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Sample records for dos genes il1b

  1. CRP and IL-1B Gene Polymorphisms and CRP in Blood in Periodontal Disease

    PubMed Central

    Auerkari, EI; Suhartono, AW; Djamal, NZ; Verisqa, F; Suryandari, DA; Kusdhany, LS; Masulili, SLC; Talbot, C

    2013-01-01

    Recent studies have suggested an association between periodontal disease (PD) and the systemic polygenic diseases such as cardiovascular disease (CVD). These are thought to be associated because of interrelated environmental, epigenetic, and genetic risk factors. The involved candidate genes include the IL-1B gene, encoding the pro-inflammatory cytokine IL-1β, and the CRP gene encoding the C-reactive protein (CRP), also a known marker of inflammation. However, as the details are not well known on the genetic variation influencing the risk factors, this work aimed to evaluate the distribution of selected polymorphisms of IL-1B and CRP genes, and serum CRP level, in comparison with the PD status. For this purpose, periodontal health was assessed, serum CRP levels measured and polymorphism status of IL-1B and CRP genes determined from samples of peripheral blood taken from 101 consenting Indonesian adult males. The results show that severe PD was significantly associated with age and smoking, as expected, but not with the polymorphisms of IL-1B or CRP (1444). However, a significantly lower fraction of subjects with normal periodontal health than subjects with PD showed the heterozygous type polymorphism of CRP (717). There was no significant difference in the fraction of cases with elevated serum CRP level between subjects with normal health and those with PD, and further study with a larger sample is recommended. The observed association between polymorphism of CRP (717) and periodontal health is suggested as a complementary indicator of the risk to PD for the Indonesian male population. PMID:24009648

  2. Impact of IL1B gene polymorphisms and interleukin 1B levels on susceptibility to spontaneous preterm birth.

    PubMed

    Langmia, Immaculate M; Apalasamy, Yamunah D; Omar, Siti Z; Mohamed, Zahurin

    2016-11-01

    Genetic factors influence susceptibility to preterm birth (PTB) and the immune pathway of PTB that involves the production of cytokines such as interleukins has been implicated in PTB disease. The aim of this study is to investigate the association of interleukin 1β (IL1B) gene polymorphisms and IL1B levels with spontaneous PTB. Peripheral maternal blood from 495 women was used for extraction of DNA and genotyping was carried out using the Sequenom MassARRAY platform. Maternal plasma was used to measure IL1B levels. There was no significant association between the allelic and genotype distribution of IL1B single nucleotide polymorphism (SNP) (rs1143634, rs1143627, rs16944) and the risk of PTB among Malaysian Malay women (rs1143634, P=0.722; rs1143627, P=0.543; rs16944, P=0.615). However, IL1B levels were significantly different between women who delivered preterm compared with those who delivered at term (P=0.030); high mean levels were observed among Malay women who delivered at preterm (mean=32.52) compared with term (mean=21.68). IL1B SNPs were not associated with IL1B plasma levels. This study indicates a significant association between IL1B levels and reduced risk of PTB among the Malaysian Malay women. This study shows the impact of IL1B levels on susceptibility to PTB disease; however, the high levels of IL1B observed among women in the preterm group are not associated with IL1B SNPs investigated in this study; IL1B high levels may be because of other factors not explored in this study and therefore warrant further investigation.

  3. IL1B Gene Variation and Internalizing Symptoms in Maltreated Preschoolers

    PubMed Central

    Ridout, Kathryn K.; Parade, Stephanie H.; Seifer, Ronald; Price, Lawrence H.; Gelernter, Joel; Feliz, Paloma; Tyrka, Audrey R.

    2015-01-01

    Evidence now implicates inflammatory proteins in the neurobiology of internalizing disorders. Genetic factors may influence individual responses to maltreatment; however, little work has examined inflammatory genetic variants in adults and none in children. The present study examined the role of an IL1B variant in preschoolers exposed to maltreatment and other forms of adversity in internalizing symptom development. One hundred ninety-eight families were enrolled, with one child (age 3-5 years) from each family. Adversity measures included child protective service documentation of moderate-severe maltreatment in the last 6 months and interview-assessed contextual stressors. Internalizing symptoms were measured using the Child Behavior Checklist (CBCL) and the Diagnostic Infant and Preschool Assessment (DIPA). Maltreated children had higher MDD and PTSD symptoms and marginally higher internalizing symptoms on the CBCL. Controlling for age, sex and race, IL1B genotype was associated with MDD symptoms (p = .002). Contextual stressors were significantly associated with MDD and PTSD and marginally with internalizing symptoms. The IL1B genotype interacted with contextual stress such that children homozygous for the minor allele had more MDD symptoms (p = .045). These results suggest that genetic variants of IL1B may modulate the development of internalizing symptoms in the face of childhood adversity. PMID:25422961

  4. Association of Interleukin 1 beta (IL-1B) gene polymorphism with early pregnancy loss risk in the North Indian population.

    PubMed

    Nair, R R; Khanna, A; Singh, K

    2014-02-01

    C+3953T IL-1 B single-nucleotide polymorphism (SNP) genotyping was carried out in 140 unrelated early pregnancy loss (EPL) patients and in 198 fertile healthy control women and in chorionic villous samples by PCR-RFLP. In Indian population, this is the first report on association of IL-1 B SNP C+3953T polymorphism and EPL.

  5. Variants in LTA, TNF, IL1B and IL10 genes associated with the clinical course of sepsis.

    PubMed

    Montoya-Ruiz, Carolina; Jaimes, Fabián A; Rugeles, Maria T; López, Juan Álvaro; Bedoya, Gabriel; Velilla, Paula A

    2016-12-01

    The aim of this study was to explore the association between some SNPs of the TNF, LTA, IL1B and IL10 genes with cytokine concentrations and clinical course in Colombian septic patients. We conducted a cross-sectional study to genotype 415 septic patients and 205 patients without sepsis for the SNPs -308(G/A) rs1800629 of TNF; +252 (G/A) rs909253 of LTA; -511(A/G) rs16944 and +3953(C/T) rs1143634 of IL1B; and -1082(A/G) rs1800896, -819(C/T) rs1800871 and -592(C/A) rs1800872 of IL10. The association of theses SNPs with the following parameters was evaluated: (1) the presence of sepsis; (2) severity and clinical outcomes; (3) APACHE II and SOFA scores; and (4) procalcitonin, C-reactive protein, tumor necrosis factor, lymphotoxin alpha, interleukin 1 beta and interleukin 10 plasma concentrations. We found an association between the SNP LTA +252 with the development of sepsis [OR 1.29 (1.00-1.68)]; the SNP IL10 -1082 with sepsis severity [OR 0.53 (0.29-0.97)]; the TNF -308 with mortality [OR 0.33 (0.12-0.95)]; and the IL10 -592 and IL10 -1082 with admission to the intensive care unit (ICU) [OR 3.36 (1.57-7.18)] and [OR 0.18 (0.04-0.86)], respectively. None of the SNPs were associated with cytokine levels, procalcitonin and C-reactive protein serum concentrations, nor with APACHE II and SOFA scores. Our results suggest that these genetic variants play an important role in the development of sepsis and its clinical course.

  6. Relationships of common polymorphisms in IL-6, IL-1A, and IL-1B genes with susceptibility to osteoarthritis: a meta-analysis.

    PubMed

    Cai, Hao; Sun, Huan-Jian; Wang, You-Hua; Zhang, Zhe

    2015-08-01

    Observational and experimental studies have arrived at inconsistent conclusions about whether common polymorphisms in IL-6, IL-1A, and IL-1B genes are associated with an increased risk of osteoarthritis (OA). Therefore, we undertook a comprehensive meta-analysis to more systematically summarize the relationships of IL-6, IL-1A, and IL-1B genetic polymorphisms with susceptibility to OA. We screened the PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, China BioMedicine (CBM), and China National Knowledge Infrastructure (CNKI) databases up to 31 March 2014. We used STATA software to analyze statistical data. Odds ratios (ORs) and their corresponding 95 % confidence intervals (95 % CIs) were calculated. Seventeen independent case-control studies were included in this meta-analysis with a total number of 7,491 subjects, comprised of 3,293 OA patients and 4,729 healthy controls. Our results indicate that IL-6, IL-1A, and IL-1B genetic polymorphisms are statistically correlated with an increased risk of OA under the allele and dominant models. According to a subgroup analysis based on disease, a higher frequency of IL-6 genetic polymorphisms was observed among knee OA and hand OA patients, but not among hip OA and DIP OA patients. A higher frequency of IL-1A genetic polymorphisms were found among hip OA patients, hand OA, hip OA and DIP OA patients. Furthermore, we observed a higher IL-1B polymorphism frequency among knee OA and hip OA patients, but not among hand OA patients. Our findings provide evidence that IL-6, IL-1A, and IL-1B genetic polymorphisms may be correlated with susceptibility to OA.

  7. Role of the polymorphic IL-1B, IL-1RN and TNF-A genes in distal gastric cancer in Mexico.

    PubMed

    Garza-González, Elvira; Bosques-Padilla, Francisco Javier; El-Omar, Emad; Hold, Georgina; Tijerina-Menchaca, Rolando; Maldonado-Garza, Héctor Jesus; Pérez-Pérez, Guillermo Ignacio

    2005-03-20

    Several cytokine gene polymorphisms have been associated with increased risk of distal gastric cancer (GC) and its precursor histological markers in Caucasian, Asian and Portuguese populations although little is known about their role in other ethnic groups. Our study investigates the role of the IL-1B-31, IL-1RN and TNF-A-308 gene polymorphisms as risk factors for the development of GC in a Mexican population. We studied 278 patients who were enrolled at the Hospital Universitario Dr. Jose Eleuterio Gonzalez, Universidad Autonoma de Nuevo Leon. The subjects were divided into 2 groups. Sixty-three patients with histologically confirmed distal GC (mean age = 58.8 years, range = 22-84, F:M = 0.56), and 215 patients with no evidence of distal or proximal GC (mean age = 56.1 years, range = 18-92, F:M = 1.17). The IL-1B-31 and the TNF-A-308 polymorphisms were determined by PCR-RFLP and pyrosequencing, respectively, in all cases and controls. The VNTR polymorphism in intron 2 of the 1L-1RN gene was typed by PCR in 25 cases and 201 controls. The H. pylori status was determined by histology, rapid urease test, culture and serology for non-cancer controls and by histology for the GC cases. The carriage of the proinflammatory IL-1B-31*C allele was associated with increased risk of distal GC (odds ratio [OR] = 7.63, 95% confidence interval [CI] = 1.73-46.94, p = 0.003). When cases and controls were matched by age and gender, the OR value was higher (OR = 8.05, 95% CI = 1.8-50.22, p = 0.001). When only H. pylori GC cases and controls were compared, the OR value was 7.8 (95% CI = 1.05-161.8, p = 0.04). No association was found between any of the other polymorphisms studied and distal GC. In this Mexican population, the IL-1B proinflammatory genotype increases the risk of distal GC. These findings are similar to previous reports in Caucasian populations and underscore the importance of cytokine gene polymorphisms in the development of distal GC.

  8. Regulated transcription of human matrix metalloproteinase 13 (MMP13) and interleukin-1β (IL1B) genes in chondrocytes depends on methylation of specific proximal promoter CpG sites.

    PubMed

    Hashimoto, Ko; Otero, Miguel; Imagawa, Kei; de Andrés, María C; Coico, Jonathan M; Roach, Helmtrud I; Oreffo, Richard O C; Marcu, Kenneth B; Goldring, Mary B

    2013-04-05

    The role of DNA methylation in the regulation of catabolic genes such as MMP13 and IL1B, which have sparse CpG islands, is poorly understood in the context of musculoskeletal diseases. We report that demethylation of specific CpG sites at -110 bp and -299 bp of the proximal MMP13 and IL1B promoters, respectively, detected by in situ methylation analysis of chondrocytes obtained directly from human cartilage, strongly correlated with higher levels of gene expression. The methylation status of these sites had a significant impact on promoter activities in chondrocytes, as revealed in transfection experiments with site-directed CpG mutants in a CpG-free luciferase reporter. Methylation of the -110 and -299 CpG sites, which reside within a hypoxia-inducible factor (HIF) consensus motif in the respective MMP13 and IL1B promoters, produced the most marked suppression of their transcriptional activities. Methylation of the -110 bp CpG site in the MMP13 promoter inhibited its HIF-2α-driven transactivation and decreased HIF-2α binding to the MMP13 proximal promoter in chromatin immunoprecipitation assays. In contrast to HIF-2α, MMP13 transcriptional regulation by other positive (RUNX2, AP-1, ELF3) and negative (Sp1, GATA1, and USF1) factors was not affected by methylation status. However, unlike the MMP13 promoter, IL1B was not susceptible to HIF-2α transactivation, indicating that the -299 CpG site in the IL1B promoter must interact with other transcription factors to modulate IL1B transcriptional activity. Taken together, our data reveal that the methylation of different CpG sites in the proximal promoters of the human MMP13 and IL1B genes modulates their transcription by distinct mechanisms.

  9. Promoter Variation and Expression Levels of Inflammatory Genes IL1A, IL1B, IL6 and TNF in Blood of Spinocerebellar Ataxia Type 3 (SCA3) Patients.

    PubMed

    Raposo, Mafalda; Bettencourt, Conceição; Ramos, Amanda; Kazachkova, Nadiya; Vasconcelos, João; Kay, Teresa; Bruges-Armas, Jácome; Lima, Manuela

    2017-03-01

    Age at onset in spinocerebellar ataxia type 3 (SCA3/MJD) is incompletely explained by the size of the CAG tract at the ATXN3 gene, implying the existence of genetic modifiers. A role of inflammation in SCA3 has been postulated, involving altered cytokines levels; promoter variants leading to alterations in cytokines expression could influence onset. Using blood from 86 SCA3 patients and 106 controls, this work aimed to analyse promoter variation of four cytokines (IL1A, IL1B, IL6 and TNF) and to investigate the association between variants detected and their transcript levels, evaluated by quantitative PCR. Moreover, the effect of APOE isoforms, known to modulate cytokines, was investigated. Correlations between cytokine variants and onset were tested; the cumulative modifier effects of cytokines and APOE were analysed. Patients carrying the IL6*C allele had a significant earlier onset (4 years in average) than patients carrying the G allele, in agreement with lower mRNA levels produced by IL6*C carriers. The presence of APOE*ɛ2 allele seems to anticipate onset in average 10 years in patients carrying the IL6*C allele; a larger number of patients will be needed to confirm this result. These results highlight the pertinence of conducting further research on the role of cytokines as SCA3 modulators, pointing to the presence of shared mechanisms involving IL6 and APOE.

  10. Phosphorylation of IRF8 in a Pre-associated Complex with Spi-1/PU.1 and Non-phosphorylated Stat1 is Critical for LPS Induction of the IL1B Gene

    PubMed Central

    Unlu, Sebnem; Kumar, Arvind; Waterman, Wayne R.; Tsukada, Junichi; Wang, Kent Z.Q.; Galson, Deborah L.; Auron, Philip E

    2009-01-01

    Rapid induction of transcription is known to be mediated by factors which bind DNA following post-translational modification. We report here that non-tyrosine phosphorylated (NTP)-Stat1 is involved in a cooperative interaction with Spi-1/PU.1 and IRF8 to form a pre-associated, poised complex is for IL1B gene induction. A double point mutation at a putative STAT binding site, which overlaps this composite Spi-1•IRF8 site located in the LPS and IL-1 response element (LILRE), inhibited human IL1B LPS-dependent reporter activity to about 10 percent of the control wild type vector. Chromatin immunoprecipitation revealed stimulation-independent constitutive binding of IRF8, Spi-1 and NTP-Stat1 at the LILRE, while binding of C/EBPβ was induced to an adjacent C/EBPβ site after LPS stimulation. In contrast to Stat1, IRF8 was tyrosine phosphorylated following LPS treatment. Supporting the involvement of NTP-Stat1, LPS-induced IL1B reporter activity in monocytes was enhanced by ectopic expression of NTP-Stat1Y701F. In contrast, co-expression of a Y211F IRF8 mutein functioned as a dominant-negative inhibitor of LPS-induced IL1B reporter activity. In vitro DNA binding using extracts from LPS-treated monocytes confirmed that the LILRE enhancer constitutively binds a trimolecular complex containing IRF8, Spi-1 and NTP-Stat1. Binding studies using in vitro-expressed proteins revealed that NTP-Stat1 enhanced the binding of Spi-1 and IRF8 to the LILRE. Co-expression of TRAF6, an LPS surrogate, with Spi-1 and IRF8 enhanced IL1B reporter activity in HEK293R cells, which was dramatically reduced when Y211F IRF8 was co-expressed. These results suggest that the rapid transcriptional induction of an important inflammatory gene is dependent upon constitutive cooperative binding of a Spi-1•IRF8•NTP-Stat1 complex to the LILRE, which primes the gene for immediate induction following IRF8 phosphorylation. Phosphorylation of chromatin pre-associated factors like IRF8 may be an important

  11. Interactions between diet, lifestyle and IL10, IL1B, and PTGS2/COX-2 gene polymorphisms in relation to risk of colorectal cancer in a prospective Danish case-cohort study.

    PubMed

    Andersen, Vibeke; Holst, René; Kopp, Tine Iskov; Tjønneland, Anne; Vogel, Ulla

    2013-01-01

    Diet contributes to colorectal cancer development and may be potentially modified. We wanted to identify the biological mechanisms underlying colorectal carcinogenesis by assessment of diet-gene interactions. The polymorphisms IL10 C-592A (rs1800872), C-rs3024505-T, IL1b C-3737T (rs4848306), G-1464C (rs1143623), T-31C (rs1143627) and PTGS2 (encoding COX-2) A-1195G (rs689466), G-765C (rs20417), and T8473C (rs5275) were assessed in relation to risk of colorectal cancer (CRC) and interaction with diet (red meat, fish, fibre, cereals, fruit and vegetables) and lifestyle (non-steroid-anti-inflammatory drug use and smoking status) was assessed in a nested case-cohort study of nine hundred and seventy CRC cases and 1789 randomly selected participants from a prospective study of 57,053 persons. IL1b C-3737T, G-1464C and PTGS2 T8473C variant genotypes were associated with risk of CRC compared to the homozygous wildtype genotype (IRR=0.81, 95%CI: 0.68-0.97, p=0.02, and IRR=1.22, 95%CI: 1.04-1.44, p=0.02, IRR=0.75, 95%CI: 0.57-0.99, p=0.04, respectively). Interactions were found between diet and IL10 rs3024505 (P-value for interaction (P(int)); meat=0.04, fish=0.007, fibre=0.0008, vegetables=0.0005), C-592A (P(int); fibre=0.025), IL1b C-3737T (Pint; vegetables=0.030, NSAID use=0.040) and PTGS2 genotypes G-765C (P(int); meat=0.006, fibre=0.0003, fruit 0.004), and T8473C (P(int); meat 0.049, fruit=0.03) and A-1195G (P(int); meat 0.038, fibre 0.040, fruit=0.059, vegetables=0.025, and current smoking=0.046). Genetically determined low COX-2 and high IL-1β activity were associated with increased risk of CRC in this northern Caucasian cohort. Furthermore, interactions were found between IL10, IL1b, and PTGS2 and diet and lifestyle factors in relation to CRC. The present study demonstrates that gene-environment interactions may identify genes and environmental factors involved in colorectal carcinogenesis.

  12. Tensile strain and magnetic particle force application do not induce MAP3K8 and IL-1B differential gene expression in a similar manner to fluid shear stress in human mesenchymal stem cells.

    PubMed

    Glossop, John R; Cartmell, Sarah H

    2010-10-01

    Mechanical forces, important in a variety of cellular processes, including proliferation, differentiation and gene expression, are also key in the development, remodelling and maintenance of load-bearing tissues such as cartilage and bone. Thus, there is great interest in using in vitro mechanical conditioning of mesenchymal stem cells (MSCs), multipotent adult stem cells, for tissue engineering of these tissues. In a previous gene expression study, we reported a potentially important role for mitogen-activated protein kinase kinase kinase 8 (MAP3K8) and interleukin-1β (IL-1B) in MAPK signalling in MSCs exposed to fluid shear stress. In this follow-up study, we examined the expression of these genes in MSCs exposed to other types of mechanical force: uniaxial tensile strain (3% cell elongation) and forces generated through the exposure of magnetic particle-labelled MSCs to an oscillating magnetic field (maximum field strength 90 mT). Exposure to both types of mechanical force for 1 h did not significantly alter the gene expression of MAP3K8 or IL-1B over the 24 h period subsequent to force exposure. These data demonstrate that uniaxial tensile strain and magnetic particle-based forces do not induce MAP3K8-related MAPK signalling in the same manner as does fluid flow-induced shear stress. This illustrates divergence in the process of mechanotransduction in mechanically stimulated MSCs. Copyright © 2010 John Wiley & Sons, Ltd.

  13. Association study of functional polymorphisms in interleukins and interleukin receptors genes: IL1A, IL1B, IL1RN, IL6, IL6R, IL10, IL10RA and TGFB1 in schizophrenia in Polish population.

    PubMed

    Kapelski, Pawel; Skibinska, Maria; Maciukiewicz, Malgorzata; Wilkosc, Monika; Frydecka, Dorota; Groszewska, Agata; Narozna, Beata; Dmitrzak-Weglarz, Monika; Czerski, Piotr; Pawlak, Joanna; Rajewska-Rager, Aleksandra; Leszczynska-Rodziewicz, Anna; Slopien, Agnieszka; Zaremba, Dorota; Twarowska-Hauser, Joanna

    2015-12-01

    Schizophrenia has been associated with a large range of autoimmune diseases, with a history of any autoimmune disease being associated with a 45% increase in risk for the illness. The inflammatory system may trigger or modulate the course of schizophrenia through complex mechanisms influencing neurodevelopment, neuroplasticity and neurotransmission. In particular, increases or imbalance in cytokine before birth or during the early stages of life may affect neurodevelopment and produce vulnerability to the disease. A total of 27 polymorphisms of IL1N gene: rs1800587, rs17561; IL1B gene: rs1143634, rs1143643, rs16944, rs4848306, rs1143623, rs1143633, rs1143627; IL1RN gene: rs419598, rs315952, rs9005, rs4251961; IL6 gene: rs1800795, rs1800797; IL6R gene: rs4537545, rs4845617, rs2228145, IL10 gene: rs1800896, rs1800871, rs1800872, rs1800890, rs6676671; IL10RA gene: rs2229113, rs3135932; TGF1B gene: rs1800469, rs1800470; each selected on the basis of molecular evidence for functionality, were investigated in this study. Analysis was performed on a group of 621 patients with diagnosis of schizophrenia and 531 healthy controls in Polish population. An association of rs4848306 in IL1B gene, rs4251961 in IL1RN gene, rs2228145 and rs4537545 in IL6R with schizophrenia have been observed. rs6676671 in IL10 was associated with early age of onset. Strong linkage disequilibrium was observed between analyzed polymorphisms in each gene, except of IL10RA. We observed that haplotypes composed of rs4537545 and rs2228145 in IL6R gene were associated with schizophrenia. Analyses with family history of schizophrenia, other psychiatric disorders and alcohol abuse/dependence did not show any positive findings. Further studies on larger groups along with correlation with circulating protein levels are needed.

  14. A novel STAT-like factor mediates lipopolysaccharide, interleukin 1 (IL-1), and IL-6 signaling and recognizes a gamma interferon activation site-like element in the IL1B gene.

    PubMed Central

    Tsukada, J; Waterman, W R; Koyama, Y; Webb, A C; Auron, P E

    1996-01-01

    Binding of many cytokines to their cognate receptors immediately activates Jak tyrosine kinases and their substrates, STAT (signal transducers and activators of transcription) DNA-binding proteins. The DNA binding targets of STATs are sequence elements related to the archetypal gamma interferon activation site, GAS. However, association of interleukin 1 (IL-1) with Jak-STAT signaling has remained unresolved. We now report an element termed LILRE (lipopolysaccharide [LPS] and IL-1-responsive element) in the human prointerleukin 1beta gene (IL1B) which can be immediately induced by either lipopolysaccharide (LPS) or IL-1 protein to bind a tyrosine-phosphorylated protein. This LPS- and IL-1-induced factor (LIL factor) is recognized by an antibody raised against the N terminus of Stat1, but not by those specific for either the C terminus of Stat1 or any other GAS-binding STAT. Phosphotyrosine (P-Tyr) specifically inhibits formation of the LIL factor-DNA complex, suggesting the importance of P-Tyr for the DNA-binding activity, as has been found for all STAT dimers. Analysis of DNA-binding specificity demonstrates that the LIL factor possesses a novel GAS-like binding activity that contrasts with those of other STATs in a requirement for a G residue at position 8 (TTCCTGAGA). Further investigation has revealed that IL-6, but neither IL-4 nor gamma interferon, activates the LIL factor. Thus, the existence of such a STAT-like factor (LIL-Stat) relates the LPS and IL-1 signaling pathway to other cytokine receptor signaling pathways via the activation of STATs. Moreover, the unique DNA-binding specificity and antigenicity of this factor suggest that LPS, IL-1, and IL-6 may use a common signaling pathway. PMID:8628285

  15. Regulatory mechanism for expression of IL1B receptors in the uterine endometrium and effects of IL1B on prostaglandin synthetic enzymes during the implantation period in pigs.

    PubMed

    Seo, Heewon; Choi, Yohan; Shim, Jangsoo; Choi, Youngsok; Ka, Hakhyun

    2012-08-01

    During the implantation period, the porcine conceptus secretes interleukin-1beta (IL1B) that may be involved in the establishment of pregnancy in pigs. However, the regulatory mechanism for IL1B receptor expression and the function of IL1B in the uterine endometrium are not well elucidated. In this study, we determined IL1B receptor expression in the uterine endometrium of pigs during pregnancy. IL1B receptor subtypes, IL1 receptor type I (IL1R1) and IL1 receptor accessory protein (IL1RAP) were expressed in the uterine endometrium with the expression being most abundant on Day 12 of pregnancy primarily in the luminal and glandular epithelial cells. Expression of IL1R1 mRNA increased in response to IL1B in a dose-dependent manner, and expression of IL1RAP mRNA increased in response to both IL1B and estradiol, indicating that expression of endometrial IL1B receptors was regulated cooperatively by IL1B and estrogen of conceptus origin. During the peri-implantation period, the porcine uterine endometrium actively synthesizes and secretes prostaglandins (PGs). IL1B increased expression of PTGS1 and PTGS2 genes that are rate-limiting for PG synthesis in the uterine endometrium. Collectively, the results indicated that IL1B regulates expression of IL1R1 and IL1RAP and stimulates expression of PTGS1 and PTGS2 that are considered to be the most rate-limiting enzymes for endometrial synthesis of PGs during the peri-implantation period of pregnancy in pigs.

  16. IL1B — EDRN Public Portal

    Cancer.gov

    From NCBI Gene: The protein encoded by this gene is a member of the interleukin 1 cytokine family. This cytokine is produced by activated macrophages as a proprotein, which is proteolytically processed to its active form by caspase 1 (CASP1/ICE). This cytokine is an important mediator of the inflammatory response, and is involved in a variety of cellular activities, including cell proliferation, differentiation, and apoptosis. The induction of cyclooxygenase-2 (PTGS2/COX2) by this cytokine in the central nervous system (CNS) is found to contribute to inflammatory pain hypersensitivity. This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2. [provided by RefSeq, Jul 2008

  17. Association of neuropeptide Y (NPY), interleukin-1B (IL1B) genetic variants and correlation of IL1B transcript levels with vitiligo susceptibility.

    PubMed

    Laddha, Naresh C; Dwivedi, Mitesh; Mansuri, Mohmmad Shoab; Singh, Mala; Patel, Hetanshi H; Agarwal, Nishtha; Shah, Anish M; Begum, Rasheedunnisa

    2014-01-01

    Vitiligo is a depigmenting disorder resulting from loss of functional melanocytes in the skin. NPY plays an important role in induction of immune response by acting on a variety of immune cells. NPY synthesis and release is governed by IL1B. Moreover, genetic variability in IL1B is reported to be associated with elevated NPY levels. Aim of the present study was to explore NPY promoter -399T/C (rs16147) and exon2 +1128T/C (rs16139) polymorphisms as well as IL1B promoter -511C/T (rs16944) polymorphism and to correlate IL1B transcript levels with vitiligo. PCR-RFLP method was used to genotype NPY -399T/C SNP in 454 patients and 1226 controls; +1128T/C SNP in 575 patients and 1279 controls and IL1B -511C/T SNP in 448 patients and 785 controls from Gujarat. IL1B transcript levels in blood were also assessed in 105 controls and 95 patients using real-time PCR. Genotype and allele frequencies for NPY -399T/C, +1128T/C and IL1B -511C/T SNPs differed significantly (p<0.0001, p<0.0001; p = 0.0161, p = 0.0035 and p<0.0001, p<0.0001) between patients and controls. 'TC' haplotype containing minor alleles of NPY polymorphisms was significantly higher in patients and increased the risk of vitiligo by 2.3 fold (p<0.0001). Transcript levels of IL1B were significantly higher, in patients compared to controls (p = 0.0029), in patients with active than stable vitiligo (p = 0.015), also in female patients than male patients (p = 0.026). Genotype-phenotype correlation showed moderate association of IL1B -511C/T polymorphism with higher IL1B transcript levels. Trend analysis revealed significant difference between patients and controls for IL1B transcript levels with respect to different genotypes. Our results suggest that NPY -399T/C, +1128T/C and IL1B -511C/T polymorphisms are associated with vitiligo and IL1B -511C/T SNP influences its transcript levels leading to increased risk for vitiligo in Gujarat population. Up-regulation of IL1B transcript in patients

  18. Association of Neuropeptide Y (NPY), Interleukin-1B (IL1B) Genetic Variants and Correlation of IL1B Transcript Levels with Vitiligo Susceptibility

    PubMed Central

    Laddha, Naresh C.; Dwivedi, Mitesh; Mansuri, Mohmmad Shoab; Singh, Mala; Patel, Hetanshi H.; Agarwal, Nishtha; Shah, Anish M.; Begum, Rasheedunnisa

    2014-01-01

    Background Vitiligo is a depigmenting disorder resulting from loss of functional melanocytes in the skin. NPY plays an important role in induction of immune response by acting on a variety of immune cells. NPY synthesis and release is governed by IL1B. Moreover, genetic variability in IL1B is reported to be associated with elevated NPY levels. Objectives Aim of the present study was to explore NPY promoter −399T/C (rs16147) and exon2 +1128T/C (rs16139) polymorphisms as well as IL1B promoter −511C/T (rs16944) polymorphism and to correlate IL1B transcript levels with vitiligo. Methods PCR-RFLP method was used to genotype NPY -399T/C SNP in 454 patients and 1226 controls; +1128T/C SNP in 575 patients and 1279 controls and IL1B −511C/T SNP in 448 patients and 785 controls from Gujarat. IL1B transcript levels in blood were also assessed in 105 controls and 95 patients using real-time PCR. Results Genotype and allele frequencies for NPY −399T/C, +1128T/C and IL1B −511C/T SNPs differed significantly (p<0.0001, p<0.0001; p = 0.0161, p = 0.0035 and p<0.0001, p<0.0001) between patients and controls. ‘TC’ haplotype containing minor alleles of NPY polymorphisms was significantly higher in patients and increased the risk of vitiligo by 2.3 fold (p<0.0001). Transcript levels of IL1B were significantly higher, in patients compared to controls (p = 0.0029), in patients with active than stable vitiligo (p = 0.015), also in female patients than male patients (p = 0.026). Genotype-phenotype correlation showed moderate association of IL1B -511C/T polymorphism with higher IL1B transcript levels. Trend analysis revealed significant difference between patients and controls for IL1B transcript levels with respect to different genotypes. Conclusion Our results suggest that NPY −399T/C, +1128T/C and IL1B −511C/T polymorphisms are associated with vitiligo and IL1B −511C/T SNP influences its transcript levels leading to increased risk for vitiligo in

  19. IL1B-CGTC haplotype is associated with colorectal cancer in admixed individuals with increased African ancestry

    PubMed Central

    Sanabria-Salas, María Carolina; Hernández-Suárez, Gustavo; Umaña-Pérez, Adriana; Rawlik, Konrad; Tenesa, Albert; Serrano-López, Martha Lucía; Sánchez de Gómez, Myriam; Rojas, Martha Patricia; Bravo, Luis Eduardo; Albis, Rosario; Plata, José Luis; Green, Heather; Borgovan, Theodor; Li, Li; Majumdar, Sumana; Garai, Jone; Lee, Edward; Ashktorab, Hassan; Brim, Hassan; Li, Li; Margolin, David; Fejerman, Laura; Zabaleta, Jovanny

    2017-01-01

    Single-nucleotide polymorphisms (SNPs) in cytokine genes can affect gene expression and thereby modulate inflammation and carcinogenesis. However, the data on the association between SNPs in the interleukin 1 beta gene (IL1B) and colorectal cancer (CRC) are conflicting. We found an association between a 4-SNP haplotype block of the IL1B (-3737C/-1464G/-511T/-31C) and CRC risk, and this association was exclusively observed in individuals with a higher proportion of African ancestry, such as individuals from the Coastal Colombian region (odds ratio, OR 2.06; 95% CI 1.31–3.25; p < 0.01). Moreover, a significant interaction between this CRC risk haplotype and local African ancestry dosage was identified in locus 2q14 (p = 0.03). We conclude that Colombian individuals with high African ancestry proportions at locus 2q14 harbour more IL1B-CGTC copies and are consequently at an increased risk of CRC. This haplotype has been previously found to increase the IL1B promoter activity and is the most frequent haplotype in African Americans. Despite of limitations in the number of samples and the lack of functional analysis to examine the effect of these haplotypes on CRC cell lines, our results suggest that inflammation and ethnicity play a major role in the modulation of CRC risk. PMID:28157220

  20. IL1B and DEFB1 Polymorphisms Increase Susceptibility to Invasive Mold Infection After Solid-Organ Transplantation.

    PubMed

    Wójtowicz, Agnieszka; Gresnigt, Mark S; Lecompte, Thanh; Bibert, Stephanie; Manuel, Oriol; Joosten, Leo A B; Rüeger, Sina; Berger, Christoph; Boggian, Katia; Cusini, Alexia; Garzoni, Christian; Hirsch, Hans H; Weisser, Maja; Mueller, Nicolas J; Meylan, Pascal R; Steiger, Jürg; Kutalik, Zoltan; Pascual, Manuel; van Delden, Christian; van de Veerdonk, Frank L; Bochud, Pierre-Yves

    2015-05-15

    Single-nucleotide polymorphisms (SNPs) in immune genes have been associated with susceptibility to invasive mold infection (IMI) among hematopoietic stem cell but not solid-organ transplant (SOT) recipients. Twenty-four SNPs from systematically selected genes were genotyped among 1101 SOT recipients (715 kidney transplant recipients, 190 liver transplant recipients, 102 lung transplant recipients, 79 heart transplant recipients, and 15 recipients of other transplants) from the Swiss Transplant Cohort Study. Association between SNPs and the end point were assessed by log-rank test and Cox regression models. Cytokine production upon Aspergillus stimulation was measured by enzyme-linked immunosorbent assay in peripheral blood mononuclear cells (PBMCs) from healthy volunteers and correlated with relevant genotypes. Mold colonization (n = 45) and proven/probable IMI (n = 26) were associated with polymorphisms in the genes encoding interleukin 1β (IL1B; rs16944; recessive mode, P = .001 for colonization and P = .00005 for IMI, by the log-rank test), interleukin 1 receptor antagonist (IL1RN; rs419598; P = .01 and P = .02, respectively), and β-defensin 1 (DEFB1; rs1800972; P = .001 and P = .0002, respectively). The associations with IL1B and DEFB1 remained significant in a multivariate regression model (P = .002 for IL1B rs16944; P = .01 for DEFB1 rs1800972). The presence of 2 copies of the rare allele of rs16944 or rs419598 was associated with reduced Aspergillus-induced interleukin 1β and tumor necrosis factor α secretion by PBMCs. Functional polymorphisms in IL1B and DEFB1 influence susceptibility to mold infection in SOT recipients. This observation may contribute to individual risk stratification. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. The IL1B-511 Polymorphism (rs16944 AA Genotype) Is Increased in Aspirin-Exacerbated Respiratory Disease in Mexican Population.

    PubMed

    Falfán-Valencia, Ramcés; Pavón-Romero, Gandhi F; Camarena, Angel; García, María de la Luz; Galicia-Negrete, Gustavo; Negrete-García, María Cristina; Teran, Luis Manuel

    2012-01-01

    Aspirin exacerbated respiratory disease (AERD) is characterized by chronic hyperplastic rhinosinusitis, nasal polyposis, asthma, and aspirin sensitivity. The mechanisms which produce these manifestations of intolerance are not fully defined, current research focuses on cyclooxygenase 1 (COX-1) inhibition, metabolism of arachidonic acid, and the COX pathway to the lipoxygenase (LO) route, inducing increased synthesis of leukotrienes (LT). The biological plausibility of this model has led to the search for polymorphisms in genes responsible for proinflammatory cytokines synthesis, such as IL1B and IL8. We performed a genetic association study between IL8-251 (rs4073) and IL1B-511 (rs16944) polymorphisms in AERD, aspirin-tolerant asthma (ATA), and healthy control subjects. Using allelic discrimination by real-time PCR, we found statistically nonsignificant associations between AERD, ATA, and healthy control subjects for the GG and GA genotypes of IL1B (rs16944). Interestingly, the AA genotype showed an increased frequency in the AERD patients versus the ATA group (GF = 0.19 versus 0.07, p = 0.018, OR 2.98, and 95% CI 1.17-7.82). This is the first observation that IL1B polymorphisms are involved in AERD. Thus, future studies must investigate whether interleukin-1β is released in the airways of AERD patients and whether it relates to genetic polymorphisms in the IL1B gene.

  2. Analysis of multiple cytokine polymorphisms in individuals with untreated deep carious lesions reveals IL1B (rs1143643) as a susceptibility factor for periapical lesion development.

    PubMed

    Dill, Alisa; Letra, Ariadne; Chaves de Souza, Letícia; Yadlapati, Mamatha; Biguetti, Claudia Cristina; Garlet, Gustavo Pompermaier; Vieira, Alexandre R; Silva, Renato Menezes

    2015-02-01

    It has been proposed that individual genetic predisposition may contribute to persistent apical periodontitis. Cytokines are associated with levels of inflammation and are involved in caries, pulpal, and periapical tissue destruction. We hypothesized that polymorphisms in cytokine genes may contribute to an individual's increased susceptibility to apical tissue destruction in response to deep carious lesions. Subjects with deep carious lesions with or without periapical lesions (≥3 mm) were recruited at the University of Pittsburgh, Pittsburgh, PA, and the University of Texas at Houston, Houston, TX. Genomic DNA samples of 316 patients were sorted into 2 groups: 136 cases with deep carious lesions and periapical lesions (cases) and 180 cases with deep carious lesions but no periapical lesions (controls). Nine single-nucleotide polymorphisms in IL1B, IL6, TNF, RANK, RANKL, and OPG genes were selected for genotyping. Genotypes were generated by end point analysis using TaqMan chemistry (Invitrogen, Carlsbad, CA) in a real-time polymerase chain reaction instrument. Allele and genotype frequencies were compared among cases and controls using the PLINK program (http://pngu.mgh.harvard.edu/purcell/plink/). Ninety-three human periapical granulomas and 24 healthy periodontal ligament tissues collected postoperatively were used for messenger RNA expression analyses of IL1B. A single-nucleotide polymorphism in IL1B (rs1143643) showed allelic (P = .02) and genotypic (P = .004) association with cases of deep caries and periapical lesions. We also observed altered transmission of IL1B marker haplotypes (P = .02) in these individuals. IL1B was highly expressed in granulomas (P < .001). Variations in IL1B may be associated with periapical lesion formation in individuals with untreated deep carious lesions. Future studies could help predict host susceptibility to developing periapical lesions. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All

  3. Association of Neuropeptide-Y (NPY) and Interleukin-1beta (IL1B), Genotype-Phenotype Correlation and Plasma Lipids with Type-II Diabetes.

    PubMed

    Patel, Roma; Dwivedi, Mitesh; Mansuri, Mohmmad Shoab; Ansarullah; Laddha, Naresh C; Thakker, Ami; Ramachandran, A V; Begum, Rasheedunnisa

    2016-01-01

    Neuropeptide Y (NPY) is known to play a role in the regulation of satiety, energy balance, body weight, and insulin release. Interleukin-1beta (IL1B) has been associated with loss of beta-cell mass in type-II diabetes (TIID). The present study attempts to investigate the association of NPY exon2 +1128 T/C (Leu7Pro; rs16139), NPY promoter -399 T/C (rs16147) and IL1B -511 C/T (rs16944) polymorphisms with TIID and their correlation with plasma lipid levels, BMI, and IL1B transcript levels. PCR-RFLP was used for genotyping these polymorphisms in a case-control study involving 558 TIID patients and 1085 healthy age-matched controls from Gujarat. Linkage disequilibrium and haplotype analysis of the NPY polymorphic sites were performed to assess their association with TIID. IL1B transcript levels in PBMCs were also assessed in 108 controls and 101 patients using real-time PCR. Our results show significant association of both structural and promoter polymorphisms of NPY (p<0.0001 and p<0.0001 respectively) in patients with TIID. However, the IL1B C/T polymorphism did not show any association (p = 0.3797) with TIID patients. Haplotype analysis revealed more frequent association of CC and CT haplotypes (p = 3.34 x 10-5, p = 6.04 x 10-9) in diabetics compared to controls and increased the risk of diabetes by 3.02 and 2.088 respectively. Transcript levels of IL1B were significantly higher (p<0.0001) in patients as compared to controls. Genotype-phenotype correlation of IL1B polymorphism did not show any association with its higher transcript levels. In addition, NPY +1128 T/C polymorphism was found to be associated with increased plasma LDL levels (p = 0.01). The present study provides an evidence for a strong correlation between structural and promoter polymorphisms of NPY gene and upregulation of IL1B transcript levels with susceptibility to TIID and altering the lipid metabolism in Gujarat population.

  4. Association of Neuropeptide-Y (NPY) and Interleukin-1beta (IL1B), Genotype-Phenotype Correlation and Plasma Lipids with Type-II Diabetes

    PubMed Central

    Mansuri, Mohmmad Shoab; Ansarullah; Laddha, Naresh C.; Thakker, Ami; Ramachandran, A. V.; Begum, Rasheedunnisa

    2016-01-01

    Background Neuropeptide Y (NPY) is known to play a role in the regulation of satiety, energy balance, body weight, and insulin release. Interleukin-1beta (IL1B) has been associated with loss of beta-cell mass in type-II diabetes (TIID). Objectives The present study attempts to investigate the association of NPY exon2 +1128 T/C (Leu7Pro; rs16139), NPY promoter -399 T/C (rs16147) and IL1B -511 C/T (rs16944) polymorphisms with TIID and their correlation with plasma lipid levels, BMI, and IL1B transcript levels. Methods PCR-RFLP was used for genotyping these polymorphisms in a case-control study involving 558 TIID patients and 1085 healthy age-matched controls from Gujarat. Linkage disequilibrium and haplotype analysis of the NPY polymorphic sites were performed to assess their association with TIID. IL1B transcript levels in PBMCs were also assessed in 108 controls and 101 patients using real-time PCR. Results Our results show significant association of both structural and promoter polymorphisms of NPY (p<0.0001 and p<0.0001 respectively) in patients with TIID. However, the IL1B C/T polymorphism did not show any association (p = 0.3797) with TIID patients. Haplotype analysis revealed more frequent association of CC and CT haplotypes (p = 3.34 x 10−5, p = 6.04 x 10−9) in diabetics compared to controls and increased the risk of diabetes by 3.02 and 2.088 respectively. Transcript levels of IL1B were significantly higher (p<0.0001) in patients as compared to controls. Genotype-phenotype correlation of IL1B polymorphism did not show any association with its higher transcript levels. In addition, NPY +1128 T/C polymorphism was found to be associated with increased plasma LDL levels (p = 0.01). Conclusion The present study provides an evidence for a strong correlation between structural and promoter polymorphisms of NPY gene and upregulation of IL1B transcript levels with susceptibility to TIID and altering the lipid metabolism in Gujarat population. PMID:27749914

  5. Altered promoter methylation of PDK4, IL1 B, IL6, and TNF after Roux-en Y gastric bypass.

    PubMed

    Kirchner, Henriette; Nylen, Carolina; Laber, Samantha; Barrès, Romain; Yan, Jie; Krook, Anna; Zierath, Juleen R; Näslund, Erik

    2014-01-01

    Early benefits of Roux-en Y gastric bypass (RYGB) are partly mediated by the caloric restriction that patients undergo before and acutely after the procedure. Altered DNA methylation occurs in metabolic diseases including obesity, as well as in skeletal, muscle eight months after RYGB. The objective of this study was to test whether promoter methylation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1 A), pyruvate dehydrogenase kinase isozyme-4 (PDK4), transcription factor A (TFAM), interleukin-1 beta (IL1 B), interleukin-6 (IL6) and tumor necrosis factor-α (TNF) is altered in blood after a very low calorie diet (VLCD) or RYGB. Obese nondiabetic patients (n = 18, body mass index [BMI] 42.3 ± 4.9 kg/m(2)) underwent a 14-day VLCD followed by RYGB. Nonobese patients (n = 6, BMI 25.7 ± 2.1 kg/m(2)) undergoing elective cholecystectomy served as controls. DNA methylation of selected promoter regions was measured in whole blood before and after VLCD. A subgroup of seven patients was studied 1-2 days and 12 ± 3 months after RYGB. Promoter methylation was measured using methylated DNA capture and quantitative real-time polymerase chain reaction (PCR). VLCD decreased promoter methylation of PPARGC1 A. Methylation of PPARGC1 A, TFAM, IL1 B, IL6, and TNF promoters was changed two days after RYGB. Similar changes were also seen on day one after cholecystectomy. Moreover, methylation increased in PDK4, IL1 B, IL6, and TNF promoters 12 months after RYGB. RYGB induced more profound epigenetic changes than VLCD in promoters of the tested genes in whole blood. Changes in DNA methylation may contribute to the improved overall metabolic health after RYGB. Copyright © 2014 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

  6. IL1B and VWF variants are associated with fibrinolytic early recanalization in patients with ischemic stroke.

    PubMed

    Fernández-Cadenas, Israel; Del Río-Espínola, Alberto; Giralt, Dolors; Domingues-Montanari, Sophie; Quiroga, Adoracion; Mendióroz, Maite; Ruíz, Agustin; Ribó, Marc; Serena, Joaquin; Obach, Victor; Freijo, Mari Mar; Martí-Fábregas, Joan; Delgado, Pilar; Montaner, Joan

    2012-10-01

    There is a great interindividual variability among patients with acute ischemic stroke regarding the response to intravenous tissue-type plasminogen activator treatment. The aim of this study was to identify genetic variants associated with recanalization, and thus treatment efficacy, after tissue-type plasminogen activator administration. A total of 140 single nucleotide polymorphisms from 97 candidate genes were successfully genotyped by SNPlex in 2 cohorts, accounting for 497 prospectively recruited tissue-type plasminogen activator-treated patients, of whom 33% recanalized during tissue-type plasminogen activator infusion. Functional studies were then performed, including assessment of interleukin 1B mRNA levels and von Willebrand factor, FIII, FVII, FVIII, and FX protein activity. After replication, the following single nucleotide polymorphisms were associated with early recanalization: rs1143627 in IL1B gene (CC: 53.1% of recanalization, A-carriers: 32.7%; P=0.022; replication cohort: P=0.046), rs16944 in IL1B gene (AA: 50% of recanalization, G-carriers: 32%; P=0.038; replication cohort: P=0.049), and rs1063856 in the vWF gene (GG: 53.8% of recanalization, A-carriers: 31.5%; P=0.006; replication cohort: P=0.046). The functional studies revealed an association between the rs1063856 single nucleotide polymorphisms in vWF and FVIII activity (AA: 115.93%, AG: 156.07%, GG: 83.42%; P=0.005). Three single nucleotide polymorphisms were associated with tissue-type plasminogen activator efficacy in the Spanish population, and their mechanism of action might be associated with the activity of coagulation factors.

  7. Allele, genotype, and composite genotype effects of IL-1A +4845 and IL-1B +3954 polymorphisms for chronic periodontitis in an Indian population.

    PubMed

    Gayathri, R; Saadi, Abdul Vahab; Bhat, K Mahalinga; Bhat, Subraya G; Satyamoorthy, Kapaettu

    2011-01-01

    The pro-inflammatory cytokine interleukin-1 (IL-1) is a key modulator of host responses to microbial infection and a major modulator of extracellular matrix catabolism and bone resorption, and polymorphisms in the IL-1 gene cluster have been associated with an increased risk of developing severe adult periodontitis. A case control study was performed to determine the role of IL-1A+4845 and IL-1B+3954 polymorphisms in the predisposition to chronic periodontitis. The study was conducted with 103 unrelated participants recruited from Manipal College of Dental Sciences, Manipal, which included 51 chronic periodontitis patients and 52 normal periodontally healthy individuals. Extensive clinical data were collected, bone loss was the major outcome variable and smokers and diabetics were excluded from the study to eliminate the influence of these risk factors. Genomic DNA was isolated from the blood samples of participants for genotyping IL-1A+4845 and IL-1B+3954 polymorphisms by polymerase chain reaction-restriction fragment length polymorphism and the data statistically analyzed. Allele 2 of the IL-1A+4845 polymorphism was carried by 38% of all participants; of these only 6 were homozygous for the allele. Allele 2 of the IL-1B+3954 was carried by 21% of the subjects; only 1 was homozygous for allele 2. The composite genotype was carried by 31% of the cases and by 38% of the controls. Overall, 35% participants carried the composite IL-1 genotype. No statistically significant association was found for the distributions. The distribution of the IL-1 positive composite genotype is in concordance with the frequencies reported in the Caucasians. Association was not found for the effect of allele, genotype, composite genotype, and haplotypes of IL-1A+4845 and IL-1B+3954 polymorphisms with periodontitis. Its utility as a risk marker in this population was not borne out by the study.

  8. Capsaicin consumption, Helicobacter pylori CagA status and IL1B-31C>T genotypes: a host and environment interaction in gastric cancer.

    PubMed

    López-Carrillo, Lizbeth; Camargo, M Constanza; Schneider, Barbara G; Sicinschi, Liviu A; Hernández-Ramírez, Raúl U; Correa, Pelayo; Cebrian, Mariano E

    2012-06-01

    Gastric cancer (GC) has been associated with a complex combination of genetic and environmental factors. In contrast to most countries, available information on GC mortality trends showed a gradual increase in Mexico. Our aim was to explore potential interactions among dietary (chili pepper consumption), infectious (Helicobacter pylori) and genetic factors (IL1B-31 genotypes) on GC risk. The study was performed in three areas of Mexico, with different GC mortality rates. We included 158 GC patients and 317 clinical controls. Consumption of capsaicin (Cap), the pungent active substance of chili peppers, was estimated by food frequency questionnaire. H. pylori CagA status was assessed by ELISA, and IL1B-31 genotypes were determined by TaqMan assays and Pyrosequencing in DNA samples. Multivariate unconditional logistic regression was used to estimate potential interactions. Moderate to high Cap consumption synergistically increased GC risk in genetically susceptible individuals (IL1B-31C allele carriers) infected with the more virulent H. pylori (CagA+) strains. The combined presence of these factors might explain the absence of a decreasing trend for GC in Mexico. However, further research on gene-environment interactions is required to fully understand the factors determining GC patterns in susceptible populations, with the aim of recommending preventive measures for high risk individuals.

  9. Association of IL1B -511C/-31T haplotype and Helicobacter pylori vacA genotypes with gastric ulcer and chronic gastritis

    PubMed Central

    2010-01-01

    Background The association between proinflammatory cytokine gene polymorphisms and gastric diseases related to Helicobacter pylori varies by population and geographic area. Our objective was to determine if the IL-1B -511 T>C and -31 C>T polymorphisms and H. pylori vacA genotypes are associated with risk of chronic gastritis and gastric ulcer in a Mexican population. Methods We conducted endoscopic studies in 128 patients with symptoms of dyspepsia. We took two biopsies from the body, antrum, or ulcer edge from each patient, and classified our histopathological findings according to the Sydney System. H. pylori infection and vacA genotyping were accomplished via PCR from total DNA of the gastric biopsies. We confirmed the presence of anti-H. pylori serum IgG and IgM in 102 control subjects. In both case subjects and control subjects, the IL-1B -511 T>C polymorphism was genotyped by PCR-RFLPs and the IL-1B -31 C>T polymorphism was genotyped by pyrosequencing. Results Sixty-two point seven (62.7%) of the 102 control subjects were H. pylori-seropositive. Among the case subjects, 100 were diagnosed with chronic gastritis and 28 with gastric ulcer. We found that 77% of the patients with chronic gastritis and 85.7% of the patients with gastric ulcer were H. pylori-positive. The predominant H. pylori genotype was vacA s1m1 (58.4%) and the most frequent subtype was vacA s1. The -511 TC, (rs16944 -511 T>C) genotype and the -511C allele were associated with chronic gastritis (OR = 3.1, 95% CI = 1.4-6.8 and OR = 3.0, 95% CI = 1.4-6.0, respectively). The subjects carrying -31T (rs1143627 -31 C>T) were found to be at a higher risk of having chronic gastritis (OR = 2.8, 95% CI = 1.3-5.8). The IL-1B -511C/-31T haplotype was associated with chronic gastritis (OR = 2.1, 95% CI = 1.2-3.8) but not with gastric ulcer. Conclusions The H. pylori vacA genotypes identified herein were similar to those reported for other regions of Mexico. The vacA s1m1 genotype was not associated with

  10. Autophagy-dependent PELI3 degradation inhibits proinflammatory IL1B expression.

    PubMed

    Giegerich, Annika Klara; Kuchler, Laura; Sha, Lisa Katharina; Knape, Tilo; Heide, Heinrich; Wittig, Ilka; Behrends, Christian; Brüne, Bernhard; von Knethen, Andreas

    2014-01-01

    Lipopolysaccharide (LPS)-induced activation of TLR4 (toll-like receptor 4) is followed by a subsequent overwhelming inflammatory response, a hallmark of the first phase of sepsis. Therefore, counteracting excessive innate immunity by autophagy is important to contribute to the termination of inflammation. However, the exact molecular details of this interplay are only poorly understood. Here, we show that PELI3/Pellino3 (pellino E3 ubiquitin protein ligase family member 3), which is an E3 ubiquitin ligase and scaffold protein in TLR4-signaling, is impacted by autophagy in macrophages (MΦ) after LPS stimulation. We noticed an attenuated mRNA expression of proinflammatory Il1b (interleukin 1, β) in Peli3 knockdown murine MΦ in response to LPS treatment. The autophagy adaptor protein SQSTM1/p62 (sequestosome 1) emerged as a potential PELI3 binding partner in TLR4-signaling. siRNA targeting Sqstm1 and Atg7 (autophagy related 7), pharmacological inhibition of autophagy by wortmannin as well as blocking the lysosomal vacuolar-type H(+)-ATPase by bafilomycin A1 augmented PELI3 protein levels, while inhibition of the proteasome had no effect. Consistently, treatment to induce autophagy by MTOR (mechanistic target of rapamycin (serine/threonine kinase)) inhibition or starvation enhanced PELI3 degradation and reduced proinflammatory Il1b expression. PELI3 was found to be ubiquitinated upon LPS stimulation and point mutation of PELI3-lysine residue 316 (Lys316Arg) attenuated Torin2-dependent degradation of PELI3. Immunofluorescence analysis revealed that PELI3 colocalized with the typical autophagy markers MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 β) and LAMP2 (lysosomal-associated membrane protein 2). Our observations suggest that autophagy causes PELI3 degradation during TLR4-signaling, thereby impairing the hyperinflammatory phase during sepsis.

  11. TNF, IL6, and IL1B Polymorphisms Are Associated with Severe Influenza A (H1N1) Virus Infection in the Mexican Population

    PubMed Central

    García-Ramírez, Román Alejandro; Ramírez-Venegas, Alejandra; Quintana-Carrillo, Roger; Camarena, Ángel Eduardo; Falfán-Valencia, Ramcés; Mejía-Aranguré, Juan Manuel

    2015-01-01

    Background Hypercytokinemia is the main immunopathological mechanism contributing to a more severe clinical course in influenza A (H1N1) virus infections. Most patients infected with the influenza A (H1N1) pdm09 virus had increased systemic levels of pro-inflammatory cytokines; including interleukin IL-6, IL-8, and tumor necrosis factor-alpha (TNF-α). We propose that single-nucleotide polymorphisms (SNPs) in the promoter regions of pro-inflammatory genes are associated with the severity of influenza A (H1N1) pdm09 virus infection. Methods 145 patients with influenza A (H1N1) (pA/H1N1), 133 patients with influenza-like illness (ILI), and 360 asymptomatic healthy contacts (AHCs) were included. Eleven SNPs were genotyped in six genes (TNF, LT, IL1B, IL6, CCL1, and IL8) using real-time PCR; the ancestral genotype was used for comparison. Genotypes were correlated with 27 clinical severity variables. Ten cytokines (GM-CSF, TNF-α, IL-2, IL-1β, IL-6, IL-8, IFN-γ, IL-10, IL-5, and IL-4) were measured on a Luminex 100. Results The IL6 rs1818879 (GA) heterozygous genotype was associated with severe influenza A (H1N1) virus infection (odds ratio [OR] = 5.94, 95% confidence interval [CI] 3.05–11.56), and two IL1B SNPs, rs16944 AG and rs3136558 TC, were associated with a decreased risk of infection (OR = 0.52 and OR = 0.51, respectively). Genetic susceptibility was determined (pA/H1N1 vs. AHC): the LTA rs909253 TC heterozygous genotype conferred greater risk (OR = 1.9), and a similar association was observed with the IL1B rs3136558 CC genotype (OR = 1.89). Additionally, severely ill patients were compared with moderately ill patients. The TNF-238 GA genotype was associated with an increased risk of disease severity (OR = 16.06, p = 0.007). Compared with ILIs, patients with severe pA/H1N1 infections exhibited increased serum IL-5 (p <0.001) and IL-6 (p  =  0.007) levels. Conclusions The TNF gene was associated with disease severity, whereas IL1B and IL6 SNPs were

  12. Circulating Levels of IL-1B+IL-6 Cause ER Stress and Dysfunction in Islets From Prediabetic Male Mice

    PubMed Central

    O'Neill, Christina M.; Lu, Christine; Corbin, Kathryn L.; Sharma, Poonam R.; Dula, Stacey B.; Carter, Jeffrey D.; Ramadan, James W.; Xin, Wenjun; Lee, Jae K.

    2013-01-01

    Elevated levels of circulating proinflammatory cytokines are associated with obesity and increased risk of type 2 diabetes, but the mechanism is unknown. We tested whether proinflammatory cytokines IL-1B+IL-6 at low picogram per milliliter concentrations (consistent with serum levels) could directly trigger pancreatic islet dysfunction. Overnight exposure to IL-1B+IL-6 in islets isolated from normal mice and humans disrupted glucose-stimulated intracellular calcium responses; cytokine-induced effects were more severe among islets from prediabetic db/db mice that otherwise showed no signs of dysfunction. IL-1B+IL-6 exposure reduced endoplasmic reticulum (ER) calcium storage, activated ER stress responses (Nos2, Bip, Atf4, and Ddit3 [CHOP]), impaired glucose-stimulated insulin secretion, and increased cell death only in islets from prediabetic db/db mice. Furthermore, we found increased serum levels of IL-1B and IL-6 in diabetes-prone mice at an age before hyperglycemia was exhibited, suggesting that low-grade systemic inflammation develops early in the disease process. In addition, we implanted normal outbred and inbred mice with subcutaneous osmotic mini-pumps containing IL-1B+IL-6 to mimic the serum increases found in prediabetic db/db mice. Both IL-1B and IL-6 were elevated in serum from cytokine-pump mice, but glucose tolerance and blood glucose levels did not differ from controls. However, when compared with controls, isolated islets from cytokine-pump mice showed deficiencies in calcium handling and insulin secretion that were similar to observations with islets exposed to cytokines in vitro. These findings provide proof of principle that low-grade systemic inflammation is present early in the development of type 2 diabetes and can trigger ER stress-mediated islet dysfunction that can lead to islet failure. PMID:23836031

  13. Effect of Porphyromonas gingivalis and Lactobacillus acidophilus on secretion of IL1B, IL6, and IL8 by gingival epithelial cells.

    PubMed

    Zhao, Jun-jun; Feng, Xi-ping; Zhang, Xiu-li; Le, Ke-yi

    2012-08-01

    Porphyromonas gingivalis alters cytokine expression in gingival epithelial cells, stimulating inflammatory responses that may lead to periodontal disease. This study explored the effect of Lactobacillus acidophilus on the specific expressions of the interleukins (ILs) IL1B, IL6, and IL8 induced by the pathogen. Human gingival epithelial cells were co-cultured with P. gingivalis, L. acidophilus, or L. acidophilus + P. gingivalis; the control group consisted of the cells alone. Protein and gene expression levels of the ILs were detected using ELISA and qRT-PCR, respectively. The supernatant from the P. gingivalis group held significantly higher protein and mRNA levels of IL1B, IL6, and IL8, compared to the control group. In the mixed bacterial group (L. acidophilus + P. gingivalis), the levels of all three ILs decreased with increasing concentrations of L. acidophilus and were significantly different from the P. gingivalis group. This suggests that in gingival cells, L. acidophilus offsets the P. gingivalis-induced secretion of these ILs in a dose-dependent manner.

  14. Pharmacogenetic analysis of the effects of polymorphisms in APOE, IDE and IL1B on a ketone body based therapeutic on cognition in mild to moderate Alzheimer's disease; a randomized, double-blind, placebo-controlled study

    PubMed Central

    2011-01-01

    Background To examine the effect of genetic variation in APOE, IDE and IL1B on the response to induced ketosis in the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) in subjects with mild to moderate Alzheimer's disease (AD). Methods Genotype effects on ADAS-Cog scores from a randomized, double-blind, placebo-controlled study in mild to moderate AD were examined by an overall two way analysis of variance. In addition, interactions with the carriage status of the epsilon 4 allele of the APOE gene (APOE4) were examined. Results Significant differences in response to induced ketosis were found among non-carriers of putative gain-of-function polymorphisms in rs1143627 and rs16944 in the IL1B gene and among variants of the polymorphism rs2251101 in the IDE gene. Significant differences were found among non-carriers of the APOE4 gene, with notable improvement among the E3/E3 genotype group. Conclusions Variants in APOE, IL1B and IDE may influence the cognitive response to induced ketosis in patients with mild to moderate AD. Trial registration This trial was registered with ClinicalTrials.gov, registry number NCT00142805. PMID:21992747

  15. Assessment of single nucleotide polymorphism at IL-1A+4845 and IL-1B+3954 as genetic susceptibility test for chronic periodontitis in Maharashtrian ethnicity.

    PubMed

    Agrawal, Amit A; Kapley, Atya; Yeltiwar, Ramreddy K; Purohit, Hemant J

    2006-09-01

    The inflammatory response that is directed in large part by proinflammatory cytokine interleukin (IL)-1 is genetically determined, with some people having a more vigorous response than others to the same stimulus. The reason for this is speculated that the dysregulated production of IL-1 in some individuals overrides the feedback mechanisms that normally master the dose of inflammation to a level sufficient to fight microbial invasion without long-lasting damage to the tissues involved. The aims of the present study were to determine the distribution of IL-1 gene polymorphism (IL-1A+4845 and IL-1B+3954) and their association with periodontal disease severity and to determine the significance of detecting the composite genotype (IL-1A allele2+IL-1B allele2) versus detecting either of them alone. A total of 120 subjects were included and divided into four groups of 30 subjects each, namely, healthy, mild, moderate, and severe periodontitis groups. After a complete clinical examination, DNA was isolated from 0.5 ml blood. Specific primers were used to detect the presence of IL-1 gene polymorphism with the help of polymerase chain reaction (PCR) and subsequent allele detection with restriction fragment length polymorphism (RFLP) and separation by gel electrophoresis. The distribution of the allele1 homozygous genotype was 3% in the severe periodontitis group, and the distribution for the allele2 genotype was 30%. A higly significant difference (Wilcoxon signed-rank test; P<0.001) was seen between subjects positive and negative for the composite genotype. Results of the present study reinforced the association of the IL-1 genotype as a risk factor for severe chronic periodontitis. Positivity for the composite genotype was found to be significantly associated with severe chronic periodontitis (odds ratio [OR]=12.42).

  16. Analysis of the association of IL1B(C-511T) polymorphism with dental implant loss and the clusterization phenomenon.

    PubMed

    Dirschnabel, Acir José; Alvim-Pereira, Fabiano; Alvim-Pereira, Cláudia Cristina; Bernardino, José Fábio; Rosa, Edvaldo Antonio Ribeiro; Trevilatto, Paula Cristina

    2011-11-01

    Endosteous dental implants consist in the treatment of choice to replace tooth loss. The knowledge that implant loss tends to cluster in subsets of individuals may indicate that host immune-inflammatory response is influenced by genetic factors. Interleukin-1 (IL-1) is a key mediator of inflammatory processes and functional polymorphisms in IL1 gene could be candidate genetic risk factors to study susceptibility to implant failure. The objective of this study was to investigate the association between IL1B (C-511T) genetic polymorphism and dental implant loss in a Brazilian population and its influence in the clusterization phenomenon. The sample composed of 277 unrelated, both gender, mean age 53.63 ± 11.14 years individuals, divided into test group - 92 subjects with implant loss, and control group - 185 subjects with no implant loss. Patients' socioeconomic profile and clinical variables were investigated. Genomic DNA from oral mucosa was analyzed by polymerase chain reaction-restriction fragment length polymorphism. There was significant difference between the groups in medical treatment (P=0.040), edentulism (P=0.019), and mean number of placed implants (P=0.001). There was difference between groups with and without implant loss neither considering genotypes (P=0.279) nor alleles (P=0.168) for IL1B (C-511T) polymorphism. When individuals showing up to one implant failure (n=254) were investigated vs. patients presenting multiple implant loss (n=23), no difference was either observed between groups for genotype (P=0.083) and allele (P=0.838) frequencies. The borderline association of the study polymorphism with implant loss suggests further IL1 haplotype analysis to elucidate the global involvement of IL-1 proteins in the modulation of the osseointegration process. © 2011 John Wiley & Sons A/S.

  17. PTPN22 regulates NLRP3-mediated IL1B secretion in an autophagy-dependent manner

    PubMed Central

    Spalinger, Marianne R.; Lang, Silvia; Gottier, Claudia; Dai, Xuezhi; Rawlings, David J.; Chan, Andrew C.; Rogler, Gerhard; Scharl, Michael

    2017-01-01

    ABSTRACT A variant within the gene locus encoding PTPN22 (protein tyrosine phosphatase, non-receptor type 22) emerged as an important risk factor for auto-inflammatory disorders, including rheumatoid arthritis, systemic lupus erythematosus and type 1 diabetes, but at the same time protects from Crohn disease, one of the 2 main forms of inflammatory bowel diseases. We have previously shown that loss of PTPN22 results in decreased NLRP3 (NLR family pyrin domain containing 3) activation and that this effect is mediated via enhanced NLRP3 phosphorylation. However, it is unclear how phosphorylation of NLRP3 mediates its inhibition. Here, we demonstrate that loss of macroautophagy/autophagy abrogates the inhibitory effect on NLRP3 activation observed upon loss of PTPN22. Phosphorylated, but not nonphosphorylated NLRP3 is found in autophagosomes, indicating that NLRP3 phosphorylation mediates its inactivation via promoting sequestration into phagophores, the precursors to autophagosomes. This finding shows that autophagy and NLRP3 inflammasome activation are connected, and that PTPN22 plays a key role in the regulation of those 2 pathways. Given its role in inflammatory disorders, PTPN22 might be an attractive therapeutic target, and understanding the cellular mechanisms modulated by PTPN22 is of crucial importance. PMID:28786745

  18. Indomethacin treatment prior to pentylenetetrazole-induced seizures downregulates the expression of il1b and cox2 and decreases seizure-like behavior in zebrafish larvae.

    PubMed

    Barbalho, Patrícia Gonçalves; Lopes-Cendes, Iscia; Maurer-Morelli, Claudia Vianna

    2016-03-09

    It has been demonstrated that the zebrafish model of pentylenetetrazole (PTZ)-evoked seizures and the well-established rodent models of epilepsy are similar pertaining to behavior, electrographic features, and c-fos expression. Although this zebrafish model is suitable for studying seizures, to date, inflammatory response after seizures has not been investigated using this model. Because a relationship between epilepsy and inflammation has been established, in the present study we investigated the transcript levels of the proinflammatory cytokines interleukin-1 beta (il1b) and cyclooxygenase-2 (cox2a and cox2b) after PTZ-induced seizures in the brain of zebrafish 7 days post fertilization. Furthermore, we exposed the fish to the nonsteroidal anti-inflammatory drug indomethacin prior to PTZ, and we measured its effect on seizure latency, number of seizure behaviors, and mRNA expression of il1b, cox2b, and c-fos. We used quantitative real-time PCR to assess the mRNA expression of il1b, cox2a, cox2b, and c-fos, and visual inspection was used to monitor seizure latency and the number of seizure-like behaviors. We found a short-term upregulation of il1b, and we revealed that cox2b, but not cox2a, was induced after seizures. Indomethacin treatment prior to PTZ-induced seizures downregulated the mRNA expression of il1b, cox2b, and c-fos. Moreover, we observed that in larvae exposed to indomethacin, seizure latency increased and the number of seizure-like behaviors decreased. This is the first study showing that il1b and cox-2 transcripts are upregulated following PTZ-induced seizures in zebrafish. In addition, we demonstrated the anticonvulsant effect of indomethacin based on (1) the inhibition of PTZ-induced c-fos transcription, (2) increase in seizure latency, and (3) decrease in the number of seizure-like behaviors. Furthermore, anti-inflammatory effect of indomethacin is clearly demonstrated by the downregulation of the mRNA expression of il1b and cox2b. Our results

  19. Zinc ferrite nanoparticles activate IL-1b, NFKB1, CCL21 and NOS2 signaling to induce mitochondrial dependent intrinsic apoptotic pathway in WISH cells.

    PubMed

    Saquib, Quaiser; Al-Khedhairy, Abdulaziz A; Ahmad, Javed; Siddiqui, Maqsood A; Dwivedi, Sourabh; Khan, Shams T; Musarrat, Javed

    2013-12-01

    The present study has demonstrated the translocation of zinc ferrite nanoparticles (ZnFe2O4-NPs) into the cytoplasm of human amnion epithelial (WISH) cells, and the ensuing cytotoxicity and genetic damage. The results suggested that in situ NPs induced oxidative stress, alterations in cellular membrane and DNA strand breaks. The [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) and neutral red uptake (NRU) cytotoxicity assays indicated 64.48 ± 1.6% and 50.73 ± 2.1% reduction in cell viability with 100 μg/ml of ZnFe2O4-NPs exposure. The treated WISH cells exhibited 1.2-fold higher ROS level with 0.9-fold decline in membrane potential (ΔΨm) and 7.4-fold higher DNA damage after 48h of ZnFe2O4-NPs treatment. Real-time PCR (qPCR) analysis of p53, CASP 3 (caspase-3), and bax genes revealed 5.3, 1.6, and 14.9-fold upregulation, and 0.18-fold down regulation of bcl 2 gene vis-à-vis untreated control. RT(2) Profiler™ PCR array data elucidated differential up-regulation of mRNA transcripts of IL-1b, NFKB1, NOS2 and CCL21 genes in the range of 1.5 to 3.7-folds. The flow cytometry based cell cycle analysis suggested the transfer of 15.2 ± 2.1% (p<0.01) population of ZnFe2O4-NPs (100 μg/ml) treated cells into apoptotic phase through intrinsic pathway. Over all, the data revealed the potential of ZnFe2O4-NPs to induce cellular and genetic toxicity in cells of placental origin. Thus, the significant ROS production, reduction in ΔΨm, DNA damage, and activation of genes linked to inflammation, oxidative stress, proliferation, DNA damage and repair could serve as the predictive toxicity and stress markers for ecotoxicological assessment of ZnFe2O4-NPs induced cellular and genetic damage.

  20. Pandemic influenza A/H1N1 virus infection and TNF, LTA, IL1B, IL6, IL8, and CCL polymorphisms in Mexican population: a case–control study

    PubMed Central

    2012-01-01

    Background Some patients have a greater response to viral infection than do others having a similar level of viral replication. Hypercytokinemia is the principal immunopathological mechanism that contributes to a severer clinical course in cases of influenza A/H1N1. The benefit produced, or damage caused, by these cytokines in severe disease is not known. The genes that code for these molecules are polymorphic and certain alleles have been associated with susceptibility to various diseases. The objective of the present study was to determine whether there was an association between polymorphisms of TNF, LTA, IL1B, IL6, IL8, and CCL1 and the infection and severity of the illness caused by the pandemic A/H1N1 in Mexico in 2009. Methods Case–control study. The cases were patients confirmed with real time PCR with infection by the A/H1N1 pandemic virus. The controls were patients with infection like to influenza and non-familial healthy contacts of the patients with influenza. Medical history and outcome of the disease was registered. The DNA samples were genotyped for polymorphisms TNF rs361525, rs1800629, and rs1800750; LTA rs909253; IL1B rs16944; IL6 rs1818879; IL8 rs4073; and CCL1 rs2282691. Odds ratio (OR) and the 95% confidence interval (95% CI) were calculated. The logistic regression model was adjusted by age and severity of the illness in cases. Results Infection with the pandemic A/H1N1 virus was associated with the following genotypes: TNF rs361525 AA, OR = 27.00; 95% CI = 3.07–1248.77); LTA rs909253 AG (OR = 4.33, 95% CI = 1.82–10.32); TNF rs1800750 AA (OR = 4.33, 95% CI = 1.48–12.64); additionally, LTA rs909253 AG showed a limited statistically significant association with mortality (p = 0.06, OR = 3.13). Carriers of the TNF rs1800629 GA genotype were associated with high levels of blood urea nitrogen (p = 0.05); those of the TNF rs1800750 AA genotype, with high levels of creatine phosphokinase (p=0.05). The IL1B rs16944 AA genotype was associated

  1. Zinc ferrite nanoparticles activate IL-1b, NFKB1, CCL21 and NOS2 signaling to induce mitochondrial dependent intrinsic apoptotic pathway in WISH cells

    SciTech Connect

    Saquib, Quaiser; Al-Khedhairy, Abdulaziz A.; Ahmad, Javed; Siddiqui, Maqsood A.; Dwivedi, Sourabh; Khan, Shams T.; Musarrat, Javed

    2013-12-01

    The present study has demonstrated the translocation of zinc ferrite nanoparticles (ZnFe{sub 2}O{sub 4}-NPs) into the cytoplasm of human amnion epithelial (WISH) cells, and the ensuing cytotoxicity and genetic damage. The results suggested that in situ NPs induced oxidative stress, alterations in cellular membrane and DNA strand breaks. The [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) and neutral red uptake (NRU) cytotoxicity assays indicated 64.48 ± 1.6% and 50.73 ± 2.1% reduction in cell viability with 100 μg/ml of ZnFe{sub 2}O{sub 4}-NPs exposure. The treated WISH cells exhibited 1.2-fold higher ROS level with 0.9-fold decline in membrane potential (ΔΨm) and 7.4-fold higher DNA damage after 48 h of ZnFe{sub 2}O{sub 4}-NPs treatment. Real-time PCR (qPCR) analysis of p53, CASP 3 (caspase-3), and bax genes revealed 5.3, 1.6, and 14.9-fold upregulation, and 0.18-fold down regulation of bcl 2 gene vis-à-vis untreated control. RT{sup 2} Profiler™ PCR array data elucidated differential up-regulation of mRNA transcripts of IL-1b, NFKB1, NOS2 and CCL21 genes in the range of 1.5 to 3.7-folds. The flow cytometry based cell cycle analysis suggested the transfer of 15.2 ± 2.1% (p < 0.01) population of ZnFe{sub 2}O{sub 4}-NPs (100 μg/ml) treated cells into apoptotic phase through intrinsic pathway. Over all, the data revealed the potential of ZnFe{sub 2}O{sub 4}-NPs to induce cellular and genetic toxicity in cells of placental origin. Thus, the significant ROS production, reduction in ΔΨm, DNA damage, and activation of genes linked to inflammation, oxidative stress, proliferation, DNA damage and repair could serve as the predictive toxicity and stress markers for ecotoxicological assessment of ZnFe{sub 2}O{sub 4}-NPs induced cellular and genetic damage. - Highlights: • First report on the molecular toxicity of ZnFe{sub 2}O{sub 4}-NPs in cells of placental origin • WISH cells treated with ZnFe{sub 2}O{sub 4}-NPs exhibited cytoplasmic

  2. Macrophage-derived LIF and IL1B regulate alpha(1,2)fucosyltransferase 2 (Fut2) expression in mouse uterine epithelial cells during early pregnancy.

