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Intermediary Metabolism (intermediary + metabolism)
Selected AbstractsIntermediate metabolism in normal pregnancy and in gestational diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 4 2003G. Di Cianni Abstract Complex though integrated hormonal and metabolic changes characterize pregnancy. In the face of progressive decline in insulin action, glucose homeostasis is maintained through a compensatory increase in insulin secretion. This switches energy production from carbohydrates to lipids, making glucose readily available to the fetus. This precise and entangled hormonal and metabolic condition can, however, be disrupted and diabetic hyperglycemia can develop (gestational diabetes). The increase in plasma glucose level is believed to confer significant risk of complications to both the mother and the fetus and the newborn. Moreover, exposition of fetal tissues to the diabetic maternal environment can translate into an increased risk for development of diabetes and/or the metabolic syndrome in the adult life. In women with previous gestational diabetes, the risk of developing type 2 diabetes is greatly enhanced, to the point that GDM represents an early stage in the natural history of type 2 diabetes. In these women, accurate follow-up and prevention strategies are needed to reduce the subsequent development of overt diabetes. This paper will review current knowledge on the modifications occurring in normal pregnancy, while outlining the mechanisms. In this paper, we will review the changes of intermediary metabolism occurring during pregnancy. In particular, we will outline the mechanisms responsible for gestational diabetes; the link between these alterations and associated maternal and neonatal morbidity will be examined. Copyright © 2003 John Wiley & Sons, Ltd. [source] Levels of transaminases, alkaline phosphatase, and protein in tissues of Clarias gariepienus fingerlings exposed to sublethal concentrations of cadmium chlorideENVIRONMENTAL TOXICOLOGY, Issue 6 2008Babu Velmurugan Abstract The freshwater fish, Clarias gariepienus fingerlings, were exposed to sublethal concentrations (1.7 and 3.4 mg/L) of cadmium chloride for 12 days. Aspartate aminotransferase (AAT), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total protein levels were assayed in the gill, brain, and muscle of the fish at regular intervals of 6 and 12 days. The activities of AAT, ALT, and ALP of the treated fishes increased significantly in all the tissues compared with the control fish. Protein level in all the tissues showed a significant decrease in comparison to unexposed controls throughout the experimental periods. These results revealed that cadmium chloride effects the intermediary metabolism of C. gariepienus fingerlings and that the assayed enzymes can work as good biomarkers of contamination. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2008. [source] A multivariate biomarker-based model predicting population-level responses of Daphnia magnaENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 9 2003Wim M. De Coen Abstract A multivariate model is proposed relating short-term biomarker measurements in Daphnia magna to chronic effects (21-d exposure) occurring at the population level (time to death, mean brood size, mean total young per female, intrinsic rate of natural increase, net reproductive rate, and growth). The results of the short-term exposure (48h-96 h) to eight model toxicants (cadmium, chromium, mercury, tributyl tin, linear alkylsulfonic acid, sodium pentachlorophenolate, lindane, and 2,4-dichloro-phenoxyacetic acid) on the following biomarkers were used for the multivariate model: digestive enzymes (amylase, cellulase, ,-galactosidase, trypsin, and esterase), enzymes of the intermediary metabolism (glycogen phosphorylase, glucose-6-phosphate de-hydrogenase, pyruvate kinase, lactate dehydrogenase, and isocitrate dehydrogenase), cellular energy allocation (CEA) (protein, carbohydrate, and lipid content and electron transport activity), and DNA damage and antioxidative stress activity. Using partial least squares to latent structures (PLS), a two-component model was obtained with R2 of 0.68 and a Q2 value of 0.60 based on the combined analysis of a limited number of the 48- and 96-h biomarker responses. For the individual population-level responses, the R2 values varied from 0.66 to 0.77 and the Q2 values from 0.52 to 0.69. Energy-related biomarkers (cellular energy allocation, lipid contents, anaerobic metabolic activity,pyruvate kinase, and lactate dehydrogenase), combined with parameters related to oxidative stress (catalase) and DNA damage measured after 48 and 96 h of exposure, were able to predict long-term effects at higher levels of biological organization. [source] Effects of Valproate on Acylcarnitines in Children with Epilepsy Using ESI-MS/MSEPILEPSIA, Issue 1 2007Tamara Werner Summary:,Purpose: To determine the influence of valproate (VPA) treatment on acylcarnitines in children with epilepsy. Methods: Determination of acylcarnitines (including free carnitine and acylcarnitines from C2 to C18) in dried blood