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Expression regulation of MAO isoforms in monocytic cells in response to Th2 cytokines
No full textBackground: Th2-cytokines, such as interleukins-4 and –13 (IL-4, IL-13), have been identified as alternative stimuli of monocytes/macrophages. We have recently profiled the gene-expression pattern of IL-4-teated human peripheral monocytes and found that 15-lipoxygenase-1 (15-LOX1) and monoamine oxidase A (MAO-A) are among the five most strongly upregulated gene products in IL-4-treated cells. Transfection of monocytic cells (U937) with 15-LOX1 also induced MAO-A expression. These data suggested that 15-LOX1 products might play a role in the IL4-induced signaling cascade leading to expression of MAO-A in human monocytes. Material/Methods: To test this hypothesis we incubated wild-type and 15-LOX1-transfected U937 cells with different concentrations of either IL-4 or 15-LOX-products [13S-H(p)ODE, 15S-H(p)ETE] and quantified the expression of 15-LOX1, MAO-A, and MAO-B by activity assays and real-time RT-PCR. Results: Wild-type U937 cells express neither MAO-A nor MAO-B, but after three days of IL4 treatment, MAO-A mRNA was detected. A similar isoform-specific expression of MAO-A mRNA was observed when U937 cells were transfected with 15-LOX1 or when the cells were incubated with primary 15-LOX1 products (hydroperoxy fatty acids) or H2O2. In contrast, the corresponding hydroxy fatty acids were ineffective. Conclusions: These data indicate that increased intracellular peroxide concentrations (oxidative stress) induce MAO-A expression in monocytes/macrophages, which normally do not express the enzyme. Our findings also suggest that IL-4-induced upregulation of MAO-A expression in human peripheral monocytes may proceed via 15-LOX1-dependent and 15-LOX1-independent pathways. The biological role of MAO-A expression for monocyte function is discussed
Platelet monoamine oxidase activity in alcoholics with and without a family history of alcoholism
No full textA number of studies point at platelet monoamine oxidase (MAO) activity being reduced in alcoholics with a family history of drinking, this being a possible vulnerability marker for alcoholism. To test this hypothesis, we examined a group of recently detoxified alcoholics with high (n = 25) and low genetic loading for alcoholism (n = 28) and a group of healthy controls (n = 21). Clinical assessments were made using the SCID II interview for psychiatric disorders, the Family History Assessment Module and the Semi-Structural Assessment of Genetics in Alcoholism, a questionnaire especially designed for genetic studies. Platelet MAO activity with and without ethanol stimulation and the percentage of MAO activity with ethanol did not differ between groups. The only significant difference was a lower inhibition of MAO activity with ethanol in alcoholics both with and without a family history compared to controls. In patients with antisocial personality traits, platelet MAO activity was also not found to be different from other alcoholics. Our findings question the hypothesis of reduced platelet MAO activity to be a possible vulnerability marker for alcoholism. Copyright (C) 2000 S. Karger AG. Basel
Early postnatal inhibition of serotonin synthesis results in long-term reductions of perseverative behaviors, but not aggression, in MAO A-deficient mice
No full textMonoamine oxidase (MAO) A, the major enzyme catalyzing the oxidative degradation of serotonin (5-hydroxytryptamine, 5-HT), plays a key role in emotional regulation. In humans and mice, MAO-A deficiency results in high 5-HT levels, antisocial, aggressive, and perseverative behaviors. We previously showed that the elevation in brain 5-HT levels in MAO-A knockout (KO) mice is particularly marked during the first two weeks of postnatal life. Building on this finding, we hypothesized that the reduction of 5-HT levels during these early stages may lead to enduring attenuations of the aggression and other behavioral aberrances observed in MAO-A KO mice. To test this possibility, MAO-A KO mice were treated with daily injections of a 5-HT synthesis blocker, the tryptophan hydroxylase inhibitor p-chloro-phenylalanine (pCPA, 300 mg/kg/day, IP), from postnatal day 1 through 7. As expected, this regimen significantly reduced 5-HT forebrain levels in MAO-A KO pups. These neurochemical changes persisted throughout adulthood, and resulted in significant reductions in marble-burying behavior, as well as increases in spontaneous alternations within a T-maze. Conversely, pCPA-treated MAO-A KO mice did not exhibit significant changes in anxiety-like behaviors in a novel open-field and elevated plus-maze; furthermore, this regimen did not modify their social deficits, aggressive behaviors and impairments in tactile sensitivity. Treatment with pCPA from postnatal day 8 through 14 elicited similar, yet milder, behavioral effects on marble-burying behavior. These results suggest that early developmental enhancements in 5-HT levels have long-term effects on the modulation of behavioral flexibility associated with MAO-A deficiency