    PubMed

    Jasper, Melinda J; Care, Alison S; Sullivan, Brad; Ingman, Wendy V; Aplin, John D; Robertson, Sarah A

    2011-01-01

    Macrophages accumulate within stromal tissue subjacent to the luminal epithelium in the mouse uterus during early pregnancy after seminal fluid exposure at coitus. To investigate their role in regulating epithelial cell expression of fucosylated structures required for embryo attachment and implantation, fucosyltransferase enzymes Fut1, Fut2 (Enzyme Commission number [EC] 2.4.1.69), and Fut4 (EC 2.4.1.214) and Muc1 and Muc4 mRNAs were quantified by quantitative real-time PCR in uterine epithelial cells after laser capture microdissection in situ or after epithelial cell coculture with macrophages or macrophage-secreted factors. When uterine macrophage recruitment was impaired by mating with seminal plasma-deficient males, epithelial cell Fut2 expression on Day 3.5 postcoitus (pc) was reduced compared to intact-mated controls. Epithelial cell Fut2 was upregulated in vitro by coculture with macrophages or macrophage-conditioned medium (MCM). Macrophage-derived cytokines LIF, IL1B, and IL12 replicated the effect of MCM on Fut2 mRNA expression, and MCM-stimulated expression was inhibited by anti-LIF and anti-IL1B neutralizing antibodies. The effects of acute macrophage depletion on fucosylated structures detected with lectins Ulex europaeus 1 (UEA-1) and Lotus tetragonolobus purpureas (LTP), or LewisX immunoreactivity, were quantified in vivo in Cd11b-dtr transgenic mice. Depletion of macrophages caused a 30% reduction in luminal epithelial UEA-1 staining and a 67% reduction in LewisX staining in uterine tissues of mice hormonally treated to mimic early pregnancy. Together, these data demonstrate that uterine epithelial Fut2 mRNA expression and terminal fucosylation of embryo attachment ligands is regulated in preparation for implantation by factors including LIF and IL1B secreted from macrophages recruited during the inflammatory response to insemination.

  3. A combination of alleles 2 of interleukin (IL)-1A(-889) and IL-1B(+3954) is associated with lower gingival bleeding tendency in plaque-induced gingivitis in young adults of Arabic heritage.

    PubMed

    Müller, H P; Barrieshi-Nusair, K M

    2007-09-01

    The aim of this study was to investigate the possible association of a distinct combination of polymorphisms in the interleukin (IL)-1 gene cluster on gingival bleeding tendency in young adult Arabs with plaque-induced gingivitis. Fifty otherwise healthy, nonsmoking volunteers, 19-28 years of age, participated. Clinical examinations included periodontal probing depth, bleeding on probing, and plaque index. Probing was done with a pressure-controlled probe at about 1.27 MPa. Examinations were repeated after 2 and 4 weeks. Polymorphisms in the IL-1 gene cluster were assessed using a reverse hybridization assay. A subject carrying alleles 2 at IL-1A ( -889 ) and IL-1B ( +3954 ) was designated genotype-positive. Twenty-six subjects were genotype-positive (52%). A repeated measures two-level (occasion, subject) model of the proportion of sites bleeding on probing, which was adjusted for gender, average plaque index, probing depth, and calculus, revealed a significantly lower proportion of bleeding sites in genotype-positive subjects (estimate -0.050, standard error 0.025, p < 0.05). Biserial correlations of bleeding proportions were high (0.71-0.78), confirming the steady-state plaque environment. It was concluded that inflammatory responses to dental plaque were considerably dampened in genotype-positive, nonsmoking young adults of Arabic heritage.

  4. Structures of Mycobacterium tuberculosis DosR and DosR-DNA Complex Involved in Gene Activation during Adaptation to Hypoxic Latency

    SciTech Connect

    Wisedchaisri, Goragot; Wu, Meiting; Rice, Adrian E; Roberts, David M; Sherman, David R; Hol, Wim G.J.

    2010-07-20

    On encountering low oxygen conditions, DosR activates the transcription of 47 genes, promoting long-term survival of Mycobacterium tuberculosis in a non-replicating state. Here, we report the crystal structures of the DosR C-terminal domain and its complex with a consensus DNA sequence of the hypoxia-induced gene promoter. The DosR C-terminal domain contains four {alpha}-helices and forms tetramers consisting of two dimers with non-intersecting dyads. In the DNA-bound structure, each DosR C-terminal domain in a dimer places its DNA-binding helix deep into the major groove, causing two bends in the DNA. DosR makes numerous protein-DNA base contacts using only three amino acid residues per subunit: Lys179, Lys182, and Asn183. The DosR tetramer is unique among response regulators with known structures.

  5. DosR-regulon genes induction in Mycobacterium bovis BCG under aerobic conditions.

    PubMed

    Flores Valdez, Mario Alberto; Schoolnik, Gary K

    2010-05-01

    In this report we demonstrated that under aerobic conditions, Mycobacterium bovis BCG expressing an hsp60-driven second copy of the hypoxia-related transcriptional regulator DosR increased 2-fold or greater the expression of 38 out of the 48 genes belonging to the DosR regulon, including the latency antigens Rv1733c, Rv2029, Rv2627, and Rv2628. Expression of DosR under these conditions slightly delayed in vitro growth, but did not promote a non-replicating state as opposed to microaerobic and hypoxic adaptation. Our results suggest BCG producing DosR can be cultured under standard in vitro conditions, allowing evaluation of this strain as a latency-specific vaccine candidate.

  6. Associations between Interleukin-1 Gene Polymorphisms and Coronary Heart Disease Risk: A Meta-Analysis

    PubMed Central

    Zhou, Liang; Cai, Jianguang; Liu, Gang; Wei, Yuan; Tang, Hui

    2012-01-01

    Objective A great number of studies regarding the associations between IL-1B-511, IL-1B+3954 and IL-1RN VNTR polymorphisms within the IL-1gene cluster and coronary heart disease (CHD) have been published. However, results have been inconsistent. In this study, a meta-analysis was performed to investigate the associations. Methods Published literature from PubMed and Embase databases were searched for eligible publications. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random- or fixed- effect model. Results Thirteen studies (3,219 cases/2,445 controls) for IL-1B-511 polymorphism, nine studies (1,828 cases/1,818 controls) for IL-1B+3954 polymorphism and twelve studies (2,987 cases/ 2,208 controls) for IL-1RN VNTR polymorphism were included in this meta analysis. The results indicated that both IL-1B-511 and IL-1B+3954 polymorphisms were not associated with CHD risk (IL-1B-511 T vs. C: OR = 0.98, 95%CI 0.87–1.09; IL-1B+3954 T vs. C: OR = 1.06, 95%CI 0.95–1.19). Similarly, there was no association between IL-1RN VNTR polymorphism and CHD risk (*2 vs. L: OR = 1.00, 95%CI 0.85–1.17). Conclusions This meta-analysis suggested that there were no associations between IL-1 gene cluster polymorphisms and CHD. PMID:23029154

  7. [The character of the morphological changes of the mucous membrane of the large intestine and the genetic polymorphism of IL-1RA, IL-1B, IL-4 TNFA in patient with irritable bowel syndrome].

    PubMed

    Sarsenbaeva, A S; Ivanova, E L; Burmistrova, A L; Drozdov, I V

    2013-01-01

    The aim of this study was to evaluate the presence or absence of a relationship between the variants of the course of IBS and their association with genetic polymorphisms of genes and intergenic interaction of cytokines. The sample consisted of 81 patients, the diagnosis was verified according to the criteria of the Rome III, were isolated psychopathological, morphological complications, extra-intestinal symptoms. Polymorphism genotyping IL-1Ra, IL-b, IL-4, TNFa performed by PCR. Statistical treatment are a non-parametric analysis of multiple comparisons, hierarchical log-linear analysis. It is found out the relation between the clinical variants with morphological changes of the mucous membrane of the large intestine, the association between gender characteristics of patients with IBS is established and with genetic polymorphisms of cytokines.

  8. Psychotropic drug effects on gene transcriptomics relevant to Alzheimer disease.

    PubMed

    Lauterbach, Edward C

    2012-01-01

    Psychotropics are widely prescribed in Alzheimer disease (AD) without regard to their pathobiological effects. Results summarize a comprehensive survey of psychotropic effects on messenger ribonucleic acid (mRNA) expression for 52 genes linked to AD. Pending future investigations, current data indicate that atypical antipsychotics, lithium, and fluoxetine reduce AD risk, whereas other drug classes promote risk. Risk may be attenuated by antipsychotics and lithium (down-regulate TNF), atypical antipsychotics (down-regulate TF), risperidone (down-regulates IL1B), olanzapine (up-regulates TFAM, down-regulates PRNP), fluoxetine (up-regulates CLU, SORCS1, NEDD9, GRN, and ECE1), and lithium coadministered with antipsychotics (down-regulates IL1B). Risk may be enhanced by neuroleptics (up-regulate TF), haloperidol (up-regulates IL1B and PION), olanzapine (down-regulates THRA and PRNP, up-regulates IL1A), and chlorpromazine, imipramine, maprotiline, fluvoxamine, and diazepam (up-regulate IL1B). There were no results for dextromethorphan-plus-quinidine. Fluoxetine effects on CLU, NEDD9, and GRN were statistically robust. Drug effects on specific variants, polymorphisms, genotypes, and other genes (CCR2, TF, and PRNP) are detailed. Translational AD risk applications and their limitations related to specific genes, mutations, variants, polymorphisms, genotypes, brain site, sex, clinical population, AD stage, and other factors are discussed. This report provides an initial summary and framework to understand the potential impact of psychotropic drugs on AD-relevant genes.

  9. Interleukin-1 gene polymorphisms and gastric cancer risk in a high-risk Italian population.

    PubMed

    Palli, D; Saieva, C; Luzzi, I; Masala, G; Topa, S; Sera, F; Gemma, S; Zanna, I; D'Errico, M; Zini, E; Guidotti, S; Valeri, A; Fabbrucci, P; Moretti, R; Testai, E; del Giudice, G; Ottini, L; Matullo, G; Dogliotti, E; Gomez-Miguel, M J

    2005-09-01

    Host genetic factors, including the IL1 gene cluster, play a key role in determining the long-term outcome of Helicobacter pylori infection. The aim of the study was to investigate the relationship between selected IL1 loci polymorphisms and gastric cancer risk in an Italian population. In a case-control study we compared the IL1B-31 and IL1B+3954 biallelic and IL1RN pentaallelic variable number of tandem repeats (VNTR) polymorphisms in 185 gastric cancer patients and 546 controls randomly sampled from the general population of an area at high gastric cancer risk (Tuscany, Central Italy). Genotype frequencies of the IL1B-31 T/C, IL1B+3954 C/T, and IL1RN polymorphisms among our population controls were in Hardy-Weinberg equilibrium. In multivariate analyses, no increase in gastric cancer risk was observed for the IL1B-31*C- and IL1B+3954*T- carriers; a significant 50% increase emerged for IL1RN*2 allele carriers (OR = 1.49; 95% CI: 1.01-2.21). Analyses based on combined genotypes showed also that the association with IL1RN*2 allele was limited to two-variant allele carriers who were also homozygous for the IL1B-31*T allele (OR = 2.23; 95% CI: 1.18-4.23) with a statistically significant interaction between these two genotypes (p= 0.043). Haplotype analysis showed an increased risk for the haplotype IL1RN*2/IL1B-31*T. Our results suggest that host genetic factors (such as the IL1RN and the IL1B-31 polymorphisms) interact in the complex process of gastric carcinogenesis in this high-risk Italian population. Overall, this effect appears more modest than previously reported in other populations, supporting the hypothesis that other still-to-be-defined factors are important in gastric carcinogenesis. These findings might be due to a haplotype effect.

  10. Gene polymorphism of interleukin 1 and 8 in chronic gastritis patients infected with Helicobacter pylori

    PubMed Central

    2014-01-01

    Background Epidemiological investigations have indicated that Helicobacter pylori induces inflammation in the gastric mucosa regulated by several interleukins. The genes IL1B and IL8 are suggested as key factors in determining the risk of gastritis. The aim of this paper was to evaluate the association of gene polymorphism of interleukin-1 and interleukin-8 with chronic gastrits in H. pylori infected patients. A total of 60 patients underwent endoscopic procedure. Biopsy samples were collected for urease test, histopathological and molecular exams. The DNA of theses samples was extracted for detection of H. pylori and analysis of the genes mentioned above. Patients with gastritis had a higher frequency of H. pylori-positive samples. Results H. pylori was detected in 30/60 patients (50%) by PCR. As for polymorphism of interleukin 8 (-251) gene we observed a statistical difference when analyzed TA (p = 0.039) and TT (p = 0.047) genotypes. In the IL1B31 there was a statistical difference in TT (p = 0.01) genotype and in the IL1B-511 there wasn’t any statistical difference. Conclusion Our results suggest a strong correlation between the presence of chronic gastritis and infection by H. pylori and that IL1B-31TT and IL8-251TT genotypes appear to act as protective factors against H. pylori infection while IL8-251TA genotype may comprise a risk factor for infection with this bacterium. PMID:24803922

  11. [Influence of interleukin-1 beta gene polymorphism and childhood maltreatment on antidepressant treatment].

    PubMed

    Chen, Ying; Zhang, Zhijun; Xu, Zhi; Pu, Mengjia; Geng, Leiyu

    2015-12-01

    To explore the influence of interleukin-1 beta (IL1B) gene polymorphism and childhood maltreatment on antidepressant treatment. Two hundred and four patients with major depressive disorder (MDD) have received treatment with single antidepressant drugs and were followed up for 8 weeks. Hamilton depression scale-17 (HAMD-17) was used to evaluate the severity of depressive symptoms and therapeutic effect. Childhood maltreatment was assessed using Childhood Trauma Questionnaire, a 28-item Short Form (CTQ-SF). Single nucleotide polymorphism (SNP) of the IL1B gene was determined using a SNaPshot method. Correlation of rs16944 gene polymorphism with response to treatment was analyzed using Unphased 3.0.13 software. The main and interactive effects of SNP and childhood maltreatment on the antidepressant treatment were analyzed using Logistic regression analysis. No significant difference of gender, age, year of education, family history, episode time, and antidepressant agents was detected between the remitters and non-remitters. Association analysis has found that the SNP rs16944 in the IL1B AA genotype carriers antidepressant response was poorer (χ2=3.931, P=0.047). No significant difference was detected in the CTQ scores between the two groups. Genetic and environmental interaction analysis has demonstrated a significant correlation between rs16944 AA genotype and childhood maltreatment and poorer response to antidepressant treatment. The SNP rs16944 in the IL1B gene and its interaction with childhood maltreatment may influence the effect of antidepressant treatment for patients with MDD.

  12. Association between interleukin-1 gene polymorphism and severity of chronic periodontitis in a south Indian population group

    PubMed Central

    Archana, P. M.; Salman, A. Arif; Kumar, T. S. S; Saraswathi, P. K.; Panishankar, K. H.; Kumarasamy, P.

    2012-01-01

    Background: Periodontitis is a bacterial disease modified by multiple factors. Interleukin-1 (IL-1) is a key regulator of the host response and a major modulator of extracellular matrix catabolism and bone resorption. It has been reported that variations in IL-1 gene are associated with increased susceptibility to periodontitis. The aims of the study were 1) to analyze the distribution of single nucleotide polymorphism of IL-1 (IL-1A-+4845 and IL-1B-+3954) and 2) to correlate the association of the composite genotype with the severity of chronic periodontitis. Materials and Methods: Sixty patients aged above 35 years were selected. Following a periodontal examination, using the clinical parameters plaque index, gingival bleeding index, probing depth, and clinical attachment loss (CAL), the selected subjects were categorized into four groups of differing disease severity based on CAL. Five milliliters of venous blood was drawn. DNA was isolated by phenol chloroform method. Amplification of IL-1A+4845 and IL-1B+3954 was done by polymerase chain reaction (PCR). Detection of genotype was done using restriction fragment length polymorphism using the enzymes FnU4HI for IL-1A and TaqI for IL-1B. The results obtained were analyzed statistically. Results: The frequencies of IL-1A-+4845 and IL-1B-+3954were significantly greater in severe periodontitis patients. The distribution of composite genotype (allele 2 of IL-1A+4845and allele 2 of IL-1B+3954) also correlated with the severity of periodontitis. Genotype-positive subjects had a higher mean bleeding index (%) when compared to genotype-negative patients. But no correlation was observed between mean plaque level among genotype-positive and -negative subjects. Conclusion: IL-1 gene polymorphism IL-1A+4845, IL-1B+3954 and composite genotype is an indicator of susceptibility to severe periodontitis in adults. PMID:23055581

  13. Interleukin-1 gene polymorphisms in chronic gastritis patients infected with Helicobacter pylori as risk factors of gastric cancer development.

    PubMed

    Hnatyszyn, Andrzej; Wielgus, Karolina; Kaczmarek-Rys, Marta; Skrzypczak-Zielinska, Marzena; Szalata, Marlena; Mikolajczyk-Stecyna, Joanna; Stanczyk, Jerzy; Dziuba, Ireneusz; Mikstacki, Adam; Slomski, Ryszard

    2013-12-01

    Epidemiological investigations indicated association of the Helicobacter pylori infections with the occurrence of inflammatory conditions of the gastric mucosa and development of chronic gastritis and intestinal type of gastric cancer. IL1A and IL1B genes have been proposed as key factors in determining risk of gastritis and malignant transformation. The aim of this paper was to evaluate association of interleukin-1 gene polymorphisms with chronic gastritis, atrophy, intestinal metaplasia, dysplasia and intestinal type of gastric cancer in H. pylori-infected patients. Patients subjected to analysis represent group of 144 consecutive cases that suffered from dyspepsia with coexisting infection of H. pylori and chronic gastritis, chronic atrophic gastritis, intestinal metaplasia, dysplasia or gastric cancer. Molecular studies involved analysis of -889C>T polymorphism of IL1A gene and +3954C>T polymorphism of IL1B gene. Statistical analysis of association of polymorphism -889C>T of gene IL1A with changes in gastric mucosa showed lack of significance, whereas +3954C>T polymorphism of IL1B gene showed significant association. Frequency of allele T of +3954C>T polymorphism of IL1B gene was higher in group of patients with chronic gastritis, atrophy, intestinal metaplasia, dysplasia or intestinal type of gastric cancer (32.1 %) as compared with population group (23 %), χ(2) = 4.61 and p = 0.03. This corresponds to odds ratio: 1.58, 95 % CI: 1.04-2.4. Our results indicate that +3954C>T polymorphism of IL1B gene increase susceptibility to inflammatory response of gastric mucosa H. pylori-infected patients and plays a significant role in the development of chronic gastritis, atrophy, intestinal metaplasia, dysplasia and the initiation of carcinogenesis.

  14. Evaluation of interleukin -1B (+3954) gene polymorphism in patients with chronic and aggressive periodontitis: A genetic association study

    PubMed Central

    Masamatti, Sujata S.; Kumar, Ashish; Baron, Tarun Kumar A.; Mehta, Dhoom S.; Bhat, Kishore

    2012-01-01

    Background: IL-1 cytokines have central roles in the pathogenesis of periodontal disease. Polymorphism in the locus +3954 (C/T) of the human IL-1B gene has been shown to affect the levels of this cytokine. Aim: The aim of the present study was to investigate the association between the IL-1 B (+3954) gene polymorphism and the occurrence of different clinical forms of periodontitis. Materials and Methods: Genomic DNA was obtained from 90 individuals and amplified using the PCR with specific primers flanking the locus +3954 of IL-1B. PCR products were submitted to restriction endonuclease digestion and analyzed by gel electrophoresis, allowing for the determination of the genotypes and detection of the polymorphism. Statistical Analysis: Fisher's exact test was used for comparing the frequency of genotype distributions between groups. Results: The chronic periodontitis group displayed a higher percentage of T alleles (38%) when compared to the aggressive periodontitis group (20%) and to the control group (19%). Conclusion: Our study data states that polymorphism in the locus +3954 of IL-1B gene could be a risk factor for chronic periodontitis in a sample of Indian population of Karnataka state. PMID:22919211

  15. The Regulation of Uterine Proinflammatory Gene Expression during Pregnancy in the Live-Bearing Lizard, Pseudemoia entrecasteauxii.

    PubMed

    Hendrawan, Kevin; Whittington, Camilla M; Brandley, Matthew C; Belov, Katherine; Thompson, Michael B

    2017-03-10

    The evolutionary transition from egg-laying to live-bearing in amniote vertebrates (reptiles and mammals) requires the development of a closer association between the maternal and embryonic tissue to facilitate gas and nutrient exchange with the embryo. Because the embryo is an allograft to the father and mother, it could be considered foreign by the maternal immune system and thus be immunologically rejected during pregnancy. In eutherian ("placental") mammals, the proinflammatory genes interleukin 1B (IL1B), tumor necrosis factor (TNF) and tumor necrosis factor receptor superfamily 1A (TNFRSF1A) are tightly regulated in the pregnant uterus to prevent embryonic rejection. We tested whether inflammation is similarly regulated in pregnant viviparous reptiles by comparing the expression of IL1B, TNF, and TNFRSF1A in the pregnant and nonpregnant uterus of the viviparous lizard, Pseudemoia entrecasteauxii. We found statistically significant support for the downregulation of pregnant uterine TNF mRNA expression in P. entrecasteauxii, but no statistically significant changes in mRNA expression of TNFRSF1A or IL1B between pregnant and nonpregnant uteri. Although these genes are apparently not regulated at the transcriptional level, our immunofluorescence microscopy analyses nonetheless demonstrate that the IL1B proteins are stored intracellularly during pregnancy, possibly resulting in inhibition of inflammatory response. We therefore conclude that processes of both transcriptional (TNF) and posttranslational (IL1B) gene regulation may reduce inflammation in the pregnant uterus of this viviparous reptile. Our study is important because it demonstrates that regulating the maternal immune system to prevent embryonic rejection may be important in reptilian pregnancy as it is in mammalian pregnancy.

  16. Cytokine gene polymorphism associations with congenital cytomegalovirus infection and sensorineural hearing loss.

    PubMed

    Kasztelewicz, B; Czech-Kowalska, J; Lipka, B; Milewska-Bobula, B; Borszewska-Kornacka, M K; Romańska, J; Dzierżanowska-Fangrat, K

    2017-05-13

    Cytomegalovirus (CMV) is the most common viral agent of congenital infections and a leading nongenetic cause of sensorineural hearing loss (SNHL). The host immunologic factors that render a developing foetus prone to intrauterine CMV infection and development of hearing loss are unknown. The aim of this study was to assess the potential associations between the polymorphisms within cytokine and cytokine receptors genes, and the risk of congenital CMV infection, and the hearing outcome. A panel of 11 candidate single nucleotide polymorphisms (SNPs): TNF rs1799964, TNF rs1800629, TNFRSF1A rs4149570, IL1B rs16944, IL1B rs1143634, IL10 rs1800896, IL10RA rs4252279, IL12B rs3212227, CCL2 rs1024611, CCL2 rs13900, CCR5 rs333 was genotyped in 470 infants (72 with confirmed intrauterine CMV infection and 398 uninfected controls), and related to congenital CMV infection, and the outcome. In multivariate analysis, the IL1B rs16944 TT and TNF rs1799964 TC genotypes were significantly associated with intrauterine CMV infection (aOR = 2.32; 95% CI, 1.11-4.89; p = 0.032, and aOR = 2.17, 95% CI, 1.25-3.77; p = 0.007, respectively). Twenty-two out of 72 congenitally infected newborns had confirmed SNHL. Carriers of CT or TT genotype of CCL2 rs13900 had increased risk of hearing loss at birth and at 6 months of age (aOR = 3.59; p = 0.028 and aOR = 4.10; p = 0.039, respectively). This is the first study to report an association between SNPs in IL1B, TNF, and CCL2, and susceptibility to congenital CMV infection (IL1B and TNF) and SNHL (CCL2).

  17. An Association Between Functional Polymorphisms of the Interleukin 1 Gene Complex and Schizophrenia Using Transmission Disequilibrium Test.

    PubMed

    Kapelski, Pawel; Skibinska, Maria; Maciukiewicz, Malgorzata; Pawlak, Joanna; Dmitrzak-Weglarz, Monika; Szczepankiewicz, Aleksandra; Zaremba, Dorota; Twarowska-Hauser, Joanna

    2016-12-01

    IL1 gene complex has been implicated in the etiology of schizophrenia. To assess whether IL1 gene complex is associated with susceptibility to schizophrenia in Polish population we conducted family-based study. Functional polymorphisms from IL1A (rs1800587, rs17561, rs11677416), IL1B (rs1143634, rs1143643, rs16944, rs4848306, rs1143623, rs1143633, rs1143627) and IL1RN (rs419598, rs315952, rs9005, rs4251961) genes were genotyped in 143 trio with schizophrenia. Statistical analysis was performed using transmission disequilibrium test. We have found a trend toward an association of rs1143627, rs16944, rs1143623 in IL1B gene with the risk of schizophrenia. Our results show a protective effect of allele T of rs4251961 in IL1RN against schizophrenia. We also performed haplotype analysis of IL1 gene complex and found a trend toward an association with schizophrenia of GAGG haplotype (rs1143627, rs16944, rs1143623, rs4848306) in IL1B gene, haplotypes: TG (rs315952, rs9005) and TT (rs4251961, rs419598) in IL1RN. Haplotype CT (rs4251961, rs419598) in IL1RN was found to be associated with schizophrenia. After correction for multiple testing associations did not reach significance level. Our results might support theory that polymorphisms of interleukin 1 complex genes (rs1143627, rs16944, rs1143623, rs4848306 in IL1B gene and rs4251961, rs419598, rs315952, rs9005 in IL1RN gene) are involved in the pathogenesis of schizophrenia, however, none of the results reach significance level after correction for multiple testing.

  18. Polymorphic Regions in the Interleukin-1 Gene and Susceptibility to Chronic Periodontitis: A Genetic Association Study

    PubMed Central

    Lavu, Vamsi; Venkatesan, Vettriselvi; Lakkakula, Bhaskar Venkata Kameswara Subrahmanya; Venugopal, Priyanka; Paul, Solomon Franklin Durairaj

    2015-01-01

    Objective: The objectives of this study were to determine the association between single nucleotide polymorphisms (SNPs) in IL1B (−511, +3954), IL1A (−889, +4845), and the variable number of tandem repeats (VNTRs) polymorphism in the IL-1RN gene with chronic periodontitis susceptibility and to analyze gene–gene interactions in a hospital-based sample population from South India. Subjects and Methods: A total of 400 individuals were recruited for this study; 200 individuals with healthy gingiva and 200 chronic periodontitis patients. Genomic DNA was isolated from peripheral blood samples and genotyping was performed for the above-mentioned single nucleotide and VNTR polymorphisms by polymerase chain reaction, DNA sequencing, and agarose gel electrophoresis. Results: A higher proportion of the variant alleles were observed in the chronic periodontitis group for all the SNPs examined. The SNP at +3954 (C>T) in the IL1B gene was found to be significantly associated with chronic periodontitis (p=0.007). VNTR genotypes (χ2 value: 5.163, df=1, p=0.023) and alleles (χ2 value: 6.818, df=1, p=0.009) were found to have a significant association with chronic periodontitis susceptibility. Conclusion: In the study population examined, the SNP in the IL1B gene (+3954) and VNTR polymorphisms in the IL1RN gene were found to have a significant association with chronic periodontitis susceptibility. PMID:25710474

  19. H pylori seropositivity and cytokine gene polymorphisms

    PubMed Central

    Saijo, Yasuaki; Yoshioka, Eiji; Fukui, Tomonori; Kawaharada, Mariko; Sata, Fumihiro; Sato, Hirokazu; Kishi, Reiko

    2007-01-01

    AIM: To investigate whether the pro- and anti-inflammatory cytokine gene polymorphisms, IL1B-511C/T, IL1B-31C/T, IL6-634C/G, TNF-1031T/C, TNF-857C/T, and IL10-1082A/G, interact with smoking and drinking habits to influence infection with H pylori. METHODS: The subjects were 410 Japanese transit company employees. C-reactive protein and conventional cardiovascular risk factors were evaluated. Serum anti-H pylori antibodies were measured. The genotypes of IL1B-511C/T, IL1B-31C/T, IL6-634C/G, TNF-1031T/C, TNF-857C/T, and IL10-1082A/G polymorphisms were determined by allelic discrimination using fluorogenic probes and a 5´nuclease assay. RESULTS: In gender- and age-adjusted logistic analyses, the subjects with TNF-857T/T had a significantly lower odds ratio (OR) for H pylori seropositivity (reference -857C/C; OR = 0.15, 95%CI: 0.03-0.59, P = 0.007). After stratification according to smoking and drinking status, among never-smokers, the subjects with IL1B-511C/T had a significantly lower OR (reference -511C/C; OR = 0.30, 95%CI: 0.10-0.90, P = 0.032). Among drinkers in the 1-5 times/wk category, the subjects with IL1B-511T/T had a significantly lower OR (reference C/C; OR = 0.38, 95%CI: 0.16-0.95, P = 0.039), and the subjects with IL1B-31C/T and T/T had a significantly higher OR (reference C/C; C/T: OR = 2.59, 95%CI, P = 0.042: 1.04-6.47; C/C: OR = 3.17, 95%CI: 1.23-8.14, P = 0.017). Among current smokers, the subjects with IL6-634C/G had a significantly higher OR (reference C/C; OR = 2.28, 95%CI: 1.13-4.58, P = 0.021). However, the interactions terms between the aforementioned genotypes and lifestyles were not statistically significant. CONCLUSION: Contrary to previous findings, the results herein suggest that the TNF-857T/T genotype may be protective against chronic infection with H pylori. Drinking and smoking habits may influence the effect of cytokine gene polymorphisms. Further studies are required to clarify the effects of the pro- and anti-inflammatory cytokine

  20. Effect of interleukin-1beta gene functional polymorphism on dorsolateral prefrontal cortex activity in schizophrenic patients.

    PubMed

    Papiol, Sergi; Molina, Vicente; Rosa, Araceli; Sanz, Javier; Palomo, Tomás; Fañanás, Lourdes

    2007-12-05

    Hypoactivity of the dorsolateral prefrontal cortex (DLPFC) during cognitive tasks is among the most consistent findings in schizophrenia. The biological factors contributing to this hypofrontality are only partially known. Previous reports have shown the influence of genes mapped to IL-1 cluster (i) in the risk to develop schizophrenia and (ii) on brain morphological abnormalities in these patients. Moreover, Interleukin-1beta (IL-1beta), encoded by IL-1B gene (IL-1 cluster, chromosome 2q13) has a key role in dopaminergic differentiation and dendrite growth in developing cortical neurons. The authors explored the role of a genetic functional polymorphism at IL-1B gene in relation to DLPFC activity. DLPFC (left and right) metabolic activity was measured in a sample of 19 DSM-IV diagnosed schizophrenic patients of Spanish origin using a procedure based on MRI/PET image fusion. During PET studies, subjects performed a contingent Continuous Performance Test aiming to activate DLPFC. Functional promoter polymorphism -511 C/T (rs16944) of IL-1B gene was genotyped in these patients. Those patients who were allele 2 (-511 T) carriers showed a lower metabolic activity in the left DLPFC with respect to patients homozygous for allele 1 (-511 C) (U = 16, z = -2.32, P = 0.02). Our results suggest that hypofrontality reported in some schizophrenic patients might be explained, at least in part, by this functional polymorphism at IL-1B gene. Genetic variants with influence on brain functionality may account for the neurocognitive heterogeneity observed in schizophrenic patients.

  1. Clinical associations of host genetic variations in the genes of cytokines in critically ill patients.

    PubMed

    Belopolskaya, O B; Smelaya, T V; Moroz, V V; Golubev, A M; Salnikova, L E

    2015-06-01

    Host genetic variations may influence a changing profile of biochemical markers and outcome in patients with trauma/injury. The objective of this study was to assess clinical associations of single nucleotide polymorphisms (SNPs) in the genes of cytokines in critically ill patients. A total of 430 patients were genotyped for SNPs in the genes of pro- (IL1B, IL6, IL8) and anti-inflammatory (IL4, IL10, IL13) cytokines. The main end-points were sepsis, mortality and adult respiratory distress syndrome (ARDS). We evaluated the dynamic levels of bilirubin, blood urea nitrogen, creatine kinase, creatinine and lactate dehydrogenase in five points of measurements (between 1 and 14 days after admission) and correlated them with SNPs. High-producing alleles of proinflammatory cytokines protected patients against sepsis (IL1B -511A and IL8 -251A) and mortality (IL1B -511A). High-producing alleles of anti-inflammatory cytokines IL4 -589T and IL13 431A (144Gln) were less frequent in ARDS patients. The carriers of IL6 -174C/C genotypes were prone to the increased levels of biochemical markers and acute kidney and liver insufficiency. Genotype-dependent differences in the levels of biochemical indicators gradually increased to a maximal value on the 14th day after admission. These findings suggest that genetic variability in pro- and anti-inflammatory cytokines may contribute to different clinical phenotypes in patients at high risk of critical illness.

  2. Dataset of proinflammatory cytokine and cytokine receptor gene expression in rainbow trout (Oncorhynchus mykiss) measured using a novel GeXP multiplex, RT-PCR assay.

    PubMed

    Kutyrev, Ivan; Cleveland, Beth; Leeds, Timothy; Wiens, Gregory D

    2017-04-01

    A GeXP multiplex, RT-PCR assay was developed and optimized that simultaneously measures expression of a suite of immune-relevant genes in rainbow trout (Oncorhynchus mykiss), concentrating on tumor necrosis factor and interleukin-1 ligand/receptor systems and acute phase response genes. The dataset includes expression values for drpt, il11a, il1b1, il1b2, il1b3, il1r-like-1(e3-5), il1r-like-1(e9-11), il1r1-like-a, il1r1-like-b, il1r2, saa, tnfa1, tnfa2, tnfa3, tnfrsf1a, tnfrsf1a-like-a, tnfrsf1a-like-b, tnfrsf5, and tnfrsf9. Gene expression was measured at four time-points post-challenge in both a resistant line (ARS-Fp-R) and a susceptible line (ARS-Fp-S) of rainbow trout. In addition, fish body weight, spleen index and the Flavobacterium psychrophilum load are reported. These data are an extension of information presented and discussed in "Proinflammatory cytokine and cytokine receptor gene expression kinetics following challenge with Flavobacterium psychrophilum in resistant and susceptible lines of rainbow trout (Oncorhynchus mykiss)" (Kutyrev et al., 2016) [1].

  3. Clinical Relevance of Cytokines Gene Polymorphisms and Protein Levels in Gingival Cervical Fluid from Chronic Periodontitis Patients.

    PubMed

    Lavu, Vamsi; Venkatesan, Vettriselvi; Venugopal, Priyanka; Lakkakula, Bhaskar Venkata Kameswara Subrahmanya; Paul, Solomon Franklin Durairaj; Peria, Kumarasamy; Rao, Suresh Ranga

    2017-03-01

    Cytokines are suggested to play a role in periodontitis. To determine and compare the levels of Interleukin-1 beta (IL-1β) and Tumor necrosis factor alpha (TNF-α) in gingival crevicular fluid (GCF) samples amongst healthy individuals and those with chronic periodontitis. Further to compare the GCF cytokine levels in three genotype classes defined by the respective gene polymorphisms. The study was conducted on 41 chronic periodontitis patients and 40 healthy volunteers. IL-1β and TNF-α were quantified in GCF by cytometric bead array. DNA was extracted from peripheral blood samples and genotyping of IL1B +3954C/T (rs1143634) IL1B -511G/A (rs16944), TNFA -1031T/C (rs1799964) and TNFA -863C/A (rs1800630) polymorphisms were performed using Sanger sequencing and Taqman SNP genotyping assays methods. Both IL-1β and TNF-α levels were significantly higher in chronic periodontitis group compared to the controls. IL-1β and TNF-α levels did not significantly differ in genotype classes of the respective polymorphism (IL1B -511G/A, TNFA -1031T/C and TNFA -863C/A). However, individuals with CT genotype of IL1B +3954C/T showed higher levels of IL-1β in the gingival crevicular fluid (ANOVA p<0.05). The results of this study revealed the presence of higher levels of IL-1β and TNF-α in subjects with periodontitis and genetic control of IL-1β levels in our samples of Indians.

  4. Genetic variants in interleukin genes are associated with breast cancer risk and survival in a genetically admixed population: the Breast Cancer Health Disparities Study

    PubMed Central

    Slattery, Martha L.; Herrick, Jennifer S.; Torres-Mejia, Gabriella; John, Esther M.; Giuliano, Anna R.; Hines, Lisa M.; Stern, Mariana C.; Baumgartner, Kathy B.; Presson, Angela P.; Wolff, Roger K.

    2014-01-01

    Interleukins (ILs) are key regulators of immune response. Genetic variation in IL genes may influence breast cancer risk and mortality given their role in cell growth, angiogenesis and regulation of inflammatory process. We examined 16 IL genes with breast cancer risk and mortality in an admixed population of Hispanic/Native American (NA) (2111 cases and 2597 controls) and non-Hispanic white (NHW) (1481 cases and 1585 controls) women. Adaptive Rank Truncated Product (ARTP) analysis was conducted to determine gene significance and lasso (least absolute shrinkage and selection operator) was used to identify potential gene by gene and gene by lifestyle interactions. The pathway was statistically significant for breast cancer risk overall (P ARTP = 0.0006), for women with low NA ancestry (P ARTP = 0.01), for premenopausal women (P ARTP = 0.02), for estrogen receptor (ER)+/progesterone receptor (PR)+ tumors (P ARTP = 0.03) and ER−/PR− tumors (P ARTP = 0.02). Eight of the 16 genes evaluated were associated with breast cancer risk (IL1A, IL1B, IL1RN, IL2, IL2RA, IL4, IL6 and IL10); four genes were associated with breast cancer risk among women with low NA ancestry (IL1B, IL6, IL6R and IL10), two were associated with breast cancer risk among women with high NA ancestry (IL2 and IL2RA) and four genes were associated with premenopausal breast cancer risk (IL1A, IL1B, IL2 and IL3). IL4, IL6R, IL8 and IL17A were associated with breast cancer-specific mortality. We confirmed associations with several functional polymorphisms previously associated with breast cancer risk and provide support that their combined effect influences the carcinogenic process. PMID:24670917

  5. Genetic variants in interleukin genes are associated with breast cancer risk and survival in a genetically admixed population: the Breast Cancer Health Disparities Study.

    PubMed

    Slattery, Martha L; Herrick, Jennifer S; Torres-Mejia, Gabriella; John, Esther M; Giuliano, Anna R; Hines, Lisa M; Stern, Mariana C; Baumgartner, Kathy B; Presson, Angela P; Wolff, Roger K

    2014-08-01

    Interleukins (ILs) are key regulators of immune response. Genetic variation in IL genes may influence breast cancer risk and mortality given their role in cell growth, angiogenesis and regulation of inflammatory process. We examined 16 IL genes with breast cancer risk and mortality in an admixed population of Hispanic/Native American (NA) (2111 cases and 2597 controls) and non-Hispanic white (NHW) (1481 cases and 1585 controls) women. Adaptive Rank Truncated Product (ARTP) analysis was conducted to determine gene significance and lasso (least absolute shrinkage and selection operator) was used to identify potential gene by gene and gene by lifestyle interactions. The pathway was statistically significant for breast cancer risk overall (P ARTP = 0.0006), for women with low NA ancestry (P(ARTP) = 0.01), for premenopausal women (P(ARTP) = 0.02), for estrogen receptor (ER)+/progesterone receptor (PR)+ tumors (P(ARTP) = 0.03) and ER-/PR- tumors (P(ARTP) = 0.02). Eight of the 16 genes evaluated were associated with breast cancer risk (IL1A, IL1B, IL1RN, IL2, IL2RA, IL4, IL6 and IL10); four genes were associated with breast cancer risk among women with low NA ancestry (IL1B, IL6, IL6R and IL10), two were associated with breast cancer risk among women with high NA ancestry (IL2 and IL2RA) and four genes were associated with premenopausal breast cancer risk (IL1A, IL1B, IL2 and IL3). IL4, IL6R, IL8 and IL17A were associated with breast cancer-specific mortality. We confirmed associations with several functional polymorphisms previously associated with breast cancer risk and provide support that their combined effect influences the carcinogenic process.

  6. The prognostic value of four interleukin-1 gene polymorphisms in caucasian women with breast cancer – a multicenter study

    PubMed Central

    2009-01-01

    Background The proinflammatory cytokine interleukin-1 (IL-1) is known to play an important role in the carcinogenesis of breast cancer. Although IL-1 gene polymorphisms were reported to be associated with increased risk of breast cancer, their influence on survival of Caucasian breast cancer patients remains to be shown. Methods We studied the influence of four common gene polymorphisms (IL1A -889C/T, IL1B -511C/T, IL1B +3953E1/E2, and IL1RN long/2) of the IL-1 family on survival in 262 Caucasian patients with breast cancer by univariate and multivariate survival analysis. The combined effect of the four gene polymorphisms on overall survival was studied by haplotype analysis. Results In the present study 38 cases of cancer related death and a median time of follow-up (range) of 55.3 (0.4–175.8) months was observed. IL1RN 2/2 (homozygous mutant) gene polymorphism was associated with shortened disease free and overall survival in a univariate (p = 0.001 and p = 0.01, respectively) and multivariate analysis (p = 0.002, Odds Ratio [95% Confidence Interval] = 3.6 [1.6–8.0] and p = 0.05, Odds Ratio = 3.0 [1.1–9.3], respectively). Presence of the homozygous mutant genotype of the IL1A -889 and IL1B +3953 gene polymorphism was associated with overall survival in the univariate (p = 0.004 and p = 0.002, respectively), but not in the multivariate analysis. No association was observed between all possible haplotype combinations and overall survival. Conclusion Carriage of the mutant alleles of IL1RN was independently associated with shortened disease free and overall survival rates in Caucasian patients with breast cancer. PMID:19267917

  7. Gene-environment interactions linking air pollution and inflammation in Parkinson's disease.

    PubMed

    Lee, Pei-Chen; Raaschou-Nielsen, Ole; Lill, Christina M; Bertram, Lars; Sinsheimer, Janet S; Hansen, Johnni; Ritz, Beate

    2016-11-01

    Both air pollution exposure and systemic inflammation have been linked to Parkinson's disease (PD). In the PASIDA study, 408 incident cases of PD diagnosed in 2006-2009 and their 495 population controls were interviewed and provided DNA samples. Markers of long term traffic related air pollution measures were derived from geographic information systems (GIS)-based modeling. Furthermore, we genotyped functional polymorphisms in genes encoding proinflammatory cytokines, namely rs1800629 in TNFα (tumor necrosis factor alpha) and rs16944 in IL1B (interleukin-1β). In logistic regression models, long-term exposure to NO2 increased PD risk overall (odds ratio (OR)=1.06 per 2.94μg/m(3) increase, 95% CI=1.00-1.13). The OR for PD in individuals with high NO2 exposure (≧75th percentile) and the AA genotype of IL1B rs16944 was 3.10 (95% CI=1.14-8.38) compared with individuals with lower NO2 exposure (<75th percentile) and the GG genotype. The interaction term was nominally significant on the multiplicative scale (p=0.01). We did not find significant gene-environment interactions with TNF rs1800629. Our finds may provide suggestive evidence that a combination of traffic-related air pollution and genetic variation in the proinflammatory cytokine gene IL1B contribute to risk of developing PD. However, as statistical evidence was only modest in this large sample we cannot rule out that these results represent a chance finding, and additional replication efforts are warranted.

  8. Upregulation of genes orchestrating keratinocyte differentiation, including the novel marker gene ID2, by contact sensitizers in human bulge-derived keratinocytes.

    PubMed

    Yoshikawa, Yoshie; Sasahara, Yusuke; Kitano, Yukio; Kanazawa, Nozomi; Shima, Hiroki; Hashimoto-Tamaoki, Tomoko

    2010-01-01

    In the epidermis, keratinocytes are involved in physical and first-line immune protection of the host. In this study, we analyzed the molecular responses to certain contact sensitizers (2,4-dinitrochlorobenzene and NiSO(4)) and irritants (sodium dodecyl sulfate and benzalkonium chloride) in cultured human keratinocytes from the bulge region of a plucked hair follicle (bulge-derived keratinocytes [BDKs]) and compared these molecular responses to those with the human monocytic leukemia cell line, THP-1. The BDKs, individually established without invasive biopsies, showed high reactivity to these stimulants. As a primary response to the contact sensitizers, the NRF2-mediated signaling pathway was upregulated in BDKs and THP-1. The expression of IL1B and IL8 genes was not induced by the irritants but by the sensitizers in THP-1. However, the expression of the IL1B and IL8 genes was induced at higher levels by the irritants in BDKs than by the sensitizers. Many genes orchestrating keratinocyte differentiation, including ID2, were significantly upregulated in response to the sensitizers in BDKs but not those in THP-1. The use of the ID2 gene to discriminate between sensitizers and irritants might be effective as a novel marker for application during in vitro sensitization with BDKs.

  9. Polymorphisms of interleukin-1 Beta and interleukin-17Alpha genes are associated with restless legs syndrome.

    PubMed

    Hennessy, Mary Dawn; Zak, Rochelle S; Gay, Caryl L; Pullinger, Clive R; Lee, Kathryn A; Aouizerat, Bradley E

    2014-04-01

    Dopamine, iron, and inflammatory pathways are considered important to the development of restless legs syndrome (RLS). Recent genetic studies support involvement of dopamine and iron; however, cytokine gene variation in the inflammatory component remains unexplored. A recent study reported a high prevalence of RLS among HIV-infected adults. We estimate occurrence of RLS in an ethnically diverse sample of HIV-infected adults and examine differences in demographic factors, clinical characteristics, and biomarkers relating to dopamine, iron, and inflammation between adults with and without RLS symptoms. A prospective longitudinal study aimed at identifying biomarkers of RLS symptom experience among HIV-infected adults. 316 HIV-positive adults were evaluated using International RLS Study Group criteria. Genes were chosen for hypothesized relationships to dopamine (NOS1, NOS2), iron (HFE) or inflammation-mediated by cytokine genes (interferon [IFN], interleukin [IL], nuclear factor kappa-B [NFKB], and tumor necrosis factor alpha [TNFA]). Similar to general population estimates, 11% of the sample met all four RLS diagnostic criteria. Controlling for race, gender, and hemoglobin, carrying two copies of the minor allele for IL1B rs1143643, rs1143634, or rs1143633 or carrying the minor allele for IL17A rs8193036 was associated with increased likelihood of meeting RLS diagnostic criteria. This study provides preliminary evidence of a genetic association between IL1B and IL17A genes and RLS.

  10. Interleukin gene polymorphisms and breast cancer: a case control study and systematic literature review

    PubMed Central

    Balasubramanian, SP; Azmy, IAF; Higham, SE; Wilson, AG; Cross, SS; Cox, A; Brown, NJ; Reed, MW

    2006-01-01

    Background Interleukins and cytokines play an important role in the pathogenesis of many solid cancers. Several single nucleotide polymorphisms (SNPs) identified in cytokine genes are thought to influence the expression or function of these proteins and many have been evaluated for their role in inflammatory disease and cancer predisposition. The aim of this study was to evaluate any role of specific SNPs in the interleukin genes IL1A, IL1B, IL1RN, IL4R, IL6 and IL10 in predisposition to breast cancer susceptibility and severity. Methods Candidate single nucleotide polymorphisms (SNPs) in key cytokine genes were genotyped in breast cancer patients and in appropriate healthy volunteers who were similar in age, race and sex. Genotyping was performed using a high throughput allelic discrimination method. Data on clinico-pathological details and survival were collected. A systematic review of Medline English literature was done to retrieve previous studies of these polymorphisms in breast cancer. Results None of the polymorphisms studied showed any overall predisposition to breast cancer susceptibility, severity or to time to death or occurrence of distant metastases. The results of the systematic review are summarised. Conclusion Polymorphisms within key interleukin genes (IL1A, IL1B, IL1RN, IL4R, IL6 and IL10 do not appear to play a significant overall role in breast cancer susceptibility or severity. PMID:16842617

  11. Head kidney, liver and skin histopathology and gene expression in gilthead seabream (Sparus aurata L.) exposed to highly polluted marine sediments from Portman Bay (Spain).

    PubMed

    Ben Hamed, Said; Guardiola, Francisco; Cuesta, Alberto; Martínez, Salvadora; Martínez-Sánchez, María José; Pérez-Sirvent, Carmen; Esteban, María Ángeles

    2017-05-01

    Biomarkers have become crucial tools in modern environmental assessment as they can help to predict magnitude of pollution. The head-kidney (HK) and liver (hematopoietic and xenobiotic metabolism organs, respectively) are the key organs in all fish toxicological studies, although the skin has received less attention in this respect. The impact of two different types of polluted sediment collected from Portman Bay (Spain) on HK, liver and skin gene expression in gilthead seabream (Sparus aurata L.) exposed for two weeks to the sediments was determined by real time-PCR. The expression levels of different antioxidant enzyme genes [superoxide dismutase (sod) glutathione reductase (gr) and catalase (cat)] and immune-related genes [interleukin -1β (il-1b), immunoglobulin M (igm), T-Cell receptor (tcr-b), cyclooxygenase-2 (cox-2), colony-stimulating factor 1-receptor (csf-1r) and hepcidin (hep)] was analysed. Expression varied depending on both the organ and gene studied: tcr-b, csf-1r and hep genes were down-regulated in HK, as were gr, tcr-b and il-1b in liver and gr and il-1b in skin, while cox-2 was up-regulated in skin after exposure to both sediments. Concomitantly, histopathological alterations were also studied in HK, liver and skin. While no significant changes were detected in skin cells of fish reared in aquaria with polluted sediments marked changes in the general morphology of HK and liver were observed, accompanied by a substantial degree of cell death and melano-macrophage centre disorganization. The present study suggests that the biomarkers studied in gilthead seabream could be useful for assessing the impact of pollution in coastal environments. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Association analysis of the IL-1 gene cluster polymorphisms with aggressive and chronic periodontitis in the Algerian population.

    PubMed

    Boukortt, Kawther Nourelhouda; Saidi-Ouahrani, Nadjia; Boukerzaza, Boubaker; Ouhaibi-Djellouli, Hadjira; Hachmaoui, Khalida; Benaissa, Fatima Zohra; Taleb, Leila; Drabla-Ouahrani, Hayet; Deba, Tahria; Ouledhamou, Sid Ahmed; Mehtar, Nadhera; Boudjema, Abdellah

    2015-10-01

    There is strong evidence that genetic as well as environmental factors affect the development of periodontitis. Various studies suggest that genetic polymorphisms of the interleukin-1 (IL-1) genes are associated with an increased risk of developing the pathogenesis. The aim of the present study was to investigate the possible relationship between two polymorphisms of IL-1 gene cluster IL-1B (C+3954T) (rs1143634) and IL-1A (C-889T) (rs1800587) SNPs and the aggressive and chronic periodontitis risk in a case control study in Algerian population. 279 subjects were recruited and received a periodontal examination: 128 healthy controls and 151 cases. From cases, 91 patients were having a chronic disease whereas 60 subjects with aggressive form. All these subjects were genotyped for IL-1A (C-889T) and IL-1B (C+3954T) polymorphisms using TaqMan real time PCR technology. Frequencies of IL-1 alleles, genotypes and the haplotypes were also examined. Significant differences were found in the carriage rate of both minor alleles of the IL-1A (C-889T) and IL-1B (C+3954T) polymorphisms of aggressive periodontitis cases compared with healthy controls (OR [95%CI]=1.61 [1.03-2.49], p=0.03), (OR [95%CI]=1.69 [1.09-2.63], p=0.01), respectively. The result did not reach significance with the chronic form. The studied polymorphisms of the IL-1 genes appear to be associated with susceptibility to aggressive periodontitis (AgP) in the Algerian population. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Long-range DNA interactions at the IL-1/IL-36/IL-37 gene cluster (2q13) are induced by activation of monocytes.

    PubMed

    Sharaf, Nazar; Nicklin, Martin J; di Giovine, Francesco S

    2014-07-01

    The interleukin-1 gene cluster occupies a 360kb region of chromosome 2q13 and contains nine homologous genes. These include agonists and antagonists of the parallel IL-1 and IL-36 systems, and IL1F7, the gene encoding IL-37. As the genes of the cluster are structurally and functionally related and have similar mRNA kinetics, we have sought evidence for gene induction-specific looping of chromatin in the IL-1 cluster by chromatin conformation capture (3C). We show here that IL1A, IL1B and IL1F7 regulatory regions come in close proximity in LPS stimulated cells but not in resting human monocytes. This suggests that IL1A, IL1B and IL1F7 are likely transcribed by the same transcription factory. One cardinal function of transcriptional Locus Control Region (LCR) is bringing map-distant activated genes into close physical proximity within the transcription factory. Our data show distant intergenic DNA segments are also in close proximity to the regulatory regions of the three genes. This may indicate that they are co-regulated and raise the possibility of a LCR within the cluster. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Relation of atrophic gastritis with Helicobacter pylori-CagA+ and interleukin-1 gene polymorphisms

    PubMed Central

    Sierra, Rafaela; Une, Clas; Ramírez, Vanessa; Alpízar-Alpízar, Warner; González, María I; Ramírez, José A; de Mascarel, Antoine; Cuenca, Patricia; Pérez-Pérez, Guillermo; Mégraud, Francis

    2008-01-01

    AIM: To determine the association of Helicobacter pylori (H pylori) CagA+ infection and pro-inflammatory polymorphisms of the genes interleukin (IL)-1RN and IL-1B with the risk of gastric atrophy and peptic ulcers in a dyspeptic population in Costa Rica, a country with high incidence and mortality of gastric cancer. METHODS: Seven biopsy specimens, a fasting blood sample and a questionnaire concerning nutritional and sociodemographic factors were obtained from 501 consecutive patients who had undergone endoscopy for dyspeptic symptoms. A histopathological diagnosis was made. Pepsinogen concentrations were analyzed by enzyme linked immunosorbent assay (ELISA). Infection with H pylori CagA+ was determined by serology and polymerase chain reaction (PCR). IL-1B and IL-1RN polymorphisms genotyping was performed by PCR-restriction fragment length polymorphism (PCR-RFLP) and PCR respectively. RESULTS: In this dyspeptic population, 86% were H pylori positive and of these, 67.8% were positive for CagA. Atrophic antral gastritis (AAG) was associated with CagA+ status [odd ratio (OR) = 4.1; P < 0.000] and fruit consumption (OR = 0.3; P < 0.00). Atrophic body gastritis (ABG) was associated with pepsinogen PGI/PGII < 3.4 (OR = 4.9; P < 0.04) and alcohol consumption (OR = 7.3; P < 0.02). Duodenal ulcer was associated with CagA+ (OR = 2.9; P < 0.04) and smoking (OR = 2.4; P < 0.04). PGI < 60 μg/L as well as PGI/PGII < 3.4 were associated with CagA+. CONCLUSION: In a dyspeptic population in Costa Rica, H pylori CagA+ is not associated with ABG, but it is a risk factor for AAG. The pro-inflammatory cytokine polymorphisms IL-1B + 3945 and IL-1RN are not associated with the atrophic lesions of this dyspeptic population. PMID:19030199

  15. Apoptosis gene polymorphisms, age, smoking and the risk of non-small cell lung cancer.

    PubMed

    Ter-Minassian, Monica; Zhai, Rihong; Asomaning, Kofi; Su, Li; Zhou, Wei; Liu, Geoffrey; Heist, Rebecca Suk; Lynch, Thomas J; Wain, John C; Lin, Xihong; De Vivo, Immaculata; Christiani, David C

    2008-11-01

    Apoptosis is important for targeting cancer cells for destruction. Various single-nucleotide polymorphisms (SNPs) in apoptotic genes have been associated with increased risks in lung cancer, particularly FAS -1377 G>A (rs2234767), FASLG -844 C>T (rs763110), IL1B +3954 C>T Phe105Phe (rs1143634) and BAT3 Ser625Pro (rs1052486). We studied the association of these SNPs with non-small cell lung cancer (NSCLC) in a large case-control study (N = 4263: 2644 cases and 1619 controls). No associations with NSCLC were observed in the main effects analysis for all four SNPs, adjusting for age, gender, smoking status, pack-years and years since smoking cessation. In subjects under age 60, for FASLG -844 C>T polymorphism, CT compared with the CC genotype, was significantly associated with increased risk of NSCLC, adjusted odds ratio (aOR) = 1.58 (1.22, 2.05), P = 0.0006 and TT aOR = 1.45 (1.01, 2.04), P = 0.04. In contrast, for those over age 60, the CT aOR = 0.91 (0.73, 1.13), P = 0.37 and TT aOR = 0.86 (0.64, 1.16), P = 0.32. The P-value for the age-genotype interaction was 0.004. For the IL1B +3954 C>T polymorphism, compared with the CC genotype, TT showed significant associations in former smokers and in men but tests of interaction were not significant (P(smoking) = 0.24, P(gender) = 0.17). No interactions were observed for FAS -1377 G>A and BAT3 Ser625Pro polymorphisms. Our findings indicate that age and smoking may modify the association of the FASLG -844 and IL1B + 3954 SNPs with the risk of NSCLC.

  16. Variation in IL10 and Other Genes Involved in the Immune Response and in Oxidation and Prostate Cancer Recurrence

    PubMed Central

    Dluzniewski, Paul J.; Wang, Ming-Hsi; Zheng, Siqun Lilly; De Marzo, Angelo M.; Drake, Charles G.; Fedor, Helen L.; Partin, Alan W.; Han, Misop; Fallin, M. Daniele; Xu, Jianfeng; Isaacs, William B.; Platz, Elizabeth A.

    2012-01-01

    Background To evaluate the association of variation in genes involved in immune response, including IL10, production and detoxification of reactive oxygen species, and repair of oxidative DNA damage with risk of recurrence after surgery for localized prostate cancer. Methods We conducted a nested case-control study of men who had a radical prostatectomy in 1993–2001. 484 recurrence cases and 484 controls were matched on age, race, and pathologic stage and grade. Germline DNA was extracted from paraffin-embedded unaffected lymph nodes. We genotyped candidate single nucleotide polymorphisms (SNPs) in IL10, CRP, GPX1, GSR, GSTP1, hOGG1, IL1B, IL1RN, IL6, IL8, MPO, NOS2, NOS3, SOD1, SOD2, SOD3, TLR4, and TNF and tagging SNPs in IL10, CRP, GSR, IL1RN, IL6, NOS2, and NOS3. We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI). Results The minor allele (A) in IL10 rs1800872, known to produce less interleukin-10, was associated with a higher risk of recurrence (OR=1.76, 95% CI: 1.00–3.10), and the minor allele (G) in rs1800896, known to produce more interleukin-10, was associated with a lower risk of recurrence (OR=0.66, 95% CI: 0.48–0.91). We also observed associations for candidate SNPs in CRP, GSTP1, and IL1B. A common IL10 haplotype and two common NOS2 haplotypes were associated with recurrence. Conclusion Variation in IL10, CRP, GSTP1, IL1B, and NOS2 was associated with recurrence independent of pathologic prognostic factors. Impact This study supports that genetic variation in immune response and oxidation influence recurrence risk and suggests genetic variation in these pathways may inform prognosis. PMID:22859398

  17. Interactions among genetic variants in apoptosis pathway genes, reflux symptoms, body mass index, and smoking indicate two distinct etiologic patterns of esophageal adenocarcinoma.

    PubMed

    Zhai, Rihong; Chen, Feng; Liu, Geoffrey; Su, Li; Kulke, Matthew H; Asomaning, Kofi; Lin, Xihong; Heist, Rebecca S; Nishioka, Norman S; Sheu, Chau-Chyun; Wain, John C; Christiani, David C

    2010-05-10

    Apoptosis pathway, gastroesophageal reflux symptoms (reflux), higher body mass index (BMI), and tobacco smoking have been individually associated with esophageal adenocarcinoma (EA) development. However, how multiple factors jointly affect EA risk remains unclear. In total, 305 patients with EA and 339 age- and sex-matched controls were studied. High-order interactions among reflux, BMI, smoking, and functional polymorphisms in five apoptotic genes (FAS, FASL, IL1B, TP53BP, and BAT3) were investigated by entropy-based multifactor dimensionality reduction (MDR), classification and regression tree (CART), and traditional logistic regression (LR) models. In LR analysis, reflux, BMI, and smoking were significantly associated with EA risk, with reflux as the strongest individual factor. No individual single nucleotide polymorphism was associated with EA susceptibility. However, there was a two-way interaction between IL1B + 3954C>T and reflux (P = .008). In both CART and MDR analyses, reflux was also the strongest individual factor for EA risk. In individuals with reflux symptoms, CART analysis indicated that strongest interaction was among variant genotypes of IL1B + 3954C>T and BAT3S625P, higher BMI, and smoking (odds ratio [OR], 5.76; 95% CI, 2.48 to 13.38), a finding independently found using MDR analysis. In contrast, for participants without reflux symptoms, the strongest interaction was found between higher BMI and smoking (OR, 3.27; 95% CI, 1.88 to 5.68), also echoed by entropy-based MDR analysis. Although a history of reflux is an important risk for EA, multifactor interactions also play important roles in EA risk. Gene-environment interaction patterns differ between patients with and without reflux symptoms.

  18. Interactions Among Genetic Variants in Apoptosis Pathway Genes, Reflux Symptoms, Body Mass Index, and Smoking Indicate Two Distinct Etiologic Patterns of Esophageal Adenocarcinoma

    PubMed Central

    Zhai, Rihong; Chen, Feng; Liu, Geoffrey; Su, Li; Kulke, Matthew H.; Asomaning, Kofi; Lin, Xihong; Heist, Rebecca S.; Nishioka, Norman S.; Sheu, Chau-Chyun; Wain, John C.; Christiani, David C.

    2010-01-01

    Purpose Apoptosis pathway, gastroesophageal reflux symptoms (reflux), higher body mass index (BMI), and tobacco smoking have been individually associated with esophageal adenocarcinoma (EA) development. However, how multiple factors jointly affect EA risk remains unclear. Patients and Methods In total, 305 patients with EA and 339 age- and sex-matched controls were studied. High-order interactions among reflux, BMI, smoking, and functional polymorphisms in five apoptotic genes (FAS, FASL, IL1B, TP53BP, and BAT3) were investigated by entropy-based multifactor dimensionality reduction (MDR), classification and regression tree (CART), and traditional logistic regression (LR) models. Results In LR analysis, reflux, BMI, and smoking were significantly associated with EA risk, with reflux as the strongest individual factor. No individual single nucleotide polymorphism was associated with EA susceptibility. However, there was a two-way interaction between IL1B + 3954C>T and reflux (P = .008). In both CART and MDR analyses, reflux was also the strongest individual factor for EA risk. In individuals with reflux symptoms, CART analysis indicated that strongest interaction was among variant genotypes of IL1B + 3954C>T and BAT3S625P, higher BMI, and smoking (odds ratio [OR], 5.76; 95% CI, 2.48 to13.38), a finding independently found using MDR analysis. In contrast, for participants without reflux symptoms, the strongest interaction was found between higher BMI and smoking (OR, 3.27; 95% CI, 1.88 to 5.68), also echoed by entropy-based MDR analysis. Conclusion Although a history of reflux is an important risk for EA, multifactor interactions also play important roles in EA risk. Gene-environment interaction patterns differ between patients with and without reflux symptoms. PMID:20385987

  19. Interleukin-1 Gene Cluster Polymorphisms and Their Association with Coronary Artery Disease: Separate Evidences from the Largest Case-Control Study amongst North Indians and an Updated Meta-Analysis

    PubMed Central

    Sinha, Nakul; Kumar, Sudeep; Sharma, Ajay Kumar; Agrawal, Suraksha

    2016-01-01

    Several researchers have reported significant association of numerous single nucleotide polymorphisms (SNPs) residing in the interleukin-1 (IL-1) gene cluster with coronary artery disease (CAD). However, their association status amongst North Indian ancestry (NIA) have never been systematically assessed. Despite a published meta-analysis on this subject, their association status worldwide as well as amongst different major ancestral subgroups still remains unclear. We therefore decided to prospectively test the association of 11 IL-1 gene cluster SNPs with CAD, vide a case-control study amongst a cohort of NIA and attempted to validate our results with the help of an updated meta-analysis of all relevant published association studies. Included studies were segregated into ancestral subgroups and association statuses for each subgroup were determined. A total of 323 cases and 400 healthy, age and sex matched controls belonging to NIA were prospectively enrolled and subsequently genotyped for 11 selected IL-1 gene cluster SNPs. Although results for none of the evaluated IL-1 gene cluster SNPs reached the adjusted level of significance (p<0.0045), clear trends of association were seen for IL1B -511 C>T and IL1RN 86bp VNTR in several of the constructed genetic models (p range = 0.01–0.044 and 0.005–0.034 respectively). The presence of >1, ‘T’ (minor) allele of IL1B -511 C>T in a genotype seemed to provide protection against CAD (OR = 0.62, p = 0.044), while the presence of >1, ‘C’ (major) allele seemed to increase the risk of CAD (OR = 1.36, p = 0.041). The minor allele (allele 2) of IL1RN 86bp VNTR and its homozygous genotype (2/2 genotype) also seemed to carry an increased risk for CAD (OR = 1.62, p = 0.005 and OR = 2.25, p = 0.031 respectively). On the other hand, several haplotype combinations constructed out of IL1B and IL1RN gene variants clearly showed statistically significant associations with CAD (p<0.0045). Our meta-analysis was conducted for 8

  20. Interleukin-1 Gene Cluster Polymorphisms and Their Association with Coronary Artery Disease: Separate Evidences from the Largest Case-Control Study amongst North Indians and an Updated Meta-Analysis.

    PubMed

    Rai, Himanshu; Sinha, Nakul; Kumar, Sudeep; Sharma, Ajay Kumar; Agrawal, Suraksha

    2016-01-01

    Several researchers have reported significant association of numerous single nucleotide polymorphisms (SNPs) residing in the interleukin-1 (IL-1) gene cluster with coronary artery disease (CAD). However, their association status amongst North Indian ancestry (NIA) have never been systematically assessed. Despite a published meta-analysis on this subject, their association status worldwide as well as amongst different major ancestral subgroups still remains unclear. We therefore decided to prospectively test the association of 11 IL-1 gene cluster SNPs with CAD, vide a case-control study amongst a cohort of NIA and attempted to validate our results with the help of an updated meta-analysis of all relevant published association studies. Included studies were segregated into ancestral subgroups and association statuses for each subgroup were determined. A total of 323 cases and 400 healthy, age and sex matched controls belonging to NIA were prospectively enrolled and subsequently genotyped for 11 selected IL-1 gene cluster SNPs. Although results for none of the evaluated IL-1 gene cluster SNPs reached the adjusted level of significance (p<0.0045), clear trends of association were seen for IL1B -511 C>T and IL1RN 86bp VNTR in several of the constructed genetic models (p range = 0.01-0.044 and 0.005-0.034 respectively). The presence of >1, 'T' (minor) allele of IL1B -511 C>T in a genotype seemed to provide protection against CAD (OR = 0.62, p = 0.044), while the presence of >1, 'C' (major) allele seemed to increase the risk of CAD (OR = 1.36, p = 0.041). The minor allele (allele 2) of IL1RN 86bp VNTR and its homozygous genotype (2/2 genotype) also seemed to carry an increased risk for CAD (OR = 1.62, p = 0.005 and OR = 2.25, p = 0.031 respectively). On the other hand, several haplotype combinations constructed out of IL1B and IL1RN gene variants clearly showed statistically significant associations with CAD (p<0.0045). Our meta-analysis was conducted for 8 previously

  1. Differentiation between Acute Skin Rejection in Allotransplantation and T-Cell Mediated Skin Inflammation Based on Gene Expression Analysis

    PubMed Central

    Wolfram, Dolores; Morandi, Evi M.; Eberhart, Nadine; Hautz, Theresa; Hackl, Hubert; Zelger, Bettina; Riede, Gregor; Wachter, Tanja; Dubrac, Sandrine; Ploner, Christian; Pierer, Gerhard; Schneeberger, Stefan

    2015-01-01

    Advances in microsurgical techniques and immunosuppressive medication have rendered transplantation of vascularized composite allografts possible, when autologous tissue is neither available nor sufficient for reconstruction. However, skin rejection and side effects of long-term immunosuppression still remain a major hurdle for wide adoption of this excellent reconstructive technique. Histopathologic changes during acute skin rejection in vascular composite allotransplantation often mimic inflammatory skin disorders and are hard to distinguish. Hence, the identification of diagnostic and therapeutic markers specific for skin rejection is of particular clinical need. Here we present novel markers allowing for early differentiation between rejection in hind limb allotransplantation and contact hypersensitivity. Assessment of Ccl7, Il18, and Il1b expression is most indicative of distinguishing skin rejection from skin inflammatory disorders. Gene expression levels varied significantly across skin types and regions, indicating localization specific mechanism of leukocyte migration and infiltration. Expression of Il12b, Il17a, and Il1b gene expression levels differed significantly between rejection and inflammation, independent of the skin type. In synopsis of the RNA expression profile and previously assessed protein expression, the Il1 family appears as a promising option for accurate skin rejection diagnosis and, as a following step, for development of novel rejection treatments. PMID:25756043

  2. Interleukin (IL)1beta, IL-1alpha, and IL-1 receptor antagonist gene polymorphisms in patients with temporal lobe epilepsy.

    PubMed

    Kanemoto, K; Kawasaki, J; Miyamoto, T; Obayashi, H; Nishimura, M

    2000-05-01

    Proinflammatory cytokines, including interleukin (IL)-1beta, are known to modulate effects of neurotoxic neurotransmitters discharged during excitation or inflammation in the central nervous system (CNS). They also regulate development of glial scars at sites of CNS injury. To elucidate a genetic predisposition of temporal lobe epilepsy with hippocampal sclerosis (TLE-HS+), we studied polymorphisms in the IL-1beta, IL-1alpha, and IL-1 receptor antagonist (IL-1RA) genes in 50 patients with TLE-HS+ and in 112 controls. Fifty-three patients who had TLE without HS were also examined (TLE-HS-) as disease controls. The distribution of the biallelic polymorphism in the promoter region at position -511 of the IL-1beta gene (IL-1B-511) was significantly different both between TLE-HS+ patients and controls and between TLE-HS+ and TLE-HS- patients. The differences were due to overrepresentation of the homozygotes for IL-1B-511*2, which is suggested to be a high producer of IL-1beta, in TLE-HS+ patients compared with both controls and TLE-HS- patients. In contrast, there was no difference between TLE-HS- patients and controls. Our data suggest that, in the homozygotes for IL-IB-511*2, minor events in development such as febrile convulsions could set up a cascade leading to HS.

  3. Effects of Thyme Extract Oils (from Thymus vulgaris, Thymus zygis, and Thymus hyemalis) on Cytokine Production and Gene Expression of oxLDL-Stimulated THP-1-Macrophages.

    PubMed

    Ocaña, A; Reglero, G

    2012-01-01

    Properties of thyme extracts from three different species (Thymus vulgaris, Thymus zygis, and Thymus hyemalis) were examined. Two oil fractions from each species were obtained by CO(2) supercritical fluid extraction. Main compounds presented in the supercritical extracts of the three thyme varieties were 1,8 cineole, thymol, camphor, borneol, and carvacrol. As a cellular model of inflammation/atherogenesis, we use human macrophages derived from THP-1 monocytes and activated by oxidized LDLs. These cells were incubated with the thyme fraction oils, and the productions and gene expressions of the inflammatory mediators TNF-α, IL-1B, IL-6, and IL-10 were determined. Thyme extracts significantly reduced production and gene expression of the proinflammatory mediators TNF-α, IL-1B, and IL-6 and highly increased these parameters on the anti-inflammatory IL-10 cytokine. Changes on production and gene expressions were dose dependent and according to the thyme content of each species. Taken together, these results may suggest that thyme extracts could have anti-inflammatory effects.

  4. Effects of Thyme Extract Oils (from Thymus vulgaris, Thymus zygis, and Thymus hyemalis) on Cytokine Production and Gene Expression of oxLDL-Stimulated THP-1-Macrophages

    PubMed Central

    Ocaña, A.; Reglero, G.

    2012-01-01

    Properties of thyme extracts from three different species (Thymus vulgaris, Thymus zygis, and Thymus hyemalis) were examined. Two oil fractions from each species were obtained by CO2 supercritical fluid extraction. Main compounds presented in the supercritical extracts of the three thyme varieties were 1,8 cineole, thymol, camphor, borneol, and carvacrol. As a cellular model of inflammation/atherogenesis, we use human macrophages derived from THP-1 monocytes and activated by oxidized LDLs. These cells were incubated with the thyme fraction oils, and the productions and gene expressions of the inflammatory mediators TNF-α, IL-1B, IL-6, and IL-10 were determined. Thyme extracts significantly reduced production and gene expression of the proinflammatory mediators TNF-α, IL-1B, and IL-6 and highly increased these parameters on the anti-inflammatory IL-10 cytokine. Changes on production and gene expressions were dose dependent and according to the thyme content of each species. Taken together, these results may suggest that thyme extracts could have anti-inflammatory effects. PMID:22577523

  5. Gene expression in blood of children and adolescents: Mediation between childhood maltreatment and major depressive disorder.

    PubMed

    Spindola, Leticia Maria; Pan, Pedro Mario; Moretti, Patricia Natalia; Ota, Vanessa Kiyomi; Santoro, Marcos Leite; Cogo-Moreira, Hugo; Gadelha, Ary; Salum, Giovanni; Manfro, Gisele Gus; Mari, Jair Jesus; Brentani, Helena; Grassi-Oliveira, Rodrigo; Brietzke, Elisa; Miguel, Euripedes Constantino; Rohde, Luis Augusto; Sato, João Ricardo; Bressan, Rodrigo Affonseca; Belangero, Sintia Iole

    2017-09-01

    Investigating major depressive disorder (MDD) in childhood and adolescence can help reveal the relative contributions of genetic and environmental factors to MDD, since early stages of disease have less influence of illness exposure. Thus, we investigated the mRNA expression of 12 genes related to the hypothalamic-pituitary-adrenal (HPA) axis, inflammation, neurodevelopment and neurotransmission in the blood of children and adolescents with MDD and tested whether a history of childhood maltreatment (CM) affects MDD through gene expression. Whole-blood mRNA levels of 12 genes were compared among 20 children and adolescents with MDD diagnosis (MDD group), 49 participants without MDD diagnosis but with high levels of depressive symptoms (DS group), and 61 healthy controls (HC group). The differentially expressed genes were inserted in a mediation model in which CM, MDD, and gene expression were, respectively, the independent variable, outcome, and intermediary variable. NR3C1, TNF, TNFR1 and IL1B were expressed at significantly lower levels in the MDD group than in the other groups. CM history did not exert a significant direct effect on MDD. However, an indirect effect of the aggregate expression of the 4 genes mediated the relationship between CM and MDD. In the largest study investigating gene expression in children with MDD, we demonstrated that NR3C1, TNF, TNFR1 and IL1B expression levels are related to MDD and conjunctly mediate the effect of CM history on the risk of developing MDD. This supports a role of glucocorticoids and inflammation as potential effectors of environmental stress in MDD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Polymorphism of the E-cadherin gene CDH1 is associated with susceptibility to vitiligo.

    PubMed

    Tarlé, Roberto Gomes; Silva de Castro, Caio Cesar; do Nascimento, Liliane Machado; Mira, Marcelo Távora

    2015-04-01

    Vitiligo is a depigmenting disorder characterized by loss of functional melanocytes from the epidermis. Experimental data suggest that defective melanocyte adhesion may underlie the pathogenesis of the disease. In particular, association between vitiligo and genetic variants of the DDR1 gene involved in melanocyte adhesion has been recently published. A subsequent, independent study revealed lower expression of DDR1 in vitiligo lesions. Here, we expand this investigation by testing for association between vitiligo and polymorphisms of CDH1, IL1B and NOV (formerly CCN3), genes belonging to the DDR1 adhesion pathway, in two population samples of distinct design. Our results reveal that alleles of marker rs10431924 of the CDH1 gene are associated with vitiligo, especially in the presence of autoimmune comorbidities.

  7. Expression of energy metabolism related genes in the gastric tissue of obese individuals with non-alcoholic fatty liver disease.