spot specimens using tandem-mass spectrometry. Longitudinal study of changes in acylcarnitines in children under VPA treatment without pretreatment (group 1) or with pretreatment with other antiepileptic drugs (group 2) before the start of VPA treatment at an early and a late treatment interval (12,66, 90,260 days after the beginning of treatment, respectively). Cross-sectional comparison of these two VPA groups and of a group receiving carbamazepine monotherapy (group 3) with controls. Results: Acylcarnitines in epileptic patients before VPA therapy did not differ from control values. In group 1, decreases of C0 (,26%), C2 (,12%), C16 (,31%), C18 (,41%), Ctotal (,10%), increases of C5OH (+31%), C8 (+33%) in the early treatment interval, and decreases of C16 (,21%), C18 (,42%), and increases of C2 (+26%), C5OH (+44%) in the late treatment interval were significant. In group 2, both in the longitudinal and the cross-sectional study, only a decrease of C18 (,41%, ,43%, respectively) in the late treatment interval was found. In group 3, no significant changes have been observed. Conclusions: We could prove changes in acylcarnitine subspecies, which were associated with VPA treatment in children with epilepsy. The treatment interval with the most marked changes coincides with the interval of highest risk for VPA-induced hepatotoxicity. The observed specific acylcarnitine pattern might point to the impaired intermediary metabolism that is responsible for VPA-induced hepatotoxicity. [source] Covariance of tricarboxylate carrier activity and lipogenesis in liver of polyunsaturated fatty acid (n-6) fed ratsFEBS JOURNAL, Issue 22 2001Vincenzo Zara The mitochondrial tricarboxylate (citrate) carrier plays an important role in hepatic intermediary metabolism because, among other functions, it supplies the cytosol with acetyl units for fatty-acid synthesis. In this study, the effect of polyunsaturated fatty acids (PUFA, n-6) on the function of this mitochondrial transporter and on lipogenic enzyme activities was investigated by feeding rats for 4 weeks with a 15%-fat diet composed of high linoleic safflower oil. Citrate transport was strongly reduced in liver mitochondria isolated from PUFA-treated rats. A reduced transport activity was also observed when solubilized mitochondrial citrate carrier from PUFA-treated rats was reconstituted into liposomes. In the same animals, a decrease of cytosolic lipogenic enzyme activities was observed. These results indicate a coordinated modulation of citrate carrier and of lipogenic enzyme activities by PUFA feeding. Kinetic analysis of the carrier activity showed that only Vmax decreased, whereas Km was almost virtually unaffected. The PUFA-mediated effect is most likely due to the reduced mRNA level and lower content of the citrate carrier protein observed in the safflower oil-fed rats. [source] Lactate and free glucose in supercooled hatchling Painted Turtles (Chrysemys picta) exposed to natural and semi-natural thermal regimesFUNCTIONAL ECOLOGY, Issue 3 2005M. J. PACKARD Summary 1Hatchlings of the North American Painted Turtle, Chrysemys picta (Schneider 1783) typically spend their first winter of life inside a shallow, terrestrial hibernaculum (the natal nest) where they commonly are exposed for extended periods to ice and cold. Current evidence indicates that turtles withstand such exposure by resisting freezing and becoming supercooled. 2Supercooled hatchlings held at constant temperatures in the laboratory experience circulatory impairment and stagnant hypoxia, and consequently rely on anaerobic metabolism to meet a portion of their energy needs. As a result, lactate accumulates in bodies of supercooled animals. 3The first experiment in the current investigation demonstrated that unfrozen hatchlings exposed to subzero temperatures like those recorded in a natural hibernaculum contained elevated quantities of lactic acid (and free glucose). This finding validates the widespread reliance on laboratory studies to gain insights regarding the physiology of animals overwintering in the field. 4In a second study, hatchling Painted Turtles held for 20 days at ,6 °C contained nearly twice as much lactate as turtles sampled after 10 days at that temperature. Hatchlings held for 10 days at ,6 °C and then for another 10 days at ,3 °C also contained more lactate than turtles sampled after 10 days at ,6 °C, but not as much as the hatchlings that spent 20 days at ,6 °C. Thus, animals held for part of the time at the higher subzero temperature still relied on anaerobic metabolism, but not to the same extent as turtles held continuously at the lower temperature. In contrast, hatchlings held for 10 days at ,6 °C and then for another 10 days at either 0 °C or +3 °C contained no more lactate than control animals that never were exposed to subzero temperatures. Hatchlings exposed for the second 10 days to either 0 °C or +3 °C apparently were able to catabolize or otherwise process all the lactate that was accumulated during the first 10 days of their treatment. 