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OBJECTIVE: Previous preliminary clinical trials have confirmed that edoxaban can be efficacious for venous thromboembolism (VTE). This meta-analysis was considered to evaluate edoxaban's short-term efficacy and safety for venous thromboembolism after arthroplasty. MATERIALS AND METHODS: A comprehensive search was performed in these databases: PubMed, MEDLINE, Web of Science, and EMBASE on March 2022. All eligible trials should be randomized controlled trials (RCTs) when evaluating short-term efficacy and safety outcomes of edoxaban for VTE after total hip or knee arthroplasty. RESULTS: Nine RCTs with 4274 patients were involved in this meta-analysis. Edoxaban in the VTE group prevented the incidence of VTE and indicated valuable clinical efficacy. The incidence of adverse events (AEs) and adverse drug reactions (ADRs) in the edoxaban group was decreased than that in other groups. Edoxaban increased the incidence of all bleeding events. However, in the edoxaban group and other groups, there was no statistical difference between major bleeding events and clinically relevant non-major or minor bleeding events. Edoxaban subgroups included edoxaban 15 mg, edoxaban 30 mg and edoxaban 60 mg prevented the incidence of VTE. Edoxaban 30 mg and 60 mg group increased the risk of all bleeding events. Edoxaban 30 mg can increase the incidence of major bleeding events. There was no difference in clinically relevant non-major or minor bleeding events. Edoxaban 30 mg can decrease the incidence of AEs. CONCLUSIONS: Edoxaban was an efficacious and safe option to prevent and treat VTE in patients undergoing arthroplasty. However, we need further trials to explore edoxaban's long-term efficacy and safety. [ABSTRACT FROM AUTHOR]

The knowledge of quantities and types of traffic participants at specific nodes dedicates crucial information to an intelligent transportation system (ITS) of a smart city. A single-layer laser scanner was employed on a static platform on the roadside to recognize pedestrians, bicycles, motorcycles, trucks, sedans and buses. The selected features were extracted and investigated for optimized classification rate. The classifier support vector machine (SVM) is configured to classify the types of traffic participants using multiclass classification approach. To improve the recognition correction rate, the K-folder cross-validation and grid search are applied in the training stage of the machine learning. The hierarchical division of the output space is proposed where five classifiers were applied to deal with the specific difficult classes. The overall accuracy of the final experiment is 85.5% where the multiclass accuracies are 91.9, 99.6, 97.8, 96.6 and 80.4%, respectively, which shows that the laser scanner used is a feasible and practical solution of this application. [ABSTRACT FROM AUTHOR]

Lidar has long been used in three-dimensional (3-D) reconstruction tasks. Herein a novel method using single layer Lidar and an inertial measurement unit (IMU) is proposed, which is expected to replace the multiple layer lidar in perceiving surrounding environment. The reconstruction is achieved in three steps: (i) Coordinate transformation and timestamp synchronization between the two sensors are first performed,(ii) The quaternion attitude is then calculated to generate the scanned plane by using the original range, roll, pitch, and yaw data measured,and (iii) The registrations between different frames of scanned planes are finally achieved by the iterative closest point (ICP) algorithm. Together, the 3-D spatial reconstruction can be obtained by using an IMU and a single layer, rather than multiple layer, lidar, which is more economical and flexible. [ABSTRACT FROM AUTHOR]

The article talks about the role of adipocyte as an endocrine organ. The author reports that a new adipocyte hormone in mice was identified by screening for genes that were induced during the differentiation of adipocytes. However, the genes were down-regulated in mature adipocytes exposed to rosiglitazone, an insulin-sensitizing drug used routinely in type 2 diabetes. A group of researchers found that resistin levels are reduced in a mouse model of insulin-deficiency diabetes and that the administration of insulin rapidly raises resistin levels to normal in adipose tissue.

