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Finally, we hope that studies on addicsin will continue to advance our understanding of the role of addicsin in the pathogenesis of diseases, such as drug abuse, and lead to the development of curative therapies. Regulation of Neuronal Glutathione Synthesis, Journal of Pharmacological Sciences Vol. Abnormal Expression of Glutamate Transporter and Transporter Interacting Molecules in Prefrontal Cortex in Elderly Patients with Schizophrenia, Schizophrenia Research Vol. The Fruit Fly: A Model Organism to Study the Genetics of Alcohol Abuse and Addictionfi Multiple Signaling Pathways Regulate Cell Surface Expression and Activity of the Excita to ry Amino Acid Carrier 1 Subtype of Glu Transporter in C6 Glioma, the Journal of Neuroscience Vol. Arl6ip1 Mediates Cisplatin-Induced Apop to sis in Caski Cervical Cancer Cells, Oncology Reports Vol. Role of Neuronal Glutamate Transporter in the Cysteine Uptake and Intracellular Glutathione Levels in Cultured Cortical Neurons, Journal of Neural Transmission Vol. Expression of Excita to ry Amino Acid Transporter Interacting Protein Transcripts in the Thalamus in Schizophrenia, Synapse Vol. Glutamatergic Theories of Schizophrenia, the Israel Journal of Psychiatry and Related Sciences Vol. Primary Structure and Functional Characterization of a High-Affinity Glutamate Transporter, Nature Vol. The Glutamate and Neutral Amino Acid Transporter Family: Physiological and Pharmacological Implications, European Journal of Pharmacology Vol. A Scoring System for Abstinence Syndrome in Morphine Dependent Mice and Application to Evaluate Morphine Type Dependence Liability of Drugs, the Japanese Journal of Pharmacology Vol. Thinking Glutamatergically: Changing Concepts of Schizophrenia Based Upon Changing Neurochemical Models, Clinical Schizophrenia & Related Psychoses Vol. Variations in Differential Gene Expression Patterns across Multiple Brain Regions in Schizophrenia, Schizophrenia Research Vol. Long-Term Regulation of Neuronal High-Affinity Glutamate and Glutamine Uptake in Aplysia, Proceedings of the National Academy of Sciences of the United States of America Vol. Long Term Potentiation and Contextual Fear Conditioning Increase Neuronal Glutamate Uptake, Nature Neuroscience Vol. Mouse Prenylated Rab Accep to r Is a Novel Golgi Membrane Protein, Biochemical and Biophysical Research Communications Vol. Pharmacological Interference with Glutamate Re-Uptake Impairs Long-Term Memory in the Honeybee, Apis Mellifera, Behavioural Brain Research Vol. Glutamate Toxicity in a Neuronal Cell Line Involves Inhibition of Cystine Transport Leading to Oxidative Stress, Neuron Vol. Genetic Dissociation of Opiate Tolerance and Physical Dependence in Delta-Opioid Recep to r-1 and Preproenkephalin Knock-out Mice, the Journal of Neuroscience Vol. Rat C6 and Human Astrocytic Tumor Cells Express a Neuronal Type of Glutamate Transporter, Brain Research. Glutamatergic Dysfunction in Schizophrenia: From Basic Neuroscience to Clinical Psychopharmacology, European Neuropsychopharmacology Vol. Chronic Inhibition of Glutamate Uptake Produces a Model of Slow Neuro to xicity, Proceedings of the National Academy of Sciences of the United States of America Vol. Knockout of Glutamate Transporters Reveals a Major Role for Astroglial Transport in Exci to to xicity and Clearance of Glutamate, Neuron Vol. N-Methyl-D-Aspartate Recep to r-Dependent Regulation of the Glutamate Transporter Excita to ry Amino Acid Carrier 1, the Journal of Biological Chemistry Vol. Interaction of L-Cysteine with a Human Excita to ry Amino Acid Transporter, the Journal of Physiology Vol. Retention of Supraspinal Delta-Like Analgesia and Loss of Morphine Tolerance in Delta Opioid Recep to r Knockout Mice, Neuron Vol. Significant contributions of horizontal/lateral gene transfer among uni-cellular [6] and multi-cellular [7] organisms during the evolution, including the evolution of pho to synthesis [8,9], have been recognized. Various perspectives on evolution of pho to synthesis have been reported in literature [8-25], whereas our understanding of transition from anaerobic to aerobic world is still fragmentary. Overall, genomic information is consistent with a high to lerance for oxygen that has been reported in the growth of Cfl. Phylogenetic analyses on the pho to systems and comparisons to the genome and reports of other pho to synthetic bacteria suggest lateral or horizontal gene transfers between Cfl. Here we probe some proposed lateral gene transfers using the phylogenetic analyses on important proteins/enzymes on chlorophyll biosynthesis, pho to synthetic electron transport chain, and central carbon metabolism.

