Lymphocyte-increasing action and hypocalcemic action of parotid gland extract.

It has previously been shown in our laboratory that the hypocalcemic substances purified from the thymus have a potent lymphocyte-increasing action in mice. Then, lymphocyte-increasing activity was examined with bovine parotid gland extracts, which showed a hypocalcemic activity as potent as that of the thymus extracts. The lymphocyte-increasing activity was assayed in the littermates of neonatal mice of Swiss-Webster strain; the materials used for this experiment were purified preparations and several fractions obtained from the parotid gland extracts in the course of purification. It was found that the potency of lymphocyte-increasing activity rose approximately in parallel with the rise in hypocalcemic activity with progress in purification. The final product, which was purified from the gland by isoelectric precipitation at pH 5.4, fractional precipitation with ammonium sulfate, chromatography on DEAE-cellulose, gel filtration on Sepharose 6B and preparative disc electrophoresis, gave a single band in polyacrylamide gel electrophoresis. Its intravenous injection in rabbits, in a dose of 10 mug/kg, produced a significant lowering in serum calcium (percent decrease 10.24 +/- 1.06%) compared with control animals given an injection of physiological saline. Intraperitoneal injection of this purified product, in a dose of 0.5 mug/mouse, in the littermates of neonatal mice, also produced a significant increase (ratio of lymphocytes to polymorphs 2.47 +/- 0.07) in lymphocytes compared with control animals injected with physiological saline (L/P ratio 1.57 +/- 0.05). These facts suggest that this purified protein fraction inherently contains both activities, but the possibility cannot be ruled out of slight contamination by a substance having a high activity. On the other hand, a fraction having no activity for lowering serum calcium but which had activity for increasing the lymphocytes was obtained. This is the first paper to report the presence of lymphocyte-increasing substances in the bovine parotid gland and the purification of one of the substances from the gland.     

Self-awareness and action

In this review we discuss how we are aware that actions are self-generated. We review behavioural data that suggest that a prediction of the sensory consequences of movement might be used to label actions and their consequences as self-generated. We also describe recent functional neuroimaging experiments and studies of neurological and psychiatric patients, which suggest that the parietal cortex plays a crucial role in the awareness of action.     

Structure and action of urocanase

Urocanase (EC 4.2.1.49) from Pseudomonas putida was crystallized after removing one of the seven free thiol groups. The crystal structure was solved by multiwavelength anomalous diffraction (MAD) using a seleno-methionine derivative and then refined at 1.14 A resolution. The enzyme is a symmetric homodimer of 2 x 557 amino acid residues with tightly bound NAD+ cofactors. Each subunit consists of a typical NAD-binding domain inserted into a larger core domain that forms the dimer interface. The core domain has a novel chain fold and accommodates the substrate urocanate in a surface depression. The NAD domain sits like a lid on the core domain depression and points with the nicotinamide group to the substrate. Substrate, nicotinamide and five water molecules are completely sequestered in a cavity. Most likely, one of these water molecules hydrates the substrate during catalysis. This cavity has to open for substrate passage, which probably means lifting the NAD domain. The observed atomic arrangement at the active center gives rise to a detailed proposal for the catalytic mechanism that is consistent with published chemical data. As expected, the variability of the residues involved is low, as derived from a family of 58 proteins annotated as urocanases in the data banks. However, one well-embedded member of this family showed a significant deviation at the active center indicating an incorrect annotation.     

The role of ventral premotor cortex in action execution and action understanding

The human ventral premotor cortex overlaps, at least in part, with Broca's region in the dominant cerebral hemisphere, that is known to mediate the production of language and contributes to language comprehension. This region is constituted of Brodmann's areas 44 and 45 in the inferior frontal gyrus. We summarize the evidence that the motor related part of Broca's region is localized in the opercular portion of the inferior frontal cortex, mainly in area 44 of Brodmann. According to our own data, there seems to be a homology between Brodmann area 44 in humans and the monkey area F5. The non-language related motor functions of Broca's region comprise complex hand movements, associative sensorimotor learning and sensorimotor integration. Brodmann's area 44 is also a part of a specialized parieto-premotor network and interacts significantly with the neighbouring premotor areas. In the ventral premotor area F5 of monkeys, the so called mirror neurons have been found which discharge both when the animal performs a goal-directed hand action and when it observes another individual performing the same or a similar action. More recently, in the same area mirror neurons responding not only to the observation of mouth actions, but also to sounds characteristic to actions have been found. In humans, through an fMRI study, it has been shown that the observation of actions performed with the hand, the mouth and the foot leads to the activation of different sectors of Broca's area and premotor cortex, according to the effector involved in the observed action, following a somatotopic pattern which resembles the classical motor cortex homunculus. On the other hand the evidence is growing that human ventral premotor cortex, especially Brodmann's area 44, is involved in polymodal action processing. These results strongly support the existence of an execution-observation matching system (mirror neuron system). It has been proposed that this system is involved in polymodal action recognition and might represent a precursor of language processing. Experimental evidence in favour of this hypothesis both in the monkey and humans is shortly reviewed.     