Bidirectional promoter of human monoamine oxidase A (MAO A) controlled by transcription factor Sp1
No full textThe core promoter region of human monoamine oxidase (MAO) A has been identified in the two 90 bp repeat sequences, which can be further divided into four imperfect tandem repeats, each containing an Sp 1 binding site in the reversed orientation. Gel retardation and DNase 1 footprinting assays identified Sp 1 to be the major transcription factor binding to MAO A core promoter. In addition, positive association has been observed between cellular Sp1 concentration and MAO A promoter or catalytic activity, indicating that Sp1 is a controlling factor for human MAO A expression. DNA fragments from MAO A core promoter exhibit promoter activity in both orientations in a transient transfection assay, using human growth hormone as the reporter gene. A DNA probe isolated from upstream of the core promoter detected positive signals in a Northern analysis, suggesting that the reverse promoter activity may endogenously transcribe a new gene located upstream of MAO A.</jats:p
Promoter organization and activity of human monoamine oxidase (MAO) A and B genes
No full textMonoamine oxidase A and B (MAO A and B) play important roles in the metabolism of biogenic and dietary amines and are encoded by two genes derived from a common ancestral gene. The promoter regions for human MAO A and B genes have been characterized using a series of 5′ flanking sequences linked to a human growth hormone reporter gene. When these constructs were transfected into NIH3T3, SHSY-5Y, and COS7 cells, the maximal promoter activity for MAO A was found in a 0.14 kilobase (kb) PvuII/DraII fragment (A0.14) and in a 0.15 kb PstI/NaeI fragment (B0.15) for MAO B. Both fragments are GC-rich, contain potential Sp1 binding sites, and are in the region where the MAO A and B 5′ flanking sequences share the highest identity (approximately 60%). However, the organization of the transcription elements is distinctly different between these two promoters. Fragment A0.14 consists of three Sp1 elements, all in reversed orientations, and lacks a TATA box. Two of the Sp1 sites are located within the downstream 90 base pair (bp) direct repeat, and the third is located at the 3′ end of the upstream 90 bp direct repeat. Fragment B0.15 contains an Sp1-CACCC-Sp1-TATA structure; deletion of any of these elements reduced promoter activity. Additional Sp1 sites, CACCC elements, CCAAT boxes, and direct repeats (four 30 bp direct repeats in MAO A and two 29 bp direct repeats in MAO B) are found in farther-upstream sequences of both genes (1.27 kb for MAO A and mostly in 0.2 kb for MAO B). Inclusion of these sequences decreased promoter activity. The different promoter organization of MAO A and B genes provides the basis for their different tissue- and cell- specific expression.</jats:p
JC and BK polyomavirus-like particles as targets of innate and adaptive humoral immunity
No full textJC polyomavirus (JCPyV) and BK polyomavirus (BKPyV) were identified as the first of now more than 12 human polyomaviruses (HPyVs). The average JCPyV and BKPyV seroprevalence rates in adults are 70% and 90%, respectively. After asymptomatic infection both viruses persist in the renourinary tract. In fact, asymptomatic viruria is detectable in one-third of general population. However, in immunocompromised patients, JCPyV and BKPyV replication may progress to significant diseases. Hence, JCPyV can cause progressive multifocal leukoencephalopathy (PML) in patients with HIV-AIDS, malignancies or autoimmune diseases under immunosuppressive treatment. BKPyV can be a cause of polyomavirus-associated nephropathy (PyVAN) in kidney transplant recipients or hemorrhagic cystitis (PyVHC) after allogeneic hematopoietic stem cell transplantation. Due to more frequent application of immunosuppression, the risk of developing these diseases has increased in the last few decades. The risk of PML development is estimated to be 100-fold higher for JCPyV-seropositive patients in comparison to JCPyV-seronegatives. Most cases of PyVAN and PyVHC have been tested positive for BKPyV at the moment of disease diagnosis. Unfortunately, there is no specific antiviral therapy against any of these HPyV diseases. Thus, current strategies to avert PyVAN or PyVHC aim at