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Several studies have shown that oxysterols result in inhibition of cholesterol efflux in the mouse and it was suggested that impairment of cholesterol homeostasis by the inhibition of cholesterol efflux may be mechanism by which oxysterols affect cellular function (Kilsdonk et al. Interestingly, 7-ke to cholesterol was shown to deplete cholesterol specifically from the raft domains in human macrophages (Gaus et al. Consequently, the use of methods of controlled manipulation of membrane cholesterol content has also increased sharply, especially as a method of studying putative cholesterol-enriched cell membrane domains (rafts). The most common means of modifying the cholesterol content of cell membranes is the incubation of cells or model membranes with cyclodextrins, a family of compounds, which, due to the presence of relatively hydrophobic cavity, can be used to extract cholesterol from cell membranes (Zidovetzki and Levitan, 2007). Under conditions commonly used for cholesterol extraction, cyclodextrins may remove cholesterol from both raft and non-raft domains of the membrane as well as alter the distribution of cholesterol between plasma and intracellular membranes. In addition, other hydrophobic molecules such as phospholipids may also be extracted from the membranes by cyclodextrins. Here, we discuss useful control strategies that may help to verify that the observed effects are due specifically to cyclodextrin-induced changes in cellular cholesterol. The ratio between the amounts of cholesterol and cyclodextrin in the complex determines whether it will act as cholesterol accep to r or as cholesterol donor (Zidovetzki and Levitan, 2007). Control of dietary intake is one of the easiest and least cost intensive means to achieve reductions in cholesterol. But in most of the alleviated levels of cholesterol cannot be controlled merely with exercise. Drug therapy is very important to Cholesterol: Biosynthesis, Functional Diversity, Homeostasis and Regulation by Natural Products 433 avoid the cardiovascular effects of high cholesterol levels in such patients. In this section of the book chapter, we have discussed the regulation cholesterol by drugs as well as will review recent work from our labora to ry for the regulation of cholesterol by natural products such as tea/green tea, policosanol and garlic compounds. Green tea has been shown to be hypocholesterolemic in animal studies, with the bulk of evidence indicating that tea polyphenols reduce the absorption of dietary and biliary cholesterol and promote its fecal excretion (Koo and Noh, 2007). Feeding studies have been equivocal on the ability of green tea extract to inhibit cholesterol synthesis. Measuring cholesterol synthesis in vivo is difficult, whereas in vitro studies are more tractable. In this regard, Gebhardt and colleagues reported that several common polyphenols (luteolin, quercetin) were able to decrease cholesterol synthesis when added to cultured hepa to cytes or hepa to ma cell cultures (Gebhardt, 2003). Moreover, the effect of black tea extract, which consists predominantly of a diverse mixture of polymerized polyphenols termed theaflavins and thearubigins, has not been examined, despite the recent clinical evidence that black tea can modestly reduce serum cholesterol levels. In normocholesterolemic patients, policosanol caused a small and generally insignificant increase in high-density lipoprotein-cholesterol, whereas in seven clinical studies of dyslipidemic patients high-density lipoprotein-cholesterol was increased by an average of 17%. Policosanol is also effective in rabbits and monkeys, where it lowers blood cholesterol and reduces the development of atherosclerotic plaques (Wang et al. The product has no evident to xicity and is available over-the-counter in many outlets. The active component(s) has not been established, but it has been shown that very long-chain alcohols can undergo oxidation to fatty acids with subsequent peroxisomal fi-oxidation, which also yields chain-shortened metabolites (Singh et al. Several studies have demonstrated that policosanol inhibits cholesterol synthesis in labora to ry animals and cultured cells, and it is thought that this is the principal mechanism by which it lowers blood cholesterol levels. In the latter study, policosanol did not affect the incorporation of [14C]mevalonate in to cholesterol, indicating that policosanol was acting at or above mevalonate synthesis. The highly reactive sulfenic acid that is formed from alliin condenses to allicin, which then rapidly recombines to various di and tri-sulfides, depending on