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Sample records for dos genes il1b

  1. Interleukin 1B gene (IL1B) variation and internalizing symptoms in maltreated preschoolers.

    PubMed

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

    2014-11-01

    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 interleukin 1B gene (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 and the Diagnostic Infant and Preschool Assessment. Maltreated children had higher major depressive disorder (MDD) and posttraumatic stress disorder symptoms and marginally higher internalizing symptoms on the Child Behavior Checklist. Controlling for age, sex, and race, IL1B genotype was associated with MDD symptoms (p = .002). Contextual stressors were significantly associated with MDD and posttraumatic stress disorder 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

  2. IL1B gene polymorphisms influence the course and severity of inflammatory bowel disease.

    PubMed

    Nemetz, A; Nosti-Escanilla, M P; Molnár, T; Köpe, A; Kovács, A; Fehér, J; Tulassay, Z; Nagy, F; García-González, M A; Peña, A S

    1999-06-01

    There is evidence of a disbalance in the inflammatory regulation of patients with inflammatory bowel diseases (IBD). Interleukin-1 beta plays an important role in the pro-inflammatory response. Our aim was to study the influence which IL1B gene polymorphisms may have on the severity and course of these diseases. Ninety-six patients with ulcerative colitis (UC), 98 patients with Crohn's disease (CD), and 132 ethnically matched healty individuals (HC) were typed for the polymorphic sites in the promoter region (position -511) and in exon 5 (position +3953) of the IL1B gene, using polymerase chain reaction (PCR)-based methods. In the CD group a significant association (P = 0.009) was found in this pair of genes. Homozygotes for allele 1 at position +3953 were more often present (69% vs 31%) in the subgroup of patients carrying at least one copy of allele 2 at position -511. This association was significant in patients with non-perforating disease (P = 0.002), but was not present in patients with perforating-fistulizing disease. The distribution of both allelic pairs in the non-fistulizing group proved to be significantly different from HC (P < 0.05), UC (P < 0.03), and the fistulizing group (P < 0.05). There was a similar association in non-operated patients (P = 0.024), whereas no such association was found in surgically treated patients. Among carriers of allele 2 at position -511, UC patients with more severe bleeding symptoms (P = 0.006) were less frequently found. These results suggest that IL1B gene polymorphisms participate in determining the course and severity of inflammatory bowel disease and contribute to explain the heterogeneity of these diseases.

  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. Analysis of IL-1α(−889) and IL-1B(+3953) Gene Polymorphism in Syrian Patients with Aggressive Periodontitis: A Pilot Study

    PubMed Central

    Shibani, Kenan; Shhab, Reem; Khattab, Razan

    2011-01-01

    Polymorphisms in IL-1 gene have been suggested to influence transcription of IL-1α and IL-1B and thereby the pathophysiology of periodontitis. Using genotyping IL-1 test, a pilot study was conducted on 32 Syrian patients with aggressive periodontitis (AgP) and 35 healthy controls to investigate the association between the IL-1α(−889), IL-1B(+3953) gene polymorphisms and AgP among schoolchildren. The results revealed a similar distribution of genotypes between patients and controls, and did not support an association between IL-1 gene polymorphisms and AgP, however, the association was significant in male patients only. To determine and confirm any susceptible or resistant genes for AgP, future studies should use many target genes and well-defined related periodontal outcomes. PMID:22203911

  5. 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

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

    2007-07-01

    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 for IL1B gene induction. A double point mutation at a putative STAT binding site, which overlaps this composite Spi-1 x 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/EBP beta was activated at an adjacent C/EBP beta 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-Stat1 Y701F. 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 x IRF8 x 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

  6. 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.

  7. 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. PMID:26481614

  8. 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

  9. Association of IL1A and IL1B loci with primary open angle glaucoma

    PubMed Central

    2010-01-01

    Background Recent studies suggest that glaucoma is a neurodegenerative disease in which secondary degenerative losses occur after primary insult by raised Intraocular pressure (IOP) or by other associated factors. It has been reported that polymorphisms in the IL1A and IL1B genes are associated with Primary Open Angle Glaucoma (POAG). The purpose of our study was to investigate the role of these polymorphisms in eastern Indian POAG patients. Methods The study involved 315 unrelated POAG patients, consisting of 116 High Tension Glaucoma (HTG) patients with intra ocular pressure (IOP) > 21 mmHg and 199 non-HTG patients (presenting IOP < 20 mmHg), and 301 healthy controls from eastern India. Genotypes were determined by polymerase chain reaction and restriction digestion for three single nucleotide polymorphisms (SNPs): IL1A (-889C/T; rs1800587), IL1B (-511C/T; rs16944) and IL1B (3953C/T; rs1143634). Haplotype frequency was determined by Haploview 4.1 software. The association of individual SNPs and major haplotypes was evaluated using chi-square statistics. The p-value was corrected for multiple tests by Bonferroni method. Results No significant difference was observed in the allele and genotype frequencies for IL1A and IL1B SNPs between total pool of POAG patients and controls. However, on segregating the patient pool to HTG and non-HTG groups, weak association was observed for IL1A polymorphism (-889C/T) where -889C allele was found to portray risk (OR = 1.380; 95% CI = 1.041-1.830; p = 0.025) for non-HTG patients. Similarly, 3953T allele of IL1B polymorphism (+3953C/T) was observed to confer risk to HTG group (OR = 1.561; 95% CI = 1.022-2.385; p = 0.039). On haplotype analysis it was observed that TTC was significantly underrepresented in non-HTG patients (OR = 0.538; 95% CI = 0.356- 0.815; p = 0.003) while TCT haplotype was overrepresented in HTG patients (OR = 1.784; 95% CI = 1.084- 2.937; p = 0.022) compared to control pool. However, after correction for

  10. IL1B genetic variation and plasma C-reactive protein level among young adults: The CARDIA study

    PubMed Central

    Enquobahrie, Daniel A.; Rice, Kenneth; Williams, O. Dale; Williams, Michelle A.; Gross, Myron D.; Lewis, Cora E.; Schwartz, Stephen M.; Siscovick, David S.

    2010-01-01

    Objective Interleukin-1B (IL1B) modulates C-reactive protein (CRP) expression. However, whether IL1B genetic variation is associated with CRP level is unknown. Further, obesity, a state of low-grade inflammation that influences cellular IL-1 functions may modify this association. Methods and results Study participants (N = 3289), 48% blacks and 52% whites, had CRP level measurements at year 7 and year 15 examinations as part of the CARDIA study. Ten tag single nucleotide polymorphisms (SNPs) that characterize common IL1B gene variation were genotyped. In SNP analysis, no significant associations with either level or change in time CRP were observed after multiple testing adjustments. However, global ILIB gene variation was associated with year 7 to year 15 change in CRP (global nominal p = 0.004, multiple testing corrected p = 0.048) among obese blacks. Compared to the commonest haplotype, a common haplotype that includes the SNP rs1143642 was associated with greater increases in CRP from year 7 to year 15 among obese blacks and whites while another common haplotype that includes the SNP rs3917356 was associated with decreased change in CRP from year 7 to year 15 among obese blacks. The rare alleles of ILIB SNPs, SNP 7114 (rs1143642) and SNP 3298 (rs3917356), were associated with greater increases and decreases in CRP from year 7 to year 15 among blacks, respectively, compared to their common variants. Conclusion IL1B genetic variation may have a role in CRP level regulation and this association may be modified by obesity. PMID:18573495

  11. 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

  12. Interaction of IL1B and IL1RN polymorphisms, smoking habit, gender, and ethnicity with aggressive and chronic periodontitis susceptibility

    PubMed Central

    Ribeiro, Magali Silveira Monteiro; Pacheco, Renata Botelho Antunes; Fischer, Ricardo Guimarães; Macedo, Jacyara Maria Brito

    2016-01-01

    Background: Although the interleukin-1 (IL-1) plays a critical role in the pathogenesis of periodontitis, associations between IL1 gene cluster polymorphisms and the disease remains unclear. Aims: To investigate the importance of IL1B-511C>T (rs16944), IL1B +3954C>T (rs1143634), and IL1RN intron 2 variable number tandem repeat (VNTR) (rs2234663) polymorphisms, individually or in combination, as the risk factors of periodontitis in a Southeastern Brazilian population with a high degree of miscegenation. Subjects and Methods: A total of 145 individuals, with aggressive (aggressive periodontitis [AgP], n = 43) and chronic (chronic periodontitis [CP], n = 52) periodontitis, and controls (n = 50) were genotyped by polymerase chain reaction (PCR) (IL1RN intron 2 VNTR) or PCR-restriction fragment length polymorphism (PCR-RFLP) (IL1B-511 C>T and IL1B + 3954C>T) techniques. Statistical Analysis: The independent t-test, Chi-square, and Fisher's exact tests were used. The SNPStats program was used for haplotype estimation and multiplicative interaction analyses. Results: The IL1B +3954T allele represented risk for CP (odds ratio [OR] = 2.84), particularly in smokers (OR = 4.43) and females (OR = 6.00). The minor alleles IL1RN*2 and *3 increased the risk of AgP (OR = 2.18), especially the IL1RN*2*2 genotype among  white Brazilians (OR = 7.80). Individuals with the combinations of the IL1B + 3954T and IL1RN*2 or *3-containing genotypes were at increased risk of developing CP (OR = 4.50). Considering the three polymorphisms (rs16944, rs1143634, and rs2234663), the haplotypes TC2 and CT1 represented risk for AgP (OR = 3.41) and CP (OR = 6.39), respectively. Conclusions: Our data suggest that the IL1B +3954C>T and IL1RN intron 2 VNTR polymorphisms are potential candidates for genetic biomarkers of periodontitis, particularly in specific groups of individuals. PMID:27630500

  13. Interaction of IL1B and IL1RN polymorphisms, smoking habit, gender, and ethnicity with aggressive and chronic periodontitis susceptibility

    PubMed Central

    Ribeiro, Magali Silveira Monteiro; Pacheco, Renata Botelho Antunes; Fischer, Ricardo Guimarães; Macedo, Jacyara Maria Brito

    2016-01-01

    Background: Although the interleukin-1 (IL-1) plays a critical role in the pathogenesis of periodontitis, associations between IL1 gene cluster polymorphisms and the disease remains unclear. Aims: To investigate the importance of IL1B-511C>T (rs16944), IL1B +3954C>T (rs1143634), and IL1RN intron 2 variable number tandem repeat (VNTR) (rs2234663) polymorphisms, individually or in combination, as the risk factors of periodontitis in a Southeastern Brazilian population with a high degree of miscegenation. Subjects and Methods: A total of 145 individuals, with aggressive (aggressive periodontitis [AgP], n = 43) and chronic (chronic periodontitis [CP], n = 52) periodontitis, and controls (n = 50) were genotyped by polymerase chain reaction (PCR) (IL1RN intron 2 VNTR) or PCR-restriction fragment length polymorphism (PCR-RFLP) (IL1B-511 C>T and IL1B + 3954C>T) techniques. Statistical Analysis: The independent t-test, Chi-square, and Fisher's exact tests were used. The SNPStats program was used for haplotype estimation and multiplicative interaction analyses. Results: The IL1B +3954T allele represented risk for CP (odds ratio [OR] = 2.84), particularly in smokers (OR = 4.43) and females (OR = 6.00). The minor alleles IL1RN*2 and *3 increased the risk of AgP (OR = 2.18), especially the IL1RN*2*2 genotype among  white Brazilians (OR = 7.80). Individuals with the combinations of the IL1B + 3954T and IL1RN*2 or *3-containing genotypes were at increased risk of developing CP (OR = 4.50). Considering the three polymorphisms (rs16944, rs1143634, and rs2234663), the haplotypes TC2 and CT1 represented risk for AgP (OR = 3.41) and CP (OR = 6.39), respectively. Conclusions: Our data suggest that the IL1B +3954C>T and IL1RN intron 2 VNTR polymorphisms are potential candidates for genetic biomarkers of periodontitis, particularly in specific groups of individuals.

  14. 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. PMID:22414649

  15. 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

  16. 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.

  17. Single nucleotide polymorphism in IL1B is associated with infection risk in paediatric acute myeloid leukaemia.

    PubMed

    Sung, L; Dix, D; Cellot, S; Gillmeister, B; Ethier, M C; Roslin, N M; Johnston, D L; Feusner, J; Mitchell, D; Lewis, V; Aplenc, R; Yanofsky, R; Portwine, C; Price, V; Zelcer, S; Silva, M; Bowes, L; Michon, B; Stobart, K; Traubici, J; Allen, U; Beyene, J; den Hollander, N; Paterson, A D

    2016-06-01

    We evaluated single nucleotide polymorphisms (SNPs) associated with infection risk in children with newly diagnosed acute myeloid leukaemia (AML). We conducted a multicentre, prospective cohort study that included children aged ≤18 years with de novo AML. DNA was isolated from blood lymphocytes or buccal swabs, and candidate gene SNP analysis was conducted. Primary outcome was the occurrence of microbiologically documented sterile site infection during chemotherapy. Secondary outcomes were Gram-positive and -negative infections, viridans group streptococcal infection and proven/probable invasive fungal infection. Interpretation was guided by consistency in risk alleles and microbiologic agent with previous literature. Over the study period 254 children and adolescents with AML were enrolled. Overall, 190 (74.8%) had at least one sterile site microbiologically documented infection. Among the 172 with inferred European ancestry and DNA available, nine significant associations were observed; two were consistent with previous literature. Allele A at IL1B (rs16944) was associated with decreased microbiologically documented infection, and allele G at IL10 (rs1800896) was associated with increased risk of Gram-positive infection. We identified SNPs associated with infection risk in paediatric AML. Genotype may provide insight into mechanisms of infection risk that could be used for supportive-care novel treatments.

  18. 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

  19. IL6 and IL1B polymorphisms are associated with fat mass in older men: the MrOS Study Sweden.

    PubMed

    Strandberg, Louise; Mellström, Dan; Ljunggren, Osten; Grundberg, Elin; Karlsson, Magnus K; Holmberg, Anna H; Orwoll, Eric S; Eriksson, Anna L; Svedberg, Johan; Bengtsson, Magnus; Ohlsson, Claes; Jansson, John-Olov

    2008-03-01

    There is growing evidence that immune functions are linked to the regulation of body fat. Our studies of knockout mice indicate that both endogenous interleukin (IL)-6 and IL-1 can suppress mature-onset obesity. We now investigated whether four common polymorphisms of the IL6 and IL1 systems are associated with the fat mass measured with dual-energy X-ray absorptiometry (DXA) in elderly men (n = 3,014). The study subjects were from the Swedish part of the MrOS multicenter population study and 69-81 years of age. The IL6 -174 G>C (Minor allele frequency (MAF) = 48%) gene promoter polymorphism was associated with the primary outcome total fat mass (P = 0.006) and regional fat masses, but not with lean body mass. The IL1B -31T>C (MAF = 34%) polymorphism was also associated with total fat (P = 0.007) and regional fat masses, but not lean body mass. The IL-1 receptor antagonist (IL-1ra) gene (IL1RN) +2018 T>C (MAF = 27%) polymorphism (in linkage disequilibrium (LD) with a well-studied variable number tandem repeat of 86 base pair (bp)) and IL1B +3953 C>T (MAF = 26%) polymorphism were not associated with total fat mass. In conclusion, the IL-1 and IL-6 systems, shown to suppress mature-onset obesity in experimental animals, contain gene polymorphisms that are associated with fat, but not lean, mass in elderly men.

  20. The effect of interleukin-1 allele 2 genotype (IL-1a(-889) and IL-1b(+3954)) on the individual's susceptibility to peri-implantitis: case-control study.

    PubMed

    Hamdy, Ahmed Abd El-Meguid Mostafa; Ebrahem, Mohamed Abd El-Moniem

    2011-06-01

    Individuals bearing the combination of interleukin (IL)-1 allele 2 at IL-1A(-889) and IL-1B(+3954) are referred to as being genotype positive and are susceptible to increased periodontal tissue destruction. The aim of this study was to assess the possible association of IL-1 allele 2 (IL-1A(-889) and IL-B(+3954)) genotypes with the severity of peri-implantitis progression and the effect of this combination on treatment outcomes. Fifty patients with International Team for Implantology implants were studied; patients ranged in age from 35-55 years, and each patient had 1 implant. According to peri-implant tissue status, patients were divided into 2 groups: group I consisted of 25 patients with peri-implantitis, and group II comprised 25 patients with healthy peri-implant tissue. Clinical parameters were assessed at baseline and after 3 and 6 months. Epithelial cells were collected from the oral mucosa by plastic spatula and were used for IL-1 genotyping by the polymerase chain reaction technique. Group I patients were subjected to a peri-implantitis treatment and maintenance program. In all, 17 patients from group I and 5 patients from group II were genotype positive, with a statistically significant difference noted between the 2 groups. Group I genotype-positive patients presented with higher scores and measurements of clinical parameters with increased suppuration from peri-implant tissues compared with group II; differences were statistically significant (P < .05). In terms of response to treatment, genotype-negative patients demonstrated better response than genotype-positive patients. The combination of IL-1 allele 2 (IL-1A(-889) and IL-1B(+3954)) in patients with inflamed periodontal or peri-implant tissues acts as a risk factor that leads to greater tissue destruction. IL-1 gene polymorphism at IL-1A(-889) and IL-1B(+3954) may affect outcomes of treatment for peri-implantitis in genotype-positive individuals. PMID:20594066

  1. 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

  2. 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

  3. DOS.

    ERIC Educational Resources Information Center

    Traven, Bill

    1988-01-01

    Discusses using the DOS PATH command (for MS-DOS) to enable the microcomputer user to move from directory to directory on a hard drive. Lists the commands to be programed, gives examples, and explains the use of each. (MVL)

  4. Role of IL1A rs1800587, IL1B rs1143627 and IL1RN rs2234677 Genotype Regarding Development of Chronic Lumbar Radicular Pain; a Prospective One-Year Study

    PubMed Central

    Moen, Aurora; Schistad, Elina Iordanova; Rygh, Lars Jørgen; Røe, Cecilie; Gjerstad, Johannes

    2014-01-01

    Previous studies indicate that lumbar radicular pain following disc herniation may be associated with release of several pro-inflammatory mediators, including interleukin-1 (IL1). In the present study, we examined how genetic variability in IL1A (rs1800587 C>T), IL1B (rs1143627 T>C) and IL1RN (rs2234677 G>A) influenced the clinical outcome the first year after disc herniation. Patients (n = 258) with lumbar radicular pain due to disc herniation were recruited from two hospitals in Norway. Pain and disability were measured by visual analogue scale (VAS) and Oswestry Disability Index (ODI) over a 12 month period. The result showed that patients with the IL1A T allele, in combination with the IL1RN A allele had more pain and a slower recovery than other patients (VAS p = 0.049, ODI p = 0.059 rmANOVA; VAS p = 0.003, ODI p = 0.050 one-way ANOVA at 12 months). However, regarding the IL1B/IL1RN genotype, no clear effect on recovery was observed (VAS p = 0.175, ODI p = 0.055 rmANOVA; VAS p = 0.105, ODI p = 0.214 one-way ANOVA at 12 months). The data suggest that the IL1A T/IL1RN A genotype, but not the IL1B T/IL1RN A genotype, may increase the risk of a chronic outcome in patients following disc herniation. PMID:25207923

  5. 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.

  6. Association of interleukin-1A, interleukin-1B and interleukin-1 receptor antagonist gene polymorphisms with multiple myeloma.

    PubMed

    Abazis-Stamboulieh, Danai; Oikonomou, Pagona; Papadoulis, Nikolaos; Panayiotidis, Panayiotis; Vrakidou, Efimia; Tsezou, Aspasia

    2007-11-01

    Interleukin-1 (IL-1) is a cytokine involved in the maturation and proliferation of B cells and plays a significant role in the development of lytic bone lesions, a major clinical feature of multiple myeloma (MM) patients. Genes that regulate products involved in the immune system are highly polymorphic and contribute to inter-individual differences that can influence the genetic predisposition and progression of particular diseases and cancers. In this study, we investigated the correlation between the single nucleotide polymorphisms IL1A -889, IL1B -511, IL1B +3954, IL1RN Mspa1 +11100 and susceptibility to MM in 74 patients and 160 controls. We found that individuals possessing IL1A -889 CT polymorphism had a higher risk in developing MM. Moreover, genotypes IL1B -511 CC, IL1B +3954 CC, IL-1RN Mspa1 +11100 CC and the combination of IL1B +3954 CC with IL1B -511 CC or IL-1RN Mspa1 +11100 CC exerted a protective effect in individuals possessing them.

  7. 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

  8. 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

  9. Genetic polymorphisms of the interleukin-1 gene and early marginal bone loss around endosseous dental implants.

    PubMed

    Shimpuku, Hitomi; Nosaka, Yasuhiro; Kawamura, Tatsuya; Tachi, Yoichi; Shinohara, Mitsuko; Ohura, Kiyoshi

    2003-08-01

    Dental implant surgery commonly proceeds in two stages. It is generally accepted that bone loss around implants does not occur at stage-II surgery because implants do not receive mechanical loading. However, early marginal bone loss around implants occasionally does occur during the healing period. Genetic polymorphisms in the interleukin-1 (IL-1) gene have been reported to be important for bone homeostasis and susceptibility to bone disease. We therefore investigated whether the idiopathic early marginal bone loss around implants is related to polymorphisms in the IL-1 gene. We performed a case-control study. Patients demonstrating marginal bone loss around implants at stage-II surgery were designated as the 'marginal bone loss (+)' group and those without bone loss as the 'marginal bone loss (-)' group. Polymorphisms of the IL-1alpha and IL-1beta genes (IL-1A-889, IL-1B-511 and IL-1B+3954) were detected by restriction fragment length polymorphism using NcoI, AvaI and TaqI after polymerase chain reactions. A total of 251 implants were placed in 39 patients. Marginal bone loss was observed in 36 implants. The patients with IL-1B-511 2/2 genotype exhibited a significantly higher occurrence of marginal bone loss than those with IL-1B-511 1/1 or 1/2 genotypes (OR=5.63; 95% CI=1.20-26.42; P=0.033). Multiple logistic regression analyses showed a markedly increased odds ratio (OR=10.86; 95% CI=1.64-71.90) in IL-1B-511 2/2 genotype carriers, while ORs of the other risk factors for bone loss, such as age, smoking status, post-menopausal women and bone quality, remained between 0.44 and 6.20. There was no significant difference in the distributions of the IL-1B+3954 and IL-1 A-889 genotypes between cases and controls. These data suggest that the IL-1B-511 2/2 genotype has a significant association with the incidence of early marginal bone loss around endosseous implants. PMID:12869004

  10. Interleukin-1 gene cluster variants in hemodialysis patients with end stage renal disease: An association and meta-analysis

    PubMed Central

    Tripathi, G.; Rangaswamy, D.; Borkar, M.; Prasad, N.; Sharma, R. K.; Sankhwar, S. N.; Agrawal, S.

    2015-01-01

    We evaluated whether polymorphisms in interleukin (IL-1) gene cluster (IL-1 alpha [IL-1A], IL-1 beta [IL-1B], and IL-1 receptor antagonist [IL-1RN]) are associated with end stage renal disease (ESRD). A total of 258 ESRD patients and 569 ethnicity matched controls were examined for IL-1 gene cluster. These were genotyped for five single-nucleotide gene polymorphisms in the IL-1A, IL-1B and IL-1RN genes and a variable number of tandem repeats (VNTR) in the IL-1RN. The IL-1B − 3953 and IL-1RN + 8006 polymorphism frequencies were significantly different between the two groups. At IL-1B, the T allele of − 3953C/T was increased among ESRD (P = 0.0001). A logistic regression model demonstrated that two repeat (240 base pair [bp]) of the IL-1Ra VNTR polymorphism was associated with ESRD (P = 0.0001). The C/C/C/C/C/1 haplotype was more prevalent in ESRD = 0.007). No linkage disequilibrium (LD) was observed between six loci of IL-1 gene. We further conducted a meta-analysis of existing studies and found that there is a strong association of IL-1 RN VNTR 86 bp repeat polymorphism with susceptibility to ESRD (odds ratio = 2.04, 95% confidence interval = 1.48-2.82; P = 0.000). IL-1B − 5887, +8006 and the IL-1RN VNTR polymorphisms have been implicated as potential risk factors for ESRD. The meta-analysis showed a strong association of IL-1RN 86 bp VNTR polymorphism with susceptibility to ESRD. PMID:25684870

  11. Interleukin-1 gene cluster variants in hemodialysis patients with end stage renal disease: An association and meta-analysis.

    PubMed

    Tripathi, G; Rangaswamy, D; Borkar, M; Prasad, N; Sharma, R K; Sankhwar, S N; Agrawal, S

    2015-01-01

    We evaluated whether polymorphisms in interleukin (IL-1) gene cluster (IL-1 alpha [IL-1A], IL-1 beta [IL-1B], and IL-1 receptor antagonist [IL-1RN]) are associated with end stage renal disease (ESRD). A total of 258 ESRD patients and 569 ethnicity matched controls were examined for IL-1 gene cluster. These were genotyped for five single-nucleotide gene polymorphisms in the IL-1A, IL-1B and IL-1RN genes and a variable number of tandem repeats (VNTR) in the IL-1RN. The IL-1B - 3953 and IL-1RN + 8006 polymorphism frequencies were significantly different between the two groups. At IL-1B, the T allele of - 3953C/T was increased among ESRD (P = 0.0001). A logistic regression model demonstrated that two repeat (240 base pair [bp]) of the IL-1Ra VNTR polymorphism was associated with ESRD (P = 0.0001). The C/C/C/C/C/1 haplotype was more prevalent in ESRD = 0.007). No linkage disequilibrium (LD) was observed between six loci of IL-1 gene. We further conducted a meta-analysis of existing studies and found that there is a strong association of IL-1 RN VNTR 86 bp repeat polymorphism with susceptibility to ESRD (odds ratio = 2.04, 95% confidence interval = 1.48-2.82; P = 0.000). IL-1B - 5887, +8006 and the IL-1RN VNTR polymorphisms have been implicated as potential risk factors for ESRD. The meta-analysis showed a strong association of IL-1RN 86 bp VNTR polymorphism with susceptibility to ESRD.

  12. Roles for the mitogen-activated protein kinase (MAPK) phosphatase, DUSP1, in feedback control of inflammatory gene expression and repression by dexamethasone.

    PubMed

    Shah, Suharsh; King, Elizabeth M; Chandrasekhar, Ambika; Newton, Robert

    2014-05-01

    Glucocorticoids act on the glucocorticoid receptor (NR3C1) to repress inflammatory gene expression. This is central to their anti-inflammatory effectiveness and rational improvements in therapeutic index depend on understanding the mechanism. Human pulmonary epithelial A549 cells were used to study the role of the mitogen-activated protein kinase (MAPK) phosphatase, dual-specificity phosphatase 1 (DUSP1), in the dexamethasone repression of 11 inflammatory genes induced, in a MAPK-dependent manner, by interleukin-1β (IL1B). Adenoviral over-expression of DUSP1 inactivated MAPK pathways and reduced expression of all 11 inflammatory genes. IL1B rapidly induced DUSP1 expression and RNA silencing revealed a transient role in feedback inhibition of MAPKs and inflammatory gene expression. With dexamethasone, which induced DUSP1 expression, plus IL1B (co-treatment), DUSP1 expression was further enhanced. At 1 h, this was responsible for the dexamethasone inhibition of IL1B-induced MAPK activation and CXCL1 and CXCL2 mRNA expression, with a similar trend for CSF2. Whereas, CCL20 mRNA was not repressed by dexamethasone at 1 h, repression of CCL2, CXCL3, IL6, and IL8 was unaffected, and PTGS2 repression was partially affected by DUSP1 knockdown. At later times, dexamethasone repression of MAPKs was unaffected by DUSP1 silencing. Likewise, 6 h post-IL1B, dexamethasone repression of all 11 mRNAs was essentially unaffected by DUSP1 knockdown. Qualitatively similar data were obtained for CSF2, CXCL1, IL6, and IL8 release. Thus, despite general roles in feedback inhibition, DUSP1 plays a transient, often partial, role in the dexamethasone-dependent repression of certain inflammatory genes. Therefore this also illustrates key roles for DUSP1-independent effectors in mediating glucocorticoid-dependent repression. PMID:24692548

  13. DOS basics

    SciTech Connect

    O`Connor, P.

    1994-09-01

    DOS is an acronym for Disk Operating System. It is actually a set of programs that allows you to control your personal computer. DOS offers the capabilities to create and manage files; organize and maintain information placed on disks; use application programs such as WordPerfect, Lotus 123, Excel, Windows, etc. In addition, DOS provides the basic utilities needed to copy files from one area to another, delete files and list files. The latest version of DOS also offers more advanced features that include hard disk compression and memory management. Basic DOS commands are discussed.

  14. [The role of cytokine gene polymorphisms in the development of hypertrophy of the tonsils of the lymphoid pharyngeal ring and atopic march in the children].

    PubMed

    Shabaldina, E V; Shabaldin, A V; Riazantsev, S V; Simbirtsev, S V

    2013-01-01

    Interleukin 1-beta (IL-1b), its endogenous receptor antagonist (IL-1 Ra), and interleukin IL-4 have been shown to play a role in immunopathological processes, such as the development of hypertrophy of the tonsils of the lymphoid pharyngeal ring and atopic march. However, the influence of Il-1 and IL-4 gene polymorphisms as etiological factors of this pathology remains obscure. The objective of the present work was to study characteristics of gene polymorphisms of proinflammatory and proallergic cytokines depending on the degree of hypertrophy of the tonsils of the lymphoid pharyngeal ring (LPR) and atopic march to selected species of the opportunistic pathogenic biota. Polymorphisms of the following genes were investigated in the children, residents of the Kemerovo region, presenting with hypertrophic tonsils of LPR: IL-1b+3953 (C->T), IL4 (70 bp VNTR), and IL-1Ra (86 bp VNTR). IL-1b, IL-1Ra, and IL-4 genotypes were determined by PCR of autosomal DNAs obtained from 129 children presenting with hypertrophic tonsils and 41 healthy children with the use of conventional genetic-statistical methods. Odds ratios (ORs) were estimated by the logistic regression models for each locus and after adjusting polymorphisms for the neighbouring loci. The 2R, 2R, Il-1Ra and T, T IL-1b genotypes occurred more frequently in the patients with isolated adenoid vegetations (20.93% and 25.58% respectively) than in the healthy children (4.95%) (OR=3.78, p=0.049; OR=3.25, p=0.047). The results of this study indicate that IL-1b and IL-1Ra gene polymorphisms play a role in the development of clinically significant features in the lymphoid pharyngeal ring.

  15. Association of interleukin-1 gene variations with moderate to severe chronic periodontitis in multiple ethnicities

    PubMed Central

    Wu, X; Offenbacher, S; Lόpez, N J; Chen, D; Wang, H-Y; Rogus, J; Zhou, J; Beck, J; Jiang, S; Bao, X; Wilkins, L; Doucette-Stamm, L; Kornman, K

    2015-01-01

    Background and Objective Genetic markers associated with disease are often non-functional and generally tag one or more functional “causative” variants in linkage disequilibrium. Markers may not show tight linkage to the causative variants across multiple ethnicities due to evolutionary divergence, and therefore may not be informative across different population groups. Validated markers of disease suggest causative variants exist in the gene and, if the causative variants can be identified, it is reasonable to hypothesize that such variants will be informative across diverse populations. The aim of this study was to test that hypothesis using functional Interleukin-1 (IL-1) gene variations across multiple ethnic populations to replace the non-functional markers originally associated with chronic adult periodontitis in Caucasians. Material and Methods Adult chronic periodontitis cases and controls from four ethnic groups (Caucasians, African Americans, Hispanics and Asians) were recruited in the USA, Chile and China. Genotypes of IL1B gene single nucleotide polymorphisms (SNPs), including three functional SNPs (rs16944, rs1143623, rs4848306) in the promoter and one intronic SNP (rs1143633), were determined using a single base extension method or TaqMan 5′ nuclease assay. Logistic regression and other statistical analyses were used to examine the association between moderate to severe periodontitis and IL1B gene variations, including SNPs, haplotypes and composite genotypes. Genotype patterns associated with disease in the discovery study were then evaluated in independent validation studies. Results Significant associations were identified in the discovery study, consisting of Caucasians and African Americans, between moderate to severe adult chronic periodontitis and functional variations in the IL1B gene, including a pattern of four IL1B SNPs (OR = 1.87, p < 0.0001). The association between the disease and this IL1B composite genotype pattern was validated

  16. 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

  17. C-reactive protein levels and common polymorphisms of the interleukin-1 gene cluster and interleukin-6 gene in patients with coronary heart disease.

    PubMed

    Latkovskis, G; Licis, N; Kalnins, U

    2004-10-01

    C-reactive protein (CRP) is an inflammatory marker associated with increased cardiovascular risk. Production of CRP is regulated by interleukin (IL)-1beta, IL-1 receptor antagonist and IL-6. In 160 patients with coronary heart disease (CHD) confirmed by angiography, we examined the relationship between CRP level and five polymorphisms in genes coding for these cytokines: IL-1B(-511), IL-1B(+3954), a variable number tandem repeat (VNTR) polymorphism in intron 2 of IL-1RN [IL-1RN(VNTR)], IL-6(-174) and IL-6(-572). CRP values were logarithmically normalized (log-CRP) for statistical calculations. In univariate analysis, carrier status for the IL-1B(+3954)T allele and IL-1RN(VNTR) allele 2 [IL-1RN(VNTR)*2] correlated with higher (P < 0.01) and lower (P < 0.05) log-CRP values, respectively. Among the potential confounding factors analysed, smoking, body mass index, total cholesterol (P < 0.05 for all) and diabetes (P = 0.056) were positively correlated with CRP level. After adjustment for non-genetic covariates, CRP levels remained significantly (P < 0.01) higher in carriers of IL-1B(+3954)T than in non-carriers: mean log-CRP (with 95% confidence interval) was 0.443 (0.311-0.574) for CT or TT genotypes compared with 0.240 (0.107-0.373) for the CC genotype, which corresponded to back-transformed CRP levels of 2.77 and 1.74 mg l(-1), respectively. Adjusted association was also significant for IL-1RN(VNTR)*2 (P < 0.01), with lower CRP levels in the presence of allele 2: the mean log-CRP value was 0.252 (0.115-0.388) for carriers and 0.421 (0.290-0.552) for non-carriers (CRP 1.79 and 2.64 mg l(-1), respectively). When alleles of both polymorphisms were entered into the model simultaneously, the association remained significant for IL-1B(+3954)T (P < 0.05), but not for IL-1RN(VNTR)*2. We conclude that IL-1B(+3954)T is associated with higher CRP levels in patients with CHD, and we found that this association was significant after adjustment for major risk factors. Our data

  18. Mycobacterium tuberculosis DosR Regulon Gene Rv0079 Encodes a Putative, ‘Dormancy Associated Translation Inhibitor (DATIN)’

    PubMed Central

    Kumar, Ashutosh; Majid, Mohammad; Kunisch, Ralph; Rani, Pittu Sandhya; Qureshi, Insaf A.; Lewin, Astrid; Hasnain, Seyed E.; Ahmed, Niyaz

    2012-01-01

    Mycobacterium tuberculosis is a major human pathogen that has evolved survival mechanisms to persist in an immune-competent host under a dormant condition. The regulation of M. tuberculosis metabolism during latent infection is not clearly known. The dormancy survival regulon (DosR regulon) is chiefly responsible for encoding dormancy related functions of M. tuberculosis. We describe functional characterization of an important gene of DosR regulon, Rv0079, which appears to be involved in the regulation of translation through the interaction of its product with bacterial ribosomal subunits. The protein encoded by Rv0079, possibly, has an inhibitory role with respect to protein synthesis, as revealed by our experiments. We performed computational modelling and docking simulation studies involving the protein encoded by Rv0079 followed by in vitro translation and growth curve analysis experiments, involving recombinant E. coli and Bacille Calmette Guérin (BCG) strains that overexpressed Rv0079. Our observations concerning the interaction of the protein with the ribosomes are supportive of its role in regulation/inhibition of translation. We propose that the protein encoded by locus Rv0079 is a ‘dormancy associated translation inhibitor’ or DATIN. PMID:22719925

  19. 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. PMID:24670917

  20. 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

  1. Variants in the interleukin-1 alpha and beta genes, and the risk for periodontal disease in dogs.

    PubMed

    Albuquerque, C; Morinha, F; Magalhães, J; Requicha, J; Dias, I; Guedes-Pinto, H; Bastos, E; Viegas, C

    2015-12-01

    Elevated levels of interleukin-1 (IL-1) have been shown to amplify the inflammatory response against periodontopathogenic bacteria.In humans,polymorphisms in the IL1A and IL1B genes are the most well-studied genetic polymorphisms associated with periodontal disease (PD). In contrast to human, there is a lack of knowledge on the genetic basis of canine PD. A case-control study was conducted in which a molecular analysis of dog IL1A and IL1B genes was performed. Of the eight genetic variants identified, seven in IL1A gene and one in IL1B gene, IL1A/1_g.388A>C and IL1A /1_g.521T>A showed statistically significant differences between groups (adjusted OR (95% CI): 0.15 (0.03-0.76),P=0.022; 5.76 (1.03-32.1),P=0.046, respectively). It suggests that in the studied population the IL1A/1_g.388C allele is associated with a decreased PD risk, whereas the IL1A/1_g.521A allele can confer an increased risk. Additionally, the IL1A/2_g.515G>T variation resulted in a change of amino acid, i.e. glycine to valine. In silico analysis suggests that this change can alter protein structure and function, predicting it to be deleterious or damaging. This work suggests that IL1 genetic variants may be important in PD susceptibility in canines.

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

    PubMed Central

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

    2015-01-01

    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. PMID:25619315

  3. Peripheral blood gene expression profile of atherosclerotic coronary artery disease in patients of different ethnicity in Malaysia.

    PubMed

    Abdullah, Mohd Hafiz Ngoo; Othman, Zulhabri; Noor, Hamdan Mohd; Arshad, Siti Suri; Yusof, Ahmad Khairuddin Mohd; Jamal, Rahman; Rahman, Abdul Rashid Abdul

    2012-09-01

    The molecular basis of coronary artery disease (CAD) has been widely studied in the western world but there is no published work on the Malaysian population. This study looked at the global gene expression profiling of the peripheral blood of patients with CAD from the 3 main ethnic groups in Malaysia. Male subjects selected were based on angiographically confirmed CAD (≥50% stenosis) and normal control subjects (0% stenosis) with age range of 55.6±5.3 and 51.0±5.5 years, respectively. The global gene expression of 12 angiographically documented CAD patients and 11 matched control subjects were performed. The combined group samples identified 6 up regulated differential expression (DE) genes (GHRL, LTA, CBS, HP, ITGA2B, and OLR1) and 12 down regulated DE genes (IL18R1, ITGA2B, IL18RAP, HP, OLR1, SOD2 ITGB3, IL1B, MMP9, PLA2G7, UTS2, and CBS) to be involved in CAD at the fold change of 1.3 with fault discovery rate (FDR) of 1%. Three genes, MMP9, IL1B, and SOD2 were down regulated in all the 3 ethnic groups making them potential biomarker candidates for CAD across all three ethnicities. Further verification in a cohort study is needed.

  4. Prediction of key genes in ovarian cancer treated with decitabine based on network strategy.

    PubMed

    Wang, Yu-Zhen; Qiu, Sheng-Chun

    2016-06-01

    The objective of the present study was to predict key genes in ovarian cancer before and after treatment with decitabine utilizing a network approach and to reveal the molecular mechanism. Pathogenic networks of ovarian cancer before and after treatment were identified based on known pathogenic genes (seed genes) and differentially expressed genes (DEGs) detected by Significance Analysis of Microarrays (SAM) method. A weight was assigned to each gene in the pathogenic network and then candidate genes were evaluated. Topological properties (degree, betweenness, closeness and stress) of candidate genes were analyzed to investigate more confident pathogenic genes. Pathway enrichment analysis for candidate and seed genes were conducted. Validation of candidate gene expression in ovarian cancer was performed by reverse transcriptase-polymerase chain reaction (RT-PCR) assays. There were 73 nodes and 147 interactions in the pathogenic network before treatment, while 47 nodes and 66 interactions after treatment. A total of 32 candidate genes were identified in the before treatment group of ovarian cancer, of which 16 were rightly candidate genes after treatment and the others were silenced. We obtained 5 key genes (PIK3R2, CCNB1, IL2, IL1B and CDC6) for decitabine treatment that were validated by RT-PCR. In conclusion, we successfully identified 5 key genes (PIK3R2, CCNB1, IL2, IL1B and CDC6) and validated them, which provides insight into the molecular mechanisms of decitabine treatment and may be potential pathogenic biomarkers for the therapy of ovarian cancer.

  5. Lack of association between human longevity and polymorphisms of IL-1 cluster, IL-6, IL-10 and TNF-alpha genes in Finnish nonagenarians.