Dispersion and natural-enemy action

Animal dispersion was defined by Wynne-Edwards (1962) as 'the placement of individuals and groups of individuals within the habitats they occupy, and the processes by which this is brought about'. This paper deals with a limited aspect of this theme, namely with the influence of the dispersion of host or enemy individuals on their mutual interaction. Obviously, there can only be a relation between feeding organisms and food, between killer and victim, if they coincide in space and in time. Thus, what first seemed to be a limited topic evolves as one of the basic chapters of relations among organisms, that of coincidence (cf. Thalenhorst, 1951). It seems to be impossible to deal with space coincidence here without mentioning time coincidence, too. Recognizing the tremendous amount of information available on this subject, I should like to give some examples only, first on enemy action without man's interference and secondly on human action which either favours or disrupts space coincidence of both groups of organisms. For the sake of brevity, the term host will be frequently used for host and prey together and examples will mostly refer to insects.     

Differential action of hepatic sympathetic neuropeptides: metabolic action of galanin, vascular action of NPY

Activation of hepatic nerves increases both hepatic glucose production (HGP) and hepatic arterial vasoconstriction, the latter best described by a decrease of hepatic arterial conductance (HAC). Because activation of canine hepatic nerves releases the neuropeptides galanin and neuropeptide Y (NPY) as well as the classical neurotransmitter norepinephrine (NE), we sought to determine the relative role of these neuropeptides vs. norepinephrine in mediating metabolic and vascular responses of the liver. We studied the effects of local exogenous infusions of galanin and NPY on HGP and HAC to predict the metabolic and vascular function of endogenously released neuropeptide. Galanin (n = 8) or NPY (n = 4) was infused with and without NE directly into the common hepatic artery of halothane-anesthetized dogs, and we measured changes in HGP and HAC. A low dose of exogenous galanin infused directly into the hepatic artery potentiated the HGP response to NE yet had little effect on HGP when infused alone. The same dose of galanin infused into a peripheral vein (n = 8) did not potentiate the HGP response to NE, suggesting that the locally infused galanin acted directly on the liver to modulate NE's metabolic action. In contrast, a large dose of exogenous NPY failed to influence HGP when infused either alone or in combination with NE. Finally, NPY, but not galanin, tended to decrease HAC when infused alone; neither neuropeptide potentiated the HAC response to NE. Therefore, both hepatic neuropeptides may contribute to the action of sympathetic nerves on liver metabolism and blood flow. It is likely that endogenous hepatic galanin acts directly on the liver to selectively modulate norepinephrine's metabolic action, whereas endogenous hepatic NPY acts independently of NE to cause vasoconstriction.     

Bio-agency and the problem of action

The Aristotle-Kant tradition requires that autonomous activity must originate within the self and points toward a new type of causation (different from natural efficient causation) associated with teleology. Notoriously, it has so far proven impossible to uncover a workable model of causation satisfying these requirements without an increasingly unsatisfying appeal to extra-physical elements tailor-made for the purpose. In this paper we first provide the essential reason why the standard linear model of efficient causation cannot support the required model of agency: its causal thread model of efficient causation cannot support the core requirement that an action is determined by, and thus an expression of, the agent’s nature. We then provide a model that corrects these deficiencies, constructed naturalistically from within contemporary biology, and argue that it provides an appropriate foundation for all the features of genuine agency. Further, we provide general characterisations of freedom and reason suitable to this bio-context (but that also capture the core classical conceptions) and show how this model reconciles them.

硫酸糖肽的生物活性及药理作用

黏多糖类物质独特的生物活性已成为生物化学和医学领域的热点。硫糖肽作为黏多糖类的一种,具有广泛的抗炎、抗溃疡作用,尤其是预防和治疗溃疡方面的优势引起人们越来越多的关注,具有广阔的药物开发和应用前景。本文就硫糖肽的生物活性及其药理作用展开综述,并结合硫糖肽的市场需求和研究现状进行了展望。     

Sphingosylphosphorylcholine-biological functions and mechanisms of action

Compared to the lysophospholipid mediators, sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA), little information is available regarding the molecular mechanisms of action, metabolism and physiological significance of the related sphingosylphosphorylcholine (SPC). S1P and LPA have recently been established as agonists at several G-protein-coupled receptors of the EDG family, S1P additionally serves an intracellular second messenger function. Several cellular effects of SPC can be explained by low-affinity binding to and activation of S1P-EDG receptors. However, certain cellular and subcellular actions of SPC are not shared by S1P, suggesting that SPC, which has been identified in normal blood plasma, ascites and various tissues, is a lipid mediator in its own right. This concept was corroborated by the recent discovery of specific high-affinity G-protein-coupled SPC receptors. In this article, our present knowledge on cellular actions and biological functions of SPC will be reviewed.