    PubMed

    Mehta, Rohini; Birerdinc, Aybike; Wang, Lei; Younoszai, Zahra; Moazzez, Amir; Elariny, Hazem; Goodman, Zachary; Chandhoke, Vikas; Baranova, Ancha; Younossi, Zobair M

    2014-04-09

    Stomach is an integral part of the energy balance regulating circuit. Studies exploring the effects of cross-system changes in the energy homeostasis in stomach tissue are scarce. The proximity of the stomach to liver--the most common secondary target affected by obesity--suggests that these two organs are exposed to each other's local secretion. Therefore, we aimed at expression profiling of energy metabolism associated genes in the gastric tissue of obese non-alcoholic fatty liver disease (NAFLD) patients. A total of 24 patients with histologically-proven NAFLD were included. In the gastric tissue, gene expression profiling of 84 energy metabolism associated genes was carried out. The accumulation of the fat in the liver parenchyma is accompanied by downregulation of genes encoding for carboxypeptidase E (CPE) and Interleukin 1B (IL1B) in the gastric mucosa of same patient. In patients with high grade hepatic steatosis, Interleukin 1 beta encoding gene with anorexigenic function, IL1B was downregulated. The levels expression of 21 genes, including ADRA2B, CNR1 and LEP were significantly altered in the gastric tissue of NAFLD patients with hepatic inflammation. There were also indications of an increase in the opioid signaling within gastric mucosa that may results in a shift to proinflammatory environment within this organ and contribute to systemic inflammation and the pathogenic processes in hepatic parenchyma. We have shown differential expression of energy metabolism associated genes in the gastric tissue of obese NAFLD patients. Importantly, these gene expression profiles are associated with changes in the hepatic parenchyma as reflected in increased scores for hepatic steatosis, inflammation, fibrosis and NASH. This study suggests the complex interplay of multiple organs in the pathogenesis of obesity-related complications such as NAFLD and provides further evidence supporting an important role for gastric tissue in promoting obesity-related complications.

  8. Expression of energy metabolism related genes in the gastric tissue of obese individuals with non-alcoholic fatty liver disease

    PubMed Central

    2014-01-01

    Background Stomach is an integral part of the energy balance regulating circuit. Studies exploring the effects of cross-system changes in the energy homeostasis in stomach tissue are scarce. The proximity of the stomach to liver - the most common secondary target affected by obesity – suggests that these two organs are exposed to each other’s local secretion. Therefore, we aimed at expression profiling of energy metabolism associated genes in the gastric tissue of obese non-alcoholic fatty liver disease (NAFLD) patients. Methods A total of 24 patients with histologically-proven NAFLD were included. In the gastric tissue, gene expression profiling of 84 energy metabolism associated genes was carried out. Results The accumulation of the fat in the liver parenchyma is accompanied by downregulation of genes encoding for carboxypeptidase E (CPE) and Interleukin 1B (IL1B) in the gastric mucosa of same patient. In patients with high grade hepatic steatosis, Interleukin 1 beta encoding gene with anorexigenic function, IL1B was downregulated. The levels expression of 21 genes, including ADRA2B, CNR1 and LEP were significantly altered in the gastric tissue of NAFLD patients with hepatic inflammation. There were also indications of an increase in the opioid signaling within gastric mucosa that may results in a shift to proinflammatory environment within this organ and contribute to systemic inflammation and the pathogenic processes in hepatic parenchyma. Conclusions We have shown differential expression of energy metabolism associated genes in the gastric tissue of obese NAFLD patients. Importantly, these gene expression profiles are associated with changes in the hepatic parenchyma as reflected in increased scores for hepatic steatosis, inflammation, fibrosis and NASH. This study suggests the complex interplay of multiple organs in the pathogenesis of obesity-related complications such as NAFLD and provides further evidence supporting an important role for gastric tissue

  9. Selection of Reference Genes for Gene Expression Studies related to lung injury in a preterm lamb model

    PubMed Central

    Pereira-Fantini, Prue M.; Rajapaksa, Anushi E.; Oakley, Regina; Tingay, David G.

    2016-01-01

    Preterm newborns often require invasive support, however even brief periods of supported ventilation applied inappropriately to the lung can cause injury. Real-time quantitative reverse transcriptase-PCR (qPCR) has been extensively employed in studies of ventilation-induced lung injury with the reference gene 18S ribosomal RNA (18S RNA) most commonly employed as the internal control reference gene. Whilst the results of these studies depend on the stability of the reference gene employed, the use of 18S RNA has not been validated. In this study the expression profile of five candidate reference genes (18S RNA, ACTB, GAPDH, TOP1 and RPS29) in two geographical locations, was evaluated by dedicated algorithms, including geNorm, Normfinder, Bestkeeper and ΔCt method and the overall stability of these candidate genes determined (RefFinder). Secondary studies examined the influence of reference gene choice on the relative expression of two well-validated lung injury markers; EGR1 and IL1B. In the setting of the preterm lamb model of lung injury, RPS29 reference gene expression was influenced by tissue location; however we determined that individual ventilation strategies influence reference gene stability. Whilst 18S RNA is the most commonly employed reference gene in preterm lamb lung studies, our results suggest that GAPDH is a more suitable candidate. PMID:27210246

  10. Strains of the East Asian (W/Beijing) Lineage of Mycobacterium tuberculosis Are DosS/DosT-DosR Two-Component Regulatory System Natural Mutants▿ †

    PubMed Central

    Fallow, Ashley; Domenech, Pilar; Reed, Michael B.

    2010-01-01

    As part of our ongoing efforts to uncover the phenotypic consequences of genetic variability among clinical Mycobacterium tuberculosis isolates, we previously reported that isolates of the “East Asian” or “W/Beijing” lineage constitutively overexpress the coordinately regulated transcriptional program known as the DosR regulon under standard in vitro conditions. This phenotype distinguishes the W/Beijing lineage from all other M. tuberculosis lineages, which normally induce expression of this regulon only once exposed to low oxygen or nitric oxide, both of which result in inhibition of bacterial respiration and replication. Transcription of the DosR regulon is controlled through a two-component regulatory system comprising the transcription factor DosR and two possible cognate histidine sensor kinases, DosS and DosT. Through sequence analysis of a carefully selected set of isolates representing each of the major M. tuberculosis lineages, we describe herein a naturally occurring frameshift mutation in the gene encoding the DosT sensor kinase for isolates of the most recently evolved W/Beijing sublineages. Intriguingly, the occurrence of the frameshift mutation correlates precisely with the appearance of the constitutive DosR regulon phenotype displayed by the same “modern” W/Beijing strains. However, complementation studies have revealed that the mutation in dosT alone is not directly responsible for the constitutive DosR regulon phenotype. Our data serve to highlight the evolutionary pressure that exists among distinct M. tuberculosis lineages to maintain tight control over DosR regulon expression. PMID:20154135

  11. Variants in the inflammatory IL6 and MPO genes modulate stroke susceptibility through main effects and gene–gene interactions

    PubMed Central

    Manso, Helena; Krug, Tiago; Sobral, João; Albergaria, Isabel; Gaspar, Gisela; Ferro, José M; Oliveira, Sofia A; Vicente, Astrid M

    2011-01-01

    There is substantial evidence that inflammation within the central nervous system contributes to stroke risk and recovery. Inflammatory conditions increase stroke risk, and the inflammatory response is of major importance in recovery and healing processes after stroke. We investigated the role of inflammatory genes IL1B, IL6, MPO, and TNF in stroke susceptibility and recovery in a population sample of 672 patients and 530 controls, adjusting for demographic, clinical and lifestyle risk factors, and stroke severity parameters. We also considered the likely complexity of inflammatory mechanisms in stroke, by assessing the combined effects of multiple genes. Two interleukin 6 (IL6) and one myeloperoxidase (MPO) single-nucleotide polymorphisms were significantly associated with stroke risk (0.022gene variants of low to moderate effect in stroke risk. An epistatic interaction between the IL6 and MPO genes was also identified in association with stroke susceptibility (P=0.031 after 1,000 permutations). In a subset of 546 patients, one IL6 haplotype was associated with stroke outcome at 3 months (correctedP=0.024), an intriguing finding warranting further validation. Our findings support the association of the IL6 gene and present novel evidence for the involvement of MPO in stroke susceptibility, suggesting a modulation of stroke risk by main gene effects, clinical and lifestyle factors, and gene–gene interactions. PMID:21407237

  12. DOS cones along atomic chains

    NASA Astrophysics Data System (ADS)

    Kwapiński, Tomasz

    2017-03-01

    The electron transport properties of a linear atomic chain are studied theoretically within the tight-binding Hamiltonian and the Green’s function method. Variations of the local density of states (DOS) along the chain are investigated. They are crucial in scanning tunnelling experiments and give important insight into the electron transport mechanism and charge distribution inside chains. It is found that depending on the chain parity the local DOS at the Fermi level can form cone-like structures (DOS cones) along the chain. The general condition for the local DOS oscillations is obtained and the linear behaviour of the local density function is confirmed analytically. DOS cones are characterized by a linear decay towards the chain which is in contrast to the propagation properties of charge density waves, end states and Friedel oscillations in one-dimensional systems. We find that DOS cones can appear due to non-resonant electron transport, the spin–orbit scattering or for chains fabricated on a substrate with localized electrons. It is also shown that for imperfect chains (e.g. with a reduced coupling strength between two neighboring sites) a diamond-like structure of the local DOS along the chain appears.

  13. PCB related effects thresholds as derived through gene transcript profiles in locally contaminated ringed seals (Pusa hispida).

    PubMed

    Brown, Tanya M; Ross, Peter S; Reimer, Ken J; Veldhoen, Nik; Dangerfield, Neil J; Fisk, Aaron T; Helbing, Caren C

    2014-11-04

    Causal evidence linking toxic injury to polychlorinated biphenyl (PCB) exposure is typically confounded by the complexity of real-world contaminant mixtures to which aquatic wildlife are exposed. A local PCB "hotspot" on the Labrador coast provided a rare opportunity to evaluate the effects of PCBs on the health of a marine mammal as this chemical dominated their persistent organic pollutant (POP) burdens. The release of approximately 260 kg of PCBs by a military radar facility over a 30 year period (1970-2000) contaminated some local marine biota, including the ringed seal (Pusa hispida). The abundance profiles of eight health-related gene transcripts were evaluated in liver samples collected from 43 ringed seals in the affected area. The mRNA transcript levels of five gene targets, including aryl hydrocarbon receptor (Ahr), interleukin-1 β (Il1b), estrogen receptor α (Esr1), insulin like growth factor receptor 1 (Igf1), and glucocorticoid receptor α (Nr3c1) correlated with increasing levels of blubber PCBs. PCB threshold values calculated using best-fit hockey-stick regression models for these five genes averaged 1,680±206 ng/g lw, with the lowest, most conservative, being 1,370 ng/g lw for Il1b. Approximately 14% of the seals in the region exceeded this threshold. The dominance of PCBs in the seals studied enabled an assessment of the effects of this chemical on gene transcripts involved in regulating the health of a highly mobile predator, something that is rarely possible in the world of complex mixtures.

  14. Apoptosis gene polymorphisms, age, smoking and the risk of non-small cell lung cancer

    PubMed Central

    Ter-Minassian, Monica; Zhai, Rihong; Asomaning, Kofi; Su, Li; Zhou, Wei; Liu, Geoffrey; Heist, Rebecca Suk; Lynch, Thomas J.; Wain, John C.; Lin, Xihong; DeVivo, Immaculata; Christiani, David C.

    2008-01-01

    Apoptosis is important for targeting cancer cells for destruction. Various single-nucleotide polymorphisms (SNPs) in apoptotic genes have been associated with increased risks in lung cancer, particularly FAS −1377 G>A (rs2234767), FASLG −844 C>T (rs763110), IL1B +3954 C>T Phe105Phe (rs1143634) and BAT3 Ser625Pro (rs1052486). We studied the association of these SNPs with non-small cell lung cancer (NSCLC) in a large case–control study (N = 4263: 2644 cases and 1619 controls). No associations with NSCLC were observed in the main effects analysis for all four SNPs, adjusting for age, gender, smoking status, pack-years and years since smoking cessation. In subjects under age 60, for FASLG −844 C>T polymorphism, CT compared with the CC genotype, was significantly associated with increased risk of NSCLC, adjusted odds ratio (aOR) = 1.58 (1.22, 2.05), P  = 0.0006 and TT aOR = 1.45 (1.01, 2.04), P = 0.04. In contrast, for those over age 60, the CT aOR = 0.91 (0.73, 1.13), P = 0.37 and TT aOR = 0.86 (0.64, 1.16), P = 0.32. The P-value for the age–genotype interaction was 0.004. For the IL1B +3954 C>T polymorphism, compared with the CC genotype, TT showed significant associations in former smokers and in men but tests of interaction were not significant (Psmoking = 0.24, Pgender = 0.17). No interactions were observed for FAS −1377 G>A and BAT3 Ser625Pro polymorphisms. Our findings indicate that age and smoking may modify the association of the FASLG −844 and IL1B  + 3954 SNPs with the risk of NSCLC. PMID:18757527

  15. Differential distribution of allelic variants in cytokine genes among African Americans and White Americans.

    PubMed

    Ness, Roberta B; Haggerty, Catherine L; Harger, Gail; Ferrell, Robert

    2004-12-01

    Racial disparities in health are largely unexplained. Because many diseases causing premature mortality among African Americans are mediated by the immune system, the authors explored the race-specific distribution of allelic variants in cytokine genes known to stimulate inflammation. The authors studied women seeking prenatal care and delivering singletons in uncomplicated first births at a US hospital in 1997-2001. A total of 179 African-American women and 396 White women were evaluated for functionally relevant allelic variants in cytokine genes. African-American women were significantly more likely to carry allelic variants known to up-regulate proinflammatory cytokines; odds ratios increased with allele dose. Odds ratios for African Americans versus Whites in genotypes up-regulating proinflammatory interleukin (IL) 1 (IL1A-4845G/G, IL1A-889T/T, IL1B-3957C/C, and IL1B-511A/A) ranged from 2.1 to 4.9. The proinflammatory cytokine interleukin-6 IL6-174 G/G genotype was 36.5 times (95% confidence interval (CI): 8.8, 151.9) more common among African Americans. Genotypes known to down-regulate the antiinflammatory interleukin-10 (IL10-819 T/T and IL10-1082 A/A) were elevated 3.5-fold (95% CI: 1.8, 6.6) and 2.8-fold (95% CI: 1.6, 4.9) in African Americans. Cytokine genotypes found to be more common in African-American women were consistently those that up-regulate inflammation.

  16. Genes

    MedlinePlus

    ... Search Search MedlinePlus GO GO About MedlinePlus Site Map FAQs Customer Support Health Topics Drugs & Supplements Videos & Tools Español You Are Here: Home → Medical Encyclopedia → Genes URL of this page: //medlineplus.gov/ency/article/ ...

  17. A study of the interleukin-1 gene cluster polymorphisms and inflammatory external root resorption in replanted permanent teeth.

    PubMed

    Bastos, J V; Côrtes, M I S; Silva, J F C; Goulart, E M A; Colosimo, E A; Gomez, R S; Dutra, W O

    2015-09-01

    To investigate whether single nucleotide polymorphisms (SNPs) within the interleukin-1 gene cluster (IL1) are associated with the occurrence and severity of inflammatory external root resorption (IERR) after replantation of avulsed permanent teeth. Indexes of IERR were radiographically assessed in 182 mature replanted permanent teeth from 146 patients at the onset of endodontic therapy. DNA was extracted from buccal mucosa cells and genotyped using TaqMan probes-based assays for the SNPs IL1A -889C/T (rs 180058), IL1B +3954C/T (rs1143634) and IL1RN +2018C/T (rs419598). Teeth were grouped into two categories: IERR absent to mild (indexes ≤ 4) and moderate to severe IERR (indexes > 4). Genetic variations in the IL1 gene cluster were tested for their effect on the occurrence and extension of IERR using the GEE model (generalized estimation equation). Patient's age at the moment of injury, timing of pulpectomy, extra-alveolar period and storage condition of the avulsed teeth was included as possible confounders. No association was found between SNPs IL1A -889C/T, IL1B +3954C/T (rs1143634) and IL1RN +2018C/T (rs419598) and IERR indexes. Timing of pulpectomy (OR 3.5 IC 95% 2.0-6.2 P < 0.001) and patient's age at the moment of trauma (OR 0.29 IC 95% 0.12-0.67 P = 0.004) significantly affected the risk of developing severe IERR. While timing of pulpectomy and patient's age at the moment of trauma were confirmed as important risk factors, SNPs within the IL1 gene cluster did not affect the susceptibility for IERR after replantation of permanent teeth. © 2014 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  18. Altered Gene Transcription in Human Cells Treated with Ludox® Silica Nanoparticles

    PubMed Central

    Fede, Caterina; Millino, Caterina; Pacchioni, Beniamina; Celegato, Barbara; Compagnin, Chiara; Martini, Paolo; Selvestrel, Francesco; Mancin, Fabrizio; Celotti, Lucia; Lanfranchi, Gerolamo; Mognato, Maddalena; Cagnin, Stefano

    2014-01-01

    Silica (SiO2) nanoparticles (NPs) have found extensive applications in industrial manufacturing, biomedical and biotechnological fields. Therefore, the increasing exposure to such ultrafine particles requires studies to characterize their potential cytotoxic effects in order to provide exhaustive information to assess the impact of nanomaterials on human health. The understanding of the biological processes involved in the development and maintenance of a variety of pathologies is improved by genome-wide approaches, and in this context, gene set analysis has emerged as a fundamental tool for the interpretation of the results. In this work we show how the use of a combination of gene-by-gene and gene set analyses can enhance the interpretation of results of in vitro treatment of A549 cells with Ludox® colloidal amorphous silica nanoparticles. By gene-by-gene and gene set analyses, we evidenced a specific cell response in relation to NPs size and elapsed time after treatment, with the smaller NPs (SM30) having higher impact on inflammatory and apoptosis processes than the bigger ones. Apoptotic process appeared to be activated by the up-regulation of the initiator genes TNFa and IL1b and by ATM. Moreover, our analyses evidenced that cell treatment with Ludox® silica nanoparticles activated the matrix metalloproteinase genes MMP1, MMP10 and MMP9. The information derived from this study can be informative about the cytotoxicity of Ludox® and other similar colloidal amorphous silica NPs prepared by solution processes. PMID:25170680

  19. Effect of gene environment interactions on lung function and cardiovascular disease in COPD

    PubMed Central

    Hackett, Tillie-Louise; Stefanowicz, Dorota; Aminuddin, Farzian; Sin, Don D; Connett, John E; Anthonisen, Nicholas R; Paré, Peter D; Sandford, Andrew J

    2011-01-01

    Background: The objective of this study was to determine if gene-environment interactions between cigarette smoking and interleukin-6 (IL6), interferon-γ (IFNG), interleukin-1β (IL1B), or interleukin-1 receptor antagonist (IL1RN) single nucleotide polymorphisms are associated with lung function decline and cardiovascular disease in chronic obstructive pulmonary disease (COPD). Methods: Single nucleotide polymorphisms (SNPs) in IL6, IFNG, IL1B, and IL1RN were genotyped in the Lung Health Study and correlated with rate of decline of forced expiratory volume in 1 second (FEV1) over 5 years, baseline FEV1, serum protein levels, cardiovascular disease, and interactions with smoking. Results: The IL6 rs2069825 single nucleotide polymorphism was associated with the rate of decline of prebronchodilator FEV1 (P = 0.049), and was found to have a significant interaction (P = 0.004) with mean number of cigarettes smoked per day. There was also a significant interaction of IFNG rs2069727 with smoking on prebronchodilator (P = 0.008) and postbronchodilator (P =0.01) FEV1. The IL6 polymorphism was also associated with cardiovascular disease in heterozygous individuals (P = 0.044), and was found to have a significant interaction with smoking (P = 0.024). None of the genetic variants were associated with their respective serum protein levels. Conclusion: The results suggest interactions of IL6 rs2069825 and IFNG rs2069727 single nucleotide polymorphisms with cigarette smoking on measures of lung function. The IL6 rs2069825 single nucleotide polymorphism also interacted with smoking to affect the risk of cardiovascular disease in COPD patients. PMID:21814463

  20. Agaricus bisporus powder improved cutaneous mucosal and serum immune parameters and up-regulated intestinal cytokines gene expression in common carp (Cyprinus carpio) fingerlings.

    PubMed

    Khodadadian Zou, Hassan; Hoseinifar, Seyed Hossein; Kolangi Miandare, Hamed; Hajimoradloo, Abdolmajid

    2016-11-01

    The aim of the present study was to investigate immunomodulatory effects of Agaricus bisporus, white bottom mushroom powder (WBMP) on common carp (Cyprinus carpio) fingerlings. Carps were fed on different levels of WBMP (0, 0.5, 1 and 2%) for 8 weeks and at the end of feeding trial, skin mucus immune parameters (total Ig, lysozyme and protease activity), cytokines gene expression (TNF-alpha, IL1b, IL8) in intestine as well as serum non-specific immune parameters (total Ig, lysozyme and ACH50) were measured. The results showed significant dose dependent increase of skin mucus immune parameters in carps fed WBMP (P < 0.05). While, no significant difference was observed between 0.5% WBMP and control group (P > 0.05). In case of serum non-specific immune parameters, except lysozyme activity, other parameters (Ig total and ACH50) were significantly affected by dietary inclusion of WBMP (P < 0.05). Also, evaluation of cytokines gene expression in the intestine of carps revealed remarkable up-regulation of TNF-alpha in fish fed 2% WBMP supplemented diet compared other treatment (P < 0.05). Likewise, IL1b gene expression was significantly increased in 1 and 2% WBMP treatments compared to the 0.5% WBMP and control groups (P < 0.05). IL8 gene expression was not affected by inclusion of WBMP in carp diet (P > 0.05). Furthermore, feeding on WBMP supplemented diet significantly improved growth performance (P < 0.05). These results indicated that WBMP can be considered as a promising immunostimulants in early stage of common carp culture.

  1. A DOS Primer for Librarians.

    ERIC Educational Resources Information Center

    Beecher, Henry

    1989-01-01

    Presents a basic orientation to the functions and capabilities of disk operating systems (DOS), aimed at the nontechnically oriented user of IBM personal computers and compatible microcomputers. Areas discussed include booting up, the use of floppy and hard disks, file storage and manipulation, and directories. Further readings are provided. (CLB)

  2. A DOS Primer for Librarians.

    ERIC Educational Resources Information Center

    Beecher, Henry

    1989-01-01

    Presents a basic orientation to the functions and capabilities of disk operating systems (DOS), aimed at the nontechnically oriented user of IBM personal computers and compatible microcomputers. Areas discussed include booting up, the use of floppy and hard disks, file storage and manipulation, and directories. Further readings are provided. (CLB)

  3. Different Roles of DosS and DosT in the Hypoxic Adaptation of Mycobacteria▿

    PubMed Central

    Kim, Min-Ju; Park, Kwang-Jin; Ko, In-Jeong; Kim, Young Min; Oh, Jeong-Il

    2010-01-01

    The DosS (DevS) and DosT histidine kinases form a two-component system together with the DosR (DevR) response regulator in Mycobacterium tuberculosis. DosS and DosT, which have high sequence similarity to each other over the length of their amino acid sequences, contain two GAF domains (GAF-A and GAF-B) in their N-terminal sensory domains. Complementation tests in conjunction with phylogenetic analysis showed that DevS of Mycobacterium smegmatis is more closely related to DosT than DosS. We also demonstrated in vivo that DosS and DosT of M. tuberculosis play a differential role in hypoxic adaptation. DosT responds to a decrease in oxygen tension more sensitively and strongly than DosS, which might be attributable to their different autooxidation rates. The different responsiveness of DosS and DosT to hypoxia is due to the difference in their GAF-A domains accommodating the hemes. Multiple alignment analysis of the GAF-A domains of mycobacterial DosS (DosT) homologs and subsequent site-directed mutagenesis revealed that just one substitution of E87, D90, H97, L118, or T169 of DosS with the corresponding residue of DosT is sufficient to convert DosS to DosT with regard to the responsiveness to changes in oxygen tension. PMID:20675480

  4. Interleukin (IL)-1 gene polymorphisms: relevance of disease severity associated alleles with IL-1beta and IL-1ra production in multiple sclerosis.

    PubMed Central

    Schrijver, Hans M; van As, Jaco; Crusius, J Bart A; Dijkstra, Christien D; Uitdehaag, Bernard M J

    2003-01-01

    BACKGROUND: Multiple sclerosis (MS) is an autoimmune disorder, with a considerable genetic influence on susceptibility and disease course. Cytokines play an important role in MS pathophysiology, and genes encoding various cytokines are logical candidates to assess possible associations with MS susceptibility and disease course. We previously reported an association of a combination of polymorphisms in the interleukin (IL)-1B and IL-1 receptor antagonist (IL-1RN) genes (i.e. IL-1RN allele 2+/IL-1B(+3959)allele 2-) with disease severity in MS. Extending this observation, we investigated whether IL-1beta and IL-1ra production differed depending on carriership of this gene combination. METHODS: Twenty MS patients and 20 controls were selected based upon carriership of the specific combination. In whole blood, in vitro IL-1beta and IL-1ra production was determined by enzyme-linked immunosorbent-assay after 6 and 24 h of stimulation with lipopolysaccharide. RESULTS: Carriers of the specific combination produced more IL-1ra, especially in MS patients, although not significantly. IL-1ra production was significantly higher in individuals homozygous for IL-1RN allele 2. In patients, Il-1ra production was higher and IL-1beta production lower compared with controls. In primary progressive patients, the IL-1beta /IL-1ra ratio was significantly lower than in relapsing-remitting patients. CONCLUSION: Our results suggest higher in vitro IL-1ra production in carriers of IL-1RN allele 2, with an indication of an allelic dose-effect relationship. PMID:12775358

  5. Laparotomy in Mice Induces Blood Cell Expression of Inflammatory and Stress Genes

    PubMed Central

    Isoda, Fumiko; Mobbs, Charles

    2015-01-01

    Surgical trauma induces immune and stress responses although its effects on postsurgical inflammatory and stress gene expression remain poorly characterized. This study sought to improve current scientific knowledge by investigating the effects of laparotomy on mouse blood cell inflammatory and stress gene expression. Three-month-old male C57BL/6J mice were subjected to 2% isoflurane or 2% isoflurane with laparotomy and sacrificed 4 h postintervention. Blood was collected and blood cell expression of 158 genes central to inflammatory and stress responses was assayed using quantitative polymerase chain reaction arrays. Mice subjected to isoflurane with laparotomy, compared with mice receiving isoflurane alone, had >2-fold upregulation of genes in inflammation (Osm, IL1rn, IL1b, and Csf1), oxidative stress (Hmox1), heat shock (Hspa1b), growth arrest (Cdkn1a), and DNA repair (Ugt1a2). These genes demonstrated similar expression patterns by Pearson correlation and cluster analysis. Thus, laparotomy induces coordinated, postsurgical blood cell expression of unique inflammatory and stress genes whose roles in influencing surgical outcomes need further investigation. PMID:25406893

  6. TNF-A AND IL-1B ARE NOT ESSENTIAL TO THE INFLAMMATORY RESPONSE IN LPS INDUCED AIRWAY DISEASE. (R826711C002)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  7. COMPARISON OF METAL-INDUCED ALVEOLAR EPITHELIAL INJURY AND CHEMOKINE PRODUCTION DURING PRE,-SIMULTANEOUS, OR CONTINUED EXPOSURE TO TNFA, IL-1B, AND IFNY

    EPA Science Inventory


    Epidemiological studies have linked air pollution exposure to adverse respiratory health effects, especially in individuals with inflammatory airways disease. Symptomatic asthmatics appear to be at greatest risk. We previously demonstrated that exposure of rats to particulate...

  8. COMPARISON OF METAL-INDUCED ALVEOLAR EPITHELIAL INJURY AND CHEMOKINE PRODUCTION DURING PRE,-SIMULTANEOUS, OR CONTINUED EXPOSURE TO TNFA, IL-1B, AND IFNY

    EPA Science Inventory


    Epidemiological studies have linked air pollution exposure to adverse respiratory health effects, especially in individuals with inflammatory airways disease. Symptomatic asthmatics appear to be at greatest risk. We previously demonstrated that exposure of rats to particulate...

  9. Bacterial LPS differently modulates inflammasome gene expression and IL-1β secretion in trophoblast cells, decidual stromal cells, and decidual endothelial cells.

    PubMed

    Pontillo, A; Girardelli, M; Agostinis, C; Masat, E; Bulla, R; Crovella, S

    2013-05-01

    Three Nod-like receptors (NLR family, pyrin domain containing 1/NLRP1, NLR family, pyrin domain containing 3/NLRP3, NLR family, CARD domain containing 4/NLRC4) and the adaptor molecule PYD and CARD domain containing protein/PYCARD are involved in the assembling of multiprotein complexes known as inflammasomes, leading to caspase 1 activation and consequent interleukin (IL)-1β secretion. Considering that inflammasomes are involved in sensing pathogens and in triggering inflammatory and immune response, we hypothesized that they could also act in the placenta as an efficient innate mechanism during pregnancy infections. For this reason the activation of inflammasome was tested in 3 human placental cell populations in the presence of a common gram-negative compound (lipopolysaccharide [LPS]). The transcription of NLRP1, NLRP3, NLRC4, PYCARD, CASP1, and IL1B genes and the secretion of IL-1β were evaluated in human first trimester cytotrophoblasts (CTBs), decidual stromal cells (DSCs), and endothelial cells (DECs) stimulated with LPS. In CTBs and DSCs, LPS induced an augmented expression of CASP1 and IL1B and the specific upregulation of NLRP3 within the 3 NLRs tested. Moreover, LPS induced secretion of IL-1β from CTBs and DSCs. These results suggest the involvement of NLRP3 inflammasome in the placental innate response. The LPS did not affect inflammasome gene transcription and IL-1β production in DECs. Bacterial LPS enhances NLRP3 inflammasome components in trophoblast and DSCs, suggesting that this innate immune complex could play a key role in placental immune defense.

  10. Polymorphisms in cytokine genes IL6, TNF, IL10, IL17A and IFNG influence susceptibility to complicated skin and skin structure infections.

    PubMed

    Stappers, M H T; Thys, Y; Oosting, M; Plantinga, T S; Ioana, M; Reimnitz, P; Mouton, J W; Netea, M G; Joosten, L A B; Gyssens, I C

    2014-12-01

    Complicated skin and skin structure infections (cSSSIs) are caused by Gram-positive and Gram-negative, aerobic and anaerobic pathogens, with a polymicrobial aetiology being frequent. Recognition of invading pathogens by the immune system results in the production of pro- and anti-inflammatory cytokines, which are extremely important for intercellular communication and control of infection. This study assessed whether genetic variation in genes encoding cytokines influences the susceptibility to cSSSIs. For the association study, 318 patients with cSSSI and 328 healthy controls were genotyped for single nucleotide polymorphisms (SNPs) in cytokine genes IL1A, IL1B, IL1RN, TNF, IL10, IL17A, IL17F and IFNG. For immunological validation, peripheral blood mononuclear cells (PBMCs) from 74 healthy individuals, genotyped for SNPs of interest, were stimulated with Staphylococcus aureus or Escherichia coli and corresponding cytokine levels were determined by enzyme-linked immunosorbent assay (ELISA). Polymorphisms IL6 rs1800797, TNF rs1800629, IL10 rs1800871, IL17A rs8193036 and IFNG rs2069705 influenced susceptibility to cSSSIs. No differences in cytokine responses, stratified for genotype, were detected after PBMC stimulation. No association with cSSSIs was observed for polymorphisms IL1A rs17561 and rs1800587, IL1B rs16944 and rs1143627, IL1RN rs4251961, TNF rs361525, IL10 rs1800896, IL17A rs2275913 and IL17F rs763780. In conclusion, polymorphisms in IL6, TNF, IL10, IL17A and IFNG are associated with susceptibility to cSSSIs.

  11. Changes in gene expression and hearing thresholds after cochlear implantation

    PubMed Central

    Zhang, Hongzheng; Stark, Gemaine; Reiss, Lina

    2016-01-01

    Hypothesis Gene expression changes occur in conjunction with hearing threshold changes after cochlear implantation. Background Between 30–50% of individuals who receive electro-acoustic stimulation (EAS) cochlear implants lose residual hearing after cochlear implantation, reducing the benefits of EAS. The mechanism underlying this hearing loss is unknown; potential pathways include mechanical damage, inflammation, or tissue remodeling changes. Methods Guinea pigs were implanted in one ear with cochlear implant electrode arrays, with non-implanted ears serving as controls, and allowed to recover for 1, 3, 7, or 14 days. Hearing threshold changes were measured over time. Cochlear ribonucleic acid was analyzed using real-time quantitative reverse transcription-polymerase chain reaction from the following gene families: cytokines, tight junction claudins, ion and water (aquaporin) transport channels, gap junction connexins, and tissue remodeling genes. Results Significant increases in expression were observed for cochlear inflammatory genes (Cxcl1, IL-1b, TNFα and Tnfrsf1a/b) and ion homeostasis genes (Scnn1γ, Aqp3 and Gjb3). Upregulation of tissue remodeling genes (TGF-β, MMP2, MMP9) as well as a paracrine gene (CTGF) was also observed. Hearing loss occurred rapidly, peaking at 3 days with some recovery at 7 and 14 days after implantation. MM9 exhibited extreme upregulation of expression and was qualitatively associated with changes in hearing thresholds. Conclusion Cochlear implantation induces similar changes as middle ear inflammation for genes involved in inflammation and ion and water transport function, whereas tissue remodeling changes differ markedly. The upregulation of MMP9 with hearing loss is consistent with previous findings linking stria vascularis vessel changes with cochlear implant-induced hearing loss. PMID:25970030

  12. Cytokine gene polymorphisms and outcome after traumatic brain injury.

    PubMed

    Waters, Ryan J; Murray, Gordon D; Teasdale, Graham M; Stewart, Janice; Day, Ian; Lee, Robert J; Nicoll, James A R

    2013-10-15

    Clinical outcome after traumatic brain injury (TBI) is variable and cannot easily be predicted. There is increasing evidence to suggest that there may be genetic influences on outcome. Cytokines play an important role in mediating the inflammatory response provoked within the central nervous system after TBI. This study was designed to identify associations between cytokine gene polymorphisms and clinical outcome 6 months after head injury. A prospectively identified cohort of patients (n=1096, age range 0-93 years, mean age 37) was used. Clinical outcome at 6 months was assessed using the Glasgow Outcome Scale. In an initial screen of 11 cytokine gene single nucleotide polymorphisms (SNPs) previously associated with disease susceptibility or outcome (TNFA -238 and -308, IL6 -174, -572 and -597, IL1A -889, IL1B -31, -511 and +3953, and TGFB -509 and -800), TNFA -308 was identified as having a likely association. The TNFA -308 SNP was further evaluated, and a significant association was identified, with 39% of allele 2 carriers having an unfavorable outcome compared with 31% of non-carriers (adjusted odds ratio 1.67, confidence interval 1.19-2.35, p=0.003). These findings are consistent with experimental and clinical data suggesting that neuroinflammation has an impact on clinical outcome after TBI and that tumor necrosis factor alpha plays an important role in this process.

  13. New associations: INFG and TGFB1 genes and the inhibitor development in severe haemophilia A.

    PubMed

    de Alencar, J B; Macedo, L C; de Barros, M F; Rodrigues, C; Shinzato, A H; Pelissari, C B; Machado, J; Sell, A M; Visentainer, J E L

    2015-07-01

    The development of factor VIII (FVIII) inhibitor is the main complication of replacement therapy in patients with haemophilia A (HA). A ratio of 5-7% of individuals HA develops antibodies (inhibitors) against the FVIII infused during the treatment, thereby reducing their pro-coagulant activity. The immunomodulatory cytokine genes have been related to the risk of development of alloantibodies in several studies, mainly in HA with severe form. We investigated the polymorphisms in regulatory regions of cytokine genes (IL1A, IL1B, IL1R, IL1RA, IL4RA, IL12, INFG, TGFB1, TNF, IL2, IL4, IL6, IL10) that could influence the risk of developing inhibitors in patients with severe HA. The genotyping of cytokine genes of 117 patients with HA was performed by polymerase chain reaction with sequence-specific primers (PCR-SSP) using the protocol recommended by the manufacturer (Invitrogen kit Cytokines(®) , Canoga Park, USA) RESULTS: From the cohort of 117 patients with severe HA, 35 developed inhibitors. There was a higher frequency of +874 T allele in INFG and of +869 TT and TG/TG in TGFB1 genes on patients with inhibitors. This suggests that polymorphisms in INFG and in TGFB1 genes are related to risk of developing inhibitor, and could contribute to a genetic profile of the individual HA for the risk of inhibitors development to FVIII. © 2015 John Wiley & Sons Ltd.

  14. Gene Expression Profile of High IFN-γ Producers Stimulated with Leishmania braziliensis Identifies Genes Associated with Cutaneous Leishmaniasis

    PubMed Central

    Carneiro, Marcia W.; Fukutani, Kiyoshi F.; Andrade, Bruno B.; Curvelo, Rebecca P.; Cristal, Juqueline R.; Carvalho, Augusto M.; Barral, Aldina

    2016-01-01

    Background The initial response to Leishmania parasites is essential in determining disease development or resistance. In vitro, a divergent response to Leishmania, characterized by high or low IFN-γ production has been described as a potential tool to predict both vaccine response and disease susceptibility in vivo. Methods and findings We identified uninfected and healthy individuals that were shown to be either high- or low IFN-γ producers (HPs and LPs, respectively) following stimulation of peripheral blood cells with Leishmania braziliensis. Following stimulation, RNA was processed for gene expression analysis using immune gene arrays. Both HPs and LPs were shown to upregulate the expression of CXCL10, IFI27, IL6 and LTA. Genes expressed in HPs only (CCL7, IL8, IFI44L and IL1B) were associated with pathways related to IL17 and TREM 1 signaling. In LPs, uniquely expressed genes (for example IL9, IFI44, IFIT1 and IL2RA) were associated with pathways related to pattern recognition receptors and interferon signaling. We then investigated whether the unique gene expression profiles described here could be recapitulated in vivo, in individuals with active Cutaneous Leishmaniasis or with subclinical infection. Indeed, using a set of six genes (TLR2, JAK2, IFI27, IFIT1, IRF1 and IL6) modulated in HPs and LPs, we could successfully discriminate these two clinical groups. Finally, we demonstrate that these six genes are significantly overexpressed in CL lesions. Conclusion Upon interrogation of the peripheral response of naive individuals with diverging IFN-γ production to L. braziliensis, we identified differences in the innate response to the parasite that are recapitulated in vivo and that discriminate CL patients from individuals presenting a subclinical infection. PMID:27870860

  15. Activation of the transcription factor nuclear factor-kappa B in uterine luminal epithelial cells by interleukin 1 Beta 2: a novel interleukin 1 expressed by the elongating pig conceptus.

    PubMed

    Mathew, Daniel J; Newsom, Emily M; Guyton, Jennifer M; Tuggle, Christopher K; Geisert, Rodney D; Lucy, Matthew C

    2015-04-01

    Conceptus mortality is greatest in mammals during the peri-implantation period, a time when conceptuses appose and attach to the uterine surface epithelium while releasing proinflammatory molecules. Interleukin 1 beta (IL1B), a master proinflammatory cytokine, is released by the primate, rodent, and pig blastocyst during the peri-implantation period and is believed to be essential for establishment of pregnancy. The gene encoding IL1B has duplicated in the pig, resulting in a novel gene. Preliminary observations indicate that the novel IL1B is specifically expressed by pig conceptuses during the peri-implantation period. To verify this, IL1B was cloned from mRNA isolated from Day 12 pig conceptuses and compared with IL1B cloned from mRNA isolated from pig peripheral blood leukocytes (PBLs). The pig conceptuses, but not the PBLs, expressed a novel IL1B, referred to here as interleukin 1 beta 2 (IL1B2). Porcine endometrium was treated with recombinant porcine interleukin 1 beta 1 (IL1B1), the prototypical cytokine, and IL1B2 proteins. Immunohistochemistry and real-time RT-PCR were used to measure activation of nuclear factor-kappa B (NFKB) and NFKB-regulated transcripts, respectively, within the endometrium. Both IL1B1 and IL1B2 activated NFKB in the uterine luminal epithelium within 4 h. The NFKB activation and related gene expression, however, were lower in endometrium treated with IL1B2, suggesting that the conceptus-derived cytokine may have reduced activity within the uterus. In conclusion, the peri-implantation pig conceptus expresses a novel IL1B that can activate NFKB within the uterine surface epithelium, likely creating a proinflammatory microenvironment during establishment of pregnancy in the pig. © 2015 by the Society for the Study of Reproduction, Inc.

  16. Prepartal dietary energy level affects peripartal bovine blood neutrophil metabolic, antioxidant, and inflammatory gene expression.

    PubMed

    Zhou, Z; Bu, D P; Vailati Riboni, M; Khan, M J; Graugnard, D E; Luo, J; Cardoso, F C; Loor, J J

    2015-08-01

    During the dry period, cows can easily overconsume higher-grain diets, a scenario that could impair immune function during the peripartal period. Objectives were to investigate the effects of energy overfeeding on expression profile of genes associated with inflammation, lipid metabolism, and neutrophil function, in 12 multiparous Holstein cows (n=6/dietary group) fed control [CON, 1.34 Mcal/kg of dry matter (DM)] or higher-energy (HE, 1.62 Mcal/kg of DM) diets during the last 45 d of pregnancy. Blood was collected to evaluate 43 genes in polymorphonuclear neutrophil leukocytes (PMNL) isolated at -14, 7, and 14 d relative to parturition. We detected greater expression of inflammatory-related cytokines (IL1B, STAT3, NFKB1) and eicosanoid synthesis (ALOX5AP and PLA2G4A) in HE cows than in CON cows. Around parturition, all cows had a close balance in mRNA expression of the pro-inflammatory IL1B and the anti-inflammatory IL10, with greater expression of both in cows fed HE than CON. The expression of CCL2, LEPR, TLR4, IL6, and LTC4S was undetectable. Cows in the HE group had greater expression of genes involved in PMNL adhesion, motility, migration, and phagocytosis, which was similar to expression of genes related to the pro-inflammatory cytokine. This response suggests that HE cows experienced a chronic state of inflammation. The greater expression of G6PD in HE cows could have been associated with the greater plasma insulin, which would have diverted glucose to other tissues. Cows fed the HE diet also had greater expression of transcription factors involved in metabolism of long-chain fatty acids (PPARD, RXRA), suggesting that immune cells might be predisposed to use endogenous ligands such as nonesterified fatty acids available in the circulation when glucose is in high demand for milk synthesis. The lower overall expression of SLC2A1 postpartum than prepartum supports this suggestion. Targeting interleukin-1β signaling might be of value in terms of controlling

  17. Genome Wide Host Gene Expression Analysis in Chicken Lungs Infected with Avian Influenza Viruses.

    PubMed

    Ranaware, Pradip B; Mishra, Anamika; Vijayakumar, Periyasamy; Gandhale, Pradeep N; Kumar, Himanshu; Kulkarni, Diwakar D; Raut, Ashwin Ashok

    2016-01-01

    The molecular pathogenesis of avian influenza infection varies greatly with individual bird species and virus strain. The molecular pathogenesis of the highly pathogenic avian influenza virus (HPAIV) or the low pathogenic avian influenza virus (LPAIV) infection in avian species remains poorly understood. Thus, global immune response of chickens infected with HPAI H5N1 (A/duck/India/02CA10/2011) and LPAI H9N2 (A/duck/India/249800/2010) viruses was studied using microarray to identify crucial host genetic components responsive to these infection. HPAI H5N1 virus induced excessive expression of type I IFNs (IFNA and IFNG), cytokines (IL1B, IL18, IL22, IL13, and IL12B), chemokines (CCL4, CCL19, CCL10, and CX3CL1) and IFN stimulated genes (OASL, MX1, RSAD2, IFITM5, IFIT5, GBP 1, and EIF2AK) in lung tissues. This dysregulation of host innate immune genes may be the critical determinant of the severity and the outcome of the influenza infection in chickens. In contrast, the expression levels of most of these genes was not induced in the lungs of LPAI H9N2 virus infected chickens. This study indicated the relationship between host immune genes and their roles in pathogenesis of HPAIV infection in chickens.

  18. Genome Wide Host Gene Expression Analysis in Chicken Lungs Infected with Avian Influenza Viruses

    PubMed Central

    Gandhale, Pradeep N.; Kumar, Himanshu; Kulkarni, Diwakar D.

    2016-01-01

    The molecular pathogenesis of avian influenza infection varies greatly with individual bird species and virus strain. The molecular pathogenesis of the highly pathogenic avian influenza virus (HPAIV) or the low pathogenic avian influenza virus (LPAIV) infection in avian species remains poorly understood. Thus, global immune response of chickens infected with HPAI H5N1 (A/duck/India/02CA10/2011) and LPAI H9N2 (A/duck/India/249800/2010) viruses was studied using microarray to identify crucial host genetic components responsive to these infection. HPAI H5N1 virus induced excessive expression of type I IFNs (IFNA and IFNG), cytokines (IL1B, IL18, IL22, IL13, and IL12B), chemokines (CCL4, CCL19, CCL10, and CX3CL1) and IFN stimulated genes (OASL, MX1, RSAD2, IFITM5, IFIT5, GBP 1, and EIF2AK) in lung tissues. This dysregulation of host innate immune genes may be the critical determinant of the severity and the outcome of the influenza infection in chickens. In contrast, the expression levels of most of these genes was not induced in the lungs of LPAI H9N2 virus infected chickens. This study indicated the relationship between host immune genes and their roles in pathogenesis of HPAIV infection in chickens. PMID:27071061

  19. The DosR regulon of M. tuberculosis and antibacterial tolerance

    PubMed Central

    Bartek, I.L.; Rutherford, R.; Gruppo, V.; Morton, R.A.; Morris, R.P.; Klein, M.R.; Visconti, K.C.; Ryan, G.J.; Schoolnik, G.K.; Lenaerts, A.; Voskuil, M.I.

    2009-01-01

    Summary Adaptation of Mycobacterium tuberculosis to an anaerobic dormant state that is tolerant to several antibacterials is mediated largely by a set of highly expressed genes controlled by DosR. A DosR mutant was constructed to investigate whether the DosR regulon is involved in antibacterial tolerance. We demonstrate that induction of the regulon is not required for drug tolerance either in vivo during a mouse infection or in vitro during anaerobic dormancy. Thus, drug tolerance observed in these models is due to other mechanisms such as the bacilli simply being in a non-replicating or low metabolic state. Our data also demonstrate that the DosR regulon is not essential for virulence during chronic murine infection. However, decreased lung pathology was observed in the DosR mutant. We also show that the DosR regulon genes are more highly conserved in environmental mycobacteria, than in pathogenic mycobacteria lacking a latent phase or environmental reservoir. It is possible that the DosR regulon could contribute to drug tolerance in human infections; however, it is not the only mechanism and not the primary mechanism for tolerance during a mouse infection. These data suggest that the regulon evolved not for pathogenesis or drug tolerance but for adaptation to anaerobic conditions in the environment and has been adapted by M. tuberculosis for survival during latent infection. PMID:19577518

  20. DIGLIB. PC-DOS Graphics Subroutine Library

    SciTech Connect

    Burleson, R.R.

    1989-02-01

    DIGLIB is a collection of general graphics subroutines. It was designed to be small, reasonably fast, device-independent, and compatible with DEC-supplied operating systems for VAXes, PDP-11s, and LSI-11s, and the DOS operating system for IBM PCs and IBM-compatible machines. DIGLIB/PC runs on IBM PCs under PC-DOS or MS-DOS. The software is readily usable by casual programmers for two-dimensional plotting.

  1. Nrf2-related gene expression and exposure to traffic-related air pollution in elderly subjects with cardiovascular disease: An exploratory panel study.

    PubMed

    Wittkopp, Sharine; Staimer, Norbert; Tjoa, Thomas; Stinchcombe, Timothy; Daher, Nancy; Schauer, James J; Shafer, Martin M; Sioutas, Constantinos; Gillen, Daniel L; Delfino, Ralph J

    2016-01-01

    Gene expression changes are linked to air pollutant exposures in in vitro and animal experiments. However, limited data are available on how these outcomes relate to ambient air pollutant exposures in humans. We performed an exploratory analysis testing whether gene expression levels were associated with air pollution exposures in a Los Angeles area cohort of elderly subjects with coronary artery disease. Candidate genes (35) were selected from published studies of gene expression-pollutant associations. Expression levels were measured weekly in 43 subjects (≤ 12 weeks) using quantitative PCR. Exposures included gaseous pollutants O3, nitrogen oxides (NOx), and CO; particulate matter (PM) pollutants elemental and black carbon (EC, BC); and size-fractionated PM mass. We measured organic compounds from PM filter extracts, including polycyclic aromatic hydrocarbons (PAHs), and determined the in vitro oxidative potential of particle extracts. Associations between exposures and gene expression levels were analyzed using mixed-effects regression models. We found positive associations of traffic-related pollutants (EC, BC, primary organic carbon, PM 0.25-2.5 PAH and/or PM 0.25 PAH, and NOx) with NFE2L2, Nrf2-mediated genes (HMOX1, NQO1, and SOD2), CYP1B1, IL1B, and SELP. Findings suggest that NFE2L2 gene expression links associations of traffic-related air pollution with phase I and II enzyme genes at the promoter transcription level.

  2. Nrf2-related gene expression and exposure to traffic-related air pollution in elderly subjects with cardiovascular disease: An exploratory panel study

    PubMed Central

    Wittkopp, Sharine; Staimer, Norbert; Tjoa, Thomas; Stinchcombe, Timothy; Daher, Nancy; Schauer, James J.; Shafer, Martin M.; Sioutas, Constantinos; Gillen, Daniel L.; Delfino, Ralph J.

    2015-01-01

    Gene expression changes are linked to air pollutant exposures in in vitro and animal experiments. However, limited data are available on how these outcomes relate to ambient air pollutant exposures in humans. We performed an exploratory analysis testing whether gene expression levels were associated with air pollution exposures in a Los Angeles area cohort of elderly subjects with coronary artery disease. Candidate genes (35) were selected from published studies of gene expression-pollutant associations. Expression levels were measured weekly in 43 subjects (≤12 weeks) using quantitative PCR. Exposures included gaseous pollutants O3, nitrogen oxides (NOx), and CO; particulate matter (PM) pollutants elemental and black carbon (EC, BC); and size-fractionated PM mass. We measured organic compounds from PM filter extracts, including polycyclic aromatic hydrocarbons (PAHs), and determined the in vitro oxidative potential of particle extracts. Associations between exposures and gene expression levels were analyzed using mixed-effects regression models. We found positive associations of traffic-related pollutants (EC, BC, primary organic carbon, PM0.25-2.5 PAH and/or PM0.25 PAH, and NOx) with NFE2L2, Nrf2-mediated genes (HMOX1, NQO1, and SOD2), CYP1B1, IL1B, and SELP. Findings suggest that NFE2L2 gene expression links associations of traffic-related air pollution with phase I and II enzyme genes at the promoter transcription level. PMID:25564368

  3. Proinflammatory cytokine and cytokine receptor gene expression kinetics following challenge with Flavobacterium psychrophilum in resistant and susceptible lines of rainbow trout (Oncorhynchus mykiss).

    PubMed

    Kutyrev, Ivan; Cleveland, Beth; Leeds, Timothy; Wiens, Gregory D

    2016-11-01

    Flavobacterium psychrophilum (Fp) is the causative agent of bacterial cold water disease (BCWD) which causes appreciable economic losses in rainbow trout aquaculture. We previously reported development of a genetic line, designated ARS-Fp-R that exhibits higher survival relative to a susceptible line, designated ARS-Fp-S, following either laboratory or natural on-farm challenge. The objectives of this study were to determine the temporal kinetics of gene expression between experimentally-challenged ARS-Fp-R and ARS-Fp-S fish and the correlation between gene expression and pathogen load. We developed a GeXP multiplex RT-PCR assay to simultaneously examine expression of immune-relevant genes, concentrating on tumor necrosis factor and interleukin-1 ligand/receptor systems and acute phase response genes. Spleen tissue was sampled at 6 h, 24 h, 48 h and 144 h post-challenge and pathogen load quantified by qPCR. Transcript abundance of cytokine genes tnfa1, tnfa2, tnfa3, il1b1, il1b2, il11a; acute phase response genes saa and drtp1; and putative cytokine receptors il1r1-like-b, il1r2, tnfrsf1a, tnfrsf9, tnfrsf1a-like-b increased following challenge while the transcript abundance of il1r-like-1 and tnfrsf1a-like-a decreased compared to PBS-injected line-matched control fish. Principal component analysis identified transcript levels of genes il1r-like-1 and tnfrsf1a-like-a as exhibiting differential expression between genetic lines. In summary, Fp i.p. injection challenge elicited a proinflammatory cytokine gene expression response in the spleen, with ARS-Fp-R line fish exhibiting modestly higher basal expression levels of several putative cytokine receptors. This study furthers the understanding of the immune response following Fp challenge and differences in gene expression associated with selective breeding for disease resistance. Published by Elsevier Ltd.

  4. Role of familiarity versus interleukin-1 genes cluster polymorphisms in chronic periodontitis.

    PubMed

    Zuccarello, Daniela; Bazzato, M Federica; Ferlin, Alberto; Pengo, Manuel; Frigo, Anna Chiara; Favero, Giovanni; Foresta, Carlo; Stellini, Edoardo

    2014-02-10

    Periodontitis (PO) is a multifactorial disease affecting about 10% to 20% of the general population. Several studies have suggested that part of the clinical variability in PO might be explained by genetic factors. Among the candidate genes for PO, IL1 gene polymorphisms have been broadly investigated, with variable results, for their relationship with the disease. We studied three IL1 polymorphisms, IL1A C[-889]T (rs1800587), IL1B C[3953/4]T (rs1143634), and IL1RN VNTR [+2018] (rs419598) in relation to different life styles and familiarities. We did not find correlation between these IL1 polymorphisms and chronic PO, as well as between chronic PO and life styles (smoking, alcohol, coffee, fizzy drink and fish). We found a strong correlation, also after adjustment for age, between familiarity and PO onset (P=0.0062; OR 5.754, 95% CI 1.644-20.145). In conclusion, we did confirm the previously suggested association between PO and IL1 gene cluster polymorphisms, and between PO and four common risk factors (coffee, smoking, alcohol and fizzy drinks) and one common protective factor (fish). On the contrary, we found a strong role of familiarity. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. The effect of dexamethasone/cell-penetrating peptide nanoparticles on gene delivery for inner ear therapy.

    PubMed

    Yoon, Ji Young; Yang, Keum-Jin; Park, Shi-Nae; Kim, Dong-Kee; Kim, Jong-Duk

    Dexamethasone (Dex)-loaded PHEA-g-C18-Arg8 (PCA) nanoparticles (PCA/Dex) were developed for the delivery of genes to determine the synergistic effect of Dex on gene expression. The cationic PCA nanoparticles were self-assembled to create cationic micelles containing an octadecylamine (C18) core with Dex and an arginine 8 (Arg8) peptide shell for electrostatic complexation with nucleic acids (connexin 26 [Cx26] siRNA, green fluorescent protein [GFP] DNA or brain-derived neurotrophic factor [BDNF] pDNA). The PCA/Dex nanoparticles conjugated with Arg8, a cell-penetrating peptide that enhances permeability through a round window membrane in the inner ear for gene delivery, exhibited high uptake efficiency in HEI-OC1 cells. This potential carrier co-delivering Dex and the gene into inner ear cells has a diameter of 120-140 nm and a zeta potential of 20-25 mV. Different types of genes were complexed with the Dex-loaded PCA nanoparticle (PCA/Dex/gene) for gene expression to induce additional anti-inflammatory effects. PCA/Dex showed mildly increased expression of GFP and lower mRNA expression of inflammatory cytokines (IL1b, IL12, and INFr) than did Dex-free PCA nanoparticles and Lipofectamine(®) reagent in HEI-OC1 cells. In addition, after loading Cx26 siRNA onto the surface of PCA/Dex, Cx26 gene expression was downregulated according to real-time polymerase chain reaction for 24 h, compared with that using Lipofectamine reagent. After loading BDNF DNA into PCA/Dex, increased expression of BDNF was observed for 30 h, and its signaling pathway resulted in an increase in phosphorylation of Akt, observed by Western blotting. Thus, Dex within PCA/Dex/gene nanoparticles created an anti-inflammatory effect and enhanced gene expression.

  6. Inter-Tissue Gene Co-Expression Networks between Metabolically Healthy and Unhealthy Obese Individuals.

    PubMed

    Kogelman, Lisette J A; Fu, Jingyuan; Franke, Lude; Greve, Jan Willem; Hofker, Marten; Rensen, Sander S; Kadarmideen, Haja N

    2016-01-01

    Obesity is associated with severe co-morbidities such as type 2 diabetes and nonalcoholic steatohepatitis. However, studies have shown that 10-25 percent of the severely obese individuals are metabolically healthy. To date, the identification of genetic factors underlying the metabolically healthy obese (MHO) state is limited. Systems genetics approaches have led to the identification of genes and pathways in complex diseases. Here, we have used such approaches across tissues to detect genes and pathways involved in obesity-induced disease development. Expression data of 60 severely obese individuals was accessible, of which 28 individuals were MHO and 32 were metabolically unhealthy obese (MUO). A whole genome expression profile of four tissues was available: liver, muscle, subcutaneous adipose tissue and visceral adipose tissue. Using insulin-related genes, we used the weighted gene co-expression network analysis (WGCNA) method to build within- and inter-tissue gene networks. We identified genes that were differentially connected between MHO and MUO individuals, which were further investigated by homing in on the modules they were active in. To identify potentially causal genes, we integrated genomic and transcriptomic data using an eQTL mapping approach. Both IL-6 and IL1B were identified as highly differentially co-expressed genes across tissues between MHO and MUO individuals, showing their potential role in obesity-induced disease development. WGCNA showed that those genes were clustering together within tissues, and further analysis showed different co-expression patterns between MHO and MUO subnetworks. A potential causal role for metabolic differences under similar obesity state was detected for PTPRE, IL-6R and SLC6A5. We used a novel integrative approach by integration of co-expression networks across tissues to elucidate genetic factors related to obesity-induced metabolic disease development. The identified genes and their interactions give more

  7. Inter-Tissue Gene Co-Expression Networks between Metabolically Healthy and Unhealthy Obese Individuals

    PubMed Central

    Kogelman, Lisette J. A.; Fu, Jingyuan; Franke, Lude; Greve, Jan Willem; Hofker, Marten; Rensen, Sander S.; Kadarmideen, Haja N.

    2016-01-01

    Background Obesity is associated with severe co-morbidities such as type 2 diabetes and nonalcoholic steatohepatitis. However, studies have shown that 10–25 percent of the severely obese individuals are metabolically healthy. To date, the identification of genetic factors underlying the metabolically healthy obese (MHO) state is limited. Systems genetics approaches have led to the identification of genes and pathways in complex diseases. Here, we have used such approaches across tissues to detect genes and pathways involved in obesity-induced disease development. Methods Expression data of 60 severely obese individuals was accessible, of which 28 individuals were MHO and 32 were metabolically unhealthy obese (MUO). A whole genome expression profile of four tissues was available: liver, muscle, subcutaneous adipose tissue and visceral adipose tissue. Using insulin-related genes, we used the weighted gene co-expression network analysis (WGCNA) method to build within- and inter-tissue gene networks. We identified genes that were differentially connected between MHO and MUO individuals, which were further investigated by homing in on the modules they were active in. To identify potentially causal genes, we integrated genomic and transcriptomic data using an eQTL mapping approach. Results Both IL-6 and IL1B were identified as highly differentially co-expressed genes across tissues between MHO and MUO individuals, showing their potential role in obesity-induced disease development. WGCNA showed that those genes were clustering together within tissues, and further analysis showed different co-expression patterns between MHO and MUO subnetworks. A potential causal role for metabolic differences under similar obesity state was detected for PTPRE, IL-6R and SLC6A5. Conclusions We used a novel integrative approach by integration of co-expression networks across tissues to elucidate genetic factors related to obesity-induced metabolic disease development. The identified

  8. The effect of dexamethasone/cell-penetrating peptide nanoparticles on gene delivery for inner ear therapy

    PubMed Central

    Yoon, Ji Young; Yang, Keum-Jin; Park, Shi-Nae; Kim, Dong-Kee; Kim, Jong-Duk

    2016-01-01

    Dexamethasone (Dex)-loaded PHEA-g-C18-Arg8 (PCA) nanoparticles (PCA/Dex) were developed for the delivery of genes to determine the synergistic effect of Dex on gene expression. The cationic PCA nanoparticles were self-assembled to create cationic micelles containing an octadecylamine (C18) core with Dex and an arginine 8 (Arg8) peptide shell for electrostatic complexation with nucleic acids (connexin 26 [Cx26] siRNA, green fluorescent protein [GFP] DNA or brain-derived neurotrophic factor [BDNF] pDNA). The PCA/Dex nanoparticles conjugated with Arg8, a cell-penetrating peptide that enhances permeability through a round window membrane in the inner ear for gene delivery, exhibited high uptake efficiency in HEI-OC1 cells. This potential carrier co-delivering Dex and the gene into inner ear cells has a diameter of 120–140 nm and a zeta potential of 20–25 mV. Different types of genes were complexed with the Dex-loaded PCA nanoparticle (PCA/Dex/gene) for gene expression to induce additional anti-inflammatory effects. PCA/Dex showed mildly increased expression of GFP and lower mRNA expression of inflammatory cytokines (IL1b, IL12, and INFr) than did Dex-free PCA nanoparticles and Lipofectamine® reagent in HEI-OC1 cells. In addition, after loading Cx26 siRNA onto the surface of PCA/Dex, Cx26 gene expression was downregulated according to real-time polymerase chain reaction for 24 h, compared with that using Lipofectamine reagent. After loading BDNF DNA into PCA/Dex, increased expression of BDNF was observed for 30 h, and its signaling pathway resulted in an increase in phosphorylation of Akt, observed by Western blotting. Thus, Dex within PCA/Dex/gene nanoparticles created an anti-inflammatory effect and enhanced gene expression. PMID:27895484

  9. Unique Regulation of the DosR Regulon in the Beijing Lineage of Mycobacterium tuberculosis.

    PubMed

    Domenech, Pilar; Zou, Jason; Averback, Alexandra; Syed, Nishath; Curtis, Daniele; Donato, Samuel; Reed, Michael B

    2017-01-15

    The DosR regulon, a set of 48 genes normally expressed in Mycobacterium tuberculosis under conditions that inhibit aerobic respiration, is controlled via the DosR-DosS/DosT two-component system. While the regulon requires induction in most M. tuberculosis isolates, for members of the Beijing lineage, its expression is uncoupled from the need for signaling. In our attempts to understand the mechanistic basis for this uncoupling in the Beijing background, we previously reported the identification of two synonymous single-nucleotide polymorphisms (SNPs) within the adjacent Rv3134c gene. In the present study, we have interrogated the impact of these SNPs on dosR expression in wild-type strains, as well as a range of dosR-dosS-dosT mutants, for both Beijing and non-Beijing M. tuberculosis backgrounds. In this manner, we have unequivocally determined that the C601T dosR promoter SNP is the sole requirement for the dramatic shift in the pattern of DosR regulon expression seen in this globally important lineage. Interestingly, we also show that DosT is completely nonfunctional within these strains. Thus, a complex series of evolutionary steps has led to the present-day Beijing DosR phenotype that, in turn, potentially confers a fitness advantage in the face of some form of host-associated selective pressure. Mycobacterium tuberculosis strains of the Beijing lineage have been described as being of enhanced virulence compared to other lineages, and in certain regions, they are associated with the dramatic spread of multidrug-resistant tuberculosis (TB). In terms of trying to understand the functional basis for these broad epidemiological phenomena, it is interesting that, in contrast to the other major lineages, the Beijing strains all constitutively overexpress members of the DosR regulon. Here, we identify the mutational events that led to the evolution of this unique phenotype. In addition, our work highlights the fact that important phenotypic differences exist between

  10. Self-regulating the effortful "social dos".

    PubMed

    Cortes, Kassandra; Kammrath, Lara K; Scholer, Abigail A; Peetz, Johanna

    2014-03-01

    In the current research, we explored differences in the self-regulation of the personal dos (i.e., engaging in active and effortful behaviors that benefit the self) and in the self-regulation of the social dos (engaging in those same effortful behaviors to benefit someone else). In 6 studies, we examined whether the same trait self-control abilities that predict task persistence on personal dos would also predict task persistence on social dos. That is, would the same behavior, such as persisting through a tedious and attentionally demanding task, show different associations with trait self-control when it is framed as benefitting the self versus someone else? In Studies 1-3, we directly compared the personal and social dos and found that trait self-control predicted self-reported and behavioral personal dos but not social dos, even when the behaviors were identical and when the incentives were matched. Instead, trait agreeableness--a trait linked to successful self-regulation within the social domain--predicted the social dos. Trait self-control did not predict the social dos even when task difficulty increased (Study 4), but it did predict the social don'ts, consistent with past research (Studies 5-6). The current studies provide support for the importance of distinguishing different domains of self-regulated behaviors and suggest that social dos can be successfully performed through routes other than traditional self-control abilities. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

  11. A longitudinal study of gene expression in healthy individuals

    PubMed Central

    Karlovich, Chris; Duchateau-Nguyen, Guillemette; Johnson, Andrea; McLoughlin, Patricia; Navarro, Mercidita; Fleurbaey, Carole; Steiner, Lori; Tessier, Michel; Nguyen, Tracy; Wilhelm-Seiler, Monika; Caulfield, John P

    2009-01-01

    Background The use of gene expression in venous blood either as a pharmacodynamic marker in clinical trials of drugs or as a diagnostic test requires knowledge of the variability in expression over time in healthy volunteers. Here we defined a normal range of gene expression over 6 months in the blood of four cohorts of healthy men and women who were stratified by age (22–55 years and > 55 years) and gender. Methods Eleven immunomodulatory genes likely to play important roles in inflammatory conditions such as rheumatoid arthritis and infection in addition to four genes typically used as reference genes were examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), as well as the full genome as represented by Affymetrix HG U133 Plus 2.0 microarrays. Results Gene expression levels as assessed by qRT-PCR and microarray were relatively stable over time with ~2% of genes as measured by microarray showing intra-subject differences over time periods longer than one month. Fifteen genes varied by gender. The eleven genes examined by qRT-PCR remained within a limited dynamic range for all individuals. Specifically, for the seven most stably expressed genes (CXCL1, HMOX1, IL1RN, IL1B, IL6R, PTGS2, and TNF), 95% of all samples profiled fell within 1.5–2.5 Ct, the equivalent of a 4- to 6-fold dynamic range. Two subjects who experienced severe adverse events of cancer and anemia, had microarray gene expression profiles that were distinct from normal while subjects who experienced an infection had only slightly elevated levels of inflammatory markers. Conclusion This study defines the range and variability of gene expression in healthy men and women over a six-month period. These parameters can be used to estimate the number of subjects needed to observe significant differences from normal gene expression in clinical studies. A set of genes that varied by gender was also identified as were a set of genes with elevated expression in a subject with

  12. A longitudinal study of gene expression in healthy individuals.

    PubMed

    Karlovich, Chris; Duchateau-Nguyen, Guillemette; Johnson, Andrea; McLoughlin, Patricia; Navarro, Mercidita; Fleurbaey, Carole; Steiner, Lori; Tessier, Michel; Nguyen, Tracy; Wilhelm-Seiler, Monika; Caulfield, John P

    2009-06-07

    The use of gene expression in venous blood either as a pharmacodynamic marker in clinical trials of drugs or as a diagnostic test requires knowledge of the variability in expression over time in healthy volunteers. Here we defined a normal range of gene expression over 6 months in the blood of four cohorts of healthy men and women who were stratified by age (22-55 years and > 55 years) and gender. Eleven immunomodulatory genes likely to play important roles in inflammatory conditions such as rheumatoid arthritis and infection in addition to four genes typically used as reference genes were examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), as well as the full genome as represented by Affymetrix HG U133 Plus 2.0 microarrays. Gene expression levels as assessed by qRT-PCR and microarray were relatively stable over time with approximately 2% of genes as measured by microarray showing intra-subject differences over time periods longer than one month. Fifteen genes varied by gender. The eleven genes examined by qRT-PCR remained within a limited dynamic range for all individuals. Specifically, for the seven most stably expressed genes (CXCL1, HMOX1, IL1RN, IL1B, IL6R, PTGS2, and TNF), 95% of all samples profiled fell within 1.5-2.5 Ct, the equivalent of a 4- to 6-fold dynamic range. Two subjects who experienced severe adverse events of cancer and anemia, had microarray gene expression profiles that were distinct from normal while subjects who experienced an infection had only slightly elevated levels of inflammatory markers. This study defines the range and variability of gene expression in healthy men and women over a six-month period. These parameters can be used to estimate the number of subjects needed to observe significant differences from normal gene expression in clinical studies. A set of genes that varied by gender was also identified as were a set of genes with elevated expression in a subject with iron deficiency anemia and

  13. Targeted resequencing implicates the familial Mediterranean fever gene MEFV and the toll-like receptor 4 gene TLR4 in Behçet disease

    PubMed Central

    Kirino, Yohei; Zhou, Qing; Ishigatsubo, Yoshiaki; Mizuki, Nobuhisa; Tugal-Tutkun, Ilknur; Seyahi, Emire; Özyazgan, Yilmaz; Ugurlu, Serdal; Erer, Burak; Abaci, Neslihan; Ustek, Duran; Meguro, Akira; Ueda, Atsuhisa; Takeno, Mitsuhiro; Inoko, Hidetoshi; Ombrello, Michael J.; Satorius, Colleen L.; Maskeri, Baishali; Mullikin, James C.; Sun, Hong-Wei; Gutierrez-Cruz, Gustavo; Kim, Yoonhee; Wilson, Alexander F.; Kastner, Daniel L.; Gül, Ahmet; Remmers, Elaine F.

    2013-01-01

    Genome-wide association studies (GWAS) are a powerful means of identifying genes with disease-associated common variants, but they are not well-suited to detecting genes with disease-associated rare and low-frequency variants. In the current study of Behçet disease (BD), nonsynonymous variants (NSVs) identified by deep exonic resequencing of 10 genes found by GWAS (IL10, IL23R, CCR1, STAT4, KLRK1, KLRC1, KLRC2, KLRC3, KLRC4, and ERAP1) and 11 genes selected for their role in innate immunity (IL1B, IL1R1, IL1RN, NLRP3, MEFV, TNFRSF1A, PSTPIP1, CASP1, PYCARD, NOD2, and TLR4) were evaluated for BD association. A differential distribution of the rare and low-frequency NSVs of a gene in 2,461 BD cases compared with 2,458 controls indicated their collective association with disease. By stringent criteria requiring at least a single burden test with study-wide significance and a corroborating test with at least nominal significance, rare and low-frequency NSVs in one GWAS-identified gene, IL23R (P = 6.9 × 10−5), and one gene involved in innate immunity, TLR4 (P = 8.0 × 10−4), were associated with BD. In addition, damaging or rare damaging NOD2 variants were nominally significant across all three burden tests applied (P = 0.0063–0.045). Furthermore, carriage of the familial Mediterranean fever gene (MEFV) mutation Met694Val, which is known to cause recessively inherited familial Mediterranean fever, conferred BD risk in the Turkish population (OR, 2.65; P = 1.8 × 10−12). The disease-associated NSVs in MEFV and TLR4 implicate innate immune and bacterial sensing mechanisms in BD pathogenesis. PMID:23633568

  14. Canakinumab reverses overexpression of inflammatory response genes in tumour necrosis factor receptor-associated periodic syndrome

    PubMed Central

    Torene, Rebecca; Nirmala, Nanguneri; Obici, Laura; Cattalini, Marco; Tormey, Vincent; Caorsi, Roberta; Starck-Schwertz, Sandrine; Letzkus, Martin; Hartmann, Nicole; Abrams, Ken; Lachmann, Helen; Gattorno, Marco

    2017-01-01

    Objective To explore whether gene expression profiling can identify a molecular mechanism for the clinical benefit of canakinumab treatment in patents with tumour necrosis factor receptor-associated periodic syndrome (TRAPS). Methods Blood samples were collected from 20 patients with active TRAPS who received canakinumab 150 mg every 4 weeks for 4 months in an open-label proof-of-concept phase II study, and from 20 aged-matched healthy volunteers. Gene expression levels were evaluated in whole blood samples by microarray analysis for arrays passing quality control checks. Results Patients with TRAPS exhibited a gene expression signature in blood that differed from that in healthy volunteers. Upon treatment with canakinumab, many genes relevant to disease pathogenesis moved towards levels seen in the healthy volunteers. Canakinumab downregulated the TRAPS-causing gene (TNF super family receptor 1A (TNFRSF1A)), the drug-target gene (interleukin (IL)-1B) and other inflammation-related genes (eg, MAPK14). In addition, several inflammation-related pathways were evident among the differentially expressed genes. Canakinumab treatment reduced neutrophil counts, but the observed expression differences remained after correction for this. Conclusions These gene expression data support a model in which canakinumab produces clinical benefit in TRAPS by increasing neutrophil apoptosis and reducing pro-inflammatory signals resulting from the inhibition of IL-1β. Notably, treatment normalised the overexpression of TNFRSF1A, suggesting that canakinumab has a direct impact on the main pathogenic mechanism in TRAPS. Trial registration number NCT01242813. PMID:27474763

  15. Using the one-lung method to link p38 to pro-inflammatory gene expression during overventilation in C57BL/6 and BALB/c mice.

    PubMed

    Siegl, Stephanie; Uhlig, Stefan

    2012-01-01

    The mechanisms of ventilator-induced lung injury (VILI), including the role of MAP kinases, are frequently studied in different mouse strains. A useful model for such studies is the isolated perfused mouse lung. As a further development we present the one-lung method that permits to continue perfusion and ventilation of the right lung after removal of the left lung. This method was used to compare the effect of high pressure ventilation (HPV) on pro-inflammatory signaling events in two widely used mouse strains (C57BL/6, BALB/c) and to further define the role of p38 in VILI. Lungs were perfused and ventilated for 30 min under control conditions before they were randomized to low (8 cm H(2)O) or high (25 cm H(2)O) pressure ventilation (HPV) for 210 min, with the left lung being removed after 180 min. In the left lung we measured the phosphorylation of p38, JNK, ERK and Akt kinase, and in the right lung gene expression and protein concentrations of Il1b, Il6, Tnf, Cxcl1, Cxcl2, and Areg. Lung mechanics and kinase activation were similar in both mouse strains. HPV increased all genes (except Tnf in BALB/c) and all mediators in both strains. The gene expression of mRNA for Il1b, Il6, Cxcl1 and Cxcl2 was higher in BALB/c mice. Backward regression of the kinase data at t = 180 min with the gene and protein expression data at t = 240 min suggested that p38 controls HPV-induced gene expression, but not protein production. This hypothesis was confirmed in experiments with the p38-kinase inhibitor SB203580. The one-lung method is useful for mechanistic studies in the lungs. While C57BL/6 show diminished pro-inflammatory responses during HPV, lung mechanics and mechanotransduction processes appear to be similar in both mouse strains. Finally, the one-lung method allowed us to link p38 to gene expression during VILI.

  16. A DOS Primer for Librarians: Part II.

    ERIC Educational Resources Information Center

    Beecher, Henry

    1990-01-01

    Provides an introduction to DOS commands and strategies for the effective organization and use of hard disks. Functions discussed include the creation of directories and subdirectories, enhanced copying, the assignment of disk drives, and backing up the hard disk. (CLB)

  17. A DOS Primer for Librarians: Part II.

    ERIC Educational Resources Information Center

    Beecher, Henry

    1990-01-01

    Provides an introduction to DOS commands and strategies for the effective organization and use of hard disks. Functions discussed include the creation of directories and subdirectories, enhanced copying, the assignment of disk drives, and backing up the hard disk. (CLB)

  18. Polymorphisms in genes controlling inflammation and tissue repair in rheumatoid arthritis: a case control study

    PubMed Central

    2011-01-01

    Background Various cytokines and inflammatory mediators are known to be involved in the pathogenesis of rheumatoid arthritis (RA). We hypothesized that polymorphisms in selected inflammatory response and tissue repair genes contribute to the susceptibility to and severity of RA. Methods Polymorphisms in TNFA, IL1B, IL4, IL6, IL8, IL10, PAI1, NOS2a, C1INH, PARP, TLR2 and TLR4 were genotyped in 376 Caucasian RA patients and 463 healthy Caucasian controls using single base extension. Genotype distributions in patients were compared with those in controls. In addition, the association of polymorphisms with the need for anti-TNF-α treatment as a marker of RA severity was assessed. Results The IL8 781 CC genotype was associated with early onset of disease. The TNFA -238 G/A polymorphism was differentially distributed between RA patients and controls, but only when not corrected for age and gender. None of the polymorphisms was associated with disease severity. Conclusions We here report an association between IL8 781 C/T polymorphism and age of onset of RA. Our findings indicate that there might be a role for variations in genes involved in the immune response and in tissue repair in RA pathogenesis. Nevertheless, additional larger genomic and functional studies are required to further define their role in RA. PMID:21385363

  19. Differential expression of brain immune genes and schizophrenia-related behavior in C57BL/6N and DBA/2J female mice.

    PubMed

    Ma, Li; Kulesskaya, Natalia; Võikar, Vootele; Tian, Li

    2015-03-30

    Mounting evidence suggests the association of immune genes with complex neuropsychiatric diseases, such as schizophrenia. However, immune gene expression in the brain and their involvement in schizophrenia-related behavior in animal models have not been well studied so far. We analyzed the social (resident-intruder) and sensorimotor gating (pre-pulse inhibition (PPI) of acoustic startle) behaviors, and expression profiles of several brain immune genes in adult C57BL/6N and DBA/2J female mice. Compared to C57BL/6N mice, DBA/2J mice exhibited less social interaction in the resident-intruder test and reduced pre-pulse inhibition. The mRNA levels of Il1b and Il6 genes were significantly higher in the cortex and hypothalamus, while the mRNA level of C1qb was lower in the cortex, hippocampus and hypothalamus of DBA/2J mice compared to C57BL/6N mice. Furthermore, Tnfsf13b was up-regulated in the cortex and hippocampus, and so did Cd47 in the hippocampus, while Cx3cl1 was down-regulated in the cortex of DBA/2J mice. Our study demonstrates the differential expression of several immune genes in C57BL/6N and DBA/2J strains and more importantly provides clues on their potential importance in regulating schizophrenia-related endophenotypes in animal models.