conditions. Ultimately these compounds are believed to yield allyl mercaptan and allyl methyl sulfide, which can react with cellular components or be eliminated on the breath. The organosulfur compounds formed in garlic are highly reactive with other sulfhydryl compounds, including cysteines found in proteins, and it is likely that the chemical modification of enzyme-sulfhydryls is responsible for the purported therapeutic effects of garlic. The question of which compounds are most important to the therapeutic effects of garlic remains unresolved, although several studies have shown that the diallyl disulfides, allyl mercaptan, and S Cholesterol: Biosynthesis, Functional Diversity, Homeostasis and Regulation by Natural Products 435 alk(en)yl cysteines are effective inhibi to rs of cholesterol synthesis in cells (Gebhardt and Beck, 1996; Liu and Yeh, 2000; Singh and Porter, 2006). Similarly, the enzyme targets that mediate the effects of garlic have not been identified.

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The eyebrow flash seems to be common to all human cultures, and to some other species. Eye contact: Mutual gaze, or the amount of time which two people spend looking at each other simul taneously. Eye contact is sometimes taken as an indica to r of intimacy; eye-contact with unknown individuals tends to be avoided. It is powerful signal in all primates, including human beings; prolonged eye contact with neutral or hostile facial expression is taken as a threat gesture, and tends to be responded to by either aggressive or avoid ance behaviour. Facial affect programme: A strategy of including behavioural change through making the individual aware of the sensations arising from facial expre ssions which are different from those that he/she uses habitually. It is thought that encouraging the continued use of positive facial expressions, as opposed to those normally used, will provide positive feedback both through social interaction and through muscular interpretation. Facial electromyography: A technique for measuring the degree of tension in facial muscles by recording the electrical discharge of the muscles. By mapping the muscle tensions occurring in different expre ssions a systematic and objective measure of facial expression can be obtained. Facial expression: Characteristics patterns of arrange ments of the muscles in the face, which provide important non-verbal clues in social interaction. Facial expression may be used either to express understanding, attitudes, emotions, or as specific cultural signals with clearly defined meanings. Some researchers have found that basic emotional Dictionary of Psychology & Allied Sciences 151 expressions seem to be common to all human cultures, and are also found in blind babies, which would seem to imply that they are innate. However, other facial expressions show cultural variability, and seem to be acquired through social interaction. Facial feedback hypothesis: the idea that our experi ence of emotion arises at least in part from our interpretations of the arrangement of our facial muscles. So mood changes may be affected by the altering of the facial expression, which will provide feedback leading to a change in the emotion that the person experience. The effect is used in studies of mood when subjects are asked to make, say, a depressed face as a part of a procedure for chan ging their mood. Factitious disorder: A mental disorder characterized by the voluntary production of unreal physical or psychological symp to ms. Unlike malingering, there is no apparent goal or obvious benefit in factitious disorder. Fac to r analysis: A statistical technique that examines population clusters to extract patterns of common ality. It is now widely recognized that the basic problem is that the child does not receive enough food to sustain appropriate growth, though this in turn in likely to result from emotional or other difficulties of the parent, the child, or both. The patient simply collapse but without biting the to ngue or incontinuance of urine or faeces. This is accom panied by lack of ability to speak or move, even though the individual hears and understands. Falsifiable hypothesis: A hypothesis stated in sufficiently precise fashion that it can be tested by acceptable rules of logic, empirical and statistical evidence, and thereby found to be either confirmed or disconfirmed. Family therapy: An approach to psychological treat ment in which the whole family is the focus, rather than an individual patient. Earlier approaches were derived from psychoanalysis and treated the family as if it had psychological processes similar to those of individuals.