Uncoupling protein-3 (UCP3) is a mitochondrial protein that can diminish the mitochondrial membrane potential. Levels of muscle Ucp3 mRNA are increased by thyroid hormone and fasting. Ucp3 has been proposed to influence metabolic efficiency and is a candidate obesity gene. We have produced a Ucp3 knockout mouse to test these hypotheses. The Ucp3 (-/-) mice had no detectable immunoreactive UCP3 by Western blotting. In mitochondria from the knockout mice, proton leak was greatly reduced in muscle, minimally reduced in brown fat, and not reduced at all in liver. These data suggest that UCP3 accounts for much of the proton leak in skeletal muscle. Despite the lack of UCP3, no consistent phenotypic abnormality was observed. The knockout mice were not obese and had normal serum insulin, triglyceride, and leptin levels, with a tendency toward reduced free fatty acids and glucose. Knockout mice showed a normal circadian rhythm in body temperature and motor activity and had normal body temperature responses to fasting, stress, thyroid hormone, and cold exposure. The base-line metabolic rate and respiratory exchange ratio were the same in knockout and control mice, as were the effects of fasting, a beta3-adrenergic agonist (CL316243), and thyroid hormone on these parameters. The phenotype of Ucp1/Ucp3 double knockout mice was indistinguishable from Ucp1 single knockout mice. These data suggest that Ucp3 is not a major determinant of metabolic rate but, rather, has other functions.

Uncoupling protein-1 (UCP1) dissipates the transmitochondrial proton gradient as heat. UCP2 and UCP3 are two recently discovered homologues that also have uncoupling activity and thus presumably have a role in energy homeostasis. We now report the genomic structure of murine UCP3 (7 exons) and UCP2 (8 exons). UCP3 is approximately 8 kilobases upstream of UCP2. An UCP3 variant mRNA, UCP3S, was also found and characterized. The effect of a high fat diet (45% versus 10%) on UCP3 and UCP2 mRNA levels was measured. Eating the 45% fat diet for eight weeks caused greater weight gain in AKR and C57BL/6J mice than in the obesity-resistant A/J mice. The high fat diet increased muscle UCP3 expression twofold in C57BL/6J animals. UCP2 expression increased slightly on the 45% fat diet in white adipose of AKR mice, but not in A/J or C57BL/6J mice. In skeletal muscle, UCP2 expression showed little variation with diet. Thus, UCP2 and UCP3 expression levels change in response to diet-induced obesity, but the changes are modest and depend on the tissue and genotype. The data suggest that it is not a reduction in UCP2 or UCP3 expression that causes obesity in the susceptible mice., (Copyright 1999 Academic Press.)

Mitochondrial FAD-linked glycerol-3-phosphate dehydrogenase (mtGPDH) is one of the two enzymes of the glycerol phosphate shuttle. This shuttle transfers reducing equivalents from the cytoplasm to the mitochondria in a unidirectional, exothermic manner. Here, the isolation and characterization of the rat nuclear gene (Gpd2) encoding mtGPDH is reported. The mtGPDH gene spans 100 kb and consists of 17 exons. The use of alternate promoters was suggested by the presence of three different first exons and confirmed by transient expression for two of them. The first exons are expressed in a tissue-restricted manner. Exon 1a was found primarily in brain, exon 1b was used in all tissues examined, and exon 1c was detected predominantly in testis. Depending on the tissue, different transcript lengths were also observed: 5.9 kb (all tissues), 3.6 kb (skeletal muscle), and 2.5 kb (testis). The length isoforms are attributable to alternate splicing and polyadenylation site use. Very high mtGPDH mRNA levels were found in brown adipose tissue, 75 fold greater than in white adipose tissue. Thyroid hormone increased mtGPDH mRNA levels in liver and heart but not in brown adipose tissue, brain, or testis. This pattern corresponds to that of thyroid hormone-induced oxygen consumption and is consistent with a role for mtGPDH in thyroid hormone-induced thermogenesis. Both thyroid-responsive and nonresponsive tissues used promoter 1b, suggesting that tissue-specific factor(s) contribute to the tissue-restricted responsiveness to thyroid hormone.