  20. Gene Expression markers of Age-Related Inflammation in Two Human Cohorts

    PubMed Central

    Pilling, Luke C.; Joehanes, Roby; Melzer, David; Harries, Lorna W.; Henley, William; Dupuis, Josée; Lin, Honghuang; Mitchell, Marcus; Hernandez, Dena; Ying, Sai-Xia; Lunetta, Kathryn L.; Benjamin, Emelia J.; Singleton, Andrew; Levy, Daniel; Munson, Peter; Murabito, Joanne M.; Ferrucci, Luigi

    2015-01-01

    Introduction Chronically elevated circulating inflammatory markers are common in older persons but mechanisms are unclear. Many blood transcripts (>800 genes) are associated with interleukin-6 protein levels (IL6) independent of age. We aimed to identify gene transcripts statistically mediating, as drivers or responders, the increasing levels of IL6 protein in blood at older ages. Methods Blood derived in-vivo RNA from the Framingham Heart Study (FHS, n=2422, ages 40–92 yrs) and InCHIANTI study (n=694, ages 30–104 yrs), with Affymetrix and Illumina expression arrays respectively (>17,000 genes tested), were tested for statistical mediation of the age-IL6 association using resampling techniques, adjusted for confounders and multiple testing. Results In FHS, IL6 expression was not associated with IL6 protein levels in blood. 102 genes (0.6% of 17,324 expressed) statistically mediated the age-IL6 association of which 25 replicated in InCHIANTI (including 5 of the 10 largest effect genes). The largest effect gene (SLC4A10, coding for NCBE, a sodium bicarbonate transporter) mediated 19% (adjusted CI 8.9 to 34.1%) and replicated by PCR in InCHIANTI (n=194, 35.6% mediated, p=0.01). Other replicated mediators included PRF1 (perforin, a cytolytic protein in cytotoxic T lymphocytes and NK cells) and IL1B (Interleukin 1 beta): few other cytokines were significant mediators. Conclusions This transcriptome-wide study on human blood identified a small distinct set of genes that statistically mediate the age-IL6 association. Findings are robust across two cohorts and different expression technologies. Raised IL6 levels may not derive from circulating white cells in age related inflammation. PMID:26087330

  1. Interleukin-1 gene cluster polymorphisms are associated with nutritional status and inflammation in patients with end-stage renal disease.

    PubMed

    Maruyama, Yukio; Nordfors, Louise; Stenvinkel, Peter; Heimburger, Olof; Bárány, Peter; Pecoits-Filho, Roberto; Axelsson, Jonas; Hoff, Catherine M; Holmes, Clifford J; Schalling, Martin; Lindholm, Bengt

    2005-01-01

    Wasting and inflammation are two common risk factors for death in patients with end-stage renal disease (ESRD). Interleukin-1beta (IL-1beta) and its receptor antagonist (IL-1Ra) may play a pivotal role in the pathogenesis of wasting and inflammation. To investigate effects of the IL-1 gene cluster polymorphisms on wasting and inflammation, we studied 189 ESRD patients (52+/- 12 years, 62% males) close to the start of renal replacement therapy. 205 healthy volunteers served as controls. We analyzed the IL-1B -511C/T, -31C/T, and +3954C/T polymorphisms as well as a variable number of a tandem repeat (VNTR) in IL-1RN. Nutritional parameters included serum albumin level, subjective global nutritional assessment (SGA), and body composition evaluated by dual-energy X-ray absorptiometry (DXA). We used serum high-sensitivity C-reactive protein (hsCRP) as a marker of inflammation. Wasting (SGA>1) was present in 31%, whereas inflammation (CRP>/=10 mg/l) was present in 36% of the patients. The male carriers of the -511T/T and -31C/C genotypes had a lower prevalence of wasting (p<0.05), higher body mass index (BMI) (p<0.05), and higher lean body mass (LBM) (p<0.01). In a stepwise multiple regression model, age (p<0.05), BMI (p<0.01) and the IL-1B -511 genotype (p<0.01) were independently associated with LBM. The carriers of the +3954T allele had a lower prevalence of inflammation (p<0.05) and lower serum hsCRP (p<0.05). The VNTR in IL-1RN was not associated with any markers. The investigated IL-1 gene cluster polymorphisms were associated with nutritional status and inflammation in ESRD patients, but marked differences were found between the genders. These polymorphisms could have prognostic utility for predicting wasting and inflammation in ESRD patients. Copyright (c) 2005 S. Karger AG, Basel.

  2. Melatonin or ramelteon therapy differentially affects hepatic gene expression profiles after haemorrhagic shock in rat--A microarray analysis.

    PubMed

    Kleber, Astrid; Ruf, Christian G; Wolf, Alexander; Fink, Tobias; Glas, Michael; Wolf, Beate; Volk, Thomas; Abend, Michael; Mathes, Alexander M

    2015-10-01

    Melatonin has been demonstrated to reduce liver damage in different models of stress. However, there is only limited information on the impact of this hormone on hepatic gene expression. The aim of this study was, to investigate the influence of melatonin or the melatonergic agonist ramelteon on hepatic gene expression profiles after haemorrhagic shock using a whole genome microarray analysis. Male Sprague-Dawley rats (200-300 g, n=4/group) underwent haemorrhagic shock (mean arterial pressure 35±5 mmHg). After 90 min of shock, animals were resuscitated with shed blood and Ringer's and treated with vehicle (5% dimethyl sulfoxide), melatonin or ramelteon (each 1.0 mg/kg intravenously). Sham-operated animals were treated likewise but did not undergo haemorrhage. After 2 h of reperfusion, the liver was harvested, and a whole genome microarray analysis was performed. Functional gene expression profiles were determined using the Panther® classification system; promising candidate genes were evaluated by quantitative polymerase chain reaction (PCR). Microarray and PCR data showed a good correlation (r(2)=0.84). A strong influence of melatonin on receptor mediated signal transduction was revealed using the functional gene expression profile analysis, whereas ramelteon mainly influenced transcription factors. Shock-induced upregulation of three candidate genes with relevant functions for hepatocytes (ppp1r15a, dusp5, rhoB) was significantly reduced by melatonin (p<0.05 vs. shock/vehicle), but not by ramelteon. Two genes previously known as haemorrhage-induced (il1b, s100a8) were transcriptionally repressed by both drugs. Melatonin and ramelteon appear to induce specific hepatic gene expression profiles after haemorrhagic shock in rats. The observed differences between both substances are likely to be attributable to a distinct mechanism of action in these agents. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Changes in Gene Expression Profiles in Response to Selenium Supplementation among Individuals with Arsenic-induced Pre-malignant Skin Lesions

    PubMed Central

    Kibriya, Muhammad G.; Jasmine, Farzana; Argos, Maria; Verret, Wendy J.; Rakibuz-Zaman, Muhammad; Ahmed, Alauddin; Parvez, Faruque; Ahsan, Habibul

    2007-01-01

    The molecular basis and downstream targets of oral selenium supplementation in individuals with elevated risk of cancer due to chronic exposure from environmental carcinogens has been largely unexplored. In this study, we investigated genome-wide differential gene expression in peripheral blood mononuclear cells (PBMC) from individuals with pre-malignant arsenic (As)-induced skin lesions before and after six months daily oral supplementation of 200 μg l-selenomethionine. The Affymetrix GeneChip Human 133A 2.0 array, containing probes for 22,277 gene transcripts, was used to assess gene expression. Three different normalization methods, RMA (Robust Multi-chip Analysis), GC-RMA and PLIER (Probe Logarithmic Intensity Error), were applied to explore differentially expressed genes. We identified a list of 28 biologically meaningful, significantly differentially expressed genes. Genes up-regulated by selenium supplementation included TNF, IL1B, IL8, SOD2, CXCL2 and several other immunological and oxidative stress-related genes. When mapped to a biological association network, many of the differentially expressed genes were found to regulate functional classes such as fibroblast growth factor, collagenase, matrix metalloproteinase and stromelysin-1, and thus, considered to affect cellular processes like apoptosis, proliferation and others. Many of the significantly up-regulated genes following selenium-supplementation were previously found by us to be down-regulated in a different set of individuals with As-induced skin lesions compared to those without. In conclusion, findings from this study may elucidate the biological effect of selenium supplementation in humans. Additionally, this study suggests that long-term selenium supplementation may revert some of the gene expression changes presumably induced by chronic As exposure in individuals with pre-malignant skin lesions. PMID:17293063

  4. Brazilian red propolis effects on peritoneal macrophage activity: Nitric oxide, cell viability, pro-inflammatory cytokines and gene expression.

    PubMed

    Bueno-Silva, Bruno; Kawamoto, Dione; Ando-Suguimoto, Ellen S; Casarin, Renato C V; Alencar, Severino M; Rosalen, Pedro L; Mayer, Marcia P A

    2017-07-31

    Propolis has been used in folk medicine since ancient times and it presented inhibitory effect on neutrophil recruitment previously. However, its effect on macrophage obtained from mice remains unclear. To demonstrate BRP effects on LPS activated peritoneal macrophage. Peritoneal macrophages, obtained from C57BL6 mice and activated with LPS, were treated with 50-80µg/mL of crude extract of Brazilian red propolis (BRP) during 48h. Cell viability, levels of NO, 20 cytokines and expression of 360 genes were evaluated. BRP 60µg/mL reduced NO production by 65% without affecting the cell viability and decreased production IL1α, IL1β, IL4, IL6, IL12p40, Il12p70, IL13, MCP1 and GM-CSF. Molecular mechanism beyond the anti-inflammatory activity may be due to BRP-effects on decreasing expression of Mmp7, Egfr, Adm, Gata3, Wnt2b, Txn1, Herpud1, Axin2, Car9, Id1, Vegfa, Hes1, Hes5, Icam1, Wnt3a, Pcna, Wnt5a, Tnfsf10, Ccl5, Il1b, Akt1, Mapk1, Noxa1 and Cdkn1b and increasing expression of Cav1, Wnt6, Calm1, Tnf, Rb1, Socs3 and Dab2. Therefore, BRP has anti-inflammatory effects on macrophage activity by reducing NO levels and diminished release and expression of pro-inflammatory cytokine and genes, respectively. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  5. 27 CFR 9.175 - Dos Rios.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... is located in northern Mendocino County, California, at the confluence of the Eel River and the Middle Fork of the Eel River. The area's boundaries are defined as follows— (1) Beginning in the... the Middle Fork of the Eel River, to the southeast corner of section 11, T21N, R13W (Dos...

  6. "DOS for Managers." Management Training Series.

    ERIC Educational Resources Information Center

    Marion County Schools, Fairmont, WV.

    A plan is provided for a lesson on disk operating systems (DOS) for managers. Twenty-five lesson objectives are listed, followed by suggestions for learning activities and special resources. In the presentation section, key points and content are provided for 25 instructional topics that correspond to the 25 lesson objectives. The topics are as…

  7. Analysis of the association between interleukin-1beta (+3954) gene polymorphism and chronic periodontitis in a sample of the south Indian population.

    PubMed

    Kaarthikeyan, Gurumoorthy; Jayakumar, Nadathur Doraisamy; Padmalatha, Ogoti; Sheeja, Varghese; Sankari, Malaippan; Anandan, Balakrisnan

    2009-01-01

    The aim of this study was to determine the association between IL-1B (+3954) gene polymorphism and chronic periodontitis in a sample of the south Indian population. This study employed a cross-sectional design involving individuals from the state of Tamil Nadu in the southern part of India. Genomic DNA was obtained from the white blood cells of 30 patients with chronic periodontitis (18 males and 12 females) and 31 healthy controls (20 males and 11 females). The age of the subjects ranged from 30 to 55 years old and all were non smokers. DNA was amplified using the polymerase chain reaction (PCR) with specific primers flanking the locus +3954 of IL-1beta gene and analyzed by 3% agarose gel electrophoresis. A Chi-square test was used to determine the genotype distribution between the groups and the relative risk was estimated with a 95% confidence interval. The chronic periodontitis group displayed a higher percentage of T allele, even though it was not statistically significant. The relative risk analysis between genotypes showed that the risk was higher for the CT genotype compared with the CC genotype and the risk was significant. In conclusion, our data suggested that there was no significant association between IL-1beta (+3954) gene polymorphism and chronic periodontitis in the south Indian population.

  8. Influence of 5-amino-3-methyl-4-isoxazolecarbohydrazide on selective gene expression in Caco-2 cultured cells.

    PubMed

    Płoszaj, Paulina; Regiec, Andrzej; Ryng, Stanisław; Piwowar, Agnieszka; Kruzel, Marian L

    2016-10-17

    The 5-amino-3-methyl-4-isoxazolecarboxylic acid hydrazide (HIX) is a synthetic isoxazole derivative with a potential for development as an anti-inflammatory drug candidate. The goal of this study was to explore in vitro autoimmune and inflammatory gene modulation by HIX in human Caco-2 cultured cells. The effect of low dose of HIX was tested on the expression level of RNA in 24h Caco-2 cultures using the QIAGEN Th17 for Autoimmunity & Inflammation RT(2) Profiler PCR Array. We choose the PCR technology as the most reliable and sensitive gene expression profiling method for analyzing specific gene regulatory networks. In all experiments, Leflunomide (5-methyl-N-[4-(trifluoromethyl)phenyl]-4-isoxazolecarboxamide), an immuno-suppressive disease-modifying antirheumatic drug was used, as a reference to clinical utility of the isoxazole derivatives. Changes in RNA levels were analyzed and differentially expressed genes with at least 2-fold change were identified. For the majority of genes tested, the effects of HIX and Leflunomide were similar, including up-regulation of CX3CL1 and IL-17F, and down-regulation of IL-10 and TLR4. However twelve genes were were differently regulated by the two compounds: interleukins (IL) IL-1B, IL-6 and a chemokine CCL22 were upregulated by HIX and significantly supressed by Leflunomide. In contrary, IL-2 and IL-27 were upregulated by Leflunomide and suppressed by HIX. The network search by Ingenuity Pathway Analysis showed, that majority of differentially expressed genes were involved in cellular inflammatory responses. These results suggest that 5-amino-3-methyl-4-isoxazolecarbohydrazide has a potential for future clinical developments with structure modification as a disease modifying agent in different than Leflunomide applications.

  9. Identification of S100A8-correlated genes for prediction of disease progression in non-muscle invasive bladder cancer

    PubMed Central

    2010-01-01

    Background S100 calcium binding protein A8 (S100A8) has been implicated as a prognostic indicator in several types of cancer. However, previous studies are limited in their ability to predict the clinical behavior of the cancer. Here, we sought to identify a molecular signature based on S100A8 expression and to assess its usefulness as a prognostic indicator of disease progression in non-muscle invasive bladder cancer (NMIBC). Methods We used 103 primary NMIBC specimens for microarray gene expression profiling. The median follow-up period for all patients was 57.6 months (range: 3.2 to 137.0 months). Various statistical methods, including the leave-one-out cross validation method, were applied to identify a gene expression signature able to predict the likelihood of progression. The prognostic value of the gene expression signature was validated in an independent cohort (n = 302). Results Kaplan-Meier estimates revealed significant differences in disease progression associated with the expression signature of S100A8-correlated genes (log-rank test, P < 0.001). Multivariate Cox regression analysis revealed that the expression signature of S100A8-correlated genes was a strong predictor of disease progression (hazard ratio = 15.225, 95% confidence interval = 1.746 to 133.52, P = 0.014). We validated our results in an independent cohort and confirmed that this signature produced consistent prediction patterns. Finally, gene network analyses of the signature revealed that S100A8, IL1B, and S100A9 could be important mediators of the progression of NMIBC. Conclusions The prognostic molecular signature defined by S100A8-correlated genes represents a promising diagnostic tool for the identification of NMIBC patients that have a high risk of progression to muscle invasive bladder cancer. PMID:20096140

  10. DOS: the discrete-ordinates system. [LMFBR

    SciTech Connect

    Rhoades, W. A.; Emmett, M. B.

    1982-09-01

    The Discrete Ordinates System determines the flux of neutrons or photons due either to fixed sources specified by the user or to sources generated by particle interaction with the problem materials. It also determines numerous secondary results which depend upon flux. Criticality searches can be performed. Numerous input, output, and file manipulation facilities are provided. The DOS driver program reads the problem specification from an input file and calls various program modules into execution as specified by the input file.

  11. DIGLIB. PC-DOS Graphics Subroutine Library

    SciTech Connect

    Brand, H.R.

    1989-02-01

    DIGLIB is a collection of general graphics subroutines. It was designed to be small, reasonably fast, device-independent, and compatible with DEC-supplied operating systems for VAXes, PDP-11s, and LSI-11s, and the DOS operating system for IBM PCs and IBM-compatible machines. DIGLIB/VMS runs on the VAX and MicroVAX series of computers under VMS. The software is readily usable by casual programmers for two-dimensional plotting.

  12. Altered cytokine gene expression in peripheral blood monocytes across the menstrual cycle in primary dysmenorrhea: a case-control study.

    PubMed

    Ma, Hongyue; Hong, Min; Duan, Jinao; Liu, Pei; Fan, Xinsheng; Shang, Erxin; Su, Shulan; Guo, Jianming; Qian, Dawei; Tang, Yuping

    2013-01-01

    Primary dysmenorrhea is one of the most common gynecological complaints in young women, but potential peripheral immunologic features underlying this condition remain undefined. In this paper, we compared 84 common cytokine gene expression profiles of peripheral blood mononuclear cells (PBMCs) from six primary dysmenorrheic young women and three unaffected controls on the seventh day before (secretory phase), and the first (menstrual phase) and the fifth (regenerative phase) days of menstruation, using a real-time PCR array assay combined with pattern recognition and gene function annotation methods. Comparisons between dysmenorrhea and normal control groups identified 11 (nine increased and two decreased), 14 (five increased and nine decreased), and 15 (seven increased and eight decreased) genes with ≥ 2-fold difference in expression (P<0.05) in the three phases of menstruation, respectively. In the menstrual phase, genes encoding pro-inflammatory cytokines (IL1B, TNF, IL6, and IL8) were up-regulated, and genes encoding TGF-β superfamily members (BMP4, BMP6, GDF5, GDF11, LEFTY2, NODAL, and MSTN) were down-regulated. Functional annotation revealed an excessive inflammatory response and insufficient TGF-β superfamily member signals with anti-inflammatory consequences, which may directly contribute to menstrual pain. In the secretory and regenerative phases, increased expression of pro-inflammatory cytokines and decreased expression of growth factors were also observed. These factors may be involved in the regulation of decidualization, endometrium breakdown and repair, and indirectly exacerbate primary dysmenorrhea. This first study of cytokine gene expression profiles in PBMCs from young primary dysmenorrheic women demonstrates a shift in the balance between expression patterns of pro-inflammatory cytokines and TGF-β superfamily members across the whole menstrual cycle, underlying the peripheral immunologic features of primary dysmenorrhea.

  13. Genes that determine immunology and inflammation modify the basic defect of impaired ion conductance in cystic fibrosis epithelia

    PubMed Central

    Becker, Tim; Kumar, Vinod; Hedtfeld, Silke; Becker, Christian; Cuppens, Harry; Tamm, Stephanie; Yarden, Jennifer; Laabs, Ulrike; Siebert, Benny; Fernandez, Luis; Macek, Milan; Radojkovic, Dragica; Ballmann, Manfred; Greipel, Joachim; Cassiman, Jean-Jacques; Wienker, Thomas F; Tümmler, Burkhard

    2010-01-01

    Background The cystic fibrosis (CF) basic defect, caused by dysfunction of the apical chloride channel CFTR in the gastrointestinal and respiratory tract epithelia, has not been employed so far to support the role of CF modifier genes. Methods Patients were selected from 101 families with a total of 171 F508del-CFTR homozygous CF patients to identify CF modifying genes. A candidate gene based association study of 52 genes on 16 different chromosomes with a total of 182 genetic markers was performed. Differences in haplotype and/or diplotype distribution between case and reference CF subpopulations were analysed. Results Variants at immunologically relevant genes were associated with the manifestation of the CF basic defect (0.01IL1B, TLR9, TNFα, CD95, STAT3 and TNFR). The intragenic background of F508del-CFTR chromosomes determined disease severity and manifestation of the basic defect (Praw=0.0009). Allele distributions comparing transmitted and non-transmitted alleles were distorted at several loci unlinked to CFTR. Conclusions The inherited capabilities of the innate and adaptive immune system determine the manifestation of the CF basic defect. Variants on F508del-CFTR chromosomes contribute to the observed patient-to-patient variability among F508del-CFTR homozygotes. A survivor effect, manifesting as a transmission disequilibrium at many loci, is consistent with the improvement of clinical care over the last decades, resulting in a depletion of risk alleles at modifier genes. Awareness of non-genetic factors such as improvement of patient care over time is crucial for the interpretation of CF modifier studies. PMID:20837493

  14. Genes that determine immunology and inflammation modify the basic defect of impaired ion conductance in cystic fibrosis epithelia.

    PubMed

    Stanke, Frauke; Becker, Tim; Kumar, Vinod; Hedtfeld, Silke; Becker, Christian; Cuppens, Harry; Tamm, Stephanie; Yarden, Jennifer; Laabs, Ulrike; Siebert, Benny; Fernandez, Luis; Macek, Milan; Radojkovic, Dragica; Ballmann, Manfred; Greipel, Joachim; Cassiman, Jean-Jacques; Wienker, Thomas F; Tümmler, Burkhard

    2011-01-01

    The cystic fibrosis (CF) basic defect, caused by dysfunction of the apical chloride channel CFTR in the gastrointestinal and respiratory tract epithelia, has not been employed so far to support the role of CF modifier genes. Patients were selected from 101 families with a total of 171 F508del-CFTR homozygous CF patients to identify CF modifying genes. A candidate gene based association study of 52 genes on 16 different chromosomes with a total of 182 genetic markers was performed. Differences in haplotype and/or diplotype distribution between case and reference CF subpopulations were analysed. Variants at immunologically relevant genes were associated with the manifestation of the CF basic defect (0.01IL1B, TLR9, TNFα, CD95, STAT3 and TNFR). The intragenic background of F508del-CFTR chromosomes determined disease severity and manifestation of the basic defect (Praw=0.0009). Allele distributions comparing transmitted and non-transmitted alleles were distorted at several loci unlinked to CFTR. The inherited capabilities of the innate and adaptive immune system determine the manifestation of the CF basic defect. Variants on F508del-CFTR chromosomes contribute to the observed patient-to-patient variability among F508del-CFTR homozygotes. A survivor effect, manifesting as a transmission disequilibrium at many loci, is consistent with the improvement of clinical care over the last decades, resulting in a depletion of risk alleles at modifier genes. Awareness of non-genetic factors such as improvement of patient care over time is crucial for the interpretation of CF modifier studies.

  15. Altered Cytokine Gene Expression in Peripheral Blood Monocytes across the Menstrual Cycle in Primary Dysmenorrhea: A Case-Control Study

    PubMed Central

    Ma, Hongyue; Hong, Min; Duan, Jinao; Liu, Pei; Fan, Xinsheng; Shang, Erxin; Su, Shulan; Guo, Jianming; Qian, Dawei; Tang, Yuping

    2013-01-01

    Primary dysmenorrhea is one of the most common gynecological complaints in young women, but potential peripheral immunologic features underlying this condition remain undefined. In this paper, we compared 84 common cytokine gene expression profiles of peripheral blood mononuclear cells (PBMCs) from six primary dysmenorrheic young women and three unaffected controls on the seventh day before (secretory phase), and the first (menstrual phase) and the fifth (regenerative phase) days of menstruation, using a real-time PCR array assay combined with pattern recognition and gene function annotation methods. Comparisons between dysmenorrhea and normal control groups identified 11 (nine increased and two decreased), 14 (five increased and nine decreased), and 15 (seven increased and eight decreased) genes with ≥2-fold difference in expression (P<0.05) in the three phases of menstruation, respectively. In the menstrual phase, genes encoding pro-inflammatory cytokines (IL1B, TNF, IL6, and IL8) were up-regulated, and genes encoding TGF-β superfamily members (BMP4, BMP6, GDF5, GDF11, LEFTY2, NODAL, and MSTN) were down-regulated. Functional annotation revealed an excessive inflammatory response and insufficient TGF-β superfamily member signals with anti-inflammatory consequences, which may directly contribute to menstrual pain. In the secretory and regenerative phases, increased expression of pro-inflammatory cytokines and decreased expression of growth factors were also observed. These factors may be involved in the regulation of decidualization, endometrium breakdown and repair, and indirectly exacerbate primary dysmenorrhea. This first study of cytokine gene expression profiles in PBMCs from young primary dysmenorrheic women demonstrates a shift in the balance between expression patterns of pro-inflammatory cytokines and TGF-β superfamily members across the whole menstrual cycle, underlying the peripheral immunologic features of primary dysmenorrhea. PMID:23390521

  16. Disk Operating System--DOS. Teacher Packet. Learning Activity Packets.

    ERIC Educational Resources Information Center

    Oklahoma State Dept. of Vocational and Technical Education, Stillwater. Curriculum and Instructional Materials Center.

    The Learning Activity Packets (LAPs) contained in this manual are designed to assist the beginning user in understanding DOS (Disk Operating System). LAPs will not work with any version below DOS Version 3.0 and do not address the enhanced features of versions 4.0 or higher. These elementary activities cover only the DOS commands necessary to…

  17. Biochemical and molecular analysis of pink tomatoes: deregulated expression of the gene encoding transcription factor SlMYB12 leads to pink tomato fruit color.

    PubMed

    Ballester, Ana-Rosa; Molthoff, Jos; de Vos, Ric; Hekkert, Bas te Lintel; Orzaez, Diego; Fernández-Moreno, Josefina-Patricia; Tripodi, Pasquale; Grandillo, Silvana; Martin, Cathie; Heldens, Jos; Ykema, Marieke; Granell, Antonio; Bovy, Arnaud

    2010-01-01

    The color of tomato fruit is mainly determined by carotenoids and flavonoids. Phenotypic analysis of an introgression line (IL) population derived from a cross between Solanum lycopersicum 'Moneyberg' and the wild species Solanum chmielewskii revealed three ILs with a pink fruit color. These lines had a homozygous S. chmielewskii introgression on the short arm of chromosome 1, consistent with the position of the y (yellow) mutation known to result in colorless epidermis, and hence pink-colored fruit, when combined with a red flesh. Metabolic analysis showed that pink fruit lack the ripening-dependent accumulation of the yellow-colored flavonoid naringenin chalcone in the fruit peel, while carotenoid levels are not affected. The expression of all genes encoding biosynthetic enzymes involved in the production of the flavonol rutin from naringenin chalcone was down-regulated in pink fruit, suggesting that the candidate gene underlying the pink phenotype encodes a regulatory protein such as a transcription factor rather than a biosynthetic enzyme. Of 26 MYB and basic helix-loop-helix transcription factors putatively involved in regulating transcription of genes in the phenylpropanoid and/or flavonoid pathway, only the expression level of the MYB12 gene correlated well with the decrease in the expression of structural flavonoid genes in peel samples of pink- and red-fruited genotypes during ripening. Genetic mapping and segregation analysis showed that MYB12 is located on chromosome 1 and segregates perfectly with the characteristic pink fruit color. Virus-induced gene silencing of SlMYB12 resulted in a decrease in the accumulation of naringenin chalcone, a phenotype consistent with the pink-colored tomato fruit of IL1b. In conclusion, biochemical and molecular data, gene mapping, segregation analysis, and virus-induced gene silencing experiments demonstrate that the MYB12 transcription factor plays an important role in regulating the flavonoid pathway in tomato fruit

  18. Genes and Gene Therapy

    MedlinePlus

    ... correctly, a child can have a genetic disorder. Gene therapy is an experimental technique that uses genes to ... or prevent disease. The most common form of gene therapy involves inserting a normal gene to replace an ...

  19. miRNA signatures and transcriptional regulation of their target genes in vitiligo.

    PubMed

    Mansuri, Mohmmad Shoab; Singh, Mala; Begum, Rasheedunnisa

    2016-10-01

    miRNAs are small non-coding RNA molecules that post-transcriptionally regulate gene expression. We have earlier reported the skin miRNA expression profiling in patients with non-segmental vitiligo. In the present study, we show the expression of previously identified skin miRNAs signatures in blood and their target genes in whole blood and PBMCs as well as skin micro-environment of vitiligo patients and controls. miRNA expression profiling in whole blood was performed using customized TaqMan(®) Low Density Array. We predicted the potential targets of differentially expressed miRNAs and investigated their expression levels in skin, whole blood and PBMCs from patients and controls using Real-time PCR. Our results showed miR-1, miR-184, miR-328, miR-383 and miR-577 hold similar pattern of expression as of skin, suggesting their potent eminence for being putative markers for vitiligo. In silico target prediction revealed miR-1 targets EDN1, G6PD, HSP60, HSP70, SERP1, SIRT1 & TYR; miR-184 targets EZR & LAMP1; miR-328 targets IL1B, POLH & TRPM1; miR-383 targets EDN1 & TYRP1; and miR-577 targets PTPN22 & TYRP1 which were corroborated by our validation study. In conclusion, the present study for the first time provides new insights into the crucial role of miRNA regulated gene network involved in oxidative stress, autoimmunity and ER stress mediated pathogenesis of vitiligo. Copyright © 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  20. Thyroid active agents T3 and PTU differentially affect immune gene transcripts in the head kidney of rainbow trout (Oncorynchus mykiss).

    PubMed

    Quesada-García, Alba; Encinas, Paloma; Valdehita, Ana; Baumann, Lisa; Segner, Helmut; Coll, Julio M; Navas, José M

    2016-05-01

    In mammals, numerous reports describe an immunomodulating effect of thyroid-active compounds. In contrast, only few reports have been published on this subject in fish. We previously demonstrated that immune cells of rainbow trout (Oncorhynchus mykiss) possess thyroid hormone receptors (THRs) and that exposure of trout to the thyroid hormone 3,3',5-triiodo-l-thyronine (T3) or the antithyroid drug propylthiouracil (PTU) alters immune cell transcript levels of THR and several immune genes. The present study aims to further characterize the immunomodulating action of thyroid-active compounds in trout immune cells. We report here the use of a custom-designed 60-mer oligo immune-targeted microarray for rainbow trout to analyze the gene expression profiles induced in the head kidney by T3 and PTU. Morphometric analyses of the thyroid showed that PTU exposure increased the size of the epithelial cells, whereas T3 induced no significant effects. Both T3 and PTU had diverse and partly contrasting effects on immune transcript profiles. The strongest differential effects of T3 and PTU on gene expressions were those targeting the Mitogen Associated Protein Kinase (MAPK), NFkB, Natural Killer (NK) and Toll-Like Receptor (TLR) pathways, a number of multipath genes (MPG) such as those encoding pleiotropic transcription factors (atf1, junb, myc), as well as important pro-inflammatory genes (tnfa, tnf6, il1b) and interferon-related genes (ifng, irf10). With these results we show for the first time in a fish species that the in vivo thyroidal status modulates a diversity of immune genes and pathways. This knowledge provides the basis to investigate both mechanisms and consequences of thyroid hormone- and thyroid disruptor-mediated immunomodulation for the immunocompetence of fish.

  1. Concurrent host-pathogen gene expression in the lungs of pigs challenged with Actinobacillus pleuropneumoniae.

    PubMed

    Brogaard, Louise; Klitgaard, Kirstine; Heegaard, Peter M H; Hansen, Mette Sif; Jensen, Tim Kåre; Skovgaard, Kerstin

    2015-05-28

    Actinobacillus pleuropneumoniae causes pleuropneumonia in pigs, a disease which is associated with high morbidity and mortality, as well as impaired animal welfare. To obtain in-depth understanding of this infection, the interplay between virulence factors of the pathogen and defense mechanisms of the porcine host needs to be elucidated. However, research has traditionally focused on either bacteriology or immunology; an unbiased picture of the transcriptional responses can be obtained by investigating both organisms in the same biological sample. Host and pathogen responses in pigs experimentally infected with A. pleuropneumoniae were analyzed by high-throughput RT-qPCR. This approach allowed concurrent analysis of selected genes encoding proteins known or hypothesized to be important in the acute phase of this infection. The expression of 17 bacterial and 31 porcine genes was quantified in lung samples obtained within the first 48 hours of infection. This provided novel insight into the early time course of bacterial genes involved in synthesis of pathogen-associated molecular patterns (lipopolysaccharide, peptidoglycan, lipoprotein) and genes involved in pattern recognition (TLR4, CD14, MD2, LBP, MYD88) in response to A. pleuropneumoniae. Significant up-regulation of proinflammatory cytokines such as IL1B, IL6, and IL8 was observed, correlating with protein levels, infection status and histopathological findings. Host genes encoding proteins involved in iron metabolism, as well as bacterial genes encoding exotoxins, proteins involved in adhesion, and iron acquisition were found to be differentially expressed according to disease progression. By applying laser capture microdissection, porcine expression of selected genes could be confirmed in the immediate surroundings of the invading pathogen. Microbial pathogenesis is the product of interactions between host and pathogen. Our results demonstrate the applicability of high-throughput RT-qPCR for the elucidation

  2. Beyond an AFLP genome scan towards the identification of immune genes involved in plague resistance in Rattus rattus from Madagascar.

    PubMed

    Tollenaere, C; Jacquet, S; Ivanova, S; Loiseau, A; Duplantier, J-M; Streiff, R; Brouat, C

    2013-01-01

    Genome scans using amplified fragment length polymorphism (AFLP) markers became popular in nonmodel species within the last 10 years, but few studies have tried to characterize the anonymous outliers identified. This study follows on from an AFLP genome scan in the black rat (Rattus rattus), the reservoir of plague (Yersinia pestis infection) in Madagascar. We successfully sequenced 17 of the 22 markers previously shown to be potentially affected by plague-mediated selection and associated with a plague resistance phenotype. Searching these sequences in the genome of the closely related species Rattus norvegicus assigned them to 14 genomic regions, revealing a random distribution of outliers in the genome (no clustering). We compared these results with those of an in silico AFLP study of the R. norvegicus genome, which showed that outlier sequences could not have been inferred by this method in R. rattus (only four of the 15 sequences were predicted). However, in silico analysis allowed the prediction of AFLP markers distribution and the estimation of homoplasy rates, confirming its potential utility for designing AFLP studies in nonmodel species. The 14 genomic regions surrounding AFLP outliers (less than 300 kb from the marker) contained 75 genes encoding proteins of known function, including nine involved in immune function and pathogen defence. We identified the two interleukin 1 genes (Il1a and Il1b) that share homology with an antigen of Y. pestis, as the best candidates for genes subject to plague-mediated natural selection. At least six other genes known to be involved in proinflammatory pathways may also be affected by plague-mediated selection. © 2012 Blackwell Publishing Ltd.

  3. Genetic Associations of Interleukin-related Genes with Graves’ Ophthalmopathy: a Systematic Review and Meta-analysis

    PubMed Central

    Wong, Kah Hie; Rong, Shi Song; Chong, Kelvin K. L.; Young, Alvin L.; Pang, Chi Pui; Chen, Li Jia

    2015-01-01

    Graves’ ophthalmopathy (GO) is the commonest extra-thyroidal manifestation of Graves’ disease (GD). Associations between interleukin-related (IL) gene polymorphisms and GO have been reported in different populations. We aim to confirm such associations by conducting a meta-analysis. Totally 382 publications were retrieved in MEDLINE and EMBASE up to 25/2/2015. After removing the duplicates and assessing the studies, we retrieved 16 studies that met the selection criteria for meta-analysis, involving 12 polymorphisms in 8 IL-related genes, and 1650 GO cases and 2909 GD controls. The summary odds ratio (OR) and 95% confidence intervals (CI) were estimated. We found one polymorphism in IL1A (rs1800587, c.-889C>T) showing a suggestive association with GO in the meta-analysis (allelic model [T vs. C]: OR = 1.62, 95% CI: 1.00–2.62, P = 0.050, I2 = 53.7%; recessive model [TT vs. TC + CC]: OR = 2.39, 95% CI: 1.07–5.37, P = 0.039, I2 = 23.6%; heterozygous model [TC vs. CC]: OR = 1.52, 95% CI: 1.04–2.22, P = 0.034, I2 = 37.0%). No association with GO was detected for the other 7 genes (IL1B, IL1RA, IL4, IL6, IL12B, IL13 and IL23R). Our results thus indicate that IL1A is likely to be a genetic biomarker for GO. Further studies with larger sample sizes are warranted to confirm the associations of IL1A and other IL-related genes with GO. PMID:26578206

  4. Association of cytokine gene polymorphisms in CWP and its severity in Turkish coal workers

    SciTech Connect

    Ates, I.; Suzen, H.S.; Yucesoy, B.; Tekin, I.O.; Karakaya, A.

    2008-10-15

    Cytokines appear to play a key role in some inflammatory reactions affecting the interactions among pro- and anti-inflammatory mechanisms that result in several diseases such as coal workers' pneumoconiosis (CWP). In this study, to determine the cytokine gene profiles of Turkish coal miners, we performed genotyping analysis to investigate the polymorphisms of CWP-related pro-inflammatory (TNFA, IL1A, IL1B, and IL6) and anti-inflammatory cytokines (IL-1RN and TGFB1). Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. TNFA (-238) gene polymorphism principally affected CWP development and severity (OR=3.47: 95% CI, 1.12-10.77 and OR=4.30: 95% CI, 1.25-14.74, respectively) and also risk of CWP (OR=3.79: 95% CI, 1.37-10.46). The TNFA (-308) variant was associated with a risk for the CWP severity (OR = 2.84: 95% CI, 1.08-7.39). A protective effect of IL6 was found on the development (OR = 0.48: 95% CI, 0.21-0.93) and severity of CWP (OR = 0.37: 95% CI, 0.15-0.91). We suggest that TNFA (-238) variant may be a risk factor in both development and the severity, of CWP while TNFA (-308) variant seems to be important only in disease severity On the other hand, IL6 variant may have a protective effect on the development and disease severity.

  5. Subclinical Pregnancy Toxemia-Induced Gene Expression Changes in Ovine Placenta and Uterus

    PubMed Central

    Kasimanickam, Ramanathan K.

    2016-01-01

    The objective was to elucidate gene expression differences in uterus, caruncle, and cotyledon of ewes with subclinical pregnancy toxemia (SCPT) and healthy ewes, and to identify associated biological functions and pathways involved in pregnancy toxemia. On Day 136 (±1 day) post-breeding, ewes (n = 18) had body condition score (BCS; 1–5; 1, emaciated; 5, obese) assessed, and blood samples were collected for plasma glucose and β-hydroxybutyrate (BHBA) analyses. The ewes were euthanized, and tissue samples were collected from the gravid uterus and placentomes. Based on BCS (2.0 ± 0.02), glucose (2.4 ± 0.33), and BHBA (0.97 ± 0.06) concentrations, ewes (n = 10) were grouped as healthy (n = 5) and subclinical SCPT (n = 5) ewes. The mRNA expressions were determined by quantitative PCR method, and prediction of miRNA partners and target genes for the predicted miRNA were identified using miRDB (http://mirdb.org/miRDB/). Top ranked target genes were used to identify associated biological functions and pathways in response to SPCT using PANTHER. The angiogenesis genes VEGF and PlGF, and AdipoQ, AdipoR2, PPARG, LEP, IGF1, IGF2, IL1b, and TNFα mRNA expressions were lower in abundances, whereas hypoxia genes eNOS, HIF1a, and HIF 2a, and sFlt1 and KDR mRNA expressions were greater in abundances in uterus and placenta of SCPT ewes compared to healthy ewes (P < 0.05). The predicted miRNA and associated target genes contributed to several biological processes, including apoptosis, biological adhesion, biological regulation, cellular component biogenesis, cellular process, developmental process, immune system process, localization, metabolic process, multicellular organismal process, reproduction, and response to stimulus. The target genes were involved in several pathways including angiogenesis, cytoskeletal regulation, hypoxia response via HIF activation, interleukin signaling, ubiquitin proteasome, and VEGF signaling pathway. In

  6. Association of the −31C/T functional polymorphism in the interleukin-1β gene with the intractability of Graves' disease and the proportion of T helper type 17 cells

    PubMed Central

    Hayashi, F; Watanabe, M; Nanba, T; Inoue, N; Akamizu, T; Iwatani, Y

    2009-01-01

    Interleukin (IL)-1β is a proinflammatory cytokine and has been implicated in the pathogenesis of several autoimmune diseases. To evaluate the hypothesis that the functional −31C/T polymorphism (rs1143627) in the gene encoding IL-1β is associated with the intractability and the severity of autoimmune thyroid diseases, we genotyped this polymorphism in 64 patients with intractable Graves' disease (GD), 28 GD patients in remission, 49 patients with Hashimoto's disease (HD) who developed hypothyroidism (severe HD), 28 untreated euthyroid HD patients (mild HD) and 59 healthy volunteers. The −31T allele, which is related to the high producibility of IL-1β, was significantly more frequent in patients with intractable GD than in those with GD in remission (P = 0·0017; odds ratio 2·8; 95% confidence interval 1·5-5·3), although there was no difference in this frequency between two groups of HD patients. We showed additionally that the proportion of IL-17-producing T helper type 17 (Th17) cells, whose differentiation and proliferation are promoted by IL-1β, was higher in autoimmune thyroid disease patients with the T allele than in those with CC genotypes. In conclusion, our data indicated that the T allele of −31C/T polymorphism in the IL1B gene was involved in the intractability of GD, and this involvement may arise through the differentiation and proliferation of Th17 cells. PMID:19793334

  7. Gene expression profiling in the lungs of pigs with different susceptibilities to Glässer's disease

    PubMed Central

    2010-01-01

    Background Haemophilus parasuis is the causative agent of Glässer's disease in pigs. Currently, little is known about the molecular mechanisms that contribute to disease susceptibility. This study used a porcine oligonucleotide microarray to identify genes that were differentially expressed (DE) in the lungs of colostrum-deprived animals previously characterized as being either 'Fully Resistant' (FR) or 'Susceptible' to infection by H. parasuis in a bacterial challenge experiment. Results Gene expression profiles of 'FR' and 'Susceptible' animals were obtained by the identification of genes that were differentially expressed between each of these groups and mock-inoculated 'Control' animals. At 24 hours post-inoculation, a total of 21 and 58 DE genes were identified in 'FR' and 'Susceptible' animals respectively. At 72 hours, the numbers of genes were 20 and 347 respectively. 'FR' animals at 24 hours exhibited an increased expression of genes encoding extracellular matrix and TGF-β signalling components, possibly indicative of tissue repair following the successful early resolution of infection. The gene expression profile of 'FR' animals at 72 hours supported the hypothesis that higher levels of antibacterial activity were responsible for the 'FR' phenotype, possibly due to an increase in natural immunoglobulin A and decrease in signalling by the immunoregulatory transcription factor peroxisome proliferator-activated receptor gamma (PPAR-γ). The expression profile of 'Susceptible' animals at both time-points was characterized by an imbalance in signalling between pro and anti-inflammatory cytokines and an increased expression of genes involved in biological processes associated with inflammation. These include the pro-inflammatory cytokine genes resistin (RETN) and interleukin 1-beta (IL1B). At 72 hours, a reduction in the expression of genes involved in antigen presentation by both MHC class I and II molecules was observed, which could have contributed to the

  8. Interleukin 1 gene cluster SNPs (rs1800587, rs1143634) influences post-orthodontic root resorption in endodontic and their contralateral vital control teeth differently.

    PubMed

    Iglesias-Linares, A; Yañez-Vico, R M; Ballesta, S; Ortiz-Ariza, E; Mendoza-Mendoza, A; Perea, E; Solano-Reina, E

    2012-11-01

    To investigate whether the genetic variants of the interleukin-1 gene cluster (IL1) are associated with a possible genetically induced variability in post-orthodontic external apical root resorption (EARR) in root filled teeth and their control counterparts with vital pulps. One hundred and forty-six maxillary premolars were evaluated radiographically following orthodontic treatment. Genetic screening was performed on orthodontic patients for two single-nucleotide polymorphisms (SNPs: rs1800587 and rs1143634) in the IL1 gene cluster. Subjects were divided into two groups according to the presence or absence of radiographic post-orthodontic EARR (>2 mm) in root filled teeth and their controls with vital pulps. Logistic regression analysis was performed to obtain an adjusted estimation between EARR and IL1 polymorphisms. Allelic frequencies, genotype distributions, and adjusted odds ratio (OR), at 95% confidence interval, were also calculated. Whilst no clear statistical association was found for gene variations in IL1A, a sound association was found in the comparative analysis of subjects homozygous [2/2(TT)] for the IL1B gene, which resulted in a two times increased risk of suffering post-orthodontic EARR in root filled teeth [OR, 2.032 (P = 0.031); CI,1.99-14.77] when compared with their controls with vital pulps. There was, however, a shared predisposition to EARR in controls with vital pulps and root filled teeth of subjects homozygous for allele 1 [OR, 5.05 (P = 0.002)] and [OR, 2.77 (P = 0.037)], respectively. Genetic variations in the interleukin-1β gene (rs1143634) predispose root filled teeth to EARR for matched pairs secondary to orthodontic treatment in a different way from their control teeth with vital pulps in subjects homozygous for allele 2 [2/2(TT)]. © 2012 International Endodontic Journal.

  9. Gene expression analysis of the microdissected trophoblast layer of human placenta after the spontaneous onset of labor.

    PubMed

    Kim, Soo Hyun; Shim, Sung Han; Sung, Se Ra; Lee, Kyung A; Shim, Jung Yun; Cha, Dong Hyun; Lee, Kyoung Jin

    2013-01-01

    Despite increasing evidence that human parturition is associated with alteration in gene expression in the uteroplacental unit, the precise mechanisms that elicit spontaneous term labor in humans remain unknown. Our goal in this study was to compare the mRNA expression pattern of the trophoblast layer of normal term placenta between women who had given natural birth (labor group) and those who had undergone an elective cesarean section without labor (non-labor group). We collected placental tissue samples from six pregnant women after term vaginal deliveries (labor group) and from six pregnant women after scheduled Cesarean sections (non-labor group). Frozen sections were made immediately after placental delivery. Because the placenta is a heterogeneous tissue composed of several cell types, we used laser capture microdissection to separate the trophoblast layer from the rest of the placental tissues. A number of genes were differentially expressed in the trophoblast layer when the labor and non-labor groups were compared. The expression of SIRT1, KAP1, and CRH was significantly lower in the trophoblast layer of the labor group than of the non-labor group. The expression of IL-1b, NF-kB1 and TLR 8 in the labor group was significantly higher than that in the non-labor group. Human term labor may be closely associated with inflammatory response. We suggest that downregulation of SIRT1, KAP1, and CRH gene expression in the trophoblast may play a key role in parturition and initiation of labor in pregnant human females.

  10. Role of gene polymorphisms in gastric cancer and its precursor lesions: Current knowledge and perspectives in Latin American countries

    PubMed Central

    Chiurillo, Miguel Angel

    2014-01-01

    Latin America shows one of the highest incidence rates of gastric cancer in the world, with variations in mortality rates among nations or even within countries belonging to this region. Gastric cancer is the result of a multifactorial complex process, for which a multistep model of carcinogenesis is currently accepted. Additionally to the infection with Helicobacter pylori, that plays a major role, environmental factors as well as genetic susceptibility factors are significant players at different stages in the gastric cancer process. The differences in population origin, demographic structure, socio-economic development, and the impact of globalization lifestyles experienced in Latin America in the last decades, all together offer opportunities for studying in this context the influence of genetic polymorphisms in the susceptibility to gastric cancer. The aim of this article is to discuss current trends on gastric cancer in Latin American countries and to review the available published information about studies of association of gene polymorphisms involved in gastric cancer susceptibility from this region of the world. A total of 40 genes or genomic regions and 69 genetic variants, 58% representing markers involved in inflammatory response, have been used in a number of studies in which predominates a low number of individuals (cases and controls) included. Polymorphisms of IL-1B (-511 C/T, 14 studies; -31 T/C, 10 studies) and IL-1RN (variable number of tandem repeats, 17 studies) are the most represented ones in the reviewed studies. Other genetic variants recently evaluated in large meta-analyses and associated with gastric cancer risk were also analyzed in a few studies [e.g., prostate stem cell antigen (PSCA), CDH1, Survivin]. Further and better analysis centered in gene polymorphisms linked to other covariates, epidemiological studies and the information provided by meta-analyses and genome-wide association studies should help to improve our understanding of

  11. Gene expression profiling of porcine mammary epithelial cells after challenge with Escherichia coli and Staphylococcus aureus in vitro.

    PubMed

    Jaeger, Alexandra; Bardehle, Danilo; Oster, Michael; Günther, Juliane; Muráni, Eduard; Ponsuksili, Siriluck; Wimmers, Klaus; Kemper, Nicole

    2015-05-06

    Postpartum Dysgalactia Syndrome (PDS) represents a considerable health problem of postpartum sows, primarily indicated by mastitis and lactation failure. The poorly understood etiology of this multifactorial disease necessitates the use of the porcine mammary epithelial cell (PMEC) model to identify how and to what extent molecular pathogen defense mechanisms prevent bacterial infections at the first cellular barrier of the gland. PMEC were isolated from three lactating sows and challenged with heat-inactivated potential mastitis-causing pathogens Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) for 3 h and 24 h, in vitro. We focused on differential gene expression patterns of PMEC after pathogen challenge in comparison with the untreated control by performing microarray analysis. Our results show that a core innate immune response of PMEC is partly shared by E. coli and S. aureus. But E. coli infection induces much faster and stronger inflammatory response than S. aureus infection. An immediate and strong up-regulation of genes encoding cytokines (IL1A and IL8), chemokines (CCL2, CXCL1, CXCL2, CXCL3, and CXCL6) and cell adhesion molecules (VCAM1, ICAM1, and ITGB3) was explicitly obvious post-challenge with E. coli inducing a rapid recruitment and activation of cells of host defense mediated by IL1B and TNF signaling. In contrast, S. aureus infection rather induces the expression of genes encoding monooxygenases (CYP1A1, CYP3A4, and CYP1B1) initiating processes of detoxification and pathogen elimination. The results indicate that the course of PDS depends on the host recognition of different structural and pathogenic profiles first, which critically determines the extent and effectiveness of cellular immune defense after infection.

  12. Gene Expression Analysis of the Microdissected Trophoblast Layer of Human Placenta after the Spontaneous Onset of Labor

    PubMed Central

    Kim, Soo Hyun; Shim, Sung Han; Sung, Se Ra; Lee, Kyung A.; Shim, Jung Yun; Cha, Dong Hyun; Lee, Kyoung Jin

    2013-01-01

    Background Despite increasing evidence that human parturition is associated with alteration in gene expression in the uteroplacental unit, the precise mechanisms that elicit spontaneous term labor in humans remain unknown. Our goal in this study was to compare the mRNA expression pattern of the trophoblast layer of normal term placenta between women who had given natural birth (labor group) and those who had undergone an elective cesarean section without labor (non-labor group). Methods We collected placental tissue samples from six pregnant women after term vaginal deliveries (labor group) and from six pregnant women after scheduled Cesarean sections (non-labor group). Frozen sections were made immediately after placental delivery. Because the placenta is a heterogeneous tissue composed of several cell types, we used laser capture microdissection to separate the trophoblast layer from the rest of the placental tissues. Results A number of genes were differentially expressed in the trophoblast layer when the labor and non-labor groups were compared. The expression of SIRT1, KAP1, and CRH was significantly lower in the trophoblast layer of the labor group than of the non-labor group. The expression of IL-1b, NF-kB1 and TLR 8 in the labor group was significantly higher than that in the non-labor group. Conclusions Human term labor may be closely associated with inflammatory response. We suggest that downregulation of SIRT1, KAP1, and CRH gene expression in the trophoblast may play a key role in parturition and initiation of labor in pregnant human females. PMID:24147045

  13. Inhibitors of Mycobacterium tuberculosis DosRST signaling and persistence.

    PubMed

    Zheng, Huiqing; Colvin, Christopher J; Johnson, Benjamin K; Kirchhoff, Paul D; Wilson, Michael; Jorgensen-Muga, Katriana; Larsen, Scott D; Abramovitch, Robert B

    2017-02-01

    The Mycobacterium tuberculosis (Mtb) DosRST two-component regulatory system promotes the survival of Mtb during non-replicating persistence (NRP). NRP bacteria help drive the long course of tuberculosis therapy; therefore, chemical inhibition of DosRST may inhibit the ability of Mtb to establish persistence and thus shorten treatment. Using a DosRST-dependent fluorescent Mtb reporter strain, a whole-cell phenotypic high-throughput screen of a ∼540,000 compound small-molecule library was conducted. The screen discovered novel inhibitors of the DosRST regulon, including three compounds that were subject to follow-up studies: artemisinin, HC102A and HC103A. Under hypoxia, all three compounds inhibit Mtb-persistence-associated physiological processes, including triacylglycerol synthesis, survival and antibiotic tolerance. Artemisinin functions by disabling the heme-based DosS and DosT sensor kinases by oxidizing ferrous heme and generating heme-artemisinin adducts. In contrast, HC103A inhibits DosS and DosT autophosphorylation activity without targeting the sensor kinase heme.

  14. Pilot study of small bowel mucosal gene expression in patients with irritable bowel syndrome with diarrhea.

    PubMed

    Camilleri, Michael; Carlson, Paula; Valentin, Nelson; Acosta, Andres; O'Neill, Jessica; Eckert, Deborah; Dyer, Roy; Na, Jie; Klee, Eric W; Murray, Joseph A

    2016-09-01

    Prior studies in with irritable bowel syndrome with diarrhea (IBS-D) patients showed immune activation, secretion, and barrier dysfunction in jejunal or colorectal mucosa. We measured mRNA expression by RT-PCR of 91 genes reflecting tight junction proteins, chemokines, innate immunity, ion channels, transmitters, housekeeping genes, and controls for DNA contamination and PCR efficiency in small intestinal mucosa from 15 IBS-D and 7 controls (biopsies negative for celiac disease). Fold change was calculated using 2((-ΔΔCT)) formula. Nominal P values (P < 0.05) were interpreted with false detection rate (FDR) correction (q value). Cluster analysis with Lens for Enrichment and Network Studies (LENS) explored connectivity of mechanisms. Upregulated genes (uncorrected P < 0.05) were related to ion transport (INADL, MAGI1, and SONS1), barrier (TJP1, 2, and 3 and CLDN) or immune functions (TLR3, IL15, and MAPKAPK5), or histamine metabolism (HNMT); downregulated genes were related to immune function (IL-1β, TGF-β1, and CCL20) or antigen detection (TLR1 and 8). The following genes were significantly upregulated (q < 0.05) in IBS-D: INADL, MAGI1, PPP2R5C, MAPKAPK5, TLR3, and IL-15. Among the 14 nominally upregulated genes, there was clustering of barrier and PDZ domains (TJP1, TJP2, TJP3, CLDN4, INADL, and MAGI1) and clustering of downregulated genes (CCL20, TLR1, IL1B, and TLR8). Protein expression of PPP2R5C in nuclear lysates was greater in patients with IBS-D and controls. There was increase in INADL protein (median 9.4 ng/ml) in patients with IBS-D relative to controls (median 5.8 ng/ml, P > 0.05). In conclusion, altered transcriptome (and to lesser extent protein) expression of ion transport, barrier, immune, and mast cell mechanisms in small bowel may reflect different alterations in function and deserves further study in IBS-D.

  15. Single Nucleotide Variants of Candidate Genes in Aggrecan Metabolic Pathway Are Associated with Lumbar Disc Degeneration and Modic Changes

    PubMed Central

    Dissanayake, Poruwalage Harsha; Senarath, Upul; Wijayaratne, Lalith Sirimevan; Karunanayake, Aranjan Lional; Dissanayake, Vajira Harshadeva Weerabaddana

    2017-01-01

    Introduction Lumbar disc degeneration (LDD) is genetically determined and severity of LDD is associated with Modic changes. Aggrecan is a major proteoglycan in the intervertebral disc and end plate. Progressive reduction of aggrecan is a main feature of LDD and Modic changes. Objectives The study investigated the associations of single nucleotide variants (SNVs) of candidate genes in the aggrecan metabolic pathway with the severity of LDD and Modic changes. In-silico functional analysis of significant SNVs was also assessed. Methods A descriptive cross sectional study was carried out on 106 patients with chronic mechanical low back pain. T1, T2 sagittal lumbar MRI scans were used to assess the severity of LDD and Modic changes. 62 SNVs in ten candidate genes (ACAN, IL1A, IL1B, IL6, MMP3, ADAMTS4, ADAMTS5, TIMP1, TIMP2 and TIMP3) were genotyped on Sequenom MassARRAY iPLEX platform. Multiple linear regression analysis was carried out using PLINK 1.9 in accordance with additive genetic model. In-silico functional analysis was carried out using Provean, SIFT, PolyPhen and Mutation Taster. Results Mean age was 52.42±9.42 years. 74 (69.8%) were females. The rs2856836, rs1304037, rs17561 and rs1800587 variants of the IL1A gene were associated with the severity of LDD and Modic changes. The rs41270041 variant of the ADAMTS4 gene and the rs226794 variant of the ADAMTS5 gene were associated with severity of LDD while the rs34884997 variant of the ADAMTS4 gene, the rs55933916 variant of the ADAMTS5 gene and the rs9862 variant of the TIMP3 gene were associated with severity of Modic changes. The rs17561 variant of the IL1A gene was predicted as pathogenic by the PolyPhen prediction tool. Conclusions SNVs of candidate genes in ACAN metabolic pathway are associated with severity of LDD and Modic changes in patients with chronic mechanical low back pain. Predictions of in-silico functional analysis of significant SNVs are inconsistent. PMID:28081267

  16. Host Genes and Resistance/Sensitivity to Military Priority Pathogens

    DTIC Science & Technology

    2012-06-01

    Acinetobacter baumannii (Ab), Leishmania major (Lm), SARS, H5Ni avian influenza ) using BXD recombinant inbred mice. We have identified 38 phenotypes...Burkholderia pseudomallei, Severe Acute Respiratory Syndrome (SARS-CoV), highly pathogenic H5N1 Avian Influenza virus, Francisella tularensis and multidrug...signaling negatively affects the outcome of infections with West Nile Virus [48] or influenza virus [49]. The fact that IL- 1b is deleterious in

  17. Midkine in the mouse ventral tegmental area limits ethanol intake and Ccl2 gene expression.

    PubMed

    Chen, H; He, D; Lasek, A W

    2017-09-01

    Midkine (MDK) is a cytokine and neurotrophic factor that is more highly expressed in the brains of alcoholics and in mice predisposed to drink large amounts of ethanol, suggesting that MDK may regulate ethanol consumption. Here we measured ethanol consumption in male and female Mdk knockout (-/-) mice using the two-bottle choice and the drinking in the dark (DID) tests. We found that Mdk -/- mice consumed significantly more ethanol than wild-type controls in both tests. To determine if MDK acts in the ventral tegmental area (VTA) to regulate ethanol consumption, we delivered lentivirus expressing a Mdk shRNA into the VTA of male C57BL/6J mice to locally knockdown Mdk and performed the DID test. Mice expressing a Mdk shRNA in the VTA consumed more ethanol than mice expressing a control non-targeting shRNA, demonstrating that the VTA is one site in the brain through which MDK acts to regulate ethanol consumption. Since MDK also controls the expression of inflammatory cytokines in other organs, we examined gene expression of interleukin-1 beta (Il1b), tumor necrosis factor alpha (Tnfα) and the chemokine (C-C motif) ligand 2 (Ccl2) in the VTA of Mdk -/- mice and in mice expressing Mdk shRNA in the VTA. Expression of Ccl2 was elevated in the VTA of Mdk -/- mice and in mice expressing Mdk shRNA in the VTA. These results demonstrate that MDK functions in the VTA to limit ethanol consumption and levels of CCL2, a chemokine known to increase ethanol consumption. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  18. Genetic variation within the interleukin-1 gene cluster and ischemic stroke.

    PubMed

    Olsson, Sandra; Holmegaard, Lukas; Jood, Katarina; Sjögren, Marketa; Engström, Gunnar; Lövkvist, Håkan; Blomstrand, Christian; Norrving, Bo; Melander, Olle; Lindgren, Arne; Jern, Christina

    2012-09-01

    Evidence is emerging that inflammation plays a key role in the pathophysiology of ischemic stroke (IS). The aim of this study was to investigate whether genetic variation in the interleukin-1α, interleukin-1β, and interleukin-1 receptor antagonist genes (IL1A, IL1B, and IL1RN) is associated with IS and/or any etiologic subtype of IS. Twelve tagSNPs were analyzed in the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS), which comprises 844 patients with IS and 668 control subjects. IS subtypes were defined according to the Trial of Org 10172 in Acute Stroke Treatment criteria in SAHLSIS. The Lund Stroke Register and the Malmö Diet and Cancer study were used as a replication sample for overall IS (in total 3145 patients and 1793 control subjects). The single nucleotide polymorphism rs380092 in IL1RN showed an association with overall IS in SAHLSIS (OR, 1.21; 95% CI, 1.02-1.43; P=0.03), which was replicated in the Lund Stroke Register and the Malmö Diet and Cancer study sample. An association was also detected in all samples combined (OR, 1.12; 95% CI, 1.04-1.21; P=0.03). Three single nucleotide polymorphisms in IL1RN (including rs380092) were nominally associated with the subtype of cryptogenic stroke in SAHLSIS, but the statistical significance did not remain after correction for multiple testing. Furthermore, increased plasma levels of interleukin-1 receptor antagonist were observed in the subtype of cryptogenic stroke compared with controls. This comprehensive study, based on a tagSNP approach and replication, presents support for the role of IL1RN in overall IS.

  19. Polymorphisms in the IL-1A gene are correlated with levels of interleukin-1alpha protein in gingival crevicular fluid of teeth with severe periodontal disease.

    PubMed

    Shirodaria, S; Smith, J; McKay, I J; Kennett, C N; Hughes, F J

    2000-11-01

    Interleukin-1 (IL-1) is a potent stimulator of bone resorption and is strongly implicated in the destruction due to bystander damage seen in periodontal disease. Recent studies suggest that polymorphisms of the (IL-1) gene complex may be significant risk factors for a number of chronic inflammatory diseases. The severity of periodontal disease has been positively associated with carriage of allele 2 at position -889 of the IL-1A gene in conjunction with allele 2 of the IL-1B gene at position +3953. In this study, we tested the hypothesis that allele 2 of the IL-1A gene at position -889 might act to elevate levels of IL-1alpha protein in patients with periodontal disease. Since levels of IL-1alpha protein are low in healthy individuals, we used a group of patients with severe periodontal disease to investigate if levels of IL-1alpha protein in gingival crevicular fluid can be correlated to patient genotype. IL-1alpha levels were measured by enzyme immunoassay in 46 patients with severe periodontal disease. These patients were genotyped by PCR and allele-specific restriction digests. The carriage rate for allele 2 in the diseased population was 68%. Overall, the carriage of allele 2 was associated with almost a four-fold increase in IL-1alpha protein levels. Differences were most pronounced in non-smokers, while heavy smokers showed reduced levels of IL-1alpha protein regardless of genotype. These results suggest a mechanism whereby this genetic polymorphism acts to modulate IL-1alpha protein production and may influence the pathogenesis of periodontal disease by affecting the extent of IL-1-associated bystander damage.

  20. Keratin gene expression profiles after digit amputation in C57BL/6 vs. regenerative MRL mice imply an early regenerative keratinocyte activated-like state

    PubMed Central

    Cheng, Chia-Ho; Leferovich, John; Zhang, Xiang-Ming; Bedelbaeva, Khamilia; Gourevitch, Dmitri; Hatcher, Cathy J.; Basson, Craig T.; Heber-Katz, Ellen

    2013-01-01

    Mouse strains C57BL/6 (B6) and MRL were studied by whole mouse genome chip microarray analyses of RNA isolated from amputation sites at different times pre- and postamputation at the midsecond phalange of the middle digit. Many keratin genes were highly differentially expressed. All keratin genes were placed into three temporal response classes determined by injury/preinjury ratios. One class, containing only Krt6 and Krt16, were uniquely expressed relative to the other two classes and exhibited different temporal responses in MRL vs. B6. Immunohistochemical staining for Krt6 and Krt16 in tissue sections, including normal digit, flank skin, and small intestine, and from normal and injured ear pinna tissue exhibited staining differences in B6 (low) and MRL (high) that were consistent with the microarray results. Krt10 staining showed no injury-induced differences, consistent with microarray expression. We analyzed Krt6 and Krt16 gene association networks and observed in uninjured tissue several genes with higher expression levels in MRL, but not B6, that were associated with the keratinocyte activated state: Krt6, Krt16, S100a8, S100a9, and Il1b; these data suggest that keratinocytes in the MRL strain, but not in B6, are in an activated state prior to wounding. These expression levels decreased in MRL at all times postwounding but rose in the B6, peaking at day 3. Other keratins significantly expressed in the normal basal keratinocyte state showed no significant strain differences. These data suggest that normal MRL skin is in a keratinocyte activated state, which may provide it with superior responses to wounding. PMID:23512742

  1. An essential role for IFN-β in the induction of IFN-stimulated gene expression by LPS in macrophages.

    PubMed

    Sheikh, Faruk; Dickensheets, Harold; Gamero, Ana M; Vogel, Stefanie N; Donnelly, Raymond P

    2014-10-01

    TLR agonists such as LPS and poly(I:C) induce expression of type I IFNs, such as IFN-α and -β, by macrophages. To examine the role of IFN-β in the induction of ISGs by LPS, we compared the ability of LPS to induce ISGF3 activity and ISG expression in bone marrow-derived macrophages from WT and Ifnb1(-/-) mice. We found that LPS treatment activated ISGF3 and induced expression of ISGs such as Oas1, Mx1, Ddx58 (RIG-I), and Ifih1 (MDA5) in WT macrophages, but not in macrophages derived from Ifnb1(-/-) mice or Ifnar1(-/-) mice. The inability of LPS to induce activation of ISGF3 and ISG expression in Ifnb1(-/-) macrophages correlated with the failure of LPS to induce activation of STAT1 and -2 in these cells. Consistent with these findings, LPS treatment also failed to induce ISG expression in bone marrow-derived macrophages from Stat2 KO mice. Although activation of ISGF3 and induction of ISG expression by LPS was abrogated in Ifnb1(-/-) and Ifnar1(-/-) macrophages, activation of NF-κB and induction of NF-κB-responsive genes, such as Tnf (TNF-α) and Il1b (IL-1β), were not affected by deletion of either the IFN-β or IFN-αR1 genes. These findings demonstrate that induction of ISGF3 activity and ISG expression by LPS is critically dependent on intermediate production of IFN-β and autocrine signaling through type I IFN receptors.

  2. [The influence of interleukin gene polymorphism on the serum cytokine level in the patients presenting with chonic suppurative otitis media].

    PubMed

    Baike, E V; Vitkovsky, Yu A; Dutova, A A

    The objective of the present work was to study the influence of allelic variant associations of 1-beta interleukin (C3953T, &511C, T31C), interleukin-6 (C174G), and tumour necrosis factor-alpha (G308A) gene polymorphisms on the serum cytokine level in the patients presenting with chronic suppurative otitis media. A total of 299 patients at the age varying from 16 to 55 years with this condition divided into three groups were examined. Group 1 was comprised of 146 patients suffering from the tubotympanic form of chronic suppurative otitis media (CSOM). Group 2 was composed of 153 patients with epitympanic antral form of this condition. The control group included 183 subjects who have never suffered pathological changes in the middle ear. Human genomic DNA was analyzed with the use of the polymerase chain reaction (PCR). The serum cytokine levels were measured by the solid-state enzyme immunoassay in the beginning and at the end of the treatment period. The study has demonstrated that 56.2% of the healthy residents of the trans-Baikal region had the C/T Il-1b (C3953T) genotype. 79.1% of the patients presenting with the carious carious-destructive form of chronic suppurative otitis media were the heterozygous carriers of the T511C gene of 1-beta interleukin and had the maximally high concentrations of this interleukin in the blood serum. A rise in the production of the pro-inflammatory mediator (IL-6) was found to be related to the severity of the inflammatory process in the middle ear. The TNF-alpha content in the patients with CSOM during the active period of the disease proved to increase by a factor of 6 in comparison with that in the subjects of the control group irrespective of the type of mutation.

  3. Association of IL10 and other immune response- and obesity-related genes with prostate cancer in CLUE II.

    PubMed

    Wang, Ming-Hsi; Helzlsouer, Kathy J; Smith, Michael W; Hoffman-Bolton, Judith A; Clipp, Sandra L; Grinberg, Viktoriya; De Marzo, Angelo M; Isaacs, William B; Drake, Charles G; Shugart, Yin Yao; Platz, Elizabeth A

    2009-06-01

    Chronic intra-prostatic inflammation and obesity are thought to influence prostate carcinogenesis. Thus, variants in genes in these pathways could be associated with prostate cancer risk. We genotyped 17 common single nucleotide polymorphisms (SNPs) in RNASEL, TLR4, IL1B, IL6, IL8, IL10, TNF, CRP, ADIPOQ, LEP, PPARG, and TCF7L2 in 258 white prostate cancer cases and 258 matched controls nested in CLUE II. Single-locus analyses were conducted using conditional logistic regression. TagSNPs were selected in IL10, CRP, and TLR4 and haplotype analyses were done. The A allele of IL10 -1082G>A (rs1800896), known to result in lower levels of this anti-inflammatory cytokine, was positively associated with risk (AG vs. GG, OR = 1.69, 95% CI: 1.10-2.60; AA vs. GG, OR = 1.81, 95% CI: 1.11-2.96; P (trend) = 0.02). Associations of IL10 haplotypes with prostate cancer were explained by high linkage disequilibrium between two tagSNPs (rs1800890 and rs3024496) and -1082G>A. A TLR4 candidate SNP (rs4986790; AG/GG vs. AA, OR = 0.60, 95% CI: 0.33-1.08; P(trend) = 0.09), known to have decreased expression and be associated with lower circulating levels of inflammatory mediators, and tagSNP (rs10116253; CC vs. TT, OR = 3.05, 95% CI: 1.11-8.41), but not haplotypes, were associated with risk. None of the other candidate SNPs or haplotypes was statistically significantly associated with risk. Our prospective study suggests that genetic variation in IL10 and possibly TLR4 is associated with prostate cancer risk. Although none of the SNPs in the obesity genes tested was associated, this does not rule out a complex role of obesity and its metabolic consequences in prostate cancer etiology. . (c) 2009 Wiley-Liss, Inc.

  4. CRONUS, A Distributed Operating System. Volume 4. CRONUS DOS implementation

    DTIC Science & Technology

    1988-06-01

    3 VI’(of i,:oa4r) TC- ’ CRON S, A DISTRIBUTED OPERATING S YS^4T EM: CRONUS DOS Implementation .131N Laboratories Incorporated R~. Schantz, K...Classification) CRONUS , A DISTRIBUTED OPERATING SYSTEM: CRONUS DOS Implementation 1Z.P ERSONAL AUTHOR(S) R. Schantz, K. Schroder, M. Barrow, G. Bono, M. Dean, R...second contract phase for development of the Cronus Project. ’% Cronus is the name given to the distributed operating system (DOS) and system

  5. Heat Stress and Lipopolysaccharide Stimulation of Chicken Macrophage-Like Cell Line Activates Expression of Distinct Sets of Genes.

    PubMed

    Slawinska, Anna; Hsieh, John C; Schmidt, Carl J; Lamont, Susan J

    2016-01-01

    Acute heat stress requires immediate adjustment of the stressed individual to sudden changes of ambient temperatures. Chickens are particularly sensitive to heat stress due to development of insufficient physiological mechanisms to mitigate its effects. One of the symptoms of heat stress is endotoxemia that results from release of the lipopolysaccharide (LPS) from the guts. Heat-related cytotoxicity is mitigated by the innate immune system, which is comprised mostly of phagocytic cells such as monocytes and macrophages. The objective of this study was to analyze the molecular responses of the chicken macrophage-like HD11 cell line to combined heat stress and lipopolysaccharide treatment in vitro. The cells were heat-stressed and then allowed a temperature-recovery period, during which the gene expression was investigated. LPS was added to the cells to mimic the heat-stress-related endotoxemia. Semi high-throughput gene expression analysis was used to study a gene panel comprised of heat shock proteins, stress-related genes, signaling molecules and immune response genes. HD11 cell line responded to heat stress with increased mRNA abundance of the HSP25, HSPA2 and HSPH1 chaperones as well as DNAJA4 and DNAJB6 co-chaperones. The anti-apoptotic gene BAG3 was also highly up-regulated, providing evidence that the cells expressed pro-survival processes. The immune response of the HD11 cell line to LPS in the heat stress environment (up-regulation of CCL4, CCL5, IL1B, IL8 and iNOS) was higher than in thermoneutral conditions. However, the peak in the transcriptional regulation of the immune genes was after two hours of temperature-recovery. Therefore, we propose the potential influence of the extracellular heat shock proteins not only in mitigating effects of abiotic stress but also in triggering the higher level of the immune responses. Finally, use of correlation networks for the data analysis aided in discovering subtle differences in the gene expression (i.e. the role

  6. Heat Stress and Lipopolysaccharide Stimulation of Chicken Macrophage-Like Cell Line Activates Expression of Distinct Sets of Genes

    PubMed Central

    Slawinska, Anna; Hsieh, John C.; Schmidt, Carl J.; Lamont, Susan J.

    2016-01-01

    Acute heat stress requires immediate adjustment of the stressed individual to sudden changes of ambient temperatures. Chickens are particularly sensitive to heat stress due to development of insufficient physiological mechanisms to mitigate its effects. One of the symptoms of heat stress is endotoxemia that results from release of the lipopolysaccharide (LPS) from the guts. Heat-related cytotoxicity is mitigated by the innate immune system, which is comprised mostly of phagocytic cells such as monocytes and macrophages. The objective of this study was to analyze the molecular responses of the chicken macrophage-like HD11 cell line to combined heat stress and lipopolysaccharide treatment in vitro. The cells were heat-stressed and then allowed a temperature-recovery period, during which the gene expression was investigated. LPS was added to the cells to mimic the heat-stress-related endotoxemia. Semi high-throughput gene expression analysis was used to study a gene panel comprised of heat shock proteins, stress-related genes, signaling molecules and immune response genes. HD11 cell line responded to heat stress with increased mRNA abundance of the HSP25, HSPA2 and HSPH1 chaperones as well as DNAJA4 and DNAJB6 co-chaperones. The anti-apoptotic gene BAG3 was also highly up-regulated, providing evidence that the cells expressed pro-survival processes. The immune response of the HD11 cell line to LPS in the heat stress environment (up-regulation of CCL4, CCL5, IL1B, IL8 and iNOS) was higher than in thermoneutral conditions. However, the peak in the transcriptional regulation of the immune genes was after two hours of temperature-recovery. Therefore, we propose the potential influence of the extracellular heat shock proteins not only in mitigating effects of abiotic stress but also in triggering the higher level of the immune responses. Finally, use of correlation networks for the data analysis aided in discovering subtle differences in the gene expression (i.e. the role

  7. Divorce Matters: Visitation Dos and Don'ts

    MedlinePlus

    divorce matters Visitation dos and don’ts For both parents and children, visitation is critical to maintaining ... sense of connectedness both during and after a divorce. But in the early stages of family restructuring ...

