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521.
We determined the complete amino acid sequences of the Erabu sea snake (Laticaudia semifasciata) hemoglobin by analyzing the intact globin chains, enzymatically digested fragments, and chemical cleavage fragments to clarify the molecular evolution and phylogenetic classification of the sea snake. The Erabu sea snake has two types of hemoglobin components, Hb-I and Hb-II, which contain different α- and β-chains. This is the second report of the complete primary structure for hemoglobin of snakes. The sequences were compared with those of other reptilian hemoglobins. Amino acids at positions critical for the structure and physiological functions of hemoglobin were loosely conserved. The requirements for binding of ATP and of diphosphoglycerate as allosteric effectors of β-globins seemed to be fulfilled. 相似文献
522.
Methioninase of Pseudomonas putida was purified to homogeneity, as judged by polyacrylamide gel electrophoresis, with a specific activity 270-fold higher than that of the crude extract. 1. The purified enzyme had an S20,w of 8.37, a molecular weight of 160,000, and an isoelectric point of 5.6. 2. A break in the Arrhenius plot was observed at 40 degrees and the activation energies below and above this temperature were 15.5 and 2.97 kcal per mole, respectively. 3. In addition to L-methionine, various S-substituted derivatives of homocysteine and cysteine could serve as substrates. D-Methionine, 2-oxo-4-methylthiobutanoate, and related non sulfur-containing amino acids were inert. Equimolar formation of alpha-ketobutyrate and CH3SH was observed with methionine as a substrate. 4. In addition to the protein peak at 278 nm, two absorption maxima were observed at 345 and 430 nm at pH 7.5. Hydroxylamine removed the enzyme-bound pyridoxal phosphate, resulting in almost complete resolution with the concomitant disappearance of both peaks. Reconstruction of the treated enzyme could be achieved by addition of the cofactor; the Km value was calculated to be 0.37 muM. 5. The reported purified enzyme should be designated as L-methionine methanethiollyase (deaminating). 相似文献
523.
Haraguchi T Yanaka N Eguchi Y Kudo T Hirata A Kato N 《Bioscience, biotechnology, and biochemistry》2011,75(7):1383-1385
In this study, we investigated the effect of fish oil on gene expression in the cerebral cortex, and found that 5-aminolevulinate synthase 2 (ALAS2) mRNA expression was up-regulated by fish oil feeding. ALAS2 promoter activity was found to be regulated by retinoic acid. Our results suggest that fish oil modulates neuronal functions via heme synthesis. 相似文献
524.
Colleen Young Tomoharu Eguchi Jack A. Ames Michelle Staedler Brian B. Hatfield Mike Harris Emily A. Golson‐Fisch 《Marine Mammal Science》2019,35(4):1512-1526
Enumerating and examining marine animal carcasses is important for quantifying mortality rates and determining causes of mortality. Drifter experiments are one tool for estimating at‐sea mortality and determining factors affecting carcass drift, but they require validation to confirm drifters accurately replicate the drift characteristics of the species of interest. The goal of this study was to determine whether dummies constructed from car tires were appropriate substitutes for sea otter (Enhydra lutris) carcasses. We released 33 sets of targets (carcasses and dummies) in a one‐to‐one ratio on 15 randomly chosen dates between January 1995 and December 1996. They were telemetrically tracked until they beached or were no longer detected. Beaching rates were similar between carcasses (69.7%) and dummies (66.7%). Our results indicated that there was no statistical difference in the drifting pattern, as measured by distance traveled and location, between carcasses and dummies, and that cumulative wind speed, days since release, and release month were predictors of drift patterns. We concluded that dummies constructed from car tires do imitate sea otter carcasses and could be used to estimate at‐sea mortality of sea otters, or, if released during or after an oil spill, could be used to direct search efforts for carcasses. 相似文献
525.