Transcription initiation factor TFIIF is a tetramer consisting of two large subunits (TFIIF alpha or RAP74) and two small subunits (TFIIF beta or RAP30). We report here the molecular cloning of a Drosophila cDNA encoding TFIIF beta. The cDNA clone contains an open-reading frame encoding a 277 amino acid polypeptide having a calculated molecular mass of 32,107 Da. Comparison of the deduced amino acid sequence with the corresponding sequences from vertebrates showed only 50% identity, with four insertion/deletion points. For transcription activity in a TFIIF-depleted Drosophila nuclear extract, both TFIIF alpha and TFIIF beta are essential. Moreover, Drosophila TFIIF beta interacts with both Drosophila and human TFIIF alpha in vitro. Thus we conclude that isolated cDNA encodes bona fide TFIIF beta. The structural domains of TFIIF beta and its sequence similarity to bacterial delta factors are discussed.

Hepatic sulfation of heterocyclic and non-heterocyclic arylamines was studied to assess enzymes responsible for their metabolisms. Both 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)- and non-IQ-type (beta-carboline) heterocyclic amines were N-sulfated to form their sulfamates in cytosols of rat livers in the presence of 3'-phosphoadenosine-5'-phosphosulfate (PAPS). An arylsulfo-transferase, ST1A1, whose cDNA was isolated from a rat cDNA library, was expressed in COS-1 cells. The expressed enzyme catalyzed N-sulfation of IQ, but not appreciably those of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-I), and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2). N-Sulfation of heterocyclic amines except IQ was higher in hepatic cytosols of female rats than of male rats. These results suggest the involvement of at least plural forms of sulfotransferase on the N-sulfation. In addition, N-sulfation of IQ was also observed in cytosol of a human liver, suggesting that N-sulfation is one of the metabolic pathways of heterocyclic amines in humans as well as rats. Hepatic sulfotransferase also catalyzes metabolic activation of N-hydroxy derivatives of carcinogenic arylamines. Using anti-HAST (hydroxylarylamine sulfotransferase) antibodies and ST1A1 cDNA as screening probes, several cDNA clones were isolated from the cDNA library. A new member of arylsulfotransferase, ST1C1, whose cDNA shows considerable sequence similarity to ST1A1 cDNA, was found to catalyze O-sulfation of N-hydroxy-2-acetylaminofluorence by the cDNA expression in COS-1 cells. From the close similarity of ontogenic profile and sex-specific expression of ST1C1 and HAST, ST1C1 cDNA was shown to encode a major sulfotransferase (HAST) mediating the metabolic activation of N-hydroxyarylamines in rat livers. In addition, properties of PAPS-dependent N-hydroxyarylamine activation and sulfotransferase in human livers are also discussed.

Transcription initiation factor TFIID is a multisubunit complex containing a TATA-box-binding factor (TFIID tau/TBP) and associated polypeptide factors (TAFs) with sizes ranging from M(r) approximately 20,000 to > 200,000. As a result of direct promoter interactions, TFIID nucleates the assembly of RNA polymerase II and other initiation factors into a functional preinitiation complex. Although the native TFIID complex mediates both basal and activator-dependent transcription in reconstituted systems, TBP itself is competent for only basal transcription. Thus, TAFs are essential cofactors for regulated transcription. The complementary DNAs encoding the p230 (M(r) 230,000), p110 and p85 subunits of TFIID have recently been cloned. Here we report the molecular cloning and characterization of the p62, p42, p28 and p22 subunits. These participate in a network of heterogeneous protein-protein interactions within TFIID. Sequence similarities between p62/p42 and the histones H4/H3, respectively, suggest that these subunits have a functional relationship with chromatin.

A TATA box-binding initiation factor, TFIID, plays a central role in the transcriptional regulation by activators. Using anti-TFIID tau (a TATA box-binding component of native TFIID) immunoaffinity chromatography, nine polypeptides (230, 110, 85, 62, 58, 42, 28, 22, and 21 kDa) were identified as native Drosophila TFIID components that are tightly associated with TFIID tau. To verify the functional activity of the purified TFIID complex, template DNA and other transcription factors were reconstituted with purified TFIID bound to the antibody-Sepharose matrix. Immobilized TFIID mediated not only basal transcription but transcriptional activation by upstream stimulatory factor (USF). On the other hand, recombinant TFIID tau immobilized on the same antibody-Sepharose matrix could not mediate activation by USF. These results suggest that one or more of these additional polypeptides are required as functional TFIID subunits for activator-dependent transcription in conjunction with TFIID tau. As further evidence of the relevance of the Drosophila TFIID components identified in this analysis, including the previously unrecognized p230 (Dynlacht, B. D., Hoey, T., and Tjian, R. (1991) Cell 66, 563-576), protein blot analysis showed that TFIID tau interacts specifically and exclusively with p230. This suggests that p230 is an integral subunit of TFIID and that it may play a major role in tethering other subunits to TFIID tau.