5Free glucose in bodies of hatchlings was elevated in all animals exposed to subzero temperatures, even when the initial exposure was followed by 10 days at temperatures as high as +3 °C. This finding has important implications with regard to the substrate that is used to support intermediary metabolism in supercooled turtles as well as to the metabolic pathways that are used to remove accumulated lactate once body temperature of the turtles rises at least to 0 °C. [source] Intrahepatic amino acid and glucose metabolism in a D -galactosamine,induced rat liver failure modelHEPATOLOGY, Issue 2 2001Kosuke Arai A better understanding of the hepatic metabolic pathways affected by fulminant hepatic failure (FHF) would help develop nutritional support and other nonsurgical medical therapies for FHF. We used an isolated perfused liver system in combination with a mass-balance model of hepatic intermediary metabolism to generate a comprehensive map of metabolic alterations in the liver in FHF. To induce FHF, rats were fasted for 36 hours, during which they received 2 D -galactosamine injections. The livers were then perfused for 60 minutes via the portal vein with amino acid,supplemented Eagle minimal essential medium containing 3% wt/vol bovine serum albumin and oxygenated with 95% O2/5% CO2. Control rats were fasted for 36 hours with no other treatment before perfusion. FHF rat livers exhibited reduced amino acid uptake, a switch from gluconeogenesis to glycolysis, and a decrease in urea synthesis, but no change in ammonia consumption compared with normal fasted rat livers. Mass-balance analysis showed that hepatic glucose synthesis was inhibited as a result of a reduction in amino acid entry into the tricarboxylic acid cycle by anaplerosis. Furthermore, FHF inhibited intrahepatic aspartate synthesis, which resulted in a 50% reduction in urea cycle flux. Urea synthesis by conversion of exogenous arginine to ornithine was unchanged. Ammonia removal was quantitatively maintained by glutamine synthesis from glutamate and a decrease in the conversion of glutamate to ,-ketoglutarate. Mass-balance analysis of hepatic metabolism will be useful in characterizing changes during FHF, and in elucidating the effects of nutritional supplements and other treatments on hepatic function. [source] Fasting modulates metabolic responses to cortisol, GH and IGF-I in Arctic charr hepatocytesJOURNAL OF FISH BIOLOGY, Issue 6 2005Ø. Aas-Hansen Hepatocytes in primary culture from fed and 2 month fasted Arctic charr Salvelinus alpinus were exposed to physiological doses of either cortisol, salmon growth hormone (GH), salmon insulin-like growth factor-I (IGF-I) or a combination of salmon GH and salmon IGF-I. Fasting significantly lowered medium glucose levels compared to the fed fish, but had no significant effects on hepatocyte glycogen content or on the activities of enzymes involved in the intermediary metabolism. Cortisol treatment had no effect on hepatocyte glycogen content or on the enzyme activities investigated, but resulted in a significant increase in medium glucose concentration in hepatocytes isolated from fasted, but not fed fish. GH and IGF-I treatments, both singly and in combination, significantly increased the glycogen content of hepatocytes isolated from fed fish, with less pronounced effects on hepatocytes isolated from fasted fish. The combination of GH and IGF-I significantly increased lactate dehydrogenase activity regardless of the feeding state and significantly reduced the phosphenolpyruvate carboxykinase activity and medium glucose concentration in hepatocytes isolated from fed fish. Further, GH and IGF-I significantly increased the activities of alanine aminotransferase and aspartate aminotransferase in hepatocytes isolated from fasted fish, but not fed fish. There were no effects of GH, IGF-I, or their combination, on glucose 6-phosphate dehydrogenase or 3-hydroxyacyl-CoA dehydrogenase activities. The results demonstrated that nutritional status of the animal modulates hepatocyte responsiveness to metabolic hormones, and suggested a role for GH and IGF-I in hepatic glycogen conservation. [source] Mass spectrometry in newborn and metabolic screening: historical perspective and future directionsJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 2 2009Donald H. Chace Abstract The growth of mass spectrometry (MS) in clinical chemistry has primarily occurred in two areas: the traditional clinical chemistry areas of toxicology and therapeutic drug monitoring and more recent, human genetics and metabolism, specifically inherited disorders of intermediary metabolism and newborn screening. Capillary gas chromatography and electrospray tandem MS are the two most common applications used to detect metabolic disease in screening, diagnostics and disease monitoring of treated patients. A few drops of blood from several million newborn infants are screened annually throughout the world making this the largest application of MS in medicine. Understanding the technique, how it grew from a few dozen samples per week in the early 1990s to increasing daily volume today will provide important information for new tests that either expand newborn screening or screening in other areas of metabolism and endocrinology. There