A Wree C D Johnson J Font-Burgada A Eguchi D Povero M Karin A E Feldstein 《Cell death and differentiation》2015,22(12):1985-1994
Liver cancer is a major health-care concern and its oncogenic mechanisms are still largely unclear. Persistent hepatocyte cell death is a common feature among various chronic liver diseases, the blocking of which presents as logical treatment. Therefore, we aimed at investigating tumor development in mice with hepatocyte-specific Bid depletion – a BH3-only Bcl-2 family member that amplifies apoptotic death signals. Hepatocyte-specific conditional Bid-knockout mice (BidΔhep) were injected with 25 mg/kg diethylnitrosamine (DEN) at 14 days of age, and liver tumorigenesis was investigated 9 months later. Additionally, different models of acute liver injury were used including: acute high-dose DEN challenge, 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet and carbon tetrachloride (CCL4) injection. BidΔhep mice developed significantly fewer tumors, showed smaller maximal and average tumor size and reduced tumor incidence. In the acute DEN model, 48 h post injection we observed a significant reduction in liver injury in BidΔhep animals, assessed via serum transaminases and liver histopathology. Furthermore, TNF-α, IL-1ß, cJUN and IL-6 mRNA expression was reduced. These findings were accompanied by reduced compensatory hepatocyte proliferation in BidΔhep mice when compared with controls by immunohistochemistry for Ki67 and proliferating cell nuclear antigen 48 h after DEN injection. In the acute CCL4 model, BidΔhep mice displayed reductions in liver injury and inflammation when compared with controls. No differences in liver injury and serum bilirubin levels were detected in BidΔhep and Bidflo/flo mice fed with DDC, which induces bile duct injury and a ductular reaction. Our study demonstrates that in DEN-induced hepatocellular carcinoma, the inhibition of hepatocyte death pathways through Bid deletion protects animals from tumorigenesis. These results suggest that reducing hepatocyte cell death, liver inflammation and compensatory proliferation has a stronger beneficial effect than the potential side effect of enhancing tumor cell survival.Liver cancer is a major health-care concern with diverse etiology. Viral hepatitis, alcoholic liver disease, carcinogen exposure and metabolic liver diseases are known major causes.1 Recent studies indicate that the incidence of hepatocellular carcinoma (HCC) is rising in the westernized world. Since effective and established chemotherapeutic agents for HCC are currently unavailable and its recurrence rate is high, the overall prognosis of HCC remains poor. The development of HCC, accounting for ~75% of primary malignant liver tumors, has also been linked to chronic viral infections, alcoholic and non-alcoholic fatty liver disease, to exposure to toxic chemicals, such as polycystic aromatic hydrocarbons and nitrosamines, and is more frequently found in patients with preexisting liver cirrhosis and liver inflammation.2, 3 HCC that closely resembles the human disease can be induced in mice with a single postnatal injection of the tumor initiator diethylnitrosamine (DEN).4 Many investigators have employed DEN to induce liver tumors in mice by i.p. injecting 14-day-old pups, giving rise to HCC 8–9 months later.5, 6 In the DEN model, carcinogen-induced DNA damage promotes cell death, causing a Kupffer cell-mediated inflammatory response that further stimulates tumor development via hepatocyte compensatory proliferation.7Notably, hepatocyte cell death is a common, yet integral, feature in various chronic liver diseases that result in cirrhosis and hepatocarcinogenesis. Apoptotic cell death has evolved as a pivotal event in several liver diseases. In particular, mounting evidence supports a central role for this form of cell death in liver injury associated with non-alcoholic fatty liver disease (NAFLD), currently the most common form of chronic liver disease in both adults and children that has been linked to HCC development even in the absence of liver cirrhosis. NAFLD has been recognized, as one of the key drivers for the increase in the number of cases of HCC.8, 9 NAFLD, a spectrum of disorders related to the abnormal accumulation of fat in the liver, affects approximately 20–30% of the adult population in the United States and many other westernized countries and is closely associated with obesity, insulin resistance and type 2 diabetes.10 Growing epidemiological evidence link NAFLD to the increase in HCC rates. Moreover, several reports suggest that HCC may arise in histologically confirmed NAFLD without cirrhosis.11, 12, 13 Improving our understanding of the molecular mechanisms determining HCC development and progression, in particular in the context of NAFLD, is integral to the development of novel therapeutic strategies for this disease. Therefore, the blocking of hepatocyte death pathways, especially apoptotic cell death, presents itself as a logical treatment point of chronic liver disease and, concomitantly, as a preventive measure for liver cancer. However, it is not clear how a general suppression of cell death, especially apoptosis, would affect pre-neoplastic cells, with putative potential to enhance tumorigenesis.Bid is a BH3-only Bcl-2 family member that is cleaved by caspase-8 into its active form, tBID, which links the extrinsic and intrinsic apoptosis pathways. tBid formation is crucial for amplification of apoptotic death signals in cells like hepatocytes (called type 2 cells), where activation of the mitochondrial pathway is essential for cell death to occur. Bid, however, is dispensable for apoptosis in most other cell types (called type 1 cells). We recently demonstrated that hepatocyte-specific BID-deficient mice are resistant to the lethal effects of Fas activation in vivo.14 Here, we tested the hypothesis that selective ablation of Bid in hepatocytes modulates the development of liver tumors. Using the hepatocyte-specific Bid knockout mouse – BidΔhep – model, we show that the inhibition of hepatocyte apoptosis protects from tumorigenesis in two patho-physiologically relevant murine models of HCC. Our data suggest that reducing hepatocyte cell death, liver inflammation and compensatory proliferation has a pronounced beneficial effect vis-a-vis the potential side effect of enhancing tumor cell survival. 相似文献
526.
