding a low fat (LF) diet. Within HF fed rats, type of fat did not affect body composition or insulin action. Six months of feeding a low fat diet led to only a slight decline in insulin action, with no difference due to type of dietary fat. From 6–9 months, insulin action became more impaired in LF rats fed the saturated diet than in LF rats fed the polyunsaturated diet. By 12 months, all groups were obese and had a similar impairment in insulin action. The amount and type of fat in the diet did not influence the overall degree of impairment in insulin action but did affect the time course. Both feeding a high fat diet and feeding a low fat saturated diet accelerated the impairment in insulin action relative to rats fed a low fat polyunsaturated fat diet.     

A Quantitative Description of the Relationship between the Area of Rabbit Ventricular Action Potentials and the Pattern of Stimulation

Intracellular microelectrodes were used to record action potentials from fibres of the isolated rabbit right ventricle and the areas of the action potentials were measured. The action potential area was found to depend in a reproducible way on the preceding pattern of stimulation. A mathematical model reproducing all the observed changes in the action potential area was developed. In the model the action potential area is taken as a linear function of the product of two time and stimulation dependent variables, M and N. The behaviour of each variable between action potentials is described by the solution of a second order differential equation. During each action potential the variables are assumed to change discontinuously, the magnitudes of the discontinuous changes being given by a set of subsidiary equations. It was found that the behaviour of all the fibres tested was described by the same set of equations, each single fibre being characterized by a set of ten independent constants.