are numerous challenges to the further expansion of MS in clinical chemistry but also many new opportunities in closely related applications. The model of newborn screening and MS in medicine may be useful in developing other applications that go beyond newborns and inherited metabolic disease. As MS continues to expand in clinical chemistry, it is clear that two features will drive its success. These features are excellent selectivity and multiple analyte or profile analysis; features recognized in the 1950s and remain true today. Copyright © 2008 John Wiley & Sons, Ltd. [source] House cleaning, a part of good housekeepingMOLECULAR MICROBIOLOGY, Issue 1 2006Michael Y. Galperin Summary Cellular metabolism constantly generates by-products that are wasteful or even harmful. Such compounds are excreted from the cell or are removed through hydrolysis to normal cellular metabolites by various ,house-cleaning' enzymes. Some of the most important contaminants are non-canonical nucleoside triphosphates (NTPs) whose incorporation into the nascent DNA leads to increased mutagenesis and DNA damage. Enzymes intercepting abnormal NTPs from incorporation by DNA polymerases work in parallel with DNA repair enzymes that remove lesions produced by modified nucleotides. House-cleaning NTP pyrophosphatases targeting non-canonical NTPs belong to at least four structural superfamilies: MutT-related (Nudix) hydrolases, dUTPase, ITPase (Maf/HAM1) and all-, NTP pyrophosphatases (MazG). These enzymes have high affinity (Km's in the micromolar range) for their natural substrates (8-oxo-dGTP, dUTP, dITP, 2-oxo-dATP), which allows them to select these substrates from a mixture containing a ,1000-fold excess of canonical NTPs. To date, many house-cleaning NTPases have been identified only on the basis of their side activity towards canonical NTPs and NDP derivatives. Integration of growing structural and biochemical data on these superfamilies suggests that their new family members cleanse the nucleotide pool of the products of oxidative damage and inappropriate methylation. House-cleaning enzymes, such as 6-phosphogluconolactonase, are also part of normal intermediary metabolism. Genomic data suggest that house-cleaning systems are more abundant than previously thought and include numerous analogous enzymes with overlapping functions. We discuss the structural diversity of these enzymes, their phylogenetic distribution, substrate specificity and the problem of identifying their true substrates. [source] Three temporal classes of gene expression during the Chlamydia trachomatis developmental cycleMOLECULAR MICROBIOLOGY, Issue 4 2000E. I. Shaw The obligate intracellular bacterium Chlamydia trachomatis has a unique developmental cycle that involves functionally and morphologically distinct cell types adapted for extracellular survival and intracellular multiplication. Infection is initiated by an environmentally resistant cell type called an elementary body (EB). Over the first several hours of infection, EBs differentiate into a larger replicative form, termed the reticulate body (RB). Late in the infectious process, RBs asynchronously begin to differentiate back to EBs, which accumulate within the lumen of the inclusion until released from the host cell for subsequent rounds of infection. In an effort to characterize temporal gene expression in relation to the chlamydial developmental cycle, we have used quantitative,competitive polymerase chain reaction (QC-PCR) and reverse transcription (RT)-PCR techniques. These analyses demonstrate that C. trachomatis double their DNA content every 2,3 h, with synthesis beginning between 2 and 4 h after infection. We determined the onset of transcription of specific temporal classes of developmentally expressed genes. RT-PCR analysis was performed on several genes encoding key enzymes or components of essential biochemical pathways and functions. This comparison encompassed approximately 8% of open reading frames on the C. trachomatis genome. In analysis of total RNA samples harvested at 2, 6, 12 and 20 h after infection, using conditions under which a single chlamydial transcript per infected cell is detected, three major temporal classes of gene expression were resolved. Initiation of transcription appears to occur in three temporal classes which we have operationally defined as: early, which are detected by 2 h after infection during the germination of EBs to RBs; mid-cycle, which appear between 6 and 12 h after infection and represent transcripts expressed during the growth and multiplication of RBs; or late, which appear between 12 and 20 h after infection and represent those genes transcribed during the terminal differentiation of RBs to EBs. Collectively, the data suggest that chlamydial early gene functions are weighted toward initiation of macromolecular synthesis and the establishment of their intracellular niche by modification of the inclusion membrane. Surprisingly, representative enzymes of intermediary metabolism and structural proteins do not appear to be transcribed until 10,12 h after infection; coinciding with the onset of observed binary fission of RBs. Late