    PubMed

    Wang, X Y; Hurme, M; Jylhä, M; Hervonen, A

    2001-12-01

    There has been increasing interest in research on genetic basis of longevity. Aging is accompanied by immune deterioration and dysregulation of cytokines. Increased IL-6 concentration in vivo and enhanced IL-6, IL-1beta, and TNF-alpha production in vitro have been reported in healthy elderly people. Cytokine gene polymorphisms have been demonstrated to be associated with cytokine production both in vivo and in vitro, and with some diseases. Thus, gene polymorphisms of cytokine may play a role in longevity by modulating an individual's responses to life-threatening disorders. Cytokine gene polymorphisms at IL1A-889, IL1B+3953, IL1B-511, IL1RN VNTR, IL6-174, IL10-1082, and TNFA-308 were genotyped in 250 Finnish nonagenarians (52 men and 198 women) and in 400 healthy blood donors (18-60 years) as controls. No statistically significant differences were found in the genotype distributions, allelic frequencies and A2+ carrier status of IL-1alpha, IL-1beta, IL-1RA, IL-6, IL-10, and TNF-alpha genes between nonagenarians and younger controls within Finnish population, nor between male and female nonagenarians. No differences emerged between nonagenarians and younger controls by comparing different IL-1 gene cluster haplotypes. Thus, there is no evidence of an association of IL-1 complex, IL-6, IL-10, and TNF-alpha gene polymorphisms with longevity, alone or in combination.

  6. 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

  7. 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

  8. Effects of date palm fruit extracts on skin mucosal immunity, immune related genes expression and growth performance of common carp (Cyprinus carpio) fry.

    PubMed

    Hoseinifar, Seyed Hossein; Khalili, Mohsen; Rufchaei, Rudabeh; Raeisi, Mojtaba; Attar, Marzieh; Cordero, Héctor; Esteban, M Ángeles

    2015-12-01

    The aim of this study was to investigate the effects of date palm fruit extracts (DPFE) on skin mucosal immunity, immune related genes expression and growth performance of fry common carp (Cyprinus carpio). One hundred and twenty specimens (4.06 ± 0.13 g) were supplied and allocated into six aquaria; specimens in three aquaria were fed non-supplemented diet (control) while the fish in the other 3 aquaria were fed with DPFE at 200 ml kg(-1). At the end of feeding trial (8 weeks) skin mucus immune parameters (total immunoglobulins, lysozyme, protease and alkaline phosphatase activity) and immune related gene expression (tumor necrosis factor α [tnfa], lysozyme [ly] and interleukin-1-beta, [il1b]) in the head-kidney were studied. The results revealed that feeding carp fry with 200 ml kg(-1) DPFE remarkably elevated the three skin mucus immune parameters tested (P < 0.05). However, evaluation of immune related gene expression demonstrated that the expression of tnfa and il1b was considerably decreased (P < 0.05) in fish fed DPFE diet, while the expression of ly remained similar (P > 0.05) compared to control fish (fed control diet). Furthermore, growth performance parameters were significantly improved in fry fed DPFE (P < 0.05). More studies are needed to understand different aspects of DPFE administration in fry mucosal immunity. PMID:26439417

  9. 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.

  10. Allelic variation at the interleukin 1β gene is associated with decreased bone mass in patients with inflammatory bowel diseases

    PubMed Central

    Nemetz, A; Toth, M; Garcia-Gonzalez, M; Zagoni, T; Feher, J; Pena, A; Tulassay, Z

    2001-01-01

    BACKGROUND—Interleukin 1β (IL-1β) and its natural antagonist have been implicated in the pathogenesis of inflammatory bowel disease (IBD). Both cytokines influence bone formation. IL-1β stimulates osteoclast activity while interleukin 1 receptor antagonist (IL-1ra) enhances bone formation.
AIMS—To determine whether the decreased bone mass in IBD is related to gene polymorphisms coding for IL-1β and IL-1ra, and thus identify patients with an increased risk.
METHODS—Bone mineral densitometry was performed at the femoral neck, lumbar spine, and the distal third of the radius in 75 IBD patients (34 men/41 women; 40.3 (1.6) years) and in 58 healthy controls (HC; 28 men/30 women; 32.4 (1.2) years). Values were correlated with the TaqI and AvaI gene polymorphisms in the IL1B and the variable number of tandem repeats gene polymorphism in the IL1RN gene.
RESULTS—In IBD patients, but not in HC, carriers of allele 2 at the AvaI gene polymorphism (IL1B-511*2) had significantly lower Z scores at the lumbar spine (−0.82 (0.13) v −0.29 (0.21) p=0.03) and the femoral neck (−0.59 (0.14) v 0.15 (0.19); p=0.003) than non-carriers. These patients also had a higher risk for osteopenia or osteoporosis at the femoral neck (odds ratio 3.63 (95% confidence interval 0.95-13.93)). No association was found between bone mass and the other gene polymorphisms analysed in IBD patients or in HC.
CONCLUSIONS—Our results suggest that genetic variability may be a major determinant of bone loss in IBD. Carriers of IL1B-511*2, who are hypersecretors of IL-1β, have a higher risk of presenting with low bone mass in IBD. Screening for this allele may contribute to determination of the risk of bone loss at the time of disease onset.


Keywords: inflammatory bowel diseases; ulcerative colitis; Crohn's disease; osteoporosis; bone density; genetic polymorphisms; interleukin 1 PMID:11600466

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

    PubMed

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

    2016-05-23

    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.

  12. Association of IL-1 gene complex members with ankylosing spondylitis in Chinese Han population.

    PubMed

    Guo, Z S; Li, C; Lin, Z M; Huang, J X; Wei, Q J; Wang, X W; Xie, Y Y; Liao, Z T; Chao, S Y; Gu, J R

    2010-02-01

    There are reports of IL-1 complex gene polymorphisms in ankylosing spondylitis (AS; MIM 106300), but the results have been inconsistent among populations. Moreover, few studies examine the association between IL-1 complex gene polymorphisms and clinical symptoms of AS patients. We investigated polymorphisms of IL-1 complex with AS in the Chinese Han population in this study. Chinese Han AS patients and ethnically matched healthy controls were genotyped for five single nucleotide polymorphisms (IL1beta+3953, beta-511, F10.3, RN.4, RN.6/1) and the IL1RN.VNTR of IL-1 gene cluster. Allele, Genotype and haplotype frequencies were compared between cases and controls by SHEsis software. The frequency of allele C of the marker IL1F10.3 was significantly increased in AS patients versus controls [p = 0.001, odds ratio (OR) = 1.54, 95% confidence interval (CI) = 1.19-1.20; p = 0.002, respectively]. Strong linkage disequilibrium was identified between IL1B-511, IL1B+3953 and RN4 in both patients and healthy controls (D' > 0.95). Haplotypes of pairs of these markers (6) were also significantly associated with AS. The strongest associations observed was between allele combination B-511-T/B+3953-C/F10.3-C/RN4-T/RN2VNTR-1/RN6.1-C and AS (p = 3.32 x 10(-5), OR = 4.41, 95% CI=2.1-9.3). Clinical manifestation showed week association between RN2VNTR A2 allele and risk of peripheral arthritis (OR = 0.2, 95% CI = 0.07-0.91). The IL-1 gene cluster is associated with AS in Chinese population. This finding provides strong statistical support for the previously observed relationship and indicates possible association between clinical manifestation and genetic factor.

  13. HLA and interleukin 1 gene polymorphisms in primary biliary cirrhosis: associations with disease progression and disease susceptibility

    PubMed Central

    Donaldson, P; Agarwal, K; Craggs, A; Craig, W; James, O; Jones, D

    2001-01-01

    BACKGROUND AND AIMS—Twin and family studies suggest that there is a genetic component to primary biliary cirrhosis (PBC) but the genetic associations which have been described are weak with marked variations between centres. PBC is heterogeneous and genetic associations with disease progression may be obscured when the PBC population is analysed only as a whole and not subdivided.
METHODS—We have investigated two candidate gene loci in 164 well characterised patients, 88 (54%) of whom had advanced disease.
RESULTS—There was an increased frequency of the HLA DRB1*0801-DQA1*0401-DQB1*0402 haplotype in patients who had progressed to late stage disease (23% v 2% of controls; p=0000044; odds ratio (OR) 15.5, 95% confidence interval (CI) 3.52-68.4) but not in those with early stage disease (4% v 2%). Patients had a higher frequency of the IL-1B*1,1 genotype and lower frequencies of the IL-1B*1,2 and *2,2 genotypes (p=0.00078; OR 2.37, 95% CI 1.38-4.06), and higher frequency of the IL-1RN*1,1 genotype and lower frequency of the IL-1RN*1,2 genotype (p=0.0011; OR 2.28, 95% CI 1.34-3.89). The difference in the IL-1B*1,1 genotype distribution was most marked in patients with early stage disease (77% v 43% of controls; p=0.000003; OR 4.8, 95% CI 2.31-10) but the IL-1RN genotype distribution was similar in patients with early and late stage disease.
CONCLUSIONS—These data indicate a complex relationship between immunoregulatory genes and PBC. While the IL-1 genes are markers of both disease susceptibility and progression, HLA genes appear to be principally associated with disease progression.


Keywords: human leucocyte antigens; primary biliary cirrhosis; interleukin 1 PMID:11171832

  14. Epithelial Cell Gene Expression Induced by Intracellular Staphylococcus aureus

    PubMed Central

    Li, Xianglu; Fusco, William G.; Seo, Keun S.; Bayles, Kenneth W.; Mosley, Erin E.; McGuire, Mark A.; Bohach, Gregory A.

    2009-01-01

    HEp-2 cell monolayers were cocultured with intracellular Staphylococcus aureus, and changes in gene expression were profiled using DNA microarrays. Intracellular S. aureus affected genes involved in cellular stress responses, signal transduction, inflammation, apoptosis, fibrosis, and cholesterol biosynthesis. Transcription of stress response and signal transduction-related genes including atf3, sgk, map2k1, map2k3, arhb, and arhe was increased. In addition, elevated transcription of proinflammatory genes was observed for tnfa, il1b, il6, il8, cxcl1, ccl20, cox2, and pai1. Genes involved in proapoptosis and fibrosis were also affected at transcriptional level by intracellular S. aureus. Notably, intracellular S. aureus induced strong transcriptional down-regulation of several cholesterol biosynthesis genes. These results suggest that epithelial cells respond to intracellular S. aureus by inducing genes affecting immunity and in repairing damage caused by the organism, and are consistent with the possibility that the organism exploits an intracellular environment to subvert host immunity and promote colonization. PMID:20016671

  15. 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

  16. 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

    2014-11-01

    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.

  17. Host Gene Polymorphisms in Relation to Helicobacter Pylori Infection and Associated Diseases in a Population Based Cohort

    PubMed Central

    Ryberg, Anna; Petersson, Fredrik; Redeen, Stefan; Eriksson, Olle; Borch, Kurt

    2013-01-01

    Background This prospective population based cohort study explores possible associations between host gene polymorphisms, blood group and life style factors on the one hand, and Helicobacter pylori infection, peptic ulcer, and the grade of inflammation, atrophy and intestinal metaplasia of the gastric mucosa, on the other hand. Methods The study population (472 volunteers) has previously undergone screening with gastroduodenoscopy, biopsy and blood sampling. The host gene polymorphisms of IL1B-31C/T, IFNGR1-56T/C, the IL1RN VNTR in exon 2 and the HLA-DRB1 gene alleles were analyzed using PCR and pyrosequencing. Results H. pylori infection was negatively related to HLA DRB1*03 (odds ratio (OR) 95% CI: 0.388 - 0.989) and was more frequent in individuals with blood group O than A (OR 95% CI: 1.121 - 2.677). There was a lower risk of moderate to severe inflammation in the antrum among individuals with IL1B-31 TC compared to CC carriers (OR 95% CI: 0.094 - 0.733). The IL1RN*L2 genotype was associated with higher risk of IM in the antrum than the *LL genotype (OR 95% CI: 1.570 - 15.878). There was a negative relation between the HLA DRB1 alleles *04 (OR 95% CI: 0.234 - 0.831) and *08 (OR 95% CI: 0.013 - 0.915), and IM in the antrum. Conclusion The IL1RN VNTR and the IL1β-31 alleles seem to be associated with intestinal metaplasia of the corpus mucosa and the grade of inflammation of the antrum, respectively. However, no unambiguous correlations could be identified between the host polymorphisms and the occurrence of H. pylori infection, peptic ulcer, and the grade of inflammation, atrophy and IM of the gastric mucosa.

  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. 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

  20. Laparotomy in mice induces blood cell expression of inflammatory and stress genes.

    PubMed

    Ko, Fred; Isoda, Fumiko; Mobbs, Charles

    2015-04-01

    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.

  1. Lactobacillus acidophilus L-92 Cells Activate Expression of Immunomodulatory Genes in THP-1 Cells

    PubMed Central

    YANAGIHARA, Sae; GOTO, Hiroaki; HIROTA, Tatsuhiko; FUKUDA, Shinji; OHNO, Hiroshi; YAMAMOTO, Naoyuki

    2014-01-01

    To understand the immunomodulatory effects of Lactobacillus acidophilus L-92 cells suggested from our previous study of in vivo anti-allergy and anti-virus effects, host immune responses in macrophage-like THP-1 cells after 4 h (the early phase) and 24 h (the late phase) of cocultivation with L-92 cells were investigated by transcriptome analysis. In the early phase of L-92 treatment, various transcription regulator genes, such as, NFkB1, NFkB2, JUN, HIVEP2 and RELB, and genes encoding chemokines and cytokines, such as CCL4, CXCL11, CCL3 and TNF, were upregulated. Two transmembrane receptor genes, TLR7 and ICAM1, were also upregulated in the early phase of treatment. In contrast, many transmembrane receptor genes, such as IL7R, CD80, CRLF2, CD86, CD5, HLA-DQA1, IL2RA, IL15RA and CSF2RA, and some cytokine genes, including IL6, IL23A and CCL22, were significantly upregulated in the late phase after L-92 exposure. Some genes encoding cytokines, such as IL1A, IL1B and IL8, and the enzyme IDO1 were upregulated at both the early and the late phases of treatment. These results suggest that probiotic L-92 might promote Th1 and regulatory T-cell responses by activation of the MAPK signaling pathway, followed by the NOD-like receptor signaling pathway in THP-1 cells. PMID:25379363

  2. 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

  3. Francisella tularensis alters human neutrophil gene expression: insights into the molecular basis of delayed neutrophil apoptosis.

    PubMed

    Schwartz, Justin T; Bandyopadhyay, Sarmistha; Kobayashi, Scott D; McCracken, Jenna; Whitney, Adeline R; Deleo, Frank R; Allen, Lee-Ann H

    2013-01-01

    We demonstrated recently that Francisella tularensis profoundly impairs human neutrophil apoptosis, but how this is achieved is largely unknown. Herein we used human oligonucleotide microarrays to test the hypothesis that changes in neutrophil gene expression contribute to this phenotype, and now demonstrate that F. tularensis live vaccine strain (LVS) caused significant changes in neutrophil gene expression over a 24-hour time period relative to the uninfected controls. Of approximately 47,000 genes analyzed, 3,435 were significantly up- or downregulated by LVS, including 365 unique genes associated with apoptosis and cell survival. Specific targets in this category included genes asso-ciated with the intrinsic and extrinsic apoptotic pathways (CFLAR, TNFAIP3, TNFRSF10D, SOD2, BCL2A1, BIRC4, PIM2, TNFSF10, TNFRSF10C, CASP2 and CASP8) and genes that act via the NFĸB pathway and other mechanisms to prolong cell viability (NFKB1, NFKB2 and RELA, IL1B, CAST, CDK2,GADD45B, BCL3, BIRC3, CDK2, IL1A, PBEF1, IL6, CXCL1, CCL4 and VEGF). The microarray data were confirmed by qPCR and pathway analysis. Moreover, we demonstrate that the X-linked inhibitor of apoptosis protein remained abundant in polymorphonuclear leukocytes over 48 h of LVS infection, whereas BAX mRNA and protein were progressively downregulated. These data strongly suggest that antiapoptotic and prosurvival mechanisms collaborate to sustain the viability of F. tularensis--infected neutrophils. PMID:22986450

  4. The influence of cytokine gene polymorphisms on the risk of developing gastric cancer in patients with Helicobacter pylori infection

    PubMed Central

    Stubljar, David; Jeverica, Samo; Jukic, Tomislav; Skvarc, Miha; Pintar, Tadeja; Tepes, Bojan; Kavalar, Rajko; Stabuc, Borut; Peterlin, Borut; Ihan, Alojz

    2015-01-01

    Background Helicobacter pylori infection is the main cause of gastric cancer. The disease progression is influenced by the host inflammatory responses, and cytokine single nucleotide polymorphisms (SNPs) may have a role in the course of the disease. The aim of our study was to investigate proinflammatory cytokine polymorphisms, previously associated with the development of gastric cancer, in a Slovenian population. Patients and methods. In total 318 patients and controls were selected for the study and divided into three groups: (i) patients with gastric cancer (n = 58), (ii) patients with chronic gastritis (n = 60) and (iii) healthy control group (n = 200). H. pylori infection in patient groups was determined by serology, histology and culture. Four proinflammatory gene polymorphisms were determined (IL-1β, IL-1ra, TNF-α, TLR-4) in all subjects. Results We found a statistically significant difference between males and females for the groups (p = 0.025). Odds ratio (OR) for gastric cancer risk for females was 0.557 (95% confidence interval [CI]: 0.233–1.329) and for chronic gastritis 2.073 (95% CI: 1.005–4.277). IL-1B-511*T/T homozygous allele for cancer group had OR = 2.349 (95% CI: 0.583–9.462), heterozygous IL-1B-511*T had OR = 1.470 (95% CI: 0.583–3.709) and heterozygotes in TNF-A-308 genotype for chronic gastritis had OR = 1.402 (95% CI: 0.626–3.139). Other alleles had OR less than 1. Conclusions We could not prove association between gastric cancer and chronic gastritis due to H. pylori in any cytokine SNPs studied in Slovenian population. Other SNPs might be responsible besides infection with H. pylori for the progression from atrophy to neoplastic transformation. PMID:26401131

  5. 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)

  6. 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

  7. Cytokine Gene Polymorphisms and Outcome after Traumatic Brain Injury

    PubMed Central

    Waters, Ryan J.; Murray, Gordon D.; Teasdale, Graham M.; Stewart, Janice; Day, Ian; Lee, Robert J.

    2013-01-01

    Abstract 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. PMID:23768161

  8. 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.

  9. [Distribution of allelic variants of promotor sites of cytokine genes and endothelial growth factor gene among healthy subjects and patients with rheumatoid arthritis in a Russian Europeoid population].

    PubMed

    Konenkov, V I; Golovanova, O V; Prokof'ev, V F; Shevchenko, A V; Zonova, E V; Korolev, M A; Leonova, Iu B; Khalaĭdzhi, N A; Lapsina, S A

    2010-01-01

    The article reports results of the first study of cytokine gene polymorphic sites and analysis of distribution of their complexes among healthy subjects and patients with rheumatoid arthritis (RA) representative of the Russian Europeoid population; their possible prognostic significance is evaluated. Comprehensive analysis of the frequency of allelic variants of cytokine genes IL1B C-31T, IL6 G-174C, TNFA A-238G, TNFA A-308G, TNFA A-863C, IL4 C-590T, IL10 A-592C and VEGF C-2578A was performed for 513 residents of the Novosibirsk region showing no obvious signs of any diseases and 125 RA patients. The results suggest association of RA with certain alleles of pro- and anti-inflammatory cytokine genes. Complex indices reflecting combinations of genotypes of two, three, four, five, six and seven loci of the explored cytokine genes found in individual patient demonstrate their high specificity for RA. It is supposed that these findings can be used in further clinical studies for the development of algorithm designed to detect risk groups among clinically healthy subjects.

  10. HIV-associated mucosal gene expression: region-specific alterations

    PubMed Central

    Voigt, Robin M.; Keshavarzian, Ali; Losurdo, John; Swanson, Garth; Siewe, Basile; Forsyth, Christopher B.; French, Audrey L.; Demarais, Patricia; Engen, Phillip; Raeisi, Shohreh; Mutlu, Ece; Landay, Alan L.

    2016-01-01

    Objective Despite the use of HAART to control HIV, systemic immune activation and inflammation persists with the consequence of developing serious non-AIDS events. The mechanisms that contribute to persistent systemic immune activation have not been well defined. The intestine is the major source of “sterile” inflammation and plays a critical role in immune function; thus, we sought to determine whether intestinal gene expression was altered in virally controlled HIV-infected individuals. Design and methods Gene expression was compared in biopsy samples collected from HIV-uninfected and HIV-infected individuals from the ileum, right colon (ascending colon), and left colon (sigmoid). Affymetrix gene arrays were performed on tissues and pathway analyses were conducted. Gene expression was correlated with systemic markers of intestinal barrier dysfunction and inflammation and intestinal microbiota composition. Results Genes involved in cellular immune response, cytokine signaling, pathogen-influenced signaling, humoral immune response, apoptosis, intracellular and second messenger signaling, cancer, organismal growth and development, and proliferation and development were upregulated in the intestine of HIV-infected individuals with differences observed in the ileum, right, and left colon. Gene expression in the ileum primarily correlated with systemic markers of inflammation (e.g., IL7R, IL2, and TLR2 with serum TNF) whereas expression in the colon correlated with the microbiota community (e.g., IFNG, IL1B, and CD3G with Bacteroides). Conclusion These data demonstrate persistent, proinflammatory changes in the intestinal mucosa of virally suppressed HIV-infected individuals. These changes in intestinal gene expression may be the consequence of or contribute to barrier dysfunction and intestinal dysbiosis observed in HIV. PMID:25587909

  11. METHYL ESTER OF AVENANTHRAMIDE-C INHIBITS TNFa- AND IL-1b-INDUCED NF-kB ACTIVATION IN ENDOTHELIAL CELLS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Atherosclerosis is an age-associated chronic inflammatory disease of arteries accompanied by the expression of endothelial pro-inflammatory molecules. Avenanthramides (Avns) are polyphenols found exclusively in oats. We have reported that avenanthramide-enriched mixtures extracted from oats signific...

  12. 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...

  13. 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

  14. 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

  15. The Mycobacterium DosR regulon structure and diversity revealed by comparative genomic analysis.

    PubMed

    Chen, Tian; He, Liming; Deng, Wanyan; Xie, Jianping

    2013-01-01

    Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), which claims approximately two million people annually, remains a global health concern. The non-replicating or dormancy like state of this pathogen which is impervious to anti-tuberculosis drugs is widely recognized as the culprit for this scenario. The dormancy survival regulator (DosR) regulon, composed of 48 co-regulated genes, is held as essential for Mtb persistence. The DosR regulon is regulated by a two-component regulatory system consisting of two sensor kinases-DosS (Rv3132c) and DosT (Rv2027c), and a response regulator DosR (Rv3133c). The underlying regulatory mechanism of DosR regulon expression is very complex. Many factors are involved, particularly the oxygen tension. The DosR regulon enables the pathogen to persist during lengthy hypoxia. Comparative genomic analysis demonstrated that the DosR regulon is widely distributed among the mycobacterial genomes, ranging from the pathogenic strains to the environmental strains. In-depth studies on the DosR response should provide insights into its role in TB latency in vivo and shape new measures to combat this exceeding recalcitrant pathogen.

  16. 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. PMID:25564368

  17. 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

  18. 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.

  19. 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

  20. Cytokine gene polymorphisms, cytokine levels and the risk of colorectal neoplasia in a screened population of Northeast Scotland

    PubMed Central

    Basavaraju, U; Shebl, FM; Palmer, AJ; Berry, S; Hold, GL; El-Omar, EM; Rabkin, CS

    2014-01-01

    Background and Aims Cytokine gene polymorphisms modify expression and their circulating protein levels reflect inflammatory response. Chronic inflammation plays key role in pathogenesis of colorectal neoplasia (CRN) associated with inflammatory bowel disease (IBD), but it is not clear if inflammation is a cause or effect of tumours in sporadic CRN. We therefore investigated association of cytokine gene polymorphisms and circulating cytokine levels on risk of CRN in North East Scotland, which has a high incidence of CRN. Methods We recruited two groups of subjects from a screening colonoscopy cohort, either pre-procedure or 3–24 months post-procedure. Participants with (CRN) were compared to participants with no evidence of CRN (controls). Blood-derived DNA was used to genotype polymorphisms in IL1B, IL1-RN, IL6, IL8, IL10, PTGS2 and TNFA genes. Circulating levels of high-sensitivity C-reactive protein (Hs-CRP) and 6 cytokines (IL-1beta, IL-4, IL-6, IL-8, IL-10 and TNF-alpha) were measured. In order to examine effect of CRN resection on marker levels, we used propensity score matching. Results There were 884 subjects eligible for analysis, including 388 CRN cases and 496 controls. Cases were older (mean age 64 vs. 62 yrs, p<0.01) and more likely to be male (67% vs. 55%, p<0.001). Controls were more likely to be regular users of NSAID (p<0.0001). Compared to homozygous carriage of respective common alleles, pro-inflammatory CC genotypes of IL1B-31 C>T [OR (95% CI) 1.68 (1.03–2.73)] and PTGS2-765 C>G [OR (95% CI) 2.97 (1.05–8.46)] were each associated with increased CRN risk. Conversely, carriage of the A allele of IL8-251 A>T was associated with lower CRN risk compared to the TT genotype [ORs (95% CI) 0.60 (0.41–0.86) for heterozygous, 0.88 (0.57–1.37) for homozygous, and 0.68 (0.48–0.95) for heterozygous and homozygous combined]. Compared to post-procedure cases, IL8, TNFα, and CRP levels were significantly higher in pre-procedure cases, but IL4 and IL

  1. C-reactive protein levels are influenced by common IL-1 gene variations.

    PubMed

    Berger, Peter; McConnell, Joseph P; Nunn, Martha; Kornman, Kenneth S; Sorrell, Julian; Stephenson, Katherine; Duff, Gordon W

    2002-02-21

    Elevated markers of systemic inflammation are associated with the development of acute coronary syndromes, but there is no current explanation for increased inflammation in overtly healthy individuals. The influence of genetic control of the inflammatory response on the observed variability is unknown. We studied the frequency of four polymorphisms in interleukin (IL) 1 genes, known to modulate inflammation, in 454 individuals undergoing coronary angiography and analysed their influence on plasma C-reactive protein (CRP) and fibrinogen levels. Females and smokers had higher levels of CRP than males (Pi = 0.001) and non-smokers (Pi = 0.001). Patients with genotype 2.2 for the IL-1B(+3954) polymorphism had twice the median CRP levels of patients who were genotype 1.1 (4.33 vs 2.01 mg/l; P = 0.001). Patients with genotype 1.2 or 2.2 at the IL-1A(+4845) polymorphism also had higher median CRP (2.92 vs 2.05 mg/l, Pi = 0.023). In multivariate analyses, CRP levels remained significantly associated with IL-1 polymorphisms after adjustment for smoking, gender and age. Fibrinogen levels had similar associations with the IL-1 genotypes. These data indicate that IL-1 gene polymorphisms known to affect the inflammatory response are highly related to plasma levels of CRP and fibrinogen in patients referred for coronary angiography.

  2. Transciptomic study of mucosal immune, antioxidant and growth related genes and non-specific immune response of common carp (Cyprinus carpio) fed dietary Ferula (Ferula assafoetida).

    PubMed

    Safari, Roghieh; Hoseinifar, Seyed Hossein; Nejadmoghadam, Shabnam; Jafar, Ali

    2016-08-01

    A 8-weeks feeding trial was conducted to examine the effects of different levels (0, 0.5, 1 and 2%) of dietary Ferula (Ferula assafoetida) on expression of antioxidant enzymes (GSR, GPX and GSTA), immune (TNF-alpha, IL1B, IL- 8 and LYZ) and growth (GH, IGF1 and Ghrl) genes as well as cutaneous mucus and serum non-specific immune response in common carp. The results revealed Ferula significantly increased antioxidant gene expression (GSR and GSTA) in a dose dependent manner (P < 0.05). The expression of immune growth related genes were significantly higher in Ferula fed fish compared control group (P < 0.05). The effects of Ferula on expression of genes was more pronounced in higher doses. Feeding on Ferula supplemented diet remarkably increased skin mucus lysozyme activity (P < 0.05). However, evaluation of mucus total Ig and protease activity revealed no significant difference between control and treated groups (P > 0.05). Regarding non-specific humoral response, serum total Ig, lysozyme and ACH50 showed no remarkable variation between Ferula fed carps and control group (P > 0.05). These results indicated up-regulation of growth and health related genes in Ferula fed common carp. Further studies using pathogen or stress challenge is required to conclude that transcriptional modulation is beneficial in common carp. PMID:27241284

  3. 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.

  4. Concurrent genotyping of Helicobacter pylori virulence genes and human cytokine SNP sites using whole genome amplified DNA derived from minute amounts of gastric biopsy specimen DNA

    PubMed Central

    Ryberg, Anna; Borch, Kurt; Sun, Yi-Qian; Monstein, Hans-Jürg

    2008-01-01

    Background Bacterial and cellular genotyping is becoming increasingly important in the diagnosis of infectious diseases. However, difficulties in obtaining sufficient amount of bacterial and cellular DNA extracted from the same human biopsy specimens is often a limiting factor. In this study, total DNA (host and bacterial DNA) was isolated from minute amounts of gastric biopsy specimens and amplified by means of whole genome amplification using the multiple displacement amplification (MDA) technique. Subsequently, MDA-DNA was used for concurrent Helicobacter pylori and human host cellular DNA genotyping analysis using PCR-based methods. Results Total DNA was isolated from gastric biopsy specimens of 12 subjects with gastritis and 16 control subjects having a normal mucosa. The DNA was amplified using a multiple displacement amplification (MDA) kit. Next, concurrent genotyping was performed using H. pylori-specific virulence gene PCR amplification assays, pyrosequencing of bacterial 16S rDNA and PCR characterisation of various host genes. This includes Interleukin 1-beta (IL1B) and Interferon-gamma receptor (IFNGR1) SNP analysis, and Interleukin-1 receptor antagonist (IL1RN) variable tandem repeats (VNTR) in intron 2. Finally, regions of the vacA-gene were PCR amplified using M13-sequence tagged primers which allowed for direct DNA sequencing, omitting cloning of PCR amplicons. H. pylori specific multiplex PCR assays revealed the presence of H. pylori cagA and vacA genotypic variations in 11 of 12 gastritis biopsy specimens. Using pyrosequencing, 16S rDNA variable V3 region signatures of H. pylori were found in 11 of 12 individuals with gastritis, but in none of the control subjects. Similarly, IL1B and IFNGR1-SNP and IL1RN-VNTR patterns could be established in all individuals. Furthermore, sequencing of M13-sequence tagged vacA-PCR amplicons revealed the presence of highly diverse H. pylori vacA-s/i/m regions. Conclusion The PCR-based molecular typing methods

  5. Variable number of tandem repeat polymorphisms of the interleukin-1 receptor antagonist gene IL-1RN: a novel association with the athlete status

    PubMed Central

    2010-01-01

    Background The interleukin-1 (IL-1) family of cytokines is involved in the inflammatory and repair reactions of skeletal muscle during and after exercise. Specifically, plasma levels of the IL-1 receptor antagonist (IL-1ra) increase dramatically after intense exercise, and accumulating evidence points to an effect of genetic polymorphisms on athletic phenotypes. Therefore, the IL-1 family cytokine genes are plausible candidate genes for athleticism. We explored whether IL-1 polymorphisms are associated with athlete status in European subjects. Methods Genomic DNA was obtained from 205 (53 professional and 152 competitive non-professional) Italian athletes and 458 non-athlete controls. Two diallelic polymorphisms in the IL-1β gene (IL-1B) at -511 and +3954 positions, and a variable number tandem repeats (VNTR) in intron 2 of the IL-1ra gene (IL-1RN) were assessed. Results We found a 2-fold higher frequency of the IL-1RN 1/2 genotype in athletes compared to non-athlete controls (OR = 1.93, 95% CI = 1.37-2.74, 41.0% vs. 26.4%), and a lower frequency of the 1/1 genotype (OR = 0.55, 95% CI = 0.40-0.77, 43.9% vs. 58.5%). Frequency of the IL-1RN 2/2 genotype did not differ between groups. No significant differences between athletes and controls were found for either -511 or +3954 IL-1B polymorphisms. However, the haplotype (-511)C-(+3954)T-(VNTR)2 was 3-fold more frequent in athletes than in non-athletes (OR = 3.02, 95% CI = 1.16-7.87). Interestingly, the IL-1RN 1/2 genotype was more frequent in professional than in non-professional athletes (OR = 1.92, 95% CI = 1.02-3.61, 52.8% vs. 36.8%). Conclusions Our study found that variants at the IL-1ra gene associate with athletic status. This confirms the crucial role that cytokine IL-1ra plays in human physical exercise. The VNTR IL-1RN polymorphism may have implications for muscle health, performance, and/or recovery capacities. Further studies are needed to assess these specific issues. As VNTR IL-1RN polymorphism is

  6. Network analysis of inflammatory genes and their transcriptional regulators in coronary artery disease.

    PubMed

    Nair, Jiny; Ghatge, Madankumar; Kakkar, Vijay V; Shanker, Jayashree

    2014-01-01

    Network analysis is a novel method to understand the complex pathogenesis of inflammation-driven atherosclerosis. Using this approach, we attempted to identify key inflammatory genes and their core transcriptional regulators in coronary artery disease (CAD). Initially, we obtained 124 candidate genes associated with inflammation and CAD using Polysearch and CADgene database for which protein-protein interaction network was generated using STRING 9.0 (Search Tool for the Retrieval of Interacting Genes) and visualized using Cytoscape v 2.8.3. Based on betweenness centrality (BC) and node degree as key topological parameters, we identified interleukin-6 (IL-6), vascular endothelial growth factor A (VEGFA), interleukin-1 beta (IL-1B), tumor necrosis factor (TNF) and prostaglandin-endoperoxide synthase 2 (PTGS2) as hub nodes. The backbone network constructed with these five hub genes showed 111 nodes connected via 348 edges, with IL-6 having the largest degree and highest BC. Nuclear factor kappa B1 (NFKB1), signal transducer and activator of transcription 3 (STAT3) and JUN were identified as the three core transcription factors from the regulatory network derived using MatInspector. For the purpose of validation of the hub genes, 97 test networks were constructed, which revealed the accuracy of the backbone network to be 0.7763 while the frequency of the hub nodes remained largely unaltered. Pathway enrichment analysis with ClueGO, KEGG and REACTOME showed significant enrichment of six validated CAD pathways - smooth muscle cell proliferation, acute-phase response, calcidiol 1-monooxygenase activity, toll-like receptor signaling, NOD-like receptor signaling and adipocytokine signaling pathways. Experimental verification of the above findings in 64 cases and 64 controls showed increased expression of the five candidate genes and the three transcription factors in the cases relative to the controls (p<0.05). Thus, analysis of complex networks aid in the prioritization of

  7. 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)

  8. DOS Batch Files As Control Programs

    NASA Technical Reports Server (NTRS)

    Van Dyk, David A.

    1991-01-01

    Computer-programming technique circumvents maximum of 640K imposed on random-access memory (RAM) by DOS (Disk Operating System) software. Involves breaking application program into smaller programs. Each resulting subprogram, when compiled and linked, must be small enough to fit within 640K of RAM. Retrieved from storage on disk as needed. In terms of DOS software, each subprogram ".EXE" file executed in "stand-alone" manner.

  9. Relationship Between IL1 Gene Polymorphisms and Periodontal Disease in Japanese Women

    PubMed Central

    Miyake, Yoshihiro; Hanioka, Takashi; Arakawa, Masashi

    2014-01-01

    Epidemiological evidence on the relationship between IL1A and/or IL1B polymorphisms and periodontal disease is inconsistent. We investigated associations between three IL1 single-nucleotide polymorphisms (SNPs) in genes encoding interleukin (IL) -1α (rs1800587) and IL-1β (rs1143634 and rs16944) and the risk of periodontal disease among young Japanese women. A case–control study was performed with a total of 1150 women, including 131 subjects who had at least one tooth with a probing pocket depth of 4 mm or deeper and 1019 periodontally healthy controls. Compared with a reference group of women with the GG genotype of SNP rs16944, those with the GA genotype had a significantly reduced risk of periodontal disease, while there was no significant relationship between the AA genotype and periodontal disease. No evident relationships were observed between SNP rs1800587 or rs1143634 and periodontal disease. Our study did not reveal any evidence of interaction between the IL1 polymorphisms and smoking. The results of this study showed that the heterozygous variant genotype of the IL1 rs16944 was significantly associated with a reduced risk of periodontal disease in young Japanese women. Smoking did not significantly modify the gene–disease associations under study. PMID:24460370

  10. Changes in gene expression profiles in response to selenium supplementation among individuals with arsenic-induced pre-malignant skin lesions.

    PubMed

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

    2007-03-01

    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 6 months daily oral supplementation of 200 microg 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.

  11. Expression of mesenchymal stem cells-related genes and plasticity of aspirated follicular cells obtained from infertile women.

    PubMed

    Dzafic, Edo; Stimpfel, Martin; Novakovic, Srdjan; Cerkovnik, Petra; Virant-Klun, Irma

    2014-01-01

    After removal of oocytes for in vitro fertilization, follicular aspirates which are rich in somatic follicular cells are discarded in daily medical practice. However, there is some evidence that less differentiated cells with stem cell characteristics are present among aspirated follicular cells (AFCs). The aim of this study was to culture AFCs in vitro and to analyze their gene expression profile. Using the RT2 Profiler PCR array, we investigated the expression profile of 84 genes related to stemness, mesenchymal stem cells (MCSs), and cell differentiation in AFCs enriched by hypoosmotic protocol from follicular aspirates of infertile women involved in assisted reproduction programme in comparison with bone marrow-derived mesenchymal stem cells (BM-MSCs) and fibroblasts. Altogether the expression of 57 genes was detected in AFCs: 16 genes (OCT4, CD49f, CD106, CD146, CD45, CD54, IL10, IL1B, TNF, VEGF, VWF, HDAC1, MITF, RUNX2, PPARG, and PCAF) were upregulated and 20 genes (FGF2, CASP3, CD105, CD13, CD340, CD73, CD90, KDR, PDGFRB, BDNF, COL1A1, IL6, MMP2, NES, NUDT6, BMP6, SMURF2, BMP4, GDF5, and JAG1) were downregulated in AFCs when compared with BM-MSCs. The genes which were upregulated in AFCs were mostly related to MSCs and connected with ovarian function, and differed from those in fibroblasts. The cultured AFCs with predominating granulosa cells were successfully in vitro differentiated into adipogenic-, osteogenic-, and pancreatic-like cells. The upregulation of some MSC-specific genes and in vitro differentiation into other types of cells indicated a subpopulation of AFCs with specific stemness, which was not similar to those of BM-MSCs or fibroblasts.

  12. Linkage disequilibrium analysis of case-control data: an application to generalized aggressive periodontitis.

    PubMed

    Scapoli, C; Trombelli, L; Mamolini, E; Collins, A

    2005-02-01

    Several studies have shown a role for the involvement of interleukin (IL)-1 gene cluster polymorphisms in the risk of periodontal diseases. In the present study, we tested polymorphisms, derived from genes of the IL-1 cluster, for association with generalized aggressive periodontitis (GAP) through both allelic association and by constructing a linkage disequilibrium (LD) map of the 2q13-14 disease candidate region. The IL-1RN (VNTR) genotype distribution observed was significantly different in GAP and control subjects (P=0.019). We also observed some evidence for an association between GAP and the IL-1B(+3953) polymorphism (P=0.039). The pattern of association in the region, represented as an LD map, identifies a recombination hot area between the IL-1B(+3953) and IL-1B(-511) polymorphisms. Multilocus modelling of association with disease gives a location for the peak association at the IL-1B(+3953) marker, although support for the peak is not significant. Haplotype analysis identifies a IL-1B(+3953)-IL-1B(-511) haplotype as having the lowest P-value in the region. Recognition of the presence of a recombination hot area between the IL-1B(+3953) and IL-1B(-511) polymorphisms will have an important bearing on future efforts to develop higher resolution SNP analysis in this region for both this and other diseases for which this cluster is implicated.

  13. Expression of luteal estrogen receptor, interleukin-1, and apoptosis-associated genes after PGF2alpha administration in rabbits at different stages of pseudopregnancy.

    PubMed

    Maranesi, M; Zerani, M; Lilli, L; Dall'Aglio, C; Brecchia, G; Gobbetti, A; Boiti, C

    2010-08-01

    The dynamic expression for estrogen receptor subtype-1 (ESR1), interleukin-1beta (IL1B), and apoptosis-associated genes, as well as nitric oxide synthase activity, were examined in corpora lutea (CL) of rabbits after prostaglandin F(2alpha) (PGF(2alpha)) administration on either day 4 or day 9 of pseudopregnancy. By reverse transcriptase polymerase chain reaction, the steady-state level of ESR1 transcript was lower (P < 0.01) and that of anti-apoptotic B-cell CLL/lymphoma 2 (BCL2) -like 1 (BCL2L1) was greater in day 4 (P < 0.01) than in day 9 CL. Western blot analysis revealed that BCL2-associated X protein (BAX) abundance was greater in day 4 (P < 0.01) than in day 9 CL, whereas BCL2L1 protein was undetectable at both luteal stages. After PGF(2alpha), ESR1 transcript decreased (P < 0.01) in day 9 CL, whereas IL1B mRNA showed a transitory increase (P < 0.01) at both stages. The pro-apoptotic tumor protein p53 (TP53) gene had diminished (P < 0.01) on day 4 and on day 9 after a transitory increase (P < 0.01), whereas the BAX/BCL2L1 expression ratio increased (P < 0.01) in day 9 CL 24 h after treatment. Following PGF(2alpha), TP53 protein increased (P < 0.01) at both luteal stages, and BAX decreased (P < 0.01) in day 4 CL but increased (P < 0.01) 24 h later in day 9 CL; BCL2L1 became detectable 6 h later in day 4 CL. Nitric oxide synthase activity temporarily increased (P < 0.01) following PGF(2alpha). These findings suggest that PGF(2alpha) regulates luteolysis by ESR1 mRNA down-regulation and modulation of pro- and anti-apoptotic pathways in CL that have acquired a luteolytic capacity.