  8. A novel exonic variant (221delT) in the LGALS13 gene encoding placental protein 13 (PP13) is associated with preterm labour in a low risk population.

    PubMed

    Gebhardt, S; Bruiners, N; Hillermann, R

    2009-11-01

    Predicting adverse pregnancy outcome in low risk patients in a community with poor socio-economic circumstances is difficult, yet about 5% of these pregnancies will result in preterm labour or severe pre-eclampsia. In this study we aimed to identify markers in pro- and anti-inflammatory genes that may contribute to disease and possibly disease prediction in a low risk community setting. A prospective study was undertaken on 450 consecutive low risk primigravid patients. Blood obtained at first booking was screened for known immunological gene variants (IL4 -590, IL1B +3953, IL1RN, IL10 -1082; -819; -592 and TNFA -308; -238; +488) as well as for novel variants in the LGALS13 gene coding for placental protein 13 (PP13). The incidence of preterm labour and pre-eclampsia was 7.1% and 6.8% respectively. A novel exonic variant (221delT) in the LGALS13 gene increased the risk for preterm labour in the total study group (relative risk RR 2.27). Maternal carriage of the interleukin-1 RN*2 allele was associated with an increased risk of hypertension in pregnancy in the Coloured subgroup of the study cohort (RR 2.53). There was an increased risk for preterm labour in the same subgroup with carriage of the TNFA -308 A-allele (TNF2) (RR 2.53). No significance was found for the other variants examined. We conclude that single nucleotide polymorphisms (SNPs) in certain genes regulating implantation and inflammation may contribute to the complex etiology of pre-eclampsia and preterm labour. The association between the 221delT deletion and adverse pregnancy outcome needs to be confirmed in different populations.

  9. The first characterization of two type I interferons in turbot (Scophthalmus maximus) reveals their differential role, expression pattern and gene induction.

    PubMed

    Pereiro, P; Costa, M M; Díaz-Rosales, P; Dios, S; Figueras, A; Novoa, B

    2014-08-01

    Type I interferons (IFNs) are considered the main cytokines directing the antiviral immune response in vertebrates. These molecules are able to induce the transcription of interferon-stimulated genes (ISGs) which, using different blocking mechanisms, reduce the viral proliferation in the host. In addition, a contradictory role of these IFNs in the protection against bacterial challenges using murine models has been observed, increasing the survival or having a detrimental effect depending on the bacteria species. In teleosts, a variable number of type I IFNs has been described with different expression patterns, protective capabilities or gene induction profiles even for the different IFNs belonging to the same species. In this work, two type I IFNs (ifn1 and ifn2) have been characterized for the first time in turbot (Scophthalmus maximus), showing different properties. Whereas Ifn1 reflected a clear antiviral activity (over-expression of ISGs and protection against viral haemorrhagic septicaemia virus), Ifn2 was not able to induce this response, although both transcripts were up-regulated after viral challenge. On the other hand, turbot IFNs did not show any protective effect against the bacteria Aeromonas salmonicida, although they were induced after bacterial challenge. Both IFNs induced the expression of several immune genes, but the effect of Ifn2 was mainly limited to the site of administration (intramuscular injection). Interestingly, Ifn2 but not Ifn1 induced an increase in the expression level of interleukin-1 beta (il1b). Therefore, the role of Ifn2 could be more related with the immune regulation, being involved mainly in the inflammation process.

  10. Brain Region–Specific Alterations in the Gene Expression of Cytokines, Immune Cell Markers and Cholinergic System Components during Peripheral Endotoxin–Induced Inflammation

    PubMed Central

    Silverman, Harold A; Dancho, Meghan; Regnier-Golanov, Angelique; Nasim, Mansoor; Ochani, Mahendar; Olofsson, Peder S; Ahmed, Mohamed; Miller, Edmund J; Chavan, Sangeeta S; Golanov, Eugene; Metz, Christine N; Tracey, Kevin J; Pavlov, Valentin A

    2014-01-01

    Inflammatory conditions characterized by excessive peripheral immune responses are associated with diverse alterations in brain function, and brain-derived neural pathways regulate peripheral inflammation. Important aspects of this bidirectional peripheral immune–brain communication, including the impact of peripheral inflammation on brain region–specific cytokine responses, and brain cholinergic signaling (which plays a role in controlling peripheral cytokine levels), remain unclear. To provide insight, we studied gene expression of cytokines, immune cell markers and brain cholinergic system components in the cortex, cerebellum, brainstem, hippocampus, hypothalamus, striatum and thalamus in mice after an intraperitoneal lipopolysaccharide injection. Endotoxemia was accompanied by elevated serum levels of interleukin (IL)-1β, IL-6 and other cytokines and brain region–specific increases in Il1b (the highest increase, relative to basal level, was in cortex; the lowest increase was in cerebellum) and Il6 (highest increase in cerebellum; lowest increase in striatum) mRNA expression. Gene expression of brain Gfap (astrocyte marker) was also differentially increased. However, Iba1 (microglia marker) mRNA expression was decreased in the cortex, hippocampus and other brain regions in parallel with morphological changes, indicating microglia activation. Brain choline acetyltransferase (Chat ) mRNA expression was decreased in the striatum, acetylcholinesterase (Ache) mRNA expression was decreased in the cortex and increased in the hippocampus, and M1 muscarinic acetylcholine receptor (Chrm1) mRNA expression was decreased in the cortex and the brainstem. These results reveal a previously unrecognized regional specificity in brain immunoregulatory and cholinergic system gene expression in the context of peripheral inflammation and are of interest for designing future antiinflammatory approaches. PMID:25299421

  11. miR-9 modulates the expression of interferon-regulated genes and MHC class I molecules in human nasopharyngeal carcinoma cells

    SciTech Connect

    Gao, Fei; Zhao, Zun-Lan; Zhao, Wen-Tao; Fan, Quan-Rong; Wang, Sheng-Chun; Li, Jing; Zhang, Yu-Qing; Shi, Jun-Wen; Lin, Xiao-Lin; Yang, Sheng; Xie, Rao-Ying; Liu, Wei; Zhang, Ting-Ting; Sun, Yong-Liang; Xu, Kang; Yao, Kai-Tai; Xiao, Dong

    2013-02-15

    Highlights: ► miR-9 can negatively or positively modulate interferon-induced gene expression. ► miR-9 can up-regulate major histocompatibility complex class I molecule expression. ► miR-9 can down-regulate the expression of interleukin-related genes. -- Abstract: The functions of miR-9 in some cancers are recently implicated in regulating proliferation, epithelial–mesenchymal transition (EMT), invasion and metastasis, apoptosis, and tumor angiogenesis, etc. miR-9 is commonly down-regulated in nasopharyngeal carcinoma (NPC), but the exact roles of miR-9 dysregulation in the pathogenesis of NPC remains unclear. Therefore, we firstly used miR-9-expressing CNE2 cells to determine the effects of miR-9 overexpression on global gene expression profile by microarray analysis. Microarray-based gene expression data unexpectedly demonstrated a significant number of up- or down-regulated immune- and inflammation-related genes, including many well-known interferon (IFN)-induced genes (e.g., IFI44L, PSMB8, IRF5, PSMB10, IFI27, PSB9{sub H}UMAN, IFIT2, TRAIL, IFIT1, PSB8{sub H}UMAN, IRF1, B2M and GBP1), major histocompatibility complex (MHC) class I molecules (e.g., HLA-B, HLA-C, HLA-F and HLA-H) and interleukin (IL)-related genes (e.g., IL20RB, GALT, IL7, IL1B, IL11, IL1F8, IL1A, IL6 and IL7R), which was confirmed by qRT-PCR. Moreover, the overexpression of miR-9 with the miRNA mimics significantly up- or down-regulated the expression of above-mentioned IFN-inducible genes, MHC class I molecules and IL-related genes; on the contrary, miR-9 inhibition by anti-miR-9 inhibitor in CNE2 and 5–8F cells correspondingly decreased or increased the aforementioned immune- and inflammation-related genes. Taken together, these findings demonstrate, for the first time, that miR-9 can modulate the expression of IFN-induced genes and MHC class I molecules in human cancer cells, suggesting a novel role of miR-9 in linking inflammation and cancer, which remains to be fully characterized.

  12. RNA Sequencing Identifies Multiple Fusion Transcripts, Differentially Expressed Genes, and Reduced Expression of Immune Function Genes in BRAF (V600E) Mutant vs BRAF Wild-Type Papillary Thyroid Carcinoma

    PubMed Central

    Chindris, Ana-Maria; Asmann, Yan W.; Casler, John D.; Serie, Daniel J.; Reddi, Honey V.; Cradic, Kendall W.; Rivera, Michael; Grebe, Stefan K.; Necela, Brian M.; Eberhardt, Norman L.; Carr, Jennifer M.; McIver, Bryan; Copland, John A.; Aubrey Thompson, E.

    2014-01-01

    Context: The BRAF V600E mutation (BRAF-MUT) confers an aggressive phenotype in papillary thyroid carcinoma, but unidentified additional genomic abnormalities may be required for full phenotypic expression. Objective: RNA sequencing (RNA-Seq) was performed to identify genes differentially expressed between BRAF-MUT and BRAF wild-type (BRAF-WT) tumors and to correlate changes to patient clinical status. Design: BRAF-MUT and BRAF-WT tumors were identified in patients with T1N0 and T2–3N1 tumors evaluated in a referral medical center. Gene expression levels were determined (RNA-Seq) and fusion transcripts were detected. Multiplexed capture/detection and digital counting of mRNA transcripts (nCounter, NanoString Technologies) validated RNA-Seq data for immune system-related genes. Patients: BRAF-MUT patients included nine women, three men; nine were TNM stage I and three were stage III. Three (25%) had tumor infiltrating lymphocytes. BRAF-WT included five women, three men; all were stage I, and five (62.5%) had tumor infiltrating lymphocytes. Results: RNA-Seq identified 560 of 13 085 genes differentially expressed between BRAF-MUT and BRAF-WT tumors. Approximately 10% of these genes were related to MetaCore immune function pathways; 51 were underexpressed in BRAF-MUT tumors, whereas 4 (HLAG, CXCL14, TIMP1, IL1RAP) were overexpressed. The four most differentially overexpressed immune genes in BRAF-WT tumors (IL1B; CCL19; CCL21; CXCR4) correlated with lymphocyte infiltration. nCounter confirmed the RNA-Seq expression level data. Eleven different high-confidence fusion transcripts were detected (four interchromosomal; seven intrachromosomal) in 13 of 20 tumors. All in-frame fusions were validated by RT-PCR. Conclusion: BRAF-MUT papillary thyroid cancers have reduced expression of immune/inflammatory response genes compared with BRAF-WT tumors and correlate with lymphocyte infiltration. In contrast, HLA-G and CXCL14 are overexpressed in BRAF-MUT tumors. Sixty-five percent

  13. RNA sequencing identifies multiple fusion transcripts, differentially expressed genes, and reduced expression of immune function genes in BRAF (V600E) mutant vs BRAF wild-type papillary thyroid carcinoma.

    PubMed

    Smallridge, Robert C; Chindris, Ana-Maria; Asmann, Yan W; Casler, John D; Serie, Daniel J; Reddi, Honey V; Cradic, Kendall W; Rivera, Michael; Grebe, Stefan K; Necela, Brian M; Eberhardt, Norman L; Carr, Jennifer M; McIver, Bryan; Copland, John A; Thompson, E Aubrey

    2014-02-01

    The BRAF V600E mutation (BRAF-MUT) confers an aggressive phenotype in papillary thyroid carcinoma, but unidentified additional genomic abnormalities may be required for full phenotypic expression. RNA sequencing (RNA-Seq) was performed to identify genes differentially expressed between BRAF-MUT and BRAF wild-type (BRAF-WT) tumors and to correlate changes to patient clinical status. BRAF-MUT and BRAF-WT tumors were identified in patients with T1N0 and T2-3N1 tumors evaluated in a referral medical center. Gene expression levels were determined (RNA-Seq) and fusion transcripts were detected. Multiplexed capture/detection and digital counting of mRNA transcripts (nCounter, NanoString Technologies) validated RNA-Seq data for immune system-related genes. BRAF-MUT patients included nine women, three men; nine were TNM stage I and three were stage III. Three (25%) had tumor infiltrating lymphocytes. BRAF-WT included five women, three men; all were stage I, and five (62.5%) had tumor infiltrating lymphocytes. RNA-Seq identified 560 of 13 085 genes differentially expressed between BRAF-MUT and BRAF-WT tumors. Approximately 10% of these genes were related to MetaCore immune function pathways; 51 were underexpressed in BRAF-MUT tumors, whereas 4 (HLAG, CXCL14, TIMP1, IL1RAP) were overexpressed. The four most differentially overexpressed immune genes in BRAF-WT tumors (IL1B; CCL19; CCL21; CXCR4) correlated with lymphocyte infiltration. nCounter confirmed the RNA-Seq expression level data. Eleven different high-confidence fusion transcripts were detected (four interchromosomal; seven intrachromosomal) in 13 of 20 tumors. All in-frame fusions were validated by RT-PCR. BRAF-MUT papillary thyroid cancers have reduced expression of immune/inflammatory response genes compared with BRAF-WT tumors and correlate with lymphocyte infiltration. In contrast, HLA-G and CXCL14 are overexpressed in BRAF-MUT tumors. Sixty-five percent of tumors had between one and three fusion transcripts

  14. Characteristic Changes in Decidual Gene Expression Signature in Spontaneous Term Parturition

    PubMed Central

    El-Azzamy, Haidy; Balogh, Andrea; Romero, Roberto; Xu, Yi; LaJeunesse, Christopher; Plazyo, Olesya; Xu, Zhonghui; Price, Theodore G.; Dong, Zhong; Tarca, Adi L.; Papp, Zoltan; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn; Kim, Chong Jai; Gomez-Lopez, Nardhy; Than, Nandor Gabor

    2017-01-01

    Background The decidua has been implicated in the “terminal pathway” of human term parturition, which is characterized by the activation of pro-inflammatory pathways in gestational tissues. However, the transcriptomic changes in the decidua leading to terminal pathway activation have not been systematically explored. This study aimed to compare the decidual expression of developmental signaling and inflammation-related genes before and after spontaneous term labor in order to reveal their involvement in this process. Methods Chorioamniotic membranes were obtained from normal pregnant women who delivered at term with spontaneous labor (TIL, n = 14) or without labor (TNL, n = 15). Decidual cells were isolated from snap-frozen chorioamniotic membranes with laser microdissection. The expression of 46 genes involved in decidual development, sex steroid and prostaglandin signaling, as well as pro- and anti-inflammatory pathways, was analyzed using high-throughput quantitative real-time polymerase chain reaction (qRT-PCR). Chorioamniotic membrane sections were immunostained and then semi-quantified for five proteins, and immunoassays for three chemokines were performed on maternal plasma samples. Results The genes with the highest expression in the decidua at term gestation included insulin-like growth factor-binding protein 1 (IGFBP1), galectin-1 (LGALS1), and progestogen-associated endometrial protein (PAEP); the expression of estrogen receptor 1 (ESR1), homeobox A11 (HOXA11), interleukin 1β (IL1B), IL8, progesterone receptor membrane component 2 (PGRMC2), and prostaglandin E synthase (PTGES) was higher in TIL than in TNL cases; the expression of chemokine C-C motif ligand 2 (CCL2), CCL5, LGALS1, LGALS3, and PAEP was lower in TIL than in TNL cases; immunostaining confirmed qRT-PCR data for IL-8, CCL2, galectin-1, galectin-3, and PAEP; and no correlations between the decidual gene expression and the maternal plasma protein concentrations of CCL2, CCL5, and IL-8 were

  15. Immersion infection of germ-free zebrafish with Listeria monocytogenes induces transient expression of innate immune response genes

    PubMed Central

    Shan, Ying; Fang, Chun; Cheng, Changyong; Wang, Yong; Peng, Jinrong; Fang, Weihuan

    2015-01-01

    Zebrafish, Denio rerio, can be an alternative to other classic animal models for human infectious diseases to examine the processes of microbial infections and host–pathogen interactions in vivo because of their small body dimension but large clutch size. We established germ-free zebrafish infection models of Listeria monocytogenes through different routes of infection: oral immersion and injection via yolk sac, brain ventricle and blood island. Immersion of zebrafish larva even with 1010 CFU/mL L. monocytogenes EGDe strain in egg water was unable to cause mortality, but GFP-expressing bacteria in the gut lumen can be observed in frozen sections. Several selected maker genes of the innate immune system, including cyp1a, irg1l, il1b, and mmp9, were significantly induced by oral immersion not only with strain EGDe, but also with strain M7 and L. innocua, though to a lesser degree (P < 0.01). Such induction appears to be transient with peak at 48 h post-infection, but returned to basal level at 72 h post-infection. Of the three injection routes, mortality after infection by yolk sac was 80% in early stage of infection. Few eggs can survive and hatch. Injection into zebrafish embryos via brain ventricle or blood island led to progressive lethal infection. L. mocytogenes EGDe showed steady replication in the fish embryos and was far more pathogenic than strain M7, which is consistent with findings in the murine model. We conclude that zebrafish can serve as susceptible and microscopically visible infection models for L. monocytogenes via different routes and can be applied to further studies on the interactions between bacterial virulence factors and host immune responses. PMID:25972853

  16. Transcription factors NF-IL6 and CREB recognize a common essential site in the human prointerleukin 1 beta gene.

    PubMed Central

    Tsukada, J; Saito, K; Waterman, W R; Webb, A C; Auron, P E

    1994-01-01

    A site located between -2782 and -2729 of the human prointerleukin-1 beta (IL1B) gene functions as a strong lipopolysaccharide (LPS)-responsive enhancer independent of the previously identified enhancer located between -2896 and -2846 (F. Shirakawa, K. Saito, C.A. Bonagura, D.L. Galson, M. J. Fenton, A. C. Webb, and P. E. Auron, Mol. Cell. Biol. 13:1332-1344, 1993). Although these two enhancers appear to function cooperatively in the native sequence context, they function independently as LPS-responsive elements upon removal of an interposed silencer sequence. The new enhancer is not induced by dibutyryl cyclic AMP (dbcAMP) alone but is superinduced by costimulation with LPS-dbcAMP. This pattern of induction depends upon the nature of the sequence, a composite NF-IL6-cAMP response element (CRE) binding site. This pseudosymmetrical sequence is shown to contrast with a classical symmetric CRE which responds to dbcAMP but not LPS. DNA binding studies using in vivo nuclear extract, recombinant proteins, and specific antibodies show that LPS induces the formation of two different complexes at the enhancer: (i) an NF-IL6-CREB heterodimer and (ii) a heterodimer consisting of NF-IL6 and a non-CREB, CRE-binding protein. Cotransfection studies using NF-IL6 and CREB expression vectors show that NF-IL6 transactivates the enhancer in the presence of LPS, whereas CREB acts either positively or negatively, depending upon its cAMP-regulated phosphorylation state. Our data demonstrate that the newly identified enhancer is a specialized LPS-responsive sequence which can be modulated by cAMP as a result of the involvement of NF-IL6-CRE-binding protein heterodimers. Images PMID:7935442

  17. GFAP and vimentin deficiency alters gene expression in astrocytes and microglia in wild-type mice and changes the transcriptional response of reactive glia in mouse model for Alzheimer's disease.

    PubMed

    Kamphuis, Willem; Kooijman, Lieneke; Orre, Marie; Stassen, Oscar; Pekny, Milos; Hol, Elly M

    2015-06-01

    Reactive astrocytes with an increased expression of intermediate filament (IF) proteins Glial Fibrillary Acidic Protein (GFAP) and Vimentin (VIM) surround amyloid plaques in Alzheimer's disease (AD). The functional consequences of this upregulation are unclear. To identify molecular pathways coupled to IF regulation in reactive astrocytes, and to study the interaction with microglia, we examined WT and APPswe/PS1dE9 (AD) mice lacking either GFAP, or both VIM and GFAP, and determined the transcriptome of cortical astrocytes and microglia from 15- to 18-month-old mice. Genes involved in lysosomal degradation (including several cathepsins) and in inflammatory response (including Cxcl5, Tlr6, Tnf, Il1b) exhibited a higher AD-induced increase when GFAP, or VIM and GFAP, were absent. The expression of Aqp4 and Gja1 displayed the same pattern. The downregulation of neuronal support genes in astrocytes from AD mice was absent in GFAP/VIM null mice. In contrast, the absence of IFs did not affect the transcriptional alterations induced by AD in microglia, nor was the cortical plaque load altered. Visualizing astrocyte morphology in GFAP-eGFP mice showed no clear structural differences in GFAP/VIM null mice, but did show diminished interaction of astrocyte processes with plaques. Microglial proliferation increased similarly in all AD groups. In conclusion, absence of GFAP, or both GFAP and VIM, alters AD-induced changes in gene expression profile of astrocytes, showing a compensation of the decrease of neuronal support genes and a trend for a slightly higher inflammatory expression profile. However, this has no consequences for the development of plaque load, microglial proliferation, or microglial activation. © 2015 Wiley Periodicals, Inc.

  18. Polymorphisms in ATP-binding cassette transporter genes and interaction with diet and life style factors in relation to colorectal cancer in a Danish prospective case-cohort study.

    PubMed

    Kopp, Tine Iskov; Andersen, Vibeke; Tjonneland, Anne; Vogel, Ulla

    2015-01-01

    The ATP-binding cassette (ABC) transporter family transports various molecules across the enterocytes in the gut protecting the intestine against potentially harmful substances. Moreover, ABC transporters are involved in mucosal immune defence through interaction with cytokines. The study aimed to assess whether polymorphisms in ABCB1, ABCC2 and ABCG2 were associated with risk of colorectal cancer (CRC) and to investigate gene-environment (dietary factors, smoking and use of non-steroidal anti-inflammatory drugs) and gene-gene interactions between previously studied polymorphisms in IL1B and IL10 and ABC transporter genes in relation to CRC risk. We used a Danish prospective case-cohort study of 1010 CRC cases and 1829 randomly selected participants from the Danish Diet, Cancer and Health cohort. Incidence rate ratios were calculated based on Cox' proportional hazards model. None of the polymorphisms were associated with CRC, but ABCB1 and ABCG2 haplotypes were associated with risk of CRC. ABCB1/rs1045642 interacted with intake of cereals and fiber (p-Value for interaction (P(int)) = 0.001 and 0.01, respectively). In a three-way analysis, both ABCB1/rs1045642 and ABCG2/rs2231137 in combination with IL10/rs3024505 interacted with fiber intake in relation to risk of CRC (P(int) = 0.0007 and 0.009). Our results suggest that the ABC transporters P-glycoprotein/multidrug resistance 1 and BRCP, in cooperation with IL-10, are involved in the biological mechanism underlying the protective effect of fiber intake in relation to CRC. These results should be replicated in other cohorts to rule out chance findings.

  19. Expression, maturation and turnover of DrrS, an unusually stable, DosR regulated small RNA in Mycobacterium tuberculosis

    PubMed Central

    Moores, Alexandra; Riesco, Ana B.; Schwenk, Stefan

    2017-01-01

    Mycobacterium tuberculosis depends on the ability to adjust to stresses encountered in a range of host environments, adjustments that require significant changes in gene expression. Small RNAs (sRNAs) play an important role as post-transcriptional regulators of prokaryotic gene expression, where they are associated with stress responses and, in the case of pathogens, adaptation to the host environment. In spite of this, the understanding of M. tuberculosis RNA biology remains limited. Here we have used a DosR-associated sRNA as an example to investigate multiple aspects of mycobacterial RNA biology that are likely to apply to other M. tuberculosis sRNAs and mRNAs. We have found that accumulation of this particular sRNA is slow but robust as cells enter stationary phase. Using reporter gene assays, we find that the sRNA core promoter is activated by DosR, and we have renamed the sRNA DrrS for DosR Regulated sRNA. Moreover, we show that DrrS is transcribed as a longer precursor, DrrS+, which is rapidly processed to the mature and highly stable DrrS. We characterise, for the first time in mycobacteria, an RNA structural determinant involved in this extraordinary stability and we show how the addition of a few nucleotides can lead to acute destabilisation. Finally, we show how this RNA element can enhance expression of a heterologous gene. Thus, the element, as well as its destabilising derivatives may be employed to post-transcriptionally regulate gene expression in mycobacteria in combination with different promoter variants. Moreover, our findings will facilitate further investigations into the severely understudied topic of mycobacterial RNA biology and into the role that regulatory RNA plays in M. tuberculosis pathogenesis. PMID:28323872

  20. Expression, maturation and turnover of DrrS, an unusually stable, DosR regulated small RNA in Mycobacterium tuberculosis.

    PubMed

    Moores, Alexandra; Riesco, Ana B; Schwenk, Stefan; Arnvig, Kristine B

    2017-01-01

    Mycobacterium tuberculosis depends on the ability to adjust to stresses encountered in a range of host environments, adjustments that require significant changes in gene expression. Small RNAs (sRNAs) play an important role as post-transcriptional regulators of prokaryotic gene expression, where they are associated with stress responses and, in the case of pathogens, adaptation to the host environment. In spite of this, the understanding of M. tuberculosis RNA biology remains limited. Here we have used a DosR-associated sRNA as an example to investigate multiple aspects of mycobacterial RNA biology that are likely to apply to other M. tuberculosis sRNAs and mRNAs. We have found that accumulation of this particular sRNA is slow but robust as cells enter stationary phase. Using reporter gene assays, we find that the sRNA core promoter is activated by DosR, and we have renamed the sRNA DrrS for DosR Regulated sRNA. Moreover, we show that DrrS is transcribed as a longer precursor, DrrS+, which is rapidly processed to the mature and highly stable DrrS. We characterise, for the first time in mycobacteria, an RNA structural determinant involved in this extraordinary stability and we show how the addition of a few nucleotides can lead to acute destabilisation. Finally, we show how this RNA element can enhance expression of a heterologous gene. Thus, the element, as well as its destabilising derivatives may be employed to post-transcriptionally regulate gene expression in mycobacteria in combination with different promoter variants. Moreover, our findings will facilitate further investigations into the severely understudied topic of mycobacterial RNA biology and into the role that regulatory RNA plays in M. tuberculosis pathogenesis.

  1. Impact of TLR5 rs5744174 on stroke risk, gene expression and on inflammatory cytokines, and lipid levels in stroke patients.

    PubMed

    Gu, Lian; Huang, Jingyan; Tan, Jinjing; Wei, Qiugui; Jiang, Haiyun; Shen, Tingting; Liang, Baoyun; Tang, Nong

    2016-09-01

    Many studies reported that toll-like receptors (TLRs) played an important role in the process of ischemic stroke (IS). However, the impact of TLR5 rs5744174 on stroke risk, gene expression and on inflammatory cytokines, and lipid levels in ischemic stroke patients has not yet been reported and was therefore the subject of this study. In this case-control study, a total of 816 ischemic stroke patients and 816 healthy controls were genotyped using Sequenom MassArray technology. The mRNA expression of TLR5 was detected through quantitative real-time PCR among 52 ischemic stroke patients. The levels of IL-1b, IL-6, IL-8, and TNFα were measured by ELISA among 62 IS patients. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were determined among 816 IS patients using a Hitachi 7600 Automatic Biochemistry Analyzer. Our result showed TLR5 rs5744174 polymorphism was not associated with stroke risk, TLR5 mRNA expression and inflammatory cytokines of IS patients (P > 0.050), but was significantly associated with HDL-C (recessive model: β = - 0.14, 95 % CI: -0.24 to -0.03, P = 0.009). TLR5 rs5744174 polymorphism may have no impact on the stroke risk, gene expression and inflammatory cytokines, but may influence the HDL-C serum level of IS patients in Chinese Han population.

  2. Izabel dos Santos and the training of the health workers.

    PubMed

    Paiva, Carlos Henrique Assunção

    2015-06-01

    This article discusses the career of Izabel dos Santos (1927-2010) as a means of examining the connections between health schools and agendas in contemporary Brazil. The article highlights dos Santos's training and her work in the Serviço Especial de Saúde Pública (SESP- Special Public Health Service), the Pan American Health Organization (PAHO) and in the formulation and implementation of national training programs for human resources within the area of health from the late 1970s onwards. The article highlights dos Santos's central role in the formulation and implementation of training policies for health workers, especially nursing technicians and assistants, and demonstrates how she occupies an important place in the history of Brazilian public health.

  3. Isotopic and chemical investigations on Angra dos Reis

    NASA Technical Reports Server (NTRS)

    Wasserburg, G. J.; Tera, F.; Papanastassiou, D. A.; Huneke, J. C.

    1977-01-01

    Isotope ratios and chemical abundance measurements for a variety of elements are reported for total meteorite and mineral separates of the Angra dos Reis achondrite. U-Pb, Th-Pb, and Pb-Pb ages are concordant at 4.54 eons for the total meteorite and for high-purity whitlockite, which indicates that Angra dos Reis is an early planetary differentiate that has not been disturbed for these systems since 4.54 eons ago. The implications of different ratios of Sr-87 and Sr-86 found in different components are discussed. Xe isotopic measurements show that Pu-244 was enriched in the whitlockite relative to the pyroxene by a factor of about 18. Chemical enrichment factors between the whitlockite and the fassaitic pyroxene in Angra dos Reis are presented

  4. When worlds collide - Mac to MS-DOS. [Data transfer to and from Apple Macintosh computers and MS-DOS based personal computers

    SciTech Connect

    Busbey, A.B.

    1989-04-01

    A number of methods and products, both hardware and software, to allow data exchange between Apple Macintosh computers and MS-DOS based systems. These included serial null modem connections, MS-DOS hardware and/or software emulation, MS-DOS disk-reading hardware and networking.

  5. 48 CFR 619.402-70 - DOS designee.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Section 619.402-70 Federal Acquisition Regulations System DEPARTMENT OF STATE SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Cooperation with the Small Business Administration 619.402-70 DOS designee. Where the FAR requires action by a Small Business Administration procurement center representative, but one has not been...

  6. Special Section--Library Workstations: Mac and DOS.

    ERIC Educational Resources Information Center

    Valauskas, Ed; Flower, Eric

    1993-01-01

    Two articles discuss the library hardware marketplace. The first examines the Apple Macintosh in libraries from 1984 to the present, including linking libraries, computers, and endusers over large geographic distances. The second article discusses upgrading components of systems in the IBM compatible, MS-DOS, and Windows environments as costs…

  7. Immunoglobulin genes

    SciTech Connect

    Honjo, T. ); Alt, F.W. . Hudson Labs.); Rabbitts, T.H. )

    1989-01-01

    This book reports on the structure, function, and expression of the genes encoding antibodies in normal and neoplastic cells. Topics covered are: B Cells; Organization and rearrangement of immunoglobin genes; Immunoglobin genes in disease; Immunoglobin gene expression; and Immunoglobin-related genes.

  8. Studying Genes

    MedlinePlus

    ... Sheets What are genes? Genes are segments of DNA that contain instructions for building the molecules that ... proteins. Parents pass their genes to their offspring. DNA is shaped like a corkscrew-twisted ladder, called ...

  9. Microarray analysis of inflammatory response-related gene expression in the uteri of dogs with pyometra.

    PubMed

    Bukowska, D; Kempisty, B; Zawierucha, P; Jopek, K; Piotrowska, H; Antosik, P; Ciesiółka, S; Woźna, M; Brüssow, K P; Jaśkowski, J M

    2014-01-01

    Pyometra, which is accompanied by bacterial contamination of the uterus, is defined as a complex disease associated with the activation of several systems, including the immune system. The objective of the study was to evaluate the gene expression profile in dogs with pyometra compared with those that were clinically normal. The study included uteri from 43 mongrel bitches (23 with pyometra, 20 clinically healthy). RNA used for the microarray study was pooled to four separated vials for control and pyometra. A total of 17,138 different transcripts were analyzed on the uteri of female dogs with pyometra and of healthy controls. From 264 inflammatory response-related transcripts, we found 23 transcripts that revealed a 10- to 77-fold increased expression. Thereby, the expression of interleukin 8 (IL8), interleukin-1-beta (IL1B), interleukin 18 receptor (IL18RAP), interleukin 1-alpha (IL1A), interleukin receptor antagonist (IL1RN) and interleukin 6 (IL6) increased 77-, 20-, 17-, 13-, 13- and 11-fold, respectively. Furthermore, the expression of the calcium binding proteins S100A8 was 44-fold higher, and that of S100A12 and S100A9 37-fold, respectively, in the uteri of canines with pyometra compared with that of the controls. Moreover, the expression of the transcripts of toll-like receptors (TLR8 and TLR2), integrin beta 2 (ITGB2), chemokine ligand 3 (CCL3), semaphorin 7A (SEMA7A), CD14 and prostaglandin-endoperoxide synthase 2 (PTGS2) was increased between 10- and 18-fold. Furthermore, after using RT-qPCR we found an increased expression of AOAH, IL1A, IL8, CCL3, IL1RN and SERPINE 1 mRNAs which can be served also as markers of the occurrence of pyometra in domestic bitches. In summary, it is concluded that up-regulation of interleukins may be used as a marker of the inflammatory response in dogs with pyometra. Moreover, all of the 23 up-regulated transcripts may be novel molecular markers of the pathogenesis of canine pyometra. Several proteins--–products of these

  10. Ultrafast ligand dynamics in the heme-based GAF sensor domains of the histidine kinases DosS and DosT from Mycobacterium tuberculosis†

    PubMed Central

    Vos, Marten H.; Bouzhir-Sima, Latifa; Lambry, Jean-Christophe; Luo, Hao; Eaton-Rye, Julian J.; Ioanoviciu, Alexandra; Ortiz de Montellano, Paul R.; Liebl, Ursula

    2011-01-01

    The transcriptional regulator DosR from M. tuberculosis plays a crucial role in the virulence to dormancy transition of the pathogen. DosR can be activated by DosT and DosS, two histidine kinases with heme-containing sensor GAF domains, capable of diatomic ligand binding, To investigate the initial processes occurring upon ligand dissociation, we performed ultrafast time-resolved absorption spectroscopy of the isolated sensor domains ligated with O2, NO and CO. The results reveal a relatively closed heme pocket for both proteins. For DosT the yield of O2 escape from the heme pocket on the picoseconds timescale upon photodissociation was found to be very low (1.5%), similar to other heme-based oxygen sensor proteins, implying that this sensor acts as an effective O2 trap. Remarkably, this yield is an order of magnitude higher in DosS (18%). For CO, by contrast, the fraction of CO rebinding within the heme pocket is higher in DosS. Experiments with mutant DosT sensor domains and molecular dynamics simulations indicate an important role in ligand discrimination of the distal tyrosine, present in both proteins, which forms a hydrogen bond with heme-bound O2. We conclude that despite their similarity, DosT and DosS display ligand-specific different primary dynamics during the initial phases of intra-protein signaling. The distal tyrosine, present in both proteins, plays an important role in these processes. PMID:22142262

  11. Gene Therapy

    MedlinePlus

    ... cells in an effort to treat or stop disease. Genes contain your DNA — the code that controls much of your body's form and function, from making you grow taller to regulating your body systems. Genes that don't work properly can cause disease. Gene therapy replaces a faulty gene or adds ...

  12. Deceiving entropy-based DoS detection

    NASA Astrophysics Data System (ADS)

    Özçelik, Ä.°lker; Brooks, Richard R.

    2014-06-01

    Denial of Service (DoS) attacks disable network services for legitimate users. A McAfee report shows that eight out of ten Critical Infrastructure Providers (CIPs) surveyed had a significant Distributed DoS (DDoS) attack in 2010.1 Researchers proposed many approaches for detecting these attacks in the past decade. Anomaly based DoS detection is the most common. In this approach, the detector uses statistical features; such as the entropy of incoming packet header fields like source IP addresses or protocol type. It calculates the observed statistical feature and triggers an alarm if an extreme deviation occurs. However, intrusion detection systems (IDS) using entropy based detection can be fooled by spoofing. An attacker can sniff the network to collect header field data of network packets coming from distributed nodes on the Internet and fuses them to calculate the entropy of normal background traffic. Then s/he can spoof attack packets to keep the entropy value in the expected range during the attack. In this study, we present a proof of concept entropy spoofing attack that deceives entropy based detection approaches. Our preliminary results show that spoofing attacks cause significant detection performance degradation.

  13. The NLRP3 and CASP1 gene polymorphisms are associated with developing of acute coronary syndrome: a case-control study.

    PubMed

    Gonzalez-Pacheco, Hector; Vargas-Alarcon, Gilberto; Angeles-Martinez, Javier; Martinez-Sanchez, Carlos; Perez-Mendez, Oscar; Herrera-Maya, Gabriel; Martinez-Rios, Marco Antonio; Peña-Duque, Marco Antonio; Posadas-Romero, Carlos; Fragoso, Jose Manuel

    2017-08-01

    The protein products of NLRP3 and CASP1 genes are involved in the cleavage of pro-IL-1B and pro-IL-18 leading to the active cytokines, which play an important role in the development of the acute coronary syndrome (ACS). The aim of the present study was to evaluate whether NLRP3 and CASP1 gene polymorphisms are biomarkers of ACS susceptibility in Mexican population. Two polymorphisms of the CASP1 gene [G+7/in6A (rs501192) and A10370-G Exon-6 (rs580253)] and one of the NLRP3 gene [UTR'3 G37562-C (rs10754558)] were genotyped by 5' exonuclease TaqMan assays in a group of 617 patients with ACS and 609 control individuals. Under recessive model, the CASP1 G+7/in6A polymorphism was associated with an increased risk of developing ACS when compared to healthy controls (OR = 1.76, 95% CI 1.08-2.86, P Res  = 0.022). In the same way, under recessive model, the CASP1 A10370-G was associated with increased risk of ACS (OR = 1.75, 95% CI 1.07-2.85, P Res  = 0.025). Moreover, under co-dominant, dominant, over-dominant, and additive models, the NLRP3 UTR'3 G37562-C was associated with a decreased risk of ACS (OR = 0.45, 95%CI 0.22-0.92, P Co-dom  = 0.006; OR = 0.61, 95%CI 0.44-0.84, P Dom  = 0.002; OR = 0.67, 95%CI 0.48-0.94, P Over-dom  = 0.02; and OR = 0.65, 95%CI 0.50-0.94, P Add  = 0.02, respectively). In summary, this study demonstrates that the G+7/in6A and A10370-G polymorphisms of the CASP1 gene are associated with increased risk of developing ACS, whereas the UTR'3 G37562-C polymorphism of the NLRP3 gene is associated with a decreased risk of developing ACS in Mexican population.

  14. Inflammatory Genes and Psychological Factors Predict Induced Shoulder Pain Phenotype

    PubMed Central

    George, Steven Z.; Parr, Jeffrey J.; Wallace, Margaret R.; Wu, Samuel S.; Borsa, Paul A.; Dai, Yunfeng; Fillingim, Roger B.

    2014-01-01

    Purpose The pain experience has multiple influences but little is known about how specific biological and psychological factors interact to influence pain responses. The current study investigated the combined influences of genetic (pro-inflammatory) and psychological factors on several pre-clinical shoulder pain phenotypes. Methods An exercise-induced shoulder injury model was used, and a priori selected genetic (IL1B, TNF/LTA region, IL6 single nucleotide polymorphisms, SNPs) and psychological (anxiety, depressive symptoms, pain catastrophizing, fear of pain, kinesiophobia) factors were included as the predictors of interest. The phenotypes were pain intensity (5-day average and peak reported on numerical rating scale), upper-extremity disability (5-day average and peak reported on the QuickDASH instrument), and duration of shoulder pain (in days). Results After controlling for age, sex, and race, the genetic and psychological predictors were entered separately as main effects and interaction terms in regression models for each pain phenotype. Results from the recruited cohort (n = 190) indicated strong statistical evidence for the interactions between 1) TNF/LTA SNP rs2229094 and depressive symptoms for average pain intensity and duration and 2) IL1B two-SNP diplotype and kinesiophobia for average shoulder pain intensity. Moderate statistical evidence for prediction of additional shoulder pain phenotypes included interactions of kinesiophobia, fear of pain, or depressive symptoms with TNF/LTA rs2229094 and IL1B. Conclusion These findings support the combined predictive ability of specific genetic and psychological factors for shoulder pain phenotypes by revealing novel combinations that may merit further investigation in clinical cohorts, to determine their involvement in the transition from acute to chronic pain conditions. PMID:24598699

  15. 33 CFR 105.245 - Declaration of Security (DoS).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... DoS and for handling DoS requests from a vessel. (b) At MARSEC Level 1, a facility receiving a cruise ship or a manned vessel carrying Certain Dangerous Cargo, in bulk, must comply with the following:...

  16. 33 CFR 105.245 - Declaration of Security (DoS).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... DoS and for handling DoS requests from a vessel. (b) At MARSEC Level 1, a facility receiving a cruise ship or a manned vessel carrying Certain Dangerous Cargo, in bulk, must comply with the following:...

  17. 33 CFR 105.245 - Declaration of Security (DoS).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... DoS and for handling DoS requests from a vessel. (b) At MARSEC Level 1, a facility receiving a cruise ship or a manned vessel carrying Certain Dangerous Cargo, in bulk, must comply with the following:...

  18. Gene Positioning

    PubMed Central

    Ferrai, Carmelo; de Castro, Inês Jesus; Lavitas, Liron; Chotalia, Mita; Pombo, Ana

    2010-01-01

    Eukaryotic gene expression is an intricate multistep process, regulated within the cell nucleus through the activation or repression of RNA synthesis, processing, cytoplasmic export, and translation into protein. The major regulators of gene expression are chromatin remodeling and transcription machineries that are locally recruited to genes. However, enzymatic activities that act on genes are not ubiquitously distributed throughout the nucleoplasm, but limited to specific and spatially defined foci that promote preferred higher-order chromatin arrangements. The positioning of genes within the nuclear landscape relative to specific functional landmarks plays an important role in gene regulation and disease. PMID:20484389

  19. Interleukins as new prognostic genetic biomarkers in non-small cell lung cancer.

    PubMed

    Pérez-Ramírez, Cristina; Cañadas-Garre, Marisa; Alnatsha, Ahmed; Molina, Miguel Ángel; Robles, Ana I; Villar, Eduardo; Delgado, Juan Ramón; Faus-Dáder, María José; Calleja-Hernández, Miguel Ángel

    2017-09-01

    Surgery is the standard treatment for early-stage NSCLC, and platinum-based chemotherapy remains as the treatment of choice for advanced-stage NSCLC patients with naïve EGFR status. However, overall 5-years relative survival rates are low. Interleukins (ILs) are crucial for processes associated with tumor development. In NSCLC, IL1B, IL6, IL12A, IL13 and IL16 gene polymorphisms may contribute to individual variation in terms of patient survival. The purpose of this study was to evaluate the association between IL gene polymorphisms and survival in NSCLC patients. A prospective cohorts study was performed, including 170 NSCLC patients (114 Stage IIIB-IV, 56 Stage I-IIIA). IL1B (C > T; rs1143634), IL1B (C > T; rs12621220), IL1B (C > G; rs1143623), IL1B (A > G; rs16944), IL1B (C > T; rs1143627), IL6 (C > G; rs1800795), IL12A (C > T; rs662959), IL13 (A > C; rs1881457) and IL16 (G > T; rs7170924) gene polymorphisms were analyzed by PCR Real-Time. Patients with IL16 rs7170924-GG genotype were in higher risk of death (p = 0.0139; HR = 1.82; CI95% = 1.13-2.94) Furthermore, carriers of the TT genotype for IL12A rs662959 presented higher risk of progression in the non-resected NSCLC patient subgroup (p = 0.0412; HR = 4.49; CI95% = 1.06-18.99). The rest of polymorphisms showed no effect of on outcomes. Our results suggest that IL16 rs7170924-GG and IL12A rs662959-TT genotypes predict higher risk of death and progression, respectively, in NSCLC patients. No influence of IL1B rs12621220, IL1B rs1143623, IL1B rs16944, IL1B rs1143627, IL6 rs1800795, IL13 rs1881457 on NSCLC clinical outcomes was found in our patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Gene doping.

    PubMed

    Azzazy, Hassan M E

    2010-01-01

    Gene doping abuses the legitimate approach of gene therapy. While gene therapy aims to correct genetic disorders by introducing a foreign gene to replace an existing faulty one or by manipulating existing gene(s) to achieve a therapeutic benefit, gene doping employs the same concepts to bestow performance advantages on athletes over their competitors. Recent developments in genetic engineering have contributed significantly to the progress of gene therapy research and currently numerous clinical trials are underway. Some athletes and their staff are probably watching this progress closely. Any gene that plays a role in muscle development, oxygen delivery to tissues, neuromuscular coordination, or even pain control is considered a candidate for gene dopers. Unfortunately, detecting gene doping is technically very difficult because the transgenic proteins expressed by the introduced genes are similar to their endogenous counterparts. Researchers today are racing the clock because assuring the continued integrity of sports competition depends on their ability to develop effective detection strategies in preparation for the 2012 Olympics, which may mark the appearance of genetically modified athletes.

  1. Gene therapy.

    PubMed

    Williamson, B

    1982-07-29

    Gene therapy is not yet possible, but may become feasible soon, particularly for well understood gene defects. Although treatment of a patient raises no ethical problems once it can be done well, changing the genes of an early embryo is more difficult, controversial and unlikely to be required clinically.

  2. Detection of DoS attacks using intrusion detection sensors

    NASA Astrophysics Data System (ADS)

    Ramakrishna, Pathmenanthan; Maarof, Mohd A.

    2002-09-01

    Intrusion detection systems have usually been developed using large host-based components. These components impose an extra load on the system where they run (sometimes even requiring a dedicated system) and are subject to tampering or disabling by an intruder. Additionally, intrusion detection systems have usually obtained information about host behavior through indirect means, such as audit trails or network packet traces. This potentially allows intruders to modify the information before the intrusion detection system obtains it and slows down the detection and prevention of DoS attacks, making it possible for an intruder to hide his activities. In this paper we propose work that will attempt to show that it is possible to perform intrusion detection mechanism of DoS attacks using small sensors embedded in a computer system. These sensors will look for signs of specific intrusions. They will perform target monitoring by observing the behavior of the through an audit trail or other indirect means in real time while the Snort IDS running. Furthermore, by being built into the computer system it could provide a flexible alert sensor which may not impose a considerable extra load on the host they monitor.

  3. Gene Therapy

    PubMed Central

    Scheller, E.L.; Krebsbach, P.H.

    2009-01-01

    Gene therapy is defined as the treatment of disease by transfer of genetic material into cells. This review will explore methods available for gene transfer as well as current and potential applications for craniofacial regeneration, with emphasis on future development and design. Though non-viral gene delivery methods are limited by low gene transfer efficiency, they benefit from relative safety, low immunogenicity, ease of manufacture, and lack of DNA insert size limitation. In contrast, viral vectors are nature’s gene delivery machines that can be optimized to allow for tissue-specific targeting, site-specific chromosomal integration, and efficient long-term infection of dividing and non-dividing cells. In contrast to traditional replacement gene therapy, craniofacial regeneration seeks to use genetic vectors as supplemental building blocks for tissue growth and repair. Synergistic combination of viral gene therapy with craniofacial tissue engineering will significantly enhance our ability to repair and replace tissues in vivo. PMID:19641145

  4. Aggressive periodontitis and chronic arthritis: blood mononuclear cell gene expression and plasma protein levels of cytokines and cytokine inhibitors.

    PubMed

    Sørensen, Lars K; Havemose-Poulsen, Anne; Bendtzen, Klaus; Holmstrup, Palle

    2009-02-01

    Cytokines and cytokine inhibitors have been associated with many immunoinflammatory diseases. In the present study, we examined whether peripheral blood mononuclear cell (PBMC) gene expression mirrors the corresponding plasma levels of clinically important pro- and anti-inflammatory cytokines and cytokine receptors in patients with periodontitis and patients with arthritis representing two examples of chronic inflammatory diseases, such as periodontitis and arthritis. To identify possible disease-specific characteristics of subjects with periodontitis relative to subjects with chronic inflammation in general, patients with arthritis (juvenile idiopathic arthritis [JIA] and rheumatoid arthritis [RA]) were included. The study population consisted of white adults <35 years of age diagnosed with localized aggressive periodontitis (LAgP; n = 18), generalized aggressive periodontitis (GAgP; n = 27), JIA (n = 10), and RA (n = 23) and healthy controls (n = 25). PBMC transcripts of interleukin (IL) 1 alpha (IL1A), IL 1 beta (IL1B), IL 1 receptor antagonist (IL1RN), IL6, IL10, tumor necrosis factor alpha (TNFA), TNF alpha receptor I (TNFRI), and TNFRII were measured using real-time reverse transcription-polymerase chain reaction and compared to the corresponding plasma protein levels measured by enzyme-linked immunosorbent assay and a multiplex antibody bead assay. Compared to controls, soluble (s) TNF-RII levels were significantly elevated in patients with GAgP (P = 0.001) or JIA (P = 0.002), and PBMC TNFA transcript levels were lower in patients with JIA (P = 0.001). A negative correlation was found between IL6 expression and IL-6 plasma levels in patients with JIA versus controls, and a positive correlation/association was found between TNFRI expression and sTNF-RI plasma levels in patients with LAgP and RA. The study demonstrated only a few changes in the PBMC expression of various cytokine and cytokine inhibitor genes in aggressive periodontitis and chronic arthritis

  5. Association of IL10 and Other Immune Response- and Obesity-Related Genes with Prostate Cancer in CLUE II

    PubMed Central

    Wang, Ming-Hsi; Helzlsouer, Kathy J.; Smith, Michael W.; Hoffman-Bolton, Judith A.; Clipp, Sandra L.; Grinberg, Viktoriya; De Marzo, Angelo M.; Isaacs, William B.; Drake, Charles G.; Shugart, Yin Yao; Platz, Elizabeth A.

    2010-01-01

    BACKGROUND Chronic intra-prostatic inflammation and obesity are thought to influence prostate carcinogenesis. Thus, variants in genes in these pathways could be associated with prostate cancer risk. METHODS We genotyped 17 common single nucleotide polymorphisms (SNPs) in RNASEL, TLR4, IL1B, IL6, IL8, IL10, TNF, CRP, ADIPOQ, LEP, PPARG, and TCF7L2 in 258 white prostate cancer cases and 258 matched controls nested in CLUE II. Single-locus analyses were conducted using conditional logistic regression. TagSNPs were selected in IL10, CRP, and TLR4 and haplotype analyses were done. RESULTS The A allele of IL10 -1082G>A (rs1800896), known to result in lower levels of this anti-inflammatory cytokine, was positively associated with risk (AG vs. GG, OR=1.69, 95% CI: 1.10–2.60; AA vs. GG, OR=1.81, 95% CI: 1.11–2.96; Ptrend=0.02). Associations of IL10 haplotypes with prostate cancer were explained by high linkage disequilibrium between two tagSNPs (rs1800890 and rs3024496) and -1082G>A. A TLR4 candidate SNP (rs4986790; AG/GG vs. AA, OR=0.60, 95% CI: 0.33–1.08; Ptrend=0.09), known to have decreased expression and be associated with lower circulating levels of inflammatory mediators, and tagSNP (rs10116253; CC vs. TT, OR=3.05, 95% CI: 1.11–8.41), but not haplotypes, were associated with risk. None of the other candidate SNPs or haplotypes was statistically significantly associated with risk. CONCLUSION Our prospective study suggests that genetic variation in IL10 and possibly TLR4 is associated with prostate cancer risk. Although none of the SNPs in the obesity genes tested was associated, this does not rule out a complex role of obesity and its metabolic consequences in prostate cancer etiology. PMID:19267370

  6. Schizophrenia Susceptibility Genes Directly Implicated in the Life Cycles of Pathogens: Cytomegalovirus, Influenza, Herpes simplex, Rubella, and Toxoplasma gondii

    PubMed Central

    Carter, C.J.

    2009-01-01

    Many genes implicated in schizophrenia can be related to glutamatergic transmission and neuroplasticity, oligodendrocyte function, and other families clearly related to neurobiology and schizophrenia phenotypes. Others appear rather to be involved in the life cycles of the pathogens implicated in the disease. For example, aspartylglucosaminidase (AGA), PLA2, SIAT8B, GALNT7, or B3GAT1 metabolize chemical ligands to which the influenza virus, herpes simplex, cytomegalovirus (CMV), rubella, or Toxoplasma gondii bind. The epidermal growth factor receptor (EGR/EGFR) is used by the CMV to gain entry to cells, and a CMV gene codes for an interleukin (IL-10) mimic that binds the host cognate receptor, IL10R. The fibroblast growth factor receptor (FGFR1) is used by herpes simplex. KPNA3 and RANBP5 control the nuclear import of the influenza virus. Disrupted in schizophrenia 1 (DISC1) controls the microtubule network that is used by viruses as a route to the nucleus, while DTNBP1, MUTED, and BLOC1S3 regulate endosomal to lysosomal routing that is also important in viral traffic. Neuregulin 1 activates ERBB receptors releasing a factor, EBP1, known to inhibit the influenza virus transcriptase. Other viral or bacterial components bind to genes or proteins encoded by CALR, FEZ1, FYN, HSPA1B, IL2, HTR2A, KPNA3, MED12, MED15, MICB, NQO2, PAX6, PIK3C3, RANBP5, or TP53, while the cerebral infectivity of the herpes simplex virus is modified by Apolipoprotein E (APOE). Genes encoding for proteins related to the innate immune response, including cytokine related (CCR5, CSF2RA, CSF2RB, IL1B, IL1RN, IL2, IL3, IL3RA, IL4, IL10, IL10RA, IL18RAP, lymphotoxin-alpha, tumor necrosis factor alpha [TNF]), human leukocyte antigen (HLA) antigens (HLA-A10, HLA-B, HLA-DRB1), and genes involved in antigen processing (angiotensin-converting enzyme and tripeptidyl peptidase 2) are all concerned with defense against invading pathogens. Human microRNAs (Hsa-mir-198 and Hsa-mir-206) are predicted to bind

  7. Schizophrenia susceptibility genes directly implicated in the life cycles of pathogens: cytomegalovirus, influenza, herpes simplex, rubella, and Toxoplasma gondii.

    PubMed

    Carter, C J

    2009-11-01

    Many genes implicated in schizophrenia can be related to glutamatergic transmission and neuroplasticity, oligodendrocyte function, and other families clearly related to neurobiology and schizophrenia phenotypes. Others appear rather to be involved in the life cycles of the pathogens implicated in the disease. For example, aspartylglucosaminidase (AGA), PLA2, SIAT8B, GALNT7, or B3GAT1 metabolize chemical ligands to which the influenza virus, herpes simplex, cytomegalovirus (CMV), rubella, or Toxoplasma gondii bind. The epidermal growth factor receptor (EGR/EGFR) is used by the CMV to gain entry to cells, and a CMV gene codes for an interleukin (IL-10) mimic that binds the host cognate receptor, IL10R. The fibroblast growth factor receptor (FGFR1) is used by herpes simplex. KPNA3 and RANBP5 control the nuclear import of the influenza virus. Disrupted in schizophrenia 1 (DISC1) controls the microtubule network that is used by viruses as a route to the nucleus, while DTNBP1, MUTED, and BLOC1S3 regulate endosomal to lysosomal routing that is also important in viral traffic. Neuregulin 1 activates ERBB receptors releasing a factor, EBP1, known to inhibit the influenza virus transcriptase. Other viral or bacterial components bind to genes or proteins encoded by CALR, FEZ1, FYN, HSPA1B, IL2, HTR2A, KPNA3, MED12, MED15, MICB, NQO2, PAX6, PIK3C3, RANBP5, or TP53, while the cerebral infectivity of the herpes simplex virus is modified by Apolipoprotein E (APOE). Genes encoding for proteins related to the innate immune response, including cytokine related (CCR5, CSF2RA, CSF2RB, IL1B, IL1RN, IL2, IL3, IL3RA, IL4, IL10, IL10RA, IL18RAP, lymphotoxin-alpha, tumor necrosis factor alpha [TNF]), human leukocyte antigen (HLA) antigens (HLA-A10, HLA-B, HLA-DRB1), and genes involved in antigen processing (angiotensin-converting enzyme and tripeptidyl peptidase 2) are all concerned with defense against invading pathogens. Human microRNAs (Hsa-mir-198 and Hsa-mir-206) are predicted to bind

  8. Mycobacterium tuberculosis DosR is Required for Activity of the PmbtB and PmbtI Promoters under Hypoxia

    PubMed Central

    Schreuder, Lise J.; Parish, Tanya

    2014-01-01

    Mycobacterium tuberculosis has the ability to survive for extended periods of time under conditions of low oxygen, low pH, low iron and low nutrients. The mycobactins (M. tuberculosis siderophores) play a key role in scavenging iron from the environment and are induced in response to low iron in an IdeR-regulated manner. We demonstrate that the promoters of two mycobactin gene (mbt) operons are also expressed during adaptation to low oxygen, and that this expression is dependent on the DosR regulator. Up-regulation of mbt operons induced by low iron was not DosR-dependent. DosR is a member of a two component regulatory system which responds to oxygen availability. Deletion of the DosR regulator led to increased expression of bacterioferritin and increased capacity to grow under iron depletion. These data provide a link between the mycobacterial response to two conditions likely to be encountered in vivo, low iron and low oxygen. PMID:25211224

  9. Gene network and pathway analysis of bovine mammary tissue challenged with Streptococcus uberis reveals induction of cell proliferation and inhibition of PPARγ signaling as potential mechanism for the negative relationships between immune response and lipid metabolism

    PubMed Central

    2009-01-01

    Background Information generated via microarrays might uncover interactions between the mammary gland and Streptococcus uberis (S. uberis) that could help identify control measures for the prevention and spread of S. uberis mastitis, as well as improve overall animal health and welfare, and decrease economic losses to dairy farmers. The main objective of this study was to determine the most affected gene networks and pathways in mammary tissue in response to an intramammary infection (IMI) with S. uberis and relate these with other physiological measurements associated with immune and/or metabolic responses to mastitis challenge with S. uberis O140J. Results Streptococcus uberis IMI resulted in 2,102 (1,939 annotated) differentially expressed genes (DEG). Within this set of DEG, we uncovered 20 significantly enriched canonical pathways (with 20 to 61 genes each), the majority of which were signaling pathways. Among the most inhibited were LXR/RXR Signaling and PPARα/RXRα Signaling. Pathways activated by IMI were IL-10 Signaling and IL-6 Signaling which likely reflected counter mechanisms of mammary tissue to respond to infection. Of the 2,102 DEG, 1,082 were up-regulated during IMI and were primarily involved with the immune response, e.g., IL6, TNF, IL8, IL10, SELL, LYZ, and SAA3. Genes down-regulated (1,020) included those associated with milk fat synthesis, e.g., LPIN1, LPL, CD36, and BTN1A1. Network analysis of DEG indicated that TNF had positive relationships with genes involved with immune system function (e.g., CD14, IL8, IL1B, and TLR2) and negative relationships with genes involved with lipid metabolism (e.g., GPAM, SCD, FABP4, CD36, and LPL) and antioxidant activity (SOD1). Conclusion Results provided novel information into the early signaling and metabolic pathways in mammary tissue that are associated with the innate immune response to S. uberis infection. Our study indicated that IMI challenge with S. uberis (strain O140J) elicited a strong

  10. Sedimentation survey of Lago Dos Bocas, Puerto Rico, June 1985

    USGS Publications Warehouse

    Quinones, Ferdinand; Melendez, Frank; Bonnet, Carlos

    1989-01-01

    A survey of the sedimentation of Dos Bocas reservoir, in central Puerto Rico, was conducted during July 1985. The survey showed that the capacity of the reservoir has declined from 30,420 acre-ft in 1942 to about 19,620 acre-ft. Sediment is accumulating in the reservoir at an average rate of about 251 acre-ft/yr, or about 0.83%/yr of the original capacity. The expected usable life of the reservoir on the basis of the long-term sedimentation rate is about 78 years. However, the sedimentation rate appears to have increased significantly since 1979. During the last six years, the average sedimentation rate has exceeded 600 acre-ft/yr. If this rate is maintained, the expected usable life of the reservoir would be about 32 years. (Author 's abstract)

  11. Document image archive transfer from DOS to UNIX

    NASA Technical Reports Server (NTRS)

    Hauser, Susan E.; Gill, Michael J.; Thoma, George R.

    1994-01-01

    An R&D division of the National Library of Medicine has developed a prototype system for automated document image delivery as an adjunct to the labor-intensive manual interlibrary loan service of the library. The document image archive is implemented by a PC controlled bank of optical disk drives which use 12 inch WORM platters containing bitmapped images of over 200,000 pages of medical journals. Following three years of routine operation which resulted in serving patrons with articles both by mail and fax, an effort is underway to relocate the storage environment from the DOS-based system to a UNIX-based jukebox whose magneto-optical erasable 5 1/4 inch platters hold the images. This paper describes the deficiencies of the current storage system, the design issues of modifying several modules in the system, the alternatives proposed and the tradeoffs involved.

  12. Gene dispensability.

    PubMed

    Korona, Ryszard

    2011-08-01

    Genome-wide mutagenesis studies indicate that up to about 90% of genes in bacteria and 80% in eukaryotes can be inactivated individually leaving an organism viable, often seemingly unaffected. Several strategies are used to learn what these apparently dispensable genes contribute to fitness. Assays of growth under hundreds of physical and chemical stresses are among the most effective experimental approaches. Comparative studies of genomic DNA sequences continue to be valuable in discriminating between the core bacterial genome and the more variable niche-specific genes. The concept of the core genome appears currently unfeasible for eukaryotes but progress has been made in understanding why they contain numerous gene duplicates.

  13. Mycobacterium tuberculosis growth following aerobic expression of the DosR regulon.

    PubMed

    Minch, Kyle; Rustad, Tige; Sherman, David R

    2012-01-01

    The Mycobacterium tuberculosis regulator DosR is induced by multiple stimuli including hypoxia, nitric oxide and redox stress. Overlap of these stimuli with conditions thought to promote latency in infected patients fuels a model in which DosR regulon expression is correlated with bacteriostasis in vitro and a proxy for latency in vivo. Here, we find that inducing the DosR regulon to wildtype levels in aerobic, replicating M. tuberculosis does not alter bacterial growth kinetics. We conclude that DosR regulon expression alone is insufficient for bacterial latency, but rather is expressed during a range of growth states in a dynamic environment.

  14. Trichoderma genes

    DOEpatents

    Foreman, Pamela [Los Altos, CA; Goedegebuur, Frits [Vlaardingen, NL; Van Solingen, Pieter [Naaldwijk, NL; Ward, Michael [San Francisco, CA

    2012-06-19

    Described herein are novel gene sequences isolated from Trichoderma reesei. Two genes encoding proteins comprising a cellulose binding domain, one encoding an arabionfuranosidase and one encoding an acetylxylanesterase are described. The sequences, CIP1 and CIP2, contain a cellulose binding domain. These proteins are especially useful in the textile and detergent industry and in pulp and paper industry.

  15. Gene therapy.

    PubMed

    Drugan, A; Miller, O J; Evans, M I

    1987-01-01

    Severe genetic disorders are potentially correctable by the addition of a normal gene into tissues. Although the technical problems involving integration, stable expression, and insertional damage to the treated cell are not yet fully solved, enough scientific progress has already been made to consider somatic cell gene therapy acceptable from both the ethical and scientific viewpoints. The resolutions to problems evolving from somatic cell gene therapy will help to overcome the technical difficulties encountered presently with germ line gene manipulation. This procedure would then become morally permissible as it will cause, in time, a reduction in the pool of abnormal genes in the population. Enhancement genetic engineering is technically feasible but morally unacceptable. Eugenic genetic engineering is not technically possible or ethically permissible in the foreseeable future.

  16. Activation of ATP binding for the autophosphorylation of DosS, a Mycobacterium tuberculosis histidine kinase lacking an ATP lid motif.

    PubMed

    Cho, Ha Yeon; Lee, Young-Hoon; Bae, Young-Seuk; Kim, Eungbin; Kang, Beom Sik

    2013-05-03

    The sensor histidine kinases of Mycobacterium tuberculosis, DosS and DosT, are responsible for sensing hypoxic conditions and consist of sensor and kinase cores responsible for accepting signals and phosphorylation activity, respectively. The kinase core contains a dimerization and histidine phosphate-accepting (DHp) domain and an ATP binding domain (ABD). The 13 histidine kinase genes of M. tuberculosis can be grouped based on the presence or absence of the ATP lid motif and F box (elements known to play roles in ATP binding) in their ABDs; DosS and DosT have ABDs lacking both these elements, and the crystal structures of their ABDs indicated that they were unsuitable for ATP binding, as a short loop covers the putative ATP binding site. Although the ABD alone cannot bind ATP, the kinase core is functional in autophosphorylation. Appropriate spatial arrangement of the ABD and DHp domain within the kinase core is required for both autophosphorylation and ATP binding. An ionic interaction between Arg(440) in the DHp domain and Glu(537) in the short loop of the ABD is available and may open the ATP binding site, by repositioning the short loop away from the site. Mutations at Arg(440) and Glu(537) reduce autophosphorylation activity. Unlike other histidine kinases containing an ATP lid, which protects bound ATP, DosS is unable to accept ATP until the ABD is properly positioned relative to the histidine; this may prevent unexpected ATP reactions. ATP binding can, therefore, function as a control mechanism for histidine kinase activity.

  17. Changes in the colon microbiota and intestinal cytokine gene expression following minimal intestinal surgery

    PubMed Central

    Lapthorne, Susan; Bines, Julie E; Fouhy, Fiona; Dellios, Nicole L; Wilson, Guineva; Thomas, Sarah L; Scurr, Michelle; Stanton, Catherine; Cotter, Paul D; Pereira-Fantini, Prue M

    2015-01-01

    AIM: To investigate the impact of minor abdominal surgery on the caecal microbial population and on markers of gut inflammation. METHODS: Four week old piglets were randomly allocated to a no-surgery “control” group (n = 6) or a “transection surgery” group (n = 5). During the transection surgery procedure, a conventional midline incision of the lower abdominal wall was made and the small intestine was transected at a site 225 cm proximal to the ileocaecal valve, a 2 cm segment was removed and the intestine was re-anastomosed. Piglets received a polymeric infant formula diet throughout the study period and were sacrificed at two weeks post-surgery. Clinical outcomes including weight, stool consistency and presence of stool fat globules were monitored. High throughput DNA sequencing of colonic content was used to detect surgery-related disturbances in microbial composition at phylum, family and genus level. Diversity and richness estimates were calculated for the control and minor surgery groups. As disturbances in the gut microbial community are linked to inflammation we compared the gene expression of key inflammatory cytokines (TNF, IL1B, IL18, IL12, IL8, IL6 and IL10) in ileum, terminal ileum and colon mucosal extracts obtained from control and abdominal surgery groups at two weeks post-surgery. RESULTS: Changes in the relative abundance of bacterial species at family and genus level were confined to bacterial members of the Proteobacteria and Bacteroidetes phyla. Family level compositional shifts included a reduction in the relative abundance of Enterobacteriaceae (22.95 ± 5.27 vs 2.07 ± 0.72, P < 0.01), Bacteroidaceae (2.54 ± 0.56 vs 0.86 ± 0.43, P < 0.05) and Rhodospirillaceae (0.40 ± 0.14 vs 0.00 ± 0.00, P < 0.05) following transection surgery. Similarly, at the genus level, changes associated with transection surgery were restricted to members of the Proteobacteria and Bacteroidetes phyla and included decreased relative abundance of

  18. Cmr is a redox-responsive regulator of DosR that contributes to M. tuberculosis virulence

    PubMed Central

    Bochkareva, Aleksandra; Rolfe, Matthew D.; Hunt, Debbie M.; Kahramanoglou, Christina; Braun, Yvonne; Rodgers, Angela; Blockley, Alix; Coade, Stephen; Lougheed, Kathryn E.A.; Hafneh, Nor Azian; Glenn, Sarah M.; Crack, Jason C.; Le Brun, Nick E.; Saldanha, José W.; Makarov, Vadim; Nobeli, Irene; Mukamolova, Galina V.; Buxton, Roger S.; Green, Jeffrey

    2017-01-01

    Abstract Mycobacterium tuberculosis (MTb) is the causative agent of pulmonary tuberculosis (TB). MTb colonizes the human lung, often entering a non-replicating state before progressing to life-threatening active infections. Transcriptional reprogramming is essential for TB pathogenesis. In vitro, Cmr (a member of the CRP/FNR super-family of transcription regulators) bound at a single DNA site to act as a dual regulator of cmr transcription and an activator of the divergent rv1676 gene. Transcriptional profiling and DNA-binding assays suggested that Cmr directly represses dosR expression. The DosR regulon is thought to be involved in establishing latent tuberculosis infections in response to hypoxia and nitric oxide. Accordingly, DNA-binding by Cmr was severely impaired by nitrosation. A cmr mutant was better able to survive a nitrosative stress challenge but was attenuated in a mouse aerosol infection model. The complemented mutant exhibited a ∼2-fold increase in cmr expression, which led to increased sensitivity to nitrosative stress. This, and the inability to restore wild-type behaviour in the infection model, suggests that precise regulation of the cmr locus, which is associated with Region of Difference 150 in hypervirulent Beijing strains of Mtb, is important for TB pathogenesis. PMID:28482027

  19. Degradability of dimethyl terephthalate by Variovorax paradoxus T4 and Sphingomonas yanoikuyae DOS01 isolated from deep-ocean sediments.

    PubMed

    Wang, Yu Ping; Gu, Ji-Dong

    2006-08-01

    Two strains of bacteria were isolated from deep-ocean sediments of the South China Sea using enrichment culturing technique and they were identified as Sphingomonas yanoikuyae DOS01 (AY878409) and Variovorax paradoxus T4 (AY878410) based on 16S rRNA gene sequences. S. yanoikuyae DOS01 was only capable of transforming dimethyl terephthalate (DMTP) to monomethyl terephthalate (MMTP) without further degradation while V. paradoxus T4 exhibited ability in mineralizing DMTP as the sole source of carbon and energy. The biochemical pathway of DMTP degradation was through MMTP and terephthalic acid (TA) as major detectable degradation intermediates in the culture media by both microorganisms. V. paradoxus T4 utilized DMTP and MMTP via hydrolysis of diester and monoester in the initial steps in degradation as confirmed by total organic carbon analysis of the culture medium and esterase activity assay of the lysed cells and fraction. The specific hydrolysis activity of esterase induced by DMTP or MMTP showed that greater hydrolysis of p-nitrophenyl acetate by esterase induced by DMTP-grown cells than that induced by MMTP. Results of this research suggest that the cleavage of the two identical carboxylic ester groups of phthalate diester are carried out by highly specific esterases of the same bacteria in the environment.

  20. [Gene and gene sequence patenting].

    PubMed

    Bergel, S D

    1998-01-01

    According to the author, the patenting of elements isolated or copied from the human body boils down to the issue of genes and gene sequences. He describes the current situation from the comparative law standpoint (U.S. and Spanish law mainly) and then esamines the biotechnology industry's position.

  1. [Sleep genes].

    PubMed

    Prospéro-García, O; Guzmán, K; Méndez-Diaz, M; Herrera-Solís, A; Ruiz-Contreras, A

    Sleep is a non-learned adaptive strategy that depends on the expression of several neurotransmitters and other molecules. The expression of some of these molecules depends on a number of different genes. Sleep disorders are associated with an inadequate expression of some molecules, which therefore indicates that these genes that code for these molecules participate in the regulation of normal sleep. To discuss the evidence on gene regulation over the occurrence of sleep and its architecture, as well as of sleep disorders, which supports the participation of specific genes. We describe the evidence on sleep in mammals, particularly in humans, in addition to studies with twins that demonstrate the influence of genes on sleep regulation. We also discuss several sleep disorders, which in this study only serves to emphasise how certain specific genes, under normal conditions, participate in the expression of sleep. Furthermore, evidence is also provided for other molecules, such as endocannibinoids, involved in sleep regulation. Lastly, we report on studies conducted with different strains of mice that show differences in the amount of sleep they express, possibly as an epiphenomenon of their different genetic loads. A number of different genes have been described as those responsible for making us sleep, although sleeping also depends on our interaction with the environment. This interaction is what makes us express sleep at times that are best suited to favouring our survival.

  2. Gene Therapy.

    PubMed

    Thorne, Barb; Takeya, Ryan; Vitelli, Francesca; Swanson, Xin

    2017-03-14

    Gene therapy refers to a rapidly growing field of medicine in which genes are introduced into the body to treat or prevent diseases. Although a variety of methods can be used to deliver the genetic materials into the target cells and tissues, modified viral vectors represent one of the more common delivery routes because of its transduction efficiency for therapeutic genes. Since the introduction of gene therapy concept in the 1970s, the field has advanced considerably with notable clinical successes being demonstrated in many clinical indications in which no standard treatment options are currently available. It is anticipated that the clinical success the field observed in recent years can drive requirements for more scalable, robust, cost effective, and regulatory-compliant manufacturing processes. This review provides a brief overview of the current manufacturing technologies for viral vectors production, drawing attention to the common upstream and downstream production process platform that is applicable across various classes of viral vectors and their unique manufacturing challenges as compared to other biologics. In addition, a case study of an industry-scale cGMP production of an AAV-based gene therapy product performed at 2,000 L-scale is presented. The experience and lessons learned from this largest viral gene therapy vector production run conducted to date as discussed and highlighted in this review should contribute to future development of commercial viable scalable processes for vial gene therapies.

  3. DosS Is required for the complete virulence of mycobacterium tuberculosis in mice with classical granulomatous lesions.

    PubMed

    Gautam, Uma S; McGillivray, Amanda; Mehra, Smriti; Didier, Peter J; Midkiff, Cecily C; Kissee, Ryan S; Golden, Nadia A; Alvarez, Xavier; Niu, Tianhua; Rengarajan, Jyothi; Sherman, David R; Kaushal, Deepak

    2015-06-01

    Mycobacterium tuberculosis (Mtb) must counter hypoxia within granulomas to persist. DosR, in concert with sensor kinases DosS and DosT, regulates the response to hypoxia. Yet Mtb lacking functional DosR colonize the lungs of C57Bl/6 mice, presumably owing to the lack of organized lesions with sufficient hypoxia in that model. We compared the phenotype of the Δ-dosR, Δ-dosS, and Δ-dosT mutants to Mtb using C3HeB/FeJ mice, an alternate mouse model where lesions develop hypoxia. C3HeB/FeJ mice were infected via aerosol. The progression of infection was analyzed by tissue bacterial burden and histopathology. A measure of the comparative global immune responses was also analyzed. Although Δ-dosR and Δ-dosT grew comparably to wild-type Mtb, Δ-dosS exhibited a significant defect in bacterial burden and pathology in vivo, accompanied by ablated proinflammatory response. Δ-dosS retained the ability to induce DosR. The Δ-dosS mutant was also attenuated in murine macrophages ex vivo, with evidence of reduced expression of the proinflammatory signature. Our results show that DosS, but not DosR and DosT, is required by Mtb to survive in C3HeB/FeJ mice. The attenuation of Δ-dosS is not due to its inability to induce the DosR regulon, nor is it a result of the accumulation of hypoxia. That the in vivo growth restriction of Δ-dosS could be mimicked ex vivo suggested sensitivity to macrophage oxidative burst. Anoxic caseous centers within tuberculosis lesions eventually progress to cavities. Our results provide greater insight into the molecular mechanisms of Mtb persistence within host lungs.

  4. Pathways and gene networks mediating the regulatory effects of cannabidiol, a nonpsychoactive cannabinoid, in autoimmune T cells.

    PubMed

    Kozela, Ewa; Juknat, Ana; Gao, Fuying; Kaushansky, Nathali; Coppola, Giovanni; Vogel, Zvi

    2016-06-03

    Our previous studies showed that the non-psychoactive cannabinoid, cannabidiol (CBD), ameliorates the clinical symptoms in mouse myelin oligodendrocyte glycoprotein (MOG)35-55-induced experimental autoimmune encephalomyelitis model of multiple sclerosis (MS) as well as decreases the memory MOG35-55-specific T cell (TMOG) proliferation and cytokine secretion including IL-17, a key autoimmune factor. The mechanisms of these activities are currently poorly understood. Herein, using microarray-based gene expression profiling, we describe gene networks and intracellular pathways involved in CBD-induced suppression of these activated memory TMOG cells. Encephalitogenic TMOG cells were stimulated with MOG35-55 in the presence of spleen-derived antigen presenting cells (APC) with or without CBD. mRNA of purified TMOG was then subjected to Illumina microarray analysis followed by ingenuity pathway analysis (IPA), weighted gene co-expression network analysis (WGCNA) and gene ontology (GO) elucidation of gene interactions. Results were validated using qPCR and ELISA assays. Gene profiling showed that the CBD treatment suppresses the transcription of a large number of proinflammatory genes in activated TMOG. These include cytokines (Xcl1, Il3, Il12a, Il1b), cytokine receptors (Cxcr1, Ifngr1), transcription factors (Ier3, Atf3, Nr4a3, Crem), and TNF superfamily signaling molecules (Tnfsf11, Tnfsf14, Tnfrsf9, Tnfrsf18). "IL-17 differentiation" and "IL-6 and IL-10-signaling" were identified among the top processes affected by CBD. CBD increases a number of IFN-dependent transcripts (Rgs16, Mx2, Rsad2, Irf4, Ifit2, Ephx1, Ets2) known to execute anti-proliferative activities in T cells. Interestingly, certain MOG35-55 up-regulated transcripts were maintained at high levels in the presence of CBD, including transcription factors (Egr2, Egr1, Tbx21), cytokines (Csf2, Tnf, Ifng), and chemokines (Ccl3, Ccl4, Cxcl10) suggesting that CBD may promote exhaustion of memory TMOG cells. In

  5. America Inc.: John Dos Passos'"USA" as Professional Writing Textbook.

    ERIC Educational Resources Information Center

    Di Renzo, Anthony

    While working as a special consultant for General Mills in 1948, John Dos Passos wrote a report explaining the latest scientific research and technological advancements and how the postwar economy was affecting General Mills and the cereal market. General Mills, using a real writer for a corporate freelance, profited from Dos Passos' expertise and…

  6. Genes V.

    SciTech Connect

    Lewin, B.