gene functions appear to be predominately those associated with the terminal differentiation of RBs back to EBs. [source] Reflections on the application of 13C-MRS to research on brain metabolismNMR IN BIOMEDICINE, Issue 6-7 2003Peter Morris Abstract The power of 13C-MRS lies in its unique chemical specificity, enabling detection and quantification of metabolic intermediates which would not be so readily monitored using conventional radiochemical techniques. Examples from animal studies, by examination of tissue extracts from the whole brain, brain slices and cultured cells, include observation of intermediates such as citrate and triose phosphates which have yielded novel information on neuronal/glial relationships. The use of 13C-labelled acetate as a specific precursor for glial metabolism provided evidence in support of the view that some of the GABA produced in the brain is derived from glial glutamine. Such studies have also provided direct evidence on the contribution of anaplerotic pathways to intermediary metabolism. Analogous studies are now being performed on the human brain, where 13C-acetate is used to quantitate the overall contribution of glial cells to intermediary metabolism, and use of 13C-glucose enables direct calculation of rates of flux through the TCA (FTCA) and of the glutamate,glutamine cycle (FCYC), leading to the conclusion that the rate of glial recycling of glutamate accounts for some 50% of FTCA. The rate of 0.74,,mol,min,1,g,1 for FTCA is compatible with PET rates of CMRglc of 0.3,0.4,,mol,min,1,g,1 (since each glucose molecule yields two molecules of pyruvate entering the TCA). Our brain activation studies showed a 60% increase in FTCA, which is very similar to the increases in CBF and in CMRglc observed in PET activation studies. Copyright © 2003 John Wiley & Sons, Ltd. [source] Proteomic analysis of S-nitrosylated proteins in Arabidopsis thaliana undergoing hypersensitive responsePROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 7 2008Maria C. Romero-Puertas Abstract Nitric oxide (NO) has a fundamental role in the plant hypersensitive disease resistance response (HR), and S-nitrosylation is emerging as an important mechanism for the transduction of its bioactivity. A key step toward elucidating the mechanisms by which NO functions during the HR is the identification of the proteins that are subjected to this PTM. By using a proteomic approach involving 2-DE and MS we characterized, for the first time, changes in S-nitrosylated proteins in Arabidopsis thaliana undergoing HR. The 16 S-nitrosylated proteins identified are mostly enzymes serving intermediary metabolism, signaling and antioxidant defense. The study of the effects of S-nitrosylation on the activity of the identified proteins and its role during the execution of the disease resistance response will help to understand S-nitrosylation function and significance in plants. [source] Proteomic analysis of growth phase-dependent proteins of Streptococcus pneumoniaePROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 4 2006Kwang-Jun Lee Abstract Streptococcus pneumoniae is an important human pathogen that causes a variety of diseases, such as pneumonia, bacteremia, meningitis, otitis media, and sinusitis, in both adults and children. The global pattern of growth phase-dependent protein expression of S. pneumoniae during in vitro culture was analyzed using 2-DE combined with MALDI-TOF MS and LC/ESI-MS/MS. Several protein production patterns were observed at four time points throughout the growth stage, although some protein levels did not change significantly. We focused on the switch in protein expression at the transition from log growth phase to stationary phase. Proteins that were significantly induced or repressed at this point are likely to be involved in central intermediary metabolism, amino acid synthesis, nucleotide, and fatty acid metabolism, cell wall synthesis, protein degradation, and stress responses. This global expression profiling approach has revealed previously unrecognized relationships between proteins in the life of this pathogen. [source] Requirement for amino acids in ontogeny of fishAQUACULTURE RESEARCH, Issue 5 2010Roderick Nigel Finn Abstract Amino acids are vital for all living organisms. During early fish ontogeny, they are important fuel molecules, signalling factors and major substrates for the synthesis of a wide range of bioactive molecules and proteins. Because the majority of fish eggs are cleidoic, i.e. closed free-living systems following ovulation and activation, early development of fish depends on the maternal provision of amino acids during oogenesis. While more than 600 proteins have been identified in the growing oocytes of fish, the major vehicles for supplying amino acids to the growing oocyte before ovulation are the vitellogenins, of which many genes and multiple forms are known. Here we review the importance of amino acids for the intermediary metabolism of fish embryos and larvae, where amino acids have been shown to be the preferred catabolic substrate. Subsequently, we address the specialization of the lysosomal pathway involved in the uptake