  14. 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

  15. 27 CFR 9.175 - Dos Rios.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... TREASURY LIQUORS AMERICAN VITICULTURAL AREAS Approved American Viticultural Areas § 9.175 Dos Rios. (a... 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...

  16. "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…

  17. Intermittent neonatal hypoxia elicits the upregulation of inflammatory-related genes in adult male rats through long-lasting programming effects.

    PubMed

    Gehrand, Ashley L; Kaldunski, Mary L; Bruder, Eric D; Jia, Shuang; Hessner, Martin J; Raff, Hershel

    2015-12-01

    The long-term effects of neonatal intermittent hypoxia (IH), an accepted model of apnea-induced hypoxia, are unclear. We have previously shown lasting "programming" effects on the HPA axis in adult rats exposed to neonatal IH. We hypothesized that neonatal rat exposure to IH will subsequently result in a heightened inflammatory state in the adult. Rat pups were exposed to normoxia (control) or six cycles of 5% IH or 10% IH over one hour daily from postnatal day 2-6. Plasma samples from blood obtained at 114 days of age were analyzed by assessing the capacity to induce transcription in a healthy peripheral blood mononuclear cell (PBMC) population and read using a high-density microarray. The analysis of plasma from adult rats previously exposed to neonatal 5% IH versus 10% IH resulted in 2579 significantly regulated genes including increased expression of Cxcl1, Cxcl2, Ccl3, Il1a, and Il1b. We conclude that neonatal exposure to intermittent hypoxia elicits a long-lasting programming effect in the adult resulting in an upregulation of inflammatory-related genes. PMID:26660555

  18. Serine 83 in DosR, a response regulator from Mycobacterium tuberculosis, promotes its transition from an activated, phosphorylated state to an inactive, unphosphorylated state.

    PubMed

    Cho, Ha Yeon; Kang, Beom Sik

    2014-02-21

    A sensor kinase, DosS, and its corresponding response regulator, DosR, constitute a two component system for regulating gene expression under hypoxic conditions in Mycobacterium tuberculosis. Among response regulators in M. tuberculosis, NarL has high sequence similarity to DosR, and autophosphorylated DosS transfers its phosphate group not only to DosR but also to NarL. Phosphorylated DosR is more rapidly dephosphorylated than phosphorylated NarL. DosR and NarL differ with respect to the amino acids at positions T+1 and T+2 around the phosphorylation sites in the N-terminal phosphoacceptor domain; NarL has S83 and Y84, whereas DosR has A90 and H91. A DosR S83A mutant shows prolonged phosphorylation. Structural comparison with a histidinol phosphate phosphatase suggests that the hydroxyl group of DosR S83 could play a role in activating the water molecule involved in the triggering of autodephosphorylation.

  19. Peripheral blood leukocytes of cows with subclinical endometritis show an altered cellular composition and gene expression.

    PubMed

    Düvel, Anna; Maaß, Janine; Heppelmann, Maike; Hussen, Jamal; Koy, Mirja; Piechotta, Marion; Sandra, Olivier; Smith, David G E; Sheldon, Iain Martin; Dieuzy-Labaye, Isabelle; Zieger, Peter; Schuberth, Hans Joachim

    2014-04-15

    Subclinical endometritis (SCE) is an important postpartum disease in dairy cows, but conventional cytobrush diagnosis often gives imprecise results. The aim of this study was to analyze disease-associated changes in peripheral blood as potential diagnostic parameters. Cellular subpopulations of blood leukocytes from cows with or without SCE (45-55 days postpartum) were flow-cytometrically quantified. Gene expression of whole blood leukocytes was assessed by PAXgene analysis. Subclinical endometritis cows showed significantly higher number of blood mononuclear cells and neutrophils. Among mononuclear cells, numbers of B-cells, NK-cells, and CD172a-positive monocytes were significantly elevated. Compared with non-SCE cows, blood leukocytes of SCE cows significantly expressed higher copy numbers of CXCL8, TNF, and IL12. To test whether circulating plasma factors are responsible for these changes, leukocytes, polymorphonuclear cells, and monocyte subpopulations (classical, intermediate, nonclassical) of healthy cows were stimulated with plasma of SCE and non-SCE cows. Although gene expression of whole leukocytes and polymorphonuclear cells remained unaltered, plasma from SCE animals significantly elevated expressed messenger RNA copy numbers of CXCL8, CXCL1, and IL1B in intermediate monocytes. In conclusion, elevated number of selected mononuclear subpopulations in peripheral blood and enhanced expression of distinct genes encoding for inflammatory mediators in blood leukocytes reflect the subclinical uterine inflammatory process in cows. Whether the observed changes in the periphery of SCE cows are the consequence of the uterine inflammatory process, or whether they affect the pathogenesis of the disease is currently unknown. PMID:24560452

  20. 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 ...

  1. 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.

  2. 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.

  3. From DOS to UNIX: An independent's experience

    SciTech Connect

    Hepguler, G.; Meehan, D.N.

    1993-06-01

    Union Pacific Resources Co. (UPRC) is a large independent operator with about 100 petroleum engineers. UPRC has a reasonably sophisticated PC network with many hundreds of PC's connected by several local area network (LAN) servers. Essentially all engineers have a 386-based PC on their desks with access to a host of software packages, peripheral devices, and mainframe computers, Many engineers have acquired 486-based PC's. UPRC's solution has involved migrating from a DOS-based platform on individual users' desks to UNIX workstations. Dozens of UNIX workstations are networked; some are on the desk', while others are located in central locations. Reservoir simulation, geostatistical modeling, image processing, and log analysis are now done exclusively on the UNIX workstations. Numerous DOS-based programs, however, have not yet been migrated into the UNIX environment. This paper describes the topography of both PC DOS and UNIX workstations networks in UPRC and examines the flow of information in each network configuration to identify differences. The successes and failures of various techniques for providing access to both platforms are presented.

  4. 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. PMID:26963519

  5. 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.

  6. Polymorphisms in immunoregulatory genes and the risk of histologic chorioamnionitis in Caucasoid women: a case control study

    PubMed Central

    Annells, Margaret F; Hart, Prue H; Mullighan, Charles G; Heatley, Susan L; Robinson, Jeffrey S; McDonald, Helen M

    2005-01-01

    Background Chorioamnionitis is a common underlying cause of preterm birth (PTB). It is hypothesised that polymorphisms in immunoregulatory genes influence the host response to infection and subsequent preterm birth. The relationship between histologic chorioamnionitis and 22 single nucleotide polymorphisms in 11 immunoregulatory genes was examined in a case-control study. Methods Placentas of 181 Caucasoid women with spontaneous PTB prior to 35 weeks were examined for histologic chorioamnionitis. Polymorphisms in genes IL1A, IL1B, IL1RN, IL1R1, tumour necrosis factor (TNF), IL4, IL6, IL10, transforming growth factor beta-1 (TGFB1), Fas (TNFRSF6), and mannose-binding lectin (MBL2) were genotyped by polymerase chain reaction and sequence specific primers. Multivariable logistic regression including demographic and genetic variables and Kaplan-Meier survival analyses of genotype frequencies and pregnancy outcome were performed. Results Sixty-nine (34%) women had histologic evidence of acute chorioamnionitis. Carriage of the IL10-1082A/-819T/592A (ATA) haplotype [Multivariable Odds ratio (MOR) 1.9, P = 0.05] and MBL2 codon 54Asp allele (MOR 2.0, P = 0.04), were positively associated with chorioamnionitis, while the TNFRSF6-1377A/-670G (AG) haplotype (MOR 0.4, P = 0.03) and homozygosity for TGFB1-800G/509T (GT) haplotype (MOR 0.2, P = 0.04) were negatively associated. Conclusion These findings demonstrate that polymorphisms in immunoregulatory genes IL10, MBL2, TNFRSF6 and TGFB1 may influence susceptibility to chorioamnionitis. PMID:15723707

  7. Association of Variants in Genes Related to the Immune Response and Obesity with Benign Prostatic Hyperplasia in CLUE II

    PubMed Central

    Lopez, David S.; Peskoe, Sarah B.; Tsilidis, Konstantinos K.; Hoffman-Bolton, Judy; Helzlsouer, Kathy J.; Isaacs, William B.; Smith, Michael W.; Platz, Elizabeth A.

    2014-01-01

    BACKGROUND Chronic inflammation and obesity may contribute to the genesis or progression of benign prostatic hyperplasia (BPH) and BPH-associated lower urinary tract symptoms (LUTS). The influence of variants in genes related to these states on BPH has not been studied extensively. Thus, we evaluated the association of 17 single nucleotide polymorphisms (SNPs) in immune response genes (IL1B, IL6, IL8, IL10, TNF, CRP, TLR4, RNASEL) and genes involved in obesity, including insulin regulation (LEP, ADIPOQ, PPARG, TCF7L2), with BPH. METHODS BPH cases (N=568) and age-frequency matched controls (N=568) were selected from among adult male CLUE II cohort participants who responded in 2000 to a mailed questionnaire. BPH was defined as BPH surgery, use of BPH medications, or symptomatic BPH (American Urological Association Symptom Index Score ≥15). Controls were men who had not had BPH surgery, did not use BPH medications, and whose symptom score was ≤7. Age-adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression. RESULTS None of the candidate SNPs was statistically significantly associated with BPH. However, we could not rule out possible weak associations for CRP rs1205 (1082C>T), ADIPOQ rs1501299 (276C>A), PPARG rs1801282 (-49C>G), and TCF7L2 rs7903146 (47833T>C). After summing risk alleles, men with ≥4 had an increased BPH risk compared with those with ≤1 (OR, 1.78; 95% CI, 1.10-2.89; Ptrend=0.006). CONCLUSION SNPs in genes related to immune response and obesity, especially in combination, may be associated with BPH. PMID:25224558

  8. 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.

  9. 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

  10. 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.

  11. Comparison of cytokine gene polymorphisms among Greek patients with invasive meningococcal disease or viral meningitis.

    PubMed

    Titmarsh, Callum J; Moscovis, Sophia M; Hall, Sharron; Tzanakaki, Georgina; Kesanopoulos, Konstantinos; Xirogianni, Athanasia; Scott, Rodney J; Blackwell, C Caroline

    2013-05-01

    High levels of pro-inflammatory cytokines are implicated in the severity of invasive meningococcal disease (IMD) and viral meningitis (VM). This study compared single-nucleotide polymorphisms (SNPs) in pro- and anti-inflammatory cytokine genes among patients with VM or IMD. Patient DNA samples were prepared by the National Meningitis Reference Laboratory in Athens: n=98 for IMD and n=53 for VM. The results for both patient groups were compared with data published for healthy Greek control data. Real-time PCR was used to assess the interleukin (IL) gene SNPs IL6 G-174C, IL1B C-511T, IL1RN T+2018C, IL10 G-1082A and IL8 A-251T and the tumour necrosis factor α (TNF-α) SNP TNFA G-308A. Differences were compared by Fisher's exact test. The genotype for high IL-6 responses was predominant among IMD (51%, P=0.0008) and VM (74.5%, P<0.0001) patients compared with the controls (31%). The genotype associated with high TNF-α responses was 5% among controls and lower for IMD (1.1%, P=0.0014) and VM (0%, P=0.052). There was no difference for IL-8 SNPs between controls and IMD (P=0.162), but the difference was significant for VM (P=0.0025). IL-6 (P=0.024) and IL-8 (P=0.00004) SNPs differed between IMD and VM. Reports on associations between IL-8 SNPs and cytokine responses differ. Because of its role in neutrophil attraction, differences in frequencies of the IL-8 SNP for IMD and VM require further investigation.

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

    PubMed

    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 conclusion

  13. 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

  14. 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

  15. Association of common polymorphisms in IL10, and in other genes related to inflammatory response and obesity with colorectal cancer

    PubMed Central

    Tsilidis, Konstantinos K.; Helzlsouer, Kathy J.; Smith, Michael W.; Grinberg, Victoriya; Hoffman-Bolton, Judith; Clipp, Sandra L.; Visvanathan, Kala

    2011-01-01

    Objective and methods The association of 17 candidate single nucleotide polymorphisms (SNPs) in IL10 and other immune response genes (CRP, TLR4, IL6, IL1B, IL8, TNF, RNASEL) and genes related to obesity (PPARG, TCF7L2, ADIPOQ, LEP) with colorectal cancer was investigated. Haplotype tagging SNPs were chosen for IL10, CRP, and TLR4. Incident colorectal cancer cases (n = 208) and matched controls (n = 381) were identified between baseline in 1989 and 2003 among participants in the CLUE II cohort. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using conditional logistic regression. Results Compared with the AA genotype at the candidate IL10-1082 locus (rs1800896), carrying one (OR, 0.79; 95% CI, 0.53–1.18) or two (OR, 0.58; 95% CI, 0.35–0.95) G alleles, a known higher producer of the anti-inflammatory cytokine IL-10, was associated with lower risk of colorectal cancer (ptrend = 0.03). Statistically significant associations with colorectal cancer were observed for three tagSNPs in IL10 (rs1800890, rs3024496, rs3024498) and one common haplotype, but these associations were due to high linkage disequilibrium with IL10-1082. Two CRP haplotypes (global p = 0.04) and TLR4 tagSNPs (rs7873784, rs11536891), but not TLR4 haplotypes, were associated with colorectal cancer. Conclusions Our study suggests that polymorphisms in IL10, and also possibly in CRP and other genes related to immune response or obesity may be associated with colorectal cancer. PMID:19760027

  16. 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

  17. 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. PMID:27445342

  18. 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.

  19. 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

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

    PubMed

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

    2013-06-01

    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.

  1. Embryonic exposure to carbendazim induces the transcription of genes related to apoptosis, immunotoxicity and endocrine disruption in zebrafish (Danio rerio).

    PubMed

    Jiang, Jinhua; Wu, Shenggan; Wu, Changxing; An, Xuehua; Cai, Leiming; Zhao, Xueping

    2014-12-01

    Carbendazim is one of the most widespread environmental contaminant that can cause major concern to human and animal reproductive system. To date, very few studies have been conducted on the toxic effect of carbendazim in the non-target organism zebrafish (Danio rerio). The study presented here aimed to assess how carbendazim triggers apoptosis, immunotoxicity and endocrine disruption pathways in zebrafish during its embryo development. Our results demonstrated that the expression patterns of many key genes involved in cell apoptosis pathway (e.g. P53, Mdm2, Bbc3 and Cas8) were significantly up-regulated upon the exposure to carbendazim at the concentration of 500 μg/L, while the Bcl2 and Cas3 were down-regulated at the same concentration, interestingly, the expression level of Ogg1 decreased at all the exposure concentrations. It was also observed that the mRNA levels of CXCL-C1C, CCL1, IL-1b and TNFα which were closely related to the innate immune system, were affected in newly hatched zebrafish after exposed to different concentrations of carbendazim. Moreover, the expression of genes that are involved in the hypothalamic-pituitary-gonadal/thyroid (HPG/HPT) axis including VTG, ERα, ERβ2, Dio1, Dio2, Thraa and Thrb were all down-regulated significantly after the exposure to carbendazim. The expression levels of two cytochrome P450 aromatases CYP19a and CYP19b were increased significantly after 20 and 100 μg/L carbendazim exposure, respectively. Taken together, our results indicated that carbendazim had the potential to induce cell apoptosis and cause immune toxicity as well as endocrine disruption in zebrafish during the embryo developmental stage. The information presented here also help to elucidate the environmental risks caused by the carbendazim-induced toxicity in aquatic organisms.

  2. Embryonic exposure to carbendazim induces the transcription of genes related to apoptosis, immunotoxicity and endocrine disruption in zebrafish (Danio rerio).

    PubMed

    Jiang, Jinhua; Wu, Shenggan; Wu, Changxing; An, Xuehua; Cai, Leiming; Zhao, Xueping

    2014-12-01

    Carbendazim is one of the most widespread environmental contaminant that can cause major concern to human and animal reproductive system. To date, very few studies have been conducted on the toxic effect of carbendazim in the non-target organism zebrafish (Danio rerio). The study presented here aimed to assess how carbendazim triggers apoptosis, immunotoxicity and endocrine disruption pathways in zebrafish during its embryo development. Our results demonstrated that the expression patterns of many key genes involved in cell apoptosis pathway (e.g. P53, Mdm2, Bbc3 and Cas8) were significantly up-regulated upon the exposure to carbendazim at the concentration of 500 μg/L, while the Bcl2 and Cas3 were down-regulated at the same concentration, interestingly, the expression level of Ogg1 decreased at all the exposure concentrations. It was also observed that the mRNA levels of CXCL-C1C, CCL1, IL-1b and TNFα which were closely related to the innate immune system, were affected in newly hatched zebrafish after exposed to different concentrations of carbendazim. Moreover, the expression of genes that are involved in the hypothalamic-pituitary-gonadal/thyroid (HPG/HPT) axis including VTG, ERα, ERβ2, Dio1, Dio2, Thraa and Thrb were all down-regulated significantly after the exposure to carbendazim. The expression levels of two cytochrome P450 aromatases CYP19a and CYP19b were increased significantly after 20 and 100 μg/L carbendazim exposure, respectively. Taken together, our results indicated that carbendazim had the potential to induce cell apoptosis and cause immune toxicity as well as endocrine disruption in zebrafish during the embryo developmental stage. The information presented here also help to elucidate the environmental risks caused by the carbendazim-induced toxicity in aquatic organisms. PMID:25304545

  3. 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

  4. Recovery of CD4+ T Cells in HIV patients with a stable virologic response to antiretroviral therapy is associated with polymorphisms of interleukin-6 and central major histocompatibility complex genes.

    PubMed

    Fernandez, Sonia; Rosenow, Ann A; James, Ian R; Roberts, Steven G; Nolan, Richard C; French, Martyn A; Price, Patricia

    2006-01-01

    We investigated whether polymorphisms in genes associated with HIV disease progression and/or immune activation affect CD4+ T-cell recovery in HIV patients who began combination antiretroviral therapy (ART) with advanced immunodeficiency and achieved stable control of plasma viremia. Patients with CD4 T-cell counts <300 cells/microL (n = 33) and >400 cells/microL (n = 37) on ART were compared. A multiple case-control logistic regression associated carriage of BAT1(1,2) or interleukin (IL)6-174(2,2) with low CD4 T-cell counts (P = 0.012). BAT1*2 uniquely marks the central major histocompatibility complex region of a conserved haplotype (HLA-A1,B8,BAT1*2,TNFA-308*2,DR3,DQ2). There was no association between alleles carried at CCR5Delta32, CCR5 59029, CCR5 59353, CCR2+190 (V64I), SDF1 3'UTR, IL1A+4845, IL1B+3953, IL4-589, IL10-592, IL10-R1+536, IL10-R1+1112, IL12B 3'UTR, TNFA-308, or TNFA-1031 and CD4 T-cell counts. We suggest that immune activation and/or CD4 T-cell apoptosis in HIV patients on effective ART is influenced by genetic factors.

  5. Fast interrupt platform for extended DOS

    NASA Technical Reports Server (NTRS)

    Duryea, T. W.

    1995-01-01

    Extended DOS offers the unique combination of a simple operating system which allows direct access to the interrupt tables, 32 bit protected mode access to 4096 MByte address space, and the use of industry standard C compilers. The drawback is that fast interrupt handling requires both 32 bit and 16 bit versions of each real-time process interrupt handler to avoid mode switches on the interrupts. A set of tools has been developed which automates the process of transforming the output of a standard 32 bit C compiler to 16 bit interrupt code which directly handles the real mode interrupts. The entire process compiles one set of source code via a make file, which boosts productivity by making the management of the compile-link cycle very simple. The software components are in the form of classes written mostly in C. A foreground process written as a conventional application which can use the standard C libraries can communicate with the background real-time classes via a message passing mechanism. The platform thus enables the integration of high performance real-time processing into a conventional application framework.

  6. Teaching Bibliometric Analysis and MS/DOS Commands.

    ERIC Educational Resources Information Center

    Dou, Henri; And Others

    1988-01-01

    Outlines the steps involved in bibliometric studies, and demonstrates the ability to execute simple studies on microcomputers by downloading files using only the capability of MS/DOS. Detailed illustrations of the MS/DOS commands used are provided. (eight references) (CLB)

  7. 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.

  8. 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

  9. The Heme-Based Oxygen-Sensor Phosphodiesterase Ec DOS (DosP): Structure-Function Relationships

    PubMed Central

    Shimizu, Toru

    2013-01-01

    Escherichia coli Direct Oxygen Sensor (Ec DOS, also known as Ec DosP) is a heme-based O2-sensing phosphodiesterase from Escherichia coli that catalyzes the conversion of cyclic-di-GMP to linear di-GMP. Cyclic-di-GMP is an important second messenger in bacteria, highlighting the importance of understanding structure-function relationships of Ec DOS. Ec DOS is composed of an N-terminal heme-bound O2-sensing PAS domain and a C-terminal phosphodiesterase catalytic domain. Notably, its activity is markedly enhanced by O2 binding to the heme Fe(II) complex in the PAS sensor domain. X-ray crystal structures and spectroscopic and catalytic characterization of the wild-type and mutant proteins have provided important structural and functional clues to understanding the molecular mechanism of intramolecular catalytic regulation by O2 binding. This review summarizes the intriguing findings that have obtained for Ec DOS. PMID:25586128

  10. 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.

  11. 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

  12. Genes and gene regulation

    SciTech Connect

    MacLean, N.

    1988-01-01

    Genetics has long been a central topic for biologists, and recent progress has captured the public imagination as well. This book addresses questions that are at the leading edge of this continually advancing discipline. In tune with the increasing emphasis on molecular biology and genetic engineering, this text emphasizes the molecular aspects of gene expression, and the evolution of gene sequence organization and control. It reviews the genetic material of viruses, bacteria, and of higher organisms. Cells and organisms are compared in terms of gene numbers, their arrangements within a cell, and the control mechanisms which regulate the activity of genes.

  13. Influence of interleukin-1 gene polymorphism on periodontal regeneration in intrabony defects.

    PubMed

    Christgau, M; Aslanidis, C; Felden, A; Hiller, K A; Schmitz, G; Schmalz, G

    2003-02-01

    The aim of this controlled retrospective study was to evaluate the influence of an IL-1 gene polymorphism on the clinical and radiographic healing outcomes of GTR therapy. The study included 47 adult periodontitis patients with 94 deep intrabony defects treated by GTR using different membrane materials. The following clinical parameters were recorded at baseline and 12 months after surgery: papillary bleeding index (PBI), gingival recession (REC), probing pocket depth (PPD), clinical attachment level (CAL), and the vertical relative attachment gain (V-rAG). Bone changes in the defect regions due to GTR therapy were quantitatively evaluated using digital subtraction radiography (DSR). Polymorphisms of the IL-1A gene at position - 889 and of the IL-1B gene at position + 3953 were analyzed by PCR. Statistical analysis was performed using the Mann-Whitney-U and the Wilcoxon-Signed-Rank tests (alpha = 0.05). The study comprised 19 IL-1 genotype positive (IL-1 +) patients and 28 IL-1 genotype negative (IL-1 -) patients. Twelve months after GTR therapy, both patient groups revealed statistically significant PPD reductions and CAL gain [median (25/75% percentiles)]: Delta PPD [IL-1 + : 4.0 (2.5/5.0) mm; IL-1-: 3.8 (3.0/4.9) mm], Delta CAL [IL-1 + : 3.5 (3.0/4.8) mm; IL-1 -: 3.0 (1, 2/4, 5) mm]. V-rAG amounted to 60.0 (47.7/78.6)% in IL-1 + patients and 53.1 (43.4/81.9)% in IL-1 - patients. Both patient groups showed significant bone density gain in 40% (IL-1 +) and 43.6% (IL-1 -) of the initial defect area due to GTR. Neither the clinical nor the radiographic healing parameters revealed any statistically significant differences in the GTR healing outcome between IL-1 + and IL-1 - patients. In conclusion, these 12-month findings indicate that the IL-1 gene polymorphism has no influence on the clinical and radiographic regeneration results following GTR therapy.

  14. Interleukin-1β gene variants are associated with QTc interval prolongation following cardiac surgery: a prospective observational study

    PubMed Central

    Kertai, Miklos D.; Ji, Yunqi; Li, Yi-Ju; Mathew, Joseph P.; Daubert, James P.; Podgoreanu, Mihai V.

    2016-01-01

    Background We characterized cardiac surgery-induced dynamic changes of the corrected QT (QTc) interval and tested the hypothesis that genetic factors are associated with perioperative QTc prolongation independent of clinical and procedural factors. Methods All study subjects were ascertained from a prospective study of patients who underwent elective cardiac surgery during August 1999 to April 2002. We defined a prolonged QTc interval as >440 msec, measured from 24-hr pre- and postoperative 12-lead electrocardiograms. The association of 37 single nucleotide polymorphisms (SNPs) in 21 candidate genes – involved in modulating arrhythmia susceptibility pathways with postoperative QTc changes–was investigated in a two-stage design with a stage I cohort (n = 497) nested within a stage II cohort (n = 957). Empirical P values (Pemp) were obtained by permutation tests with 10,000 repeats. Results After adjusting for clinical and procedural risk factors, we selected four SNPs (P value range, 0.03-0.1) in stage I, which we then tested in the stage II cohort. Two functional SNPs in the pro-inflammatory cytokine interleukin-1β (IL1β), rs1143633 (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.53 to 0.95; Pemp = 0.02) and rs16944 (OR, 1.31; 95% CI, 1.01 to 1.70; Pemp = 0.04), remained independent predictors of postoperative QTc prolongation. The ability of a clinico-genetic model incorporating the two IL1B polymorphisms to classify patients at risk for developing prolonged postoperative QTc was superior to a clinical model alone, with a net reclassification improvement of 0.308 (P = 0.0003) and an integrated discrimination improvement of 0.02 (P = 0.000024). Conclusion The results suggest a contribution of IL1β in modulating susceptibility to postoperative QTc prolongation after cardiac surgery. PMID:26858093

  15. 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

  16. Studying Genes

    MedlinePlus

    ... Area What are genes? Genes are sections of DNA that contain instructions for making the molecules—many ... material in an organism. This includes genes and DNA elements that control the activity of genes. Does ...

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

    PubMed

    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

    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_HUMAN, IFIT2, TRAIL, IFIT1, PSB8_HUMAN, 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.

  18. Modic changes and interleukin 1 gene locus polymorphisms in occupational cohort of middle-aged men

    PubMed Central

    Solovieva, Svetlana; Luoma, Katariina; Raininko, Raili; Leino-Arjas, Päivi; Riihimäki, Hilkka

    2009-01-01

    According to recent systematic reviews, Modic changes are associated with low-back pain. However, their pathophysiology remains largely unknown. A previous study of Northern Finnish males implicated that IL1A and MMP3 polymorphisms play a role in type II Modic changes. The purpose of the current study was to examine the association of IL1 cluster polymorphisms with Modic changes amongst middle-aged men in Southern Finland. The final study sample consisted of 108 men from three different occupations, who underwent magnetic resonance imaging (MRI) with a 0.1 T-scanner. Six single nucleotide polymorphisms (SNP) in the IL1 gene cluster (IL1A c.1-889C>T; IL1B c.3954C>T; IL1RN c.1812G>A; IL1RN c.1887G>C; IL1RN c.11100T>C; IL1RN c.1506G>A) were genotyped with the SNP-TRAP method or by allele-specific primer extension on modified microarray. In all, 45 subjects had Modic changes at one or more disc levels. The presence of the minor allele of IL1A (c.1-889C>T) was associated with these changes (any Modic change p = 0.031, type II changes p = 0.036). The carriers of the T-allele had a 2.5-fold risk of Modic change and the association was independent of the other IL1 gene cluster loci studied. In addition, a minor haplotype, with a frequency of 7.5% in the study population, including the minor alleles of IL1A c.1-889C>T, IL1RN c.1812G>A, and IL1RN c.1506G>A, was significantly associated with Modic changes. This observation is in accordance with the previous finding from a different geographical area, and thus confirms the importance of the IL1A gene in the pathophysiology of Modic changes. PMID:19701653

  19. 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.

  20. Inflammation- and lipid metabolism-related gene network expression in visceral and subcutaneous adipose depots of Holstein cows.

    PubMed

    Ji, P; Drackley, J K; Khan, M J; Loor, J J

    2014-01-01

    This experiment was conducted to determine the effects of energy overfeeding on gene expression in mesenteric (MAT), omental (OAT), and subcutaneous (SAT) adipose tissue (AT) from nonpregnant and nonlactating Holstein cows. Eighteen cows were randomly assigned to either a controlled energy [LE, net energy for lactation (NE(L)) = 1.35 Mcal/kg of dry matter (DM)] or moderate energy-overfed group (HE, NE(L) = 1.62 Mcal/kg of DM) for 8 wk. Cows were then euthanized and subsamples of MAT, OAT, and SAT were harvested for transcript profiling via quantitative PCR of 34 genes involved in lipogenesis, triacylglycerol (TAG) synthesis, lactate signaling, hepatokine signaling, lipolysis, transcription regulation, and inflammation. The interaction of dietary energy and adipose depot was not significant for any gene analyzed except LPL, which indicated a consistent response to diet. Expression of ACACA and FASN was greater in SAT than MAT, whereas expression of SCD and ADFP were greatest in SAT, intermediate in OAT, and lowest in MAT. However, the 2 visceral depots had greater expression of THRSP, ACLY, LPL, FABP4, GPAM, and LPIN1 compared with SAT. The transcription factor SREBF1 was more highly expressed in MAT and SAT than in OAT. The expression of PNPLA2 was greater in visceral AT sites than in SAT, but other lipolysis-related genes were not differentially expressed among AT depots. Visceral AT depots had greater expression of LEP, ADIPOQ, and SAA3 compared with SAT. Moreover, MAT had greater expression than SAT of proinflammatory cytokines (IL1B and IL6), IL6 receptor (IL6R), and chemokines (CCL2 and CCL5). However, TNF expression was greatest in SAT, lowest in OAT, and intermediate in MAT. Overall, results indicated that visceral AT might be more active in uptake of preformed long-chain fatty acids than SAT, whereas de novo fatty acid synthesis could make a greater contribution to the intracellular pool of fatty acids in SAT than in visceral AT. The visceral AT compared

  1. 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

  2. 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

  3. Diet-induced obesity alters immune cell infiltration and expression of inflammatory cytokine genes in mouse ovarian and peri-ovarian adipose depot tissues.

    PubMed

    Nteeba, J; Ortinau, L C; Perfield, J W; Keating, A F

    2013-11-01

    Dysregulation of immune cells and/or altered inflammatory signaling have been implicated with reproductive dysfunction. Physiological changes leading to perturbations in the profile of immune cells and/or pro-inflammatory cytokines in or around female reproductive tissue could potentially have profound effects on ovarian function. Obesity is associated with chronic low-grade inflammation due, in part, to increased immune cell infiltration and inflammation in visceral adipose depots. This study investigated the impact of diet-induced obesity on immune cell infiltration and inflammation in peri-ovarian adipose tissue and mRNA expression of key inflammatory markers and microRNAs (miRs) in ovarian tissue. Six-week-old female C57Bl/6J mice were fed a standard chow or high-fat diet (HFD; 60% kcal fat) for approximately 7 months, at which time peri-ovarian adipose tissue and ovarian tissues were collected. Histological analysis of peri-ovarian adipose tissue from obese mice revealed increased (P < 0.05) adipocyte size and the presence of crown-like structures, the morphological presentation of infiltrating immune cells in adipose tissue, along with increases (P < 0.05) in the mRNA levels of markers of T-cells, activated macrophages, inflammatory cytokines, and chemokines. Ovarian mRNA levels of Il1b, Il6, Tnfa, p55, p75, Ccl2, Ikbkb, and Rela were higher in obese tissue (P < 0.05), with a strong trend (P = 0.06) for an increase in Nos2 and RELA protein. Additionally, ovarian miR125b and miR143 levels were decreased (P = 0.1). These data demonstrate that diet-induced obesity elevates expression of inflammatory-mediator genes in both the ovary and surrounding adipose depot, potentially negatively affecting ovarian function.

  4. Dos dosis de vacuna contra los VPH pueden proteger

    Cancer.gov

    Dos dosis de Cervarix, la vacuna contra virus del papiloma humano (VPH), fueron tan efectivas como la pauta normal actual de tres dosis después de cuatro años de seguimiento. El estudio de vacuna en Costa Rica, patrocinado por el NCI, fue diseñado para ev

  5. 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…

  6. MS DOS Tool Software Including Public Domain, Grades K-6.

    ERIC Educational Resources Information Center

    New York City Board of Education, Brooklyn, NY. Div. of Computer Information Services.

    This curriculum guide is designed to assist teachers and supervisors in introducing lower elementary students to the MS DOS computer and the word processing program PC Write. Accompanying this guide are two program disks: PC Write, which is a public domain word processing program and Disk Care, which reinforces rules for caring for disks. The…

  7. Associations between polymorphisms of interleukin-6 and related cytokine genes and serum liver damage markers: a cross-sectional study in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study.

    PubMed

    Sugimoto, Yuka; Wakai, Kenji; Nakagawa, Hiroko; Suma, Shino; Sasakabe, Tae; Sakamoto, Tatsuhiko; Takashima, Naoyuki; Suzuki, Sadao; Ogawa, Shin; Ohnaka, Keizo; Kuriyama, Nagato; Arisawa, Kokichi; Mikami, Haruo; Kubo, Michiaki; Hosono, Satoyo; Hamajima, Nobuyuki; Tanaka, Hideo

    2015-02-25

    Cytokines, including interleukin-6 (IL-6), play an important role in the liver. The aim of this study was to investigate associations between common polymorphisms in potential functional promoters of cytokine genes and liver damage markers among enrollees of a large Japanese cohort study. Subjects included 3257 Japanese individuals (1608 men and 1649 women, aged 35-69 years). Six single nucleotide polymorphisms (SNPs) in the promoter regions of five cytokine genes, IL1B (T-31C), IL6 (C-634G), IL8 (T-251A), IL10 (T-819C), tumor necrosis factor-A (TNFA) (T-1031C), and TNFA (C-857T), were genotyped by polymerase chain reaction. Information regarding alcohol intake, smoking habits, height, and weight was collected by a self-administered questionnaire. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured during a routine health check-up. Of the six SNPs genotyped, an IL6 polymorphism (rs1800796, C-634G) was most strongly associated with a liver damage marker, AST. Mean serum AST was significantly different among the three genotypes (mean ± SD, 22.7 ± 7.3 IU/L for CC, 22.8 ± 7.7 IU/L for CG, and 24.3 ± 8.6 IU/L for GG, p=0.011 by analysis of variance). The differences remained significant after adjustment for potential confounders by general linear models. The variations in mean serum AST and ALT levels were marked especially among men. Thus, the functional polymorphism IL6 C-634G may affect serum AST and ALT levels, possibly through different IL-6 production.

  8. Amphetamine and environmentally induced hyperthermia differentially alter the expression of genes regulating vascular tone and angiogenesis in the meninges and associated vasculature.

    PubMed

    Thomas, Monzy; George, Nysia I; Patterson, Tucker A; Bowyer, John F

    2009-10-01

    An amphetamine (AMPH) regimen that does not produce a prominent blood-brain barrier breakdown was shown to significantly alter the expression of genes regulating vascular tone, immune function, and angiogenesis in vasculature associated with arachnoid and pia membranes of the forebrain. Adult-male Sprague-Dawley rats were given either saline injections during environmentally-induced hyperthermia (EIH) or four doses of AMPH with 2 h between each dose (5, 7.5, 10, and 10 mg/kg d-AMPH, s.c.) that produced hyperthermia. Rats were sacrificed either 3 h or 1 day after dosing, and total RNA and protein was isolated from the meninges, arachnoid and pia membranes, and associated vasculature (MAV) that surround the forebrain. Vip, eNos, Drd1a, and Edn1 (genes regulating vascular tone) were increased by either EIH or AMPH to varying degrees in MAV, indicating that EIH and AMPH produce differential responses to enhance vasodilatation. AMPH, and EIH to a lesser extent, elicited a significant inflammatory response at 3 h as indicated by an increased MAV expression of cytokines Il1b, Il6, Ccl-2, Cxcl1, and Cxcl2. Also, genes related to heat shock/stress and disruption of vascular homeostasis such as Icam1 and Hsp72 were also observed. The increased expression of Ctgf and Timp1 and the decreased expression of Akt1, Anpep, and Mmp2 and Tek (genes involved in stimulating angiogenesis) from AMPH exposure suggest that angiogenesis was arrested or disrupted in MAV to a greater extent by AMPH compared to EIH. Alterations in vascular-related gene expression in the parietal cortex and striatum after AMPH were less in magnitude than in MAV, indicating less of a disruption of vascular homeostasis in these two regions. Changes in the levels of insulin-like growth factor binding proteins Igfbp1, 2, and 5 in MAV, compared to those in striatum and parietal cortex, imply an interaction between these regions to regulate the levels of insulin-like growth factor after AMPH damage. Thus, the

  9. 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.

  10. Adipose and liver gene expression profiles in response to treatment with a nonsteroidal antiinflammatory drug after calving in grazing dairy cows.

    PubMed

    Vailati Riboni, M; Meier, S; Priest, N V; Burke, C R; Kay, J K; McDougall, S; Mitchell, M D; Walker, C G; Crookenden, M; Heiser, A; Roche, J R; Loor, J J

    2015-05-01

    The peripartal or transition period in dairy cattle is often characterized by an inflammatory state that, if not controlled, could be detrimental to production, health, and fertility. Approaches to control the postpartal degree of inflammation include treatments with nonsteroidal antiinflammatory drugs (NSAID) postcalving, which have improved cow production and health. To date, most of the research on NSAID has been conducted in confinement cows that reach milk production levels substantially greater than those on pasture. Furthermore, little data are available on the effect of NSAID on the mRNA expression of inflammation and metabolism-related genes. Transcription regulation is an important mechanism of inflammation and metabolic control. The present study was conducted to examine hepatic and adipose tissue gene expression in response to injections of an NSAID, carprofen, on 1, 3, and 5 d after calving. Grazing Holstein-Friesian cows from a control group and 1 treated with carprofen during the first 5 d postcalving were used. Liver and subcutaneous adipose tissue biopsies were harvested at -1, 1, and 2 wk relative to parturition. More than 30 genes associated with fatty acid oxidation, growth hormone/insulin-like growth factor-1 axis, hepatokines, lipoprotein metabolism, gluconeogenesis, and inflammation were analyzed. After calving, data suggest that both tissues respond to inflammation signals at the onset of lactation. Administration of NSAID led to greater hepatic expression of pyruvate dehydrogenase kinase, isozyme 4 (PDK4), which helps regulate gluconeogenesis, and microsomal triglyceride transfer protein (MTTP), important for the assembly and secretion of very low-density lipoproteins. In adipose tissue, NSAID administration resulted in greater expression of the inflammation-related genes interleukin-1, β (IL1B), interleukin-6 receptor (IL6R), toll-like receptor 4 (TLR4), and chemokine (C-C motif) ligand 5 (CCL5). The data support the role of inflammation

  11. Adipose and liver gene expression profiles in response to treatment with a nonsteroidal antiinflammatory drug after calving in grazing dairy cows.