identifying patients with BKPyV viremia and reducing immunosuppression. Similar strategies for PML have not been effective, since JCPyV viremia is usually not detected prior to or at the diagnosis of disease. The fate of BKPyV and JCPyV virus-like particles (VLPs) was examined in an animal model corresponding to primary viremia in non-immune host. Radioactively labeled VLPs were used to assess blood decay, organ, and hepatocellular distribution of ligand, and non-labeled VLPs to examine cellular uptake by immunohisto- and cytochemistry. Rapid distribution of both BKPyV and JCPyV VLPs to the liver was observed, with lesser uptake in kidney and spleen. Liver uptake was predominantly observed in LSECs. Blood half-life and tissue distribution of both wild-type JCPyV VLPs and two mutant JCPyV VLPs (L55F and S269F), lacking sialic acid binding affinity, were similar, indicating involvement of non-sialic acid receptors in cellular uptake. We concluded that LSECs very effectively cleared a large fraction of blood-borne BKPyV and JCPyV VLPs, indicating a central role of these cells in early removal of polyomavirus from the circulation. Moreover, we observed that a subpopulation of endothelial cells in kidney, the main organ of polyomavirus persistence, showed selective and rapid uptake of VLPs, suggesting a role in viremic organ tropism (Simon-Santamaria et al., p. 54). Giving the increasing clinical need to reliably determine JCPyV and BKPyV IgG levels in patients at risk, we first reviewed and optimized serological tools for JCPyV and BKPyV IgG detection including virus-like particle (VLP)-based ELISA. We demonstrated that although no statistically significant differences in intraassay and interassay variability were revealed for JCPyV serology of 400-fold diluted sera from healthy donors, qualitative differences were seen in the identification of the individual JCPyV serostatus. The cause of discordance for approximately 10% of sera resulted from a low IgG activity close to the cutoff of the assay. Therefore we standardized the ELISA using reference serum for normalization. Moreover, we developed a preadsorption assay with cutoff of 35% reduction of the JCPyV IgG activity after preincubation with JCPyV VLPs. Importantly, we excluded BKPyV antibody cross-reactivity by testing JCPyV IgG positive sera in preadsorption assay using BKPyV VLPs. In conclusion, we showed that VLP-based ELISA with normalization can serve as a reliable tool for JCPyV IgG serology. Additionally, the preadsorption assay can help with unequivocal determination of JCPyV serostatus for samples with low IgG levels. (Kardas et al., p. 72). We also normalized this VLP-based ELISA for BKPyV IgG detection and showed that for seroepidemiology studies, normalized JCPyV and BKPyV IgG ELISA at 1:200 serum dilution provides optimal sensitivity and specificity with the lowest false-positive and false-negative rate. However, for individual risk assessment, 100-, 200-, and 400-fold dilutions combined with preadsorption for low-reactive sera might be the most appropriate (Kardas et al., p. 82). This improved ELISA was used to investigate JCPyV and BKPyV specific antibody levels in several clinical studies: (1) one case of PML patient where positive JCPyV IgG status was compatible with other PML-indicating symptoms (Kurmann et al., p. 90); (2) one case of PyVAN caused by JCPyV rather than BKPyV, as confirmed by JCPyV IgG/IgM positive and BKPyV IgG/IgM negative results (Lautenschlager et al., 99); (3) one case of PyVHC patient after allogeneic hematopoietic stem cell transplantation where increasing BKPyV IgG activities were in line with progression of BKPyV viremia (Koskenvuo et al., p. 106). Further, by serological testing of 122 immunocompetent and 63 immunocompromised patients we demonstrated that the BKPyV IgG level is age-dependent, with the highest values between 20 and 30 years (Schmidt et al., p. 119). In another study we compared serological outcomes of ELISA utilizing two different antigens in terms of prognostic value in prostate cancer development. To accomplish this we utilized improved ELISA for BKPyV IgG activity to both BKPyV VLPs and BKPyV LTag. Testing of 226 patients undergoing radical prostatectomy for primary prostate cancer revealed that BKPyV VP1 serostatus, in contrast to BKPyV LTag, has no prognostic value in prostate cancer progression (Keller et al., p. 125). In conclusion, we provided a new input into knowledge about tropism and clearance of polyomaviruses from blood. Moreover, we established a reliable and sensitive VLP-based assay for specific detection of JCPyV and BKPyV IgG and IgM. Serostatus based on ELISA results was compatible with other symptoms of BKPyV- and JCPyV-related diseases
