Aromatic l-Amino Acid Decarboxylase Activity of the Rat Retina Is Modulated In Vivo by Environmental Light Maria Hadjiconstantinou

Aromatic L-amino acid decarboxylase (AAAD) activity of rat retina is low in animals placed in the dark. When the room lights are turned on, activity rises for almost 3 h and reaches values that are about twice the values found in the dark. A study of the kinetics of the enzyme revealed that the apparent Km values for L-3,4-dihydroxyphenylalanine and pyridoxal-5'-phosphate were unchanged in light- and dark-exposed animals, whereas the Vmax increased in the light. Treating the animals with cycloheximide before exposure to light prevented the increase of enzyme activity. Immunotitration with antibodies to AAAD suggested that more enzyme molecules are present in the light than in the dark. When the room lights are turned off AAAD activity drops rapidly at first and then more slowly, suggesting that at least two processes are responsible for the fall of enzyme activity. Exposure to short periods of dark followed by light results in a rapid increase of AAAD activity. Mixing homogenates from light- and dark-exposed rats results in activity values that are less than expected, suggesting the presence of an endogenous inhibitor(s). These studies demonstrate that AAAD activity is modulated in vivo.     

Bivariate optimization of pedalling rate and crank arm length in cycling

The contribution of this paper is a bivariate optimization of cycling performance. Relying on a biomechanical model of the lower limb, a cost function derived from the joint moments developed during cycling is computed. At constant average power, both pedalling rate (i.e. rpm) and crank arm length are systematically varied to explore the relation between these variables and the cost function. A crank arm length of 170 mm and pedalling rate of 100 rpm correspond closely to the cost function minimum. In cycling situations where the rpm deviates from 100 rpm, however, crank arms of length other than 170 mm yield minimum cost function values. In addition, the sensitivity of optimization results to both increased power and anthropometric parameter variations is examined. At increased power, the cost function minimum is more strongly related to the pedalling rate, with higher pedalling rates corresponding to the minimum. Anthropometric parameter variations influence the results significantly. In general it is found that the cost function minimum for tall people occurs at longer crank arm lengths and lower pedalling rates than the length and rate for short people.     

Glycine decarboxylase is confined to the bundle-sheath cells of leaves of C3−C4 intermediate species

Immunogold labelling has been used to determine the cellular distribution of glycine decarboxylase in leaves of C₃, C₃–C₄ intermediate and C₄ species in the genera Moricandia, Panicum, Flaveria and Mollugo. In the C₃ species Moricandia foleyi and Panicum laxum, glycine decarboxylase was present in the mitochondria of both mesophyll and bundle-sheath cells. However, in all the C₃–C₄ intermediate (M. arvensis var. garamatum, M. nitens, M. sinaica, M. spinosa, M. suffruticosa, P. milioides, Flaveria floridana, F. linearis, Mollugo verticillata) and C₄ (P. prionitis, F. trinervia) species studied glycine decarboxylase was present in the mitochondria of only the bundle-sheath cells. The bundle-sheath cells of all the C₃–C₄ intermediate species have on their centripetal faces numerous mitochondria which are larger in profile area than those in mesophyll cells and are in close association with chloroplasts and peroxisomes. Confinement of glycine decarboxylase to the bundle-sheath cells is likely to improve the potential for recapture of photorespired CO₂ via the Calvin cycle and could account for the low rate of photorespiration in all C₃–C₄ intermediate species.Abbreviation and symbol kDa kilodaltons - CO₂ compensation point     

Human debrisoquine 4-hydroxylase (P450IID1): cDNA and deduced amino acid sequence and assignment of the CYP2D locus to chromosome 22

The enzyme P450db1 (db1) is responsible for the common human defect in drug oxidation known as the "debrisoquine/sparteine polymorphism." Polyclonal antibody against the rat db1 protein was used to screen a human liver lambda gt11 library for the db1 cDNA clone. A cDNA containing the full protein coding sequence was isolated; the deduced NH2-terminal sequence of this cDNA was identical to that derived from direct sequencing of the purified human db1 protein. Comparison of the human db1 with rat db1 revealed 71 and 73% similarities of nucleotides and amino acids, respectively. By use of human-rodent somatic cell hybrids the db1 gene was localized to human chromosome 22 (CYP2D locus).     

Radical functionalism: The life and work of Karl Polanyi

Conclusion In concluding, let us restate the main theoretical arguments concerning Austria-Hungary and Malinowski-Polanyi. There are many more aspects of this latter contrast which I have not dwelt on, including those of temper and personality. My concern was to show that it is not enough to trace ideas back to their origin in an undifferentiated Central Europe, for we need to be quite clear about the context in which those ideas were initially taken on board. Mach was an appropriate philosopher for the ordered bureaucracy of Austria, and he embodies the individual-centered and fundamentally conservative message, which I see articulated later in very different (and non-positivist) styles by Popper, Hayek, Schumpeter, etc. This was the message accepted in its fundamentals by Malinowski in Cracow. The Hungarian half of the Empire had quite different traditions, and one might even say that political dilemmas in this half of the Empire were so pressing that they had no time for philosophy. By the time Polanyi was growing up in Budapest, nationalist fervor was at its height, and a nineteenth century heritage of liberal, even radical thought, was under pressure from the extreme right. Polanyi's Jewish family background probably pushed him towards the Left in his early years, though it in no way interfered with this Hungarian patriotism. When he read Mach, he accepted the individualist and positivist aspects of the message, but he could never endorse the conservative respect for tradition that underpinned Malinowski's functionalism. This is what makes his position so interesting, and he maintained it throughout his career.In this light, Polanyi's economic anthropology is an authentic cultural product of Central Europe. Malinowski, to the extent that he took on board the basic social theory of Austrian liberal conservatism, sold out to the West, and to an ideological tradition which has an alternative home in another country on the periphery of industrial capitalism: Enlightenment Scotland. Austria-Hungary also produced intellectuals who sold out in the other direction, and abandoned all notion of intellectual autonomy for the individual by capitulating to the total discipline of the revolutionary Party. This tradition is that of Russia and Lenin, and the best known Central European intellectual recruit was Lukács, perhaps because he studied idealists in Germany rather than the positivists in Vienna. Karl Polanyi was unable to give unswerving loyalty either to the capitalist ideology of the West, or to the ideology of the new tributary mode of production in the East. The middle position, which I believe he occupied throughout his life, is one that will never satisfy ideologues, and it is hard to infuse it with the same intellectual elegance. Still, just as his historical researches showed the real possibilities for combining modes of economic integration, and his life experiences showed the folly of concentration on only one, so Hungarians have learned from history that they are best off with the sort of mixed economy they have today. His popularity in Hungary is therefore unsurprising, and one may hope that the practical message of his anthropology will not be permanently forgotten in the West.Christopher H. Hann is a Professor of Social Anthropology, University of Kent, Canterbury.     