    PubMed

    Vailati Riboni, M; Meier, S; Priest, N V; Burke, C R; Kay, J K; McDougall, S; Mitchell, M D; Walker, C G; Crookenden, M; Heiser, A; Roche, J R; Loor, J J

    2015-05-01

    The peripartal or transition period in dairy cattle is often characterized by an inflammatory state that, if not controlled, could be detrimental to production, health, and fertility. Approaches to control the postpartal degree of inflammation include treatments with nonsteroidal antiinflammatory drugs (NSAID) postcalving, which have improved cow production and health. To date, most of the research on NSAID has been conducted in confinement cows that reach milk production levels substantially greater than those on pasture. Furthermore, little data are available on the effect of NSAID on the mRNA expression of inflammation and metabolism-related genes. Transcription regulation is an important mechanism of inflammation and metabolic control. The present study was conducted to examine hepatic and adipose tissue gene expression in response to injections of an NSAID, carprofen, on 1, 3, and 5 d after calving. Grazing Holstein-Friesian cows from a control group and 1 treated with carprofen during the first 5 d postcalving were used. Liver and subcutaneous adipose tissue biopsies were harvested at -1, 1, and 2 wk relative to parturition. More than 30 genes associated with fatty acid oxidation, growth hormone/insulin-like growth factor-1 axis, hepatokines, lipoprotein metabolism, gluconeogenesis, and inflammation were analyzed. After calving, data suggest that both tissues respond to inflammation signals at the onset of lactation. Administration of NSAID led to greater hepatic expression of pyruvate dehydrogenase kinase, isozyme 4 (PDK4), which helps regulate gluconeogenesis, and microsomal triglyceride transfer protein (MTTP), important for the assembly and secretion of very low-density lipoproteins. In adipose tissue, NSAID administration resulted in greater expression of the inflammation-related genes interleukin-1, β (IL1B), interleukin-6 receptor (IL6R), toll-like receptor 4 (TLR4), and chemokine (C-C motif) ligand 5 (CCL5). The data support the role of inflammation

  12. Gene doping.

    PubMed

    Harridge, Stephen D R; Velloso, Cristiana P

    2008-01-01

    Gene doping is the misuse of gene therapy to enhance athletic performance. It has recently been recognised as a potential threat and subsequently been prohibited by the World Anti-Doping Agency. Despite concerns with safety and efficacy of gene therapy, the technology is progressing steadily. Many of the genes/proteins which are involved in determining key components of athletic performance have been identified. Naturally occurring mutations in humans as well as gene-transfer experiments in adult animals have shown that altered expression of these genes does indeed affect physical performance. For athletes, however, the gains in performance must be weighed against the health risks associated with the gene-transfer process, whereas the detection of such practices will provide new challenges for the anti-doping authorities.

  13. A natural product based DOS library of hybrid systems.

    PubMed

    Prabhu, Ganesh; Agarwal, Shalini; Sharma, Vijeta; Madurkar, Sanjay M; Munshi, Parthapratim; Singh, Shailja; Sen, Subhabrata

    2015-05-01

    Here we described a natural product inspired modular DOS strategy for the synthesis of a library of hybrid systems that are structurally and stereochemically disparate. The main scaffold is a pyrroloisoquinoline motif, that is synthesized from tandem Pictet-Spengler lactamization. The structural diversity is generated via "privileged scaffolds" that are attached at the appropriate site of the motif. Screening of the library compounds for their antiplasmodial activity against chloroquine sensitive 3D7 cells indicated few compounds with moderate activity (20-50 μM). A systematic comparison of structural intricacy between the library members and a natural product dataset obtained from ZINC(®) revealed comparable complexity. PMID:25794788

  14. 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

  15. 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

  16. Trichoderma genes

    SciTech Connect

    Foreman, Pamela; Goedegebuur, Frits; Van Solingen, Pieter; Ward, Michael

    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.

  17. [Gene therapy].

    PubMed

    Rodríguez-Fragoso, L

    1997-01-01

    In the last years there has been much progress in our understanding of molecular mechanisms in the pathogenesis of disease. In this review we provide an overview of gene therapy, its most actualized techniques for gene delivery, and we give specific examples of laboratory and clinical achievements to date. The development of methods for delivering genes to mammalian cells has stimulated great interest in the possibility of treating human disease by gene-based therapies. As a result, concepts and methods that would have been considered purely science fiction 50 years ago are now used in the treatment of diseases. The widespread application of gene therapy technology to many diseases is already breaking down the traditional boundaries of modern medicine. However, despite its progress, several key technical drawbacks need to be overcome before gene therapy can be used safely and effectively in clinical settings. Technological developments, particularly in the areas of gene delivery and cell transplantation, will be critical for the successful practice of gene therapy.

  18. Gene Therapy

    PubMed Central

    Baum, Bruce J

    2014-01-01

    Applications of gene therapy have been evaluated in virtually every oral tissue, and many of these have proved successful at least in animal models. While gene therapy will not be used routinely in the next decade, practitioners of oral medicine should be aware of the potential of this novel type of treatment that doubtless will benefit many patients with oral diseases. PMID:24372817

  19. 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)

  20. 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.

  1. 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

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

    PubMed Central

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

    2015-01-01

    Objective: 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. Methods: 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. Results: 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). Conclusions: No single marker was significantly associated with either rate of lung function decline or serum CRP levels. PMID:26722511

  3. 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.

  4. 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 Central

    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. PMID:25084004

  5. 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)

  6. 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…

  7. Alterations of gene expression and protein synthesis in co-cultured adipose tissue-derived stem cells and squamous cell-carcinoma cells: consequences for clinical applications

    PubMed Central

    2014-01-01

    Introduction This is the first study evaluating the interactions of human adipose tissue derived stem cells (ADSCs) and human squamous cell carcinoma cells (SCCs), with regard to a prospective cell-based skin regenerative therapy and a thereby unintended co-localization of ADSCs and SCCs. Methods ADSCs were co-cultured with A431-SCCs and primary SCCs (pSCCs) in a transwell system, and cell-cell interactions were analyzed by assessing doubling time, migration and invasion, angiogenesis, quantitative real time PCR of 229 tumor associated genes, and multiplex protein assays of 20 chemokines and growth factors and eight matrix metalloproteinases (MMPS). Results of co-culture were compared to those of the respective mono-culture. Results ADSCs’ proliferation on the plate was significantly increased when co-cultured with A431-SCCs (P = 0.038). PSCCs and ADSCs significantly decreased their proliferation in co-culture if cultured on the plate (P <0.001 and P = 0.03). The migration of pSCC was significantly increased in co-culture (P = 0.009), as well as that of ADSCs in A431-SCC-co-culture (P = 0.012). The invasive behavior of pSCCs and A431-SCCs was significantly increased in co-culture by a mean of 33% and 35%, respectively (P = 0.038 and P <0.001). Furthermore, conditioned media from co-cultured ADSC-A431-SCCs and co-cultured ADSCs-pSCCs induced tube formation in an angiogenesis assay in vitro. In A431-SCC-co-culture 36 genes were up- and 6 were down-regulated in ADSCs, in A431-SCCs 14 genes were up- and 8 genes were down-regulated. In pSCCs-co-culture 36 genes were up-regulated in ADSCs, two were down-regulated, one gene was up-regulated in pSCC, and three genes were down-regulated. Protein expression analysis revealed that three proteins were exclusively produced in co-culture (CXCL9, IL-1b, and MMP-7). In A431-SCC-co-culture the concentration of 17 proteins was significantly increased compared to the ADSCs mono-culture (2.8- to 357-fold

  8. 33 CFR 106.250 - Declaration of Security (DoS).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., ensure the Facility Security Officer (FSO) and Master, Vessel Security Officer (VSO), or their designated... FSO and Master, VSO, or their designated representatives, must sign the written DoS. (c) Neither...

  9. 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

  10. The DosR Regulon Modulates Adaptive Immunity and Is Essential for Mycobacterium tuberculosis Persistence

    PubMed Central

    Mehra, Smriti; Foreman, Taylor W.; Didier, Peter J.; Ahsan, Muhammad H.; Hudock, Teresa A.; Kissee, Ryan; Golden, Nadia A.; Gautam, Uma S.; Johnson, Ann-Marie; Alvarez, Xavier; Russell-Lodrigue, Kasi E.; Doyle, Lara A.; Roy, Chad J.; Niu, Tianhua; Blanchard, James L.; Khader, Shabaana A.; Lackner, Andrew A.; Sherman, David R.

    2015-01-01

    Rationale: Hypoxia promotes dormancy by causing physiologic changes to actively replicating Mycobacterium tuberculosis. DosR controls the response of M. tuberculosis to hypoxia. Objectives: To understand DosR's contribution in the persistence of M. tuberculosis, we compared the phenotype of various DosR regulon mutants and a complemented strain to M. tuberculosis in macaques, which faithfully model M. tuberculosis infection. Methods: We measured clinical and microbiologic correlates of infection with M. tuberculosis relative to mutant/complemented strains in the DosR regulon, studied lung pathology and hypoxia, and compared immune responses in lung using transcriptomics and flow cytometry. Measurements and Main Results: Despite being able to replicate initially, mutants in DosR regulon failed to persist or cause disease. On the contrary, M. tuberculosis and a complemented strain were able to establish infection and tuberculosis. The attenuation of pathogenesis in animals infected with the mutants coincided with the appearance of a Th1 response and organization of hypoxic lesions wherein M. tuberculosis expressed dosR. The lungs of animals infected with the mutants (but not the complemented strain) exhibited early transcriptional signatures of T-cell recruitment, activation, and proliferation associated with an increase of T cells expressing homing and proliferation markers. Conclusions: Delayed adaptive responses, a hallmark of M. tuberculosis infection, not only lead to persistence but also interfere with the development of effective antituberculosis vaccines. The DosR regulon therefore modulates both the magnitude and the timing of adaptive immune responses in response to hypoxia in vivo, resulting in persistent infection. Hence, DosR regulates key aspects of the M. tuberculosis life cycle and limits lung pathology. PMID:25730547

  11. Association between Interleukin-1B C-31T Polymorphism and Obesity in Japanese

    PubMed Central

    Suzuki, Koji; Inoue, Takashi; Yanagisawa, Atsumi; Kimura, Asami; Ito, Yoshinori; Hamajima, Nobuyuki

    2009-01-01

    Background Recent studies have revealed a close relationship between obesity and polymorphism in the inflammation gene. However, the association between interleukin-1beta (IL-1β) and obesity remains controversial. We therefore investigated the association between IL-1B C-31T polymorphism and obesity in Japanese. Methods The participants were 802 inhabitants (281 men and 521 women) of Japan, aged 39 to 88 years, who attended a health examination in 2003. Body height, weight, waist and hip circumferences, and body fat percentage were measured. The IL-1B C-31T polymorphism was genotyped by polymerase chain reaction with confronting 2-pair primers. The association between IL-1B C-31T genotypes and various indices of obesity was then investigated. The confounding factor-adjusted odds ratios (OR) and 95% confidence intervals (CI) for obesity were calculated for each IL-1B C-31T genotype by using unconditional logistic regression analysis. Results Among male carriers of the CT and TT genotypes, the ORs for high body fat percentage were 2.58 (95% CI, 1.17–6.34) and 2.81 (1.17–7.33), respectively, as compared to carriers of the CC genotype (P for trend = 0.037). Among women, carriers of the TT genotype had significantly higher ORs for high BMI (OR, 2.13; 95% CI, 1.25–3.67) and large waist circumference (2.49; 1.37–4.66), as compared to women with the CC genotype (P for trend = 0.005 and 0.004, respectively). Conclusions The IL-1B C-31T polymorphism is associated with obesity in Japanese. Men and women with the TT genotype of IL-1B C-31T had a higher risk for obesity than those with the CC genotype. PMID:19398847

  12. Genes and Hearing Loss

    MedlinePlus

    ... Meeting Calendar Find an ENT Doctor Near You Genes and Hearing Loss Genes and Hearing Loss Patient ... mutation may only have dystopia canthorum. How Do Genes Work? Genes are a road map for the ...

  13. 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. PMID:8594596

  14. 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.

  15. 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

  16. 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

  17. Documenting 35 Years of Land Cover Change: Lago Cachet Dos Drainage, Chile

    NASA Astrophysics Data System (ADS)

    Friesen, B.; Nimick, D.; McGrath, D.; Cole, C.

    2014-12-01

    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 m3) rapidly drains from the lake and flows south-southeast through the Colonia Glacier. These catastrophic events cause massive erosion of lake-bed and 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 thickness and 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 km2 in 1979 to 4.41 km2 in 2014, primarily due to erosion of valley-fill deposits at 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.

  18. 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.

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

    PubMed

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

    2010-05-01

    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.

  20. Organization of immunoglobulin genes.

    PubMed

    Tonegawa, S; Brack, C; Hozumi, N; Pirrotta, V

    1978-01-01

    The nucleotide-sequence determination of a cloned, embryonic Vlambda gene directly demonstrated that V genes are separate from a corresponding C gene in embryonic cells. Analysis by restriction enzymes of total cellular DNA from various sources strongly suggested that the two separate immunoglobulin genes become continuous during differentiation of B lymphocytes. There seems to be a strict correlation between the joining event and activation of the joined genes. Cloning of more immunoglobulin genes from embryo and plasma cells will not only provide direct demonstration of such a gene-joining event but also help in the elucidation of a possible relationship of the event to gene activation mechanisms.

  1. 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. PMID:23082866

  2. Gene doping: gene delivery for olympic victory

    PubMed Central

    Gould, David

    2013-01-01

    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. PMID:23082866

  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. 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…

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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…

  10. 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

  11. MIIS to MS-DOS: Microcomputer Options for Online Catalog Support.

    ERIC Educational Resources Information Center

    Grotophorst, Clyde W.

    1986-01-01

    Describes use of personal computer at George Mason University to provide support to the online catalog. Merging of bibliographic information in MS-DOS format into database management system and experimentation with full-text retrieval packages (ZyIndex and SIRE) are discussed. Addresses and price information for hardware and software packages…

  12. 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

  13. 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…

  14. MS DOS Tool Software Including Public Domain, Grades 6-12.

    ERIC Educational Resources Information Center

    New York City Board of Education, Brooklyn, NY.

    This curriculum guide is designed to assist teachers and supervisors in introducing middle and high school students to the MS DOS computer and its functional application software in word processing, database management, and spreadsheet analysis. The guide begins by introducing students to computers: when and how they are used, hardware and…

  15. 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.

  16. 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.

  17. Interleukin-1 polymorphisms are associated with the inflammatory response in human muscle to acute resistance exercise

    PubMed Central

    Dennis, Richard A; Trappe, Todd A; Simpson, Pippa; Carroll, Chad; Emma Huang, B; Nagarajan, Radhakrishnan; Bearden, Edward; Gurley, Cathy; Duff, Gordon W; Evans, William J; Kornman, Kenneth; Peterson, Charlotte A

    2004-01-01

    Inflammation appears to play an important role in the repair and regeneration of skeletal muscle after damage. We tested the hypothesis that the severity of the inflammatory response in muscle after an acute bout of resistance exercise is associated with single nucleotide polymorphisms (SNPs) previously shown to alter interleukin-1 (IL-1) activity. Using a double-blind prospective design, sedentary young men were screened (n = 100) for enrolment (n = 24) based upon having 1 of 4 haplotype patterns composed of five polymorphic sites in the IL-1 gene cluster: IL-1A (+4845), IL-1B (+3954), IL-1B (−511), IL-1B (−3737) and IL-1RN (+2018). Subjects performed a standard bout of resistance leg exercise and vastus lateralis biopsies were obtained pre-, and at 24, and 72 h post-exercise. Inflammatory marker mRNAs (IL-1β, IL-6 and tumor necrosis factor-α (TNF-α)) and the number of CD68+ macrophages were quantified. Considerable variation was observed in the expression of these gene products between subjects. At 72 h post-exercise, IL-1β had increased in a number of subjects (n = 10) and decreased (n = 4) or did not change (n = 10) in others. Inflammatory responses were significantly associated with specific haplotype patterns and were also influenced by individual SNPs. Subjects with genotypes 1.1 at IL-1B (+3954) or 2.2 at IL-1B (−3737) had approximately a 2-fold higher median induction of several markers, but no increase in macrophages, suggesting that cytokine gene expression is elevated per macrophage. The IL-1RN (+2018) SNP maximized the response specifically within these groups and was associated with increased macrophage recruitment. This is the first report that IL-1 genotype is associated with the inflammation of skeletal muscle following acute resistance exercise that may potentially affect the adaptations to chronic resistance exercise. PMID:15331687

  18. 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

  19. 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…

  20. Compare Gene Profiles

    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 Linuxmore » environment in serial or parallel mode.« less

  1. Role of inflammatory parameters in the susceptibility of cerebral thrombosis.

    PubMed

    Qi, X F; Feng, T J; Yang, P; Feng, H Y; Zhang, P; Kong, L Y; Liang, D L; Li, P F; Na, W; Li, Y W; Wang, Y

    2014-04-16

    We aimed to investigate the association of inflammation-related genes such as IL-10, IL-6 and IL-1B with risk of ischemic stroke. We included 426 cases with ischemic stroke and 426 health controls from Xinxiang, China. Genomic DNA was extracted from the buffy coat layer of collected blood with the TIANamp blood DNA kit. Diabetes, hypertension, obesity, and smoking habits were associated with risk of ischemic stroke. We found that individuals carrying the CC genotype of IL-1B rs1864169 had a higher risk of ischemic stroke when compared with the TT genotype (OR = 1.80, 95%CI = 1.16-2.80). The IL-6 rs1800796 TT genotype was associated with increased risk of ischemic stroke. We found that IL-1B rs1864169 and IL-6 rs1800796 polymorphisms may interact with diabetes, hypertension and obesity. Our study suggests that IL-6 rs1800796 and IL-1B rs1864169 polymorphisms are associated with ischemic stroke risk in the Chinese population.

  2. First report of White spot syndrome virus in farmed and wild penaeid shrimp from lagoa dos patos estuary, southern brazil

    PubMed Central

    Cavalli, Lissandra Souto; Romano, Luis Alberto; Marins, Luis Fernando; Abreu, Paulo César

    2011-01-01

    In this study, we detected White spot syndrome virus (WSSV) in wild Farfantepenaeus paulensis collected in the Lagoa dos Patos estuary and cultivated Litopenaeus vannamei. This is the first report of WSSV in F. paulensis from Lagoa dos Patos and farmed L. vannamei shrimps in Rio Grande do Sul. PMID:24031739

  3. First report of White spot syndrome virus in farmed and wild penaeid shrimp from lagoa dos patos estuary, southern brazil.

    PubMed

    Cavalli, Lissandra Souto; Romano, Luis Alberto; Marins, Luis Fernando; Abreu, Paulo César

    2011-07-01

    In this study, we detected White spot syndrome virus (WSSV) in wild Farfantepenaeus paulensis collected in the Lagoa dos Patos estuary and cultivated Litopenaeus vannamei. This is the first report of WSSV in F. paulensis from Lagoa dos Patos and farmed L. vannamei shrimps in Rio Grande do Sul.

  4. 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…

  5. 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

  6. ACONF DOS

    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. Themore » 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.« less

  7. [Genes associated to cancer].

    PubMed

    Peralta-Rodríguez, Raúl; Valdivia, Alejandra; Mendoza, Mónica; Rodríguez, Jade; Marrero, Daniel; Paniagua, Lucero; Romero, Pablo; Taniguchi, Keiko; Salcedo, Mauricio

    2015-01-01

    In 2010, in a cancer genes census, 291 genes were enumerated. These represent near to the 1 % of the total genes, for which there is enough biological evidence that they belong to a new genes classification, known as the cancer genes. These have been defined as the causal genes for sporadic or familiar cancer, when they mutate. The mutation types for these genes includes amplifications, point mutations, deletions, genomic rearranges, amongst others, which lead to a protein over-expression, muting, production of chimeric proteins or a de novo expression. In conjunction these genomic alterations or those of the genetic expression, when they affect specific genes which contribute to the development of cancer, are denominated as cancer genes. It is possible that the list of these alterations will grow longer due to new strategies being developed, for example, the genomic analysis.

  8. Gene doping in sports.

    PubMed

    Unal, Mehmet; Ozer Unal, Durisehvar

    2004-01-01

    Gene or cell doping is defined by the World Anti-Doping Agency (WADA) as "the non-therapeutic use of genes, genetic elements and/or cells that have the capacity to enhance athletic performance". New research in genetics and genomics will be used not only to diagnose and treat disease, but also to attempt to enhance human performance. In recent years, gene therapy has shown progress and positive results that have highlighted the potential misuse of this technology and the debate of 'gene doping'. Gene therapies developed for the treatment of diseases such as anaemia (the gene for erythropoietin), muscular dystrophy (the gene for insulin-like growth factor-1) and peripheral vascular diseases (the gene for vascular endothelial growth factor) are potential doping methods. With progress in gene technology, many other genes with this potential will be discovered. For this reason, it is important to develop timely legal regulations and to research the field of gene doping in order to develop methods of detection. To protect the health of athletes and to ensure equal competitive conditions, the International Olympic Committee, WADA and International Sports Federations have accepted performance-enhancing substances and methods as being doping, and have forbidden them. Nevertheless, the desire to win causes athletes to misuse these drugs and methods. This paper reviews the current status of gene doping and candidate performance enhancement genes, and also the use of gene therapy in sports medicine and ethics of genetic enhancement.

  9. 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.

  10. Protecting Web Services against DoS Attacks: A Case-Based Reasoning Approach

    NASA Astrophysics Data System (ADS)

    Pinzón, Cristian; de Paz, Juan F.; Zato, Carolina; Pérez, Javier

    The real-time detection is a key factor to detect and block DoS attacks within Web services. DoS attacks can be generated for different techniques that take advantage of points vulnerable within Web services. This paper describes a novel proposal based on a real time agent to classify user requests and detect and block malicious SOAP messages. The classification mechanism is based on a Case-Base Reasoning (CBR) model, where the different CBR phases are time bounded. Within the reuse phase of the CBR cycle is incorporated a mixture of experts to choose the most suitable technique of classification depending on the feature of the attack and the available time to solve the classification. A prototype of the architecture was developed and the results obtained are presented in this study.

  11. Perspectivas Futuras para o Observatório do Pico dos Dias

    NASA Astrophysics Data System (ADS)

    Bruch, Albert

    2004-02-01

    Com o Observatório Gemini plenamente operacional e o telescópio SOAR iniciando suas operações em breve, a astronomia observacional brasileira encontra-se no auge de uma transformação profunda que terá um impacto grave no Observatório do Pico dos Dias - OPD. Refletimos aqui sobre a natureza desse impacto e estratégias para manter a competitividade do OPD. Não queremos apresentar receitas prontas, mas idéias que poderão servir como base de discussão sobre o uso inteligente dos telescópios do OPD como parte do conjunto de instrumentos disponíveis à comunidade astronômica brasileira.

  12. An alternate hypothesis for the origin of Angra dos Reis - Porphyry, not cumulate

    NASA Technical Reports Server (NTRS)

    Treiman, A. H.

    1989-01-01

    The Angra dos Reis achondrite is a unique meteorite of potentially great importance for understanding the origins of the solar system and of the terrestrial planets. It is proposed that the meteorite, which consists of megacrysts of Al-Ti augite (fassaite) in skeletal or cellular shapes, olivine, and possibly whitlockite in a fine-grained groundmass of the same materials plus spinel, is a porphyritic igneous rock modified by metamorphism. In this interpretation, the megacrysts represent cellular-textured phenocrysts, and the fine-grain groundmass represents crystallized or devitrified magma. Phase equilibria suggest that Angra dos Reis-like compositions could grow phenocrysts of fassaite pyroxene, olivine, and whitlockite. These same compositions could crystallize, without crystal sorting or accumulation, to an almost monomineralic fassaite pyroxenite.

  13. 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…

  14. 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

  15. 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.

  16. 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%. PMID:27494411

  17. 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%.

  18. 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.

  19. 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. PMID:26470920

  20. 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.

  1. 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

  2. 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…

  3. CEST MRI reporter genes.

    PubMed

    Liu, Guanshu; Bulte, Jeff W M; Gilad, Assaf A

    2011-01-01

    In recent years, several reporter genes have been developed that can serve as a beacon for non-invasive magnetic resonance imaging (MRI). Here, we provide a brief summary of recent advances in MRI reporter gene technology, as well as detailed "hands-on" protocols for cloning, expression, and imaging of reporter genes based on chemical exchange saturation transfer (CEST).

  4. Using 4DOS Batch Files To Create an Infrastructure That Makes It Easy for Students To Create and Maintain HTML Web Pages.

    ERIC Educational Resources Information Center

    Snyder, Robin M.

    This paper describes the use of simple 4DOS batch files to automate the creation and maintenance of an infrastructure to assist students in creating and maintaining HTML World Wide Web pages. Background is provided on Web pages, DOS, 4DOS, and batch files. The assumptions made in creating the infrastructure are summarized, and program statements…

  5. In-Vivo Gene Signatures of Mycobacterium tuberculosis in C3HeB/FeJ Mice

    PubMed Central

    Gautam, Uma Shankar; Mehra, Smriti; Kaushal, Deepak

    2015-01-01

    Despite considerable progress in understanding the pathogenesis of Mycobacterium tuberculosis (Mtb), development of new therapeutics and vaccines against it has proven difficult. This is at least in part due to the use of less than optimal models of in-vivo Mtb infection, which has precluded a study of the physiology of the pathogen in niches where it actually persists. C3HeB/FeJ (Kramnik) mice develop human-like lesions when experimentally infected with Mtb and thus make available, a faithful and highly tractable system to study the physiology of the pathogen in-vivo. We compared the transcriptomics of Mtb and various mutants in the DosR (DevR) regulon derived from Kramnik mouse granulomas to those cultured in-vitro. We recently showed that mutant ΔdosS is attenuated in C3HeB/FeJ mice. Aerosol exposure of mice with the mutant mycobacteria resulted in a substantially different and a relatively weaker transcriptional response (< = 20 genes were induced) for the functional category ‘Information Pathways’ in Mtb:ΔdosR; ‘Lipid Metabolism’ in Mtb:ΔdosT; ‘Virulence, Detoxification, Adaptation’ in both Mtb:ΔdosR and Mtb:ΔdosT; and ‘PE/PPE’ family in all mutant strains compare to wild-type Mtb H37Rv, suggesting that the inability to induce DosR functions to different levels can modulate the interaction of the pathogen with the host. The Mtb genes expressed during growth in C3HeB/FeJ mice appear to reflect adaptation to differential nutrient utilization for survival in mouse lungs. The genes such as glnB, Rv0744c, Rv3281, sdhD/B, mce4A, dctA etc. downregulated in mutant ΔdosS indicate their requirement for bacterial growth and flow of carbon/energy source from host cells. We conclude that genes expressed in Mtb during in-vivo chronic phase of infection in Kramnik mice mainly contribute to growth, cell wall processes, lipid metabolism, and virulence. PMID:26270051

  6. 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

  7. Human disease genes.

    PubMed

    Jimenez-Sanchez, G; Childs, B; Valle, D

    2001-02-15

    The complete human genome sequence will facilitate the identification of all genes that contribute to disease. We propose that the functional classification of disease genes and their products will reveal general principles of human disease. We have determined functional categories for nearly 1,000 documented disease genes, and found striking correlations between the function of the gene product and features of disease, such as age of onset and mode of inheritance. As knowledge of disease genes grows, including those contributing to complex traits, more sophisticated analyses will be possible; their results will yield a deeper understanding of disease and an enhanced integration of medicine with biology.

  8. Journey from Jumping Genes to Gene Therapy.

    PubMed

    Whartenby, Katharine A

    2015-01-01

    Gene therapy for cancer is a still evolving approach that resulted from a long history of studies into genetic modification of organisms. The fascination with manipulating gene products has spanned hundreds if not thousands of years, beginning with observations of the hereditary nature of traits in plants and culminating to date in the alteration of genetic makeup in humans via modern technology. From early discoveries noting the potential for natural mobility of genetic material to the culmination of clinical trials in a variety of disease, gene transfer has had an eventful and sometimes tumultuous course. Within the present review is a brief history of the biology of gene transfer, how it came to be applied to genetic diseases, and its early applications to cancer therapies. Some of the different types of methods used to modify cells, the theories behind the approaches, and some of the limitations encountered along the way are reviewed. PMID:27279244

  9. 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.

  10. Gene conversion in human rearranged immunoglobulin genes.

    PubMed

    Darlow, John M; Stott, David I

    2006-07-01

    Over the past 20 years, many DNA sequences have been published suggesting that all or part of the V(H) segment of a rearranged immunoglobulin gene may be replaced in vivo. Two different mechanisms appear to be operating. One of these is very similar to primary V(D)J recombination, involving the RAG proteins acting upon recombination signal sequences, and this has recently been proven to occur. Other sequences, many of which show partial V(H) replacements with no addition of untemplated nucleotides at the V(H)-V(H) joint, have been proposed to occur by an unusual RAG-mediated recombination with the formation of hybrid (coding-to-signal) joints. These appear to occur in cells already undergoing somatic hypermutation in which, some authors are convinced, RAG genes are silenced. We recently proposed that the latter type of V(H) replacement might occur by homologous recombination initiated by the activity of AID (activation-induced cytidine deaminase), which is essential for somatic hypermutation and gene conversion. The latter has been observed in other species, but not in human Ig genes, so far. In this paper, we present a new analysis of sequences published as examples of the second type of rearrangement. This not only shows that AID recognition motifs occur in recombination regions but also that some sequences show replacement of central sections by a sequence from another gene, similar to gene conversion in the immunoglobulin genes of other species. These observations support the proposal that this type of rearrangement is likely to be AID-mediated rather than RAG-mediated and is consistent with gene conversion.

  11. Retrieval with gene queries

    PubMed Central

    Sehgal, Aditya K; Srinivasan, Padmini

    2006-01-01

    Background 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. Results 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. Conclusion 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. PMID:16630348

  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. Characterization of a cAMP responsive transcription factor, Cmr (Rv1675c), in TB complex mycobacteria reveals overlap with the DosR (DevR) dormancy regulon

    PubMed Central

    Ranganathan, Sridevi; Bai, Guangchun; Lyubetskaya, Anna; Knapp, Gwendowlyn S.; Peterson, Matthew W.; Gazdik, Michaela; C. Gomes, Antonio L.; Galagan, James E.; McDonough, Kathleen A.

    2016-01-01

    Mycobacterium tuberculosis (Mtb) Cmr (Rv1675c) is a CRP/FNR family transcription factor known to be responsive to cAMP levels and during macrophage infections. However, Cmr's DNA binding properties, cellular targets and overall role in tuberculosis (TB) complex bacteria have not been characterized. In this study, we used experimental and computational approaches to characterize Cmr's DNA binding properties and identify a putative regulon. Cmr binds a 16-bp palindromic site that includes four highly conserved nucleotides that are required for DNA binding. A total of 368 binding sites, distributed in clusters among ∼200 binding regions throughout the Mycobacterium bovis BCG genome, were identified using ChIP-seq. One of the most enriched Cmr binding sites was located upstream of the cmr promoter, and we demonstrated that expression of cmr is autoregulated. cAMP affected Cmr binding at a subset of DNA loci in vivo and in vitro, including multiple sites adjacent to members of the DosR (DevR) dormancy regulon. Our findings of cooperative binding of Cmr to these DNA regions and the regulation by Cmr of the DosR-regulated virulence gene Rv2623 demonstrate the complexity of Cmr-mediated gene regulation and suggest a role for Cmr in the biology of persistent TB infection. PMID:26358810

  14. 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.

  15. 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. PMID:25685510

  16. 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

  17. Oncogenes, genes, and growth factors

    SciTech Connect

    Guroff, G.

    1989-01-01

    This book contains 12 chapters. Some of the chapter titles are: The Epidermal Growth Factor Receptor Gene; Structure and Expression of the Nerve Growth Factor Gene; The Erythropoietin Gene; The Interleukin-2 Gene; The Transferrin Gene; and The Transferrin Receptor Gene.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. Do housekeeping genes exist?

    PubMed

    Zhang, Yijuan; Li, Ding; 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

  4. Towards Consensus Gene Ages.

    PubMed

    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. 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.

  6. Notch signaling genes

    PubMed Central

    Terragni, Jolyon; Zhang, Guoqiang; Sun, Zhiyi; Pradhan, Sriharsa; Song, Lingyun; Crawford, Gregory E; Lacey, Michelle; Ehrlich, Melanie

    2014-01-01

    Notch intercellular signaling is critical for diverse developmental pathways and for homeostasis in various types of stem cells and progenitor cells. Because Notch gene products need to be precisely regulated spatially and temporally, epigenetics is likely to help control expression of Notch signaling genes. Reduced representation bisulfite sequencing (RRBS) indicated significant hypomethylation in myoblasts, myotubes, and skeletal muscle vs. many nonmuscle samples at intragenic or intergenic regions of the following Notch receptor or ligand genes: NOTCH1, NOTCH2, JAG2, and DLL1. An enzymatic assay of sites in or near these genes revealed unusually high enrichment of 5-hydroxymethylcytosine (up to 81%) in skeletal muscle, heart, and cerebellum. Epigenetics studies and gene expression profiles suggest that hypomethylation and/or hydroxymethylation help control expression of these genes in heart, brain, myoblasts, myotubes, and within skeletal muscle myofibers. Such regulation could promote cell renewal, cell maintenance, homeostasis, and a poised state for repair of tissue damage. PMID:24670287

  7. Gene therapy for radioprotection.

    PubMed

    Everett, W H; Curiel, D T

    2015-03-01

    Radiation therapy is a critical component of cancer treatment with over half of patients receiving radiation during their treatment. Despite advances in image-guided therapy and dose fractionation, patients receiving radiation therapy are still at risk for side effects due to off-target radiation damage of normal tissues. To reduce normal tissue damage, researchers have sought radioprotectors, which are agents capable of protecting tissue against radiation by preventing radiation damage from occurring or by decreasing cell death in the presence of radiation damage. Although much early research focused on small-molecule radioprotectors, there has been a growing interest in gene therapy for radioprotection. The amenability of gene therapy vectors to targeting, as well as the flexibility of gene therapy to accomplish ablation or augmentation of biologically relevant genes, makes gene therapy an excellent strategy for radioprotection. Future improvements to vector targeting and delivery should greatly enhance radioprotection through gene therapy.

  8. 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.

  9. 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.

  10. 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.

  11. Dosimetry and Vibration measurements in BIOLAB and EMCS (Dos-ViBE)

    NASA Astrophysics Data System (ADS)

    Ideström, Johan Olof; Hendrik Anken, Ralf; Reitz, Guenther; Berger, Thomas; Hauslage, Jens; Schuber, Marianne; Fossum, Knut R.; Vanhavere, Filip

    Space irradiation and vibrations in even small dosages can impact biological experiments and have not yet been measured in the biological payloads of the Columbus module at the Interna-tional Space Station (ISS). Installing active dosimeters and accelerometers in the Experiment Containers (EC) of Biolab and the European Modular Cultivation System (EMCS), to sur-vey in-situ the radiation and vibrations in these facilities, should be performed to serve as a reference of the space conditions to future experiments. To monitor the radiation field, the space radiation should be measured with an active dosime-ter inside the Multi-User-Facilities, as close to the actual shielding conditions of the biological experiments as possible. To measure the full spectrum of vibration frequencies, several instru-ments with different measurement ranges and sensitivity should be combined. The radiation and vibrations should be measured simultaneously in Biolab and EMCS to compare their radiation shielding and sensitivities to vibrations from the ISS. The radiation could also be measured with passive dosimeters. On the one hand this would be a back-up to the active dosimeter and on the other hand it would provide additional data since the passive dosimeters can give additional information on the radiation LET spectrum. As a response to ESA's Announcement of Opportunity (ILSRA-2009), a joint experiment in Biolab and EMCS, entitled Dos-ViBE, was proposed by the co-authors. The objectives and experimental flow of Dos-ViBE are outlined in this presentation.

  12. 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

  13. Supervised clustering of genes

    PubMed Central

    Dettling, Marcel; Bühlmann, Peter

    2002-01-01

    Background We focus on microarray data where experiments monitor gene expression in different tissues and where each experiment is equipped with an additional response variable such as a cancer type. Although the number of measured genes is in the thousands, it is assumed that only a few marker components of gene subsets determine the type of a tissue. Here we present a new method for finding such groups of genes by directly incorporating the response variables into the grouping process, yielding a supervised clustering algorithm for genes. Results An empirical study on eight publicly available microarray datasets shows that our algorithm identifies gene clusters with excellent predictive potential, often superior to classification with state-of-the-art methods based on single genes. Permutation tests and bootstrapping provide evidence that the output is reasonably stable and more than a noise artifact. Conclusions In contrast to other methods such as hierarchical clustering, our algorithm identifies several gene clusters whose expression levels clearly distinguish the different tissue types. The identification of such gene clusters is potentially useful for medical diagnostics and may at the same time reveal insights into functional genomics. PMID:12537558

  14. 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.

  15. Integron associated mobile genes

    PubMed Central

    Labbate, Maurizio; Boucher, Yan; Luu, Ivan; Chowdhury, Piklu Roy; Stokes, H.W.

    2012-01-01

    Lateral gene transfer (LGT) impacts on the evolution of prokaryotes in both the short and long-term. The short-term impacts of mobilized genes are a concern to humans since LGT explains the global rise of multi drug resistant pathogens seen in the past 70 years. However, LGT has been a feature of prokaryotes from the earliest days of their existence and the concept of a bifurcating tree of life is not entirely applicable to prokaryotes since most genes in extant prokaryotic genomes have probably been acquired from other lineages. Successful transfer and maintenance of a gene in a new host is understandable if it acts independently of cell networks and confers an advantage. Antibiotic resistance provides an example of this whereby a gene can be advantageous in virtually any cell across broad species backgrounds. In a longer evolutionary context however laterally transferred genes can be assimilated into even essential cell networks. How this happens is not well understood and we discuss recent work that identifies a mobile gene, unique to a cell lineage, which is detrimental to the cell when lost. We also present some additional data and believe our emerging model will be helpful in understanding how mobile genes integrate into cell networks. PMID:22754748

  16. Your Genes, Your Choices

    MedlinePlus

    Table of Contents Your Genes, Your Choices describes the Human Genome Project, the science behind it, and the ethical, legal, and social issues that are ... Nothing could be further from the truth. Your Genes, Your Choices points out how the progress of ...

  17. What Is a Gene?

    MedlinePlus

    ... a new kind of medicine — so new that scientists are still doing experiments to see if it works. It uses the technology of genetic engineering to treat a disease caused by a gene that has changed in some way. One method being tested is replacing sick genes with healthy ...

  18. 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

  19. 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.

  20. 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.

  1. Engineered gene circuits

    NASA Astrophysics Data System (ADS)

    Hasty, Jeff; McMillen, David; Collins, J. J.

    2002-11-01

    A central focus of postgenomic research will be to understand how cellular phenomena arise from the connectivity of genes and proteins. This connectivity generates molecular network diagrams that resemble complex electrical circuits, and a systematic understanding will require the development of a mathematical framework for describing the circuitry. From an engineering perspective, the natural path towards such a framework is the construction and analysis of the underlying submodules that constitute the network. Recent experimental advances in both sequencing and genetic engineering have made this approach feasible through the design and implementation of synthetic gene networks amenable to mathematical modelling and quantitative analysis. These developments have signalled the emergence of a gene circuit discipline, which provides a framework for predicting and evaluating the dynamics of cellular processes. Synthetic gene networks will also lead to new logical forms of cellular control, which could have important applications in functional genomics, nanotechnology, and gene and cell therapy.

  2. A gene expression screen.

    PubMed Central

    Wang, Z; Brown, D D

    1991-01-01

    A gene expression screen identifies mRNAs that differ in abundance between two mRNA mixtures by a subtractive hybridization method. The two mRNA populations are converted to double-stranded cDNAs, fragmented, and ligated to linkers for polymerase chain reaction (PCR) amplification. The multiple cDNA fragments isolated from any given gene can be treated as alleles in a genetic screen. Probability analysis of the frequency with which multiple alleles are found provides an estimation of the total number of up- and down-regulated genes. We have applied this method to genes that are differentially expressed in amphibian tadpole tail tissue in the first 24 hr after thyroid hormone treatment, which ultimately induces tail resorption. We estimate that there are about 30 up-regulated genes; 16 have been isolated. Images PMID:1722336

  3. Autophagy genes in immunity

    PubMed Central

    Virgin, Herbert W; Levine, Beth

    2009-01-01

    In its classical form, autophagy is a pathway by which cytoplasmic constituents, including intracellular pathogens, are sequestered in a double-membrane–bound autophagosome and delivered to the lysosome for degradation. This pathway has been linked to diverse aspects of innate and adaptive immunity, including pathogen resistance, production of type I interferon, antigen presentation, tolerance and lymphocyte development, as well as the negative regulation of cytokine signaling and inflammation. Most of these links have emerged from studies in which genes encoding molecules involved in autophagy are inactivated in immune effector cells. However, it is not yet known whether all of the critical functions of such genes in immunity represent ‘classical autophagy’ or possible as-yet-undefined autophagolysosome-independent functions of these genes. This review summarizes phenotypes that result from the inactivation of autophagy genes in the immune system and discusses the pleiotropic functions of autophagy genes in immunity. PMID:19381141

  4. Genes, genome and Gestalt.

    PubMed

    Grisolia, Cesar Koppe

    2005-01-01

    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.

  5. 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

  6. 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.

  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. 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.;

  9. 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.

  10. Sm-Nd-Pu timepieces in the Angra dos Reis meteorite

    NASA Technical Reports Server (NTRS)

    Lugmair, G. W.; Marti, K.

    1977-01-01

    Isotope ratios and age estimations are presented for the ultramafic pyroxenite Angra dos Reis meteorite. A pyroxene-phosphate internal isochron age of 4.55 plus or minus 0.04 eons was obtained, in agreement with reported Pb-Pb ages. It is suggested that Sm-146 decay led to an increase in the ratio of Nd-142 to Nd-144 in pyroxene, which is greater than the ratio of the Nd isotopes in phosphates. The effect of Pu-244 on the fission xenon components in pyroxene and phosphate is examined. The ratios of Pu-244 to Nd, U-238, and Th-232 are compared for pyroxene and phosphate separates. The exposure age of the meteorite, as obtained by the Kr-81 to Kr-83 method, was found to be 55.5 plus or minus 1.2 million years.