A cDNA (PST-1) isolated from a rat liver cDNA library was expressed in COS-1 cells and found to encode a form of arylsulfotransferase (termed ST1A1), which sulfated p-nitrophenol, alpha-naphthol, minoxidil, beta-estradiol and dopamine, but not dehydroepiandrosterone and cortisol. ST1A1 showed a mobility identical with a major immunodetectable sulfotransferase contained in the livers of male and female rats in Western blots. In addition, ST1A1 mRNA was detected in the liver and extrahepatic tissues by Northern blots.

The regulatory mechanism of cytosolic sulfation of T3 has been studied in rat liver. Sulfation of T3 is sexually differentiated in adult rats of Sprague-Dawley (SD), Fisher 344, and ACI strains. In SD strain, the male animals showed 4 times higher sulfating activity than did the females. The specific activity was decreased by hypophysectomy of male adult rats, but was not affected in the females. Thus, the sex-difference was abolished in the hypophysectomized condition. Supplement of human GH intermittently twice daily for 7 days, to mimic the male secretory pattern, increased T3 sulfating activity in both sexes of hypophysectomized rats, whereas continuous infusion to mimic a female secretory pattern had no appreciable effect. Cytosolic sulfation of T3 was decreased by 25 to 30% by thyroidectomy or propylthiouracil treatment of male adult rats, and was restored by the supplementation of T3 (50 micrograms/kg daily for 7 days) to thyroidectomized rats. Administration of T3 in hypophysectomized rats almost completely restored the sulfating activity in the males and increased the activity in the females. Cytosolic T3 sulfation was inhibited by the addition of known inhibitors of phenol sulfotransferase, pentachlorophenol or 2,6-dichloro-4-nitrophenol. These results indicate a role of pituitary GH in hepatic sulfation of thyroid hormones in rats. The data obtained also raise the possibility that GH may modify the effect of thyroid hormones on the pituitary by a feed-back mechanism through changing the level of a sex-dominant phenol sulfotransferase(s) in rat livers. T3 was also sulfated in hepatic cytosols of mouse, hamster, rabbit, dog, monkey, and human.(ABSTRACT TRUNCATED AT 250 WORDS)

From liver cytosols of male Sprague-Dawley rats, two N-hydroxyarylamine sulfotransferases (HASTs) which sulfate N-hydroxy-2-acetylaminofluorene and a phenolsulfotransferase (PST-I) have been purified about 290-, 690-, and 210-fold, respectively, by the use of DEAE-anion exchange, Blue-Sepharose CL-6B, DEAE-HPLC, and ATP-agarose affinity chromatography. All three enzymes showed almost the same molecular weight of 33 kDa on SDS-polyacrylamide gel electrophoresis. In Western blots using antibody raised against HAST I, the two HASTs, but not PST-I, were detected. The content of total HAST in male rats was estimated as 4-5 micrograms/mg cytosolic protein, about 4 times higher than that in female rats. Direct comparison of the DEAE-HPLC elution profiles of cytosol showed that HAST I and HAST II were male-dominant and male-specific, respectively, in their expression in the livers. Hypophysectomy decreased the level of HAST by 60% in male rats, but had no obvious effect in female rats. Intermittent injection of growth hormone to mimic the male secretory pattern raised the content in hypophysectomized rats of both sexes close to that in intact male rats, while the continuous infusion of growth hormone to mimic the female secretory pattern showed limited effects. In addition, the administration of triiodothyronine stimulated HAST in hypophysectomized rats of both sexes, and the extent of stimulation was nearly the same as observed in the male-type growth hormone treatment. PST-I, in contrast to HAST, showed no clear sex-related difference in hepatic content, and was not apparently affected by growth hormone or triiodothyronine.(ABSTRACT TRUNCATED AT 250 WORDS)