Comparative efficiencies of bispecific F(ab′γ)2 and chimeric mouse/human IgG antibodies in recruiting cellular effectors for cytotoxicity via Fcγ receptors

Summary The three forms of Fc receptor carried by monocytes (FcRI, II) and natural killer (NK) cells (FcRIII) are all capable of mediating cell lysis. Here we compare the use of F(ab)₂ bispecific antibodies, specifically targetting individual FcR, and chimeric IgG mouse/human antibodies which are capable of targetting all FcR, for their ability to mediate target cell destruction. The derivatives are prepared by linking hinge sulphydryl residues via tandem thioether bonds, using a bismaleimide crosslinker: Fab from an anti-FcR mAb linked to Fab from a common anti-target mAb (BsAb), or Fab from the common anti-target mouse antibody linked to human Fc (FabFc or bisFabFc). All the derivatives targetting chick red blood cells gave efficient lysis, although different effector cell donors yielded differences in both the lytic levels achieved and the comparative efficiencies of derivatives. In contrast, significant lysis of the guinea pig lymphoblastic leukaemia, L₂C, regularly resulted only via the anti-FcRIII BsAb and the chimeric derivatives. These results suggest that the chimeric, Fc-containing derivatives mediate tumour cell lysis principally through FcRIII on NK cells. This is in contrast to the situation with the chick red blood cells where the chimeric derivatives appear capable of lysing erythrocytes by utilizing either monocytes or NK cells, because significant (50%) lysis occurred with effector cell populations magnetically depleted through either FcRII or FcRIII. A major difference between these two types of antibody derivative was their ability to function in the presence of high concentrations of normal human Fc. The lysis mediated by BsAb reactive with FcRI or II was unaffected by the presence of human Fc at 2.5 mg/ml (a concentration comparable with that yielded by IgG in plasma) whereas the BsAb recognizing FcRIII and all the Fc-containing derivatives were completely inhibited.This work has been supported by Tenovus, the Cancer Research Campaign, the Leukaemia Research Fund, Italfarmaco, Milano, Italy and the Imperial Cancer Research Fund     

FMRFamide modulates the action of phase shifting agents on the ocular circadian pacemakers of Aplysia and Bulla

Summary The eye of the marine mollusk Aplysia californica contains a photo-entrainable circadian pacemaker that drives an overt circadian rhythm of spontaneous compound action potentials in the optic nerve. Both light and serotonin are known to influence the phase of this ocular rhythm. The current study evaluated the effect of FMRFamide on both light and serotonin induced phase shifts of this rhythm. The application of FMRFamide was found to block serotonin induced phase shifts but, by itself, FMRFamide did not cause significant phase shifts. Furthermore, the effects of FMRFamide on light-induced phase shifts appeared to be phase dependent (i.e., the application of FMRFamide inhibited light-induced phase delays but actually enhanced the magnitude of phase advances). As in Aplysia, the eye of Bulla gouldiana also contains a circadian pacemaker. In Bulla, FMRFamide prevented light-induced phase advances and delays. Although FMRFamide alone generated phase dependent phase shifts, it did not cause phase shifts at the phases where it blocked the effects of light. These data demonstrate that FMRFamide can have pronounced modulatory effects on phase shifting inputs to the ocular pacemakers of both Aplysia and Bulla.Abbreviations ASW artificial seawater - CAP compound action potential - CT circadian time - 5-HT serotonin     

Cell type-specific gene expression in the Drosophila melanogaster male accessory gland.

The accessory gland of the male Drosophila melanogaster plays a vital role in reproduction. This secretory organ synthesizes products that are transferred to the female and are necessary to elicit the proper physiological and behavioral responses in the female. The accessory gland is composed of two morphologically distinct secretory cell types, the main cells and the secondary cells. Previous studies identified some genes expressed in main cells or in all accessory gland cells. In this paper we use P-element mediated enhancer traps to examine gene expression in the accessory gland. We show that, in addition to genes expressed in main cells only or in all accessory gland secretory cells, there are genes expressed specifically in secondary cells. Each cell type is uniform in the expression of its genes. Our results demonstrate that the two cell types are not only morphologically distinct but also biochemically distinct. We also show that the two cell types differ in their regulation of gene expression in response to mating activity.     

Viral proteases as targets for chemotherapeutic intervention

Many viruses encode proteinases that are essential for infectivity, and are consequently attractive chemotherapeutic targets. The biochemistry and structure of the human immunodeficiency virus proteinase have been characterized extensively, and potent peptide-mimetic inhibitors have been developed. Techniques and strategies used to improve the efficiency of these compounds are likely to be applicable to other viral proteinases.