  11. Duplicate genes increase gene expression diversity within and between species.

    PubMed

    Gu, Zhenglong; Rifkin, Scott A; White, Kevin P; Li, Wen-Hsiung

    2004-06-01

    Using microarray gene expression data from several Drosophila species and strains, we show that duplicated genes, compared with single-copy genes, significantly increase gene expression diversity during development. We show further that duplicate genes tend to cause expression divergences between Drosophila species (or strains) to evolve faster than do single-copy genes. This conclusion is also supported by data from different yeast strains.

  12. [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.

  13. [Is gene technology immoral?].

    PubMed

    Halter, H

    1994-10-01

    Since it came into being in the USA in the early 1970s, gene technology has always been fundamentally controversial, especially in the German-speaking countries. The optimistic--or critical--supporters of gene technology are convinced that, in view of gene technology's not otherwise attainable advantages for human and animal health, for food production and other important aims, it would be ethically unacceptable to restrict to the minimum or even ban it. On the other hand, the radical critics are convinced that gene technology, in view of its anthropologically false starting-point, the questionable interests behind it, and above all its unforeseeable, serious negative implications for mankind and environment, is unacceptable on ethical grounds. Critical reflexion on these polarized arguments must start from the question why precisely gene technology is so controversial, and what are the criteria for ethical assessment. These reflexions presuppose that the prior judgement of gene technology as a technology in the ideological field is rooted in life attitudes, history and nature in general, and this is true not only of gene technology's opponents but also its supporters. It is thus a question of one ideology vs. another. Chief importance here attaches to the mankind-nature relationship and the need to take seriously the fundamental ambivalence of all (!) human action with unforeseeable consequences. The conclusion is that neither to demonize nor to glorify gene technology, as a matter of principle, does justice to its wide and varied positive or negative potential. The ethical assessment of gene technology must be differentiated according to the aims and possible implications.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7939540

  14. Clock genes and cancer.

    PubMed

    Wood, Patricia A; Yang, Xiaoming; Hrushesky, William J M

    2009-12-01

    Period genes ( Per2, Per1) are essential circadian clock genes. They also function as negative growth regulators. Per2 mutant mice show de novo and radiation-induced epithelial hyperplasia, tumors, and an abnormal DNA damage response. Human tumors show Period gene mutations or decreased expression. Other murine clock gene mutations are not associated with a tumor prone phenotype. Shift work and nocturnal light exposure are associated with circadian clock disruption and with increased cancer risk. The mechanisms responsible for the connection between the circadian clock and cancer are not well defined. We propose that circadian disruption per se is not uniformly tumor promoting and the mechanisms for tumor promotion by specific circadian clock disturbances will differ dependent upon the genes and pathways involved. We propose that Period clock gene mutations promote tumorigenesis by unique molecular pathways. Per2 and Per1 modulate beta-catenin and cell proliferation in colon and non-colon cancer cells. Per2 mutation increases intestinal beta-catenin levels and colon polyp formation. Per2 mutation also increases Apc(Min/+)-mediated intestinal and colonic polyp formation. Intestinal tumorigenesis per se may also alter clock function as a result of increased beta-catenin destabilizing PER2 protein. Levels and circadian rhythm of PER2 in Apc(Min/+) mouse intestine are markedly decreased, and selective abnormalities in intestinal clock gene and clock-controlled gene expression are seen. We propose that tumor promotion by loss of PERIOD clock proteins is unique to these clock genes as a result of altered beta-catenin signaling and DNA damage response. PERIOD proteins may offer new targets for cancer prevention and control.

  15. Genes in sweeping competition.

    PubMed

    Nurminsky, D I

    2001-01-01

    Analysis of DNA variation is a powerful tool for detecting adaptation at the genomic level. The contribution of adaptive evolution is evident from examples of rapidly evolving genes, which represent the likely targets for strong selection. More subtle adaptation is also an integral component of routine maintenance of gene performance, continuously applied to every gene. Adaptive changes in the population are accomplished through selective sweeps, i.e. complete or partial fixation of beneficial alleles. The evidence is accumulating that selective sweeps are quite frequent events which, together with associated genetic hitchhiking, represent dominant forces that influence molecular evolution by shaping the variability pattern in the genome.

  16. A putative nitroreductase from the DosR regulon of Mycobacterium tuberculosis induces pro-inflammatory cytokine expression via TLR2 signaling pathway

    PubMed Central

    Peddireddy, Vidyullatha; Doddam, Sankara Narayana; Qureshi, Insaf A.; Yerra, Priyadarshini; Ahmed, Niyaz

    2016-01-01

    Tuberculosis caused by Mycobacterium tuberculosis is a global encumbrance and it is estimated that nearly one third population of the world acts as a reservoir for this pathogen without any symptoms. In this study, we attempted to characterise one of the genes of DosR regulon, Rv3131, a FMN binding nitroreductase domain containing protein, for its ability to alter cytokine profile, an essential feature of M. tuberculosis latency. Recombinant Rv3131 stimulated pro-inflammatory cytokines in THP-1 cells and human peripheral blood mononuclear cells in a time and dose dependent manner. In silico analyses using docking and simulations indicated that Rv3131 could strongly interact with TLR2 via a non-covalent bonding which was further confirmed using cell based colorimetric assay. In THP-1 cells treated with Rv3131 protein, a significant upsurge in the surface expression, overall induction and expression of mRNA of TLR2 was observed when analysed by flow cytometry, western blotting and real time PCR, respectively. Activation of TLR2 by Rv3131 resulted in the phosphorylation of NF- κβ. Results of this study indicate a strong immunogenic capability of Rv3131 elicited via the activation of TLR2 signalling pathway. Therefore, it can be surmised that cytokine secretion induced by Rv3131 might contribute to establishment of M. tuberculosis in the granulomas. PMID:27094446

  17. Gene structure and expression

    SciTech Connect

    Hawkins, J. )

    1990-01-01

    This book describes the structure of genes in molecular terms and summarizes present knowledge about how their activity is regulated. It covers a range of topics, including a review of the structure and replication of DNA, transcription and translation, prokaryotic and eukaryotic gene organization and expression, retroviruses and oncogenes. The book also includes a chapter on the methodology of DNA manipulation including sections on site-directed mutagenesis, the polymerase chain reaction, reporter genes and restriction fragment length polymorphisms. The hemoglobin gene system and the genetics of the proteins of the immune system are presented in the latter half of the book to show the structure and expression of the most well-studied systems in higher eukaryotes. The final chapter reviews the differences between prokaryotic and the eukaryotic genomes.

  18. 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.

  19. Epigenetics and gene expression.

    PubMed

    Gibney, E R; Nolan, C M

    2010-07-01

    Transcription, translation and subsequent protein modification represent the transfer of genetic information from the archival copy of DNA to the short-lived messenger RNA, usually with subsequent production of protein. Although all cells in an organism contain essentially the same DNA, cell types and functions differ because of qualitative and quantitative differences in their gene expression. Thus, control of gene expression is at the heart of differentiation and development. Epigenetic processes, including DNA methylation, histone modification and various RNA-mediated processes, are thought to influence gene expression chiefly at the level of transcription; however, other steps in the process (for example, translation) may also be regulated epigenetically. The following paper will outline the role epigenetics is believed to have in influencing gene expression.

  20. "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.

  1. "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. PMID:25708001

  2. Vaginal gene therapy.

    PubMed

    Rodríguez-Gascón, Alicia; Del Pozo-Rodríguez, Ana; Isla, Arantxazu; Solinís, María Angeles

    2015-09-15

    In the last years, vaginal gene therapy has gained increasing attention mainly for the treatment and control of sexually transmitted infections. DNA delivery has been also suggested to improve reproductive outcomes for women with deficiencies in the female reproductive tract. Although no product has reached clinical phase, preclinical investigations reveal the potential of the vaginal tract as an effective administration route for gene delivery. This review focuses on the main advantages and challenges of vaginal gene therapy, and on the most used nucleic acid delivery systems, including viral and non-viral vectors. Additionally, the advances in the application of vaginal gene therapy for the treatment and/or prevention of infectious diseases such as the human immunodeficiency virus (HIV), the human papillomavirus (HPV) or the herpes simplex virus (HSV) are presented.

  3. 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.

  4. [Integrons: gene collectors].

    PubMed

    Di Conza, J A; Gutkind, G O

    2010-01-01

    Integrons gained great interest due to their participation in resistance gene recruitment and expression. Their basic structure includes a fragment that encodes an integrase (intI) followed by a recognition sequence (attI) into which they may incorporate gene cassettes (encoding resistance mechanisms). A promoter (Pc) embedded within the integrase gene controls the transcription of integrated resistance markers, as these genes do not have their own promoters. When in cassettes, resistance genes are flanked by specific sequences (attC), which are recognized by the integrase that, by site specific recombination, incorporates them after attI in proper orientation for their expression. In the past, integrons were classified according to their sequence homology; currently they are classified according to their location. In general, they are divided into "mobile" integrons (those associated with insertion sequences, transposons and/or plasmids, being most of them associated with resistance mechanisms), and chromosomally-located "super" integrons with large arrangements of cassette genes. "Mobile" class 1 integrons are the most abundant in clinical isolates and are generally associated with Tn21 subgroup transposons, followed by class 2, derived primarily from Tn7. These elements are not mobile themselves, but their association with mobile platforms that facilitate horizontal transfer, explains their wide distribution among bacteria. This review also attempts to describe the mobile integrons described so far in Argentina.

  5. Identification of four soybean reference genes for gene expression normalization

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gene expression analysis requires the use of reference genes stably expressed independently of specific tissues or environmental conditions. Housekeeping genes (e.g., actin, tubulin, ribosomal, polyubiquitin and elongation factor 1-alpha) are commonly used as reference genes with the assumption tha...

  6. 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

  7. 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...-1921, Award/Modification of Interagency Acquisition Agreement. As prescribed in 617.504-70(b)(5)(i), DS-1921 is prescribed for use when awarding or modifying Economy Act Interagency Acquisition...

  8. 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.

  9. NLRP3 inflammasome is associated with the response to IFN-β in patients with multiple sclerosis

    PubMed Central

    Malhotra, Sunny; Río, Jordi; Urcelay, Elena; Nurtdinov, Ramil; Bustamante, Marta F; Fernández, Oscar; Oliver, Begoña; Zettl, Uwe; Brassat, David; Killestein, Joep; Lechner-Scott, Jeannette; Drulovic, Jelena; Chan, Andrew; Martinelli-Boneschi, Filippo; García-Merino, Antonio; Montalban, Xavier

    2015-01-01

    Evidence exists for a potential modulation of inflammasome activity by interferon beta. Here, we investigated the roles of inflammasomes [absent in melanoma 2 (AIM2); NLR family, CARD domain containing 4 (NLRC4); NLR family, pyrin domain containing 1 and 3 (NLRP1 and NLRP3)] and related cytokines (IL1B, IL10, IL18) in the response to interferon beta in patients with relapsing-remitting multiple sclerosis. Ninety-seven patients treated with interferon beta were classified into responders and non-responders according to clinical criteria after 24 months and clinical-radiological criteria after 12 months of treatment. Messenger RNA expression levels of inflammasomes and cytokines were determined by real-time polymerase chain reaction in peripheral blood mononuclear cells collected before treatment with interferon beta. In a subgroup of patients, NLRP3 and IL1B expression was also determined after 3 months (n = 32) and 12 months (n = 20) of interferon beta treatment. A polymorphism located in the NLRP3 gene, rs35829419, was genotyped in 789 multiple sclerosis patients treated with interferon beta. Baseline mRNA expression levels for NLRP3 and IL1B were increased in peripheral blood mononuclear cells from non-responders compared to responders classified according to clinical criteria after 24 months (P = 0.02 and P = 0.001, respectively). No significant differences were observed for other inflammasomes and related cytokines. Differences in NLRP3 and IL1B expression remained significant following a clinical-radiological classification after 12 months (P = 0.007 and P = 0.02, respectively). After treatment with interferon beta, NLRP3 and IL1B expression was increased in responders but unchanged in non-responders. A trend for association was observed between rs35829419 and interferon beta response (pM-H = 0.08). These results point to a role of the NLRP3 inflammasome and its related cytokine IL1B in the response to interferon beta in patients with relapsing

  10. 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

  11. 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

  12. 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

  13. 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

    2010-01-01

    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. Database

  14. 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.

  15. Saporin suicide gene therapy.

    PubMed

    Zarovni, Natasa; Vago, Riccardo; Fabbrini, Maria Serena

    2009-01-01

    New genes useful in suicide gene therapy are those encoding toxins such as plant ribosome-inactivating proteins (RIPs), which can irreversibly block protein synthesis, triggering apoptotic cell death. Plasmids expressing a cytosolic saporin (SAP) gene from common soapwort (Saponaria officinalis) are generated by placing the region encoding the mature plant toxin under the control of strong viral promoters and may be placed under tumor-specific promoters. The ability of the resulting constructs to inhibit protein synthesis is tested in cultured tumor cells co-transfected with a luciferase reporter gene. SAP expression driven by the cytomegalovirus (CMV) promoter (pCI-SAP) demonstrates that only 10 ng ofplasmid DNA per 1.6 x 10(4) B16 melanoma cells drastically reduces luciferase reporter activity to 18% of that in control cells (1). Direct intratumoral injections are performed in an aggressive melanoma model. B16 melanoma-bearing mice injected with pCI-SAP complexed with lipofectamine or N-(2,3-dioleoyloxy-1-propyl) trimethylammonium methyl sulfate (DOTAP) show a noteworthy attenuation in tumor growth, and this effect is significantly augmented by repeated administrations of the DNA complexes. Here, we describe in detail this cost-effective and safe suicide gene approach. PMID:19565907

  16. 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.

  17. 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

  18. LQTS gene LOVD database.

    PubMed

    Zhang, Tao; Moss, Arthur; Cong, Peikuan; Pan, Min; Chang, Bingxi; Zheng, Liangrong; Fang, Quan; Zareba, Wojciech; Robinson, Jennifer; Lin, Changsong; Li, Zhongxiang; Wei, Junfang; Zeng, Qiang; Qi, Ming

    2010-11-01

    The Long QT Syndrome (LQTS) is a group of genetically heterogeneous disorders that predisposes young individuals to ventricular arrhythmias and sudden death. LQTS is mainly caused by mutations in genes encoding subunits of cardiac ion channels (KCNQ1, KCNH2,SCN5A, KCNE1, and KCNE2). Many other genes involved in LQTS have been described recently(KCNJ2, AKAP9, ANK2, CACNA1C, SCNA4B, SNTA1, and CAV3). We created an online database(http://www.genomed.org/LOVD/introduction.html) that provides information on variants in LQTS-associated genes. As of February 2010, the database contains 1738 unique variants in 12 genes. A total of 950 variants are considered pathogenic, 265 are possible pathogenic, 131 are unknown/unclassified, and 292 have no known pathogenicity. In addition to these mutations collected from published literature, we also submitted information on gene variants, including one possible novel pathogenic mutation in the KCNH2 splice site found in ten Chinese families with documented arrhythmias. The remote user is able to search the data and is encouraged to submit new mutations into the database. The LQTS database will become a powerful tool for both researchers and clinicians. PMID:20809527

  19. LQTS gene LOVD database.

    PubMed

    Zhang, Tao; Moss, Arthur; Cong, Peikuan; Pan, Min; Chang, Bingxi; Zheng, Liangrong; Fang, Quan; Zareba, Wojciech; Robinson, Jennifer; Lin, Changsong; Li, Zhongxiang; Wei, Junfang; Zeng, Qiang; Qi, Ming

    2010-11-01

    The Long QT Syndrome (LQTS) is a group of genetically heterogeneous disorders that predisposes young individuals to ventricular arrhythmias and sudden death. LQTS is mainly caused by mutations in genes encoding subunits of cardiac ion channels (KCNQ1, KCNH2,SCN5A, KCNE1, and KCNE2). Many other genes involved in LQTS have been described recently(KCNJ2, AKAP9, ANK2, CACNA1C, SCNA4B, SNTA1, and CAV3). We created an online database(http://www.genomed.org/LOVD/introduction.html) that provides information on variants in LQTS-associated genes. As of February 2010, the database contains 1738 unique variants in 12 genes. A total of 950 variants are considered pathogenic, 265 are possible pathogenic, 131 are unknown/unclassified, and 292 have no known pathogenicity. In addition to these mutations collected from published literature, we also submitted information on gene variants, including one possible novel pathogenic mutation in the KCNH2 splice site found in ten Chinese families with documented arrhythmias. The remote user is able to search the data and is encouraged to submit new mutations into the database. The LQTS database will become a powerful tool for both researchers and clinicians.

  20. Gene therapy for brain tumors.

    PubMed

    Bansal, K; Engelhard, H H

    2000-09-01

    "Gene therapy" can be defined as the transfer of genetic material into a patient's cells for therapeutic purposes. To date, a diverse and creative assortment of treatment strategies utilizing gene therapy have been devised, including gene transfer for modulating the immune system, enzyme prodrug ("suicide gene") therapy, oncolytic therapy, replacement/therapeutic gene transfer, and antisense therapy. For malignant glioma, gene-directed prodrug therapy using the herpes simplex virus thymidine kinase gene was the first gene therapy attempted clinically. A variety of different strategies have now been pursued experimentally and in clinical trials. Although, to date, gene therapy for brain tumors has been found to be reasonably safe, concerns still exist regarding issues related to viral delivery, transduction efficiency, potential pathologic response of the brain, and treatment efficacy. Improved viral vectors are being sought, and potential use of gene therapy in combination with other treatments is being investigated.

  1. How old is my gene?

    PubMed Central

    Capra, John A.; Stolzer, Maureen; Durand, Dannie; Pollard, Katherine S.

    2013-01-01

    Gene functions, interactions, disease associations, and ecological distributions are all correlated with gene age. However, it is challenging to estimate the intricate series of evolutionary events leading to a modern day gene and then reduce this history to a single age estimate. Focusing on eukaryotic gene families, we introduce a framework in which to compare current strategies for quantifying gene age, discuss key differences between these methods, and highlight several common problems. We argue that genes with complex evolutionary histories do not have a single well-defined age. As a result, care must be taken to articulate the goals and assumptions of any analysis that uses gene age estimates. Recent algorithmic advances offer the promise of gene age estimates that are fast, accurate, and consistent across gene families. This will enable a shift to integrated genome-wide analyses of all events in gene evolutionary histories in the near future. PMID:23915718

  2. 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. PMID:26270219

  3. 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.

  4. 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.

  5. Geophysical maps of the Dos Cabezas Mountains Wilderness Study Area, Cochise County, Arizona

    USGS Publications Warehouse

    Abrams, G.A.

    1986-01-01

    In the Dos Cabezas Mountains the Apache Pass fault zone is the major structural feature, barely skirting the southwest side of the study area. It extends several miles to the northwest and tens of miles to the southeast, across the Chiricahua Mountains beyond Apache Pass. It is typically made up of a pair of bounding faults and some anastomosing faults between them. The study area is underlain by a variety of sedimentary, igneous, and metamorphic rocks that provide only a fragmentary record of geologic events between Precambrian and Holocene times. A suite of metamorphic and igneous (primarily crystalline) rocks forms the basement terrain. Paleozoic and Mesozoic sedimentary rocks and also Paleozoic and Mesozoic volcanic rocks overlie the basement rocks but are extensively eroded away and may be covered. A pile of volcanic rocks of Late Cretaceous and Paleocene age caps the older rocks in much of the study area. Mid-Tertiary intrusive rocks underlie the eastern part of the study area as well as some very small, widely scattered additional localities. Quaternary gravel deposits occur in the major valleys and along the mountain front.

  6. Hydra: a C-language environment for real-time DOS multitasking at the bedside.

    PubMed

    DeGaetano, A; Coleman, W P; Pizzi, R; Tomasella, E; Castagneto, M; Greco, A V

    1993-10-01

    Patient monitoring at the bedside is an inherently parallel job, best handled by multiple individual tasks running concurrently. Cost and diffusion considerations strongly favor the use of PC's at the bedside, but their most widespread operating system, DOS, is not built for multitasking. Hence, a software platform in C language has been prepared, allowing the intermediate programmer to easily write independent modules which will then run simultaneously without conflicts. Such a platform aims at allowing effortless sharing of data among concurrently running processes, while providing strong insulation between tasks, enough to allow multiple copies of any one task to run simultaneously unknown to each other. A cooperative, memory sharing multitasking paradigm has been chosen, which offers fine granularity of timeslicing and low execution overhead at the price of some loss in generality of design. Speed, data exchange capability and number of stackable windows are greater than with commercial packages like Windows or LabWindows. Dynamical reprioritization of tasks is built in, allowing the computerized monitor to focus its attention and resources on urgent tasks.

  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. 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.

  10. Open Cluster Radial Velocity determination from observations at Observatório Pico Dos Dias

    NASA Astrophysics Data System (ADS)

    Faria, M. A. F.; Monteiro, H.; Dias, W. S.; Lépine, J. R. D.

    2014-10-01

    In studies of the dynamics of the Galactic disk, such as the determination of the speed of the spiral pattern and the permanence of stars in the spiral arms, it is crucial to know orbits obtained from proper motions, radial velocities and the potential of the Galaxy. Aiming to improve the statistics of our catalog of open clusters, maintained by our research group, we determined the radial velocity of stars belonging to a group of open clusters using spectra with a resolution of 4000, obtained at the Pico dos Dias Observatory (LNA) with the 1.60 m telescope and the Coudé spectrograph. We observed the open cluster's member stars and calculated their radial speeds using standard techniques. The stars were selected from our own database based on relevant information concerning the clusters, obtained by statistical analysis of their proper motions and/or their position in the HR's diagram. In this work, we present the detailed analysis of the data reduction and radial velocity determination using synthetic spectra from different libraries. Finally we present the open cluster's radial (and spacial) velocities.

  11. 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.

  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. 32 CFR Appendix C to Part 197 - Procedures for the Department of State (DoS) Foreign Relations of the United States (FRUS) Series

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) Foreign Relations of the United States (FRUS) Series C Appendix C to Part 197 National Defense Department... 197—Procedures for the Department of State (DoS) Foreign Relations of the United States (FRUS) Series... the DoS for the FRUS series under Public Law No. 102-138. b. Request authorization from the CIA,...

  15. Human DNA repair genes.

    PubMed

    Wood, R D; Mitchell, M; Sgouros, J; Lindahl, T

    2001-02-16

    Cellular DNA is subjected to continual attack, both by reactive species inside cells and by environmental agents. Toxic and mutagenic consequences are minimized by distinct pathways of repair, and 130 known human DNA repair genes are described here. Notable features presently include four enzymes that can remove uracil from DNA, seven recombination genes related to RAD51, and many recently discovered DNA polymerases that bypass damage, but only one system to remove the main DNA lesions induced by ultraviolet light. More human DNA repair genes will be found by comparison with model organisms and as common folds in three-dimensional protein structures are determined. Modulation of DNA repair should lead to clinical applications including improvement of radiotherapy and treatment with anticancer drugs and an advanced understanding of the cellular aging process. PMID:11181991

  16. Frequent gene conversion between human red and green opsin genes.

    PubMed

    Zhao, Z; Hewett-Emmett, D; Li, W H

    1998-04-01

    To study the evolution of human X-linked red and green opsin genes, genomic sequences in large regions of the two genes were compared. The divergences in introns 3, 4, and 5 and the 3' flanking sequence of the two genes are significantly lower than those in exons 4 and 5. The homogenization mechanism of introns and the 3' flanking sequence of human red and green opsin genes is probably gene conversion, which also occurred in exons 1 and 6. At least one gene conversion event occurred in each of three regions (1, 3, and 5) in the sequences compared. In conclusion, gene conversion has occurred frequently between human red and green opsin genes, but exons 2, 3, 4, and 5 have been maintained distinct between the two genes by natural selection.

  17. Neighboring Genes Show Correlated Evolution in Gene Expression

    PubMed Central

    Ghanbarian, Avazeh T.; Hurst, Laurence D.

    2015-01-01

    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. PMID:25743543

  18. Genes and Vocal Learning

    PubMed Central

    White, Stephanie A.

    2009-01-01

    Could a mutation in a single gene be the evolutionary lynchpin supporting the development of human language? A rare mutation in the molecule known as FOXP2 discovered in a human family seemed to suggest so, and its sequence phylogeny reinforced a Chomskian view that language emerged wholesale in humans. Spurred by this discovery, research in primates, rodents and birds suggests that FoxP2 and other language-related genes are interactors in the neuromolecular networks that underlie subsystems of language, such symbolic understanding, vocal learning and theory of mind. The whole picture will only come together through comparative and integrative study into how the human language singularity evolved. PMID:19913899

  19. The gene tree delusion.

    PubMed

    Springer, Mark S; Gatesy, John

    2016-01-01

    Higher-level relationships among placental mammals are mostly resolved, but several polytomies remain contentious. Song et al. (2012) claimed to have resolved three of these using shortcut coalescence methods (MP-EST, STAR) and further concluded that these methods, which assume no within-locus recombination, are required to unravel deep-level phylogenetic problems that have stymied concatenation. Here, we reanalyze Song et al.'s (2012) data and leverage these re-analyses to explore key issues in systematics including the recombination ratchet, gene tree stoichiometry, the proportion of gene tree incongruence that results from deep coalescence versus other factors, and simulations that compare the performance of coalescence and concatenation methods in species tree estimation. Song et al. (2012) reported an average locus length of 3.1 kb for the 447 protein-coding genes in their phylogenomic dataset, but the true mean length of these loci (start codon to stop codon) is 139.6 kb. Empirical estimates of recombination breakpoints in primates, coupled with consideration of the recombination ratchet, suggest that individual coalescence genes (c-genes) approach ∼12 bp or less for Song et al.'s (2012) dataset, three to four orders of magnitude shorter than the c-genes reported by these authors. This result has general implications for the application of coalescence methods in species tree estimation. We contend that it is illogical to apply coalescence methods to complete protein-coding sequences. Such analyses amalgamate c-genes with different evolutionary histories (i.e., exons separated by >100,000 bp), distort true gene tree stoichiometry that is required for accurate species tree inference, and contradict the central rationale for applying coalescence methods to difficult phylogenetic problems. In addition, Song et al.'s (2012) dataset of 447 genes includes 21 loci with switched taxonomic names, eight duplicated loci, 26 loci with non-homologous sequences that are

  20. The gene tree delusion.

    PubMed

    Springer, Mark S; Gatesy, John

    2016-01-01

    Higher-level relationships among placental mammals are mostly resolved, but several polytomies remain contentious. Song et al. (2012) claimed to have resolved three of these using shortcut coalescence methods (MP-EST, STAR) and further concluded that these methods, which assume no within-locus recombination, are required to unravel deep-level phylogenetic problems that have stymied concatenation. Here, we reanalyze Song et al.'s (2012) data and leverage these re-analyses to explore key issues in systematics including the recombination ratchet, gene tree stoichiometry, the proportion of gene tree incongruence that results from deep coalescence versus other factors, and simulations that compare the performance of coalescence and concatenation methods in species tree estimation. Song et al. (2012) reported an average locus length of 3.1 kb for the 447 protein-coding genes in their phylogenomic dataset, but the true mean length of these loci (start codon to stop codon) is 139.6 kb. Empirical estimates of recombination breakpoints in primates, coupled with consideration of the recombination ratchet, suggest that individual coalescence genes (c-genes) approach ∼12 bp or less for Song et al.'s (2012) dataset, three to four orders of magnitude shorter than the c-genes reported by these authors. This result has general implications for the application of coalescence methods in species tree estimation. We contend that it is illogical to apply coalescence methods to complete protein-coding sequences. Such analyses amalgamate c-genes with different evolutionary histories (i.e., exons separated by >100,000 bp), distort true gene tree stoichiometry that is required for accurate species tree inference, and contradict the central rationale for applying coalescence methods to difficult phylogenetic problems. In addition, Song et al.'s (2012) dataset of 447 genes includes 21 loci with switched taxonomic names, eight duplicated loci, 26 loci with non-homologous sequences that are

  1. Huntington's disease gene located.

    PubMed

    Kolata, G

    1983-11-25

    Investigators have found a restriction enzyme marker, a piece of DNA that can be located with recombinant DNA techniques, that is so close to the Huntington's disease gene that its presence can be used as an indicator for that gene. If this marker is used as a diagnostic test for Huntington's disease, people at risk for getting the disease will be able to learn whether or not they will in fact develop the disease. The ability to predict the inevitable onset of this progressive, degenerative disease raises ethical questions about counseling, screening, and disclosure of risk status to patients and family members.

  2. Polymorphisms of inflammatory markers and risk of essential hypertension in Tatars from Russia.

    PubMed

    Timasheva, Yanina R; Nasibullin, Timur R; Imaeva, Elvira B; Erdman, Vera V; Kruzliak, Peter; Tuktarova, Ilsiyar A; Nikolaeva, Irina E; Mustafina, Olga E

    2015-01-01

    Essential hypertension (EH) is a common disease with a clear genetic component. Inflammation and endothelial dysfunction play a prominent role in the development of persistent blood pressure elevation. The aim of the current study was to detect an association between EH and polymorphic markers in genes encoding for molecules involved in the control of intercellular interactions during the inflammation process. We analysed SNPs in SELE, SELP, SELL, ICAM1, VEGFA, IL1B, IL6, IL10 and IL12B genes in a group of 534 men of Tatar ethnicity (217 patients with EH and 317 controls). Using a Markov chain Monte-Carlo-based approach (APSampler), we found genotype and allelic combinations associated with EH. The most significant associations were observed for SELE rs2076059*C-SELP rs6131*A-VEGFA -2549*I-IL1B rs16944*C (p = 3.42 × 10(-5), FDR q = 0.035) and SELE rs2076059*C-SELP rs6131*A-IL12B rs3212227*C-IL1B rs16944*C (p = 323 × 10(-4), FDR q = 0.035). PMID:25945941

  3. Differential Matrix Metalloprotease (MMP) Expression Profiles Found in Aged Gingiva

    PubMed Central

    Kim, Suhee; Ahn, Sun Hee; Lee, Jin-Sil; Song, Ji-Eun; Cho, Sung-Hyun; Jung, Seunggon; Kim, Seon-Kyu; Kim, Seok-Ho; Lee, Kwang-Pyo

    2016-01-01

    The periodontium undergoes age-related cellular and clinical changes, but the involved genes are not yet known. Here, we investigated age-related genetic changes in gingiva at the transcriptomic level. Genes that were differentially expressed between young and old human gingiva were identified by RNA sequencing and verified by real-time PCR. A total of 1939 mRNA transcripts showed significantly differential expression between young and old gingival tissues. Matrix metalloprotease (MMP) regulation was the top pathway involved in gingival aging. MMP3, MMP9, MMP12, and MMP13 were upregulated in old gingival tissues, concomitantly with interleukin-1 beta (IL1B) expression. In vitro experiments using human gingival fibroblasts (hGFs) showed that MMP12 was upregulated in old hGFs compared to young hGFs. Moreover, the MMP3, MMP9 and IL1B levels were more highly stimulated by infection with the oral bacterium, Fusobacterium nucleatum, in old hGFs compared to young hGFs. Collectively, these findings suggest that, in gingiva, the upregulation of MMP12 may be a molecular hallmark of natural aging, while the upregulations of MMP3, MMM9, and IL1B may indicate externally (e.g., infection)-induced aging. These findings contribute to our understanding of the molecular targets involved in gingival aging. PMID:27391467

  4. Gene therapy: progress and predictions

    PubMed Central

    Collins, Mary; Thrasher, Adrian

    2015-01-01

    The first clinical gene delivery, which involved insertion of a marker gene into lymphocytes from cancer patients, was published 25 years ago. In this review, we describe progress since then in gene therapy. Patients with some inherited single-gene defects can now be treated with their own bone marrow stem cells that have been engineered with a viral vector carrying the missing gene. Patients with inherited retinopathies and haemophilia B can also be treated by local or systemic injection of viral vectors. There are also a number of promising gene therapy approaches for cancer and infectious disease. We predict that the next 25 years will see improvements in safety, efficacy and manufacture of gene delivery vectors and introduction of gene-editing technologies to the clinic. Gene delivery may also prove a cost-effective method for the delivery of biological medicines. PMID:26702034

  5. Gene Characterization Index: Assessing the Depth of Gene Annotation

    PubMed Central

    Yusuf, Dimas; Brumm, Jochen; Cheung, Warren; Wahlestedt, Claes; Lenhard, Boris; Wasserman, Wyeth W.

    2008-01-01

    Background We introduce the Gene Characterization Index, a bioinformatics method for scoring the extent to which a protein-encoding gene is functionally described. Inherently a reflection of human perception, the Gene Characterization Index is applied for assessing the characterization status of individual genes, thus serving the advancement of both genome annotation and applied genomics research by rapid and unbiased identification of groups of uncharacterized genes for diverse applications such as directed functional studies and delineation of novel drug targets. Methodology/Principal Findings The scoring procedure is based on a global survey of researchers, who assigned characterization scores from 1 (poor) to 10 (extensive) for a sample of genes based on major online resources. By evaluating the survey as training data, we developed a bioinformatics procedure to assign gene characterization scores to all genes in the human genome. We analyzed snapshots of functional genome annotation over a period of 6 years to assess temporal changes reflected by the increase of the average Gene Characterization Index. Applying the Gene Characterization Index to genes within pharmaceutically relevant classes, we confirmed known drug targets as high-scoring genes and revealed potentially interesting novel targets with low characterization indexes. Removing known drug targets and genes linked to sequence-related patent filings from the entirety of indexed genes, we identified sets of low-scoring genes particularly suited for further experimental investigation. Conclusions/Significance The Gene Characterization Index is intended to serve as a tool to the scientific community and granting agencies for focusing resources and efforts on unexplored areas of the genome. The Gene Characterization Index is available from http://cisreg.ca/gci/. PMID:18213364

  6. Naming genes beyond Caenorhabditis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The nomenclature of genes in Caenorhabditis elegans is based on long-standing, successful guidelines established in the late 1970s. Over time these guidelines have matured into a comprehensive, systematic nomenclature that is easy to apply, descriptive and therefore highly informative. Recently, a f...

  7. Gene targeting in livestock.

    PubMed

    Thomson, A J; Marques, M M; McWhir, J

    2003-01-01

    The development of nuclear transfer from tissue culture cells in livestock made it possible in principle to produce animals with subtle, directed genetic changes by in vitro modification of nuclear donor cells. In the short period since nuclear transfer was first performed, gene targeting in livestock has become a reality. Although gene targeting has immediate potential in biotechnology, it is unclear whether there are practical agricultural applications, at present. The first livestock targeting experiments have been directed at engineering animals either to render their organs immunologically compatible for human transplantation, or for improving the commercial production of recombinant proteins in the transgenic mammary gland. All successful examples of targeting have involved target loci that are expressed in the nuclear donor cell line. Two important barriers to the further development of this technology are adapting protocols for non-expressed genes and modifying procedures to enhance the lifespan of targeted cells in vitro. This review provides data that illustrate the difficulty in targeting non-expressed genes and discusses some of the practical issues associated with providing targeted nuclear donor cells that are competent for nuclear transfer.

  8. Inferring horizontal gene transfer.

    PubMed

    Ravenhall, Matt; Škunca, Nives; Lassalle, Florent; Dessimoz, Christophe

    2015-05-01

    Horizontal or Lateral Gene Transfer (HGT or LGT) is the transmission of portions of genomic DNA between organisms through a process decoupled from vertical inheritance. In the presence of HGT events, different fragments of the genome are the result of different evolutionary histories. This can therefore complicate the investigations of evolutionary relatedness of lineages and species. Also, as HGT can bring into genomes radically different genotypes from distant lineages, or even new genes bearing new functions, it is a major source of phenotypic innovation and a mechanism of niche adaptation. For example, of particular relevance to human health is the lateral transfer of antibiotic resistance and pathogenicity determinants, leading to the emergence of pathogenic lineages. Computational identification of HGT events relies upon the investigation of sequence composition or evolutionary history of genes. Sequence composition-based ("parametric") methods search for deviations from the genomic average, whereas evolutionary history-based ("phylogenetic") approaches identify genes whose evolutionary history significantly differs from that of the host species. The evaluation and benchmarking of HGT inference methods typically rely upon simulated genomes, for which the true history is known. On real data, different methods tend to infer different HGT events, and as a result it can be difficult to ascertain all but simple and clear-cut HGT events. PMID:26020646

  9. Gene-Environment Interdependence

    ERIC Educational Resources Information Center

    Rutter, Michael

    2007-01-01

    Behavioural genetics was initially concerned with partitioning population variance into that due to genetics and that due to environmental influences. The implication was that the two were separate and it was assumed that gene-environment interactions were usually of so little importance that they could safely be ignored. Theoretical…

  10. Zmspds2 maize gene

    PubMed Central

    Rodríguez-Kessler, Margarita

    2008-01-01

    During the last decade, growing evidence has arisen referring the importance of the proper regulation of plant polyamine metabolism in the response to stress conditions. Being the activation of signaling pathways, the stabilization of anionic molecules and prevention of their degradation, as well as the free radical scavenger properties of polyamines some possible mechanisms exerted by these amines. Accumulation of polyamines (putrescine, spermidine and spermine) has been associated to plant tolerance to a wide array of environmental stresses. The synthesis of spermidine and spermine is mediated by aminopropyltransferases (spermidine and spermine synthases) which constitute a class of widely distributed enzymes that use decarboxylated S-adenosylmethionine as an aminopropyl donor, and putrescine or spermidine as an amino acceptor. We recently reported the effect of salt stress on the expression of aminopropyltransferase genes in maize seedlings. Our data revealed a time and NaCl dependent regulation of the Zmspds2 and Zmspds1 genes, possibly mediated by abscisic acid, since these genes were regulated at the transcriptional level by this plant hormone. In this addendum, we show that the Zmspds2 gene initially classified as spermidine synthase might encode a spermine synthase based on an in silico analysis. This is discussed in terms of protein homologies and specific amino acid substitutions between aminopropyltransferase enzymes. PMID:19704464

  11. Rhabdovirus accessory genes.

    PubMed

    Walker, Peter J; Dietzgen, Ralf G; Joubert, D Albert; Blasdell, Kim R

    2011-12-01

    The Rhabdoviridae is one of the most ecologically diverse families of RNA viruses with members infecting a wide range of organisms including placental mammals, marsupials, birds, reptiles, fish, insects and plants. The availability of complete nucleotide sequences for an increasing number of rhabdoviruses has revealed that their ecological diversity is reflected in the diversity and complexity of their genomes. The five canonical rhabdovirus structural protein genes (N, P, M, G and L) that are shared by all rhabdoviruses are overprinted, overlapped and interspersed with a multitude of novel and diverse accessory genes. Although not essential for replication in cell culture, several of these genes have been shown to have roles associated with pathogenesis and apoptosis in animals, and cell-to-cell movement in plants. Others appear to be secreted or have the characteristics of membrane-anchored glycoproteins or viroporins. However, most encode proteins of unknown function that are unrelated to any other known proteins. Understanding the roles of these accessory genes and the strategies by which rhabdoviruses use them to engage, divert and re-direct cellular processes will not only present opportunities to develop new anti-viral therapies but may also reveal aspects of cellar function that have broader significance in biology, agriculture and medicine.

  12. Genes and Vocal Learning

    ERIC Educational Resources Information Center

    White, Stephanie A.

    2010-01-01

    Could a mutation in a single gene be the evolutionary lynchpin supporting the development of human language? A rare mutation in the molecule known as FOXP2 discovered in a human family seemed to suggest so, and its sequence phylogeny reinforced a Chomskian view that language emerged wholesale in humans. Spurred by this discovery, research in…

  13. Inferring Horizontal Gene Transfer

    PubMed Central

    Lassalle, Florent; Dessimoz, Christophe

    2015-01-01

    Horizontal or Lateral Gene Transfer (HGT or LGT) is the transmission of portions of genomic DNA between organisms through a process decoupled from vertical inheritance. In the presence of HGT events, different fragments of the genome are the result of different evolutionary histories. This can therefore complicate the investigations of evolutionary relatedness of lineages and species. Also, as HGT can bring into genomes radically different genotypes from distant lineages, or even new genes bearing new functions, it is a major source of phenotypic innovation and a mechanism of niche adaptation. For example, of particular relevance to human health is the lateral transfer of antibiotic resistance and pathogenicity determinants, leading to the emergence of pathogenic lineages [1]. Computational identification of HGT events relies upon the investigation of sequence composition or evolutionary history of genes. Sequence composition-based ("parametric") methods search for deviations from the genomic average, whereas evolutionary history-based ("phylogenetic") approaches identify genes whose evolutionary history significantly differs from that of the host species. The evaluation and benchmarking of HGT inference methods typically rely upon simulated genomes, for which the true history is known. On real data, different methods tend to infer different HGT events, and as a result it can be difficult to ascertain all but simple and clear-cut HGT events. PMID:26020646

  14. Genes in mammalian reproduction

    SciTech Connect

    Gwatkin, R.B.L.

    1996-11-01

    This is an informative book which deals mainly with genomic imprinting, the role of steroid hormones in development, the expression of a variety of genes during development and the link to hereditary diseases. It is an up-to-date review in a field that is quickly changing and provides valuable basic information and current research trends.