    1994-12-31

    This fifth edition book encompasses a wide range of topics covering 1,272 pages. The book is arranged into nine parts with a total of 36 chapters. These nine parts include Introduction; DNA as a Store of Information; Translation; Constructing Cells; Control of Prokaryotypic Gene Expression; Perpetuation of DNA; Organization of the Eukaryotypic Genome; Eukaryotypic Transcription and RNA Processing; The Dynamic Genome; and Genes in Development.

  7. Radiation response and regulation of apoptosis induced by a combination of TRAIL and CHX in cells lacking mitochondrial DNA: A role for NF-{kappa}B-STAT3-directed gene expression

    SciTech Connect

    Ivanov, Vladimir N. Ghandhi, Shanaz A.; Zhou, Hongning; Huang, Sarah X.; Chai, Yunfei; Amundson, Sally A.; Hei, Tom K.

    2011-07-01

    Mitochondrial DNA depleted ({rho}{sup 0}) human skin fibroblasts (HSF) with suppressed oxidative phosphorylation were characterized by significant changes in the expression of 2100 nuclear genes, encoding numerous protein classes, in NF-{kappa}B and STAT3 signaling pathways, and by decreased activity of mitochondrial death pathway, compared to the parental {rho}{sup +} HSF. In contrast, the extrinsic TRAIL/TRAIL-Receptor mediated death pathway remained highly active, and exogenous TRAIL in a combination with cycloheximide (CHX) induced higher levels of apoptosis in {rho}{sup 0} cells compared to {rho}{sup +} HSF. Global gene expression analysis using microarray and qRT-PCR demonstrated that mRNA expression levels of many growth factors and their adaptor proteins (FGF13, HGF, IGFBP4, IGFBP6, and IGFL2), cytokines (IL6, {Oota}L17{Beta}, {Oota}L18, {Oota}L19, and {Oota}L28{Beta}) and cytokine receptors (IL1R1, IL21R, and IL31RA) were substantially decreased after mitochondrial DNA depletion. Some of these genes were targets of NF-{kappa}B and STAT3, and their protein products could regulate the STAT3 signaling pathway. Alpha-irradiation further induced expression of several NF-{kappa}B/STAT3 target genes, including IL1A, IL1B, IL6, PTGS2/COX2 and MMP12, in {rho}{sup +} HSF, but this response was substantially decreased in {rho}{sup 0} HSF. Suppression of the IKK-NF-{kappa}B pathway by the small molecular inhibitor BMS-345541 and of the JAK2-STAT3 pathway by AG490 dramatically increased TRAIL-induced apoptosis in the control and irradiated {rho}{sup +} HSF. Inhibitory antibodies against IL6, the main activator of JAK2-STAT3 pathway, added into the cell media, also increased TRAIL-induced apoptosis in HSF, especially after alpha-irradiation. Collectively, our results indicated that NF-{kappa}B activation was partially lost in {rho}{sup 0} HSF resulting in downregulation of the basal or radiation-induced expression of numerous NF-{kappa}B targets, further suppressing IL6

  8. Associations of interleukin-1 gene cluster polymorphisms with C-reactive protein concentration and lung function decline in smoking-induced chronic obstructive pulmonary disease.

    PubMed

    Wang, Yu; Shumansky, Karey; Sin, Don D; Man, S F Paul; Akhabir, Loubna; Connett, John E; Anthonisen, Nicholas R; Paré, Peter D; Sandford, Andrew J; He, Jian-Qing

    2015-01-01

    We reported association of haplotypes formed by IL-1b (IL1B)-511C/T (rs16944) and a variable number of tandem repeats (rs2234663) in intron 3 of IL-1 receptor antagonist (IL1RN) with rate of lung function decline in smoking-induced COPD. The aim of current study was to further investigate this association. We genotyped an additional 19 polymorphisms in IL1 cluster (including IL1A, IL1B and IL1RN) in non-Hispanic whites who had the fastest (n = 268) and the slowest (n = 292) decline of FEV1% predicted in the same study. We also analyzed the association of all 21 polymorphisms with serum CRP levels. None of 21 polymorphisms showed significant association with rate of decline of lung function or CRP levels after adjusting for multiple comparisons. Before adjusting for multiple comparisons, only IL1RN_19327 (rs315949) showed significant association with lung function decline (P = 0.03, additive model). The frequencies of genotypes containing the IL1RN_19327A allele were 71.9% and 62.2%, respectively in the fast and slow decline groups (P = 0.02, odds ratio = 1.6, 95% confidence interval = 1.1-2.3); the IL1B_5200 (rs1143633) and rs2234663 in IL1RN were associated with serum CRP levels (P=0.04 and 0.03, respectively). No single marker was significantly associated with either rate of lung function decline or serum CRP levels.

  9. Alpha-Lipoic Acid Downregulates IL-1β and IL-6 by DNA Hypermethylation in SK-N-BE Neuroblastoma Cells.

    PubMed

    Dinicola, Simona; Proietti, Sara; Cucina, Alessandra; Bizzarri, Mariano; Fuso, Andrea

    2017-09-26

    Alpha-lipoic acid (ALA) is a pleiotropic molecule with antioxidant and anti-inflammatory properties, of which the effects are exerted through the modulation of NF-kB. This nuclear factor, in fact, modulates different inflammatory cytokines, including IL-1b and IL-6, in different tissues and cell types. We recently showed that IL-1b and IL-6 DNA methylation is modulated in the brain of Alzheimer's disease patients, and that IL-1b expression is associated to DNA methylation in the brain of patients with tuberous sclerosis complex. These results prompted us to ask whether ALA-induced repression of IL-1b and IL-6 was dependent on DNA methylation. Therefore, we profiled DNA methylation in the 5'-flanking region of the two aforementioned genes in SK-N-BE human neuroblastoma cells cultured in presence of ALA 0.5 mM. Our experimental data pointed out that the two promoters are hypermethylated in cells supplemented with ALA, both at CpG and non-CpG sites. Moreover, the observed hypermethylation is associated with decreased mRNA expression and decreased cytokine release. These results reinforce previous findings indicating that IL-1b and IL-6 undergo DNA methylation-dependent modulation in neural models and pave the road to study the epigenetic mechanisms triggered by ALA.

  10. Transient inflammatory response mediated by interleukin-1β is required for proper regeneration in zebrafish fin fold

    PubMed Central

    Hasegawa, Tomoya; Hall, Christopher J; Crosier, Philip S; Abe, Gembu; Kawakami, Koichi; Kudo, Akira; Kawakami, Atsushi

    2017-01-01

    Cellular responses to injury are crucial for complete tissue regeneration, but their underlying processes remain incompletely elucidated. We have previously reported that myeloid-defective zebrafish mutants display apoptosis of regenerative cells during fin fold regeneration. Here, we found that the apoptosis phenotype is induced by prolonged expression of interleukin 1 beta (il1b). Myeloid cells are considered to be the principal source of Il1b, but we show that epithelial cells express il1b in response to tissue injury and initiate the inflammatory response, and that its resolution by macrophages is necessary for survival of regenerative cells. We further show that Il1b plays an essential role in normal fin fold regeneration by regulating expression of regeneration-induced genes. Our study reveals that proper levels of Il1b signaling and tissue inflammation, which are tuned by macrophages, play a crucial role in tissue regeneration. DOI: http://dx.doi.org/10.7554/eLife.22716.001 PMID:28229859

  11. Effect of pregnancy on anti-HEV antibody titres, plasma cytokines and the corresponding gene expression levels in the PBMCs of patients presenting with self-recovering clinical and subclinical hepatitis E.

    PubMed

    Ramdasi, Ashwini Y; Arya, Ravi P; Arankalle, Vidya A

    2014-01-01

    High mortality in pregnant women (PR) is a characteristic of hepatitis E in developing countries. To understand the pathogenesis of HEV infection in self-limiting disease during pregnancy, we compared clinical (PR-patients) and subclinical-HEV-infections in pregnant women in the first (SC-PR-1) and later (2nd and 3rd, SC-PR-2+3) trimesters with the respective healthy controls and acute non-PR patients. The SC-PR-2+3 exhibited lower ALT, bilirubin levels, anti-HEV-IgM/IgG titres than the acute-PR/non-PR-patients (p<0.05-0.0001). IFNγ/IL4ratios indicated Th2/Th1 bias in non-PR and PR-patients respectively. Raised levels of 10/20 plasma cytokines in the non-PR-patients reflect predominant inflammatory response, unaltered- IFNγ/reduced-IFNα responses and a robust chemokine secretion. On contrary, the acute-PR-patients exhibited drastic reduction in majority of the cytokines relative to in the non-PR-patients. Importantly, diminished or unaltered response was noted in the acute-PR-group when compared to the corresponding controls. The only exception was sIL2RA, increasing in both patient categories. Of the 14 genes evaluated, the expression of IFNγ/IL10/IL1A/IL7/CCL2/CCL3/CXCL8/CXCL10 was higher in the non-PR patients. Of these, the expression of IFNγ/IL10/IL1A/CCL2/CCL3/CXCL8 and, additionally, IL2/IL6/TNF genes was higher in the clinical-PRs. Almost identical pattern was noted in the control-PR-2+3 category indicating no influence of HEV infection. Comparison of patient-categories identified significant elevation of IFNγ(P<0.001), CCL2(p<0.01), CXCL8(P<0.05), IL1B(p<0.05) and IL10(P<0.0001) and decrease in CXCL10(<0.05) in the PR-patients. The results suggest antibody-dependent disease severity and impaired immune response in the PR patients. Higher expression of cytokine-genes in the PBMCs did not correlate with the plasma-cytokine levels in the PR-patients.

  12. Attention Genes

    ERIC Educational Resources Information Center

    Posner, Michael I.; Rothbart, Mary K.; Sheese, Brad E.

    2007-01-01

    A major problem for developmental science is understanding how the cognitive and emotional networks important in carrying out mental processes can be related to individual differences. The last five years have seen major advances in establishing links between alleles of specific genes and the neural networks underlying aspects of attention. These…

  13. Designer Genes.

    ERIC Educational Resources Information Center

    Miller, Judith; Miller, Mark

    1983-01-01

    Genetic technologies may soon help fill some of the most important needs of humanity from food to energy to health care. The research of major designer genes companies and reasons why the initial mad rush for biotechnology has slowed are reviewed. (SR)

  14. Designer Genes.

    ERIC Educational Resources Information Center

    Miller, Judith; Miller, Mark

    1983-01-01

    Genetic technologies may soon help fill some of the most important needs of humanity from food to energy to health care. The research of major designer genes companies and reasons why the initial mad rush for biotechnology has slowed are reviewed. (SR)

  15. Attention Genes

    ERIC Educational Resources Information Center

    Posner, Michael I.; Rothbart, Mary K.; Sheese, Brad E.

    2007-01-01

    A major problem for developmental science is understanding how the cognitive and emotional networks important in carrying out mental processes can be related to individual differences. The last five years have seen major advances in establishing links between alleles of specific genes and the neural networks underlying aspects of attention. These…

  16. The Rio dos Sinos watershed: an economic and social space and its interface with environmental status.

    PubMed

    Figueiredo, J A S; Drumm, E; Rodrigues, M A S; Spilki, F R

    2010-12-01

    The Rio dos Sinos watershed is located in the eastern region of the state of Rio Grande do Sul and includes 32 municipalities. These municipalities develop several different economic activities such as farming and livestock along the 190 km length of the Rio dos Sinos, one of the rivers with the worst quality of water in Brazil. The region is also characterised by growing urbanisation and heavy industrialisation. The main economic activity is the leather and footwear industry. This diversified land use puts the Rio dos Sinos watershed at risk of a wide range of potential environmental impacts. The aim of the present article is to discuss the socioeconomic process currently implemented in the Rio dos Sinos watershed and the effect of these human actions on the environmental quality described throughout this special issue of the Brazilian Journal of Biology.

  17. Linking Social Media Reports to Network Indicators of DoS Attacks

    DTIC Science & Technology

    2015-02-15

    reporting in fast-paced social media such as Twitter, but these reports are rarely linked to quantiable network behavior. A data set of network-based...FEB 2015 2. REPORT TYPE N/A 3. DATES COVERED 4. TITLE AND SUBTITLE Linking Social Media Reports to Network Indicators of DoS Attacks 5a...Random sample of 30 (D, E) pairs yielding 21 unique entities (E) Linking Social Media Reports to Network Indicators of DoS Attacks Evan Wright

  18. Measurements of degree of sensitization (DoS) in aluminum alloys using EMAT ultrasound.

    PubMed

    Li, Fang; Xiang, Dan; Qin, Yexian; Pond, Robert B; Slusarski, Kyle

    2011-07-01

    Sensitization in 5XXX aluminum alloys is an insidious problem characterized by the gradual formation and growth of beta phase (Mg(2)Al(3)) at grain boundaries, which increases the susceptibility of alloys to intergranular corrosion (IGC) and intergranular stress-corrosion cracking (IGSCC). The degree of sensitization (DoS) is currently quantified by the ASTM G67 Nitric Acid Mass Loss Test, which is destructive and time consuming. A fast, reliable, and non-destructive method for rapid detection and the assessment of the condition of DoS in AA5XXX aluminum alloys in the field is highly desirable. In this paper, we describe a non-destructive method for measurements of DoS in aluminum alloys with an electromagnetic acoustic transducer (EMAT). AA5083 aluminum alloy samples were sensitized at 100°C with processing times varying from 7days to 30days. The DoS of sensitized samples was first quantified with the ASTM 67 test in the laboratory. Both ultrasonic velocity and attenuation in sensitized specimens were then measured using EMAT and the results were correlated with the DoS data. We found that the longitudinal wave velocity was almost a constant, independent of the sensitization, which suggests that the longitudinal wave can be used to determine the sample thickness. The shear wave velocity and especially the shear wave attenuation are sensitive to DoS. Relationships between DoS and the shear velocity, as well as the shear attenuation have been established. Finally, we performed the data mining to evaluate and improve the accuracy in the measurements of DoS in aluminum alloys with EMAT. Copyright © 2010 Elsevier B.V. All rights reserved.

  19. DataPlus™ - a revolutionary applications generator for DOS hand-held computers

    Treesearch

    David Dean; Linda Dean

    2000-01-01

    DataPlus allows the user to easily design data collection templates for DOS-based hand-held computers that mimic clipboard data sheets. The user designs and tests the application on the desktop PC and then transfers it to a DOS field computer. Other features include: error checking, missing data checks, and sensor input from RS-232 devices such as bar code wands,...

  20. Polymorphisms of pro-inflammatory cytokine genes and the risk for acute suppurative or chronic nonsuppurative apical periodontitis in a Colombian population.

    PubMed

    Amaya, M P; Criado, L; Blanco, B; Gómez, M; Torres, O; Flórez, L; González, C I; Flórez, O

    2013-01-01

    To determine the association of functional single nucleotide polymorphisms in genes of the pro-inflammatory cytokines tumour necrosis factor-α, interleukin-1β, interleukin-8 and interleukin-12B with the development of two clinical forms of apical periodontitis (AP): acute suppurative and chronic nonsuppurative. The study included 120 patients from Bucaramanga City, Colombia, 63 diagnosed with acute suppurative AP (ASAP) and 57 diagnosed with chronic nonsuppurative AP (CNAP). Genotyping for IL1B +3954 (rs1143634), IL8 / CXCL8 -251 (rs4073), IL12B +1188 (rs3212227) and TNFA -308 (rs1800629) was performed by the PCR-restriction fragment length polymorphisms method. The statistical analysis was performed using STATA 10.0 and PLINK V1.07 software. Significant differences in the distribution of IL8 / CXCL8 -251 A allele (P adjusted = 0.041; OR adjusted = 0.41, CI adjusted = 0.31-0.97) and IL8 / CXCL -251 TT genotype (P adjusted = 0.04; OR adjusted = 2.24, CI adjusted = 1.04-4.84) were observed comparing patients diagnosed with ASAP and CNAP. No association was observed in genotype and allele distribution for other genetic polymorphisms analysed. This study provides molecular epidemiological evidence that suggests in the present cohort that IL8 / CXCL8 -251 T allele, which is associated with higher production of IL8/CXCL8, is also associated with a higher risk of developing acute suppurative form of AP, whereas IL8 / CXCL8 -251 A allele, which is associated with lower production of IL8/CXCL8, is associated with chronic nonsuppurative form of AP. This suggests a pivotal role for IL-8/CXCL8 in periapical disease because of its ability to induce chemotaxis and modulating the directed migration of neutrophils to the site of inflammation in response to microbial infection of pulp. © 2012 International Endodontic Journal.

  1. CRISPR/Cas9-Mediated Gene Editing in Human iPSC-Derived Macrophage Reveals Lysosomal Acid Lipase Function in Human Macrophages.

    PubMed

    Zhang, Hanrui; Shi, Jianting; Hachet, Melanie A; Xue, Chenyi; Bauer, Robert C; Jiang, Hongfeng; Li, Wenjun; Tohyama, Junichiro; Millar, John; Billheimer, Jeffrey; Phillips, Michael C; Razani, Babak; Rader, Daniel J; Reilly, Muredach P

    2017-09-07

    To gain mechanistic insights into the role of LIPA(lipase A), the gene encoding LAL (lysosomal acid lipase) protein, in human macrophages. We used CRISPR (clustered regularly interspaced short palindromic repeats )/Cas9 (CRISPR-associated protein 9) technology to knock out LIPA in human induced pluripotent stem cells and then differentiate to macrophage (human-induced pluripotent stem cells-derived macrophage [IPSDM]) to explore the human macrophage LIPA loss-of-function phenotypes. LIPA was abundantly expressed in monocyte-derived macrophages and was markedly induced on IPSDM differentiation to comparable levels as in human monocyte-derived macrophage. IPSDM with knockout of LIPA (LIPA(-/-)) had barely detectable LAL enzymatic activity. Control and LIPA(-/-) IPSDM were loaded with [(3)H]-cholesteryl oleate-labeled acetylated low-density lipoprotein followed by efflux to apolipoprotein A-I. Efflux of liberated [(3)H]-cholesterol to apolipoprotein A-I was abolished in LIPA(-/-) IPSDM, indicating deficiency in LAL-mediated lysosomal cholesteryl ester hydrolysis. In cells loaded with [(3)H]-cholesterol-labeled AcLDL (acetylated low-density lipoprotein), [(3)H]-cholesterol efflux was, however, not different between control and LIPA(-/-) IPSDM. ABCA1(ATP-binding cassette, subfamily A, member 1) expression was upregulated by AcLDL loading but to a similar extent between control and LIPA(-/-) IPSDM. In nonlipid-loaded state, LIPA(-/-) IPSDM had high levels of cholesteryl ester mass compared with minute amounts in control IPSDM. Yet, with AcLDL loading, overall cholesteryl ester mass was increased to similar levels in both control and LIPA(-/-) IPSDM. LIPA(-/-) did not impact lysosomal apolipoprotein-B degradation or expression of IL1B, IL6, and CCL5. CONCLUSIONS: LIPA(-/-) IPSDM reveals macrophage-specific hallmarks of LIPA deficiency. CRISPR/Cas9 and IPSDM provide important tools to study human macrophage biology and more broadly for future studies of disease

  2. Endothelial Genes

    DTIC Science & Technology

    2005-06-01

    Suppression subtractive hybridization re- Cancer: principles and practice of oncology. Philadelphia: Lippincott- vealed an RNA sequence (GenBank accession...Lau YC, Campbell AP, et al. Suppression subtractive hybridization : A method for generating differentially regulated or tissue-tissues, EG-1 appears to...this gene, we investigated its interaction with Src and members of the called suppression subtractive hybridization (12). In human mitogen-activated

  3. Vulnerability genes or plasticity genes?

    PubMed Central

    Belsky, J; Jonassaint, C; Pluess, M; Stanton, M; Brummett, B; Williams, R

    2009-01-01

    The classic diathesis–stress framework, which views some individuals as particularly vulnerable to adversity, informs virtually all psychiatric research on behavior–gene–environment (G × E) interaction. An alternative framework of ‘differential susceptibility' is proposed, one which regards those most susceptible to adversity because of their genetic make up as simultaneously most likely to benefit from supportive or enriching experiences—or even just the absence of adversity. Recent G × E findings consistent with this perspective and involving monoamine oxidase-A, 5-HTTLPR (5-hydroxytryptamine-linked polymorphic region polymorphism) and dopamine receptor D4 (DRD4) are reviewed for illustrative purposes. Results considered suggest that putative ‘vulnerability genes' or ‘risk alleles' might, at times, be more appropriately conceptualized as ‘plasticity genes', because they seem to make individuals more susceptible to environmental influences—for better and for worse. PMID:19455150

  4. Dos, a heme-binding PAS protein from Escherichia coli, is a direct oxygen sensor.

    PubMed

    Delgado-Nixon, V M; Gonzalez, G; Gilles-Gonzalez, M A

    2000-03-14

    A direct sensor of O(2), the Dos protein, has been found in Escherichia coli. Previously, the only biological sensors known to respond to O(2) by direct and reversible binding were the FixL proteins of Rhizobia. A heme-binding region in Dos is 60% homologous to the O(2)-sensing PAS domain of the FixL protein, but the remainder of Dos does not resemble FixL. Specifically, the C-terminal domain of Dos, presumed to be a regulatory partner that couples to its heme-binding domain, is not a histidine kinase but more closely resembles a phosphodiesterase. The absorption spectra of Dos indicate that both axial positions of the heme iron are coordinated to side chains of the protein. Nevertheless, O(2) and CO bind to Dos with K(d) values of 13 and 10 microM, respectively, indicating a strong discrimination against CO binding. Association rate constants for binding of O(2) (3 mM(-)(1) s(-)(1)), CO (1 mM(-)(1) s(-)(1)) and even NO (2 mM(-)(1) s(-)(1)) are extraordinarily low and very similar. Displacement of an endogenous ligand, probably Met 95, from the heme iron in Dos triggers a conformational change that alters the activity of the enzymatic domain. This sensing mechanism differs from that of FixL but resembles that of the CO sensor CooA of Rhodospirillum rubrum. Overall the results provide evidence for a heme-binding subgroup of PAS-domain proteins whose working range, signaling mechanisms, and regulatory partners can vary considerably.

  5. Genes and proteins of Escherichia coli (GenProtEc).

    PubMed

    Riley, M; Space, D B

    1996-01-01

    GenProtEc is a database of Escherichia coli genes and their gene products, classified by type of function and physiological role and with citations to the literature for each. Also present are data on sequence similarities among E.coli proteins with PAM values, percent identity of amino acids, length of alignment and percent aligned. The database is available as a PKZip file by ftp from mbl.edu/pub/ecoli.exe. The program runs under MS-DOS on IMB-compatible machines. GenProtEc can also be accessed through the World Wide Web at URL http://mbl.edu/html/ecoli.html.

  6. Genes and proteins of Escherichia coli (GenProtEc).

    PubMed Central

    Riley, M; Space, D B

    1996-01-01

    GenProtEc is a database of Escherichia coli genes and their gene products, classified by type of function and physiological role and with citations to the literature for each. Also present are data on sequence similarities among E.coli proteins with PAM values, percent identity of amino acids, length of alignment and percent aligned. The database is available as a PKZip file by ftp from mbl.edu/pub/ecoli.exe. The program runs under MS-DOS on IMB-compatible machines. GenProtEc can also be accessed through the World Wide Web at URL http://mbl.edu/html/ecoli.html. PMID:8594596

  7. Non-invasive tissue temperature measurements based on quantitative diffuse optical spectroscopy (DOS) of water.

    PubMed

    Chung, S H; Cerussi, A E; Merritt, S I; Ruth, J; Tromberg, B J

    2010-07-07

    We describe the development of a non-invasive method for quantitative tissue temperature measurements using Broadband diffuse optical spectroscopy (DOS). Our approach is based on well-characterized opposing shifts in near-infrared (NIR) water absorption spectra that appear with temperature and macromolecular binding state. Unlike conventional reflectance methods, DOS is used to generate scattering-corrected tissue water absorption spectra. This allows us to separate the macromolecular bound water contribution from the thermally induced spectral shift using the temperature isosbestic point at 996 nm. The method was validated in intralipid tissue phantoms by correlating DOS with thermistor measurements (R=0.96) with a difference of 1.1+/-0.91 degrees C over a range of 28-48 degrees C. Once validated, thermal and hemodynamic (i.e. oxy- and deoxy-hemoglobin concentration) changes were measured simultaneously and continuously in human subjects (forearm) during mild cold stress. DOS-measured arm temperatures were consistent with previously reported invasive deep tissue temperature studies. These results suggest that DOS can be used for non-invasive, co-registered measurements of absolute temperature and hemoglobin parameters in thick tissues, a potentially important approach for optimizing thermal diagnostics and therapeutics.

  8. Non-invasive tissue temperature measurements based on quantitative diffuse optical spectroscopy (DOS) of water

    PubMed Central

    Chung, SH; Cerussi, AE; Merritt, SI; Ruth, J; Tromberg, BJ

    2012-01-01

    We describe the development of a non-invasive method for quantitative tissue temperature measurements using Broadband diffuse optical spectroscopy (DOS). Our approach is based on well-characterized opposing shifts in near-infrared (NIR) water absorption spectra that appear with temperature and macromolecular binding state. Unlike conventional reflectance methods, DOS is used to generate scattering-corrected tissue water absorption spectra. This allows us to separate the macromolecular bound water contribution from the thermally induced spectral shift using the temperature isosbestic point at 996 nm. The method was validated in intralipid tissue phantoms by correlating DOS with thermistor measurements (R = 0.96) with a difference of 1.1 ± 0.91 °C over a range of 28–48 °C. Once validated, thermal and hemodynamic (i.e. oxy- and deoxy-hemoglobin concentration) changes were measured simultaneously and continuously in human subjects (forearm) during mild cold stress. DOS-measured arm temperatures were consistent with previously reported invasive deep tissue temperature studies. These results suggest that DOS can be used for non-invasive, co-registered measurements of absolute temperature and hemoglobin parameters in thick tissues, a potentially important approach for optimizing thermal diagnostics and therapeutics. PMID:20551502

  9. Documenting 35 years of land cover change: Lago Cachet Dos drainage, Chile

    USGS Publications Warehouse

    Friesen, Beverly A.; Nimick, David A.; Mcgrath, Daniel; Cole, Christopher J.; Wilson, Earl M.; Noble, Suzanne M.; Fahey, Mark J.; Leidich, Jonathan; O'Kuinghttons Villena, Jorge I.

    2015-01-01

    The U.S. Geological Survey (USGS) Special Applications Science Center is monitoring temporal changes at the Colonia Glacier and Lago Cachet Dos, Northern Patagonia Icefield of southern Chile. This location is one of the newest international sites in the USGS Global Fiducial Program (GFP)—a program which provides systematic monitoring of dynamic and environmentally critical areas with high-resolution imagery (http://gfp.usgs.gov/). In 2008, Lago Cachet Dos began experiencing glacial lake outburst floods (GLOFs) during which the entire pool of water (about 200 million cubic meters) rapidly drains from the lake and flows south-southeast through the Colonia Glacier. These catastrophic events cause massive erosion of valley-fill deposits and consequent upstream expansion of Lago Cachet Dos towards Lago Cachet Uno.  Panchromatic and multispectral images for 1979, 2007, and 2014 highlight the dramatic changes that have occurred at this site over a 35-year period. The lake was smallest in 1979, when the Colonia Glacier was at its maximum extent during the study period. Between 1979 and 2007, the glacier shrank causing an increase in the surface area of the lake. The size of the lake increased substantially, from 2.98 square kilometers (km2) in 1979 to 4.41 km2 in 2014, primarily due to erosion of valley-fill deposits upstream of its northern edge by the 15 GLOFs that occurred between April 2008 and February 2014. Ongoing studies of the Colonia Glacier and Lago Cachet Dos are focused on providing real-time monitoring of Lago Cachet Dos lake levels, understanding the history of advances and retreats of the Colonia Glacier, and determining the physical mechanisms and hazards associated with the GLOFs that come from Lago Cachet Dos.

  10. WE-E-BRB-10: DosCheck - an Electronic Chart Checking Tool for Dosimetrists.

    PubMed

    Yang, D; Wu, Y; Yaddanapudi, S; Moore, K; Pierbuxg, B; Brame, S; Mutic, S

    2012-06-01

    In addition to treatment planning, dosimetrists have to prepare documentation and manually enter data in treatment management system (TMS) which did not transfer or setup automatically. The required documents and data are dependent on the disease site, treatment machine and clinical workflow. Errors and inconsistencies can cause redundant work, treatment delays and potentially treatment errors. To address these issues, an electronic checking software tool, DosCheck was clinically implemented to check the existence of necessary documentations and the integrity of manually-entered data. The purpose of this software is to reduce the frequency of human errors and to improve efficiency. DosCheck reads data and documents from 1) TMS, 2) Pinnacle TPS, and 3) DICOM plan files stored in a DICOM-RT PACS. It processes documents in Word and PDF format, treatment plan data in Pinnacle native format and DICOM format, and Mosaiq data in database records. The software cross-checks data accuracy and consistency by following rules that are pre-defined according to the clinical requirements and treatment sties. It interacts with dosimetrists and presents instantaneous results via graphical user interface. DosCheck has been implemented in C#. It performs a full check for a patient with 20 seconds. It has been clinically commissioned and is used daily by all dosimetrists at our institution. Retrospective analysis shows that DosCheck identifies 30% to 40% of previously reported dosimetrist human errors. Additional ∼30% errors are checked by other tools that could be integrated DosCheck in the near future. As an electronic data checking tool, DosCheck can obtain and process data and documents from multiple clinical computer systems in the radiation oncology department, and perform checks according to clinical rules. It is able to improve the accuracy and efficiency of clinical data and document process, and therefore to reduce any potential inconsistencies and errors. © 2012 American

  11. Compare Gene Profiles

    SciTech Connect

    2014-05-31

    Compare Gene Profiles (CGP) performs pairwise gene content comparisons among a relatively large set of related bacterial genomes. CGP performs pairwise BLAST among gene calls from a set of input genome and associated annotation files, and combines the results to generate lists of common genes, unique genes, homologs, and genes from each genome that differ substantially in length from corresponding genes in the other genomes. CGP is implemented in Python and runs in a Linux environment in serial or parallel mode.

  12. Compare Gene Profiles

    SciTech Connect

    2014-05-31

    Compare Gene Profiles (CGP) performs pairwise gene content comparisons among a relatively large set of related bacterial genomes. CGP performs pairwise BLAST among gene calls from a set of input genome and associated annotation files, and combines the results to generate lists of common genes, unique genes, homologs, and genes from each genome that differ substantially in length from corresponding genes in the other genomes. CGP is implemented in Python and runs in a Linux environment in serial or parallel mode.

  13. Reagent based DOS: a "Click, Click, Cyclize" strategy to probe chemical space.

    PubMed

    Rolfe, Alan; Lushington, Gerald H; Hanson, Paul R

    2010-05-07

    The synthesis of small organic molecules as probes for discovering new therapeutic agents has been an important aspect of chemical-biology. Herein we report a reagent-based, diversity-oriented synthetic (DOS) strategy to probe chemical and biological space via a "Click, Click, Cyclize" protocol. In this DOS approach, three sulfonamide linchpins underwent cyclization protocols with a variety of reagents to yield a collection of structurally diverse S-heterocycles. In silico analysis is utilized to evaluate the diversity of the compound collection against chemical space (PC analysis), shape space (PMI) and polar surface area (PSA) calculations.

  14. Gene and enhancer traps for gene discovery.

    PubMed

    Rojas-Pierce, Marcela; Springer, Patricia S

    2003-01-01

    Gene traps and enhancer traps provide a valuable tool for gene discovery. With this system, genes can be identified based solely on the expression pattern of an inserted reporter gene. The use of a reporter gene, such as beta-glucuoronidase (GUS), provides a very sensitive assay for the identification of tissue- and cell-type specific expression patterns. In this chapter, protocols for examining and documenting GUS reporter gene activity in individual lines are described. Methods for the amplification of sequences flanking transposant insertions and subsequent molecular and genetic characterization of individual insertions are provided.

  15. Gene gymnastics

    PubMed Central

    Vijayachandran, Lakshmi S; Thimiri Govinda Raj, Deepak B; Edelweiss, Evelina; Gupta, Kapil; Maier, Josef; Gordeliy, Valentin; Fitzgerald, Daniel J; Berger, Imre

    2013-01-01

    Most essential activities in eukaryotic cells are catalyzed by large multiprotein assemblies containing up to ten or more interlocking subunits. The vast majority of these protein complexes are not easily accessible for high resolution studies aimed at unlocking their mechanisms, due to their low cellular abundance and high heterogeneity. Recombinant overproduction can resolve this bottleneck and baculovirus expression vector systems (BEVS) have emerged as particularly powerful tools for the provision of eukaryotic multiprotein complexes in high quality and quantity. Recently, synthetic biology approaches have begun to make their mark in improving existing BEVS reagents by de novo design of streamlined transfer plasmids and by engineering the baculovirus genome. Here we present OmniBac, comprising new custom designed reagents that further facilitate the integration of heterologous genes into the baculovirus genome for multiprotein expression. Based on comparative genome analysis and data mining, we herein present a blueprint to custom design and engineer the entire baculovirus genome for optimized production properties using a bottom-up synthetic biology approach. PMID:23328086

  16. Estrogenic Endocrine Disrupting Chemicals Influencing NRF1 Regulated Gene Networks in the Development of Complex Human Brain Diseases.

    PubMed

    Preciados, Mark; Yoo, Changwon; Roy, Deodutta

    2016-12-13

    these genes are involved with brain diseases, such as Alzheimer's Disease (AD), Parkinson's Disease, Huntington's Disease, Amyotrophic Lateral Sclerosis, Autism Spectrum Disorder, and Brain Neoplasms. For example, the search of enriched pathways showed that top ten E2 interacting genes in AD-APOE, APP, ATP5A1, CALM1, CASP3, GSK3B, IL1B, MAPT, PSEN2 and TNF-underlie the enrichment of the Kyoto Encyclopedia of Genes and Genomes (KEGG) AD pathway. With AD, the six E2-responsive genes are NRF1 target genes: APBB2, DPYSL2, EIF2S1, ENO1, MAPT, and PAXIP1. These genes are also responsive to the following EEDs: ethinyl estradiol (APBB2, DPYSL2, EIF2S1, ENO1, MAPT, and PAXIP1), BPA (APBB2, EIF2S1, ENO1, MAPT, and PAXIP1), dibutyl phthalate (DPYSL2, EIF2S1, and ENO1), diethylhexyl phthalate (DPYSL2 and MAPT). To validate findings from Comparative Toxicogenomics Database (CTD) curated data, we used Bayesian network (BN) analysis on microarray data of AD patients. We observed that both gender and NRF1 were associated with AD. The female NRF1 gene network is completely different from male human AD patients. AD-associated NRF1 target genes-APLP1, APP, GRIN1, GRIN2B, MAPT, PSEN2, PEN2, and IDE-are also regulated by E2. NRF1 regulates targets genes with diverse functions, including cell growth, apoptosis/autophagy, mitochondrial biogenesis, genomic instability, neurogenesis, neuroplasticity, synaptogenesis, and senescence. By activating or repressing the genes involved in cell proliferation, growth suppression, DNA damage/repair, apoptosis/autophagy, angiogenesis, estrogen signaling, neurogenesis, synaptogenesis, and senescence, and inducing a wide range of DNA damage, genomic instability and DNA methylation and transcriptional repression, NRF1 may act as a major regulator of EEDs-induced brain health deficits. In summary, estrogenic endocrine disrupting chemicals-modified genes in brain health deficits are part of both estrogen and NRF1 signaling pathways. Our findings suggest that in

  17. Sedimentation survey of Lago Dos Bocas, Utuado, Puerto Rico, January 2010

    USGS Publications Warehouse

    Soler-López, Luis R.

    2014-01-01

    Lago Dos Bocas reservoir was completed in 1942 to provide water for hydroelectric power generation along the northern coast of Puerto Rico. The reservoir had an original storage capacity of 37.50 million cubic meters (Mm3). The dam is located about 9 kilometers (km) northeast of the town of Utuado, immediately downstream of the original confluence of the Río Grande de Arecibo and the Río Caonillas (fig. 1). The Puerto Rico Electric Power Authority (PREPA) owns and operates the Lago Dos Bocas reservoir, and since 1996, the reservoir has become an essential part of the Puerto Rico Aqueduct and Sewer Authority (PRASA) North Coast Superaqueduct Project. The Superaqueduct is supplied by controlled releases for hydroelectric power generation that replenish the public-supply raw-water intake pool located about 10 km downstream from the Lago Dos Bocas Dam (fig. 1). As of 2005, the Superaqueduct supplies about 4.03 cubic meters per second (m3/s) (348,192 cubic meters per day [m3/d]) of potable water to communities along the northern coast, from Arecibo to the San Juan metropolitan area. Because of the importance of the reservoir to the North Coast Superaqueduct, the U.S. Geological Survey (USGS), in cooperation with PRASA, conducted a sedimentation survey of Lago Dos Bocas in January 2009. The results of this survey were used to estimate the useful life and the firm yield of the reservoir, and evaluate the need to dredge the reservoir.

  18. Content Analysis Schedule for Bilingual Education Programs: Programa en Dos Lenguas.

    ERIC Educational Resources Information Center

    Ludanyi, R. P.; Shore, Marietta Saravia

    This content analysis schedule for the "Programa en Dos Lenguas" of Fort Worth, Texas, presents information on the history, funding, and scope of the project. Included are sociolinguistic process variables such as the native and dominant languages of students and their interaction. Information is provided on staff selection and the…

  19. Function, regulation and pathological roles of the Gab/DOS docking proteins

    PubMed Central

    2009-01-01

    Since their discovery a little more than a decade ago, the docking proteins of the Gab/DOS family have emerged as important signalling elements in metazoans. Gab/DOS proteins integrate and amplify signals from a wide variety of sources including growth factor, cytokine and antigen receptors as well as cell adhesion molecules. They also contribute to signal diversification by channelling the information from activated receptors into signalling pathways with distinct biological functions. Recent approaches in protein biochemistry and systems biology have revealed that Gab proteins are subject to complex regulation by feed-forward and feedback phosphorylation events as well as protein-protein interactions. Thus, Gab/DOS docking proteins are at the centre of entire signalling subsystems and fulfil an important if not essential role in many physiological processes. Furthermore, aberrant signalling by Gab proteins has been increasingly linked to human diseases from various forms of neoplasia to Alzheimer's disease. In this review, we provide a detailed overview of the structure, effector functions, regulation and evolution of the Gab/DOS family. We also summarize recent findings implicating Gab proteins, in particular the Gab2 isoform, in leukaemia, solid tumours and other human diseases. PMID:19737390

  20. Pygmy Rice Rat as Potential Host of Castelo dos Sonhos Hantavirus

    PubMed Central

    Travassos da Rosa, Elizabeth S.; Medeiros, Daniele B. A.; Nunes, Márcio R.T.; Simith, Darlene B.; Pereira, Armando de Souza; Elkhoury, Mauro R.; Lavocat, Marília; Marques, Aparecido A.R.; Via, Alba Valéria; D’Andrea, Paulo; Bonvicino, Cibele R.; Lemos, Elba Regina S.

    2011-01-01

    To study the dynamics of wild rodent populations and identify potential hosts for hantavirus, we conducted an eco-epidemiologic study in Campo Novo do Parecis, Mato Grosso State, Brazil. We detected and genetically characterized Castelo dos Sonhos virus found in a species of pygmy rice rat (Oligoryzomys utiaritensis). PMID:21801642

  1. 33 CFR 106.250 - Declaration of Security (DoS).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Declaration of Security (DoS). 106.250 Section 106.250 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY MARITIME SECURITY MARINE SECURITY: OUTER CONTINENTAL SHELF (OCS) FACILITIES Outer Continental Shelf...

  2. 33 CFR 106.250 - Declaration of Security (DoS).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Declaration of Security (DoS). 106.250 Section 106.250 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY MARITIME SECURITY MARINE SECURITY: OUTER CONTINENTAL SHELF (OCS) FACILITIES Outer Continental Shelf...

  3. 33 CFR 106.250 - Declaration of Security (DoS).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Declaration of Security (DoS). 106.250 Section 106.250 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY MARITIME SECURITY MARINE SECURITY: OUTER CONTINENTAL SHELF (OCS) FACILITIES Outer Continental Shelf...

  4. 33 CFR 106.250 - Declaration of Security (DoS).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Declaration of Security (DoS). 106.250 Section 106.250 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY MARITIME SECURITY MARINE SECURITY: OUTER CONTINENTAL SHELF (OCS) FACILITIES Outer Continental Shelf...

  5. 33 CFR 106.250 - Declaration of Security (DoS).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Declaration of Security (DoS). 106.250 Section 106.250 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY MARITIME SECURITY MARINE SECURITY: OUTER CONTINENTAL SHELF (OCS) FACILITIES Outer Continental Shelf...

  6. 33 CFR 105.245 - Declaration of Security (DoS).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) of this section. (e) At MARSEC Levels 1 and 2, FSOs of facilities that frequently interface with the... part to implement a DoS with the VSO prior to any vessel-to-facility interface when he or she deems it...

  7. 33 CFR 105.245 - Declaration of Security (DoS).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) of this section. (e) At MARSEC Levels 1 and 2, FSOs of facilities that frequently interface with the... part to implement a DoS with the VSO prior to any vessel-to-facility interface when he or she deems it...

  8. Stretching the Software Dollar: MS-DOS Shareware and Public Domain Software.

    ERIC Educational Resources Information Center

    Grosch, Audrey N.

    1989-01-01

    Discusses shareware and public domain software for MS-DOS systems that are available through bulletin board systems (BBS). Problems with computer viruses are discussed; shareware available for communications, database and file management, spreadsheets, word processing, and menuing software is described; and source information for software is…

  9. Entre Dos Mundos/Between Two Worlds: Youth Violence Prevention for Acculturating Latino Families

    ERIC Educational Resources Information Center

    Smokowski, Paul R.; Bacallao, Martica

    2009-01-01

    Objective: This study evaluated the efficacy of Entre Dos Mundos/Between Two Worlds (EDM) prevention for Latino adolescents. Method: In an experimental trial to compare implementation formats, 41 Latino families were randomly assigned to EDM action-oriented skills training groups, and 47 families were randomly assigned to unstructured EDM support…

  10. Low-Budget, Cost-Effective OCR: Optical Character Recognition for MS-DOS Micros.

    ERIC Educational Resources Information Center

    Perez, Ernest

    1990-01-01

    Discusses optical character recognition (OCR) for use with MS-DOS microcomputers. Cost effectiveness is considered, three types of software approaches to character recognition are explained, hardware and operation requirements are described, possible library applications are discussed, future OCR developments are suggested, and a list of OCR…

  11. Entre Dos Mundos/Between Two Worlds: Youth Violence Prevention for Acculturating Latino Families

    ERIC Educational Resources Information Center

    Smokowski, Paul R.; Bacallao, Martica

    2009-01-01

    Objective: This study evaluated the efficacy of Entre Dos Mundos/Between Two Worlds (EDM) prevention for Latino adolescents. Method: In an experimental trial to compare implementation formats, 41 Latino families were randomly assigned to EDM action-oriented skills training groups, and 47 families were randomly assigned to unstructured EDM support…

  12. Low-Budget, Cost-Effective OCR: Optical Character Recognition for MS-DOS Micros.

    ERIC Educational Resources Information Center

    Perez, Ernest

    1990-01-01

    Discusses optical character recognition (OCR) for use with MS-DOS microcomputers. Cost effectiveness is considered, three types of software approaches to character recognition are explained, hardware and operation requirements are described, possible library applications are discussed, future OCR developments are suggested, and a list of OCR…

  13. Comparison and evaluation of atmospheric correction algorithms of QUAC, DOS, and FLAASH for HICO hyperspectral imagery

    NASA Astrophysics Data System (ADS)

    Shi, Liangliang; Mao, Zhihua; Chen, Peng; Han, Sha'ou; Gong, Fang; Zhu, Qiankun

    2016-10-01

    In order to obtain the spectral information of objects and improve the retrieval of quantitative parameters from remotely sensing data accurately on land or over water bodies, atmospheric correction is a vital step, certainly, it is also a prerequisite to hyperspectral imagery data analysis approaches. On the base of previous studies, the atmospheric correction algorithms were divided to two categories: image-based empirical and model-based correction methods. The Quick Atmospheric Correction (QUAC) and Dark Object Subtraction (DOS) methods belong to the empirical or semiempirical methods, however, the Fast Line-of-sight Atmospheric Analysis of Spectral Hypercube (FLAASH) method was developed from the radiative transfer model. In this paper, we initially evaluated the performance from Hyperspectral Imager for the Coastal Ocean (HICO) of 16 Nov 2013 using QUAC, DOS, and MODTRAN integrated in FLAASH, and compared the results of these correction methods with in situ data. The results indicate that the method of FLAASH model performs much better than DOS and QUAC in atmospheric correction for HICO hyperspectral imagery, although the DOS and QUAC method is conducted more easily and do not require inputs of complex parameters.

  14. Estrogenic Endocrine Disrupting Chemicals Influencing NRF1 Regulated Gene Networks in the Development of Complex Human Brain Diseases

    PubMed Central

    Preciados, Mark; Yoo, Changwon; Roy, Deodutta

    2016-01-01

    these genes are involved with brain diseases, such as Alzheimer’s Disease (AD), Parkinson’s Disease, Huntington’s Disease, Amyotrophic Lateral Sclerosis, Autism Spectrum Disorder, and Brain Neoplasms. For example, the search of enriched pathways showed that top ten E2 interacting genes in AD—APOE, APP, ATP5A1, CALM1, CASP3, GSK3B, IL1B, MAPT, PSEN2 and TNF—underlie the enrichment of the Kyoto Encyclopedia of Genes and Genomes (KEGG) AD pathway. With AD, the six E2-responsive genes are NRF1 target genes: APBB2, DPYSL2, EIF2S1, ENO1, MAPT, and PAXIP1. These genes are also responsive to the following EEDs: ethinyl estradiol (APBB2, DPYSL2, EIF2S1, ENO1, MAPT, and PAXIP1), BPA (APBB2, EIF2S1, ENO1, MAPT, and PAXIP1), dibutyl phthalate (DPYSL2, EIF2S1, and ENO1), diethylhexyl phthalate (DPYSL2 and MAPT). To validate findings from Comparative Toxicogenomics Database (CTD) curated data, we used Bayesian network (BN) analysis on microarray data of AD patients. We observed that both gender and NRF1 were associated with AD. The female NRF1 gene network is completely different from male human AD patients. AD-associated NRF1 target genes—APLP1, APP, GRIN1, GRIN2B, MAPT, PSEN2, PEN2, and IDE—are also regulated by E2. NRF1 regulates targets genes with diverse functions, including cell growth, apoptosis/autophagy, mitochondrial biogenesis, genomic instability, neurogenesis, neuroplasticity, synaptogenesis, and senescence. By activating or repressing the genes involved in cell proliferation, growth suppression, DNA damage/repair, apoptosis/autophagy, angiogenesis, estrogen signaling, neurogenesis, synaptogenesis, and senescence, and inducing a wide range of DNA damage, genomic instability and DNA methylation and transcriptional repression, NRF1 may act as a major regulator of EEDs-induced brain health deficits. In summary, estrogenic endocrine disrupting chemicals-modified genes in brain health deficits are part of both estrogen and NRF1 signaling pathways. Our findings

  15. Sedimentation History of Lago Dos Bocas, Puerto Rico, 1942-2005

    USGS Publications Warehouse

    Soler-López, Luis R.

    2007-01-01

    The Lago Dos Bocas Dam, located in the municipality of Utuado in north central Puerto Rico, was constructed in 1942 for hydroelectric power generation. The reservoir had an original storage capacity of 37.50 million cubic meters and a drainage area of 440 square kilometers. In 1948, the construction of the Lago Caonillas Dam on the Rio Caonillas branch of Lago Dos Bocas reduced the natural sediment-contributing drainage area to 310 square kilometers; therefore, the Lago Caonillas Dam is considered an effective sediment trap. Sedimentation in Lago Dos Bocas reservoir has reduced the storage capacity from 37.50 million cubic meters in 1942 to 17.26 million cubic meters in 2005, which represents a storage loss of about 54 percent. The long-term annual water-storage capacity loss rate remained nearly constant at about 320,000 cubic meters per year to about 1997. The inter-survey sedimentation rate between 1997 and 1999, however, is higher than the long-term rate at about 1.09 million cubic meters per year. Between 1999 and 2005 the rate is lower than the long-term rate at about 0.13 million cubic meters per year. The Lago Dos Bocas effective sediment-contributing drainage area had an average sediment yield of about 1,400 cubic meters per square kilometer per year between 1942 and 1997. This rate increased substantially by 1999 to about 4,600 cubic meters per square kilometer per year, probably resulting from the historical magnitude floods caused by Hurricane Georges in 1998. Recent data indicate that the Lago Dos Bocas drainage area sediment yield decreased substantially to about 570 cubic meters per square kilometer per year, which is much lower than the 1942-1997 area normalized sedimentation rate of 1,235 cubic meters per square kilometer per year. The impact of Hurricane Georges on the basin sediment yield could have been the cause of this change, since the magnitude of the floods could have nearly depleted the Lago Dos Bocas drainage area of easily erodible and

  16. EXCAVATOR: a computer program for efficiently mining gene expression data.

    PubMed

    Xu, Dong; Olman, Victor; Wang, Li; Xu, Ying

    2003-10-01

    Massive amounts of gene expression data are generated using microarrays for functional studies of genes and gene expression data clustering is a useful tool for studying the functional relationship among genes in a biological process. We have developed a computer package EXCAVATOR for clustering gene expression profiles based on our new framework for representing gene expression data as a minimum spanning tree. EXCAVATOR uses a number of rigorous and efficient clustering algorithms. This program has a number of unique features, including capabilities for: (i) data- constrained clustering; (ii) identification of genes with similar expression profiles to pre-specified seed genes; (iii) cluster identification from a noisy background; (iv) computational comparison between different clustering results of the same data set. EXCAVATOR can be run from a Unix/Linux/DOS shell, from a Java interface or from a Web server. The clustering results can be visualized as colored figures and 2-dimensional plots. Moreover, EXCAVATOR provides a wide range of options for data formats, distance measures, objective functions, clustering algorithms, methods to choose number of clusters, etc. The effectiveness of EXCAVATOR has been demonstrated on several experimental data sets. Its performance compares favorably against the popular K-means clustering method in terms of clustering quality and computing time.

  17. Reticulo-rumen mass, epithelium gene expression, and systemic biomarkers of metabolism and inflammation in Holstein dairy cows fed a high-energy diet.

    PubMed

    Arroyo, J M; Hosseini, A; Zhou, Z; Alharthi, A; Trevisi, E; Osorio, J S; Loor, J J

    2017-09-13

    Feeding a higher-energy diet by increasing cereal grains at the expense of forage during the last 3 to 4 wk prepartum is a traditional approach to help the rumen "adapt" to the traditional diets fed at the onset of lactation. Increasing grain/concentrate in the diet changes ruminal fermentation and in sheep and goats elicits marked changes in mRNA expression of immune-related genes in ruminal epithelium. Whether such changes at the epithelial and systemic levels occur in dairy cows when the dietary energy content increases at a fixed level of concentrate is unknown. Fourteen nonpregnant, nonlactating Holstein cows were fed a control lower-energy (CON, 1.30 Mcal/kg of dry matter) diet to meet 100% of estimated nutrient requirements for 3 wk, after which half of the cows were assigned to a higher-energy diet (OVE, 1.60 Mcal/kg of dry matter) and half of the cows continued on CON for 6 wk. Levels of forage and concentrate for CON and OVE were 80 and 79% and 20 and 21%, respectively. Plasma samples were collected 1 d before slaughter to examine biomarkers of metabolism, liver function, inflammation, and oxidative stress. The reticulo-rumen mass was recorded at slaughter, and samples of epithelium were harvested from all cows. The expression of 29 genes associated with tight junctions, immune function, and nutrient transport (volatile fatty acids, urea, and trace minerals) was examined. Overfeeding energy led to consistently greater dry matter intake over time, and lowered plasma concentrations of haptoglobin, paraoxonase, bilirubin, fatty acids, and myeloperoxidase (secreted by neutrophils). In contrast, OVE resulted in greater hydroxybutyrate and cholesterol concentrations. A greater reticulo-rumen mass in cows fed OVE did not alter genes associated with tight junctions (CDLN1, CDNL4, OCLN, TJP1), immune function (IL1B, IL10, NFKB1, TLR2, TLR4, TNF), oxidative stress (SOD1, SOD2), or most nutrient transporters. However, feeding OVE upregulated the acute-phase protein

  18. 76 FR 25733 - 60-Day Notice of Proposed Information Collection: DS-7001 and DS-7005, DOS-Sponsored Academic...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-05

    ... Notice of Proposed Information Collection: DS-7001 and DS- 7005, DOS-Sponsored Academic Exchange Program... preceding submission to OMB. We are conducting this process in accordance with the Paperwork Reduction Act of 1995. Title of Information Collection: DOS-Sponsored Academic Exchange Program Application. OMB...

  19. Observational Assessment of Preschool Disruptive Behavior, Part II: Validity of the Disruptive Behavior Diagnostic Observation Schedule (DB-DOS)

    ERIC Educational Resources Information Center

    Wakschlag, Lauren S.; Briggs-Gowan, Margaret J.; Hill, Carri; Danis, Barbara; Leventhal, Bennett L.; Keenan, Kate; Egger, Helen L.; Cicchetti, Domenic; Burns, James; Carter, Alice S.

    2008-01-01

    A study is conducted to determine whether the multidomain, multicontext Disruptive Behavior Diagnostic Observation Schedule (DB-DOS) is a valid observational method for assessing disruptive behavior of preschool children. It is concluded that the DB-DOS is a valid method for a direct observational assessment of clinically significant disruptive…

  20. Observational Assessment of Preschool Disruptive Behavior, Part II: Validity of the Disruptive Behavior Diagnostic Observation Schedule (DB-DOS)

    ERIC Educational Resources Information Center

    Wakschlag, Lauren S.; Briggs-Gowan, Margaret J.; Hill, Carri; Danis, Barbara; Leventhal, Bennett L.; Keenan, Kate; Egger, Helen L.; Cicchetti, Domenic; Burns, James; Carter, Alice S.

    2008-01-01

    A study is conducted to determine whether the multidomain, multicontext Disruptive Behavior Diagnostic Observation Schedule (DB-DOS) is a valid observational method for assessing disruptive behavior of preschool children. It is concluded that the DB-DOS is a valid method for a direct observational assessment of clinically significant disruptive…

  1. 48 CFR 653.217-70 - DOS form DS-1921, Award/Modification of Interagency Acquisition Agreement.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false DOS form DS-1921, Award... Regulations System DEPARTMENT OF STATE CLAUSES AND FORMS FORMS Prescription of Forms 653.217-70 DOS form DS-1921, Award/Modification of Interagency Acquisition Agreement. As prescribed in 617.504-70(b)(5)(i), DS...

  2. Models that Teach about the Computer: AppleWorks and ProDOS, the Computer's Memory and Disk Storage.

    ERIC Educational Resources Information Center

    Niess, Margaret L.

    1989-01-01

    This final article in a series on creating models for teaching about computer memory and disk storage and retrieval focuses on AppleWorks software and the Professional Disk Operating System (ProDOS). Instructions for creating a paper model of the AppleWorks menu system and the ProDOS disk file are given. (LRW)

  3. Gene doping: gene delivery for olympic victory.

    PubMed

    Gould, David

    2013-08-01

    With one recently recommended gene therapy in Europe and a number of other gene therapy treatments now proving effective in clinical trials it is feasible that the same technologies will soon be adopted in the world of sport by unscrupulous athletes and their trainers in so called 'gene doping'. In this article an overview of the successful gene therapy clinical trials is provided and the potential targets for gene doping are highlighted. Depending on whether a doping gene product is secreted from the engineered cells or is retained locally to, or inside engineered cells will, to some extent, determine the likelihood of detection. It is clear that effective gene delivery technologies now exist and it is important that detection and prevention plans are in place.

  4. Degrees of separation as a statistical tool for evaluating candidate genes.

    PubMed

    Nelson, Ronald M; Pettersson, Mats E

    2014-12-01

    Selection of candidate genes is an important step in the exploration of complex genetic architecture. The number of gene networks available is increasing and these can provide information to help with candidate gene selection. It is currently common to use the degree of connectedness in gene networks as validation in Genome Wide Association (GWA) and Quantitative Trait Locus (QTL) mapping studies. However, it can cause misleading results if not validated properly. Here we present a method and tool for validating the gene pairs from GWA studies given the context of the network they co-occur in. It ensures that proposed interactions and gene associations are not statistical artefacts inherent to the specific gene network architecture. The CandidateBacon package provides an easy and efficient method to calculate the average degree of separation (DoS) between pairs of genes to currently available gene networks. We show how these empirical estimates of average connectedness are used to validate candidate gene pairs. Validation of interacting genes by comparing their connectedness with the average connectedness in the gene network will provide support for said interactions by utilising the growing amount of gene network information available. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. ACONF DOS

    SciTech Connect

    Atcitty, Stanley; Butler, Paul; Symons, Phlip; & Corey, Garth

    2009-03-25

    ACONF is a system which has been developed by Sandia National Laboratories. ACONF is a system for optimizing the interaction between generator, photovoltaic system, batteries, and load in independent non-grid-tied electrical systems. It is primarily used in rural locations where running utility lines proves costly if it is possible at all. It is controlled by an Ampro PC-104 Coremodule 400 controller system. The code for this system is written in the BASIC programming language. The routine contained in this document was written originally by Phil Symons. ACONF is intended to increase the efficiency of freestanding electrical systems to increase battery life and more efficiently use generator fuel.

  6. Effect of modulation frequency bandwidth on measurement accuracy and precision for digital diffuse optical spectroscopy (dDOS)

    NASA Astrophysics Data System (ADS)

    Jung, Justin; Istfan, Raeef; Roblyer, Darren

    2014-03-01

    Near-infrared (NIR) frequency-domain Diffuse Optical Spectroscopy (DOS) is an emerging technology with a growing number of potential clinical applications. In an effort to reduce DOS system complexity and improve portability, we recently demonstrated a direct digital sampling method that utilizes digital signal generation and detection as a replacement for more traditional analog methods. In our technique, a fast analog-to-digital converter (ADC) samples the detected time-domain radio frequency (RF) waveforms at each modulation frequency in a broad-bandwidth sweep (50- 300MHz). While we have shown this method provides comparable results to other DOS technologies, the process is data intensive as digital samples must be stored and processed for each modulation frequency and wavelength. We explore here the effect of reducing the modulation frequency bandwidth on the accuracy and precision of extracted optical properties. To accomplish this, the performance of the digital DOS (dDOS) system was compared to a gold standard network analyzer based DOS system. With a starting frequency of 50MHz, the input signal of the dDOS system was swept to 100, 150, 250, or 300MHz in 4MHz increments and results were compared to full 50-300MHz networkanalyzer DOS measurements. The average errors in extracted μa and μs' with dDOS were lowest for the full 50-300MHz sweep (less than 3%) and were within 3.8% for frequency bandwidths as narrow as 50-150MHz. The errors increased to as much as 9.0% when a bandwidth of 50-100MHz was tested. These results demonstrate the possibility for reduced data collection with dDOS without critical compensation of optical property extraction.

  7. Gene Cluster Statistics with Gene Families

    PubMed Central

    Durand, Dannie

    2009-01-01

    Identifying genomic regions that descended from a common ancestor is important for understanding the function and evolution of genomes. In distantly related genomes, clusters of homologous gene pairs are evidence of candidate homologous regions. Demonstrating the statistical significance of such “gene clusters” is an essential component of comparative genomic analyses. However, currently there are no practical statistical tests for gene clusters that model the influence of the number of homologs in each gene family on cluster significance. In this work, we demonstrate empirically that failure to incorporate gene family size in gene cluster statistics results in overestimation of significance, leading to incorrect conclusions. We further present novel analytical methods for estimating gene cluster significance that take gene family size into account. Our methods do not require complete genome data and are suitable for testing individual clusters found in local regions, such as contigs in an unfinished assembly. We consider pairs of regions drawn from the same genome (paralogous clusters), as well as regions drawn from two different genomes (orthologous clusters). Determining cluster significance under general models of gene family size is computationally intractable. By assuming that all gene families are of equal size, we obtain analytical expressions that allow fast approximation of cluster probabilities. We evaluate the accuracy of this approximation by comparing the resulting gene cluster probabilities with cluster probabilities obtained by simulating a realistic, power-law distributed model of gene family size, with parameters inferred from genomic data. Surprisingly, despite the simplicity of the underlying assumption, our method accurately approximates the true cluster probabilities. It slightly overestimates these probabilities, yielding a conservative test. We present additional simulation results indicating the best choice of parameter values for data

  8. Compare Gene Calls

    SciTech Connect

    Ecale Zhou, Carol L.

    2016-07-05

    Compare Gene Calls (CGC) is a Python code used for combining and comparing gene calls from any number of gene callers. A gene caller is a computer program that predicts the extends of open reading frames within genomes of biological organisms.

  9. Autism and Genes

    ERIC Educational Resources Information Center

    National Institutes of Health, 2005

    2005-01-01

    This document defines and discusses autism and how genes play a role in the condition. Answers to the following questions are covered: (1) What are genes? (2) What is autism? (3) What causes autism? (4) Why study genes to learn about autism? (5) How do researchers look for the genes involved in autism? (screen the whole genome; conduct cytogenetic…

  10. Trace Element Distribution Between Olivine and Kirschsteinite in Angra Dos Reis

    NASA Technical Reports Server (NTRS)

    Fittipaldo, M. M.; Jones, R. H.; Shearer, C. K.

    2003-01-01

    The angrites are a small and enigmatic group of basaltic achondrites that possess unique mineralogical and chemical properties. The dominant mineralogy of the seven angrite members (Angra dos Reis, LEW 86010, LEW 87051, Asuka 881371, Sahara 99555, D Orbigny, and a new Moroccan member) is fassaite, olivine, and plagioclase. Angrites display a wide range of thermal histories, with Angra dos Reis (AdoR) exhibiting a cooling history different from that of the rapidly cooled members and from LEW86010, a more slowly cooled member. AdoR could represent either a cumulate or a porphyritic igneous rock that was later altered by metamorphism. We are re-examining the thermal history of AdoR in light of the more recently described angrite members. Our emphasis is a trace element study of low-Ca olivine, which we refer to as olivine, and high-Ca olivine, which we refer to as kirschsteinite, in AdoR.

  11. Using satellite images to monitor glacial-lake outburst floods: Lago Cachet Dos drainage, Chile

    USGS Publications Warehouse

    Friesen, Beverly A.; Cole, Christopher J.; Nimick, David A.; Wilson, Earl M.; Fahey, Mark J.; McGrath, Daniel J.; Leidich, Jonathan

    2015-01-01

    During 2008–2013, 14 GLOFs were released from Lago Cachet Dos and created environmental and safety concerns for downstream residents and to infrastructure. If GLOFs and the consequent headward erosion continue, the moraine that creates Lago Cachet Uno could be destabilized and breached, and the two lakes could merge. If the two lakes become connected, the volume of future GLOFs likely would be greater and thus cause longer and (or) more extensive flooding downstream. Additional GLOFs from Lago Cachet Dos are expected in the future, and continued environmental monitoring could provide an early warning system as well as scientific information that could increase our understanding of GLOFs and their consequences. GLOFs occur in glaciated areas around the world and remote sensing technologies can allow researchers to better understand—and potentially predict—future GLOF events.

  12. Magnetic field effects on the DOS of a Kondo quantum dot coupled to LL leads

    NASA Astrophysics Data System (ADS)

    Yang, Kai-Hua; Qin, Chang-Dong; Wang, Huai-Yu; Wang, Xu

    2017-01-01

    We investigate the joint effects of a magnetic field and electron-electron interaction on the tunneling density of states (DOS) of a quantum dot coupled to the Luttinger liquid leads in the Kondo regime. We find that for intralead electron interaction, the DOS develops two peaks deviated from the origin by the Zeeman energy. With the increase of the intralead interaction, a phase transition occurs. For moderately strong interaction, the Zeeman splitting peaks develop into two dips. The splitting of the Kondo peak and dip is not symmetric with respect to up and down spins. In the limit of strong interaction the Zeeman splitting behavior disappears and there appears a power-law scaling behavior.

  13. Application of a sparse matrix design strategy to the synthesis of dos libraries.

    PubMed

    Akella, Lakshmi B; Marcaurelle, Lisa A

    2011-07-11

    We have implemented an interactive and practical sparse matrix design strategy for the synthesis of DOS libraries, which facilitates the selection of diverse library members within a user-defined range of physicochemical properties while still maintaining synthetic efficiency. The utility of this approach is illustrated with the synthesis of an 8000-membered library of stereochemically diverse medium-sized rings accessible via a build/couple/pair DOS strategy. Diverse library members were selected from a virtual library by applying the maximum dissimilarity method, while the selection of similar analogs around each diverse product was ensured by picking near neighbors algorithmically based on fingerprint comparison. Adjustable filters on compound properties, which can be tailored to suit the needs of the target biology, facilitated subset selection from the synthetically accessible compounds.

  14. A Comparison of Three LISP Interpreters for MS-DOS-Based Microcomputers

    PubMed Central

    Kahane, Stephen N.; Johannes, Richard S.

    1985-01-01

    We report a comparison of three commercially available LISP interpreters running on MS-DOS-based microcomputers. Marked differences were found between the different products' memory addressing abilities, error handling and debugging facilities. Editing tools, tutoring environments, windowing, graphic capabilities, operating system and port call facilities are also contrasted. Speed was tested via a group of LISP functions (benchmarks) that attempt to isolate list manipulation, iteration, function calling, recursion and mathematical calculation performance.

  15. Interleukin 1B Variant -1473G/C (rs1143623) Influences Triglyceride and Interleukin 6 Metabolism

    PubMed Central

    Delgado-Lista, Javier; Garcia-Rios, Antonio; Perez-Martinez, Pablo; Solivera, Juan; Yubero-Serrano, Elena M.; Fuentes, Francisco; Parnell, Laurence D.; Shen, Jian; Gomez, Purificacion; Jimenez-Gomez, Yolanda; Gomez-Luna, Maria J.; Marin, Carmen; Belisle, Sarah E.; Rodriguez-Cantalejo, Fernando; Meydani, Simin N.; Ordovas, Jose M.; Perez-Jimenez, Francisco

    2011-01-01

    Context: IL1b (IL1B or IL1β), a key modulator of the immune response, exerts its functions mainly via IL6 regulation. Fatty meals cause transient hypertriglyceridemia and are considered to be proinflammatory, but the extent of these responses shows high interindividual susceptibility. Objective: We evaluated the influence of a genetic variant located in the promoter region of IL1B (-1473G/C) on fasting and postprandial lipids and IL6. Design, Setting, and Participants: A total of 477 people over age 65 yr were genotyped for IL1B -1473G/C, and we evaluated fasting lipids depending on genotype. Then, 88 healthy young men were also genotyped and were fed a saturated fatty acid-rich meal. Serial blood samples were drawn for 11 h after the meal, and lipid fractions and IL6 were assayed. Main Outcome and Interventions: Fasting lipids were studied in the aged persons. Fasting and postprandial measurements of lipids and IL6 were performed in the healthy young men. Results: In the aged persons, CC subjects (minor allele homozygotes) showed higher triglyceride (P = 0.002) and cholesterol (P = 0.011) levels. Healthy young male carriers of the minor C allele showed higher postprandial triglycerides (P = 0.037), and those carried into large triglyceride-rich lipoproteins (P = 0.004). In addition, they showed higher postprandial IL6 concentrations (P = 0.008). Conclusions: Our work shows that inflammatory genes may regulate fasting and postprandial lipids because the carriers of the minor allele of an IL gene variant have altered lipid metabolism. To reinforce these gene-phenotype findings, IL6 (the natural effector of IL1B) was increased in these persons. PMID:21307135

  16. Interleukin 1B variant -1473G/C (rs1143623) influences triglyceride and interleukin 6 metabolism.

    PubMed

    Delgado-Lista, Javier; Garcia-Rios, Antonio; Perez-Martinez, Pablo; Solivera, Juan; Yubero-Serrano, Elena M; Fuentes, Francisco; Parnell, Laurence D; Shen, Jian; Gomez, Purificacion; Jimenez-Gomez, Yolanda; Gomez-Luna, Maria J; Marin, Carmen; Belisle, Sarah E; Rodriguez-Cantalejo, Fernando; Meydani, Simin N; Ordovas, Jose M; Perez-Jimenez, Francisco; Lopez-Miranda, Jose

    2011-05-01

    IL1b (IL1B or IL1β), a key modulator of the immune response, exerts its functions mainly via IL6 regulation. Fatty meals cause transient hypertriglyceridemia and are considered to be proinflammatory, but the extent of these responses shows high interindividual susceptibility. We evaluated the influence of a genetic variant located in the promoter region of IL1B (-1473G/C) on fasting and postprandial lipids and IL6. A total of 477 people over age 65 yr were genotyped for IL1B -1473G/C, and we evaluated fasting lipids depending on genotype. Then, 88 healthy young men were also genotyped and were fed a saturated fatty acid-rich meal. Serial blood samples were drawn for 11 h after the meal, and lipid fractions and IL6 were assayed. MAIN OUTCOME AND INTERVENTIONS: Fasting lipids were studied in the aged persons. Fasting and postprandial measurements of lipids and IL6 were performed in the healthy young men. In the aged persons, CC subjects (minor allele homozygotes) showed higher triglyceride (P = 0.002) and cholesterol (P = 0.011) levels. Healthy young male carriers of the minor C allele showed higher postprandial triglycerides (P = 0.037), and those carried into large triglyceride-rich lipoproteins (P = 0.004). In addition, they showed higher postprandial IL6 concentrations (P = 0.008). Our work shows that inflammatory genes may regulate fasting and postprandial lipids because the carriers of the minor allele of an IL gene variant have altered lipid metabolism. To reinforce these gene-phenotype findings, IL6 (the natural effector of IL1B) was increased in these persons.

  17. Epilepsy-associated genes.

    PubMed

    Wang, Jie; Lin, Zhi-Jian; Liu, Liu; Xu, Hai-Qing; Shi, Yi-Wu; Yi, Yong-Hong; He, Na; Liao, Wei-Ping

    2017-01-01

    Development in genetic technology has led to the identification of an increasing number of genes associated with epilepsy. These discoveries will both provide the basis for including genetic tests in clinical practice and improve diagnosis and treatment of epilepsy. By searching through several databases (OMIM, HGMD, and EpilepsyGene) and recent publications on PubMed, we found 977 genes that are associated with epilepsy. We classified these genes into 4 categories according to the manifestation of epilepsy in phenotypes. We found 84 genes that are considered as epilepsy genes: genes that cause epilepsies or syndromes with epilepsy as the core symptom. 73 genes were listed as neurodevelopment-associated genes: genes associated with both brain-development malformations and epilepsy. Several genes (536) were epilepsy-related: genes associated with both physical or other systemic abnormalities and epilepsy or seizures. We found 284 additional genes putatively associated with epilepsy; this requires further verification. These integrated data will provide new insights useful for both including genetic tests in the clinical practice and evaluating the results of genetic tests. We also summarized the epilepsy-associated genes according to their function, with the goal to better characterize the association between genes and epilepsies and to further understand the mechanisms underlying epilepsy.

  18. Adaptive Suspicious Prevention for Defending DoS Attacks in SDN-Based Convergent Networks

    PubMed Central

    Dao, Nhu-Ngoc; Kim, Joongheon; Park, Minho; Cho, Sungrae

    2016-01-01

    The convergent communication network will play an important role as a single platform to unify heterogeneous networks and integrate emerging technologies and existing legacy networks. Although there have been proposed many feasible solutions, they could not become convergent frameworks since they mainly focused on converting functions between various protocols and interfaces in edge networks, and handling functions for multiple services in core networks, e.g., the Multi-protocol Label Switching (MPLS) technique. Software-defined networking (SDN), on the other hand, is expected to be the ideal future for the convergent network since it can provide a controllable, dynamic, and cost-effective network. However, SDN has an original structural vulnerability behind a lot of advantages, which is the centralized control plane. As the brains of the network, a controller manages the whole network, which is attractive to attackers. In this context, we proposes a novel solution called adaptive suspicious prevention (ASP) mechanism to protect the controller from the Denial of Service (DoS) attacks that could incapacitate an SDN. The ASP is integrated with OpenFlow protocol to detect and prevent DoS attacks effectively. Our comprehensive experimental results show that the ASP enhances the resilience of an SDN network against DoS attacks by up to 38%. PMID:27494411

  19. Adaptive Suspicious Prevention for Defending DoS Attacks in SDN-Based Convergent Networks.

    PubMed

    Dao, Nhu-Ngoc; Kim, Joongheon; Park, Minho; Cho, Sungrae

    2016-01-01

    The convergent communication network will play an important role as a single platform to unify heterogeneous networks and integrate emerging technologies and existing legacy networks. Although there have been proposed many feasible solutions, they could not become convergent frameworks since they mainly focused on converting functions between various protocols and interfaces in edge networks, and handling functions for multiple services in core networks, e.g., the Multi-protocol Label Switching (MPLS) technique. Software-defined networking (SDN), on the other hand, is expected to be the ideal future for the convergent network since it can provide a controllable, dynamic, and cost-effective network. However, SDN has an original structural vulnerability behind a lot of advantages, which is the centralized control plane. As the brains of the network, a controller manages the whole network, which is attractive to attackers. In this context, we proposes a novel solution called adaptive suspicious prevention (ASP) mechanism to protect the controller from the Denial of Service (DoS) attacks that could incapacitate an SDN. The ASP is integrated with OpenFlow protocol to detect and prevent DoS attacks effectively. Our comprehensive experimental results show that the ASP enhances the resilience of an SDN network against DoS attacks by up to 38%.

  20. FlexyDos3D: a deformable anthropomorphic 3D radiation dosimeter: radiation properties

    NASA Astrophysics Data System (ADS)

    De Deene, Y.; Skyt, P. S.; Hil, R.; Booth, J. T.

    2015-02-01

    Three dimensional radiation dosimetry has received growing interest with the implementation of highly conformal radiotherapy treatments. The radiotherapy community faces new challenges with the commissioning of image guided and image gated radiotherapy treatments (IGRT) and deformable image registration software. A new three dimensional anthropomorphically shaped flexible dosimeter, further called ‘FlexyDos3D’, has been constructed and a new fast optical scanning method has been implemented that enables scanning of irregular shaped dosimeters. The FlexyDos3D phantom can be actuated and deformed during the actual treatment. FlexyDos3D offers the additional advantage that it is easy to fabricate, is non-toxic and can be molded in an arbitrary shape with high geometrical precision. The dosimeter formulation has been optimized in terms of dose sensitivity. The influence of the casting material and oxygen concentration has also been investigated. The radiophysical properties of this new dosimeter are discussed including stability, spatial integrity, temperature dependence of the dosimeter during radiation, readout and storage, dose rate dependence and tissue equivalence. The first authors Y De Deene and P S Skyt made an equivalent contribution to the experimental work presented in this paper.

  1. Speciation genes in plants

    PubMed Central

    Rieseberg, Loren H.; Blackman, Benjamin K.