Perancangan Sistem Informasi Pengelola Barang/Inventaris Di Jc Komp
No full textInventory information system is a system used to enter inventory data into the database, so that there are no errors in input, output data, and reporting based on the desired data. based on surveys and interviews with jc comp personnel, information was obtained that the existing system in the jc comp warehouse section is still manual. therefore, the system that will be created by the author is the result of a replication of the existing system in the jc comp warehouse section. in addition to the process of input and output of goods, this information system is also equipped with features for creating data reports, input and output of goods, and searching for goods data by item name. with the inventory information system is expected to be useful for the warehouse parts jc comp. By implementing this system in the jc comp warehouse, it is hoped that it can reduce errors that may occur. this system is also expected to further speed up the process of input, output, and report generation, which in turn will help the jc comp warehouseSistem Informasi Persediaan Barang adalah sebuah sistem yang digunakan untuk memasukkan data-data persediaan barang ke dalam database, sehinggga tidak terjadi kesalahan dalam input, output data, dan pembuatan laporan berdasarkan data yang diinginkan. Berdasarkan survey dan wawancara dengan bagian personalia Jc Komp, didapatkan informasi bahwa sistem yang ada dibagian gudang Jc Komp masih manual. Oleh karena itu, sistem yang akan dibuat oleh penulis adalah hasil replikasi dari sistem yang telah ada dibagian gudang Jc Comp. Selain proses input dan output barang, pada sistem informasi ini juga dilengkapi fitur pembuatan laporan data, input, dan output barang, dan pencarian data barang berdasarkan nama barang. Dengan adanya Sistem Informasi persediaan barang ini diharapkan dapat bermanfaat bagi bagian gudang Jc Komp. Dengan diterapkannya sistem ini pada bagian gudang Jc Comp, maka diharapkan dapat mengurangi kesalahan-kesalahan yang mungkin terjadi. Sistem ini juga diharapkan dapat lebih mempercepat proses input, output, dan pembuatan laporan yang pada akhirnya dapat membantu bagian gudang Jc Komp
Primary Effusion Lymphoma Involving both Pleural and Abdominal Cavities in a Patient with Hepatitis B Virus-related Liver Cirrhosis.
No full textWCC-JC 2.0: A Web-Crawled and Manually Aligned Parallel Corpus for Japanese-Chinese Neural Machine Translation
No full textMovie and TV subtitles are frequently employed in natural language processing (NLP) applications, but there are limited Japanese-Chinese bilingual corpora accessible as a dataset to train neural machine translation (NMT) models. In our previous study, we effectively constructed a corpus of a considerable size containing bilingual text data in both Japanese and Chinese by collecting subtitle text data from websites that host movies and television series. The unsatisfactory translation performance of the initial corpus, Web-Crawled Corpus of Japanese and Chinese (WCC-JC 1.0), was predominantly caused by the limited number of sentence pairs. To address this shortcoming, we thoroughly analyzed the issues associated with the construction of WCC-JC 1.0 and constructed the WCC-JC 2.0 corpus by first collecting subtitle data from movie and TV series websites. Then, we manually aligned a large number of high-quality sentence pairs. Our efforts resulted in a new corpus that includes about 1.4 million sentence pairs, an 87% increase compared with WCC-JC 1.0. As a result, WCC-JC 2.0 is now among the largest publicly available Japanese-Chinese bilingual corpora in the world. To assess the performance of WCC-JC 2.0, we calculated the BLEU scores relative to other comparative corpora and performed manual evaluations of the translation results generated by translation models trained on WCC-JC 2.0. We provide WCC-JC 2.0 as a free download for research purposes only
Amenable L-2-Theoretic Methods and Knot Concordance
No full textWe reveal new structures in the topological knot concordance group. As a key ingredient, we develop obstructions using L-2-theoretic methods for amenable groups in Strebel's class recently introduced by Orr and the author. Concerning (h)-solvable knots, which are defined in terms of certain Whitney towers of height h in bounding 4-manifolds, we show the following: for any n>1, there are (n)-solvable but non-(n. 5)-solvable (and therefore nonslice) knots, which are not detected by prior methods using Cochran-Orr-Teichner L-2-signature obstructions as well as Levine algebraic obstructions and Casson-Gordon invariants.X1197sciescopu
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