  15. Airway gene therapy.

    PubMed

    Davies, Jane C; Alton, Eric W F W

    2005-01-01

    Given both the accessibility and the genetic basis of several pulmonary diseases, the lungs and airways initially seemed ideal candidates for gene therapy. Several routes of access are available, many of which have been refined and optimized for nongene drug delivery. Two respiratory diseases, cystic fibrosis (CF) and alpha1-antitrypsin (alpha1-AT) deficiency, are relatively common; the single gene responsible has been identified and current treatment strategies are not curative. This type of inherited disease was the obvious initial target for gene therapy, but it has become clear that nongenetic and acquired diseases, including cancer, may also be amenable to this approach. The majority of preclinical and clinical studies in the airway have involved viral vectors, although for diseases such as CF, likely to require repeated application, non-viral delivery systems have clear advantages. However, with both approaches a range of barriers to gene expression have been identified that are limiting success in the airway and alveolar region. This chapter reviews these issues, strategies aimed at overcoming them, and progress into clinical trials with non-viral vectors in a variety of pulmonary diseases.

  16. Gene stacking by recombinases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Efficient methods of stacking genes into plant genomes are needed to expedite transfer of multigenic traits into diverse crops grown in a variety of environments. Over two decades of research has identified several site-specific recombinases that carry out efficient cis and trans recombination betw...

  17. Old genes experience stronger translational selection than young genes.

    PubMed

    Yin, Hongyan; Ma, Lina; Wang, Guangyu; Li, Mengwei; Zhang, Zhang

    2016-09-15

    Selection on synonymous codon usage for translation efficiency and/or accuracy has been identified as a widespread mechanism in many living organisms. However, it remains unknown whether translational selection associates closely with gene age and acts differentially on genes with different evolutionary ages. To address this issue, here we investigate the strength of translational selection acting on different aged genes in human. Our results show that old genes present stronger translational selection than young genes, demonstrating that translational selection correlates positively with gene age. We further explore the difference of translational selection in duplicates vs. singletons and in housekeeping vs. tissue-specific genes. We find that translational selection acts comparably in old singletons and old duplicates and stronger translational selection in old genes is contributed primarily by housekeeping genes. For young genes, contrastingly, singletons experience stronger translational selection than duplicates, presumably due to redundant function of duplicated genes during their early evolutionary stage. Taken together, our results indicate that translational selection acting on a gene would not be constant during all stages of evolution, associating closely with gene age.

  18. Genes2FANs: connecting genes through functional association networks

    PubMed Central

    2012-01-01

    Background Protein-protein, cell signaling, metabolic, and transcriptional interaction networks are useful for identifying connections between lists of experimentally identified genes/proteins. However, besides physical or co-expression interactions there are many ways in which pairs of genes, or their protein products, can be associated. By systematically incorporating knowledge on shared properties of genes from diverse sources to build functional association networks (FANs), researchers may be able to identify additional functional interactions between groups of genes that are not readily apparent. Results Genes2FANs is a web based tool and a database that utilizes 14 carefully constructed FANs and a large-scale protein-protein interaction (PPI) network to build subnetworks that connect lists of human and mouse genes. The FANs are created from mammalian gene set libraries where mouse genes are converted to their human orthologs. The tool takes as input a list of human or mouse Entrez gene symbols to produce a subnetwork and a ranked list of intermediate genes that are used to connect the query input list. In addition, users can enter any PubMed search term and then the system automatically converts the returned results to gene lists using GeneRIF. This gene list is then used as input to generate a subnetwork from the user’s PubMed query. As a case study, we applied Genes2FANs to connect disease genes from 90 well-studied disorders. We find an inverse correlation between the counts of links connecting disease genes through PPI and links connecting diseases genes through FANs, separating diseases into two categories. Conclusions Genes2FANs is a useful tool for interpreting the relationships between gene/protein lists in the context of their various functions and networks. Combining functional association interactions with physical PPIs can be useful for revealing new biology and help form hypotheses for further experimentation. Our finding that disease genes in

  19. Associations between interleukin-1 gene polymorphisms and sepsis risk: a meta-analysis

    PubMed Central

    2014-01-01

    Background Previous epidemiological studies have presented conflicting evidence regarding associations between interleukin-1 (IL-1) polymorphisms and sepsis susceptibility. We have performed a meta-analysis to evaluate possible associations between IL-1 polymorphisms and sepsis risk. Methods Eligible literature was retrieved from PubMed, Embase and Web of Knowledge databases until Jun 15, 2013. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random-effects model in the overall and subgroup analysis based on ethnicity, sepsis severity and quality score. Results Eighteen studies addressing five IL-1 polymorphisms were included in this meta-analysis. For IL-1A-889 (rs1800587) polymorphism, significant association was observed in overall comparison for allelic effect (OR = 1.47, 95% CI = 1.01-2.13, P = 0.04). There were no significant associations between either IL-1B-511 (rs16944) or IL-1B-31 (rs1143627) and sepsis susceptibility in overall or subgroup analyses. For IL-1B + 3594 (rs143634) polymorphism, genotype TT decreased sepsis risk in overall analysis (OR = 0.59, 95% CI = 0.36-0.97, P = 0.04), as well as in Caucasian (OR = 0.57, 95% CI = 0.34-0.95, P = 0.03) and sepsis (OR = 0.55, 95% CI = 0.31-0.97, P = 0.04) subgroup analysis. For IL-1RN VNTR polymorphism, significant association was observed in overall comparison for allelic effect (OR = 1.40, 95% CI = 1.01-1.95, P = 0.04). Furthermore, the effect sizes of IL-1RN VNTR on sepsis risk increased with disease severity (septic shock OR > severe sepsis OR > sepsis OR). Conclusions Our meta-analysis indicated that IL-1A-889, IL-1B + 3954 and IL-1RN VNTR might be associated with sepsis susceptibility. However, further studies with larger sample sizes and from homogenous populations would be necessary to validate these findings. PMID:24428862

  20. 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

  1. Industrial scale gene synthesis.

    PubMed

    Notka, Frank; Liss, Michael; Wagner, Ralf

    2011-01-01

    The most recent developments in the area of deep DNA sequencing and downstream quantitative and functional analysis are rapidly adding a new dimension to understanding biochemical pathways and metabolic interdependencies. These increasing insights pave the way to designing new strategies that address public needs, including environmental applications and therapeutic inventions, or novel cell factories for sustainable and reconcilable energy or chemicals sources. Adding yet another level is building upon nonnaturally occurring networks and pathways. Recent developments in synthetic biology have created economic and reliable options for designing and synthesizing genes, operons, and eventually complete genomes. Meanwhile, high-throughput design and synthesis of extremely comprehensive DNA sequences have evolved into an enabling technology already indispensable in various life science sectors today. Here, we describe the industrial perspective of modern gene synthesis and its relationship with synthetic biology. Gene synthesis contributed significantly to the emergence of synthetic biology by not only providing the genetic material in high quality and quantity but also enabling its assembly, according to engineering design principles, in a standardized format. Synthetic biology on the other hand, added the need for assembling complex circuits and large complexes, thus fostering the development of appropriate methods and expanding the scope of applications. Synthetic biology has also stimulated interdisciplinary collaboration as well as integration of the broader public by addressing socioeconomic, philosophical, ethical, political, and legal opportunities and concerns. The demand-driven technological achievements of gene synthesis and the implemented processes are exemplified by an industrial setting of large-scale gene synthesis, describing production from order to delivery.

  2. Endovascular Gene Delivery from a Stent Platform: Gene- Eluting Stents

    PubMed Central

    Fishbein, Ilia; Chorny, Michael; Adamo, Richard F; Forbes, Scott P; Corrales, Ricardo A; Alferiev, Ivan S; Levy, Robert J

    2015-01-01

    A synergistic impact of research in the fields of post-angioplasty restenosis, drug-eluting stents and vascular gene therapy over the past 15 years has shaped the concept of gene-eluting stents. Gene-eluting stents hold promise of overcoming some biological and technical problems inherent to drug-eluting stent technology. As the field of gene-eluting stents matures it becomes evident that all three main design modules of a gene-eluting stent: a therapeutic transgene, a vector and a delivery system are equally important for accomplishing sustained inhibition of neointimal formation in arteries treated with gene delivery stents. This review summarizes prior work on stent-based gene delivery and discusses the main optimization strategies required to move the field of gene-eluting stents to clinical translation. PMID:26225356

  3. The Relationship between Older Drivers’ Performance on the Driving Observation Schedule (eDOS) and Cognitive Performance

    PubMed Central

    Koppel, Sjaan; Charlton, Judith; Langford, Jim; Vlahodimitrakou, Zafiroula; Di Stefano, Marilyn; Macdonald, Wendy; Mazer, Barbara; Gelinas, Isabelle; Vrkljan, Brenda; Marshall, Shawn

    2013-01-01

    Research question/Objective: The Driving Observation Schedule (eDOS) was developed for use in the Candrive/Ozcandrive five-year prospective study of older drivers to observe the driving behavior of older drivers and monitor changes in driving behaviors over time. The aim of this study is to describe participants’ driving performance during the eDOS driving task and investigate the association between driving performance and cognitive measures. Methods: A subset of Ozcandrive participants (n = 144, 104 male [72%], 40 female [28%], Mean age = 81.49 years, SD = 3.58 years, Range: 76 – 96 years) completed the eDOS driving task. Participants drove to their selected destinations (up to 4 locations), with observations of driving behaviors (both inappropriate and appropriate) recorded for specific driving maneuvers: intersection negotiation, lane-changing, merging, low speed maneuvers and maneuver-free driving. Driving behaviors (e.g. signalling, speed regulation, gap acceptance, lane position, ‘critical errors’) were scored by a trained observer and participants received an overall eDOS driving task score (Maximum = 100 points). Participants also completed a series of cognitive assessments as part of the Year 2 Candrive/Ozcandrive assessment protocols. Results: The overall eDOS driving task score was very high (M = 95.77; SD = 5.15; Range = 65.63 – 100). Detailed analyses of participants’ driving behavior revealed a high level of appropriate driving behavior (96%, n = 5,935 maneuvers), with few errors (4%, n = 252 maneuvers). While most participants’ performance on the cognitive assessments was high, some scores were below the criteria for cogntive impairment (BIC) according to conventional benchmarks: (MoCA: M = 26.56, SD = 2.12, Range = 19 – 30, % BIC = 28%; MMSE: M = 29.10, SD = 1.01, Range = 26–30, %BIC = 0%; Trails B: M = 111.66, SD = 43.53, Range = 50 – 301, %BIC = 6%). There was no significant relationship observed between participants

  4. Optimal Reference Genes for Gene Expression Normalization in Trichomonas vaginalis.

    PubMed

    dos Santos, Odelta; de Vargas Rigo, Graziela; Frasson, Amanda Piccoli; Macedo, Alexandre José; Tasca, Tiana

    2015-01-01

    Trichomonas vaginalis is the etiologic agent of trichomonosis, the most common non-viral sexually transmitted disease worldwide. This infection is associated with several health consequences, including cervical and prostate cancers and HIV acquisition. Gene expression analysis has been facilitated because of available genome sequences and large-scale transcriptomes in T. vaginalis, particularly using quantitative real-time polymerase chain reaction (qRT-PCR), one of the most used methods for molecular studies. Reference genes for normalization are crucial to ensure the accuracy of this method. However, to the best of our knowledge, a systematic validation of reference genes has not been performed for T. vaginalis. In this study, the transcripts of nine candidate reference genes were quantified using qRT-PCR under different cultivation conditions, and the stability of these genes was compared using the geNorm and NormFinder algorithms. The most stable reference genes were α-tubulin, actin and DNATopII, and, conversely, the widely used T. vaginalis reference genes GAPDH and β-tubulin were less stable. The PFOR gene was used to validate the reliability of the use of these candidate reference genes. As expected, the PFOR gene was upregulated when the trophozoites were cultivated with ferrous ammonium sulfate when the DNATopII, α-tubulin and actin genes were used as normalizing gene. By contrast, the PFOR gene was downregulated when the GAPDH gene was used as an internal control, leading to misinterpretation of the data. These results provide an important starting point for reference gene selection and gene expression analysis with qRT-PCR studies of T. vaginalis.

  5. Optimal Reference Genes for Gene Expression Normalization in Trichomonas vaginalis.

    PubMed

    dos Santos, Odelta; de Vargas Rigo, Graziela; Frasson, Amanda Piccoli; Macedo, Alexandre José; Tasca, Tiana

    2015-01-01

    Trichomonas vaginalis is the etiologic agent of trichomonosis, the most common non-viral sexually transmitted disease worldwide. This infection is associated with several health consequences, including cervical and prostate cancers and HIV acquisition. Gene expression analysis has been facilitated because of available genome sequences and large-scale transcriptomes in T. vaginalis, particularly using quantitative real-time polymerase chain reaction (qRT-PCR), one of the most used methods for molecular studies. Reference genes for normalization are crucial to ensure the accuracy of this method. However, to the best of our knowledge, a systematic validation of reference genes has not been performed for T. vaginalis. In this study, the transcripts of nine candidate reference genes were quantified using qRT-PCR under different cultivation conditions, and the stability of these genes was compared using the geNorm and NormFinder algorithms. The most stable reference genes were α-tubulin, actin and DNATopII, and, conversely, the widely used T. vaginalis reference genes GAPDH and β-tubulin were less stable. The PFOR gene was used to validate the reliability of the use of these candidate reference genes. As expected, the PFOR gene was upregulated when the trophozoites were cultivated with ferrous ammonium sulfate when the DNATopII, α-tubulin and actin genes were used as normalizing gene. By contrast, the PFOR gene was downregulated when the GAPDH gene was used as an internal control, leading to misinterpretation of the data. These results provide an important starting point for reference gene selection and gene expression analysis with qRT-PCR studies of T. vaginalis. PMID:26393928

  6. Optimal Reference Genes for Gene Expression Normalization in Trichomonas vaginalis

    PubMed Central

    dos Santos, Odelta; de Vargas Rigo, Graziela; Frasson, Amanda Piccoli; Macedo, Alexandre José; Tasca, Tiana

    2015-01-01

    Trichomonas vaginalis is the etiologic agent of trichomonosis, the most common non-viral sexually transmitted disease worldwide. This infection is associated with several health consequences, including cervical and prostate cancers and HIV acquisition. Gene expression analysis has been facilitated because of available genome sequences and large-scale transcriptomes in T. vaginalis, particularly using quantitative real-time polymerase chain reaction (qRT-PCR), one of the most used methods for molecular studies. Reference genes for normalization are crucial to ensure the accuracy of this method. However, to the best of our knowledge, a systematic validation of reference genes has not been performed for T. vaginalis. In this study, the transcripts of nine candidate reference genes were quantified using qRT-PCR under different cultivation conditions, and the stability of these genes was compared using the geNorm and NormFinder algorithms. The most stable reference genes were α-tubulin, actin and DNATopII, and, conversely, the widely used T. vaginalis reference genes GAPDH and β-tubulin were less stable. The PFOR gene was used to validate the reliability of the use of these candidate reference genes. As expected, the PFOR gene was upregulated when the trophozoites were cultivated with ferrous ammonium sulfate when the DNATopII, α-tubulin and actin genes were used as normalizing gene. By contrast, the PFOR gene was downregulated when the GAPDH gene was used as an internal control, leading to misinterpretation of the data. These results provide an important starting point for reference gene selection and gene expression analysis with qRT-PCR studies of T. vaginalis. PMID:26393928

  7. Dominance from the perspective of gene-gene and gene-chemical interactions.

    PubMed

    Gladki, Arkadiusz; Zielenkiewicz, Piotr; Kaczanowski, Szymon

    2016-02-01

    In this study, we used genetic interaction (GI) and gene-chemical interaction (GCI) data to compare mutations with different dominance phenotypes. Our analysis focused primarily on Saccharomyces cerevisiae, where haploinsufficient genes (HI; genes with dominant loss-of-function mutations) were found to be participating in gene expression processes, namely, the translation and regulation of gene transcription. Non-ribosomal HI genes (mainly regulators of gene transcription) were found to have more GIs and GCIs than haplosufficient (HS) genes. Several properties seem to lead to the enrichment of interactions, most notably, the following: importance, pleiotropy, gene expression level and gene expression variation. Importantly, after these properties were appropriately considered in the analysis, the correlation between dominance and GI/GCI degrees was still observed. Strikingly, for the GCIs of heterozygous strains, haploinsufficiency was the only property significantly correlated with the number of GCIs. We found ribosomal HI genes to be depleted in GIs/GCIs. This finding can be explained by their high variation in gene expression under different genetic backgrounds and environmental conditions. We observed the same distributions of GIs among non-ribosomal HI, ribosomal HI and HS genes in three other species: Schizosaccharomyces pombe, Drosophila melanogaster and Homo sapiens. One potentially interesting exception was the lack of significant differences in the degree of GIs between non-ribosomal HI and HS genes in Schizosaccharomyces pombe.

  8. Video movie making using remote procedure calls and 4BSD Unix sockets on Unix, UNICOS, and MS-DOS systems

    SciTech Connect

    Robertson, D.W.; Johnston, W.E.; Hall, D.E.; Rosenblum, M.

    1990-03-01

    We describe the use of the Sun Remote Procedure Call and Unix socket interprocess communication mechanisms to provide the network transport for a distributed, client-server based, image handling system. Clients run under Unix or UNICOS and servers run under Unix or MS-DOS. The use of remote procedure calls across local or wide-area networks to make video movies is addressed.

  9. Estudio fotométrico y espectroscópico de dos cúmulos abiertos jóvenes del disco con apariencia globular

    NASA Astrophysics Data System (ADS)

    Piatti, A. E.; Clariá, J. J.; Bica, E.

    Se presentan y discuten resultados obtenidos en el CASLEO y en el Observatorio de Las Campanas de dos cúmulos abiertos compactos con apariencia globular: Westerlund1 (BH197), ubicado en dirección hacia el centro galáctico, y Westerlund2. A partir de espectroscopía CCD integrada de ambos e imágenes CCD en las bandas VI obtenidas para el primero de ellos, se derivan sus parámetros fundamentales y se examinan sus apariencias estructurales. Se encuentra que Westerlund1 es un cúmulo joven (7 ± 3 millones de años), ubicado sobre el plano galáctico a 1.0 ± 0.4 kpc del sol, en una región caracterizada por una absorción excepcionalmente elevada (Av~=13.0 mag), en tanto que Westerlund2 es también un cúmulo joven (4-6 millones de años) ubicado sobre el plano, en una región afectada por una absorción menor (Av~=5.7 mag). Desde el punto de vista estructural, Westerlund 1 se presenta como uno de los pocos cúmulos abiertos jóvenes de la Galaxia con apariencia tipicamente globular, en contraste con los cúmulos azules de las Nubes de Magallanes en los cuales la apariencia globular constituye un fenómeno común. Westerlund2, aunque menos rico en estrellas, puede también ser incluído dentro de esta interesante clase de objetos.

  10. Avirulence Genes in Cereal Powdery Mildews: The Gene-for-Gene Hypothesis 2.0.

    PubMed

    Bourras, Salim; McNally, Kaitlin E; Müller, Marion C; Wicker, Thomas; Keller, Beat

    2016-01-01

    The gene-for-gene hypothesis states that for each gene controlling resistance in the host, there is a corresponding, specific gene controlling avirulence in the pathogen. Allelic series of the cereal mildew resistance genes Pm3 and Mla provide an excellent system for genetic and molecular analysis of resistance specificity. Despite this opportunity for molecular research, avirulence genes in mildews remain underexplored. Earlier work in barley powdery mildew (B.g. hordei) has shown that the reaction to some Mla resistance alleles is controlled by multiple genes. Similarly, several genes are involved in the specific interaction of wheat mildew (B.g. tritici) with the Pm3 allelic series. We found that two mildew genes control avirulence on Pm3f: one gene is involved in recognition by the resistance protein as demonstrated by functional studies in wheat and the heterologous host Nicotiana benthamiana. A second gene is a suppressor, and resistance is only observed in mildew genotypes combining the inactive suppressor and the recognized Avr. We propose that such suppressor/avirulence gene combinations provide the basis of specificity in mildews. Depending on the particular gene combinations in a mildew race, different genes will be genetically identified as the "avirulence" gene. Additionally, the observation of two LINE retrotransposon-encoded avirulence genes in B.g. hordei further suggests that the control of avirulence in mildew is more complex than a canonical gene-for-gene interaction. To fully understand the mildew-cereal interactions, more knowledge on avirulence determinants is needed and we propose ways how this can be achieved based on recent advances in the field.

  11. Avirulence Genes in Cereal Powdery Mildews: The Gene-for-Gene Hypothesis 2.0

    PubMed Central

    Bourras, Salim; McNally, Kaitlin E.; Müller, Marion C.; Wicker, Thomas; Keller, Beat

    2016-01-01

    The gene-for-gene hypothesis states that for each gene controlling resistance in the host, there is a corresponding, specific gene controlling avirulence in the pathogen. Allelic series of the cereal mildew resistance genes Pm3 and Mla provide an excellent system for genetic and molecular analysis of resistance specificity. Despite this opportunity for molecular research, avirulence genes in mildews remain underexplored. Earlier work in barley powdery mildew (B.g. hordei) has shown that the reaction to some Mla resistance alleles is controlled by multiple genes. Similarly, several genes are involved in the specific interaction of wheat mildew (B.g. tritici) with the Pm3 allelic series. We found that two mildew genes control avirulence on Pm3f: one gene is involved in recognition by the resistance protein as demonstrated by functional studies in wheat and the heterologous host Nicotiana benthamiana. A second gene is a suppressor, and resistance is only observed in mildew genotypes combining the inactive suppressor and the recognized Avr. We propose that such suppressor/avirulence gene combinations provide the basis of specificity in mildews. Depending on the particular gene combinations in a mildew race, different genes will be genetically identified as the “avirulence” gene. Additionally, the observation of two LINE retrotransposon-encoded avirulence genes in B.g. hordei further suggests that the control of avirulence in mildew is more complex than a canonical gene-for-gene interaction. To fully understand the mildew–cereal interactions, more knowledge on avirulence determinants is needed and we propose ways how this can be achieved based on recent advances in the field. PMID:26973683

  12. Chapter 15: Disease Gene Prioritization

    PubMed Central

    Bromberg, Yana

    2013-01-01

    Disease-causing aberrations in the normal function of a gene define that gene as a disease gene. Proving a causal link between a gene and a disease experimentally is expensive and time-consuming. Comprehensive prioritization of candidate genes prior to experimental testing drastically reduces the associated costs. Computational gene prioritization is based on various pieces of correlative evidence that associate each gene with the given disease and suggest possible causal links. A fair amount of this evidence comes from high-throughput experimentation. Thus, well-developed methods are necessary to reliably deal with the quantity of information at hand. Existing gene prioritization techniques already significantly improve the outcomes of targeted experimental studies. Faster and more reliable techniques that account for novel data types are necessary for the development of new diagnostics, treatments, and cure for many diseases. PMID:23633938

  13. Evolutionary genomics: transdomain gene transfers.

    PubMed

    Bordenstein, Seth R

    2007-11-01

    Biologists have until now conceded that bacterial gene transfer to multicellular animals is relatively uncommon in Nature. A new study showing promiscuous insertions of bacterial endosymbiont genes into invertebrate genomes ushers in a shift in this paradigm.

  14. Gene Therapy for Lung Cancer.

    PubMed

    Lara-Guerra, Humberto; Roth, Jack A

    2016-01-01

    Gene therapy was originally conceived to treat monogenic diseases. The replacement of a defective gene with a functional gene can theoretically cure the disease. In cancer, multiple genetic defects are present and the molecular profile changes during the course of the disease, making the replacement of all defective genes impossible. To overcome these difficulties, various gene therapy strategies have been adopted, including immune stimulation, transfer of suicide genes, inhibition of driver oncogenes, replacement of tumor-suppressor genes that could mediate apoptosis or anti-angiogenesis, and transfer of genes that enhance conventional treatments such as radiotherapy and chemotherapy. Some of these strategies have been tested successfully in non-small-cell lung cancer patients and the results of laboratory studies and clinical trials are reviewed herein. PMID:27481008

  15. Gene Testing for Hereditary Ataxia

    MedlinePlus

    ... have a family history of ataxia, but diagnostic tests for known ataxia genes cannot explain the ataxia in their family. In recent years, scientists have developed technologies to sequence thousands of genes at the same ...

  16. Investigation of the relationship between protein-protein interaction and catalytic activity of a heme-regulated phosphodiesterase from Escherichia coli (Ec DOS) by protein microarray.

    PubMed

    Sasakura, Yukie; Kanda, Katsuhiro; Yoshimura-Suzuki, Tokiko; Matsui, Takuya; Fukuzono, Shinichi; Shimizu, Toru

    2005-07-19

    Ec DOS, a heme-regulated phosphodiesterase from Escherichia coli, is composed of an N-terminal heme-bound PAS domain and a C-terminal phosphodiesterase domain. The heme redox state in the PAS domain regulates Ec DOS phosphodiesterase activity. Interestingly, the isolated heme-bound PAS fragment enhances phosphodiesterase activity of full-length Ec DOS. The enhancement is also regulated by the heme redox state of the isolated PAS domain. In the present study, we used a newly developed protein microarray system to examine the relationship between catalytic activity and the interaction of full-length Ec DOS and the isolated PAS fragment. Adenosine 3',5'-cyclic monophosphate (cAMP), a substrate of the Ec DOS phosphodiesterase, was found to be indispensable for the interaction between Ec DOS and the PAS fragment, and two phosphodiesterase inhibitors, 3-isobutyl-methyl-xanthine and etazolate hydrochloride, hindered the interaction. In addition, an enzyme with a mutation in the putative cAMP-binding sites (H590 and H594) was unable to interact with Ec DOS and lacked enzymatic activity. These results strongly suggest a close relationship between Ec DOS phosphodiesterase activity and interaction with the isolated PAS fragment. Therefore, this study provides insights into the mechanism of how the isolated PAS domain activates Ec DOS, which has important implications for the general role of the isolated PAS domain in cells. Moreover, we found that multiple microscale analyses using the protein microarray system had several advantages over conventional affinity column methods, including the quantity of protein needed, the sensitivity, the variability of immobilized protein, and the time required for the experiment. PMID:16008345

  17. RNA-mediated gene activation

    PubMed Central

    Jiao, Alan L; Slack, Frank J

    2014-01-01

    The regulation of gene expression by non-coding RNAs (ncRNAs) has become a new paradigm in biology. RNA-mediated gene silencing pathways have been studied extensively, revealing diverse epigenetic and posttranscriptional mechanisms. In contrast, the roles of ncRNAs in activating gene expression remains poorly understood. In this review, we summarize the current knowledge of gene activation by small RNAs, long non-coding RNAs, and enhancer-derived RNAs, with an emphasis on epigenetic mechanisms. PMID:24185374

  18. Gene expression technology

    SciTech Connect

    Goeddel, D.V. )

    1990-01-01

    The articles in this volume were assemble to enable the reader to design effective strategies for the expression of cloned genes and cDNAs. More than a compilation of papers describing the multitude of techniques now available for expressing cloned genes, this volume provides a manual that should prove useful for solving the majority of expression problems one likely to encounter. The four major expression systems commonly available to most investigators are stressed: Escherichia coli, Bacillus subtilis, yeast, and mammalian cells. Each of these system has its advantages and disadvantages, details of which are found in Chapter 1 and the strategic overviews for the four major sections of the volume. The papers in each of these sections provide many suggestions on how to proceed if initial expression levels are not sufficient.

  19. Brains, Genes and Primates

    PubMed Central

    Belmonte, Juan Carlos Izpisua; Callaway, Edward M.; Churchland, Patricia; Caddick, Sarah J.; Feng, Guoping; Homanics, Gregg E.; Lee, Kuo-Fen; Leopold, David A.; Miller, Cory T.; Mitchell, Jude F.; Mitalipov, Shoukhrat; Moutri, Alysson R.; Movshon, J. Anthony; Okano, Hideyuki; Reynolds, John H.; Ringach, Dario; Sejnowski, Terrence J.; Silva, Afonso C.; Strick, Peter L.; Wu, Jun; Zhang, Feng

    2015-01-01

    One of the great strengths of the mouse model is the wide array of genetic tools that have been developed. Striking examples include methods for directed modification of the genome, and for regulated expression or inactivation of genes. Within neuroscience, it is now routine to express reporter genes, neuronal activity indicators and opsins in specific neuronal types in the mouse. However, there are considerable anatomical, physiological, cognitive and behavioral differences between the mouse and the human that, in some areas of inquiry, limit the degree to which insights derived from the mouse can be applied to understanding human neurobiology. Several recent advances have now brought into reach the goal of applying these tools to understanding the primate brain. Here we describe these advances, consider their potential to advance our understanding of the human brain and brain disorders, discuss bioethical considerations, and describe what will be needed to move forward. PMID:25950631

  20. Agrobacterium virulence gene induction.

    PubMed

    Gelvin, Stanton B

    2006-01-01

    The ability of Agrobacterium to transform plants and other organisms is under highly regulated genetic control. Two Virulence (Vir) proteins, VirA and VirG, function as a two-component regulatory system to sense particular phenolic compounds synthesized by wounded plant tissues. Induction by these phenolic compounds, in the presence of certain neutral or acid sugars, results in activation of other vir genes, leading to the processing of T-DNA from the Ti-plasmid and transfer of T-DNA to recipient host cells. Many plant, and most nonplant, species do not provide sufficient quantities of the correct phenolic compounds to permit efficient Agrobacterium-mediated genetic transformation to occur. In order to transform these species, phenolic inducing compounds must be added to agrobacteria before and/or during cocultivation of recipient cells with the bacteria. This chapter discusses conditions for efficient induction of Agrobacterium virulence genes by phenolic compounds. PMID:16988335

  1. Graphene based gene transfection

    NASA Astrophysics Data System (ADS)

    Feng, Liangzhu; Zhang, Shuai; Liu, Zhuang

    2011-03-01

    Graphene as a star in materials research has been attracting tremendous attentions in the past few years in various fields including biomedicine. In this work, for the first time we successfully use graphene as a non-toxic nano-vehicle for efficient gene transfection. Graphene oxide (GO) is bound with cationic polymers, polyethyleneimine (PEI) with two different molecular weights at 1.2 kDa and 10 kDa, forming GO-PEI-1.2k and GO-PEG-10k complexes, respectively, both of which are stable in physiological solutions. Cellular toxicity tests reveal that our GO-PEI-10k complex exhibits significantly reduced toxicity to the treated cells compared to the bare PEI-10k polymer. The positively charged GO-PEI complexes are able to further bind with plasmid DNA (pDNA) for intracellular transfection of the enhanced green fluorescence protein (EGFP) gene in HeLa cells. While EGFP transfection with PEI-1.2k appears to be ineffective, high EGFP expression is observed using the corresponding GO-PEI-1.2k as the transfection agent. On the other hand, GO-PEI-10k shows similar EGFP transfection efficiency but lower toxicity compared with PEI-10k. Our results suggest graphene to be a novel gene delivery nano-vector with low cytotoxicity and high transfection efficiency, promising for future applications in non-viral based gene therapy.Graphene as a star in materials research has been attracting tremendous attentions in the past few years in various fields including biomedicine. In this work, for the first time we successfully use graphene as a non-toxic nano-vehicle for efficient gene transfection. Graphene oxide (GO) is bound with cationic polymers, polyethyleneimine (PEI) with two different molecular weights at 1.2 kDa and 10 kDa, forming GO-PEI-1.2k and GO-PEG-10k complexes, respectively, both of which are stable in physiological solutions. Cellular toxicity tests reveal that our GO-PEI-10k complex exhibits significantly reduced toxicity to the treated cells compared to the bare PEI

  2. ToppGene Suite for gene list enrichment analysis and candidate gene prioritization

    PubMed Central

    Chen, Jing; Bardes, Eric E.; Aronow, Bruce J.; Jegga, Anil G.

    2009-01-01

    ToppGene Suite (http://toppgene.cchmc.org; this web site is free and open to all users and does not require a login to access) is a one-stop portal for (i) gene list functional enrichment, (ii) candidate gene prioritization using either functional annotations or network analysis and (iii) identification and prioritization of novel disease candidate genes in the interactome. Functional annotation-based disease candidate gene prioritization uses a fuzzy-based similarity measure to compute the similarity between any two genes based on semantic annotations. The similarity scores from individual features are combined into an overall score using statistical meta-analysis. A P-value of each annotation of a test gene is derived by random sampling of the whole genome. The protein–protein interaction network (PPIN)-based disease candidate gene prioritization uses social and Web networks analysis algorithms (extended versions of the PageRank and HITS algorithms, and the K-Step Markov method). We demonstrate the utility of ToppGene Suite using 20 recently reported GWAS-based gene–disease associations (including novel disease genes) representing five diseases. ToppGene ranked 19 of 20 (95%) candidate genes within the top 20%, while ToppNet ranked 12 of 16 (75%) candidate genes among the top 20%. PMID:19465376

  3. Research on a Denial of Service (DoS) Detection System Based on Global Interdependent Behaviors in a Sensor Network Environment

    PubMed Central

    Song, Jae-gu; Jung, Sungmo; Kim, Jong Hyun; Seo, Dong Il; Kim, Seoksoo

    2010-01-01

    This research suggests a Denial of Service (DoS) detection method based on the collection of interdependent behavior data in a sensor network environment. In order to collect the interdependent behavior data, we use a base station to analyze traffic and behaviors among nodes and introduce methods of detecting changes in the environment with precursor symptoms. The study presents a DoS Detection System based on Global Interdependent Behaviors and shows the result of detecting a sensor carrying out DoS attacks through the test-bed. PMID:22163475

  4. Análise dos Conceitos Astronômicos Apresentados por Professores de Algumas Escolas Estaduais Brasileiras

    NASA Astrophysics Data System (ADS)

    Voelzke, Marcos Rincon; Gonzaga, Edson Pereira

    2011-12-01

    A razão para o desenvolvimento deste trabalho baseia-se no fato de que muitos professores da Educação Básica (EB) não lidam com conceitos relacionados à astronomia, e quando o fazem eles simplesmente seguem livros didáticos que podem conter erros conceituais. Como é de conhecimento geral a astronomia é um dos conteúdos a serem ensinados na EB fazendo parte dos Parâmetros Curriculares Nacionais e das Propostas Curriculares do Estado de São Paulo, mas é um fato, que vários pesquisadores apontam, a existência de muitos problemas no ensino da astronomia. Com o propósito de minimizar algumas dessas deficiências foi realizado um trabalho de pesquisa com a utilização de questionários pré e pós pesquisa, para tanto foi desenvolvido um Curso de Extensão Universitária para professores da Diretoria de Ensino Regional (DE) que abrange Mauá, Ribeirão Pires e Rio Grande da Serra (no Estado de São Paulo) com os seguintes objetivos: levantar concepções alternativas; subsidiar os professores por meio de palestras, debates e workshops, e verificar o sucesso da aprendizagem após o curso, adotando-se como referência, para a análise dos resultados, os dicionários de Língua Portuguesa (FERREIRA, 2004) e Enciclopédico de Astronomia e Astronáutica (MOURĀO, 1995). Portanto, dezesseis questões foram aplicadas antes e após o curso, assim pode-se verificar após a pesquisa que 100,0% dos professores sabiam os nomes das fases da Lua, 97,0% entenderam que o Sistema Solar é composto por oito planetas, 78,1% foram capazes de explicar como ocorre um eclipse lunar, um eclipse solar e um solstício, 72,7% sabiam como explicar a ocorrência das estações do ano; 64,5% explicaram corretamente a ocorrência do equinócio, 89,7% foram capazes de definir adequadamente o termo cometa; 63,6% definiram asteróide, 54,5% meteoro, 58,1% galáxia, e 42,4% planeta. Os resultados obtidos indicam uma aprendizagem significativa por parte dos participantes.

  5. Independent Gene Discovery and Testing

    ERIC Educational Resources Information Center

    Palsule, Vrushalee; Coric, Dijana; Delancy, Russell; Dunham, Heather; Melancon, Caleb; Thompson, Dennis; Toms, Jamie; White, Ashley; Shultz, Jeffry

    2010-01-01

    A clear understanding of basic gene structure is critical when teaching molecular genetics, the central dogma and the biological sciences. We sought to create a gene-based teaching project to improve students' understanding of gene structure and to integrate this into a research project that can be implemented by instructors at the secondary level…

  6. nanosheets for gene therapy

    NASA Astrophysics Data System (ADS)

    Kou, Zhongyang; Wang, Xin; Yuan, Renshun; Chen, Huabin; Zhi, Qiaoming; Gao, Ling; Wang, Bin; Guo, Zhaoji; Xue, Xiaofeng; Cao, Wei; Guo, Liang

    2014-10-01

    A new class of two-dimensional (2D) nanomaterial, transition metal dichalcogenides (TMDCs) such as MoS2, MoSe2, WS2, and WSe2 which have fantastic physical and chemical properties, has drawn tremendous attention in different fields recently. Herein, we for the first time take advantage of the great potential of MoS2 with well-engineered surface as a novel type of 2D nanocarriers for gene delivery and therapy of cancer. In our system, positively charged MoS2-PEG-PEI is synthesized with lipoic acid-modified polyethylene glycol (LA-PEG) and branched polyethylenimine (PEI). The amino end of positively charged nanomaterials can bind to the negatively charged small interfering RNA (siRNA). After detection of physical and chemical characteristics of the nanomaterial, cell toxicity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Polo-like kinase 1 (PLK1) was investigated as a well-known oncogene, which was a critical regulator of cell cycle transmission at multiple levels. Through knockdown of PLK1 with siRNA carried by novel nanovector, qPCR and Western blot were used to measure the interfering efficiency; apoptosis assay was used to detect the transfection effect of PLK1. All results showed that the novel nanocarrier revealed good biocompatibility, reduced cytotoxicity, as well as high gene-carrying ability without serum interference, thus would have great potential for gene delivery and therapy.

  7. Meta-analysis of the association between common interleukin-1 polymorphisms and dental implant failure.

    PubMed

    Liao, Jian; Li, Chao; Wang, Yong; Ten, MinHua; Sun, Xu; Tian, Ai; Zhang, Qi; Liang, Xing

    2014-05-01

    Interleukin-1 (IL) plays a pivotal role in immune-inflammatory response that maintains periodontal homeostasis. A number of epidemiological studies have been conducted to investigate the associations between common polymorphisms of IL-1 (IL-1A, IL-1B) genes and risk of peri-implant disease, but the findings remain inconclusive. Thirteen studies evaluating the association between IL-1 polymorphisms and risk for peri-implant diseases (implant failure/loss, peri-implantitis) were included. Fixed model or random-effects models were applied to calculate overall and ethnicity-specific summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) as risk estimates for IL-1 polymorphisms individually or in combination. Heterogeneity and publication bias were evaluated by Q-test, I2 statistic, Begg's funnel plot and Egger's test accordingly. The composite genotype of IL-1A (-889) and IL-1B (+3954) was associated with increased risk of implant failure/loss (OR 1.76, 95% CI 1.21-2.57) and peri-implantitis (OR 2.34, 95% CI 1.03-5.33). The significance was borderline in European descents (implant failure/loss: OR 1.48, 95% CI 0.99-2.22; peri-implantitis: OR 1.65, 95% CI 1.00-2.73). T allele of IL-1B (-511) was associated with increased risk of implant failure/loss (OR 1.28, 95% CI 1.01-1.62), while the association was not significant in European descents (OR 1.12, 95% CI 0.85-1.48). These findings support a potential role of IL-1 polymorphisms, particularly the composite genotype of IL-1A (-889) and IL-1B (+3954), in peri-implant disease susceptibility. More studies with large sample size are needed to validate the associations. PMID:24452718

  8. Pterostilbene as treatment for severe acute pancreatitis.

    PubMed

    Lin, Y J; Ding, Y; Wu, J; Ning, B T

    2016-01-01

    Acute pancreatitis (AP) has a fast onset and progression, which lead to an unfavorable prognosis. Therefore, the development of novel drugs for its treatment is critical. As a homologous derivative of resveratrol, pterostilbene exerts a variety of effects including anti-inflammatory, antioxidant, and antitumor effects. This study investigated the potential of pterostilbene for treatment of severe AP (SAP) and related mechanisms. Effects of pterostilbene were evaluated in a Wistar rat model of AP. Serum levels of amylase (AMY), creatinine (Cr), and alanine aminotransferase (ALT) were quantified. Furthermore, serum levels of tumor necrosis factor (TNF)-a and interleukin (IL)-1b were quantified using enzyme-linked immunosorbent assay. Nuclear factor (NF)-kB expression in pancreatic tissues was quantified by real-time PCR and western blotting. The production of reactive oxygen species (ROS) was determined using a spectrometer, while superoxide dismutase (SOD) activity was assayed. In the AP rat model, the expression of inflammatory markers TNF-a and IL-1b, expression of NF-kB, and serum indices (AMY, Cr, and ALT) increased compared to the corresponding levels in the control group (P < 0.05). Pterostilbene reduced serum levels of TNF-a and IL-1b; decreased NF-kB gene expression, serum indices, and ROS generation; and increased SOD activity in a dose-dependent manner. In conclusion, pterostilbene can alleviate SAP-induced tissue damage by decreasing the inflammatory response and by promoting antioxidation leading to the protection of pancreatic tissues. PMID:27525946

  9. From SNPs to Genes: Disease Association at the Gene Level

    PubMed Central

    Lehne, Benjamin; Lewis, Cathryn M.; Schlitt, Thomas

    2011-01-01

    Interpreting Genome-Wide Association Studies (GWAS) at a gene level is an important step towards understanding the molecular processes that lead to disease. In order to incorporate prior biological knowledge such as pathways and protein interactions in the analysis of GWAS data it is necessary to derive one measure of association for each gene. We compare three different methods to obtain gene-wide test statistics from Single Nucleotide Polymorphism (SNP) based association data: choosing the test statistic from the most significant SNP; the mean test statistics of all SNPs; and the mean of the top quartile of all test statistics. We demonstrate that the gene-wide test statistics can be controlled for the number of SNPs within each gene and show that all three methods perform considerably better than expected by chance at identifying genes with confirmed associations. By applying each method to GWAS data for Crohn's Disease and Type 1 Diabetes we identified new potential disease genes. PMID:21738570

  10. Physical methods for gene transfer.

    PubMed

    Alsaggar, Mohammad; Liu, Dexi

    2015-01-01

    The key impediment to the successful application of gene therapy in clinics is not the paucity of therapeutic genes. It is rather the lack of nontoxic and efficient strategies to transfer therapeutic genes into target cells. Over the past few decades, considerable progress has been made in gene transfer technologies, and thus far, three different delivery systems have been developed with merits and demerits characterizing each system. Viral and chemical methods of gene transfer utilize specialized carrier to overcome membrane barrier and facilitate gene transfer into cells. Physical methods, on the other hand, utilize various forms of mechanical forces to enforce gene entry into cells. Starting in 1980s, physical methods have been introduced as alternatives to viral and chemical methods to overcome various extra- and intracellular barriers that limit the amount of DNA reaching the intended cells. Accumulating evidence suggests that it is quite feasible to directly translocate genes into cytoplasm or even nuclei of target cells by means of mechanical force, bypassing endocytosis, a common pathway for viral and nonviral vectors. Indeed, several methods have been developed, and the majority of them share the same underlying mechanism of gene transfer, i.e., physically created transient pores in cell membrane through which genes get into cells. Here, we provide an overview of the current status and future research directions in the field of physical methods of gene transfer.