Camryn D. Allen Michelle N. Robbins Tomoharu Eguchi David W. Owens Anne B. Meylan Peter A. Meylan Nicholas M. Kellar Jeffrey A. Schwenter Hendrik H. Nollens Robin A. LeRoux Peter H. Dutton Jeffrey A. Seminoff 《PloS one》2015,10(10)
Determining sex ratios of endangered populations is important for wildlife management, particularly species subject to sex-specific threats or that exhibit temperature-dependent sex determination. Sea turtle sex is determined by incubation temperature and individuals lack external sex-based traits until sexual maturity. Previous research utilized serum/plasma testosterone radioimmunoassays (RIA) to determine sex in immature/juvenile sea turtles. However, there has been a growing application of enzyme-linked immunosorbent assay (ELISA) for wildlife endocrinology studies, but no study on sea turtles has compared the results of ELISA and RIA. This study provides the first sex ratio for a threatened East Pacific green sea turtle (Chelonia mydas) foraging aggregation, a critical step for future management of this species. Here, we validate a testosterone ELISA and compare results between RIA and ELISA of duplicate samples. The ELISA demonstrated excellent correspondence with the RIA for providing testosterone concentrations for sex determination. Neither assay proved reliable for predicting the sex of reproductively active females with increased testosterone production. We then applied ELISA to examine the sex ratio of 69 green turtles foraging in San Diego Bay, California. Of 45 immature turtles sampled, sex could not be determined for three turtles because testosterone concentrations fell between the ranges for either sex (females: 4.1–113.1 pg/mL, males: 198.4–2,613.0 pg/mL) and these turtles were not subsequently recaptured to enable sex determination; using a Bayesian model to predict probabilities of turtle sex we predicted all three ‘unknowns’ were female (> 0.86). Additionally, the model assigned all turtles with their correct sex (if determined at recapture) with 100% accuracy. Results indicated a female bias (2.83F:1M) among all turtles in the aggregation; when focusing only on putative immature turtles the sex ratio was 3.5F:1M. With appropriate validation, ELISA sexing could be applied to other sea turtle species, and serve as a crucial conservation tool. 相似文献
527.
528.
Homoisocitrate dehydrogenase (HICDH) is involved in the α-aminoadipate pathway of lysine biosynthesis in some bacteria and higher fungi, and catalyses the oxidative decarboxylation of (2R,3S)-homoisocitrate into 2-ketoadipate using NAD(+) as a coenzyme. In this study, the crystal structure of Thermus thermophilus HICDH in a binary complex with a designed inhibitor, (2S,3S)-thiahomoisocitrate, has been determined at 2.6 ? resolution. The inhibitor observed as a decarboxylated product interacts through hydrogen bonding to Arg 118, Tyr 125 and Lys 171 in the active site. The induced fitting was also observed around the region consisting of residues 120-141, which shifted up to 2.8 ? towards the active site. In addition, it was found that the complex structure adopts a closed conformation in two domains. While the structure of apo-HICDH shows that a catalytic residue Tyr 125 and Arg 85 that engages in substrate recognition are flipped out of the active site, these residues turn towards the active site in the complex structure. The results revealed that they directly interact with a substrate and are involved in catalysis or substrate recognition. Furthermore, by comparing the binary complex with the quaternary complex of Escherichia coli isocitrate dehydrogenase, the substrate recognition mechanism of HICDH is also discussed. 相似文献
529.
Two-component signal transduction systems (TCSs), utilized extensively by bacteria and archaea, are involved in the rapid adaptation of the organisms to fluctuating environments. A typical TCS transduces the signal by a phosphorelay between the sensor histidine kinase and its cognate response regulator. Recently, small-sized proteins that link TCSs have been reported and are called "connectors." Their physiological roles, however, have remained elusive. SafA (sensor associating factor A) (formerly B1500), a small (65-amino-acid [65-aa]) membrane protein, is among such connectors and links Escherichia coli TCSs EvgS/EvgA and PhoQ/PhoP. Since the activation of the EvgS/EvgA system induces acid resistance, we examined whether the SafA-activated PhoQ/PhoP system is also involved in the acid resistance induced by EvgS/EvgA. Using a constitutively active evgS1 mutant for the activation of EvgS/EvgA, we found that SafA, PhoQ, and PhoP all contributed to the acid resistance phenotype. Moreover, EvgS/EvgA activation resulted in the accumulation of cellular RpoS in the exponential-phase cells in a SafA-, PhoQ-, and PhoP-dependent manner. This RpoS accumulation was caused by another connector, IraM, expression of which was induced by the activation of the PhoQ/PhoP system, thus preventing RpoS degradation by trapping response regulator RssB. Acid resistance assays demonstrated that IraM also participated in the EvgS/EvgA-induced acid resistance. Therefore, we propose a model of a signal transduction cascade proceeding from EvgS/EvgA to PhoQ/PhoP and then to RssB (connected by SafA and IraM) and discuss its contribution to the acid resistance phenotype. 相似文献
530.