    2010-01-01

    Background Analyses of speciation genesgenes that contribute to the cessation of gene flow between populations – can offer clues regarding the ecological settings, evolutionary forces and molecular mechanisms that drive the divergence of populations and species. This review discusses the identities and attributes of genes that contribute to reproductive isolation (RI) in plants, compares them with animal speciation genes and investigates what these genes can tell us about speciation. Scope Forty-one candidate speciation genes were identified in the plant literature. Of these, seven contributed to pre-pollination RI, one to post-pollination, prezygotic RI, eight to hybrid inviability, and 25 to hybrid sterility. Genes, gene families and genetic pathways that were frequently found to underlie the evolution of RI in different plant groups include the anthocyanin pathway and its regulators (pollinator isolation), S RNase-SI genes (unilateral incompatibility), disease resistance genes (hybrid necrosis), chimeric mitochondrial genes (cytoplasmic male sterility), and pentatricopeptide repeat family genes (cytoplasmic male sterility). Conclusions The most surprising conclusion from this review is that identities of genes underlying both prezygotic and postzygotic RI are often predictable in a broad sense from the phenotype of the reproductive barrier. Regulatory changes (both cis and trans) dominate the evolution of pre-pollination RI in plants, whereas a mix of regulatory mutations and changes in protein-coding genes underlie intrinsic postzygotic barriers. Also, loss-of-function mutations and copy number variation frequently contribute to RI. Although direct evidence of positive selection on speciation genes is surprisingly scarce in plants, analyses of gene family evolution, along with theoretical considerations, imply an important role for diversifying selection and genetic conflict in the evolution of RI. Unlike in animals, however, most candidate speciation

  2. Human Gene Therapy: Genes without Frontiers?

    ERIC Educational Resources Information Center

    Simon, Eric J.

    2002-01-01

    Describes the latest advancements and setbacks in human gene therapy to provide reference material for biology teachers to use in their science classes. Focuses on basic concepts such as recombinant DNA technology, and provides examples of human gene therapy such as severe combined immunodeficiency syndrome, familial hypercholesterolemia, and…

  3. Human Gene Therapy: Genes without Frontiers?

    ERIC Educational Resources Information Center

    Simon, Eric J.

    2002-01-01

    Describes the latest advancements and setbacks in human gene therapy to provide reference material for biology teachers to use in their science classes. Focuses on basic concepts such as recombinant DNA technology, and provides examples of human gene therapy such as severe combined immunodeficiency syndrome, familial hypercholesterolemia, and…

  4. Gene regulation in cancer gene therapy strategies.

    PubMed

    Scanlon, Ian; Lehouritis, Panos; Niculescu-Duvaz, Ion; Marais, Richard; Springer, Caroline J

    2003-10-01

    Regulation of expression in gene therapy is considered to be a very desirable goal, preventing toxic effects and improving biological efficacy. A variety of systems have been reported in an ever widening range of applications, this paper describes these systems with specific reference to cancer gene therapy.

  5. Evolution by gene loss.

    PubMed

    Albalat, Ricard; Cañestro, Cristian

    2016-07-01

    The recent increase in genomic data is revealing an unexpected perspective of gene loss as a pervasive source of genetic variation that can cause adaptive phenotypic diversity. This novel perspective of gene loss is raising new fundamental questions. How relevant has gene loss been in the divergence of phyla? How do genes change from being essential to dispensable and finally to being lost? Is gene loss mostly neutral, or can it be an effective way of adaptation? These questions are addressed, and insights are discussed from genomic studies of gene loss in populations and their relevance in evolutionary biology and biomedicine.

  6. RAF1 is increased in labouring myometrium and modulates inflammation-induced pro-labour mediators.

    PubMed

    Lappas, Martha

    2016-04-01

    Inflammation plays a central role in the terminal process of human labour and delivery, including myometrial contractions. RAF1 proto-oncogene serine/threonine-protein kinase (RAF1) can activate ERK (official gene symbol MAPK1) and/or nuclear factor-kappa B (NF-κB) to regulate genes involved in inflammation. There are, however, no studies on the role of RAF1 in the processes of human labour and delivery. Thus, the aims of this study were to determine the effect of i) human labour and pro-inflammatory cytokines interleukin 1 beta (IL1B) and tumour necrosis factor (TNF) alpha on RAF1 protein expression in myometrium and ii) siRNA knockdown of RAF1 on pro-inflammatory and pro-labour mediators in human myometrial primary cells. Term labour was associated with an increase in RAF1 protein expression. Furthermore, RAF1 protein expression was increased in myometrial cells treated with IL1B and TNF, two likely factors contributing to preterm birth. Knockdown of RAF1 by siRNA in primary myometrial cells significantly decreased IL1B- and TNF-induced IL1A, IL1B, IL6, (C-X-C motif) ligand 8 (CXCL8)and chemokine (C-C motif) ligand 2 (CCL2) mRNA abundance and IL6, IL8 and CCL2; prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA levels and prostaglandin PGF2 α release; and NF-κB activation. Furthermore, RAF1 knockdown was associated with decreased activation of ERK in the presence of IL1B but not TNF. Concordantly, the ERK inhibitor U0126 significantly decreased IL1B-induced IL6, CXCL8, CCL2 and PTGS2 mRNA abundance; IL6, CXCL8, CCL2 and PGF2 α release; and NF-κB activation. In conclusion, IL1B induces the expression and secretion of pro-labour mediators through the RAF1-MAPK1-NF-κB signalling pathway. TNF, on the other hand, regulates pro-labour mediators through the RAF1-NF-κB signalling pathway via an MAPK1-independent mechanism. © 2016 Society for Reproduction and Fertility.

  7. Human gene therapy.

    PubMed

    Sandhu, J S; Keating, A; Hozumi, N

    1997-01-01

    Human gene therapy and its application for the treatment of human genetic disorders, such as cystic fibrosis, cancer, and other diseases, are discussed. Gene therapy is a technique in which a functioning gene is inserted into a human cell to correct a genetic error or to introduce a new function to the cell. Many methods, including retroviral vectors and non-viral vectors, have been developed for both ex vivo and in vivo gene transfer into cells. Vectors need to be developed that efficiently transfer genes to target cells, and promoter systems are required that regulate gene expression according to physiologic needs of the host cell. There are several safety and ethical issues related to manipulating the human genome that need to be resolved. Current gene therapy efforts focus on gene insertion into somatic cells only. Gene therapy has potential for the effective treatment of genetic disorders, and gene transfer techniques are being used for basic research, for example, in cancer, to examine the underlying mechanism of disease. There are still many technical obstacles to be overcome before human gene therapy can become a routine procedure. The current human genome project provides the sequences of a vast number of human genes, leading to the identification, characterization, and understanding of genes that are responsible for many human diseases.

  8. Study of the association between the interleukin-1 β c.3954C>T polymorphism and periodontitis in a population sample from Bahia, Brazil.

    PubMed

    Mendonça, Samir A; Teixeira, Fernanda G; Oliveira, Kamilla M; Santos, Djanilson B; Marques, Lucas M; Amorim, Maise M; Gestinari, Raquel De S

    2015-01-01

    Periodontitis is an inflammatory disease characterized by the loss of connective tissue and alveolar bone. Different factors are associated with the onset and prognosis of this disease, both environmental and genetic. The latter particularly relate to molecules secreted as a function of the host immune response, such as pro-inflammatory cytokines. Studies indicate that the polymorphism c. 3954C > T in the interleukin-1 β encoding gene (IL1B) can be considered as an aggravating factor in the periodontitis condition. This study aimed to evaluate whether there is an association between the IL1B c. 3954C > T gene polymorphism and the prevalence of periodontitis in the population from Vitória da Conquista-Bahia, Brazil. A total of 347 subjects (134 cases and 213 controls) who provided epithelial tissue of the oral cavity and saliva samples for DNA extraction and quantification of IL1B, respectively, were selected. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism followed by electrophoresis in agarose gel. The evaluation of the cytokine concentration was performed by enzyme-linked immunosorbent assay. Statistical calculations involved in this work include Chi-square test, Fisher Exact test, Mann-Whitney and Kruskal-Wallis tests. Our findings revealed that: (i) No statistically significant relationship between periodontitis and the polymorphism studied was observed; (ii) no significant difference between the concentrations of IL1B in saliva between the case and control subjects and between the genotypes of these individuals and the concentrations of this cytokine. We conclude that, in the sample evaluated, the IL1B c. 3954C > T polymorphism did not present as an etiological factor for periodontitis.

  9. Study of the association between the interleukin-1 β c.3954C>T polymorphism and periodontitis in a population sample from Bahia, Brazil

    PubMed Central

    Mendonça, Samir A.; Teixeira, Fernanda G.; Oliveira, Kamilla M.; Santos, Djanilson B.; Marques, Lucas M.; Amorim, Maise M.; Gestinari, Raquel De S.

    2015-01-01

    Background: Periodontitis is an inflammatory disease characterized by the loss of connective tissue and alveolar bone. Different factors are associated with the onset and prognosis of this disease, both environmental and genetic. The latter particularly relate to molecules secreted as a function of the host immune response, such as pro-inflammatory cytokines. Studies indicate that the polymorphism c. 3954C > T in the interleukin-1 β encoding gene (IL1B) can be considered as an aggravating factor in the periodontitis condition. Aims: This study aimed to evaluate whether there is an association between the IL1B c. 3954C > T gene polymorphism and the prevalence of periodontitis in the population from Vitória da Conquista–Bahia, Brazil. Materials and Methods: A total of 347 subjects (134 cases and 213 controls) who provided epithelial tissue of the oral cavity and saliva samples for DNA extraction and quantification of IL1B, respectively, were selected. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism followed by electrophoresis in agarose gel. The evaluation of the cytokine concentration was performed by enzyme-linked immunosorbent assay. Statistical Analysis: Statistical calculations involved in this work include Chi-square test, Fisher Exact test, Mann–Whitney and Kruskal–Wallis tests. Results: Our findings revealed that: (i) No statistically significant relationship between periodontitis and the polymorphism studied was observed; (ii) no significant difference between the concentrations of IL1B in saliva between the case and control subjects and between the genotypes of these individuals and the concentrations of this cytokine. Conclusions: We conclude that, in the sample evaluated, the IL1B c. 3954C > T polymorphism did not present as an etiological factor for periodontitis. PMID:26097351

  10. OptaDOS: A tool for obtaining density of states, core-level and optical spectra from electronic structure codes

    NASA Astrophysics Data System (ADS)

    Morris, Andrew J.; Nicholls, Rebecca J.; Pickard, Chris J.; Yates, Jonathan R.

    2014-05-01

    We present OptaDOS, a program for calculating core-electron and low-loss electron energy loss spectra (EELS) and optical spectra along with total-, projected- and joint-density of electronic states (DOS) from single-particle eigenenergies and dipole transition coefficients. Energy-loss spectroscopy is an important tool for probing bonding within a material. Interpreting these spectra can be aided by first principles calculations. The spectra are generated from the eigenenergies through integration over the Brillouin zone. An important feature of this code is that this integration is performed using a choice of adaptive or linear extrapolation broadening methods which we show produces higher accuracy spectra than standard fixed-width Gaussian broadening. OptaDOS may be straightforwardly interfaced to any electronic structure code. OptaDOS is freely available under the GNU General Public licence from http://www.optados.org.

  11. Gene therapy for blindness.

    PubMed

    Sahel, José-Alain; Roska, Botond

    2013-07-08

    Sight-restoring therapy for the visually impaired and blind is a major unmet medical need. Ocular gene therapy is a rational choice for restoring vision or preventing the loss of vision because most blinding diseases originate in cellular components of the eye, a compartment that is optimally suited for the delivery of genes, and many of these diseases have a genetic origin or genetic component. In recent years we have witnessed major advances in the field of ocular gene therapy, and proof-of-concept studies are under way to evaluate the safety and efficacy of human gene therapies. Here we discuss the concepts and recent advances in gene therapy in the retina. Our review discusses traditional approaches such as gene replacement and neuroprotection and also new avenues such as optogenetic therapies. We conjecture that advances in gene therapy in the retina will pave the way for gene therapies in other parts of the brain.

  12. T cell responses to DosR and Rpf proteins in actively and latently infected individuals from Colombia.

    PubMed

    Riaño, Felipe; Arroyo, Leonar; París, Sara; Rojas, Mauricio; Friggen, Annemieke H; van Meijgaarden, Krista E; Franken, Kees L M C; Ottenhoff, Tom H M; García, Luis F; Barrera, Luis F

    2012-03-01

    Mycobacterium tuberculosis DosR regulon-encoded proteins elicit strong immune T-cell responses in individuals with latent tuberculosis (LTBI). Also, resuscitation (Rpf) proteins can induce such responses. However, variations in the immunogenicity of the DosR and Rpf proteins have been observed in European and African populations, and no data are published from other geographic areas. In Colombian LTBI and patients with recently diagnosed PTB, we therefore studied the immune response to DosR, Rpf, stress, and nominal antigens from Mtb, in 7-day stimulated cultures. Three DosR (Rv1737c, Rv2029c, Rv2628c) and 2 Rpf (Rv0867 and Rv2389c) antigens were recognized most prominently on the basis of the net IFNγ production (DosR) or the percentage of responding individuals (Rpf). Results show that the selected DosR antigens induced a higher proportion of CD4-T cells producing IFNγ from LTBI, compared to pulmonary TB patients (PTB), while there were no differences in the proportion of CD8-T cells. An increased frequency of CD4, but not CD8 T-cells with a CD45RO(+)CD27(+) phenotype was observed in LTBI in response to Rv2029c, Rv0867c, and Rv2389c, compared to PTB. The levels of cytokines and chemokines in the supernatants of stimulated cells, showed that the DosR and Rpf antigens induced higher levels of IFNγ in cultures from LTBI compared to PTB, although the induced pattern of cytokines and chemokines was also antigen dependent. In summary, our results are consistent with the significant immunogenicity of Mtb DosR and Rpf antigens in LTBI individuals, and confirm and extend previously reported data from other TB affected human populations.

  13. Myocardial gene therapy

    NASA Astrophysics Data System (ADS)

    Isner, Jeffrey M.

    2002-01-01

    Gene therapy is proving likely to be a viable alternative to conventional therapies in coronary artery disease and heart failure. Phase 1 clinical trials indicate high levels of safety and clinical benefits with gene therapy using angiogenic growth factors in myocardial ischaemia. Although gene therapy for heart failure is still at the pre-clinical stage, experimental data indicate that therapeutic angiogenesis using short-term gene expression may elicit functional improvement in affected individuals.

  14. Evolution of Gene Expression after Gene Amplification

    PubMed Central

    Garcia, Nelson; Zhang, Wei; Wu, Yongrui; Messing, Joachim

    2015-01-01

    We took a rather unique approach to investigate the conservation of gene expression of prolamin storage protein genes across two different subfamilies of the Poaceae. We took advantage of oat plants carrying single maize chromosomes in different cultivars, called oat–maize addition (OMA) lines, which permitted us to determine whether regulation of gene expression was conserved between the two species. We found that γ-zeins are expressed in OMA7.06, which carries maize chromosome 7 even in the absence of the trans-acting maize prolamin-box-binding factor (PBF), which regulates their expression. This is likely because oat PBF can substitute for the function of maize PBF as shown in our transient expression data, using a γ-zein promoter fused to green fluorescent protein (GFP). Despite this conservation, the younger, recently amplified prolamin genes in maize, absent in oat, are not expressed in the corresponding OMAs. However, maize can express the oldest prolamin gene, the wheat high-molecular weight glutenin Dx5 gene, even when maize Pbf is knocked down (through PbfRNAi), and/or another maize transcription factor, Opaque-2 (O2) is knocked out (in maize o2 mutant). Therefore, older genes are conserved in their regulation, whereas younger ones diverged during evolution and eventually acquired a new repertoire of suitable transcriptional activators. PMID:25912045

  15. Reading and Generalist Genes

    ERIC Educational Resources Information Center

    Haworth, Claire M. A.; Meaburn, Emma L.; Harlaar, Nicole; Plomin, Robert

    2007-01-01

    Twin-study research suggests that many (but not all) of the same genes contribute to genetic influence on diverse learning abilities and disabilities, a hypothesis called "generalist genes". This generalist genes hypothesis was tested using a set of 10 DNA markers (single nucleotide polymorphisms [SNPs]) found to be associated with early reading…

  16. Reading and Generalist Genes

    ERIC Educational Resources Information Center

    Haworth, Claire M. A.; Meaburn, Emma L.; Harlaar, Nicole; Plomin, Robert

    2007-01-01

    Twin-study research suggests that many (but not all) of the same genes contribute to genetic influence on diverse learning abilities and disabilities, a hypothesis called "generalist genes". This generalist genes hypothesis was tested using a set of 10 DNA markers (single nucleotide polymorphisms [SNPs]) found to be associated with early reading…

  17. Helicobacter pylori virulence genes and host genetic polymorphisms as risk factors for peptic ulcer disease.

    PubMed

    Miftahussurur, Muhammad; Yamaoka, Yoshio

    2015-01-01

    Helicobacter pylori infection plays an important role in the pathogenesis of peptic ulcer disease (PUD). Several factors have been proposed as possible H. pylori virulence determinants; for example, bacterial adhesins and gastric inflammation factors are associated with an increased risk of PUD. However, differences in bacterial virulence factors alone cannot explain the opposite ends of the PUD disease spectrum, that is duodenal and gastric ulcers; presumably, both bacterial and host factors contribute to the differential response. Carriers of the high-producer alleles of the pro-inflammatory cytokines IL-1B, IL-6, IL-8, IL-10, and TNF-α who also carry low-producer allele of anti-inflammatory cytokines have severe gastric mucosal inflammation, whereas carriers of the alternative alleles have mild inflammation. Recent reports have suggested that the PSCA and CYP2C19 ultra-rapid metabolizer genotypes are also associated with PUD.

  18. Helicobacter pylori virulence genes and host genetic polymorphisms as risk factors for peptic ulcer disease

    PubMed Central

    Yamaoka, Yoshio; Miftahussurur, Muhammad

    2017-01-01

    Helicobacter pylori infection plays an important role in the pathogenesis of peptic ulcer disease (PUD). Several factors have been proposed as possible H. pylori virulence determinants; for example, bacterial adhesins and gastric inflammation factors are associated with an increased risk of PUD. However, differences in bacterial virulence factors alone cannot explain the opposite ends of the PUD disease spectrum, i.e., duodenal and gastric ulcers; presumably, both bacterial and host factors contribute to the differential response. Carriers of the high-producer alleles of the pro-inflammatory cytokines interleukin (IL)-1B, IL-6, IL-8, IL-10, and tumor necrosis factor-α who also carry low-producer allele carriers of anti-inflammatory cytokines have severe gastric mucosal inflammation, whereas carriers of the alternative alleles have mild inflammation. Recent reports have suggested that the PSCA and CYP2C19 ultra-rapid metabolizer genotypes are also associated with PUD. PMID:26470920

  19. Allele and genotype frequencies of polymorphisms in cytokine genes in ethnic Russian individuals from Moscow, Russia.

    PubMed

    Shadrina, Alexandra; Voronina, Elena; Zolotukhin, Igor; Filipenko, Maxim

    2017-02-01

    Two hundred and twenty eight ethnic Russian individuals from Moscow, Russia, were genotyped at 14 single nucleotide polymorphisms CCL2 A-2578G; VEGFA C-2578A, G-634C, and C+936T; TNF G+419A and G-308A; IL1A G-889A; IL1RN T+1018C; IL6G-174C and G-572C; IFNG T+874A; IL1B C-511T; IL10 A+1082G; TGFB1 C-509T. Genotypes were determined using real-time polymerase chain reaction with TaqMan probes and polymerase chain reaction followed by melting analysis of dual-labeled probe. Genotype distribution was in accordance with Hardy-Weinberg equilibrium for all studied polymorphisms. Genotype data are available in the Allele Frequencies Net Database under identifier AFND 3367 and the population name "Russia Moscow Cytokine". Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  20. Novel vaccine potential of Rv3131, a DosR regulon-encoded putative nitroreductase, against hyper-virulent Mycobacterium tuberculosis strain K.

    PubMed

    Kwon, Kee Woong; Kim, Woo Sik; Kim, Hongmin; Han, Seung Jung; Hahn, Mi-Young; Lee, Jong Seok; Nam, Ki Taek; Cho, Sang-Nae; Shin, Sung Jae

    2017-03-08

    Accumulating evidence indicates that latency-associated Mycobacterium tuberculosis (Mtb)-specific antigens from the dormancy survival regulator regulon (DosR) may be promising novel vaccine target antigens for the development of an improved tuberculosis vaccine. After transcriptional profiling of DosR-related genes in the hyper-virulent Beijing Mtb strain K and the reference Mtb strain H37Rv, we selected Rv3131, a hypothetical nitroreductase, as a vaccine antigen and evaluated its vaccine efficacy against Mtb K. Mtb K exhibited stable and constitutive up-regulation of rv3131 relative to Mtb H37Rv under three different growth conditions (at least 2-fold induction) including exponential growth in normal culture conditions, hypoxia, and inside macrophages. Mice immunised with Rv3131 formulated in GLA-SE, a well-defined TLR4 adjuvant, displayed enhanced Rv3131-specific IFN-γ and serum IgG2c responses along with effector/memory T cell expansion and remarkable generation of Rv3131-specific multifunctional CD4(+) T cells co-producing TNF-α, IFN-γ and IL-2 in both spleen and lung. Following challenge with Mtb K, the Rv3131/GLA-SE-immunised group exhibited a significant reduction in bacterial number and less extensive lung inflammation accompanied by the obvious persistence of Rv3131-specific multifunctional CD4(+) T cells. These results suggest that Rv3131 could be an excellent candidate for potential use in a multi-antigenic Mtb subunit vaccine, especially against Mtb Beijing strains.

  1. Novel vaccine potential of Rv3131, a DosR regulon-encoded putative nitroreductase, against hyper-virulent Mycobacterium tuberculosis strain K

    PubMed Central

    Kwon, Kee Woong; Kim, Woo Sik; Kim, Hongmin; Han, Seung Jung; Hahn, Mi-Young; Lee, Jong Seok; Nam, Ki Taek; Cho, Sang-Nae; Shin, Sung Jae

    2017-01-01

    Accumulating evidence indicates that latency-associated Mycobacterium tuberculosis (Mtb)-specific antigens from the dormancy survival regulator regulon (DosR) may be promising novel vaccine target antigens for the development of an improved tuberculosis vaccine. After transcriptional profiling of DosR-related genes in the hyper-virulent Beijing Mtb strain K and the reference Mtb strain H37Rv, we selected Rv3131, a hypothetical nitroreductase, as a vaccine antigen and evaluated its vaccine efficacy against Mtb K. Mtb K exhibited stable and constitutive up-regulation of rv3131 relative to Mtb H37Rv under three different growth conditions (at least 2-fold induction) including exponential growth in normal culture conditions, hypoxia, and inside macrophages. Mice immunised with Rv3131 formulated in GLA-SE, a well-defined TLR4 adjuvant, displayed enhanced Rv3131-specific IFN-γ and serum IgG2c responses along with effector/memory T cell expansion and remarkable generation of Rv3131-specific multifunctional CD4+ T cells co-producing TNF-α, IFN-γ and IL-2 in both spleen and lung. Following challenge with Mtb K, the Rv3131/GLA-SE-immunised group exhibited a significant reduction in bacterial number and less extensive lung inflammation accompanied by the obvious persistence of Rv3131-specific multifunctional CD4+ T cells. These results suggest that Rv3131 could be an excellent candidate for potential use in a multi-antigenic Mtb subunit vaccine, especially against Mtb Beijing strains. PMID:28272457

  2. DoS detection in IEEE 802.11 with the presence of hidden nodes

    PubMed Central

    Soryal, Joseph; Liu, Xijie; Saadawi, Tarek

    2013-01-01

    The paper presents a novel technique to detect Denial of Service (DoS) attacks applied by misbehaving nodes in wireless networks with the presence of hidden nodes employing the widely used IEEE 802.11 Distributed Coordination Function (DCF) protocols described in the IEEE standard [1]. Attacker nodes alter the IEEE 802.11 DCF firmware to illicitly capture the channel via elevating the probability of the average number of packets transmitted successfully using up the bandwidth share of the innocent nodes that follow the protocol standards. We obtained the theoretical network throughput by solving two-dimensional Markov Chain model as described by Bianchi [2], and Liu and Saadawi [3] to determine the channel capacity. We validated the results obtained via the theoretical computations with the results obtained by OPNET simulator [4] to define the baseline for the average attainable throughput in the channel under standard conditions where all nodes follow the standards. The main goal of the DoS attacker is to prevent the innocent nodes from accessing the channel and by capturing the channel’s bandwidth. In addition, the attacker strives to appear as an innocent node that follows the standards. The protocol resides in every node to enable each node to police other nodes in its immediate wireless coverage area. All innocent nodes are able to detect and identify the DoS attacker in its wireless coverage area. We applied the protocol to two Physical Layer technologies: Direct Sequence Spread Spectrum (DSSS) and Frequency Hopping Spread Spectrum (FHSS) and the results are presented to validate the algorithm. PMID:25685510

  3. DoS detection in IEEE 802.11 with the presence of hidden nodes.

    PubMed

    Soryal, Joseph; Liu, Xijie; Saadawi, Tarek

    2014-07-01

    The paper presents a novel technique to detect Denial of Service (DoS) attacks applied by misbehaving nodes in wireless networks with the presence of hidden nodes employing the widely used IEEE 802.11 Distributed Coordination Function (DCF) protocols described in the IEEE standard [1]. Attacker nodes alter the IEEE 802.11 DCF firmware to illicitly capture the channel via elevating the probability of the average number of packets transmitted successfully using up the bandwidth share of the innocent nodes that follow the protocol standards. We obtained the theoretical network throughput by solving two-dimensional Markov Chain model as described by Bianchi [2], and Liu and Saadawi [3] to determine the channel capacity. We validated the results obtained via the theoretical computations with the results obtained by OPNET simulator [4] to define the baseline for the average attainable throughput in the channel under standard conditions where all nodes follow the standards. The main goal of the DoS attacker is to prevent the innocent nodes from accessing the channel and by capturing the channel's bandwidth. In addition, the attacker strives to appear as an innocent node that follows the standards. The protocol resides in every node to enable each node to police other nodes in its immediate wireless coverage area. All innocent nodes are able to detect and identify the DoS attacker in its wireless coverage area. We applied the protocol to two Physical Layer technologies: Direct Sequence Spread Spectrum (DSSS) and Frequency Hopping Spread Spectrum (FHSS) and the results are presented to validate the algorithm.

  4. Studies of Brazilian meteorites. III - Origin and history of the Angra dos Reis achondrite

    NASA Technical Reports Server (NTRS)

    Prinz, M.; Keil, K.; Hlava, P. F.; Berkley, J. L.; Gomes, C. B.; Curvello, W. S.

    1977-01-01

    The mineral composition of the Angra dos Reis meteorite, which fell in 1869, is described. This achondrite contains phases reported in a meteorite for the first time. Petrofabric analysis shows that fassaite has a preferred orientation and lineation, which is interpreted as being due to cumulus processes, possibly the effect of post-depositional magmatic current flow or laminar flow of a crystalline mush. The mineral chemistry indicates crystallization from a highly silica-undersaturated melt at low pressure. Several aspects of the mineral composition are discussed with reference to the implications of crystallization conditions.

  5. Anaerobic Mycobacterium tuberculosis cell death stems from intracellular acidification mitigated by the DosR regulon.

    PubMed

    Reichlen, Matthew J; Leistikow, Rachel L; Scobey, Micah S; Born, Sarah E M; Voskuil, Martin I

    2017-09-05

    Mycobacterium tuberculosis (Mtb) is a strict aerobe capable of prolonged survival in the absence of oxygen. We investigated the ability of anaerobic Mtb to counter challenges to internal pH homeostasis in the absence of aerobic respiration, the primary mechanism of proton efflux for aerobic bacilli. Anaerobic Mtb populations were markedly impaired for survival under a mildly acidic pH relative to standard culture conditions. Acidic environmental pH greatly increased the susceptibility of anaerobic bacilli to collapse of proton motive force by protonophores, to antimicrobial compounds that target entry into the electron transport system, and to small organic acids with uncoupling activity. However, anaerobic bacilli exhibited high tolerance to these challenges at near neutral pH. At a slightly alkaline pH which was near the optimum intracellular pH, protonophore addition even improved long-term bacilli survival. Although anaerobic Mtb in acidic conditions maintained 40% lower ATP levels than bacilli at standard culture conditions, ATP loss alone could not explain the viability drop. Protonophores decreased ATP levels by more than 90% regardless of extracellular pH but were bactericidal only under acidic conditions, indicating anaerobic bacilli could survive extreme ATP loss provided the external pH was within viable intracellular parameters. Acidic conditions drastically decreased anaerobic survival of a DosR mutant while an alkaline environment improved survival of the DosR mutant. Together these findings indicate intracellular acidification is a primary challenge for anaerobic Mtb survival and that the DosR regulon plays a critical role in sustaining internal pH homeostasis.Importance: During infection, Mtb bacilli are prevalent in environments largely devoid of oxygen. Yet the factors that influence survival of these severely growth- and metabolically-limited bacilli remain poorly understood. We determined how anaerobic bacilli respond to fluctuations in

  6. Volcanic and structural controls of mineralization in the Dos Cabezas Mountains of southeastern Arizona

    SciTech Connect

    Drewes, H.; Klein, D.P.; Birmingham, S.D.

    1988-01-01

    A combination of geophysical, geochemical, and geological features suggests that a central part of the Dos Cabezas Mountains probably has considerable potential for blind deposits, chiefly base metals. The area exposes the root zone of a Paleocene( ) volcanic complex and its underlying granitic stocks, which were emplaced next to a major northwest-trending, much reactivated fault zone. The new data, combined with the knowledge of past mining activity in the area, lead them to propose several exploration targets that may lead to ore bodies in breccia pipes along the base of the volcanic pile and along a possible concealed fault or caldera margin.

  7. Pinch-off dynamics and dripping-onto-substrate (DoS) rheometry of complex fluids.

    PubMed

    Dinic, Jelena; Jimenez, Leidy Nallely; Sharma, Vivek

    2017-01-31

    Liquid transfer and drop formation/deposition processes involve complex free-surface flows including the formation of columnar necks that undergo spontaneous capillary-driven instability, thinning and pinch-off. For simple (Newtonian and inelastic) fluids, a complex interplay of capillary, inertial and viscous stresses determines the nonlinear dynamics underlying finite-time singularity as well as self-similar capillary thinning and pinch-off dynamics. In rheologically complex fluids, extra elastic stresses as well as non-Newtonian shear and extensional viscosities dramatically alter the nonlinear dynamics. Stream-wise velocity gradients that arise within the thinning columnar neck create an extensional flow field, and many complex fluids exhibit a much larger resistance to elongational flows than Newtonian fluids with similar shear viscosity. Characterization of pinch-off dynamics and the response to both shear and extensional flows that influence drop formation/deposition in microfluidic and printing applications requires bespoke instrumentation not available, or easily replicated, in most laboratories. Here we show that dripping-onto-substrate (DoS) rheometry protocols that involve visualization and analysis of capillary-driven thinning and pinch-off dynamics of a columnar neck formed between a nozzle and a sessile drop can be used for measuring shear viscosity, power law index, extensional viscosity, relaxation time and the most relevant processing timescale for printing. We showcase the versatility of DoS rheometry by characterizing and contrasting the pinch-off dynamics of a wide spectrum of simple and complex fluids: water, printing inks, semi-dilute polymer solutions, yield stress fluids, food materials and cosmetics. We show that DoS rheometry enables characterization of low viscosity printing inks and polymer solutions that are beyond the measurable range of commercially-available capillary break-up extensional rheometer (CaBER). We show that for high

  8. Age and isotopic relationships among the angrites Lewis Cliff 86010 and Angra dos Reis

    SciTech Connect

    Lugmair, G.W. ); Galer, S.J.G. Max-Planck-Inst. fuer Chemie, Mainz )

    1992-04-01

    Results of a wide-ranging isotopic investigation of the unique Antarctican angrite LEW-86010 (LEW) are presented, together with a reassessment of the type angrite Angra dos Reis (ADOR). The principal objectives of this study are to obtain precise radiometric ages, initial Sr isotopic compositions, and to search for the erstwhile presence of the short-lived nuclei {sup 146}Sm and {sup 26}Al via their daughter products. The isotopic compositions of Sm, U, Ca, and Ti were also measured. This allows a detailed appraisal to be made of the relations between, and the genealogy of, these two angrites.

  9. PrDOS: prediction of disordered protein regions from amino acid sequence.

    PubMed

    Ishida, Takashi; Kinoshita, Kengo

    2007-07-01

    PrDOS is a server that predicts the disordered regions of a protein from its amino acid sequence (http://prdos.hgc.jp). The server accepts a single protein amino acid sequence, in either plain text or FASTA format. The prediction system is composed of two predictors: a predictor based on local amino acid sequence information and one based on template proteins. The server combines the results of the two predictors and returns a two-state prediction (order/disorder) and a disorder probability for each residue. The prediction results are sent by e-mail, and the server also provides a web-interface to check the results.

  10. Use of Remote Sensing and Local Knowledge for Geoconservation of Regiao dos Lagos, Brazil

    NASA Astrophysics Data System (ADS)

    Avelar, S.; Vasconcelos, G.; Mansur, K. L.; Anjos, S. C.

    2013-12-01

    A series of lagoons can be found along the coastline of Rio de Janeiro, in the so-called Regiao dos Lagos. The lagoons differ in size, physicochemical, sedimentological and biological characteristics. Rare examples of litifying microbialites that produce stromatolites, the oldest fossils on Earth, can be found living in this lagoon system. The occurrence of stromatolites in the region is of great scientific interest because it enables the study of possible analogues of the earliest life on Earth. However, this region has been suffering from intense human activities and degradations. Geoconservation planning requires an assessment of the characteristics of the region and its potential threats. The primary goal of this study is to assess physical environmental changes and anthropogenic impacts over the last four decades in Regiao dos Lagos. Using a broad integrative assessment combining remote sensing, GIS, field studies and local knowledge of communities, land-cover and land-use classes were identified, as well as the main human activities impacting the environment. The seasonal and weekend tourism and urban sprawl in this coastal area of Rio de Janeiro triggers the occupation of new areas and the removal of natural vegetation, especially on lagoon margins. This disorderly occupation by an ever increasing population, with both legal and illegal constructions and the subsequent overload of the local infrastructure, e.g. increase of electrical energy consumption, volume of vehicles, pollution in air, water and soil and problems with water supply and wastewater treatment, are hastening the gradual degradation of the lake ecosystem. The main driving forces to environmental changes over the last four decades in Regiao dos Lagos were the change of dense vegetation, saline and bare soil classes into built-up areas, adding to the poor waste treatment and inadequate sewage disposal. This analysis provides a basis for a better control of anthropogenic impacts and

  11. The Intraplate Seismogenic Zone of Porto dos Gauchos in the Amazon Craton, Brazil

    NASA Astrophysics Data System (ADS)

    Barros, L. V.; Assumpcao, M. S.; Quintero, R. Q.

    2007-05-01

    The Porto dos Gauchos Seismogenic Zone (PGSZ), in the center north of Mato Grosso State, in the contact between the southern Amazonian Craton and northern Parecis Basin, represents one of the most important area of seismic activity in Brazil, with the largest magnitude ever observed in the stable continent of the South America plate (6.2 mb on January 31, 1955). Focal mechanism studies indicated a pure reverse faulting regime with compressional SHmax. oriented in SE-NW direction. After the 1955 earthquake, located in Serra do Tombador, a recurrent seismicity has been detected in Porto dos Gauchos, 100 km northeast of Serra do Tombador. No recent events have been detected in the area of the 1955 epicenter, suggesting a long recurrence time or mislocation of Serra do Tombador earthquake. The Porto dos Gauchos recurrent seismicity has been observed since 1959, when a 4.5 macroseismic estimated magnitude was felt by local inhabitants settled in that remote area two years earlier. In subsequent years, with deployment of regional stations in Brazilian Amazon region earthquakes were detected in 1981 (3.8 mb), 1989 (3.3 mb), 1993 (3.8 mb), 1996 (4.4 mb), 1997 (3.3 mb), and finally on March 10, 1998 (5.1 mb). The aftershocks of 1998 main shock were studied with a local network with up to eight 3- component stations. Such network detected more than 2500 events until December of 2002, when the network was deactivated, but only 100 were accurately located. Based on this set of events and a controlled source experiment we determined a 1-D velocity model for the area, a composite focal mechanism with P wave polarities, spectral analysis studies to estimate the source dimension, stress drop and moment magnitudes for the main shock and some others events of the set. On March 23, 2005 another shock occurred in the same seismogenic area of Porto dos Gauchos, with magnitude 4.7 to 5.0. One week later five stations were installed again to monitor the aftershock activity, detecting

  12. Gene hunting in autoinflammation

    PubMed Central

    2013-01-01

    Steady progress in our understanding of the genetic basis of autoinflammatory diseases has been made over the past 16 years. Since the discovery of the familial Mediterranean fever gene MEFV (also known as marenostrin) in 1997, 18 other genes responsible for monogenic autoinflammatory diseases have been identified to date. The discovery of these genes was made through the utilisation of many genetic mapping techniques, including next generation sequencing platforms. This review article clearly describes the gene hunting approaches, methods of data analysis and the technological platforms used, which has relevance to all those working within the field of gene discovery for Mendelian disorders. PMID:24070009

  13. Gene therapy review.

    PubMed

    Moss, Joseph Anthony

    2014-01-01

    The use of genes to treat disease, more commonly known as gene therapy, is a valid and promising tool to manage and treat diseases that conventional drug therapies cannot cure. Gene therapy holds the potential to control a wide range of diseases, including cystic fibrosis, heart disease, diabetes, cancer, and blood diseases. This review assesses the current status of gene therapy, highlighting therapeutic methodologies and applications, terminology, and imaging strategies. This article presents an overview of roadblocks associated with each therapeutic methodology, along with some of the scientific, social, and ethical issues associated with gene therapy.

  14. Gene therapy in periodontics.

    PubMed

    Chatterjee, Anirban; Singh, Nidhi; Saluja, Mini

    2013-03-01

    GENES are made of DNA - the code of life. They are made up of two types of base pair from different number of hydrogen bonds AT, GC which can be turned into instruction. Everyone inherits genes from their parents and passes them on in turn to their children. Every person's genes are different, and the changes in sequence determine the inherited differences between each of us. Some changes, usually in a single gene, may cause serious diseases. Gene therapy is 'the use of genes as medicine'. It involves the transfer of a therapeutic or working gene copy into specific cells of an individual in order to repair a faulty gene copy. Thus it may be used to replace a faulty gene, or to introduce a new gene whose function is to cure or to favorably modify the clinical course of a condition. It has a promising era in the field of periodontics. Gene therapy has been used as a mode of tissue engineering in periodontics. The tissue engineering approach reconstructs the natural target tissue by combining four elements namely: Scaffold, signaling molecules, cells and blood supply and thus can help in the reconstruction of damaged periodontium including cementum, gingival, periodontal ligament and bone.

  15. Regulated Gene Therapy.

    PubMed

    Breger, Ludivine; Wettergren, Erika Elgstrand; Quintino, Luis; Lundberg, Cecilia

    2016-01-01

    Gene therapy represents a promising approach for the treatment of monogenic and multifactorial neurological disorders. It can be used to replace a missing gene and mutated gene or downregulate a causal gene. Despite the versatility of gene therapy, one of the main limitations lies in the irreversibility of the process: once delivered to target cells, the gene of interest is constitutively expressed and cannot be removed. Therefore, efficient, safe and long-term gene modification requires a system allowing fine control of transgene expression.Different systems have been developed over the past decades to regulate transgene expression after in vivo delivery, either at transcriptional or post-translational levels. The purpose of this chapter is to give an overview on current regulatory system used in the context of gene therapy for neurological disorders. Systems using external regulation of transgenes using antibiotics are commonly used to control either gene expression using tetracycline-controlled transcription or protein levels using destabilizing domain technology. Alternatively, specific promoters of genes that are regulated by disease mechanisms, increasing expression as the disease progresses or decreasing expression as disease regresses, are also examined. Overall, this chapter discusses advantages and drawbacks of current molecular methods for regulated gene therapy in the central nervous system.

  16. Conventional murine gene targeting.

    PubMed

    Zimmermann, Albert G; Sun, Yue

    2013-01-01

    Murine gene knockout models engineered over the last two decades have continued to demonstrate their potential as invaluable tools in understanding the role of gene function in the context of normal human development and disease. The more recent elucidation of the human and mouse genomes through sequencing has opened up the capability to elucidate the function of every human gene. State-of-the-art mouse model generation allows, through a multitude of experimental steps requiring careful standardization, gene function to be reliably and predictably ablated in a live model system. The application of these standardized methodologies to directly target gene function through murine gene knockout has to date provided comprehensive and verifiable genetic models that have contributed tremendously to our understanding of the cellular and molecular pathways underlying normal and disease states in humans. The ensuing chapter provides an overview of the latest steps and procedures required to ablate gene function in a murine model.

  17. Retrieval with gene queries.

    PubMed

    Sehgal, Aditya K; Srinivasan, Padmini

    2006-04-21

    Accuracy of document retrieval from MEDLINE for gene queries is crucially important for many applications in bioinformatics. We explore five information retrieval-based methods to rank documents retrieved by PubMed gene queries for the human genome. The aim is to rank relevant documents higher in the retrieved list. We address the special challenges faced due to ambiguity in gene nomenclature: gene terms that refer to multiple genes, gene terms that are also English words, and gene terms that have other biological meanings. Our two baseline ranking strategies are quite similar in performance. Two of our three LocusLink-based strategies offer significant improvements. These methods work very well even when there is ambiguity in the gene terms. Our best ranking strategy offers significant improvements on three different kinds of ambiguities over our two baseline strategies (improvements range from 15.9% to 17.7% and 11.7% to 13.3% depending on the baseline). For most genes the best ranking query is one that is built from the LocusLink (now Entrez Gene) summary and product information along with the gene names and aliases. For others, the gene names and aliases suffice. We also present an approach that successfully predicts, for a given gene, which of these two ranking queries is more appropriate. We explore the effect of different post-retrieval strategies on the ranking of documents returned by PubMed for human gene queries. We have successfully applied some of these strategies to improve the ranking of relevant documents in the retrieved sets. This holds true even when various kinds of ambiguity are encountered. We feel that it would be very useful to apply strategies like ours on PubMed search results as these are not ordered by relevance in any way. This is especially so for queries that retrieve a large number of documents.

  18. RighTime: A real time clock correcting program for MS-DOS-based computer systems

    NASA Technical Reports Server (NTRS)

    Becker, G. Thomas

    1993-01-01

    A computer program is described which effectively eliminates the misgivings of the DOS system clock in PC/AT-class computers. RighTime is a small, sophisticated memory-resident program that automatically corrects both the DOS system clock and the hardware 'CMOS' real time clock (RTC) in real time. RighTime learns what corrections are required without operator interaction beyond the occasional accurate time set. Both warm (power on) and cool (power off) errors are corrected, usually yielding better than one part per million accuracy in the typical desktop computer with no additional hardware, and RighTime increases the system clock resolution from approximately 0.0549 second to 0.01 second. Program tools are also available which allow visualization of RighTime's actions, verification of its performance, display of its history log, and which provide data for graphing of the system clock behavior. The program has found application in a wide variety of industries, including astronomy, satellite tracking, communications, broadcasting, transportation, public utilities, manufacturing, medicine, and the military.

  19. Quality control and assurance for validation of DOS/I measurements

    NASA Astrophysics Data System (ADS)

    Cerussi, Albert; Durkin, Amanda; Kwong, Richard; Quang, Timothy; Hill, Brian; Tromberg, Bruce J.; MacKinnon, Nick; Mantulin, William W.

    2010-02-01

    Ongoing multi-center clinical trials are crucial for Biophotonics to gain acceptance in medical imaging. In these trials, quality control (QC) and assurance (QA) are key to success and provide "data insurance". Quality control and assurance deal with standardization, validation, and compliance of procedures, materials and instrumentation. Specifically, QC/QA involves systematic assessment of testing materials, instrumentation performance, standard operating procedures, data logging, analysis, and reporting. QC and QA are important for FDA accreditation and acceptance by the clinical community. Our Biophotonics research in the Network for Translational Research in Optical Imaging (NTROI) program for breast cancer characterization focuses on QA/QC issues primarily related to the broadband Diffuse Optical Spectroscopy and Imaging (DOS/I) instrumentation, because this is an emerging technology with limited standardized QC/QA in place. In the multi-center trial environment, we implement QA/QC procedures: 1. Standardize and validate calibration standards and procedures. (DOS/I technology requires both frequency domain and spectral calibration procedures using tissue simulating phantoms and reflectance standards, respectively.) 2. Standardize and validate data acquisition, processing and visualization (optimize instrument software-EZDOS; centralize data processing) 3. Monitor, catalog and maintain instrument performance (document performance; modularize maintenance; integrate new technology) 4. Standardize and coordinate trial data entry (from individual sites) into centralized database 5. Monitor, audit and communicate all research procedures (database, teleconferences, training sessions) between participants ensuring "calibration". This manuscript describes our ongoing efforts, successes and challenges implementing these strategies.

  20. Reproductive Dynamics of Sterna hirundinacea Lesson, 1831 in Ilha dos Cardos, Santa Catarina, Brazil

    PubMed Central

    Fracasso, Hélio Augusto Alves; Branco, Joaquim Olinto; Efe, Márcio Amorim

    2014-01-01

    In this work, we intend to describe the reproductive dynamics of Sterna hirundinacea in an island from South Brazil. We studied the reproductive biology of this species in its natural environment and provide data on their growth, survival, and reproductive success in Ilha dos Cardos, Santa Catarina, South Brazil. Samplings were carried out daily on the island throughout the reproductive seasons of 2003, 2005, and 2006 and the different stages of development of the chicks were characterized according to age, length of the beak, and plumage characteristics. We provide a basic equation Lm = 167.91 (1 − e −0.062t−(−0.23)) to determine the approximate age of individuals using their body mass. The main cause of chick mortality on the island was natural (63.17% in 2003, 81.41% in 2005, and 79.96% in 2006), whereas predation contributed to mortality in a proportion of 38.83% in 2003, 18.59% in 2005, and 20.04% in 2006. The absence in the area of the chicks' main predator, Kelp gull (Larus dominicanus), the large number of chicks that reached the final stages of development, and their reproductive success demonstrate that Ilha dos Cardos is an important breeding site for the species in southern Brazil. PMID:24977100

  1. Electron spin resonance dating of megafauna from Lagoa dos Porcos, Piauí, Brazil.

    PubMed

    Kinoshita, Angela; Mayer, Elver; Ribau Mendes, Vinícius; Figueiredo, Ana Maria G; Baffa, Oswaldo

    2014-06-01

    Excavations performed at Lagoa dos Porcos site revealed a vast amount of extinct mammal fossil remains, becoming one of the richest palaeontological occurrences in the Serra da Capivara National Park region, a UNESCO World Heritage. Although anatomic and taxonomic aspects of extinct Quaternary mammals are relatively well known, chronologic information for deposits is rare. In this context, electron spin resonance (ESR) dating of megafauna samples provides important information for establishing a chronological background. This work presents the ESR dating of two teeth, one of Gomphotheriidae and other of Toxodontinae. Dose-response curves of each sample were constructed using spectra acquired with a JEOL FA-200 X-Band spectrometer resulting in equivalent dose (De) of 220 ± 40 Gy and 39 ± 2 Gy for Toxodontinae and Gomphotheriidae tooth, respectively. The conversion of De in age was made using ROSY ESR dating software resulting in 26 ± 4 and 22 ± 3 ka. These results place Lagoa dos Porcos fossil assemblage within the Late Pleistocene. These dates overlap with a period of abrupt increase in rainfall in northeast Brazil, and it is possible that this environmental change is related to the formation of this deposit.

  2. Prevalence and predictors of orthorexia nervosa among German students using the 21-item-DOS.

    PubMed

    Depa, Julia; Schweizer, Jenny; Bekers, Sandra-Kristin; Hilzendegen, Carolin; Stroebele-Benschop, Nanette

    2017-03-01

    Orthorexia nervosa (ON) describes the constant pathological preoccupation with "healthy" nutrition. The current results regarding the prevalence of ON differ widely possibly because of invalid measurement tools. This study aimed to investigate ON prevalence in a sample of German students and to examine age, gender, semester, and nutritional knowledge as potential predictors of ON by comparing nutrition science (NS) with economics (ES) students. A total of 446 university students participated in the survey (NS 188, ES 268). ON was determined using the 21-item-DOS, which is a well-constructed, validated, and reliability-tested questionnaire. Age, gender, and semester were also assessed. Of the total sample, 3.3 % were classified as having ON and 9.0 % were at risk of developing ON. Older students scored significantly higher on the subscale "avoidance of additives" compared with younger students and students of lower semester suffered significantly more often from ON than students of higher semester. In addition, comparing field of study showed no significant difference in the prevalence of ON or the risk of developing ON between female NS and ES students. However, mean values for the three DOS subscales were higher among female NS students, albeit far below values indicating pathological behavior. The prevalence of ON appears to be low in this sample of German university students. Female NS students do not seem to have higher prevalence of ON or risk of developing ON.

  3. "Las Dos Cosas," or Why Mexican American Mothers Breast-Feed, But Not for Long.

    PubMed

    Flores, Angela; Anchondo, Inés; Huang, Cindy; Villanos, MariaTeresa; Finch, Casey

    2016-01-01

    To determine why mothers in El Paso, Texas, choose to breast-feed but not exclusively and why breast-feeding duration is short. This was a cross-sectional observational study of 300, mostly Mexican American, low-income mothers delivering at a county hospital who answered questions about breast-feeding and formula feeding, sociodemographics, and health habits. Most mothers (92.6%) in our study initiated breast-feeding, but only 20.3% breast-fed exclusively at the time of hospital discharge. Most mothers (73%) self-identified as Mexicans or Mexican Americans living on the border of the United States and Mexico. Mothers in our study chose to breast-feed if they decided to breast-feed during pregnancy, had breast-fed a previous child, had support from a female relative, and had attended college. Distinctively, most mothers in our study chose "las dos cosas" or to breast-feed and formula feed together early after birth. Acculturation failed to explain the breast-feeding decisions. Mexican American mothers who decided to breast-feed during pregnancy, breast-fed another child, attended college, and enlist a female relative's breast-feeding help were more likely to choose breast-feeding exclusively. Most Mexican American low-income mothers in our study chose "las dos cosas."

  4. RighTime: A real time clock correcting program for MS-DOS-based computer systems

    NASA Technical Reports Server (NTRS)

    Becker, G. Thomas

    1993-01-01

    A computer program is described which effectively eliminates the misgivings of the DOS system clock in PC/AT-class computers. RighTime is a small, sophisticated memory-resident program that automatically corrects both the DOS system clock and the hardware 'CMOS' real time clock (RTC) in real time. RighTime learns what corrections are required without operator interaction beyond the occasional accurate time set. Both warm (power on) and cool (power off) errors are corrected, usually yielding better than one part per million accuracy in the typical desktop computer with no additional hardware, and RighTime increases the system clock resolution from approximately 0.0549 second to 0.01 second. Program tools are also available which allow visualization of RighTime's actions, verification of its performance, display of its history log, and which provide data for graphing of the system clock behavior. The program has found application in a wide variety of industries, including astronomy, satellite tracking, communications, broadcasting, transportation, public utilities, manufacturing, medicine, and the military.

  5. Crystal Structures of the Response Regulator DosR From Mycobacterium Tuberculosis Suggest a Helix Rearrangement Mechanism for Phosphorylation Activation

    SciTech Connect

    Wisedchaisri, G.; Wu, M.; Sherman, D.R.; Hol, W.G.J.

    2009-05-26

    The response regulator DosR is essential for promoting long-term survival of Mycobacterium tuberculosis under low oxygen conditions in a dormant state and may be responsible for latent tuberculosis in one-third of the world's population. Here, we report crystal structures of full-length unphosphorylated DosR at 2.2 {angstrom} resolution and its C-terminal DNA-binding domain at 1.7 {angstrom} resolution. The full-length DosR structure reveals several features never seen before in other response regulators. The N-terminal domain of the full-length DosR structure has an unexpected ({beta}{alpha}){sub 4} topology instead of the canonical ({beta}{alpha}){sub 5} fold observed in other response regulators. The linker region adopts a unique conformation that contains two helices forming a four-helix bundle with two helices from another subunit, resulting in dimer formation. The C-terminal domain in the full-length DosR structure displays a novel location of helix {alpha}10, which allows Gln199 to interact with the catalytic Asp54 residue of the N-terminal domain. In contrast, the structure of the DosR C-terminal domain alone displays a remarkable unstructured conformation for helix {alpha}10 residues, different from the well-defined helical conformations in all other known structures, indicating considerable flexibility within the C-terminal domain. Our structures suggest a mode of DosR activation by phosphorylation via a helix rearrangement mechanism.

  6. Crystal Structures of the Response Regulator DosR from Mycobacterium tuberculosis Suggest a Helix Rearrangement Mechanism for Phosphorylation Activation

    PubMed Central

    Wisedchaisri, Goragot; Wu, Meiting; Sherman, David R.; Hol, Wim G. J.

    2008-01-01

    The response regulator DosR is essential for promoting long-term survival of Mycobacterium tuberculosis under low oxygen conditions in a dormant state and may be responsible for latent tuberculosis in one third of the world’s population. Here we report crystal structures of full-length unphosphorylated DosR at 2.2 Å and its C-terminal DNA-binding domain at 1.7 Å resolution. The full-length DosR structure reveals several features never seen before in other response regulators. The N-terminal domain of the full-length DosR structure has an unexpected (βα)4 topology instead of the canonical (βα)5 fold observed in other response regulators. The linker region adopts a unique conformation which contains two helices forming a four-helix bundle with two helices from another subunit, resulting in dimer formation. The C-terminal domain in the full-length DosR structure displays a novel location of helix α10 which provides Gln199 to interact with the catalytic Asp54 residue of the N-terminal domain. In contrast, the structure of the DosR C-terminal domain alone displays a remarkable unstructured conformation for helix α10 residues different from the well-defined helical conformations in all other known structures, indicating considerable flexibility within the C-terminal domain. Our structures suggest a mode of DosR activation by phosphorylation via a helix rearrangement mechanism. PMID:18353359

  7. Human HOX gene disorders.

    PubMed

    Quinonez, Shane C; Innis, Jeffrey W

    2014-01-01

    The Hox genes are an evolutionarily conserved family of genes, which encode a class of important transcription factors that function in numerous developmental processes. Following their initial discovery, a substantial amount of information has been gained regarding the roles Hox genes play in various physiologic and pathologic processes. These processes range from a central role in anterior-posterior patterning of the developing embryo to roles in oncogenesis that are yet to be fully elucidated. In vertebrates there are a total of 39 Hox genes divided into 4 separate clusters. Of these, mutations in 10 Hox genes have been found to cause human disorders with significant variation in their inheritance patterns, penetrance, expressivity and mechanism of pathogenesis. This review aims to describe the various phenotypes caused by germline mutation in these 10 Hox genes that cause a human phenotype, with specific emphasis paid to the genotypic and phenotypic differences between allelic disorders. As clinical whole exome and genome sequencing is increasingly utilized in the future, we predict that additional Hox gene mutations will likely be identified to cause distinct human phenotypes. As the known human phenotypes closely resemble gene-specific murine models, we also review the homozygous loss-of-function mouse phenotypes for the 29 Hox genes without a known human disease. This review will aid clinicians in identifying and caring for patients affected with a known Hox gene disorder and help recognize the potential for novel mutations in patients with phenotypes informed by mouse knockout studies.

  8. Do Housekeeping Genes Exist?

    PubMed Central

    Sun, Bingyun

    2015-01-01

    The searching of human housekeeping (HK) genes has been a long quest since the emergence of transcriptomics, and is instrumental for us to understand the structure of genome and the fundamentals of biological processes. The resolved genes are frequently used in evolution studies and as normalization standards in quantitative gene-expression analysis. Within the past 20 years, more than a dozen HK-gene studies have been conducted, yet none of them sampled human tissues completely. We believe an integration of these results will help remove false positive genes owing to the inadequate sampling. Surprisingly, we only find one common gene across 15 examined HK-gene datasets comprising 187 different tissue and cell types. Our subsequent analyses suggest that it might not be appropriate to rigidly define HK genes as expressed in all tissue types that have diverse developmental, physiological, and pathological states. It might be beneficial to use more robustly identified HK functions for filtering criteria, in which the representing genes can be a subset of genome. These genes are not necessarily the same, and perhaps need not to be the same, everywhere in our body. PMID:25970694

  9. Primetime for Learning Genes

    PubMed Central

    Keifer, Joyce

    2017-01-01

    Learning genes in mature neurons are uniquely suited to respond rapidly to specific environmental stimuli. Expression of individual learning genes, therefore, requires regulatory mechanisms that have the flexibility to respond with transcriptional activation or repression to select appropriate physiological and behavioral responses. Among the mechanisms that equip genes to respond adaptively are bivalent domains. These are specific histone modifications localized to gene promoters that are characteristic of both gene activation and repression, and have been studied primarily for developmental genes in embryonic stem cells. In this review, studies of the epigenetic regulation of learning genes in neurons, particularly the brain-derived neurotrophic factor gene (BDNF), by methylation/demethylation and chromatin modifications in the context of learning and memory will be highlighted. Because of the unique function of learning genes in the mature brain, it is proposed that bivalent domains are a characteristic feature of the chromatin landscape surrounding their promoters. This allows them to be “poised” for rapid response to activate or repress gene expression depending on environmental stimuli. PMID:28208656

  10. Primetime for Learning Genes.

    PubMed

    Keifer, Joyce

    2017-02-11

    Learning genes in mature neurons are uniquely suited to respond rapidly to specific environmental stimuli. Expression of individual learning genes, therefore, requires regulatory mechanisms that have the flexibility to respond with transcriptional activation or repression to select appropriate physiological and behavioral responses. Among the mechanisms that equip genes to respond adaptively are bivalent domains. These are specific histone modifications localized to gene promoters that are characteristic of both gene activation and repression, and have been studied primarily for developmental genes in embryonic stem cells. In this review, studies of the epigenetic regulation of learning genes in neurons, particularly the brain-derived neurotrophic factor gene (BDNF), by methylation/demethylation and chromatin modifications in the context of learning and memory will be highlighted. Because of the unique function of learning genes in the mature brain, it is proposed that bivalent domains are a characteristic feature of the chromatin landscape surrounding their promoters. This allows them to be "poised" for rapid response to activate or repress gene expression depending on environmental stimuli.

  11. Parkinson's disease: gene therapies.

    PubMed

    Coune, Philippe G; Schneider, Bernard L; Aebischer, Patrick

    2012-04-01

    With the recent development of effective gene delivery systems, gene therapy for the central nervous system is finding novel applications. Here, we review existing viral vectors and discuss gene therapy strategies that have been proposed for Parkinson's disease. To date, most of the clinical trials were based on viral vectors to deliver therapeutic transgenes to neurons within the basal ganglia. Initial trials used genes to relieve the major motor symptoms caused by nigrostriatal degeneration. Although these new genetic approaches still need to prove more effective than existing symptomatic treatments, there is a need for disease-modifying strategies. The investigation of the genetic factors implicated in Parkinson's disease is providing precious insights in disease pathology that, combined with innovative gene delivery systems, will hopefully offer novel opportunities for gene therapy interventions to slow down, or even halt disease progression.

  12. Observational Assessment of Preschool Disruptive Behavior, Part I: reliability of the Disruptive Behavior Diagnostic Observation Schedule (DB-DOS).

    PubMed

    Wakschlag, Lauren S; Hill, Carri; Carter, Alice S; Danis, Barbara; Egger, Helen L; Keenan, Kate; Leventhal, Bennett L; Cicchetti, Domenic; Maskowitz, Katie; Burns, James; Briggs-Gowan, Margaret J

    2008-06-01

    To examine the reliability of the Disruptive Behavior Diagnostic Observation Schedule (DB-DOS), a new observational method for assessing preschool disruptive behavior. The DB-DOS is a structured clinic-based assessment designed to elicit clinically salient behaviors relevant to the diagnosis of disruptive behavior in preschoolers. Child behavior is assessed in three interactional contexts that vary by partner (parent versus examiner) and level of support provided. Twenty-one disruptive behaviors are coded within two domains: problems in Behavioral Regulation and problems in Anger Modulation. A total of 364 referred and nonreferred preschoolers participated: interrater reliability and internal consistency were assessed on a primary sample (n = 335) and test-retest reliability was assessed in a separate sample (n = 29). The DB-DOS demonstrated good interrater and test-retest reliability. Confirmatory factor analysis demonstrated an excellent fit of the DB-DOS multidomain model of disruptive behavior. The DB-DOS is a reliable observational tool for clinic-based assessment of preschool disruptive behavior. This standardized assessment method holds promise for advancing developmentally sensitive characterization of preschool psychopathology.

  13. A Direct Method to Extract Transient Sub-Gap Density of State (DOS) Based on Dual Gate Pulse Spectroscopy.

    PubMed

    Dai, Mingzhi; Khan, Karim; Zhang, Shengnan; Jiang, Kemin; Zhang, Xingye; Wang, Weiliang; Liang, Lingyan; Cao, Hongtao; Wang, Pengjun; Wang, Peng; Miao, Lijing; Qin, Haiming; Jiang, Jun; Xue, Lixin; Chu, Junhao

    2016-06-14

    Sub-gap density of states (DOS) is a key parameter to impact the electrical characteristics of semiconductor materials-based transistors in integrated circuits. Previously, spectroscopy methodologies for DOS extractions include the static methods, temperature dependent spectroscopy and photonic spectroscopy. However, they might involve lots of assumptions, calculations, temperature or optical impacts into the intrinsic distribution of DOS along the bandgap of the materials. A direct and simpler method is developed to extract the DOS distribution from amorphous oxide-based thin-film transistors (TFTs) based on Dual gate pulse spectroscopy (GPS), introducing less extrinsic factors such as temperature and laborious numerical mathematical analysis than conventional methods. From this direct measurement, the sub-gap DOS distribution shows a peak value on the band-gap edge and in the order of 10(17)-10(21)/(cm(3)·eV), which is consistent with the previous results. The results could be described with the model involving both Gaussian and exponential components. This tool is useful as a diagnostics for the electrical properties of oxide materials and this study will benefit their modeling and improvement of the electrical properties and thus broaden their applications.

  14. A Direct Method to Extract Transient Sub-Gap Density of State (DOS) Based on Dual Gate Pulse Spectroscopy

    NASA Astrophysics Data System (ADS)

    Dai, Mingzhi; Khan, Karim; Zhang, Shengnan; Jiang, Kemin; Zhang, Xingye; Wang, Weiliang; Liang, Lingyan; Cao, Hongtao; Wang, Pengjun; Wang, Peng; Miao, Lijing; Qin, Haiming; Jiang, Jun; Xue, Lixin; Chu, Junhao

    2016-06-01

    Sub-gap density of states (DOS) is a key parameter to impact the electrical characteristics of semiconductor materials-based transistors in integrated circuits. Previously, spectroscopy methodologies for DOS extractions include the static methods, temperature dependent spectroscopy and photonic spectroscopy. However, they might involve lots of assumptions, calculations, temperature or optical impacts into the intrinsic distribution of DOS along the bandgap of the materials. A direct and simpler method is developed to extract the DOS distribution from amorphous oxide-based thin-film transistors (TFTs) based on Dual gate pulse spectroscopy (GPS), introducing less extrinsic factors such as temperature and laborious numerical mathematical analysis than conventional methods. From this direct measurement, the sub-gap DOS distribution shows a peak value on the band-gap edge and in the order of 1017-1021/(cm3·eV), which is consistent with the previous results. The results could be described with the model involving both Gaussian and exponential components. This tool is useful as a diagnostics for the electrical properties of oxide materials and this study will benefit their modeling and improvement of the electrical properties and thus broaden their applications.

  15. DOS-HEATING6: A general conduction code with nuclear heat generation derived from DOT-IV transport calculations

    SciTech Connect

    Williams, M.L.; Yuecel, A.; Nadkarny, S.

    1988-05-01

    The HEATING6 heat conduction code is modified to (a) read the multigroup particle fluxes from a two-dimensional DOT-IV neutron- photon transport calculation, (b) interpolate the fluxes from the DOT-IV variable (optional) mesh to the HEATING6 control volume mesh, and (c) fold the interpolated fluxes with kerma factors to obtain a nuclear heating source for the heat conduction equation. The modified HEATING6 is placed as a module in the ORNL discrete ordinates system (DOS), and has been renamed DOS-HEATING6. DOS-HEATING6 provides the capability for determining temperature distributions due to nuclear heating in complex, multi-dimensional systems. All of the original capabilities of HEATING6 are retained for the nuclear heating calculation; e.g., generalized boundary conditions (convective, radiative, finned, fixed temperature or heat flux), temperature and space dependent thermal properties, steady-state or transient analysis, general geometry description, etc. The numerical techniques used in the code are reviewed and the user input instructions and JCL to perform DOS-HEATING6 calculations are presented. Finally a sample problem involving coupled DOT-IV and DOS-HEATING6 calculations of a complex space-reactor configurations described, and the input and output of the calculations are listed. 10 refs., 11 figs., 6 tabs.

  16. A Direct Method to Extract Transient Sub-Gap Density of State (DOS) Based on Dual Gate Pulse Spectroscopy

    PubMed Central

    Dai, Mingzhi; Khan, Karim; Zhang, Shengnan; Jiang, Kemin; Zhang, Xingye; Wang, Weiliang; Liang, Lingyan; Cao, Hongtao; Wang, Pengjun; Wang, Peng; Miao, Lijing; Qin, Haiming; Jiang, Jun; Xue, Lixin; Chu, Junhao

    2016-01-01

    Sub-gap density of states (DOS) is a key parameter to impact the electrical characteristics of semiconductor materials-based transistors in integrated circuits. Previously, spectroscopy methodologies for DOS extractions include the static methods, temperature dependent spectroscopy and photonic spectroscopy. However, they might involve lots of assumptions, calculations, temperature or optical impacts into the intrinsic distribution of DOS along the bandgap of the materials. A direct and simpler method is developed to extract the DOS distribution from amorphous oxide-based thin-film transistors (TFTs) based on Dual gate pulse spectroscopy (GPS), introducing less extrinsic factors such as temperature and laborious numerical mathematical analysis than conventional methods. From this direct measurement, the sub-gap DOS distribution shows a peak value on the band-gap edge and in the order of 1017–1021/(cm3·eV), which is consistent with the previous results. The results could be described with the model involving both Gaussian and exponential components. This tool is useful as a diagnostics for the electrical properties of oxide materials and this study will benefit their modeling and improvement of the electrical properties and thus broaden their applications. PMID:27297030

  17. First-principle calculation of the electronic structure, DOS and effective mass TlInSe2

    NASA Astrophysics Data System (ADS)

    Ismayilova, N. A.; Orudzhev, G. S.; Jabarov, S. H.

    2017-05-01

    The electronic structure, density of states (DOS), effective mass are calculated for tetragonal TlInSe2 from first principle in the framework of density functional theory (DFT). The electronic structure of TlInSe2 has been investigated by Quantum Wise within GGA. The calculated band structure by Hartwigsen-Goedecker-Hutter (HGH) pseudopotentials (psp) shows both the valence band maximum and conduction band minimum located at the T point of the Brillouin zone. Valence band maximum at the T point and the surrounding parts originate mainly from 6s states of univalent Tl ions. Bottom of the conduction band is due to the contribution of 6p-states of Tl and 5s-states of In atoms. Calculated DOS effective mass for holes and electrons are mDOS h∗ = 0.830m e, mDOS h∗ = 0.492m e, respectively. Electron effective masses are fairly isotropic, while the hole effective masses show strong anisotropy. The calculated electronic structure, density of states and DOS effective masses of TlInSe2 are in good agreement with existing theoretical and experimental results.

  18. Green genes gleaned.

    PubMed

    Beale, Samuel I

    2005-07-01

    A recent paper by Ayumi Tanaka and colleagues identifying an Arabidopsis thaliana gene for 3,8-divinyl(proto)chlorophyllide 8-vinyl reductase brings a satisfying conclusion to the hunt for genes encoding enzymes for the steps in the chlorophyll biosynthetic pathway. Now, at least in angiosperm plants represented by Arabidopsis, genes for all 15 steps in the pathway from glutamyl-tRNA to chlorophylls a and b have been identified.

  19. Cell and gene therapy.

    PubMed

    Rao, Rajesh C; Zacks, David N

    2014-01-01

    Replacement or repair of a dysfunctional gene combined with promoting cell survival is a two-pronged approach that addresses an unmet need in the therapy of retinal degenerative diseases. In this chapter, we discuss various strategies toward achieving both goals: transplantation of wild-type cells to replace degenerating cells and to rescue gene function, sequential gene and cell therapy, and in vivo reprogramming of rods to cones. These approaches highlight cutting-edge advances in cell and gene therapy, and cellular lineage conversion in order to devise new therapies for various retinal degenerative diseases.

  20. Gene-Category Analysis.

    PubMed

    Bauer, Sebastian

    2017-01-01

    Gene-category analysis is one important knowledge integration approach in biomedical sciences that combines knowledge bases such as Gene Ontology with lists of genes or their products, which are often the result of high-throughput experiments, gained from either wet-lab or synthetic experiments. In this chapter, we will motivate this class of analyses and describe an often used variant that is based on Fisher's exact test. We show that this approach has some problems in the context of Gene Ontology of which users should be aware. We then describe some more recent algorithms that try to address some of the shortcomings of the standard approach.

  1. Gene therapy for haemophilia.

    PubMed

    Sharma, Akshay; Easow Mathew, Manu; Sriganesh, Vasumathi; Neely, Jessica A; Kalipatnapu, Sasank

    2014-11-14

    Haemophilia is a genetic disorder which is characterized by spontaneous or provoked, often uncontrolled, bleeding into joints, muscles and other soft tissues. Current methods of treatment are expensive, challenging and involve regular administration of clotting factors. Gene therapy has recently been prompted as a curative treatment modality. To evaluate the safety and efficacy of gene therapy for treating people with haemophilia A or B. We searched the Cochrane Cystic Fibrosis & Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Date of last search: 06 November 2014. Eligible trials included randomised or quasi-randomised clinical trials, including controlled clinical trials comparing gene therapy (with or without standard treatment) with standard treatment (factor replacement) or other 'curative' treatment such as stem cell transplantation individuals with haemophilia A or B of all ages who do not have inhibitors to factor VIII or IX. No trials of gene therapy for haemophilia were found. No trials of gene therapy for haemophilia were identified. No randomised or quasi-randomised clinical trials of gene therapy for haemophilia were identified. Thus, we are unable to determine the effects of gene therapy for haemophilia. Gene therapy for haemophilia is still in its nascent stages and there is a need for well-designed clinical trials to assess the long-term feasibility, success and risks of gene therapy for people with haemophilia.

  2. Antiangiogenic Eye Gene Therapy.

    PubMed

    Corydon, Thomas J

    2015-08-01

    The idea of treating disease in humans with genetic material was conceived over two decades ago and with that a promising journey involving development and efficacy studies in cells and animals of a large number of novel therapeutic reagents unfolded. In the footsteps of this process, successful gene therapy treatment of genetic conditions in humans has shown clear signs of efficacy. Notably, significant advancements using gene supplementation and silencing strategies have been made in the field of ocular gene therapy, thereby pinpointing ocular gene therapy as one of the compelling "actors" bringing gene therapy to the clinic. Most of all, this success has been facilitated because of (1) the fact that the eye is an effortlessly accessible, exceedingly compartmentalized, and immune-privileged organ offering a unique advantage as a gene therapy target, and (2) significant progress toward efficient, sustained transduction of cells within the retina having been achieved using nonintegrating vectors based on recombinant adeno-associated virus and nonintegrating lentivirus vectors. The results from in vivo experiments and trials suggest that treatment of inherited retinal dystrophies, ocular angiogenesis, and inflammation with gene therapy can be both safe and effective. Here, the progress of ocular gene therapy is examined with special emphasis on the potential use of RNAi- and protein-based antiangiogenic gene therapy to treat exudative age-related macular degeneration.

  3. History of gene therapy.

    PubMed

    Wirth, Thomas; Parker, Nigel; Ylä-Herttuala, Seppo

    2013-08-10

    Two decades after the initial gene therapy trials and more than 1700 approved clinical trials worldwide we not only have gained much new information and knowledge regarding gene therapy in general, but also learned to understand the concern that has persisted in society. Despite the setbacks gene therapy has faced, success stories have increasingly emerged. Examples for these are the positive recommendation for a gene therapy product (Glybera) by the EMA for approval in the European Union and the positive trials for the treatment of ADA deficiency, SCID-X1 and adrenoleukodystrophy. Nevertheless, our knowledge continues to grow and during the course of time more safety data has become available that helps us to develop better gene therapy approaches. Also, with the increased understanding of molecular medicine, we have been able to develop more specific and efficient gene transfer vectors which are now producing clinical results. In this review, we will take a historical view and highlight some of the milestones that had an important impact on the development of gene therapy. We will also discuss briefly the safety and ethical aspects of gene therapy and address some concerns that have been connected with gene therapy as an important therapeutic modality.

  4. Towards Consensus Gene Ages

    PubMed Central

    Liebeskind, Benjamin J.; McWhite, Claire D.; Marcotte, Edward M.

    2016-01-01

    Correctly estimating the age of a gene or gene family is important for a variety of fields, including molecular evolution, comparative genomics, and phylogenetics, and increasingly for systems biology and disease genetics. However, most studies use only a point estimate of a gene’s age, neglecting the substantial uncertainty involved in this estimation. Here, we characterize this uncertainty by investigating the effect of algorithm choice on gene-age inference and calculate consensus gene ages with attendant error distributions for a variety of model eukaryotes. We use 13 orthology inference algorithms to create gene-age datasets and then characterize the error around each age-call on a per-gene and per-algorithm basis. Systematic error was found to be a large factor in estimating gene age, suggesting that simple consensus algorithms are not enough to give a reliable point estimate. We also found that different sources of error can affect downstream analyses, such as gene ontology enrichment. Our consensus gene-age datasets, with associated error terms, are made fully available at so that researchers can propagate this uncertainty through their analyses (geneages.org). PMID:27259914

  5. Age and isotopic relationships among the angrites Lewis Cliff 86010 and Angra dos Reis

    NASA Technical Reports Server (NTRS)

    Lugmair, G. W.; Galer, S. J. G.

    1992-01-01

    The paper presents results of a wide-ranging isotopic investigation of the the Antarctic angrite LEW-86010 (LEW), and reassesses the type angrite Angra dos Reis (ADOR) in order to obtain precise radiometric ages and initial Sr isotopic compositions, and to search for the erstwhile presence of the short-lived nuclei Sm-146 and Al-26 via their daughter products. The isotopic compositions of Sm, U, Ca, and Ti were measured to allow a detailed appraisal to be made of the relations between, and the geneology of, these two angrites. LEW proves to be severely contaminated with modern terrestrial Pb, which is shown to result from terrestrial weathering. Concordant Pb-Pb model ages of pyroxene separates are obtained; uranium isotopic compositions are normal within error. Overall, striking age and isotopic similarities between LEW and ADOR were found, suggesting almost simultaneous production on the same asteroid, even though recent experimental studies imply that the two are not comagmatic.

  6. Estudio dinámico de un potencial perturbador dependiente de dos parámetros

    NASA Astrophysics Data System (ADS)

    Miloni, O.; Brunini, A.

    El objeto del presente trabajo consiste en el estudio dinámico de un sistema dinámico caracterizado por la función hamiltoniana correspondiente a un satélite planetario perturbado por la acción del Sol y del achatamiento del planeta madre. Cuando dicha Hamiltoniana se promedia respecto de los términos de corto período, esta queda con dos grados de libertad, y su estudio puede ser realizado con las herramientas clásicas de la dinámica no-lineal. Se tratará de determinar regiones regulares y caóticas de movimiento. En el caso de estas últimas, es de particular interés la determinación de su orígen.

  7. On securing wireless sensor network--novel authentication scheme against DOS attacks.

    PubMed

    Raja, K Nirmal; Beno, M Marsaline

    2014-10-01

    Wireless sensor networks are generally deployed for collecting data from various environments. Several applications specific sensor network cryptography algorithms have been proposed in research. However WSN's has many constrictions, including low computation capability, less memory, limited energy resources, vulnerability to physical capture, which enforce unique security challenges needs to make a lot of improvements. This paper presents a novel security mechanism and algorithm for wireless sensor network security and also an application of this algorithm. The proposed scheme is given to strong authentication against Denial of Service Attacks (DOS). The scheme is simulated using network simulator2 (NS2). Then this scheme is analyzed based on the network packet delivery ratio and found that throughput has improved.

  8. Age and isotopic relationships among the angrites Lewis Cliff 86010 and Angra dos Reis

    NASA Technical Reports Server (NTRS)

    Lugmair, G. W.; Galer, S. J. G.