  11. Horizontal gene transfer in choanoflagellates.

    PubMed

    Tucker, Richard P

    2013-01-01

    Horizontal gene transfer (HGT), also known as lateral gene transfer, results in the rapid acquisition of genes from another organism. HGT has long been known to be a driving force in speciation in prokaryotes, and there is evidence for HGT from symbiotic and infectious bacteria to metazoans, as well as from protists to bacteria. Recently, it has become clear that as many as a 1,000 genes in the genome of the choanoflagellate Monosiga brevicollis may have been acquired by HGT. Interestingly, these genes reportedly come from algae, bacteria, and other choanoflagellate prey. Some of these genes appear to have allowed an ancestral choanoflagellate to exploit nutrient-poor environments and were not passed on to metazoan descendents. However, some of these genes are also found in animal genomes, suggesting that HGT into a common ancestor of choanozoans and animals may have contributed to metazoan evolution.

  12. RANGE: Gene Transfer of Reversibly Controlled Polycistronic Genes

    PubMed Central

    Chen, Yiwei; Cao, Liji; Luo, Chonglin; Ditzel, Désirée AW; Peter, Jörg; Sprengel, Rolf

    2013-01-01

    We developed a single vector recombinant adeno-associated viral (rAAV) expression system for spatial and reversible control of polycistronic gene expression. Our approach (i) integrates the advantages of the tetracycline (Tet)-controlled transcriptional silencer tTSKid and the self-cleaving 2A peptide bridge, (ii) combines essential regulatory components as an autoregulatory loop, (iii) simplifies the gene delivery scheme, and (iv) regulates multiple genes in a synchronized manner. Controlled by an upstream Tet-responsive element (TRE), both the ubiquitous chicken β-actin promoter (CAG) and the neuron-specific synapsin-1 promoter (Syn) could regulate expression of tTSKid together with two 2A-linked reporter genes. Transduction in vitro exhibited maximally 50-fold regulation by doxycycline (Dox). Determined by gene delivery method as well as promoter, highly specific tissues were transduced in vivo. Bioluminescence imaging (BLI) visualized reversible “ON/OFF” gene switches over repeated “Doxy-Cycling” in living mice. Thus, the reversible rAAV-mediated N-cistronic gene expression system, termed RANGE, may serve as a versatile tool to achieve reversible polycistronic gene regulation for the study of gene function as well as gene therapy. PMID:23571608

  13. Diseases originate and terminate by genes: unraveling nonviral gene delivery.

    PubMed

    Swami, Rajan; Singh, Indu; Khan, Wahid; Ramakrishna, Sistla

    2013-12-01

    The world is driving in to the era of transformation of chemical therapeutic molecules to biological genetic material therapeutics, and that is where the biological drugs especially "genes" come into existence. These genes worked as "magical bullets" to specifically silence faulty genes responsible for progression of diseases. Viral gene delivery research is far ahead of nonviral gene delivery technique. However, with more advancement in polymer science, new ways are opening for better and efficient nonviral gene delivery. But efficient delivery method is always considered as a bottleneck for gene delivery as success of which will decide the fate of gene in cells. During the past decade, it became evident that extracellular as well as intracellular barriers compromise the transfection efficiency of nonviral vectors. The challenge for gene therapy research is to pinpoint the rate-limiting steps in this complex process and implement strategies to overcome the biological physiochemical and metabolic barriers encountered during targeting. The synergy between studies that investigate the mechanism of breaking in and breaking out of nonviral gene delivery carrier through various extracellular and intracellular barriers with desired characteristics will enable the rational design of vehicles and revolutionize the treatment of various diseases.

  14. The Gene Wiki: community intelligence applied to human gene annotation.

    PubMed

    Huss, Jon W; Lindenbaum, Pierre; Martone, Michael; Roberts, Donabel; Pizarro, Angel; Valafar, Faramarz; Hogenesch, John B; Su, Andrew I

    2010-01-01

    Annotating the function of all human genes is a critical, yet formidable, challenge. Current gene annotation efforts focus on centralized curation resources, but it is increasingly clear that this approach does not scale with the rapid growth of the biomedical literature. The Gene Wiki utilizes an alternative and complementary model based on the principle of community intelligence. Directly integrated within the online encyclopedia, Wikipedia, the goal of this effort is to build a gene-specific review article for every gene in the human genome, where each article is collaboratively written, continuously updated and community reviewed. Previously, we described the creation of Gene Wiki 'stubs' for approximately 9000 human genes. Here, we describe ongoing systematic improvements to these articles to increase their utility. Moreover, we retrospectively examine the community usage and improvement of the Gene Wiki, providing evidence of a critical mass of users and editors. Gene Wiki articles are freely accessible within the Wikipedia web site, and additional links and information are available at http://en.wikipedia.org/wiki/Portal:Gene_Wiki.

  15. 32 CFR Appendix C to Part 197 - Procedures for the Department of State (DoS) Foreign Relations of the United States (FRUS) Series

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... the DoS for the FRUS series under Public Law No. 102-138. b. Request authorization from the CIA, NSC.... Submit to the respective Agency a list of CIA and NSC documents copied and released to the...

  16. 32 CFR Appendix C to Part 197 - Procedures for the Department of State (DoS) Foreign Relations of the United States (FRUS) Series

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... the DoS for the FRUS series under Public Law No. 102-138. b. Request authorization from the CIA, NSC.... Submit to the respective Agency a list of CIA and NSC documents copied and released to the...

  17. 32 CFR Appendix C to Part 197 - Procedures for the Department of State (DoS) Foreign Relations of the United States (FRUS) Series

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... the DoS for the FRUS series under Public Law No. 102-138. b. Request authorization from the CIA, NSC.... Submit to the respective Agency a list of CIA and NSC documents copied and released to the...

  18. Five New Genes Linked to Colon Cancer

    MedlinePlus

    ... More Health News on: Colorectal Cancer Genes and Gene Therapy Recent Health News Related MedlinePlus Health Topics Colorectal Cancer Genes and Gene Therapy About MedlinePlus Site Map FAQs Contact Us Get ...

  19. Breast cancer susceptibility genes.

    PubMed

    Lubinski, Jan; Korzen, Marcin; Gorski, Bohdan; Cybulski, Cezary; Debniak, Tadeusz; Jakubowska, Anna; Medrek, Krzysztof; Matyjasik, Joanna; Huzarski, Tomasz; Byrski, Tomasz; Gronwald, Jacek; Masojc, Bartlomiej; Lener, Marcin; Szymanska, Anna; Szymanska-Pasternak, Jolanta; Fernandez, Pablo Serrano; Wokolorczyk, Dominika; Piegat, Andrzej; Ucinski, Michal; Domagala, Pawel; Kladny, Jozef; Gorecka, Barbara; Scott, Rodney; Narod, Steven

    2007-09-01

    In 1999 it has been recognized that 3 BRCA1 abnormalities - 5382insC, C61G and 4153delA - constitute almost 90% of all germline mutations of this gene in Poland. Due to the above findings we started performing the cheap and quick large scale testing for BRCA1 mutations and, these days, we have almost 4,000 carriers diagnosed and under direct or indirect supervision what is probably the largest number in the world. Additionally, the above results pushed us to hypothesize that genetic homogeneity will be seen in Poland in studies of other genes. Actually, the next studies allowed us to identify genes / changes associated with moderate / low breast cancer risk and showed, similarly to BRCA1, high level of genetic homogeneity. This series included BRCA2, C5972T, CHEK2 del5395; 1100delC, I157T or IVS2 + 1G > A, CDKN2A (p16) A148T, XPD Asp312Asn and Lys751Gln, CYP1B1 R48G, A119S and L43V. The results of the above studies led us in 2004 already to hypothesize that >90% of all cancers have genetic (constitutional) background. Two years later we were able to show a panel of markers covering 92% of consecutive breast cancers in Poland, and we formulated the hypothesis that all cancers have a genetic background. These days we are demonstrating for the first time that genetic components to malignancy play a role in all cancers. We are presenting it on examples of late-onset breast cancers from Poland, but it seems to be justified to expect that similar results can be achieved from other malignancies. PMID:17935274

  20. Gene transfer: transduction.

    PubMed

    Frangipani, Emanuela

    2014-01-01

    Bacteriophages able to propagate on Pseudomonas strains are very common and can be easily isolated from natural environments or lysogenic strains. The development of transducing systems has allowed bacterial geneticists to perform chromosome analyses and mutation mapping. Moreover, these systems have also been proved to be a successful tool for molecular microbiologists to introduce a foreign gene or a mutation into the chromosome of a bacterial cell. This chapter provides a description of the phage methodology illustrated by Adams in 1959 and applicable to strain PAO1 derivatives. PMID:24818891

  1. MYCN Gene Amplification

    PubMed Central

    Yoshimoto, Maisa; Caminada de Toledo, Silvia Regina; Monteiro Caran, Eliana Maria; de Seixas, Maria Teresa; de Martino Lee, Maria Lucia; de Campos Vieira Abib, Simone; Vianna, Sonia Maria Rossi; Schettini, Sergio Thomaz; Anderson Duffles Andrade, Joyce

    1999-01-01

    Neuroblastoma is the second most common solid tumor occurring in children. Amplification of the MYCN oncogene is associated with poor prognosis. To identify neuroblastoma tumors with MYCN amplification, we studied the number of copies of MYCN in interphase cells by fluorescence in situ hybridization in 20 neuroblastoma patients. MYCN amplification appeared in 7 tumor specimens. Interphase and metaphase studies showed a tumor cell population with both forms of amplification, double minutes and homogeneously staining regions, in two patients. These patients showed a smaller tumor cell subpopulation with the presence of more than one homogeneously staining region, suggesting that gene amplification was undergoing karyotype evolution. PMID:10550298

  2. Computation in gene networks

    NASA Astrophysics Data System (ADS)

    Ben-Hur, Asa; Siegelmann, Hava T.

    2004-03-01

    Genetic regulatory networks have the complex task of controlling all aspects of life. Using a model of gene expression by piecewise linear differential equations we show that this process can be considered as a process of computation. This is demonstrated by showing that this model can simulate memory bounded Turing machines. The simulation is robust with respect to perturbations of the system, an important property for both analog computers and biological systems. Robustness is achieved using a condition that ensures that the model equations, that are generally chaotic, follow a predictable dynamics.

  3. Human AZU-1 gene, variants thereof and expressed gene products

    DOEpatents

    Chen, Huei-Mei; Bissell, Mina

    2004-06-22

    A human AZU-1 gene, mutants, variants and fragments thereof. Protein products encoded by the AZU-1 gene and homologs encoded by the variants of AZU-1 gene acting as tumor suppressors or markers of malignancy progression and tumorigenicity reversion. Identification, isolation and characterization of AZU-1 and AZU-2 genes localized to a tumor suppressive locus at chromosome 10q26, highly expressed in nonmalignant and premalignant cells derived from a human breast tumor progression model. A recombinant full length protein sequences encoded by the AZU-1 gene and nucleotide sequences of AZU-1 and AZU-2 genes and variant and fragments thereof. Monoclonal or polyclonal antibodies specific to AZU-1, AZU-2 encoded protein and to AZU-1, or AZU-2 encoded protein homologs.

  4. Mycobacterium tuberculosis Response Regulators, DevR and NarL, Interact in Vivo and Co-regulate Gene Expression during Aerobic Nitrate Metabolism*

    PubMed Central

    Malhotra, Vandana; Agrawal, Ruchi; Duncan, Tammi R.; Saini, Deepak. K.; Clark-Curtiss, Josephine E.

    2015-01-01

    Mycobacterium tuberculosis genes Rv0844c/Rv0845 encoding the NarL response regulator and NarS histidine kinase are hypothesized to constitute a two-component system involved in the regulation of nitrate metabolism. However, there is no experimental evidence to support this. In this study, we established M. tuberculosis NarL/NarS as a functional two-component system and identified His241 and Asp61 as conserved phosphorylation sites in NarS and NarL, respectively. Transcriptional profiling between M. tuberculosis H37Rv and a ΔnarL mutant strain during exponential growth in broth cultures with or without nitrate defined an ∼30-gene NarL regulon that exhibited significant overlap with DevR-regulated genes, thereby implicating a role for the DevR response regulator in the regulation of nitrate metabolism. Notably, expression analysis of a subset of genes common to NarL and DevR regulons in M. tuberculosis ΔdevR, ΔdevSΔdosT, and ΔnarL mutant strains revealed that in response to nitrite produced during aerobic nitrate metabolism, the DevRS/DosT regulatory system plays a primary role that is augmented by NarL. Specifically, NarL itself was unable to bind to the narK2, acg, and Rv3130c promoters in phosphorylated or unphosphorylated form; however, its interaction with DevR∼P resulted in cooperative binding, thereby enabling co-regulation of these genes. These findings support the role of physiologically derived nitrite as a metabolic signal in mycobacteria. We propose NarL-DevR binding, possibly as a heterodimer, as a novel mechanism for co-regulation of gene expression by the DevRS/DosT and NarL/NarS regulatory systems. PMID:25659431

  5. Imprinting genes associated with endometriosis

    PubMed Central

    Kobayashi, Hiroshi

    2014-01-01

    Purpose: Much work has been carried out to investigate the genetic and epigenetic basis of endometriosis and proposed that endometriosis has been described as an epigenetic disease. The purpose of this study was to extract the imprinting genes that are associated with endometriosis development. Methods: The information on the imprinting genes can be accessed publicly from a web-based interface at http://www.geneimprint.com/site/genes-by-species. Results: In the current version, the database contains 150 human imprinted genes derived from the literature. We searched gene functions and their roles in particular biological processes or events, such as development and pathogenesis of endometriosis. From the genomic imprinting database, we picked 10 genes that were highly associated with female reproduction; prominent among them were paternally expressed genes (DIRAS3, BMP8B, CYP1B1, ZFAT, IGF2, MIMT1, or MIR296) and maternally expressed genes (DVL1, FGFRL1, or CDKN1C). These imprinted genes may be associated with reproductive biology such as endometriosis, pregnancy loss, decidualization process and preeclampsia. Discussion: This study supports the possibility that aberrant epigenetic dysregulation of specific imprinting genes may contribute to endometriosis predisposition. PMID:26417259

  6. Vectors for cancer gene therapy.

    PubMed

    Zhang, J; Russell, S J

    1996-09-01

    Many viral and non-viral vector systems have now been developed for gene therapy applications. In this article, the pros and cons of these vector systems are discussed in relation to the different cancer gene therapy strategies. The protocols used in cancer gene therapy can be broadly divided into six categories including gene transfer to explanted cells for use as cell-based cancer vaccines; gene transfer to a small number of tumour cells in situ to achieve a vaccine effect; gene transfer to vascular endothelial cells (VECs) lining the blood vessels of the tumour to interfere with tumour angiogenesis; gene transfer to T lymphocytes to enhance their antitumour effector capability; gene transfer to haemopoietic stem cells (HSCs) to enhance their resistance to cytotoxic drugs and gene transfer to a large number of tumour cells in situ to achieve nonimmune tumour reduction with or without bystander effect. Each of the six strategies makes unique demands on the vector system and these are discussed with reference to currently available vectors. Aspects of vector biology that are in need of further development are discussed in some detail. The final section points to the potential use of replicating viruses as delivery vehicles for efficient in vivo gene transfer to disseminated cancers.

  7. The Zebrafish Annexin Gene Family

    PubMed Central

    Farber, Steven A.; De Rose, Robert A.; Olson, Eric S.; Halpern, Marnie E.

    2003-01-01

    The Annexins (ANXs) are a family of calcium- and phospholipid-binding proteins that have been implicated in many cellular processes, including channel formation, membrane fusion, vesicle transport, and regulation of phospholipase A2 activity. As a first step toward understanding in vivo function, we have cloned 11 zebrafish anx genes. Four genes (anx1a, anx2a, anx5,and anx11a) were identified by screening a zebrafish cDNA library with a Xenopus anx2 fragment. For these genes, full-length cDNA sequences were used to cluster 212 EST sequences generated by the Zebrafish Genome Resources Project. The EST analysis revealed seven additional anx genes that were subsequently cloned. The genetic map positions of all 11 genes were determined by using a zebrafish radiation hybrid panel. Sequence and syntenic relationships between zebrafish and human genes indicate that the 11 genes represent orthologs of human anx1,2,4,5,6,11,13,and suggest that several zebrafish anx genes resulted from duplications that arose after divergence of the zebrafish and mammalian genomes. Zebrafish anx genes are expressed in a wide range of tissues during embryonic and larval stages. Analysis of the expression patterns of duplicated genes revealed both redundancy and divergence, with the most similar genes having almost identical tissue-specific patterns of expression and with less similar duplicates showing no overlap. The differences in gene expression of recently duplicated anx genes could explain why highly related paralogs were maintained in the genome and did not rapidly become pseudogenes. PMID:12799347

  8. Learning About Gene Regulatory Networks From Gene Deletion Experiments

    PubMed Central

    Brazma, Alvis

    2002-01-01

    Gene regulatory networks are a major focus of interest in molecular biology. A crucial question is how complex regulatory systems are encoded and controlled by the genome. Three recent publications have raised the question of what can be learned about gene regulatory networks from microarray experiments on gene deletion mutants. Using this indirect approach, topological features such as connectivity and modularity have been studied. PMID:18629255

  9. Ancient origins of axial patterning genes: Hox genes and ParaHox genes in the Cnidaria.

    PubMed

    Finnerty, J R; Martindale, M Q

    1999-01-01

    Among the bilaterally symmetrical, triploblastic animals (the Bilateria), a conserved set of developmental regulatory genes are known to function in patterning the anterior-posterior (AP) axis. This set includes the well-studied Hox cluster genes, and the recently described genes of the ParaHox cluster, which is believed to be the evolutionary sister of the Hox cluster (Brooke et al. 1998). The conserved role of these axial patterning genes in animals as diverse as frogs and flies is believed to reflect an underlying homology (i.e., all bilaterians derive from a common ancestor which possessed an AP axis and the developmental mechanisms responsible for patterning the axis). However, the origin and early evolution of Hox genes and ParaHox genes remain obscure. Repeated attempts have been made to reconstruct the early evolution of Hox genes by analyzing data from the triphoblastic animals, the Bilateria (Schubert et al. 1993; Zhang and Nei 1996). A more precise dating of Hox origins has been elusive due to a lack of sufficient information from outgroup taxa such as the phylum Cnidaria (corals, hydras, jellyfishes, and sea anemones). In combination with outgroup taxa, another potential source of information about Hox origins is outgroup genes (e.g., the genes of the ParaHox cluster). In this article, we present cDNA sequences of two Hox-like genes (anthox2 and anthox6) from the sea anemone, Nematostella vectensis. Phylogenetic analysis indicates that anthox2 (= Cnox2) is homologous to the GSX class of ParaHox genes, and anthox6 is homologous to the anterior class of Hox genes. Therefore, the origin of Hox genes and ParaHox genes occurred prior to the evolutionary split between the Cnidaria and the Bilateria and predated the evolution of the anterior-posterior axis of bilaterian animals. Our analysis also suggests that the central Hox class was invented in the bilaterian lineage, subsequent to their split from the Cnidaria.

  10. Identifying driver genes in cancer by triangulating gene expression, gene location, and survival data.

    PubMed

    Rouam, Sigrid; Miller, Lance D; Karuturi, R Krishna Murthy

    2014-01-01

    Driver genes are directly responsible for oncogenesis and identifying them is essential in order to fully understand the mechanisms of cancer. However, it is difficult to delineate them from the larger pool of genes that are deregulated in cancer (ie, passenger genes). In order to address this problem, we developed an approach called TRIAngulating Gene Expression (TRIAGE through clinico-genomic intersects). Here, we present a refinement of this approach incorporating a new scoring methodology to identify putative driver genes that are deregulated in cancer. TRIAGE triangulates - or integrates - three levels of information: gene expression, gene location, and patient survival. First, TRIAGE identifies regions of deregulated expression (ie, expression footprints) by deriving a newly established measure called the Local Singular Value Decomposition (LSVD) score for each locus. Driver genes are then distinguished from passenger genes using dual survival analyses. Incorporating measurements of gene expression and weighting them according to the LSVD weight of each tumor, these analyses are performed using the genes located in significant expression footprints. Here, we first use simulated data to characterize the newly established LSVD score. We then present the results of our application of this refined version of TRIAGE to gene expression data from five cancer types. This refined version of TRIAGE not only allowed us to identify known prominent driver genes, such as MMP1, IL8, and COL1A2, but it also led us to identify several novel ones. These results illustrate that TRIAGE complements existing tools, allows for the identification of genes that drive cancer and could perhaps elucidate potential future targets of novel anticancer therapeutics.

  11. Ancient origins of axial patterning genes: Hox genes and ParaHox genes in the Cnidaria.

    PubMed

    Finnerty, J R; Martindale, M Q

    1999-01-01

    Among the bilaterally symmetrical, triploblastic animals (the Bilateria), a conserved set of developmental regulatory genes are known to function in patterning the anterior-posterior (AP) axis. This set includes the well-studied Hox cluster genes, and the recently described genes of the ParaHox cluster, which is believed to be the evolutionary sister of the Hox cluster (Brooke et al. 1998). The conserved role of these axial patterning genes in animals as diverse as frogs and flies is believed to reflect an underlying homology (i.e., all bilaterians derive from a common ancestor which possessed an AP axis and the developmental mechanisms responsible for patterning the axis). However, the origin and early evolution of Hox genes and ParaHox genes remain obscure. Repeated attempts have been made to reconstruct the early evolution of Hox genes by analyzing data from the triphoblastic animals, the Bilateria (Schubert et al. 1993; Zhang and Nei 1996). A more precise dating of Hox origins has been elusive due to a lack of sufficient information from outgroup taxa such as the phylum Cnidaria (corals, hydras, jellyfishes, and sea anemones). In combination with outgroup taxa, another potential source of information about Hox origins is outgroup genes (e.g., the genes of the ParaHox cluster). In this article, we present cDNA sequences of two Hox-like genes (anthox2 and anthox6) from the sea anemone, Nematostella vectensis. Phylogenetic analysis indicates that anthox2 (= Cnox2) is homologous to the GSX class of ParaHox genes, and anthox6 is homologous to the anterior class of Hox genes. Therefore, the origin of Hox genes and ParaHox genes occurred prior to the evolutionary split between the Cnidaria and the Bilateria and predated the evolution of the anterior-posterior axis of bilaterian animals. Our analysis also suggests that the central Hox class was invented in the bilaterian lineage, subsequent to their split from the Cnidaria. PMID:11324016

  12. Genes and causation.

    PubMed

    Noble, Denis

    2008-09-13

    Relating genotypes to phenotypes is problematic not only owing to the extreme complexity of the interactions between genes, proteins and high-level physiological functions but also because the paradigms for genetic causality in biological systems are seriously confused. This paper examines some of the misconceptions, starting with the changing definitions of a gene, from the cause of phenotype characters to the stretches of DNA. I then assess whether the 'digital' nature of DNA sequences guarantees primacy in causation compared to non-DNA inheritance, whether it is meaningful or useful to refer to genetic programs, and the role of high-level (downward) causation. The metaphors that served us well during the molecular biological phase of recent decades have limited or even misleading impacts in the multilevel world of systems biology. New paradigms are needed if we are to succeed in unravelling multifactorial genetic causation at higher levels of physiological function and so to explain the phenomena that genetics was originally about. Because it can solve the 'genetic differential effect problem', modelling of biological function has an essential role to play in unravelling genetic causation.

  13. Gene set enrichment analysis.

    PubMed

    Tilford, Charles A; Siemers, Nathan O

    2009-01-01

    Set enrichment analytical methods have become commonplace tools applied to the analysis and interpretation of biological data. The statistical techniques are used to identify categorical biases within lists of genes, proteins, or metabolites. The goal is to discover the shared functions or properties of the biological items represented within the lists. Application of these methods can provide great biological insight, including the discovery of participation in the same biological activity or pathway, shared interacting genes or regulators, common cellular compartmentalization, or association with disease. The methods require ordered or unordered lists of biological items as input, understanding of the reference set from which the lists were selected, categorical classifiers describing the items, and a statistical algorithm to assess bias of each classifier. Due to the complexity of most algorithms and the number of calculations performed, computer software is almost always used for execution of the algorithm, as well as for presentation of the results. This chapter will provide an overview of the statistical methods used to perform an enrichment analysis. Guidelines for assembly of the requisite information will be presented, with a focus on careful definition of the sets used by the statistical algorithms. The need for multiple test correction when working with large libraries of classifiers is emphasized, and we outline several options for performing the corrections. Finally, interpreting the results of such analysis will be discussed along with examples of recent research utilizing the techniques.

  14. Tetraspanin genes in plants.

    PubMed

    Wang, Feng; Vandepoele, Klaas; Van Lijsebettens, Mieke

    2012-07-01

    Tetraspanins represent a four-transmembrane protein superfamily with a conserved structure and amino acid residues that are present in mammals, insects, fungi and plants. Tetraspanins interact with each other or with other membrane proteins to form tetraspanin-enriched microdomains that play important roles in development, pathogenesis and immune responses via facilitating cell-cell adhesion and fusion, ligand binding and intracellular trafficking. Here, we emphasize evolutionary aspects within the plant kingdom based on genomic sequence information. A phylogenetic tree based on 155 tetraspanin genes of 11 plant species revealed ancient and fast evolving clades. Tetraspanins were only present in multicellular plants, were often duplicated in the plant genomes and predicted by the electronic Fluorescent Pictograph for gene expression analysis to be either functionally redundant or divergent. Tetraspanins contain a large extracellular loop with conserved cysteines that provide the binding sites for the interactions. The Arabidopsis thaliana TETRASPANIN1/TORNADO2/EKEKO has a function in leaf and root patterning and TETRASPANIN3 was identified in the plasmodesmatal proteome, suggesting a role in cell-cell communication during plant development.

  15. Genes of aging.

    PubMed

    Hamet, Pavel; Tremblay, Johanne

    2003-10-01

    According to developmental genetics theories, aging is a genetically programmed and controlled continuum of development and maturation. Being dynamic and malleable processes, development and aging are controlled not only by genes but also by environmental and epigenetic influences that predominate in the second half of life. Genetic mutations affect many phenotypes in flies, worms, rodents, and humans which share several diseases or their equivalents, including cancer, neurodegeneration, and infectious disorders as well as their susceptibility to them. Life span and stress resistance are closely linked. Oxidative stress actually constitutes a defined hypothesis of aging in that macromolecule oxidative damage accumulates with age and tends to be associated with life expectancy. DNA methylation, a force in the regulation of gene expression, is also one of the biomarkers of genetic damage. The mitotic clock of aging is marked, if not guided, by telomeres, essential genetic elements stabilizing natural chromosomic ends. The dream of humans to live longer, healthy lives is being tested by attempts to modify longevity in animal models, frequently by dietary manipulation. The quest continues to understand the mechanisms of healthy aging, one of the most compelling areas of research in the 21st century. PMID:14577056

  16. Rare earth elements in Angra dos Reis and Lewis Cliff 86010, two meteorites with similar but distinct magma evolutions

    NASA Technical Reports Server (NTRS)

    Crozaz, Ghislaine; Mckay, Gordon

    1990-01-01

    Data are presented on ion microprobe measurements of REE and selected trace element abundances in individual grains of merrillite, fassaite, olivine, kirschsteinite, and plagioclase of Lewis Cliff 86010 (LEW 86010) meteorite and in merrillite and fassaite grains of Angra dos Reis (ADOR). Results show a close relationship between the two meteorites and support a magmatic origin for LEW 86010. However, the measurements indicate that, despite numerous common characteristics, the two meteorites must have been produced in separate magmatic events involving similar but distinct processes and parent melts.

  17. Adenoviral vector-mediated gene transfer for human gene therapy.

    PubMed

    Breyer, B; Jiang, W; Cheng, H; Zhou, L; Paul, R; Feng, T; He, T C

    2001-07-01

    Human gene therapy promises to change the practice of medicine by treating the causes of disease rather than the symptoms. Since the first clinical trial made its debut ten years ago, there are over 400 approved protocols in the United States alone, most of which have failed to show convincing data of clinical efficacy. This setback is largely due to the lack of efficient and adequate gene transfer vehicles. With the recent progress in elucidating the molecular mechanisms of human diseases and the imminent arrival of the post genomic era, there are increasing numbers of therapeutic genes or targets that are available for gene therapy. Therefore, the urgency and need for efficacious gene therapies are greater than ever. Clearly, the current fundamental obstacle is to develop delivery vectors that exhibit high efficacy and specificity of gene transfer. Recombinant adenoviruses have provided a versatile system for gene expression studies and therapeutic applications. Of late, there has been a remarkable increase in adenoviral vector-based clinical trials. Recent endeavors in the development of recombinant adenoviral vectors have focused on modification of virus tropism, accommodation of larger genes, increase in stability and control of transgene expression, and down-modulation of host immune responses. These modifications and continued improvements in adenoviral vectors will provide a great opportunity for human gene therapy to live up to its enormous potential in the second decade.

  18. Bacteriophage phiX174: gene A overlaps gene B.

    PubMed Central

    Weisbeek, P J; Borrias, W E; Langeveld, S A; Baas, P D; Van Arkel, G A

    1977-01-01

    The map position of several phiX174 mutations in the genes A and B was determined by marker rescue with DNA fragments produced by the restriction enzymes Hha I, HindII, Hae III, and Alu I. All the gene B mutants were found to be located within gene A. Genetic complementation and analysis of phage-specific protein synthesis show that, under restrictive conditions, nonsense mutants in gene A do not block the synthesis and activity of the B protein and nonsense mutants in gene B do not affect the gene A function. The map position of the COOH-terminal end of gene A was determined using an amber mutant that synthesizes slightly shortened A and A proteins. It is concluded from these experiments that gene A overlaps gene B completely (or almost completely) and that the overlap region can be translated in two ways with different reading frames: one frame for the synthesis of the A and A proteins and another for the synthesis of the B protein. Images PMID:267943

  19. Gene-targeting pharmaceuticals for single-gene disorders.

    PubMed

    Beaudet, Arthur L; Meng, Linyan

    2016-04-15

    The concept of orphan drugs for treatment of orphan genetic diseases is perceived enthusiastically at present, and this is leading to research investment on the part of governments, disease-specific foundations and industry. This review attempts to survey the potential to use traditional pharmaceuticals as opposed to biopharmaceuticals to treat single-gene disorders. The available strategies include the use of antisense oligonucleotides (ASOs) to alter splicing or knock-down expression of a transcript, siRNAs to knock-down gene expression and drugs for nonsense mutation read-through. There is an approved drug for biallelic knock-down of the APOB gene as treatment for familial hypercholesterolemia. Both ASOs and siRNAs are being explored to knock-down the transthyretin gene to prevent the related form of amyloidosis. The use of ASOs to alter gene-splicing to treat spinal muscular atrophy is in phase 3 clinical trials. Work is progressing on the use of ASOs to activate the normally silent paternal copy of the imprinted UBE3A gene in neurons as a treatment for Angelman syndrome. A gene-activation or gene-specific ramp-up strategy would be generally helpful if such could be developed. There is exciting theoretical potential for converting biopharmaceutical strategies such gene correction and CRISPR-Cas9 editing to a synthetic pharmaceutical approach. PMID:26628634

  20. Sexually antagonistic genes: experimental evidence.

    PubMed

    Rice, W R

    1992-06-01

    When selection differs between the sexes, a mutation beneficial to one sex may be harmful to the other (sexually antagonistic). Because the sexes share a common gene pool, selection in one sex can interfere with the other's adaptive evolution. Theory predicts that sexually antagonistic mutations should accumulate in tight linkage with a new sex-determining gene, even when the harm to benefit ratio is high. Genetic markers and artificial selection were used to make a pair of autosomal genes segregate like a new pair of sex-determining genes in a Drosophila melanogaster model system. A 29-generation study provides experimental evidence that sexually antagonistic genes may be common in nature and will accumulate in response to a new sex-determining gene. PMID:1604317

  1. Gene Therapy for Cartilage Repair

    PubMed Central

    Madry, Henning; Orth, Patrick; Cucchiarini, Magali

    2011-01-01

    The concept of using gene transfer strategies for cartilage repair originates from the idea of transferring genes encoding therapeutic factors into the repair tissue, resulting in a temporarily and spatially defined delivery of therapeutic molecules to sites of cartilage damage. This review focuses on the potential benefits of using gene therapy approaches for the repair of articular cartilage and meniscal fibrocartilage, including articular cartilage defects resulting from acute trauma, osteochondritis dissecans, osteonecrosis, and osteoarthritis. Possible applications for meniscal repair comprise meniscal lesions, meniscal sutures, and meniscal transplantation. Recent studies in both small and large animal models have demonstrated the applicability of gene-based approaches for cartilage repair. Chondrogenic pathways were stimulated in the repair tissue and in osteoarthritic cartilage using genes for polypeptide growth factors and transcription factors. Although encouraging data have been generated, a successful translation of gene therapy for cartilage repair will require an ongoing combined effort of orthopedic surgeons and of basic scientists. PMID:26069580

  2. Gene targeting with retroviral vectors

    SciTech Connect

    Ellis, J.; Bernstein, A. )

    1989-04-01

    The authors have designed and constructed integration-defective retroviral vectors to explore their potential for gene targeting in mammalian cells. Two nonoverlapping deletion mutants of the bacterial neomycin resistance (neo) gene were used to detect homologous recombination events between viral and chromosomal sequences. Stable neo gene correction events were selected at a frequency of approximately 1 G418/sup r/ cell per 3 x 10/sup 6/ infected cells. Analysis of the functional neo gene in independent targeted cell clones indicated that unintegrated retroviral linear DNA recombined with the target by gene conversion for variable distances into regions of nonhomology. In addition, transient neo gene correction events which were associated with the complete loss of the chromosomal target sequences were observed. These results demonstrated that retroviral vectors can recombine with homologous chromosomal sequences in rodent and human cells.

  3. The coalescent with gene conversion.

    PubMed Central

    Wiuf, C; Hein, J

    2000-01-01

    In this article we develop a coalescent model with intralocus gene conversion. The distribution of the tract length is geometric in concordance with results published in the literature. We derive a simulation scheme and deduce a number of analytical results for this coalescent with gene conversion. We compare patterns of variability in samples simulated according to the coalescent with recombination with similar patterns simulated according to the coalescent with gene conversion alone. Further, an expression for the expected number of topology shifts in a sample of present-day sequences caused by gene conversion events is derived. PMID:10790416

  4. Serial analysis of gene expression.

    PubMed

    Velculescu, V E; Zhang, L; Vogelstein, B; Kinzler, K W

    1995-10-20

    The characteristics of an organism are determined by the genes expressed within it. A method was developed, called serial analysis of gene expression (SAGE), that allows the quantitative and simultaneous analysis of a large number of transcripts. To demonstrate this strategy, short diagnostic sequence tags were isolated from pancreas, concatenated, and cloned. Manual sequencing of 1000 tags revealed a gene expression pattern characteristic of pancreatic function. New pancreatic transcripts corresponding to novel tags were identified. SAGE should provide a broadly applicable means for the quantitative cataloging and comparison of expressed genes in a variety of normal, developmental, and disease states. PMID:7570003

  5. Method for cloning genes

    SciTech Connect

    Weissman, S.M.; Pereira, D.; Sood, A.

    1988-04-19

    This patent describes a recombinant cloning vehicle comprising an inserted human gene, the improvement wherein the cloning vehicle is isolated from a recombinant clone which is isolated and identified by a process comprising the steps of: (a) effecting cDNA synthesis on a mixture of mRNAs containing a target mRNA coding for a major hisitocompatibility antigen, and isolating the resultant cDNA mixture; (b) inserting the resultant cDNA into recombinant cloning vehicles, and transforming hosts with the vehicles; and (c) separating the transformants and isolating and identifying a recombinant clone containing a DNA segment which is homologous over at least a portion thereof to at least one oligonucleotide probe specific for the DNA segment.

  6. New genes for boys

    SciTech Connect

    Sinclair, A.H.

    1995-11-01

    Sex is a fascinating topic, particularly at the level of molecular genetics, since it represents a wonderful paradigm for mammalian organ development. Recently, interest in the molecular basis for mammalian sex determination has been heating up as new pieces are added to the jigsaw puzzle of testis development. In mammals, the Y chromosome is male determining and encodes a gene referred to as TDF (testis-determining factor), which induces the indifferent embryonic gonad to develop as a testis. Subsequent male sexual differentiation is largely a consequence of hormonal secretion from the testis. In the absence of the Y chromosome, the testis-determining pathway fails to be initiated, and the embryonic gonad develops as an ovary, resulting in female development. 32 refs.

  7. Copyright and gene technology.

    PubMed

    Coke, Sue

    2002-08-01

    The rapid growth of gene technology and its commercialisation raises concerns for scientific researchers and research institutions wishing to place information in the public domain. This article examines whether copyright laws in the United States, United Kingdom and Australia provide any protection for genetically modified DNA, proteins, and genetically modified organisms, in contrast with any copyright protection extending to a record of the lettering of a sequence representing a series of nucleotides of modified DNA or the amino acids comprising a protein. Whilst it is arguable that protection may be available in the United States and the United Kingdom, it is submitted that it would be difficult to persuade a court in Australia that genetically modified DNA and genetically modified organisms directly constitute "literary" or "artistic" works.

  8. Taste Receptor Genes

    PubMed Central

    Bachmanov, Alexander A.; Beauchamp, Gary K.

    2009-01-01

    In the past several years, tremendous progress has been achieved with the discovery and characterization of vertebrate taste receptors from the T1R and T2R families, which are involved in recognition of bitter, sweet, and umami taste stimuli. Individual differences in taste, at least in some cases, can be attributed to allelic variants of the T1R and T2R genes. Progress with understanding how T1R and T2R receptors interact with taste stimuli and with identifying their patterns of expression in taste cells sheds light on coding of taste information by the nervous system. Candidate mechanisms for detection of salts, acids, fat, complex carbohydrates, and water have also been proposed, but further studies are needed to prove their identity. PMID:17444812

  9. Gene-environment interaction.

    PubMed

    Manuck, Stephen B; McCaffery, Jeanne M

    2014-01-01

    With the advent of increasingly accessible technologies for typing genetic variation, studies of gene-environment (G×E) interactions have proliferated in psychological research. Among the aims of such studies are testing developmental hypotheses and models of the etiology of behavioral disorders, defining boundaries of genetic and environmental influences, and identifying individuals most susceptible to risk exposures or most amenable to preventive and therapeutic interventions. This research also coincides with the emergence of unanticipated difficulties in detecting genetic variants of direct association with behavioral traits and disorders, which may be obscured if genetic effects are expressed only in predisposing environments. In this essay we consider these and other rationales for positing G×E interactions, review conceptual models meant to inform G×E interpretations from a psychological perspective, discuss points of common critique to which G×E research is vulnerable, and address the role of the environment in G×E interactions.

  10. Gene therapy for hemophilia

    PubMed Central

    Rogers, Geoffrey L.; Herzog, Roland W.