The regulatory mechanism of acetyltransferase and sulfotransferase, which are involved in the activation of carcinogenic arylamines and their N-hydroxy derivatives, has been studied. Cytosolic N-acetylation of 2-aminofluorene (2-AF) in hamster liver and skin showed tri-modal distribution in the presence of acetyl CoA, whereas no clear segregation was detected in the N-hydroxyarylacetamide-supported N-acetylation and acetyl CoA-dependent O-acetylation of N-hydroxy-Glu-P-1. From hamster livers, two forms of acetyltransferase, AT-I and AT-II, were purified and characterized to have different catalytic and chemical properties. AT-I was detectable in all the hamsters examined, but AT-II was detected only in the animals showing high rates of 2-AF N-acetylation. Cross-matings of the intra- and inter-phenotypes of three different acetylators (rapid, intermediate, and slow) indicate the genetic inheritance of the arylamine N-acetylation, which follows a Mendelian co-dominant trait. Cytosolic sulfotransferase catalyzes the activation of N-hydroxyarylamines and N-hydroxyarylacetamides through the enzymatic O-sulfonylation. The reaction often shows a sex-related difference in rats. Among three sulfotransferases isolated (HAST I, II, and PST I), the level of HASTs was correlated with the 3'-phosphoadenosine 5'-phosphosulfate (PAPS)-dependent activating capacity of N-hydroxy-2-acetylaminofluorene (N-hydroxy-AAF) in rat livers. In addition, hepatic content of HASTs was decreased by hypophysectomy and restored by the intermittent administration of growth hormone, which mimics the male secretory profile. These results indicate that the sex-related difference in secretory profile of pituitary growth hormone is a major determinant of the male-dominant sulfation in this species.(ABSTRACT TRUNCATED AT 250 WORDS)

In mammalian hepatic cytosol both acetyltransferase and sulfotransferase are involved in the activation of N-hydroxy derivatives of arylamines and arylamides. The role of acetyltransferase is also shown in Salmonella, whereas no rigid evidence is provided on the role of sulfotransferase in Salmonella. In Ames mutagenesis test without S9-mix, the number of revertants of Salmonella typhimurium TA98 induced was 10-fold higher with 2-hydroxyamino-3-methylimidazo[4,5-f] quinoline (N-hydroxy-IQ) than with 2-hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (N-hydroxy-Glu-P-1). The extents of the binding to calf thymus DNA of N-hydroxy-Glu-P-1 were, however, 3.9 to 8.6-fold higher than that of N-hydroxy-IQ in both acetyl CoA- and PAPS-fortified rat hepatic cytosol systems. To understand the mechanism causing the apparent discrepancy between the results of the mutation and DNA binding, the activating capacities of cytosols of S. typhimurium TA98 and TA98/1,8-DNP6 strains on the binding of N-hydroxy-Glu-P-1 and N-hydroxy-IQ have been examined in comparison with those of rat livers. Although both N-hydroxyarylamines were activated by hepatic cytosols in the presence of PAPS, no significant DNA binding of these N-hydroxyarylamines was detected in the presence of PAPS and either one of the two strains of bacterial cytosols. In addition, both cytosols of TA98 and TA98/1,8-DNP6 strains showed no measurable activity on the sulfation of p-nitrophenol, suggesting no capacity for sulfotransferase-mediated activation of N-hydroxyarylamines in Salmonella. On the contrary, the extents of the acetyl CoA-dependent binding of N-hydroxy-IQ in cytosols of TA98, but not of TA98/1,8-DNP6, were respectively 6- and 9-fold higher than those in hepatic cytosols of male and female rats, although the extents of the binding of N-hydroxy-Glu-P-1 were rather higher in hepatic than in bacterial cytosols. In addition, the covalent binding of N-hydroxy-2-acetylaminofluorene to DNA was detected in hepatic, but not in bacterial cytosols, although the binding of N-hydroxy-2-aminofluorene was detectable in both hepatic and bacterial cytosols in the presence of acetyl CoA. These results indicate that the metabolic activating capacities of Salmonella and rat liver cytosols differ qualitatively, and the difference in the substrate specificity of acetyltransferase between Salmonella and rat livers may be involved, in part, in the difference of their DNA damage in bacteria and mammals.