    1992-01-01

    The paper presents results of a wide-ranging isotopic investigation of the the Antarctic angrite LEW-86010 (LEW), and reassesses the type angrite Angra dos Reis (ADOR) in order to obtain precise radiometric ages and initial Sr isotopic compositions, and to search for the erstwhile presence of the short-lived nuclei Sm-146 and Al-26 via their daughter products. The isotopic compositions of Sm, U, Ca, and Ti were measured to allow a detailed appraisal to be made of the relations between, and the geneology of, these two angrites. LEW proves to be severely contaminated with modern terrestrial Pb, which is shown to result from terrestrial weathering. Concordant Pb-Pb model ages of pyroxene separates are obtained; uranium isotopic compositions are normal within error. Overall, striking age and isotopic similarities between LEW and ADOR were found, suggesting almost simultaneous production on the same asteroid, even though recent experimental studies imply that the two are not comagmatic.

  9. Measured oxygen fugacities of the Angra dos Reis achondrite as a function of temperature

    USGS Publications Warehouse

    Brett, R.; Stephen, Huebner J.; Sato, M.

    1977-01-01

    Measurements of the oxygen fugacity (f{hook}O2) as a function of temperature (T) were made on an interior bulk sample of the cumulate achondrite, Angra dos Reis. Data clustered between the f{hook}O2-T relationship of the iron-wu??stite assemblage and 1.2 log atm units above iron-wu??stite. Interpretation of the data indicates that, throughout most of the cooling history of the meteorite, f{hook}O2 values were defined by equilibria involving iron-bearing species at values close to the f{hook}O2 of the assemblage iron-wu??stite. Measured f{hook}O2 data are compatible with crystallization and cooling at pressures greater than 50 bars. ?? 1977.

  10. Revisiting DoS Attacks and Privacy in RFID-Enabled Networks

    NASA Astrophysics Data System (ADS)

    D'Arco, Paolo; Scafuro, Alessandra; Visconti, Ivan

    Vaudenay presented in [ASIACRYPT 2007] a general RFID security and privacy model that abstracts some previous works in a single, concise, and much more understandable framework. He introduced eight distinct notions of privacy, corresponding to adversaries of different strength, and proved some possibility and impossibility results for such privacy notions. However, some interesting problems as: 1) achieving stronger privacy using low-cost tags (i.e., tags that usually can not perform public-key cryptography), 2) achieving stronger privacy in presence of side-channel attacks (e.g., DoS attacks, detection of the outputs of identification protocols), and 3) achieving stronger privacy under standard complexity-theoretic assumptions, are still left open.

  11. An MS-DOS-based program for analyzing plutonium gamma-ray spectra

    SciTech Connect

    Ruhter, W.D.; Buckley, W.M.

    1989-09-07

    A plutonium gamma-ray analysis system that operates on MS-DOS-based computers has been developed for the International Atomic Energy Agency (IAEA) to perform in-field analysis of plutonium gamma-ray spectra for plutonium isotopics. The program titled IAEAPU consists of three separate applications: a data-transfer application for transferring spectral data from a CICERO multichannel analyzer to a binary data file, a data-analysis application to analyze plutonium gamma-ray spectra, for plutonium isotopic ratios and weight percents of total plutonium, and a data-quality assurance application to check spectral data for proper data-acquisition setup and performance. Volume 3 contains the software listings for these applications.

  12. The Secret List of Dos and Don'ts for Filmmaking

    NASA Astrophysics Data System (ADS)

    Kramer, N.

    2012-12-01

    Science is a massive black box to billions of people who walk the streets. However, the process of filmmaking can be equally as mystifying. As with the development of many scientific experiments, the process starts on a napkin at a restaurant…but then what? The road to scientific publication is propelled by a canonical list of several dos and don't that fit most situations. An equally useful list exists for up-and-coming producers. The list streamlines efforts, optimizes your use of the tools at your fingertips and enhances impact. Many fundamentals can be learned from books, but during this talk we will project and discuss several examples of best practices, from honing a story, to identifying audience appeal, filming, editing and the secrets of inexpensively acquiring expert help. Whether your goal is a two-minute webisode or a 90 minute documentary, these time-tested practices, with a little awareness, can give life to your films.;

  13. [Anterior cruciate ligament-plasty using the "U-dos" technique].

    PubMed

    Morales-Trevizo, C; Paz-García, M; Leal-Berumen, I; Leal-Contreras, C; Berumen-Nafarrate, E

    2013-01-01

    The knee is a compound diarthrodial joint, vulnerable to serious injuries such as ligament injuries of: medial collateral ligament, lateral collateral ligament, anterior cruciate ligament and posterior cruciate ligament, as cruciate ligaments limit rotation movement in the joint. The purpose of our study was to create a new technique to treat injuries of the anterior cruciate ligament, which is composed of two bundles--anteromedial and posterolateral--trying to achieve an anatomical reconstruction that allows for a normal biomechanical recovery. This technique reduces the use of fixation material and costs. The diagnosis of anterior cruciate ligament injuries was made with the pivot shift test. There are currently two repair methods for anterior cruciate ligament injuries: single bundle or double bundle repair; none of these techniques is considered as the gold standard, as their results are very similar. This paper describes a technique used for the treatment of anterior cruciate ligament injuries, known as "U-dos", and its clinical results. Cross-sectional, observational study that enrolled 20 patients with total anterior cruciate ligament injuries who underwent anterior cruciate ligament plasty using the "U-dos" technique between June 2009 and June 2010. The technique requires the use of bone bank allograft, in this case of the anterior tibial ligament. Patients were assessed using the Lysholm scale and the pivot shift test. Our results show that all the pivot shift tests were negative and assessments according to the Lysholm scale were from normal to excellent in 95% of cases (19/20). Only one failure was reported, with avulsion of the graft attachment which required a surgical intervention.

  14. Cucumber gene list 2017

    USDA-ARS?s Scientific Manuscript database

    This is an update of the 2010 version of Cucumber Gene List. Since the release of the cucumber draft genome in 2009, significant progress has been made in developing cucumber genetic and genomics resources. A number of genes or QTLs have been tagged with molecular markers, which provides us a better...

  15. Smart Genes, Stupid Science.

    ERIC Educational Resources Information Center

    Randerson, Sherman; Mahadeva, Madhu N.

    1983-01-01

    Because many people still believe that specific, identifiable genes dictate the level of human intelligence and that the number/quality of these genes can be evaluated, presents evidence from human genetics (related to nervous system development) to counter this view. Also disputes erroneous assumptions made in "heritability studies" of human…

  16. A victory for genes.

    PubMed

    2013-07-01

    The ability to patent human genes has been costly to researchers and patients, and has restricted competition in the biotech marketplace. The recent US Supreme Court decision making isolated human genes unpatentable will bring freedom of choice to the patient, and level the playing field for research and development.

  17. Genes, genome and Gestalt.

    PubMed

    Grisolia, Cesar Koppe

    2005-03-31

    According to Gestalt thinking, biological systems cannot be viewed as the sum of their elements, but as processes of the whole. To understand organisms we must start from the whole, observing how the various parts are related. In genetics, we must observe the genome over and above the sum of its genes. Either loss or addition of one gene in a genome can change the function of the organism. Genomes are organized in networks of genes, which need to be well integrated. In the case of genetically modified organisms (GMOs), for example, soybeans, rats, Anopheles mosquitoes, and pigs, the insertion of an exogenous gene into a receptive organism generally causes disturbance in the networks, resulting in the breakdown of gene interactions. In these cases, genetic modification increased the genetic load of the GMO and consequently decreased its adaptability (fitness). Therefore, it is hard to claim that the production of such organisms with an increased genetic load does not have ethical implications.

  18. [Gene therapy and ethics].

    PubMed

    Müller, H; Rehmann-Sutter, C

    1995-01-10

    Gene therapy represents a new strategy to treat human disorders. It was originally conceived as a cure for severe monogenetic disorders. Since its conception, the spectrum of possible application for gene therapy has been to include the treatment of acquired diseases, such as various forms of cancer and some viral infections, most notably human immune deficiency virus (HIV) and hepatitis B virus. Since somatic gene therapy does not cause substantially new ethical problems, it has gained broad approval. This is by no means the case with germ-line gene therapy. Practically all bodies who were evaluating the related ethical aspects wanted to ban its medical application on grounds of fundamental and pragmatic considerations. In this review, practical and ethical views concerning gene therapy are summarized which were presented at the "Junitagung 1994" of the Swiss Society for Biomedical Ethics in Basle.

  19. GIPC gene family (Review).

    PubMed

    Katoh, Masaru

    2002-06-01

    GIPC1/GIPC/RGS19IP1, GIPC2, and GIPC3 genes constitute the human GIPC gene family. GIPC1 and GIPC2 show 62.0% total-amino-acid identity. GIPC1 and GIPC3 show 59.9% total-amino-acid identity. GIPC2 and GIPC3 show 55.3% total-amino-acid identity. GIPCs are proteins with central PDZ domain and GIPC homology (GH1 and GH2) domains. PDZ, GH1, and GH2 domains are conserved among human GIPCs, Xenopus GIPC/Kermit, and Drosophila GIPC/ LP09416. Bioinformatics revealed that GIPC genes are linked to prostanoid receptor genes and DNAJB genes in the human genome as follows: GIPC1 gene is linked to prostaglandin E receptor 1 (PTGER1) gene and DNAJB1 gene in human chromosome 19p13.2-p13.1 region; GIPC2 gene to prostaglandin F receptor (PTGFR) gene and DNAJB4 gene in human chromosome 1p31.1-p22.3 region; GIPC3 gene to thromboxane A2 receptor (TBXA2R) gene in human chromosome 19p13.3 region. GIPC1 and GIPC2 mRNAs are expressed together in OKAJIMA, TMK1, MKN45 and KATO-III cells derived from diffuse-type of gastric cancer, and are up-regulated in several cases of primary gastric cancer. PDZ domain of GIPC family proteins interact with Frizzled-3 (FZD3) class of WNT receptor, insulin-like growth factor-I (IGF1) receptor, receptor tyrosine kinase TrkA, TGF-beta type III receptor (TGF-beta RIII), integrin alpha6A subunit, transmembrane glycoprotein 5T4, and RGS19/RGS-GAIP. Because RGS19 is a member of the RGS family that regulate heterotrimeric G-protein signaling, GIPCs might be scaffold proteins linking heterotrimeric G-proteins to seven-transmembrane-type WNT receptor or to receptor tyrosine kinases. Therefore, GIPC1, GIPC2 and GIPC3 might play key roles in carcinogenesis and embryogenesis through modulation of growth factor signaling and cell adhesion.

  20. 4. AERIAL VIEW OF GENE WASH RESERVOIR AND GENE CAMP ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. AERIAL VIEW OF GENE WASH RESERVOIR AND GENE CAMP LOOKING SOUTHWEST. DAM AND SPILLWAY VISIBLE IN BOTTOM OF PHOTO. - Gene Wash Reservoir & Dam, 2 miles west of Parker Dam, Parker Dam, San Bernardino County, CA

  1. Third party annotation gene data set of eutherian lysozyme genes.

    PubMed

    Premzl, Marko

    2014-12-01

    The eutherian comparative genomic analysis protocol annotated most comprehensive eutherian lysozyme gene data set. Among 209 potential coding sequences, the third party annotation gene data set of eutherian lysozyme genes included 116 complete coding sequences that first described seven major gene clusters. As one new framework of future experiments, the present integrated gene annotations, phylogenetic analysis and protein molecular evolution analysis proposed new classification and nomenclature of eutherian lysozyme genes.

  2. Gene therapy for hemophilia.

    PubMed

    Chuah, M K; Evens, H; VandenDriessche, T

    2013-06-01

    Hemophilia A and B are X-linked monogenic disorders resulting from deficiencies of factor VIII and FIX, respectively. Purified clotting factor concentrates are currently intravenously administered to treat hemophilia, but this treatment is non-curative. Therefore, gene-based therapies for hemophilia have been developed to achieve sustained high levels of clotting factor expression to correct the clinical phenotype. Over the past two decades, different types of viral and non-viral gene delivery systems have been explored for hemophilia gene therapy research with a variety of target cells, particularly hepatocytes, hematopoietic stem cells, skeletal muscle cells, and endothelial cells. Lentiviral and adeno-associated virus (AAV)-based vectors are among the most promising vectors for hemophilia gene therapy. In preclinical hemophilia A and B animal models, the bleeding phenotype was corrected with these vectors. Some of these promising preclinical results prompted clinical translation to patients suffering from a severe hemophilic phenotype. These patients receiving gene therapy with AAV vectors showed long-term expression of therapeutic FIX levels, which is a major step forwards in this field. Nevertheless, the levels were insufficient to prevent trauma or injury-induced bleeding episodes. Another challenge that remains is the possible immune destruction of gene-modified cells by effector T cells, which are directed against the AAV vector antigens. It is therefore important to continuously improve the current gene therapy approaches to ultimately establish a real cure for hemophilia.

  3. Fecundity genes in sheep.

    PubMed

    Davis, G H

    2004-07-01

    Since 1980 there has been increasing interest in the identification and utilisation of major genes for prolificacy in sheep. Mutations that increase ovulation rate have been discovered in the BMPR-1B, BMP15 and GDF9 genes, and others are known to exist from the expressed inheritance patterns although the mutations have not yet been located. In the case of BMP15, four different mutations have been discovered but each produces the same phenotype. The modes of inheritance of the different prolificacy genes include autosomal dominant genes with additive effects on ovulation rate (BMPR-1B; Lacaune), autosomal over-dominant genes with infertility in homozygous females (GDF9), X-linked over-dominant genes with infertility in homozygous females (BMP15), and X-linked maternally imprinted genes (FecX2). The size of the effect of one copy of a mutation on ovulation rate ranges from an extra 0.4 ovulations per oestrus for the FecX2 mutation to an extra 1.5 ovulations per oestrus for the BMPR-1B mutation. DNA tests enable some of these mutations to be used in genetic improvement programmes based on marker assisted selection.

  4. Gene therapy for haemophilia.

    PubMed

    Sharma, Akshay; Easow Mathew, Manu; Sriganesh, Vasumathi; Reiss, Ulrike M

    2016-12-20

    Haemophilia is a genetic disorder characterized by spontaneous or provoked, often uncontrolled, bleeding into joints, muscles and other soft tissues. Current methods of treatment are expensive, challenging and involve regular administration of clotting factors. Gene therapy has recently been prompted as a curative treatment modality. This is an update of a published Cochrane Review. To evaluate the safety and efficacy of gene therapy for treating people with haemophilia A or B. We searched the Cochrane Cystic Fibrosis & Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Date of last search: 18 August 2016. Eligible trials include randomised or quasi-randomised clinical trials, including controlled clinical trials comparing gene therapy (with or without standard treatment) with standard treatment (factor replacement) or other 'curative' treatment such as stem cell transplantation for individuals with haemophilia A or B of all ages who do not have inhibitors to factor VIII or IX. No trials of gene therapy for haemophilia were found. No trials of gene therapy for haemophilia were identified. No randomised or quasi-randomised clinical trials of gene therapy for haemophilia were identified. Thus, we are unable to determine the safety and efficacy of gene therapy for haemophilia. Gene therapy for haemophilia is still in its nascent stages and there is a need for well-designed clinical trials to assess the long-term feasibility, success and risks of gene therapy for people with haemophilia.

  5. FlyBase: genes and gene models

    PubMed Central

    Drysdale, Rachel A.; Crosby, Madeline A.

    2005-01-01

    FlyBase (http://flybase.org) is the primary repository of genetic and molecular data of the insect family Drosophilidae. For the most extensively studied species, Drosophila melanogaster, a wide range of data are presented in integrated formats. Data types include mutant phenotypes, molecular characterization of mutant alleles and aberrations, cytological maps, wild-type expression patterns, anatomical images, transgenic constructs and insertions, sequence-level gene models and molecular classification of gene product functions. There is a growing body of data for other Drosophila species; this is expected to increase dramatically over the next year, with the completion of draft-quality genomic sequences of an additional 11 Drosphila species. PMID:15608223

  6. Differentially Coexpressed Disease Gene Identification Based on Gene Coexpression Network.

    PubMed

    Jiang, Xue; Zhang, Han; Quan, Xiongwen

    2016-01-01

    Screening disease-related genes by analyzing gene expression data has become a popular theme. Traditional disease-related gene selection methods always focus on identifying differentially expressed gene between case samples and a control group. These traditional methods may not fully consider the changes of interactions between genes at different cell states and the dynamic processes of gene expression levels during the disease progression. However, in order to understand the mechanism of disease, it is important to explore the dynamic changes of interactions between genes in biological networks at different cell states. In this study, we designed a novel framework to identify disease-related genes and developed a differentially coexpressed disease-related gene identification method based on gene coexpression network (DCGN) to screen differentially coexpressed genes. We firstly constructed phase-specific gene coexpression network using time-series gene expression data and defined the conception of differential coexpression of genes in coexpression network. Then, we designed two metrics to measure the value of gene differential coexpression according to the change of local topological structures between different phase-specific networks. Finally, we conducted meta-analysis of gene differential coexpression based on the rank-product method. Experimental results demonstrated the feasibility and effectiveness of DCGN and the superior performance of DCGN over other popular disease-related gene selection methods through real-world gene expression data sets.

  7. Differentially Coexpressed Disease Gene Identification Based on Gene Coexpression Network

    PubMed Central

    Quan, Xiongwen

    2016-01-01

    Screening disease-related genes by analyzing gene expression data has become a popular theme. Traditional disease-related gene selection methods always focus on identifying differentially expressed gene between case samples and a control group. These traditional methods may not fully consider the changes of interactions between genes at different cell states and the dynamic processes of gene expression levels during the disease progression. However, in order to understand the mechanism of disease, it is important to explore the dynamic changes of interactions between genes in biological networks at different cell states. In this study, we designed a novel framework to identify disease-related genes and developed a differentially coexpressed disease-related gene identification method based on gene coexpression network (DCGN) to screen differentially coexpressed genes. We firstly constructed phase-specific gene coexpression network using time-series gene expression data and defined the conception of differential coexpression of genes in coexpression network. Then, we designed two metrics to measure the value of gene differential coexpression according to the change of local topological structures between different phase-specific networks. Finally, we conducted meta-analysis of gene differential coexpression based on the rank-product method. Experimental results demonstrated the feasibility and effectiveness of DCGN and the superior performance of DCGN over other popular disease-related gene selection methods through real-world gene expression data sets. PMID:28042568

  8. Genes and social behavior.

    PubMed

    Robinson, Gene E; Fernald, Russell D; Clayton, David F

    2008-11-07

    What genes and regulatory sequences contribute to the organization and functioning of neural circuits and molecular pathways in the brain that support social behavior? How does social experience interact with information in the genome to modulate brain activity? Here, we address these questions by highlighting progress that has been made in identifying and understanding two key "vectors of influence" that link genes, the brain, and social behavior: (i) Social information alters gene expression in the brain to influence behavior, and (ii) genetic variation influences brain function and social behavior. We also discuss how evolutionary changes in genomic elements influence social behavior and outline prospects for a systems biology of social behavior.

  9. Mycobacterium tuberculosis DevR/DosR Dormancy Regulator Activation Mechanism: Dispensability of Phosphorylation, Cooperativity and Essentiality of α10 Helix

    PubMed Central

    Sharma, Saurabh; Tyagi, Jaya Sivaswami

    2016-01-01

    DevR/DosR is a well-characterized regulator in Mycobacterium tuberculosis which is implicated in various processes ranging from dormancy/persistence to drug tolerance. DevR induces the expression of an ~48-gene dormancy regulon in response to gaseous stresses, including hypoxia. Strains of the Beijing lineage constitutively express this regulon, which may confer upon them a significant advantage, since they would be ‘pre-adapted’ to the environmental stresses that predominate during infection. Aerobic DevR regulon expression in laboratory-manipulated overexpression strains is also reported. In both instances, the need for an inducing signal is bypassed. While a phosphorylation-mediated conformational change in DevR was proposed as the activation mechanism under hypoxia, the mechanism underlying constitutive expression is not understood. Because DevR is implicated in bacterial dormancy/persistence and is a promising drug target, it is relevant to resolve the mechanistic puzzle of hypoxic activation on one hand and constitutive expression under ‘non-inducing’ conditions on the other. Here, an overexpression strategy was employed to elucidate the DevR activation mechanism. Using a panel of kinase and transcription factor mutants, we establish that DevR, upon overexpression, circumvents DevS/DosT sensor kinase-mediated or small molecule phosphodonor-dependent activation, and also cooperativity-mediated effects, which are key aspects of hypoxic activation mechanism. However, overexpression failed to rescue the defect of C-terminal-truncated DevR lacking the α10 helix, establishing the α10 helix as an indispensable component of DevR activation mechanism. We propose that aerobic overexpression of DevR likely increases the concentration of α10 helix-mediated active dimer species to above the threshold level, as during hypoxia, and enables regulon expression. This advance in the understanding of DevR activation mechanism clarifies a long standing question as to

  10. Mycobacterium tuberculosis DevR/DosR Dormancy Regulator Activation Mechanism: Dispensability of Phosphorylation, Cooperativity and Essentiality of α10 Helix.

    PubMed

    Sharma, Saurabh; Tyagi, Jaya Sivaswami

    2016-01-01

    DevR/DosR is a well-characterized regulator in Mycobacterium tuberculosis which is implicated in various processes ranging from dormancy/persistence to drug tolerance. DevR induces the expression of an ~48-gene dormancy regulon in response to gaseous stresses, including hypoxia. Strains of the Beijing lineage constitutively express this regulon, which may confer upon them a significant advantage, since they would be 'pre-adapted' to the environmental stresses that predominate during infection. Aerobic DevR regulon expression in laboratory-manipulated overexpression strains is also reported. In both instances, the need for an inducing signal is bypassed. While a phosphorylation-mediated conformational change in DevR was proposed as the activation mechanism under hypoxia, the mechanism underlying constitutive expression is not understood. Because DevR is implicated in bacterial dormancy/persistence and is a promising drug target, it is relevant to resolve the mechanistic puzzle of hypoxic activation on one hand and constitutive expression under 'non-inducing' conditions on the other. Here, an overexpression strategy was employed to elucidate the DevR activation mechanism. Using a panel of kinase and transcription factor mutants, we establish that DevR, upon overexpression, circumvents DevS/DosT sensor kinase-mediated or small molecule phosphodonor-dependent activation, and also cooperativity-mediated effects, which are key aspects of hypoxic activation mechanism. However, overexpression failed to rescue the defect of C-terminal-truncated DevR lacking the α10 helix, establishing the α10 helix as an indispensable component of DevR activation mechanism. We propose that aerobic overexpression of DevR likely increases the concentration of α10 helix-mediated active dimer species to above the threshold level, as during hypoxia, and enables regulon expression. This advance in the understanding of DevR activation mechanism clarifies a long standing question as to the

  11. Genes underlying altruism.

    PubMed

    Thompson, Graham J; Hurd, Peter L; Crespi, Bernard J

    2013-01-01

    William D. Hamilton postulated the existence of 'genes underlying altruism', under the rubric of inclusive fitness theory, a half-century ago. Such genes are now poised for discovery. In this article, we develop a set of intuitive criteria for the recognition and analysis of genes for altruism and describe the first candidate genes affecting altruism from social insects and humans. We also provide evidence from a human population for genetically based trade-offs, underlain by oxytocin-system polymorphisms, between alleles for altruism and alleles for non-social cognition. Such trade-offs between self-oriented and altruistic behaviour may influence the evolution of phenotypic diversity across all social animals.

  12. Genes underlying altruism

    PubMed Central

    Thompson, Graham J.; Hurd, Peter L.; Crespi, Bernard J.

    2013-01-01

    William D. Hamilton postulated the existence of ‘genes underlying altruism’, under the rubric of inclusive fitness theory, a half-century ago. Such genes are now poised for discovery. In this article, we develop a set of intuitive criteria for the recognition and analysis of genes for altruism and describe the first candidate genes affecting altruism from social insects and humans. We also provide evidence from a human population for genetically based trade-offs, underlain by oxytocin-system polymorphisms, between alleles for altruism and alleles for non-social cognition. Such trade-offs between self-oriented and altruistic behaviour may influence the evolution of phenotypic diversity across all social animals. PMID:24132092

  13. "Bad genes" & criminal responsibility.

    PubMed

    González-Tapia, María Isabel; Obsuth, Ingrid

    2015-01-01

    The genetics of the accused is trying to break into the courts. To date several candidate genes have been put forward and their links to antisocial behavior have been examined and documented with some consistency. In this paper, we focus on the so called "warrior gene", or the low-activity allele of the MAOA gene, which has been most consistently related to human behavior and specifically to violence and antisocial behavior. In preparing this paper we had two objectives. First, to summarize and analyze the current scientific evidence, in order to gain an in depth understanding of the state of the issue and determine whether a dominant line of generally accepted scientific knowledge in this field can be asserted. Second, to derive conclusions and put forward recommendations related to the use of genetic information, specifically the presence of the low-activity genotype of the MAOA gene, in modulation of criminal responsibility in European and US courts.

  14. Clock genes and sleep.

    PubMed

    Landgraf, Dominic; Shostak, Anton; Oster, Henrik

    2012-01-01

    In most species--from cyanobacteria to humans--endogenous clocks have evolved that drive 24-h rhythms of behavior and physiology. In mammals, these circadian rhythms are regulated by a hierarchical network of cellular oscillators controlled by a set of clock genes organized in a system of interlocked transcriptional feedback loops. One of the most prominent outputs of the circadian system is the synchronization of the sleep-wake cycle with external (day-) time. Clock genes also have a strong impact on many other biological functions, such as memory formation, energy metabolism, and immunity. Remarkably, large overlaps exist between clock gene and sleep (loss) mediated effects on these processes. This review summarizes sleep clock gene interactions for these three phenomena, highlighting potential mediators linking sleep and/or clock function to physiological output in an attempt to better understand the complexity of diurnal adaptation and its consequences for health and disease.

  15. GeneLab

    NASA Technical Reports Server (NTRS)

    Berrios, Daniel C.; Thompson, Terri G.

    2015-01-01

    NASA GeneLab is expected to capture and distribute omics data and experimental and process conditions most relevant to research community in their statistical and theoretical analysis of NASAs omics data.

  16. Cystic fibrosis modifier genes.

    PubMed Central

    Davies, Jane; Alton, Eric; Griesenbach, Uta

    2005-01-01

    Since the recognition that CFTR genotype was not a good predictor of pulmonary disease severity in CF, several candidate modifier genes have been identified. It is unlikely that a single modifier gene will be found, but more probable that several haplotypes in combination may contribute, which in itself presents a major methodological challenge. The aims of such studies are to increase our understanding of disease pathogenesis, to aid prognosis and ultimately to lead to the development of novel treatments. PMID:16025767

  17. Evolutionary Fingerprinting of Genes

    PubMed Central

    Kosakovsky Pond, Sergei L.; Scheffler, Konrad; Gravenor, Michael B.; Poon, Art F.Y.; Frost, Simon D.W.

    2010-01-01

    Over time, natural selection molds every gene into a unique mosaic of sites evolving rapidly or resisting change—an “evolutionary fingerprint” of the gene. Aspects of this evolutionary fingerprint, such as the site-specific ratio of nonsynonymous to synonymous substitution rates (dN/dS), are commonly used to identify genetic features of potential biological interest; however, no framework exists for comparing evolutionary fingerprints between genes. We hypothesize that protein-coding genes with similar protein structure and/or function tend to have similar evolutionary fingerprints and that comparing evolutionary fingerprints can be useful for discovering similarities between genes in a way that is analogous to, but independent of, discovery of similarity via sequence-based comparison tools such as Blast. To test this hypothesis, we develop a novel model of coding sequence evolution that uses a general bivariate discrete parameterization of the evolutionary rates. We show that this approach provides a better fit to the data using a smaller number of parameters than existing models. Next, we use the model to represent evolutionary fingerprints as probability distributions and present a methodology for comparing these distributions in a way that is robust against variations in data set size and divergence. Finally, using sequences of three rapidly evolving RNA viruses (HIV-1, hepatitis C virus, and influenza A virus), we demonstrate that genes within the same functional group tend to have similar evolutionary fingerprints. Our framework provides a sound statistical foundation for efficient inference and comparison of evolutionary rate patterns in arbitrary collections of gene alignments, clustering homologous and nonhomologous genes, and investigation of biological and functional correlates of evolutionary rates. PMID:19864470

  18. Interkingdom gene fusions.

    PubMed

    Wolf, Y I; Kondrashov, A S; Koonin, E V

    2000-01-01

    Genome comparisons have revealed major lateral gene transfer between the three primary kingdoms of life - Bacteria, Archaea, and Eukarya. Another important evolutionary phenomenon involves the evolutionary mobility of protein domains that form versatile multidomain architectures. We were interested in investigating the possibility of a combination of these phenomena, with an invading gene merging with a pre-existing gene in the recipient genome. Complete genomes of fifteen bacteria, four archaea and one eukaryote were searched for interkingdom gene fusions (IKFs); that is, genes coding for proteins that apparently consist of domains originating from different primary kingdoms. Phylogenetic analysis supported 37 cases of IKF, each of which includes a 'native' domain and a horizontally acquired 'alien' domain. IKFs could have evolved via lateral transfer of a gene coding for the alien domain (or a larger protein containing this domain) followed by recombination with a native gene. For several IKFs, this scenario is supported by the presence of a gene coding for a second, stand-alone version of the alien domain in the recipient genome. Among the genomes investigated, the greatest number of IKFs has been detected in Mycobacterium tuberculosis, where they are almost always accompanied by a stand-alone alien domain. For most of the IKF cases detected in other genomes, the stand-alone counterpart is missing. The results of comparative genome analysis show that IKF formation is a real, but relatively rare, evolutionary phenomenon. We hypothesize that IKFs are formed primarily via the proposed two-stage mechanism, but other than in the Actinomycetes, in which IKF generation seems to be an active, ongoing process, most of the stand-alone intermediates have been eliminated, perhaps because of functional redundancy.

  19. Gene therapy for hemophilia.

    PubMed

    Hortelano, G; Chang, P L

    2000-01-01

    Hemophilia A and B are X-linked genetic disorders caused by deficiency of the coagulation factors VIII and IX, respectively. Because of the health hazards and costs of current product replacement therapy, much effort is devoted to the development of gene therapy for these disorders. Approaches to gene therapy for the hemophilias include: ex vivo gene therapy in which cells from the intended recipients are explanted, genetically modified to secrete Factor VIII or IX, and reimplanted into the donor; in vivo gene therapy in which Factor VIII or IX encoding vectors are directly injected into the recipient; and non-autologous gene therapy in which universal cell lines engineered to secrete Factor VIII or IX are enclosed in immuno-protective devices before implantation into recipients. Research into these approaches is aided by the many murine and canine models available. While problems of achieving high and sustained levels of factor delivery, and issues related to efficacy, safety and cost are still to be resolved, progress in gene therapy for the hemophilias has been encouraging and is likely to reach human clinical trial in the foreseeable future.

  20. Gene therapy for newborns.

    PubMed

    Kohn, D B; Parkman, R

    1997-07-01

    Application of gene therapy to treat genetic and infectious diseases may have several advantages if performed in newborns. Because of the minimal adverse effect of the underlying disease on cells of the newborn, the relatively small size of infants, and the large amount of future growth, gene therapy may be more successful in newborns than in older children or adults. The presence of umbilical cord blood from newborns provides a unique and susceptible target for the genetic modification of hematopoietic stem cells. In our first trial of gene therapy in newborns, we inserted a normal adenosine deaminase gene into umbilical cord blood cells of three neonates with a congenital immune deficiency. The trial demonstrated the successful transduction and engraftment of stem cells, which continue to contribute to leukocyte production more than 3 years later. A similar approach may be taken to insert genes that inhibit replication of HIV-1 into umbilical cord blood cells of HIV-1-infected neonates. Many other metabolic and infectious disorders could be treated by gene therapy during the neonatal period if prenatal diagnoses are made and the appropriate technical and regulatory requirements have been met.

  1. Evidence for homosexuality gene

    SciTech Connect

    Pool, R.

    1993-07-16

    A genetic analysis of 40 pairs of homosexual brothers has uncovered a region on the X chromosome that appears to contain a gene or genes for homosexuality. When analyzing the pedigrees of homosexual males, the researcheres found evidence that the trait has a higher likelihood of being passed through maternal genes. This led them to search the X chromosome for genes predisposing to homosexuality. The researchers examined the X chromosomes of pairs of homosexual brothers for regions of DNA that most or all had in common. Of the 40 sets of brothers, 33 shared a set of five markers in the q28 region of the long arm of the X chromosome. The linkage has a LOD score of 4.0, which translates into a 99.5% certainty that there is a gene or genes in this area that predispose males to homosexuality. The chief researcher warns, however, that this one site cannot explain all instances of homosexuality, since there were some cases where the trait seemed to be passed paternally. And even among those brothers where there was no evidence that the trait was passed paternally, seven sets of brothers did not share the Xq28 markers. It seems likely that homosexuality arises from a variety of causes.

  2. GeneClinics

    PubMed Central

    Tarczy-Hornoch, Peter; Shannon, Paul; Baskin, Patty; Espeseth, Miriam; Pagon, Roberta A.

    2000-01-01

    GeneClinics is an online genetic information resource consisting of descriptions of specific inherited disorders (“disease profiles”) as well as information on the role of genetic testing in the diagnosis, management, and genetic counseling of patients with these inherited conditions. GeneClinics is intended to promote the use of genetic services in medical care and personal decision making by providing health care practitioners and patients with information on genetic testing for specific inherited disorders. GeneClinics is implemented as an object-oriented database containing a combination of data and semistructured text that is rendered as HTML for publishing a given “disease profile” on the Web. Content is acquired from authors via templates, converted to an XML document reflecting the underlying database schema (with tagging of embedded data), and then loaded into the database and subjected to peer review. The initial implementation of a production system and the first phase of population of the GeneClinics database content are complete. Further expansion of the content to cover more disease, significant scaling up of rate of content creation, and evaluation redesign are under way. The ultimate goal is to have an entry in GeneClinics for each entry in the GeneTests directory of medical genetics laboratories—that is, for each disease for which clinical genetic testing is available. PMID:10833163

  3. Transposons for gene therapy!

    PubMed

    Ivics, Zoltán; Izsvák, Zsuzsanna

    2006-10-01

    Gene therapy is a promising strategy for the treatment of several inherited and acquired human diseases. Several vector platforms exist for the delivery of therapeutic nucleic acids into cells. Vectors based on viruses are very efficient at introducing gene constructs into cells, but their use has been associated with genotoxic effects of vector integration or immunological complications due to repeated administration in vivo. Non-viral vectors are easier to engineer and manufacture, but their efficient delivery into cells is a major challenge, and the lack of their chromosomal integration precludes long-term therapeutic effects. Transposable elements are non-viral gene delivery vehicles found ubiquitously in nature. Transposon-based vectors have the capacity of stable genomic integration and long-lasting expression of transgene constructs in cells. Molecular reconstruction of Sleeping Beauty, an ancient transposon in fish, represents a cornerstone in applying transposition-mediated gene delivery in vertebrate species, including humans. This review summarizes the state-of-the-art in the application of transposable elements for therapeutic gene transfer, and identifies key targets for the development of transposon-based gene vectors with enhanced efficacy and safety for human applications.

  4. Creating a Global Fiducials Program (GFP) Site: Lago Cachet Dos example in Chile

    NASA Astrophysics Data System (ADS)

    Friesen, B. A.; Nimick, D. A.; Wilson, E. M.

    2012-12-01

    The USGS has been acquiring remotely sensed imagery from all over the world, collecting thousands of images at more than 200 sites, and creating Literal Image Derived Products (LIDPs) as part of the Global Fiducials Program (GFP). The GFP program enables scientists to use these images to study our rapidly changing planet at carefully selected locations around the world. New GFP Sites are created and added each year. Researchers at the University of Alaska, for instance, added areas susceptible to coastal erosion for monitoring the long-term effects of high tides and storms. This presentation will guide you through the process of creating a new GFP site for your area of interest. We will describe the components of the GFP and its archive, the Global Fiducials Library. The Global Fiducials Program—Initial Site Proposal form will be presented and we will show you how to complete each component in order to propose a new site. Lago Cachet Dos, a glacier-dammed lake in southern Chile, is currently being proposed as a new GFP site and will be used as the example for this exercise. In addition, USGS web sites will be used to illustrate how a long-term imagery record can tell a story and to demonstrate viewing and downloading the type of data that will be available online and free of charge through the GFP.

  5. A proposed application of an industrial DOS computer for distribution substation monitoring and control

    SciTech Connect

    Batur, I. . Aselsan Military); Guven, A.N.; Ozay, N. . Electrical Engineering Dept.)

    1994-04-01

    This paper presents the design and implementation of an intelligent controller intended for use in distribution substations to perform monitoring and control duties within the framework of distribution automation needs. The hardware of the developed controller is a DOS based industrial computer running on ECB-BUS. The application software handles all input/output tasks, data collection, manipulation and control decisions with its flexible structure. This embedded controller measures bus voltage, transformer and feeder currents and calculates the real and reactive power, power factor, frequency, and total harmonic distortion of voltage and current. In addition to its local and remote data acquisition and monitoring functions by means of console and SCADA outputs, the system, through its relay outputs, is capable of performing automation tasks such as integrated Volt/Var control, overload and underfrequency detection and load shedding at the substation level. This reliable, high capacity and low cost system is completely programmable so that it can handle new requirements with new configurations easily.

  6. Environmental discrimination among soft-bottom mollusc associations off Lagoa dos Patos, South Brazil

    NASA Astrophysics Data System (ADS)

    Absalão, R. S.

    1991-01-01

    Sublittoral benthic molluscs established in the outlet of Lagoa dos Patos (South Brazil) were sampled with a rectangular dredge and the malacological associations delineated by cluster analysis (WPGA) using the Baroni-Urbani and Buser similarity index. Three main associations were characterized in bands parallel to the beach with relative concordance with specific sedimentological facies. The multiple discriminant analysis showed that there was a high correlation between these associations and the following environmental parameters: depth, average grain size, skewness of the sediment, medium sand, coarse sand, total sand and total mud. The effect of reducing the multidimensionality of the data to two factors, ecologically explained, brings out the importance of depth, average grain size, total sand and total mud. The first appears to be a bathymetric gradient of stability/disturbance; the disturbance from storms becomes less frequent with increasing depth. This is partially supported by the results of the Caswell neutral model, and is in agreement with the intermediate disturbance hypothesis predictions. The second sedimentological factor is the relative percentages of sand and mud in determining the specific composition of these associations.

  7. Endocrine disruptors in water filters used in the Rio dos Sinos Basin region, Southern Brazil.

    PubMed

    Furtado, C M; von Mühlen, C

    2015-05-01

    The activated carbon filter is used in residences as another step in the treatment of drinking water, based on a physical-chemical process to absorb pollutants that are not removed in conventional treatment. Endocrine disruptors (EDCs) are exogenous substances or mixtures of substances that acts on the endocrine system similarly to the endogenously produced hormones, triggering malfunctions and harmful changes to human and animal health. The objective of the present work was to study EDCs through semi-quantitative analysis of residential water filters collected in the region of Rio dos Sinos basin, focusing on two specific classes: hormones and phenols. The solid phase extraction principle was used for the extraction of compounds and gas chromatography coupled with mass spectrometry for the separation and characterization of EDCs. Four samples of residential filters collected from public water distribution and artesian wells, from the cities of Novo Hamburgo and São Leopoldo were analysed. Using the developed methodology, it was possible to detect and comparatively quantify selected EDCs in all studied samples, which indicates the presence of these contaminants in drinking water from different sources.

  8. Urano y sus dos satélites irregulares recientemente descubiertos

    NASA Astrophysics Data System (ADS)

    Parisi, M. G.; Brunini, A.

    Hasta hace poco tiempo, Urano era el único de los Planetas Gigantes que no poseía satélites irregulares. Esto lo diferenciaba del resto de los planetas Gigantes, al igual que la peculiar oblicuidad de su eje de spin. La gran inclinación de su eje de rotación se debe probablemente a una colisión que sufrió el planeta con otro embrión planetario al final del proceso de formación. Esta colisión habría desligado satélites exteriores preexistentes del planeta. Recientemente se han descubierto dos satélites irregulares de Urano, lo que introduce algunas nuevas cotas y condiciones en el escenario de la "Hipótesis de la Gran Colisión" . Los satélites irregulares de Urano tuvieron que ser capturados en una etapa posterior a la del escenario de la Gran Colisión, de no ser así, hubieran sido eyectados del sistema por el impulso impartido con ese gran impacto. En este trabajo, se discuten los posibles mecanismos de captura de los satélites irregulares y se presenta un nuevo posible mecanismo para dicha captura.

  9. Dos and don'ts for using climate information for water resource planning and management

    NASA Astrophysics Data System (ADS)

    Vano, J. A.; Clark, M. P.; Nijssen, B.; Wood, A.; Gutmann, E. D.; Arnold, J.

    2016-12-01

    Increasingly water managers and planners are being required to incorporate climate change information into their planning processes. This is generally seen as a step in the right direction. However, the continuously evolving and expanding realm of climate information can be confusing to use and easy to apply in ways the information producers never intended, and often in ways those producers might say are not viable. Additionally, advice on how various products should be used is not usually straightforward - it may require an extended dialogue between scientists and end users, which is not always feasible with current resources. While rarely is there a one-size fits all approach, there are usually preferable paths forward. To help the water resource planning and management community navigate the ever-changing climate science landscape, we present a set of guidelines for better practices when using climate information. These are divided into two categories: (1) process-based recommendations for developing an effective approach for using climate change scenarios, and (2) product-based cautions for using climate change information. This collection of dos and don'ts provides context on why certain strategies are preferable, including real-world examples. This work is intended to provide a foundation that can be built on through dialogue within and between the climate science and application communities to increase the usefulness of climate information.

  10. Geochemical and isotopic constraints on the tectonic setting of Serra dos Carajas belt, eastern Para, Brazil

    NASA Technical Reports Server (NTRS)

    Olszewski, W. J., Jr.; Gibbs, A. K.; Wirth, K. R.

    1986-01-01

    The lower part of the Serra dos Carajas belt is the metavolcanic and metasedimentary Grao para Group (GPG). The GPG is thought to unconformably overlie the older (but undated) Xingu Complex, composed of medium and high-grade gneisses and amphibolite and greenstone belts. The geochemical data indicate that the GPG has many features in common with ancient and modern volcanic suites erupted through continental crust. The mafic rocks clearly differ from those of most Archean greenstone belts, and modern MORB, IAB, and hot-spot basalts. The geological, geochemical, and isotopic data are all consistent with deposition on continental crust, presumably in a marine basin formed by crustal extension. The isotopic data also suggest the existence of depleted mantle as a source for the parent magmas of the GPG. The overall results suggest a tectonic environment, igneous sources, and petrogenesis similar to many modern continental extensional basins, in contrast to most Archean greenstone belts. The Hammersley basin in Australia and the circum-Superior belts in Canada may be suitable Archean and Proterozoic analogues, respectively.

  11. ANALYSIS OF THE PICO DOS DIAS SURVEY HERBIG Ae/Be CANDIDATES

    SciTech Connect

    Sartori, Marilia J.; Rodrigues, Claudia V.; Batalha, Celso

    2010-01-15

    A large sample of Herbig Ae/Be (HAeBe) candidates, distributed in different Galactic regions south to declination +30 deg., were identified by the Pico dos Dias Survey (a search for young stellar objects based on IRAS colors). Most of the candidates are nearby or associated with star-forming clouds, but several others are considered isolated objects. Aiming to verify the young nature of 93 HAeBe candidates, we searched for additional information that could be useful to confirm if they are pre-main-sequence (PMS) stars or evolved objects, which coincidentally show similar IRAS colors. By adopting a spectral index that is related to the amount of infrared excess and the shape of the spectral energy distribution, we have classified the sample according to three groups, which are analyzed on the basis of (1) circumstellar luminosity; (2) spatial distribution; (3) optical polarization; (4) near-infrared colors; (5) stellar parameters (mass, age, effective temperature); and (5) intensity of emission lines. Our analysis indicates that only 76% of the studied sample, mainly the group with intermediate to low levels of circumstellar emission, can be more confidently considered PMS stars. The nature of the remaining stars, which are in the other group that contains the highest levels of infrared excess, remains to be confirmed. They share the same characteristics of evolved objects, requiring complementary studies in order to correctly classify them. At least seven objects show characteristics typical of post-asymptotic giant branch or proto-planetary nebulae.

  12. 48 CFR 653.219-70 - DOS form DS-1910, Small Business Agency Review-Actions Above the Simplified Acquisition Threshold.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false DOS form DS-1910, Small... 653.219-70 DOS form DS-1910, Small Business Agency Review—Actions Above the Simplified Acquisition Threshold. As prescribed in 619.501(c), DS-1910 is prescribed for use in documenting set-aside decisions. ...

  13. Cross-Reactive Immunity to Mycobacterium tuberculosis DosR Regulon-Encoded Antigens in Individuals Infected with Environmental, Nontuberculous Mycobacteria▿ †

    PubMed Central

    Lin, May Young; Reddy, T. B. K.; Arend, Sandra M.; Friggen, Annemieke H.; Franken, Kees L. M. C.; van Meijgaarden, Krista E.; Verduyn, Marleen J. C.; Schoolnik, Gary K.; Klein, Michel R.; Ottenhoff, Tom H. M.

    2009-01-01

    Mycobacterium tuberculosis DosR regulon-encoded antigens are highly immunogenic in M. tuberculosis-infected humans and are associated with latent tuberculosis infection. We have investigated the hypothesis that infection with or exposure to nontuberculous mycobacteria (NTM) can induce cross-reactive immunity to M. tuberculosis DosR regulon-encoded antigens since responsiveness has been observed in non-M. tuberculosis-exposed but purified protein derivative-responsive individuals. M. tuberculosis DosR regulon-encoded antigen-specific T-cell responses were studied in peripheral blood mononuclear cells (PBMCs) of NTM-infected/exposed individuals. BLASTP was used to determine the presence of M. tuberculosis DosR regulon-encoded protein orthologs among environmental mycobacteria and nonmycobacteria. Significant gamma interferon production was observed in PBMCs from NTM-infected/exposed individuals in response to M. tuberculosis DosR regulon-encoded antigens. DosR regulon-encoded protein orthologs were prominently present in tuberculous and environmental mycobacteria and surprisingly also in nonmycobacteria. The ubiquitous presence of the highly conserved DosR master regulator protein Rv3133c suggests that this is a general adaptive bacterial response regulator. We report a first series of M. tuberculosis antigens to which cross-reactive immunity is induced by NTM infection/exposure. The high conservation of M. tuberculosis DosR regulon-encoded antigens most likely enables them to induce cross-reactive T-cell responses. PMID:19737909

  14. Gene indexing: characterization and analysis of NLM's GeneRIFs.

    PubMed

    Mitchell, Joyce A; Aronson, Alan R; Mork, James G; Folk, Lillian C; Humphrey, Susanne M; Ward, Janice M

    2003-01-01

    We present an initial analysis of the National Library of Medicine's (NLM) Gene Indexing initiative. Gene Indexing occurs at the time of indexing for all 4600 journals and over 500,000 articles added to PubMed/MEDLINE each year. Gene Indexing links articles about the basic biology of a gene or protein within eight model organisms to a specific record in the NLM's LocusLink database of gene products. The result is an entry called a Gene Reference Into Function (GeneRIF) within the LocusLink database. We analyzed the numbers of GeneRIFs produced in the first year of GeneRIF production. 27,645 GeneRIFs were produced, pertaining to 9126 loci over eight model organisms. 60% of these were associated with human genes and 27% with mouse genes. About 80% discuss genes with an established MeSH Heading or other MeSH term. We developed a prototype functional alerting system for researchers based on the GeneRIFs, and a strategy to find all of the literature related to genes. We conclude that the Gene Indexing initiative adds considerable value to the life sciences research community.

  15. Harnessing gene expression networks to prioritize candidate epileptic encephalopathy genes.

    PubMed

    Oliver, Karen L; Lukic, Vesna; Thorne, Natalie P; Berkovic, Samuel F; Scheffer, Ingrid E; Bahlo, Melanie

    2014-01-01

    We apply a novel gene expression network analysis to a cohort of 182 recently reported candidate Epileptic Encephalopathy genes to identify those most likely to be true Epileptic Encephalopathy genes. These candidate genes were identified as having single variants of likely pathogenic significance discovered in a large-scale massively parallel sequencing study. Candidate Epileptic Encephalopathy genes were prioritized according to their co-expression with 29 known Epileptic Encephalopathy genes. We utilized developing brain and adult brain gene expression data from the Allen Human Brain Atlas (AHBA) and compared this to data from Celsius: a large, heterogeneous gene expression data warehouse. We show replicable prioritization results using these three independent gene expression resources, two of which are brain-specific, with small sample size, and the third derived from a heterogeneous collection of tissues with large sample size. Of the nineteen genes that we predicted with the highest likelihood to be true Epileptic Encephalopathy genes, two (GNAO1 and GRIN2B) have recently been independently reported and confirmed. We compare our results to those produced by an established in silico prioritization approach called Endeavour, and finally present gene expression networks for the known and candidate Epileptic Encephalopathy genes. This highlights sub-networks of gene expression, particularly in the network derived from the adult AHBA gene expression dataset. These networks give clues to the likely biological interactions between Epileptic Encephalopathy genes, potentially highlighting underlying mechanisms and avenues for therapeutic targets.

  16. 5. OVERHEAD VIEW OF GENE CAMP LOOKING SOUTH. GENE PUMP ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. OVERHEAD VIEW OF GENE CAMP LOOKING SOUTH. GENE PUMP PLANT IS AT CENTER WITH ADMINISTRATIVE COMPLEX IN FOREGROUND AND RESIDENTIAL AREA BEYOND PLANT. - Gene Pump Plant, South of Gene Wash Reservoir, 2 miles west of Whitsett Pump Plant, Parker Dam, San Bernardino County, CA

  17. Harnessing Gene Expression Networks to Prioritize Candidate Epileptic Encephalopathy Genes

    PubMed Central

    Oliver, Karen L.; Lukic, Vesna; Thorne, Natalie P.; Berkovic, Samuel F.; Scheffer, Ingrid E.; Bahlo, Melanie

    2014-01-01

    We apply a novel gene expression network analysis to a cohort of 182 recently reported candidate Epileptic Encephalopathy genes to identify those most likely to be true Epileptic Encephalopathy genes. These candidate genes were identified as having single variants of likely pathogenic significance discovered in a large-scale massively parallel sequencing study. Candidate Epileptic Encephalopathy genes were prioritized according to their co-expression with 29 known Epileptic Encephalopathy genes. We utilized developing brain and adult brain gene expression data from the Allen Human Brain Atlas (AHBA) and compared this to data from Celsius: a large, heterogeneous gene expression data warehouse. We show replicable prioritization results using these three independent gene expression resources, two of which are brain-specific, with small sample size, and the third derived from a heterogeneous collection of tissues with large sample size. Of the nineteen genes that we predicted with the highest likelihood to be true Epileptic Encephalopathy genes, two (GNAO1 and GRIN2B) have recently been independently reported and confirmed. We compare our results to those produced by an established in silico prioritization approach called Endeavour, and finally present gene expression networks for the known and candidate Epileptic Encephalopathy genes. This highlights sub-networks of gene expression, particularly in the network derived from the adult AHBA gene expression dataset. These networks give clues to the likely biological interactions between Epileptic Encephalopathy genes, potentially highlighting underlying mechanisms and avenues for therapeutic targets. PMID:25014031

  18. Hox genes and study of Hox genes in crustacean

    NASA Astrophysics Data System (ADS)

    Hou, Lin; Chen, Zhijuan; Xu, Mingyu; Lin, Shengguo; Wang, Lu

    2004-12-01

    Homeobox genes have been discovered in many species. These genes are known to play a major role in specifying regional identity along the anterior-posterior axis of animals from a wide range of phyla. The products of the homeotic genes are a set of evolutionarily conserved transcription factors that control elaborate developmental processes and specify cell fates in metazoans. Crustacean, presenting a variety of body plans not encountered in any other class or phylum of the Metazoa, has been shown to possess a single set of homologous Hox genes like insect. The ancestral crustacean Hox gene complex comprised ten genes: eight homologous to the hometic Hox genes and two related to nonhomeotic genes presented within the insect Hox complexes. The crustacean in particular exhibits an abundant diversity segment specialization and tagmosis. This morphological diversity relates to the Hox genes. In crustacean body plan, different Hox genes control different segments and tagmosis.

  19. Classification of genes based on gene expression analysis

    SciTech Connect

    Angelova, M. Myers, C. Faith, J.

    2008-05-15

    Systems biology and bioinformatics are now major fields for productive research. DNA microarrays and other array technologies and genome sequencing have advanced to the point that it is now possible to monitor gene expression on a genomic scale. Gene expression analysis is discussed and some important clustering techniques are considered. The patterns identified in the data suggest similarities in the gene behavior, which provides useful information for the gene functionalities. We discuss measures for investigating the homogeneity of gene expression data in order to optimize the clustering process. We contribute to the knowledge of functional roles and regulation of E. coli genes by proposing a classification of these genes based on consistently correlated genes in expression data and similarities of gene expression patterns. A new visualization tool for targeted projection pursuit and dimensionality reduction of gene expression data is demonstrated.

  20. GeneCards Version 3: the human gene integrator.

    PubMed

    Safran, Marilyn; Dalah, Irina; Alexander, Justin; Rosen, Naomi; Iny Stein, Tsippi; Shmoish, Michael; Nativ, Noam; Bahir, Iris; Doniger, Tirza; Krug, Hagit; Sirota-Madi, Alexandra; Olender, Tsviya; Golan, Yaron; Stelzer, Gil; Harel, Arye; Lancet, Doron

    2010-08-05

    GeneCards (www.genecards.org) is a comprehensive, authoritative compendium of annotative information about human genes, widely used for nearly 15 years. Its gene-centric content is automatically mined and integrated from over 80 digital sources, resulting in a web-based deep-linked card for each of >73,000 human gene entries, encompassing the following categories: protein coding, pseudogene, RNA gene, genetic locus, cluster and uncategorized. We now introduce GeneCards Version 3, featuring a speedy and sophisticated search engine and a revamped, technologically enabling infrastructure, catering to the expanding needs of biomedical researchers. A key focus is on gene-set analyses, which leverage GeneCards' unique wealth of combinatorial annotations. These include the GeneALaCart batch query facility, which tabulates user-selected annotations for multiple genes and GeneDecks, which identifies similar genes with shared annotations, and finds set-shared annotations by descriptor enrichment analysis. Such set-centric features address a host of applications, including microarray data analysis, cross-database annotation mapping and gene-disorder associations for drug targeting. We highlight the new Version 3 database architecture, its multi-faceted search engine, and its semi-automated quality assurance system. Data enhancements include an expanded visualization of gene expression patterns in normal and cancer tissues, an integrated alternative splicing pattern display, and augmented multi-source SNPs and pathways sections. GeneCards now provides direct links to gene-related research reagents such as antibodies, recombinant proteins, DNA clones and inhibitory RNAs and features gene-related drugs and compounds lists. We also portray the GeneCards Inferred Functionality Score annotation landscape tool for scoring a gene's functional information status. Finally, we delineate examples of applications and collaborations that have benefited from the GeneCards suite. Database

  1. Neighboring Genes Show Correlated Evolution in Gene Expression.

    PubMed

    Ghanbarian, Avazeh T; Hurst, Laurence D

    2015-07-01

    When considering the evolution of a gene's expression profile, we commonly assume that this is unaffected by its genomic neighborhood. This is, however, in contrast to what we know about the lack of autonomy between neighboring genes in gene expression profiles in extant taxa. Indeed, in all eukaryotic genomes genes of similar expression-profile tend to cluster, reflecting chromatin level dynamics. Does it follow that if a gene increases expression in a particular lineage then the genomic neighbors will also increase in their expression or is gene expression evolution autonomous? To address this here we consider evolution of human gene expression since the human-chimp common ancestor, allowing for both variation in estimation of current expression level and error in Bayesian estimation of the ancestral state. We find that in all tissues and both sexes, the change in gene expression of a focal gene on average predicts the change in gene expression of neighbors. The effect is highly pronounced in the immediate vicinity (<100 kb) but extends much further. Sex-specific expression change is also genomically clustered. As genes increasing their expression in humans tend to avoid nuclear lamina domains and be enriched for the gene activator 5-hydroxymethylcytosine, we conclude that, most probably owing to chromatin level control of gene expression, a change in gene expression of one gene likely affects the expression evolution of neighbors, what we term expression piggybacking, an analog of hitchhiking.

  2. Hox genes and evolution.

    PubMed

    Hrycaj, Steven M; Wellik, Deneen M

    2016-01-01

    Hox proteins are a deeply conserved group of transcription factors originally defined for their critical roles in governing segmental identity along the antero-posterior (AP) axis in Drosophila. Over the last 30 years, numerous data generated in evolutionarily diverse taxa have clearly shown that changes in the expression patterns of these genes are closely associated with the regionalization of the AP axis, suggesting that Hox genes have played a critical role in the evolution of novel body plans within Bilateria. Despite this deep functional conservation and the importance of these genes in AP patterning, key questions remain regarding many aspects of Hox biology. In this commentary, we highlight recent reports that have provided novel insight into the origins of the mammalian Hox cluster, the role of Hox genes in the generation of a limbless body plan, and a novel putative mechanism in which Hox genes may encode specificity along the AP axis. Although the data discussed here offer a fresh perspective, it is clear that there is still much to learn about Hox biology and the roles it has played in the evolution of the Bilaterian body plan.

  3. Engineered Gene Circuits

    NASA Astrophysics Data System (ADS)

    Hasty, Jeff

    2003-03-01

    Uncovering the structure and function of gene regulatory networks has become one of the central challenges of the post-genomic era. Theoretical models of protein-DNA feedback loops and gene regulatory networks have long been proposed, and recently, certain qualitative features of such models have been experimentally corroborated. This talk will focus on model and experimental results that demonstrate how a naturally occurring gene network can be used as a ``parts list'' for synthetic network design. The model formulation leads to computational and analytical approaches relevant to nonlinear dynamics and statistical physics, and the utility of such a formulation will be demonstrated through the consideration of specific design criteria for several novel genetic devices. Fluctuations originating from small molecule-number effects will be discussed in the context of model predictions, and the experimental validation of these stochastic effects underscores the importance of internal noise in gene expression. Potential biotech applications will be highlighted within the framework of cellular control schemes. Specifically, the coupling of an oscillating cellular process to a synthetic oscillator will be considered, and the resulting model behavior will be analyzed in the context of synchronization. The underlying methodology highlights the utility of engineering-based methods in the design of synthetic gene regulatory networks.

  4. Selenoprotein Gene Nomenclature.

    PubMed

    Gladyshev, Vadim N; Arnér, Elias S; Berry, Marla J; Brigelius-Flohé, Regina; Bruford, Elspeth A; Burk, Raymond F; Carlson, Bradley A; Castellano, Sergi; Chavatte, Laurent; Conrad, Marcus; Copeland, Paul R; Diamond, Alan M; Driscoll, Donna M; Ferreiro, Ana; Flohé, Leopold; Green, Fiona R; Guigó, Roderic; Handy, Diane E; Hatfield, Dolph L; Hesketh, John; Hoffmann, Peter R; Holmgren, Arne; Hondal, Robert J; Howard, Michael T; Huang, Kaixun; Kim, Hwa-Young; Kim, Ick Young; Köhrle, Josef; Krol, Alain; Kryukov, Gregory V; Lee, Byeong Jae; Lee, Byung Cheon; Lei, Xin Gen; Liu, Qiong; Lescure, Alain; Lobanov, Alexei V; Loscalzo, Joseph; Maiorino, Matilde; Mariotti, Marco; Sandeep Prabhu, K; Rayman, Margaret P; Rozovsky, Sharon; Salinas, Gustavo; Schmidt, Edward E; Schomburg, Lutz; Schweizer, Ulrich; Simonović, Miljan; Sunde, Roger A; Tsuji, Petra A; Tweedie, Susan; Ursini, Fulvio; Whanger, Philip D; Zhang, Yan

    2016-11-11

    The human genome contains 25 genes coding for selenocysteine-containing proteins (selenoproteins). These proteins are involved in a variety of functions, most notably redox homeostasis. Selenoprotein enzymes with known functions are designated according to these functions: TXNRD1, TXNRD2, and TXNRD3 (thioredoxin reductases), GPX1, GPX2, GPX3, GPX4, and GPX6 (glutathione peroxidases), DIO1, DIO2, and DIO3 (iodothyronine deiodinases), MSRB1 (methionine sulfoxide reductase B1), and SEPHS2 (selenophosphate synthetase 2). Selenoproteins without known functions have traditionally been denoted by SEL or SEP symbols. However, these symbols are sometimes ambiguous and conflict with the approved nomenclature for several other genes. Therefore, there is a need to implement a rational and coherent nomenclature system for selenoprotein-encoding genes. Our solution is to use the root symbol SELENO followed by a letter. This nomenclature applies to SELENOF (selenoprotein F, the 15-kDa selenoprotein, SEP15), SELENOH (selenoprotein H, SELH, C11orf31), SELENOI (selenoprotein I, SELI, EPT1), SELENOK (selenoprotein K, SELK), SELENOM (selenoprotein M, SELM), SELENON (selenoprotein N, SEPN1, SELN), SELENOO (selenoprotein O, SELO), SELENOP (selenoprotein P, SeP, SEPP1, SELP), SELENOS (selenoprotein S, SELS, SEPS1, VIMP), SELENOT (selenoprotein T, SELT), SELENOV (selenoprotein V, SELV), and SELENOW (selenoprotein W, SELW, SEPW1). This system, approved by the HUGO Gene Nomenclature Committee, also resolves conflicting, missing, and ambiguous designations for selenoprotein genes and is applicable to selenoproteins across vertebrates.

  5. On sports and genes.

    PubMed

    Zilberman-Schapira, Gili; Chen, Jieming; Gerstein, Mark

    2012-12-01

    Our genes influence our athletic ability. However, the causal genetic factors and mechanisms, and the extent of their effects, remain largely elusive. Many studies investigate this association between specific genes and athletic performance. Such studies have increased in number over the past few years, as recent developments and patents in DNA sequencing have made large amounts of sequencing data available for such analysis. In this paper, we consider four of the most intensively studied genes in relation to athletic ability: angiotensin I-converting enzyme, alpha-actinin 3, peroxismose proliferator-activator receptor alpha and nitric oxide synthase 3. We investigate the connection between genotype and athletic phenotype in the context of these four genes in various sport fields and across different ethnicities and genders. We do an extensive literature survey on these genes and the polymorphisms (single nucleotide polymorphisms or indels) found to be associated with athletic performance. We also present, for each of these polymorphisms, the allele frequencies in the different ethnicities reported in the pilot phase of the 1000 Genomes Project - arguably the largest human genome-sequencing endeavor to date. We discuss the considerable success, and significant drawbacks, of past research along these lines, and propose interesting directions for future research.

  6. Gene therapy for hemophilia.

    PubMed

    Ponder, Katherine P

    2006-09-01

    This review will highlight the progress achieved in the past 2 years on using gene therapy to treat hemophilia in animals and humans. There has been substantial progress in using gene therapy to treat animals with hemophilia. Novel approaches for hemophilia A in mice include expression of Factor VIII in blood cells or platelets derived from ex-vivo transduced hematopoietic stem cells, or in-vivo transfer of transposons expressing Factor VIII into endothelial cells or hepatocytes. Advances in large-animal models include the demonstration that neonatal administration of a retroviral vector expressing canine Factor VIII completely corrected hemophilia A in dogs, and that double-stranded adeno-associated virus vectors resulted in expression of Factor IX that is 28-fold that obtained using single-stranded adeno-associated virus vectors. In humans, one hemophilia B patient achieved 10% of normal activity after liver-directed gene therapy with a single-stranded adeno-associated virus vector expressing human Factor IX. Expression fell at 1 month, however, which was likely due to an immune response to the modified cells. Gene therapy has been successful in a patient with hemophilia B, but expression was unstable due to an immune response. Abrogating immune responses is the next major hurdle for achieving long-lasting gene therapy.

  7. The gene ontology categorizer.

    PubMed

    Joslyn, Cliff A; Mniszewski, Susan M; Fulmer, Andy; Heaton, Gary

    2004-08-04

    The Gene Ontology Categorizer, developed jointly by the Los Alamos National Laboratory and Procter & Gamble Corp., provides a capability for the categorization task in the Gene Ontology (GO): given a list of genes of interest, what are the best nodes of the GO to summarize or categorize that list? The motivating question is from a drug discovery process, where after some gene expression analysis experiment, we wish to understand the overall effect of some cell treatment or condition by identifying 'where' in the GO the differentially expressed genes fall: 'clustered' together in one place? in two places? uniformly spread throughout the GO? 'high', or 'low'? In order to address this need, we view bio-ontologies more as combinatorially structured databases than facilities for logical inference, and draw on the discrete mathematics of finite partially ordered sets (posets) to develop data representation and algorithms appropriate for the GO. In doing so, we have laid the foundations for a general set of methods to address not just the categorization task, but also other tasks (e.g. distances in ontologies and ontology merger and exchange) in both the GO and other bio-ontologies (such as the Enzyme Commission database or the MEdical Subject Headings) cast as hierarchically structured taxonomic knowledge systems.

  8. Hox genes and evolution

    PubMed Central

    Hrycaj, Steven M.; Wellik, Deneen M.

    2016-01-01

    Hox proteins are a deeply conserved group of transcription factors originally defined for their critical roles in governing segmental identity along the antero-posterior (AP) axis in Drosophila. Over the last 30 years, numerous data generated in evolutionarily diverse taxa have clearly shown that changes in the expression patterns of these genes are closely associated with the regionalization of the AP axis, suggesting that Hox genes have played a critical role in the evolution of novel body plans within Bilateria. Despite this deep functional conservation and the importance of these genes in AP patterning, key questions remain regarding many aspects of Hox biology. In this commentary, we highlight recent reports that have provided novel insight into the origins of the mammalian Hox cluster, the role of Hox genes in the generation of a limbless body plan, and a novel putative mechanism in which Hox genes may encode specificity along the AP axis. Although the data discussed here offer a fresh perspective, it is clear that there is still much to learn about Hox biology and the roles it has played in the evolution of the Bilaterian body plan. PMID:27239281

  9. [Gene studies and nobel prize].

    PubMed

    Guo, Jun-Ming; Xiao, Bing-Xiu

    2005-01-01

    Gene is a DNA sequence which can be expressed and produces gene products (protein or RNA). By 2003, there are 51 Nobel Prize owners related to gene studies. Among them, 44 persons are in physiology or medicine (account for 24.72% of total 178), 7 persons are in chemistry (account for 5.69% of total 123). The paper reviews them in following 6 aspects: Drosophlie melanogaster is a good material for gene study; the double helix model of DNA structure provides a hard foundation in gene study; the studies on gene regulation illuminate many functions of gene; genetic central dogma researches created 11 Noble Prize laureates; gene engineering technologies make possible to modify and use genes; and the thorough studies of gene characteristic made us easier to understand many life phenomena.

  10. Lessons Learned from Sleep Education in Schools: A Review of Dos and Don'ts

    PubMed Central

    Blunden, Sarah; Rigney, Gabrielle

    2015-01-01

    Study Objectives: Sleep duration and quality are associated with negative neuropsychological and psychosocial outcomes in children and adolescents. However, community awareness of this is low and sleep education programs in schools are attempting to address this issue. Several studies now exist assessing the efficacy of these sleep education programs for improving sleep knowledge, sleep hygiene and sleep patterns. This paper presents these sleep education programs, most particularly, it presents the strengths and weaknesses of the current available studies in the hope that this can identify areas where future sleep education programs can improve. Methods: A systematic search of all school-based sleep education studies in adolescents was undertaken. Studies were scrutinized for author, teacher and participant comment regarding strengths and limitations of each study, which were then extracted and summarized. Results: Two specific types of sleep education programs emerged from the review, those that sought to change sleep behavior and those that sought simply to disseminate information. Issues that dictated the strength or weakness of a particular study including who delivers the program, the theoretical basis, the tools utilized to measure sleep patterns, the content, and their capacity to engage students were assessed. Sleep education was considered important by teachers, students and parents alike. Conclusions: Future sleep education programs need to take into account lessons learned from previous sleep education efforts in order to maximize the potential for sleep education programs to improve the sleep health of our young people. Commentary: A commentary on this article appears in this issue on page 595. Citation: Blunden S, Rigney G. Lessons learned from sleep education in schools: a review of dos and don'ts. J Clin Sleep Med 2015;11(6):671–680. PMID:25766709

  11. Las dos cosas: an analysis of attitudes of latina women on non-exclusive breastfeeding.

    PubMed

    Bartick, Melissa; Reyes, Catherine

    2012-02-01

    Non-exclusive breastfeeding among Latina women is commonly seen in the newborn period. The reasons behind las dos cosas ("both things") are not well understood but have included the beliefs that formula has vitamins and that adding formula will result in a chubbier baby, which is desirable. Many previous studies involved Mexican and Puerto Rican women living in the mainland United States. We performed detailed semistructured interviews with 17 Latina mothers in late pregnancy or the newborn period at a community hospital and an affiliated clinic in Massachusetts, serving a large Dominican population. Women were asked about their beliefs about breastfeeding, colostrum, and infant formula. Transcripts were analyzed using Nvivo 9 software (QSR International Pty. Ltd., Melbourne, Australia) to identify the frequencies of common trends. The most common reasons for introducing formula were treatment for insufficient milk, to keep the baby fuller longer, and planning for return to work. None of the women understood the potential risks of introducing formula on the establishment of breastfeeding, particularly on milk supply. Many thought that even limited amounts of breastfeeding were sufficient to produce a healthier child, failing to understand a negative dose-response effect of formula on health and milk production. While every woman saw breastfeeding as healthier, only one saw formula as unhealthy, an important distinction. None of the women expressed familiarity with medical recommendations around breastfeeding duration or exclusivity, with many believing that breastmilk alone would be insufficient to satisfy the hunger or nutritional needs of a growing child after as little as 3 months. Women consistently demonstrated a willingness to learn from health professionals. In counseling Latina women, it may be important to discuss the risks of formula to infant health, breastfeeding, and milk supply and to include the medical recommendations for breastfeeding exclusivity

  12. GeneCards Version 3: the human gene integrator

    PubMed Central

    Safran, Marilyn; Dalah, Irina; Alexander, Justin; Rosen, Naomi; Iny Stein, Tsippi; Shmoish, Michael; Nativ, Noam; Bahir, Iris; Doniger, Tirza; Krug, Hagit; Sirota-Madi, Alexandra; Olender, Tsviya; Golan, Yaron; Stelzer, Gil; Harel, Arye; Lancet, Doron

    2010-01-01

    GeneCards (www.genecards.org) is a comprehensive, authoritative compendium of annotative information about human genes, widely used for nearly 15 years. Its gene-centric content is automatically mined and integrated from over 80 digital sources, resulting in a web-based deep-linked card for each of >73 000 human gene entries, encompassing the following categories: protein coding, pseudogene, RNA gene, genetic locus, cluster and uncategorized. We now introduce GeneCards Version 3, featuring a speedy and sophisticated search engine and a revamped, technologically enabling infrastructure, catering to the expanding needs of biomedical researchers. A key focus is on gene-set analyses, which leverage GeneCards’ unique wealth of combinatorial annotations. These include the GeneALaCart batch query facility, which tabulates user-selected annotations for multiple genes and GeneDecks, which identifies similar genes with shared annotations, and finds set-shared annotations by descriptor enrichment analysis. Such set-centric features address a host of applications, including microarray data analysis, cross-database annotation mapping and gene-disorder associations for drug targeting. We highlight the new Version 3 database architecture, its multi-faceted search engine, and its semi-automated quality assurance system. Data enhancements include an expanded visualization of gene expression patterns in normal and cancer tissues, an integrated alternative splicing pattern display, and augmented multi-source SNPs and pathways sections. GeneCards now provides direct links to gene-related research reagents such as antibodies, recombinant proteins, DNA clones and inhibitory RNAs and features gene-related drugs and compounds lists. We also portray the GeneCards Inferred Functionality Score annotation landscape tool for scoring a gene’s functional information status. Finally, we delineate examples of applications and collaborations that have benefited from the GeneCards suite

  13. FunGene: the functional gene pipeline and repository

    PubMed Central

    Fish, Jordan A.; Chai, Benli; Wang, Qiong; Sun, Yanni; Brown, C. Titus; Tiedje, James M.; Cole, James R.

    2013-01-01

    Ribosomal RNA genes have become the standard molecular markers for microbial community analysis for good reasons, including universal occurrence in cellular organisms, availability of large databases, and ease of rRNA gene region amplification and analysis. As markers, however, rRNA genes have some significant limitations. The rRNA genes are often present in multiple copies, unlike most protein-coding genes. The slow rate of change in rRNA genes means that multiple species sometimes share identical 16S rRNA gene sequences, while many more species share identical sequences in the short 16S rRNA regions commonly analyzed. In addition, the genes involved in many important processes are not distributed in a phylogenetically coherent manner, potentially due to gene loss or horizontal gene transfer. While rRNA genes remain the most commonly used markers, key genes in ecologically important pathways, e.g., those involved in carbon and nitrogen cycling, can provide important insights into community composition and function not obtainable through rRNA analysis. However, working with ecofunctional gene data requires some tools beyond those required for rRNA analysis. To address this, our Functional Gene Pipeline and Repository (FunGene; http://fungene.cme.msu.edu/) offers databases of many common ecofunctional genes and proteins, as well as integrated tools that allow researchers to browse these collections and choose subsets for further analysis, build phylogenetic trees, test primers and probes for coverage, and download aligned sequences. Additional FunGene tools are specialized to process coding gene amplicon data. For example, FrameBot produces frameshift-corrected protein and DNA sequences from raw reads while finding the most closely related protein reference sequence. These tools can help provide better insight into microbial communities by directly studying key genes involved in important ecological processes. PMID:24101916

  14. Gene therapy prospects--intranasal delivery of therapeutic genes.

    PubMed

    Podolska, Karolina; Stachurska, Anna; Hajdukiewicz, Karolina; Małecki, Maciej

    2012-01-01

    Gene therapy is recognized to be a novel method for the treatment of various disorders. Gene therapy strategies involve gene manipulation on broad biological processes responsible for the spreading of diseases. Cancer, monogenic diseases, vascular and infectious diseases are the main targets of gene therapy. In order to obtain valuable experimental and clinical results, sufficient gene transfer methods are required. Therapeutic genes can be administered into target tissues via gene carriers commonly defined as vectors. The retroviral, adenoviral and adeno-associated virus based vectors are most frequently used in the clinic. So far, gene preparations may be administered directly into target organs or by intravenous, intramuscular, intratumor or intranasal injections. It is common knowledge that the number of gene therapy clinical trials has rapidly increased. However, some limitations such as transfection efficiency and stable and long-term gene expression are still not resolved. Consequently, great effort is focused on the evaluation of new strategies of gene delivery. There are many expectations associated with intranasal delivery of gene preparations for the treatment of diseases. Intranasal delivery of therapeutic genes is regarded as one of the most promising forms of pulmonary gene therapy research. Gene therapy based on inhalation of gene preparations offers an alternative way for the treatment of patients suffering from such lung diseases as cystic fibrosis, alpha-1-antitrypsin defect, or cancer. Experimental and first clinical trials based on plasmid vectors or recombinant viruses have revealed that gene preparations can effectively deliver therapeutic or marker genes to the cells of the respiratory tract. The noninvasive intranasal delivery of gene preparations or conventional drugs seems to be very encouraging, although basic scientific research still has to continue.

  15. Down-weighting overlapping genes improves gene set analysis.

    PubMed

    Tarca, Adi Laurentiu; Draghici, Sorin; Bhatti, Gaurav; Romero, Roberto

    2012-06-19

    The identification of gene sets that are significantly impacted in a given condition based on microarray data is a crucial step in current life science research. Most gene set analysis methods treat genes equally, regardless how specific they are to a given gene set. In this work we propose a new gene set analysis method that computes a gene set score as the mean of absolute values of weighted moderated gene t-scores. The gene weights are designed to emphasize the genes appearing in few gene sets, versus genes that appear in many gene sets. We demonstrate the usefulness of the method when analyzing gene sets that correspond to the KEGG pathways, and hence we called our method Pathway Analysis with Down-weighting of Overlapping Genes (PADOG). Unlike most gene set analysis methods which are validated through the analysis of 2-3 data sets followed by a human interpretation of the results, the validation employed here uses 24 different data sets and a completely objective assessment scheme that makes minimal assumptions and eliminates the need for possibly biased human assessments of the analysis results. PADOG significantly improves gene set ranking and boosts sensitivity of analysis using information already available in the gene expression profiles and the collection of gene sets to be analyzed. The advantages of PADOG over other existing approache