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Table 4 lists similar studies on the thyroid, and Table 5 shows those on other organs. Ten mice from each group were killed at 33 weeks of age, and the remaining mice were killed when found moribund or at Table 3. Administration of phenobarbital significantly increased the inci dence (from 30% to 100%, p < 0. Eight groups of 30 male weanling C3H/HeN mice were given either a normal diet or a diet containing 1. Animals given phenobarbital only with both methionine and choline had longer survival than mice receiving no supplementation when analysed on the basis of deaths with tumours (p < 0. Treatment with phenobarbital only resulted in incidences of hepa to cellular carcinoma of 79% in animals on the normal diet, 74% in those on choline-supplemented diet, 60% with methionine supplementation and 31% with methionine plus choline supple mentation. Multiple hepa to cellular adenomas and carcinomas developed in 77% of mice exposed to phenobarbital alone. Multiple hepa to blas to mas also occurred in 11/30 (37%) mice that received pheno barbital only. Thus, in D2B6F1 mice, the development of hepa to blas to ma from its precursor cells (adenoma and carcinoma cells) is strongly increased in the presence of a promoting agent (Diwan et al. Twenty-four had type A tumours (simple nodular growth of liver parenchymal cells) and three male mice had type B tumours (areas of papilliform or adenoid growth of tumour cells with a dis to rted parenchymal structure). None of the mice exposed to saline and phenobarbital or saline alone developed tumours (Uchida & Hirono, 1979). Three animals from each group were killed at 4, 20 and 28 weeks, and six animals from each group were killed at 12, 36 and 44 weeks of age. Half of the remaining animals were killed at 52 weeks and the remainder at 60 weeks of age. Subsequent exposure to phenobarbital suppressed the development of focal hepatic lesions, decreased the number of adenomas (5/mouse at 44 weeks, 6/mouse at 52 weeks and 8/mouse at 60 weeks) and carcinomas (0 at 44 weeks, 0 at 52 weeks and 1/mouse at 60 weeks) and prolonged the latency or significantly slowed the rate at which hepa to cellular tumours developed in these mice (Diwan et al. At 5 weeks of age, they received 500 mg/L sodium phenobarbital in the drinking-water until 51 weeks of age, and the experiment was terminated 1 week later. Subsequent treatment with sodium phenobarbital also promoted the development of spontaneous liver tumours. One week later, they were given 500 mg/L sodium phenobarbital in the drinking-water until termination of the study at 50 weeks of age. At 4 weeks of age, they were given 500 mg/L sodium phenobarbital in the drinking-water until 20 or 28 weeks of age. Subsequent administration of sodium phenobarbital increased both the incidence (88% at 20 weeks, p fi 0. Subsequent administration of sodium phenobarbital decreased the incidence of hepa to cellular carcinomas (0%) and the number of adenomas per mouse (51. The authors concluded that inhibition or enhancement of hepa to carcinogenesis by phenobarbital is dependent on both the mouse strain and the age at the start of exposure (Pereira et al. Ten mice per group were killed at 12 weeks, 15 at 24 weeks and 20 at 40 weeks after weaning. Control groups received a single intraperi to neal injection of saline at 15 days of age and at weaning were exposed to either tap-water or 500 mg/L phenobarbital. No hepa to cellular foci or adenomas were seen in groups given phenobarbital only or no treatment. The type of initia to r therefore appears to be important in deter mining whether 15-day-old initiated male B6C3F1 mice respond to the promoting effects of phenobarbital (Klaunig et al. At 28 days of age (at weaning), they received either normal drinking-water (controls) or drinking-water containing 500 mg/L phenobarbital for 28 weeks. Thus, the strain of the mouse and the initiating carcinogen determine the ability of phenobarbital to either inhibit or promote hepa to cellular carcinogenesis in 15-day-old mice (Weghorst et al. At weaning (28 days of age), some groups received drinking-water containing 500 mg/L pheno barbital, while others received deionized water, for 24 weeks. The authors concluded that the sex of mice was important in determining their susceptibility to promotion by phenobarbital (Weghorst & Klaunig, 1989).