and degradation of yolk proteins. This latter pathway is specifically modified in the germline to facilitate the long-term storage of egg yolk proteins. In marine teleosts, the degradative pathway may be activated before fertilization during oocyte maturation to release free amino acids for oocyte hydration and the acquisition of egg buoyancy. In other species, including freshwater fish, a more latent activation of acid hydrolases occurs after fertilization during the four phases of yolk resorption. The developmental contributions of the yolk syncytial layer, vitelline circulation and liver are essential components of the amino acid supply during fish ontogeny. [source] Elevation of anions in exercise-induced acidosis: a study by ion-exchange chromatography/mass spectrometryBIOMEDICAL CHROMATOGRAPHY, Issue 3 2008William McKinnon Abstract Acidosis is a major factor that determines the upper limit of exercise endurance. We have previously shown that anions usually associated with intermediary metabolism are elevated in critically ill patients with metabolic acidosis and contribute significantly to acidosis generation. This study was to determine whether volunteers with normal metabolism would exhibit similar elevations in anions associated with intermediate metabolism when exposed to a short-term physiological stress leading to a brief lactic acidosis. Physiological stress was induced on five healthy male subjects by means of a ramped exercise protocol. Blood was obtained immediately prior to and post-exercise, plasma ultrafiltrate was prepared and analysed immediately both by enzyme assay and liquid chromatography coupled to electrospray,mass spectrometry (LC/ESI-MS). Metabolic acidosis concomitant with a significant increase in blood lactate occurred in each subject, but in addition, anions normally associated with intermediate metabolism were significantly elevated after exercise. The contribution of these anions to generating an acidosis, and thus potentially limiting the extent of exercise, has never been acknowledged. Copyright © 2007 John Wiley & Sons, Ltd. [source] Application of Multivariate Analysis to Optimize Function of Cultured HepatocytesBIOTECHNOLOGY PROGRESS, Issue 2 2003Christina Chan Understanding the metabolic and regulatory pathways of hepatocytes is important for biotechnological applications involving liver cells, including the development of bioartificial liver (BAL) devices. To characterize intermediary metabolism in the hepatocytes, metabolic flux analysis (MFA) was applied to elucidate the changes in intracellular pathway fluxes of primary rat hepatocytes exposed to human plasma and to provide a comprehensive snapshot of the hepatic metabolic profile. In the current study, the combination of preconditioning and plasma supplementation produced distinct metabolic states. Combining the metabolic flux distribution obtained by MFA with methodologies such as Fisher discriminant analysis (FDA) and partial least squares or projection to latent structures (PLS) provided insights into the underlying structure and causal relationship within the data. With the aid of these analyses, patterns in the cellular response of the hepatocytes that contributed to the separation of the different hepatic states were identified. Of particular interest was the recognition of distal pathways that strongly correlated with a particular hepatic function. The hepatic functions investigated were intracellular triglyceride accumulation and urea production. This study illustrates a framework for optimizing hepatic function and a possibility of identifying potential targets for improving hepatic functions. [source] Microreview: Type IV secretion in the obligatory intracellular bacterium Anaplasma phagocytophilumCELLULAR MICROBIOLOGY, Issue 9 2010Yasuko Rikihisa Summary Anaplasma phagocytophilum is an obligatory intracellular bacterium that infects neutrophils, the primary host defence cells. Consequent effects of infection on host cells result in a potentially fatal systemic disease called human granulocytic anaplasmosis. Despite ongoing reductive genome evolution and deletion of most genes for intermediary metabolism and amino acid biosynthesis, Anaplasma has also experienced expansion of genes encoding several components of the type IV secretion (T4S) apparatus. Two A. phagocytophilum T4S effector molecules are currently known; Anaplasma translocated substrate 1 (Ats-1) and ankyrin repeat domain-containing protein A (AnkA) have C-terminal positively charged amino acid residues that are recognized by the T4S coupling protein, VirD4. AnkA and Ats-1 contain eukaryotic protein motifs and are uniquely evolved in the family Anaplasmataceae; Ats-1 contains a mitochondria-targeting signal. They are abundantly produced and secreted into the host cytoplasm, are not toxic to host cells, and manipulate host cell processes to aid in the infection process. At the cellular level, the two effectors have distinct subcellular localization and signalling in host cells. Thus in this obligatory intracellular pathogen, the T4S system has evolved as a host-subversive survival factor. [source] | |||||||||||||||||||