    2015-01-01

    Hemophilia is an X-linked inherited bleeding disorder consisting of two classifications, hemophilia A and hemophilia B, depending on the underlying mutation. Although the disease is currently treatable with intravenous delivery of replacement recombinant clotting factor, this approach represents a significant cost both monetarily and in terms of quality of life. Gene therapy is an attractive alternative approach to the treatment of hemophilia that would ideally provide life-long correction of clotting activity with a single injection. In this review, we will discuss the multitude of approaches that have been explored for the treatment of both hemophilia A and B, including both in vivo and ex vivo approaches with viral and nonviral delivery vectors. PMID:25553466

  11. Gene Express Inc.

    PubMed

    Saccomanno, Colette F

    2006-07-01

    Gene Express, Inc. is a technology-licensing company and provider of Standardized Reverse Transcription Polymerase Chain Reaction (StaRT-PCR) services. Designed by and for clinical researchers involved in pharmaceutical, biomarker and molecular diagnostic product development, StaRT-PCR is a unique quantitative and standardized multigene expression measurement platform. StaRT-PCR meets all of the performance characteristics defined by the US FDA as required to support regulatory submissions [101,102] , and by the Clinical Laboratory Improvement Act of 1988 (CLIA) as necessary to support diagnostic testing [1] . A standardized mixture of internal standards (SMIS), manufactured in bulk, provides integrated quality control wherein each native template target gene is measured relative to a competitive template internal standard. Bulk production enables the compilation of a comprehensive standardized database from across multiple experiments, across collaborating laboratories and across the entire clinical development lifecycle of a given compound or diagnostic product. For the first time, all these data are able to be directly compared. Access to such a database can dramatically shorten the time from investigational new drug (IND) to new drug application (NDA), or save time and money by hastening a substantiated 'no-go' decision. High-throughput StaRT-PCR is conducted at the company's automated Standardized Expression Measurement (SEM) Center. Currently optimized for detection on a microcapillary electrophoretic platform, StaRT-PCR products also may be analyzed on microarray, high-performance liquid chromatography (HPLC), or matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) platforms. SEM Center services deliver standardized genomic data--data that will accelerate the application of pharmacogenomic technology to new drug and diagnostic test development and facilitate personalized medicine.

  12. Perfil de temperatura dos funis magnetosféricos de estrelas T Tauri com aquecimento alfvênico

    NASA Astrophysics Data System (ADS)

    Vasconcelos, M. J.

    2003-08-01

    Estrelas T Tauri Clássicas são objetos jovens circundados por discos de gás e poeira e que apresentam uma intensa atividade magnética. Seu espectro mostra linhas de emissão alargadas que são razoavelmente reproduzidas nos modelos de acresção magnetosférica. No entanto, o perfil de temperatura dos funis magnéticos é desconhecido. Aquecimento magnético compressional e difusão ambipolar foram considerados para estas estruturas, porém as temperaturas obtidas não são suficientes para explicar as observações. Neste trabalho, examinamos o aquecimento gerado pelo amortecimento de ondas Alfvén através de quatro mecanismos, os amortecimentos não-linear, turbulento, viscoso-resistivo e colisional como função da freqüência da onda. Inicialmente, a temperatura é ajustada para reproduzir as observações e o grau de turbulência requerido para que o mecanismo seja viável é calculado. Os resultados mostram que este é compatível com os dados observacionais. Apresentam-se, também, resultados preliminares do cálculo auto-consistente do perfil de temperatura dos funis, levando-se em conta fontes de aquecimento Alfvênica e fontes de resfriamento.

  13. Contributions of Gene Marking to Cell and Gene Therapies

    PubMed Central

    Barese, Cecilia N.

    2011-01-01

    Abstract The first human genetic modification studies used replication-incompetent integrating vector vectors to introduce marker genes into T lymphocytes and subsequently into hematopoietic stem cells. Such studies have provided numerous insights into the biology of hematopoiesis and immune reconstitution and contributed to clinical development of gene and cell therapies. Tracking of hematopoietic reconstitution and analysis of the origin of residual malignant disease after hematopoietic transplantation has been possible via gene marking. Introduction of selectable marker genes has enabled preselection of specific T-cell populations for tumor and viral immunotherapy and reduced the threat of graft-versus-host disease, improving the survival of patients after allogeneic marrow transplantation. Marking studies in humans, murine xenografts, and large animals have helped optimize conditions for gene transfer into CD34+ hematopoietic progenitors, contributing to the achievement of gene transfer efficiencies sufficient for clinical benefit in several serious genetic diseases such as X-linked severe combined immunodeficiency and adrenoleukodystropy. When adverse events linked to insertional mutagenesis arose in clinical gene therapy trials for inherited immunodeficiencies, additional animal studies using gene-marking vectors have greatly increased our understanding of genotoxicity. The knowledge gained from these studies is being translated into new vector designs and clinical protocols, which we hope will continue to improve the efficiency, effectiveness and safety of these promising therapeutic approaches. PMID:21261461

  14. Contributions of gene marking to cell and gene therapies.

    PubMed

    Barese, Cecilia N; Dunbar, Cynthia E

    2011-06-01

    The first human genetic modification studies used replication-incompetent integrating vector vectors to introduce marker genes into T lymphocytes and subsequently into hematopoietic stem cells. Such studies have provided numerous insights into the biology of hematopoiesis and immune reconstitution and contributed to clinical development of gene and cell therapies. Tracking of hematopoietic reconstitution and analysis of the origin of residual malignant disease after hematopoietic transplantation has been possible via gene marking. Introduction of selectable marker genes has enabled preselection of specific T-cell populations for tumor and viral immunotherapy and reduced the threat of graft-versus-host disease, improving the survival of patients after allogeneic marrow transplantation. Marking studies in humans, murine xenografts, and large animals have helped optimize conditions for gene transfer into CD34(+) hematopoietic progenitors, contributing to the achievement of gene transfer efficiencies sufficient for clinical benefit in several serious genetic diseases such as X-linked severe combined immunodeficiency and adrenoleukodystrophy. When adverse events linked to insertional mutagenesis arose in clinical gene therapy trials for inherited immunodeficiencies, additional animal studies using gene-marking vectors have greatly increased our understanding of genotoxicity. The knowledge gained from these studies is being translated into new vector designs and clinical protocols, which we hope will continue to improve the efficiency, effectiveness and safety of these promising therapeutic approaches.

  15. Candidate reference genes for gene expression studies in water lily.

    PubMed

    Luo, Huolin; Chen, Sumei; Wan, Hongjian; Chen, Fadi; Gu, Chunsun; Liu, Zhaolei

    2010-09-01

    The selection of an appropriate reference gene(s) is a prerequisite for the proper interpretation of quantitative Real-Time polymerase chain reaction data. We report the evaluation of eight candidate reference genes across various tissues and treatments in the water lily by the two software packages geNorm and NormFinder. Across all samples, clathrin adaptor complexes medium subunit (AP47) and actin 11 (ACT11) emerged as the most suitable reference genes. Across different tissues, ACT11 and elongation factor 1-alpha (EF1alpha) exhibited a stable expression pattern. ACT11 and AP47 also stably expressed in roots subjected to various treatments, but in the leaves of the same plants the most stably expressed genes were ubiquitin-conjugating enzyme 16 (UBC16) and ACT11. PMID:20452325

  16. Using Genes to Guide Prescriptions

    MedlinePlus

    ... Science > Using Genes to Guide Prescriptions Inside Life Science View All Articles | Inside Life Science Home Page Using Genes to Guide Prescriptions By ... to Zoloft: Ways Medicines Work This Inside Life Science article also appears on LiveScience . Learn about related ...

  17. Determining Semantically Related Significant Genes.

    PubMed

    Taha, Kamal

    2014-01-01

    GO relation embodies some aspects of existence dependency. If GO term xis existence-dependent on GO term y, the presence of y implies the presence of x. Therefore, the genes annotated with the function of the GO term y are usually functionally and semantically related to the genes annotated with the function of the GO term x. A large number of gene set enrichment analysis methods have been developed in recent years for analyzing gene sets enrichment. However, most of these methods overlook the structural dependencies between GO terms in GO graph by not considering the concept of existence dependency. We propose in this paper a biological search engine called RSGSearch that identifies enriched sets of genes annotated with different functions using the concept of existence dependency. We observe that GO term xcannot be existence-dependent on GO term y, if x- and y- have the same specificity (biological characteristics). After encoding into a numeric format the contributions of GO terms annotating target genes to the semantics of their lowest common ancestors (LCAs), RSGSearch uses microarray experiment to identify the most significant LCA that annotates the result genes. We evaluated RSGSearch experimentally and compared it with five gene set enrichment systems. Results showed marked improvement.

  18. From genes to genome biology

    SciTech Connect

    Pennisi, E.

    1996-06-21

    This article describes a change in the approach to mapping genomes, from looking at one gene at a time, to other approaches. Strategies include everything from lab techniques to computer programs designed to analyze whole batches of genes at once. Also included is a update on the work on the human genome.

  19. Susceptibility Genes in Thyroid Autoimmunity

    PubMed Central

    Ban, Yoshiyuki; Tomer, Yaron

    2005-01-01

    The autoimmune thyroid diseases (AITD) are complex diseases which are caused by an interaction between susceptibility genes and environmental triggers. Genetic susceptibility in combination with external factors (e.g. dietary iodine) is believed to initiate the autoimmune response to thyroid antigens. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITD. Various techniques have been employed to identify the genes contributing to the etiology of AITD, including candidate gene analysis and whole genome screening. These studies have enabled the identification of several loci (genetic regions) that are linked with AITD, and in some of these loci, putative AITD susceptibility genes have been identified. Some of these genes/loci are unique to Graves' disease (GD) and Hashimoto's thyroiditis (HT) and some are common to both the diseases, indicating that there is a shared genetic susceptibility to GD and HT. The putative GD and HT susceptibility genes include both immune modifying genes (e.g. HLA, CTLA-4) and thyroid specific genes (e.g. TSHR, Tg). Most likely, these loci interact and their interactions may influence disease phenotype and severity. PMID:15712599

  20. Gene therapy on the move

    PubMed Central

    Kaufmann, Kerstin B; Büning, Hildegard; Galy, Anne; Schambach, Axel; Grez, Manuel

    2013-01-01

    The first gene therapy clinical trials were initiated more than two decades ago. In the early days, gene therapy shared the fate of many experimental medicine approaches and was impeded by the occurrence of severe side effects in a few treated patients. The understanding of the molecular and cellular mechanisms leading to treatment- and/or vector-associated setbacks has resulted in the development of highly sophisticated gene transfer tools with improved safety and therapeutic efficacy. Employing these advanced tools, a series of Phase I/II trials were started in the past few years with excellent clinical results and no side effects reported so far. Moreover, highly efficient gene targeting strategies and site-directed gene editing technologies have been developed and applied clinically. With more than 1900 clinical trials to date, gene therapy has moved from a vision to clinical reality. This review focuses on the application of gene therapy for the correction of inherited diseases, the limitations and drawbacks encountered in some of the early clinical trials and the revival of gene therapy as a powerful treatment option for the correction of monogenic disorders. PMID:24106209

  1. Candidate gene prioritization with Endeavour.

    PubMed

    Tranchevent, Léon-Charles; Ardeshirdavani, Amin; ElShal, Sarah; Alcaide, Daniel; Aerts, Jan; Auboeuf, Didier; Moreau, Yves

    2016-07-01

    Genomic studies and high-throughput experiments often produce large lists of candidate genes among which only a small fraction are truly relevant to the disease, phenotype or biological process of interest. Gene prioritization tackles this problem by ranking candidate genes by profiling candidates across multiple genomic data sources and integrating this heterogeneous information into a global ranking. We describe an extended version of our gene prioritization method, Endeavour, now available for six species and integrating 75 data sources. The performance (Area Under the Curve) of Endeavour on cross-validation benchmarks using 'gold standard' gene sets varies from 88% (for human phenotypes) to 95% (for worm gene function). In addition, we have also validated our approach using a time-stamped benchmark derived from the Human Phenotype Ontology, which provides a setting close to prospective validation. With this benchmark, using 3854 novel gene-phenotype associations, we observe a performance of 82%. Altogether, our results indicate that this extended version of Endeavour efficiently prioritizes candidate genes. The Endeavour web server is freely available at https://endeavour.esat.kuleuven.be/.

  2. Genes, Tolerance and Systemic Autoimmunity

    PubMed Central

    Singh, Ram P.; Waldron, Richard T.; Hahn, Bevra H.

    2011-01-01

    The characterization of functional CD8+ inhibitory or regulatory T cells and their gene regulation remains a critical challenge in the field of tolerance and autoimmunity. Investigating the genes induced in regulatory cells and the regulatory networks and pathways that underlie mechanisms of immune resistance and prevent apoptosis in the CD8+ T cell compartment are crucial to understanding tolerance mechanisms in systemic autoimmunity. Little is currently known about the genetic control that governs the ability of CD8+ Ti or regulatory cells to suppress anti-DNA Ab production in B cells. Silencing genes with siRNA or shRNA and overexpression of genes with lentiviral cDNA transduction are established approaches to identifying and understanding the function of candidate genes in tolerance and immunity. Elucidation of interactions between genes and proteins, and their synergistic effects in establishing cell-cell cross talk, including receptor modulation/antagonism, are essential for delineating the roles of these cells. In this review, we will examine recent reports which describe the modulation of cells from lupus prone mice or lupus patients to confer anti-inflammatory and protective gene expression and novel associated phenotypes. We will highlight recent findings on the role of selected genes induced by peptide tolerance in CD8+ Ti. PMID:22155015

  3. Method of controlling gene expression

    DOEpatents

    Peters, Norman K.; Frost, John W.; Long, Sharon R.

    1991-12-03

    A method of controlling expression of a DNA segment under the control of a nod gene promoter which comprises administering to a host containing a nod gene promoter an amount sufficient to control expression of the DNA segment of a compound of the formula: ##STR1## in which each R is independently H or OH, is described.

  4. Fusion genes in solid tumors.

    PubMed

    Aman, P

    1999-08-01

    Tumor development in different cell types and tissue locations involves many pathways, distinct genes and exogenous factors. Tumor type-specific chromosome rearrangements resulting in fusion genes or promoter swapping are believed to be involved in the early development of many tumor types. They are present in almost all cases of a particular tumor type and cases have been described that carry only tumor type-specific translocations without any signs of other cytogenetic changes. The mechanisms behind chromosome rearrangements in solid tumors are largely unknown. Radiation is an important factor in thyroid carcinomas but no com-$bmon sequence motifs are made out in the break points of solid tumors. The fusion genes found in sarcomas are dominated by the transcription factor type of genes with the TLS/FUS and EWS series of fusion genes as the largest group. More than 50% of papillary thyroid carcinomas carry fusion proteins with tyrosine kinase activity. Rearrangements involving HMGIC, HMGIY, and PLAG1 are common in benign mesenchymal tumors and salivary gland adenomas. Many recurrent tumor translocations show a strict specificity for tumor type. This specificity can most likely be explained by the specific sets of target genes that are deregulated by the fusion gene products. Identification of the downstream target genes is currently the object of intense research and may provide us with information that will help design better diagnostic tools and eventually find a cure for these diseases.

  5. Nonviral Vectors for Gene Delivery

    NASA Astrophysics Data System (ADS)

    Baoum, Abdulgader Ahmed

    2011-12-01

    The development of nonviral vectors for safe and efficient gene delivery has been gaining considerable attention recently. An ideal nonviral vector must protect the gene against degradation by nuclease in the extracellular matrix, internalize the plasma membrane, escape from the endosomal compartment, unpackage the gene at some point and have no detrimental effects. In comparison to viruses, nonviral vectors are relatively easy to synthesize, less immunogenic, low in cost, and have no limitation in the size of a gene that can be delivered. Significant progress has been made in the basic science and applications of various nonviral gene delivery vectors; however, the majority of nonviral approaches are still inefficient and often toxic. To this end, two nonviral gene delivery systems using either biodegradable poly(D,L-lactide- co-glycolide) (PLG) nanoparticles or cell penetrating peptide (CPP) complexes have been designed and studied using A549 human lung epithelial cells. PLG nanoparticles were optimized for gene delivery by varying particle surface chemistry using different coating materials that adsorb to the particle surface during formation. A variety of cationic coating materials were studied and compared to more conventional surfactants used for PLG nanoparticle fabrication. Nanoparticles (˜200 nm) efficiently encapsulated plasmids encoding for luciferase (80-90%) and slowly released the same for two weeks. After a delay, moderate levels of gene expression appeared at day 5 for certain positively charged PLG particles and gene expression was maintained for at least two weeks. In contrast, gene expression mediated by polyethyleneimine (PEI) ended at day 5. PLG particles were also significantly less cytotoxic than PEI suggesting the use of these vehicles for localized, sustained gene delivery to the pulmonary epithelium. On the other hand, a more simple method to synthesize 50-200 nm complexes capable of high transfection efficiency or high gene knockdown was

  6. Regulation of Neuronal Gene Expression

    NASA Astrophysics Data System (ADS)

    Thiel, Gerald; Lietz, Michael; Leichter, Michael

    Humans as multicellular organisms contain a variety of different cell types where each cell population must fulfill a distinct function in the interest of the whole organism. The molecular basis for the variations in morphology, biochemistry, molecular biology, and function of the various cell types is the cell-type specific expression of genes. These genes encode proteins necessary for executing the specialized functions of each cell type within an organism. We describe here a regulatory mechanism for the expression of neuronal genes. The zinc finger protein REST binds to the regulatory region of many neuronal genes and represses neuronal gene expression in nonneuronal tissues. A negative regulatory mechanism, involving a transcriptional repressor, seems to play an important role in establishing the neuronal phenotype.

  7. Gene Therapy for Retinal Diseases

    PubMed Central

    Samiy, Nasrollah

    2014-01-01

    Gene therapy has a growing research potential particularly in the field of ophthalmic and retinal diseases owing to three main characteristics of the eye; accessibility in terms of injections and surgical interventions, its immune-privileged status facilitating the accommodation to the antigenicity of a viral vector, and tight blood-ocular barriers which save other organs from unwanted contamination. Gene therapy has tremendous potential for different ocular diseases. In fact, the perspective of gene therapy in the field of eye research does not confine to exclusive monogenic ophthalmic problems and it has the potential to include gene based pharmacotherapies for non-monogenic problems such as age related macular disease and diabetic retinopathy. The present article has focused on how gene transfer into the eye has been developed and used to treat retinal disorders with no available therapy at present. PMID:25709778

  8. [Transcriptional control of ciliary genes].

    PubMed

    Vieillard, Jennifer; Jerber, Julie; Durand, Bénédicte

    2014-11-01

    Cilia are found in many eukaryotic species and share a common microtubule architecture that can nonetheless show very diverse features within one animal. The genesis of cilia and their diversity require the expression of different specific genes. At least two classes of transcription factors are involved in ciliogenesis: the RFX family, essential for the assembly of most cilia and the FOXJ1 transcription factors that are key regulators of motile cilia assembly. These two different families of transcription factors have both specific and common target genes and they can also cooperate for the formation of cilia. In collaboration with cell type specific factors, they also contribute to the specialisation of cilia. As a consequence, the identification of RFX and FOXJ1 target genes has emerged as an efficient strategy to identify novel ciliary genes, and in particular genes potentially implicated in ciliopathies.

  9. Nanoparticle-Mediated Gene Delivery

    NASA Astrophysics Data System (ADS)

    Jin, Sha; Leach, John C.; Ye, Kaiming

    Nonviral gene delivery has been gaining considerable attention recently. Although the efficacy of DNA transfection, which is a major concern, is low in nonviral vector-mediated gene transfer compared with viral ones, nonviral vectors are relatively easy to prepare, less immunogenic and oncogenic, and have no potential of virus recombination and no limitation on the size of a transferred gene. The ability to incorporate genetic materials such as plasmid DNA, RNA, and siRNA into functionalized nanoparticles with little toxicity demonstrates a new era in pharmacotherapy for delivering genes selectively to tissues and cells. In this chapter, we highlight the basic concepts and applications of nonviral gene delivery using super paramagnetic iron oxide nanoparticles and functionalized silica nanoparticles. The experimental protocols related to these topics are described in the chapter.

  10. Gene therapy for lung disease.

    PubMed

    Ennist, D L

    1999-06-01

    Gene therapy is a new field of medical research that has great potential to influence the course of treatment of human disease. The lung has been a particularly attractive target organ for gene therapy due to its accessibility and the identification of genetic deficits for a number of lung diseases. Several clinical trials have shown evidence of low levels of gene transfer and expression, but without any benefit to the patients involved. Thus, current studies are focusing on further research and technological improvements to the vectors. Gene therapy is now beginning to benefit from a shift in emphasis from clinical trials to the development of better tools and procedures to deliver gene therapy to the bedside.

  11. Bacteria in gene therapy: bactofection versus alternative gene therapy.

    PubMed

    Pálffy, R; Gardlík, R; Hodosy, J; Behuliak, M; Resko, P; Radvánský, J; Celec, P

    2006-01-01

    Recent advances in gene therapy can be attributed to improvements of gene delivery vectors. New viral and nonviral transport vehicles that considerably increase the efficiency of transfection have been prepared. However, these vectors still have many disadvantages that are difficult to overcome, thus, a new approach is needed. The approach of bacterial delivery could in the future be important for gene therapy applications. In this article we try to summarize the most important modifications that are used for the preparation of applied strains, difficulties that are related with bacterial gene delivery and the current use of bactofection in animal experiments and clinical trials. Important differences to the alternative gene therapy (AGT) are discussed. AGT resembles bacteria-mediated protein delivery, as the therapeutical proteins are produced not by host cells but by the bacteria in situ and the expression can be regulated exogenously. Although the procedure of bacterial gene delivery is far from being definitely solved, bactofection remains a promising technique for transfection in human gene therapy.

  12. Genes and gene networks implicated in aggression related behaviour.

    PubMed

    Malki, Karim; Pain, Oliver; Du Rietz, Ebba; Tosto, Maria Grazia; Paya-Cano, Jose; Sandnabba, Kenneth N; de Boer, Sietse; Schalkwyk, Leonard C; Sluyter, Frans

    2014-10-01

    Aggressive behaviour is a major cause of mortality and morbidity. Despite of moderate heritability estimates, progress in identifying the genetic factors underlying aggressive behaviour has been limited. There are currently three genetic mouse models of high and low aggression created using selective breeding. This is the first study to offer a global transcriptomic characterization of the prefrontal cortex across all three genetic mouse models of aggression. A systems biology approach has been applied to transcriptomic data across the three pairs of selected inbred mouse strains (Turku Aggressive (TA) and Turku Non-Aggressive (TNA), Short Attack Latency (SAL) and Long Attack Latency (LAL) mice and North Carolina Aggressive (NC900) and North Carolina Non-Aggressive (NC100)), providing novel insight into the neurobiological mechanisms and genetics underlying aggression. First, weighted gene co-expression network analysis (WGCNA) was performed to identify modules of highly correlated genes associated with aggression. Probe sets belonging to gene modules uncovered by WGCNA were carried forward for network analysis using ingenuity pathway analysis (IPA). The RankProd non-parametric algorithm was then used to statistically evaluate expression differences across the genes belonging to modules significantly associated with aggression. IPA uncovered two pathways, involving NF-kB and MAPKs. The secondary RankProd analysis yielded 14 differentially expressed genes, some of which have previously been implicated in pathways associated with aggressive behaviour, such as Adrbk2. The results highlighted plausible candidate genes and gene networks implicated in aggression-related behaviour.

  13. Immunoglobulin λ Gene Rearrangement Can Precede κ Gene Rearrangement

    DOE PAGES

    Berg, Jörg; Mcdowell, Mindy; Jäck, Hans-Martin; Wabl, Matthias

    1990-01-01

    Imore » mmunoglobulin genes are generated during differentiation of B lymphocytes by joining gene segments. A mouse pre-B cell contains a functional immunoglobulin heavy-chain gene, but no light-chain gene. Although there is only one heavy-chain locus, there are two lightchain loci: κ and λ .It has been reported that κ loci in the germ-line configuration are never (in man) or very rarely (in the mouse) present in cells with functionally rearranged λ -chain genes. Two explanations have been proposed to explain this: (a) the ordered rearrangement theory, which postulates that light-chain gene rearrangement in the pre-B cell is first attempted at the κ locus, and that only upon failure to produce a functional κ chain is there an attempt to rearrange the λ locus; and (b) the stochastic theory, which postulates that rearrangement at the λ locus proceeds at a rate that is intrinsically much slower than that at the κ locus. We show here that λ -chain genes are generated whether or not the κ locus has lost its germ-line arrangement, a result that is compatible only with the stochastic theory.« less

  14. Therapeutic genes for anti-HIV/AIDS gene therapy.

    PubMed

    Bovolenta, Chiara; Porcellini, Simona; Alberici, Luca

    2013-01-01

    The multiple therapeutic approaches developed so far to cope HIV-1 infection, such as anti-retroviral drugs, germicides and several attempts of therapeutic vaccination have provided significant amelioration in terms of life-quality and survival rate of AIDS patients. Nevertheless, no approach has demonstrated efficacy in eradicating this lethal, if untreated, infection. The curative power of gene therapy has been proven for the treatment of monogenic immunodeficiensies, where permanent gene modification of host cells is sufficient to correct the defect for life-time. No doubt, a similar concept is not applicable for gene therapy of infectious immunodeficiensies as AIDS, where there is not a single gene to be corrected; rather engineered cells must gain immunotherapeutic or antiviral features to grant either short- or long-term efficacy mostly by acquisition of antiviral genes or payloads. Anti-HIV/AIDS gene therapy is one of the most promising strategy, although challenging, to eradicate HIV-1 infection. In fact, genetic modification of hematopoietic stem cells with one or multiple therapeutic genes is expected to originate blood cell progenies resistant to viral infection and thereby able to prevail on infected unprotected cells. Ultimately, protected cells will re-establish a functional immune system able to control HIV-1 replication. More than hundred gene therapy clinical trials against AIDS employing different viral vectors and transgenes have been approved or are currently ongoing worldwide. This review will overview anti-HIV-1 infection gene therapy field evaluating strength and weakness of the transgenes and payloads used in the past and of those potentially exploitable in the future.

  15. Contextual variation in young children’s observed disruptive behavior on the DB-DOS: implications for early identification

    PubMed Central

    Petitclerc, Amélie; Briggs-Gowan, Margaret J.; Estabrook, Ryne; Burns, James L.; Anderson, Erica L.; McCarthy, Kimberly J.; Wakschlag, Lauren S.

    2015-01-01

    Background Contextual variation in child disruptive behavior is well documented but remains poorly understood. We first examine how variation in observed disruptive behavior across interactional contexts is associated with maternal reports of contextual variation in oppositional-defiant behavior and functional impairment. Second, we test whether child inhibitory control explains the magnitude of contextual variation in observed disruptive behavior. Methods Participants are 497 young children (mean age = 4 years, 11 months) from a subsample of the MAPS, a sociodemographically diverse pediatric sample, enriched for risk of disruptive behavior. Observed anger modulation and behavioral regulation problems were coded on the Disruptive Behavior Diagnostic Observation Schedule (DB-DOS) during interactions with parent and examiner. Oppositional-defiant behavior, and impairment in relationships, with parents and nonparental adults, were measured with the Preschool Age Psychiatric Assessment (PAPA) interview with the mother. Functional impairment in the home and out-and-about was assessed with the Family Life Impairment Scale (FLIS), and expulsion from child care/school was measured with the baseline survey and FLIS. Results Observed disruptive behavior on the DB-DOS Parent Context was associated with oppositional-defiant behavior with parents, and with impairment at home and out-and-about. Observed disruptive behavior with the Examiner was associated with oppositional-defiant behavior with both parents and nonparental adults, impairment in relationships with nonparental adults, and child care/school expulsion. Differences in observed disruptive behavior in the Parent versus Examiner Contexts was related to the differences in maternal reports of oppositional-defiant behavior with parents versus nonparental adults. Children with larger decreases in disruptive behavior from Parent to Examiner Context had better inhibitory control and fewer attention

  16. Genes, Economics, and Happiness.

    PubMed

    De Neve, Jan-Emmanuel; Christakis, Nicholas A; Fowler, James H; Frey, Bruno S

    2012-11-01

    We explore the influence of genetic variation on subjective well-being by employing a twin design and genetic association study. In a nationally-representative twin sample, we first show that about 33% of the variation in life satisfaction is explained by genetic variation. Although previous studies have shown that baseline happiness is significantly heritable, little research has considered molecular genetic associations with subjective well-being. We study the relationship between a functional polymorphism on the serotonin transporter gene (5-HTTLPR) and life satisfaction. We initially find that individuals with the longer, transcriptionally more efficient variant of this genotype report greater life satisfaction (n=2,545, p=0.012). However, our replication attempts on independent samples produce mixed results indicating that more work needs to be done to better understand the relationship between this genotype and subjective well-being. This work has implications for how economists think about the determinants of utility, and the extent to which exogenous shocks might affect individual well-being.

  17. Environment, genes, and cancer

    SciTech Connect

    Manuel, J.

    1996-03-01

    In January, comedian George Burns turned 100 years old. In recent appearances in the media, he still seems sharp as a tack, and is still seen smoking his trademark cigars. Others of us, however, were never very funny, and would die of cancer at age 60 if we continuously smoked cigars or cigarettes. Burns presents a common but perplexing paradox; some people are able to tolerate at least moderate exposure to toxins such as cigarette smoke with little adverse affect, while others develop cancer, emphysema, or heart disease. New studies support the idea that there is an interaction between genes and the environment, and that this interaction may be an important determinant of cancer risk. To understand such risks, it is essential to look at both an individual`s genetic makeup and environmental exposures. Such studies require the collaboration of molecular epidemiologists and molecular biologists. At the NIEHS, Jack A. Taylor, a lead clinical investigator in the Epidemiology Branch, and Douglas A. Bell, an investigator with the Genetic Risk Group of the Laboratory of Biochemical Risk Analysis, have worked together and with other scientists to uncover new information in this area.

  18. RNA splicing and genes

    SciTech Connect

    Sharp, P.A.

    1988-11-25

    The splicing of long transcripts RNA (copied from DNA in the cell nucleus) into smaller specific mRNA is an important event in the regulation of gene expression in eukaryotic cells. The splicing reaction occurs as a late step in the nuclear pathway for synthesis of mRNAs. This pathway commences with initiation of transcription by RNA polymerase II and probably involves an integrated series of steps each dependent on previous events. Splicing of precursors to mRNAs involves the formation of a spliceosome complex containing 5' and 3' splice sites. This complex contains the evolutionary highly conserved small nuclear RNAs (snRNAs) Us, U4, U5, and U6. The most abundant snRNA, U1, is required to form the spliceosome and may be a part of the spliceosome. Analogues of these snRNAs have been identified in yeast. Assembly of the spliceosome probably involves the binding of a multi-snRNA complex containing U4, U5, and U6 snRNAs. Several observations suggest that the association of snRNAs in such complexes is quite dynamic. It is argued that the snRANs in the spliceosome form a catalytic RNA structure that is responsible for the cleavage and ligation steps during splicing.

  19. Genes, Economics, and Happiness *

    PubMed Central

    De Neve, Jan-Emmanuel; Christakis, Nicholas A.; Fowler, James H.; Frey, Bruno S.

    2012-01-01

    We explore the influence of genetic variation on subjective well-being by employing a twin design and genetic association study. In a nationally-representative twin sample, we first show that about 33% of the variation in life satisfaction is explained by genetic variation. Although previous studies have shown that baseline happiness is significantly heritable, little research has considered molecular genetic associations with subjective well-being. We study the relationship between a functional polymorphism on the serotonin transporter gene (5-HTTLPR) and life satisfaction. We initially find that individuals with the longer, transcriptionally more efficient variant of this genotype report greater life satisfaction (n=2,545, p=0.012). However, our replication attempts on independent samples produce mixed results indicating that more work needs to be done to better understand the relationship between this genotype and subjective well-being. This work has implications for how economists think about the determinants of utility, and the extent to which exogenous shocks might affect individual well-being. PMID:24349601

  20. [The Arabic influence in the "Colóquios dos simples e drogas da India" of Garcia da Orta].

    PubMed

    Ricordel, Joëlle

    2015-09-01

    The "Colóquios dos simples e drogas he cousas medicinais de Índia" (Conversations on the simples, drugs and medicinal substances of India) (1563) of Garcia da Orta is a botanical and pharmacognosy book. The author is a Portuguese physician who studied in the Spanish universities and practiced medicine mainly in India. He studies in short chapters presented in the form of dialogues about sixty simples. Sources to which he refers are indicative of a "classical" training, but also the mark of a curious and open mind to different cultures. The Arabic sources are numerous and mainly concern the identification of substances by abundant synonyms of their names in foreign languages and different medicinal uses that may have been done by the ancient physicians. However, Da Orta is critical with respect to these sources, seeking contradictions and differences of opinion among authors. He confronts them with the oral information collected thanks to a wide network of contacts. PMID:26529894

  1. [The Arabic influence in the "Colóquios dos simples e drogas da India" of Garcia da Orta].

    PubMed

    Ricordel, Joëlle

    2015-09-01

    The "Colóquios dos simples e drogas he cousas medicinais de Índia" (Conversations on the simples, drugs and medicinal substances of India) (1563) of Garcia da Orta is a botanical and pharmacognosy book. The author is a Portuguese physician who studied in the Spanish universities and practiced medicine mainly in India. He studies in short chapters presented in the form of dialogues about sixty simples. Sources to which he refers are indicative of a "classical" training, but also the mark of a curious and open mind to different cultures. The Arabic sources are numerous and mainly concern the identification of substances by abundant synonyms of their names in foreign languages and different medicinal uses that may have been done by the ancient physicians. However, Da Orta is critical with respect to these sources, seeking contradictions and differences of opinion among authors. He confronts them with the oral information collected thanks to a wide network of contacts.

  2. Another new and threatened species of lancehead genus Bothrops (Serpentes, Viperidae) from Ilha dos Franceses, Southeastern Brazil.

    PubMed

    Barbo, Fausto E; Gasparini, João Luiz; Almeida, Antonio P; Zaher, Hussam; Grazziotin, Felipe G; Gusmão, Rodrigo B; Ferrarini, José Mário G; Sawaya, Ricardo J

    2016-01-01

    A new insular species of the genus Bothrops is described from Ilha dos Franceses, a small island off the coast of Espírito Santo State, in southeastern Brazil. The new species differs from mainland populations of B. jararaca mainly by its small size, relative longer tail, relative smaller head length, and relative larger eyes. The new species is distinguished from B. alcatraz, B. insularis and B. otavioi by the higher number of ventral and subcaudal scales, relative longer tail and smaller head. The new species is highly abundant on the island, being nocturnal, semiarboreal, and feeding on small lizards and centipeds. Due its unique and restricted area of occurrence, declining quality of habitat, and constant use of the island for tourism, the new species may be considered as critically endangered. PMID:27394563

  3. NGC 2287: Un cúmulo abierto rico en binarias espectroscópicas de dos espectros

    NASA Astrophysics Data System (ADS)

    Levato, H.; Malaroda, S.; García, B.; Grosso, M.

    NGC 2287 contiene 100 estrellas con buena fotometría y 40 con tipos MK. En 1979 Levato et al., usando la técnica de la clasificación espectral, descubrieron que la mayoría de las estrellas en el rango B8-A0 eran binarias espectroscópicas con una inusual proporción de binarias con dos espectros. El presente proyecto tuvo el propósito de confirmar la naturaleza binaria de los miembros del cúmulo. Hemos obtenido espectros con resolución 14000 de 15 estrellas clasificadas como binarias. Los espectros, que abarcan la región λ 3500-λ 6000 Å, permitieron confirmar la naturaleza binaria de varias de las estrellas en la muestra. Hacemos notar el considerable interés astrofísico de este cúmulo abierto.

  4. Candidate gene prioritization with Endeavour

    PubMed Central

    Tranchevent, Léon-Charles; Ardeshirdavani, Amin; ElShal, Sarah; Alcaide, Daniel; Aerts, Jan; Auboeuf, Didier; Moreau, Yves

    2016-01-01

    Genomic studies and high-throughput experiments often produce large lists of candidate genes among which only a small fraction are truly relevant to the disease, phenotype or biological process of interest. Gene prioritization tackles this problem by ranking candidate genes by profiling candidates across multiple genomic data sources and integrating this heterogeneous information into a global ranking. We describe an extended version of our gene prioritization method, Endeavour, now available for six species and integrating 75 data sources. The performance (Area Under the Curve) of Endeavour on cross-validation benchmarks using ‘gold standard’ gene sets varies from 88% (for human phenotypes) to 95% (for worm gene function). In addition, we have also validated our approach using a time-stamped benchmark derived from the Human Phenotype Ontology, which provides a setting close to prospective validation. With this benchmark, using 3854 novel gene–phenotype associations, we observe a performance of 82%. Altogether, our results indicate that this extended version of Endeavour efficiently prioritizes candidate genes. The Endeavour web server is freely available at https://endeavour.esat.kuleuven.be/. PMID:27131783

  5. Nonadditive gene expression in polyploids.

    PubMed

    Yoo, Mi-Jeong; Liu, Xiaoxian; Pires, J Chris; Soltis, Pamela S; Soltis, Douglas E

    2014-01-01

    Allopolyploidy involves hybridization and duplication of divergent parental genomes and provides new avenues for gene expression. The expression levels of duplicated genes in polyploids can show deviation from parental additivity (the arithmetic average of the parental expression levels). Nonadditive expression has been widely observed in diverse polyploids and comprises at least three possible scenarios: (a) The total gene expression level in a polyploid is similar to that of one of its parents (expression-level dominance); (b) total gene expression is lower or higher than in both parents (transgressive expression); and (c) the relative contribution of the parental copies (homeologs) to the total gene expression is unequal (homeolog expression bias). Several factors may result in expression nonadditivity in polyploids, including maternal-paternal influence, gene dosage balance, cis- and/or trans-regulatory networks, and epigenetic regulation. As our understanding of nonadditive gene expression in polyploids remains limited, a new generation of investigators should explore additional phenomena (i.e., alternative splicing) and use other high-throughput "omics" technologies to measure the impact of nonadditive expression on phenotype, proteome, and metabolome. PMID:25421600

  6. Simulating evolution by gene duplication.

    PubMed

    Ohta, T

    1987-01-01

    By considering the recent finding that unequal crossing over and other molecular interactions are contributing to the evolution of multigene families, a model of the origin of repetitive genes was studied by Monte Carlo simulations. Starting from a single gene copy, how genetic systems evolve was examined under unequal crossing over, random drift and natural selection. Both beneficial and deteriorating mutations were incorporated, and the latter were assumed to occur ten times more frequently than the former. Positive natural selection favors those chromosomes with more beneficial mutations in redundant copies than others in the population, but accumulation of deteriorating mutations (pseudogenes) have no effect on fitness so long as there remains a functional gene. The results imply the following: Positive natural selection is needed in order to acquire gene families with new functions. Without it, too many pseudogenes accumulate before attaining a functional gene family. There is a large fluctuation in the outcome even if parameters are the same. When unequal crossing over occurs more frequently, the system evolves more rapidly. It was also shown, under realistic values of parameters, that the genetic load for acquiring a new gene is not as large as J.B.S. Haldane suggested, but not so small as in a model in which a system for selection started from already redundant genes. PMID:3557113

  7. Linking Genes to Cardiovascular Diseases: Gene Action and Gene-Environment Interactions.

    PubMed

    Pasipoularides, Ares

    2015-12-01

    A unique myocardial characteristic is its ability to grow/remodel in order to adapt; this is determined partly by genes and partly by the environment and the milieu intérieur. In the "post-genomic" era, a need is emerging to elucidate the physiologic functions of myocardial genes, as well as potential adaptive and maladaptive modulations induced by environmental/epigenetic factors. Genome sequencing and analysis advances have become exponential lately, with escalation of our knowledge concerning sometimes controversial genetic underpinnings of cardiovascular diseases. Current technologies can identify candidate genes variously involved in diverse normal/abnormal morphomechanical phenotypes, and offer insights into multiple genetic factors implicated in complex cardiovascular syndromes. The expression profiles of thousands of genes are regularly ascertained under diverse conditions. Global analyses of gene expression levels are useful for cataloging genes and correlated phenotypes, and for elucidating the role of genes in maladies. Comparative expression of gene networks coupled to complex disorders can contribute insights as to how "modifier genes" influence the expressed phenotypes. Increasingly, a more comprehensive and detailed systematic understanding of genetic abnormalities underlying, for example, various genetic cardiomyopathies is emerging. Implementing genomic findings in cardiology practice may well lead directly to better diagnosing and therapeutics. There is currently evolving a strong appreciation for the value of studying gene anomalies, and doing so in a non-disjointed, cohesive manner. However, it is challenging for many-practitioners and investigators-to comprehend, interpret, and utilize the clinically increasingly accessible and affordable cardiovascular genomics studies. This survey addresses the need for fundamental understanding in this vital area.

  8. Application of geostatistical methods to arsenic data from soil samples of the Cova dos Mouros mine (Vila Verde-Portugal).

    PubMed

    Reis, A P; Sousa, A J; Da Silva, E Ferreira; Fonseca, E Cardoso

    2005-09-01

    A total of 286 soil samples were collected in the Cova dos Mouros area. All samples were dry sieved into the <200 mesh size fraction and analysed for Fe, Cu, Zn, Pb, Co, Ni, Bi and Mn by atomic absorption spectrometry (AAS) and for As, Se, Sb and Te by atomic absorption spectrometry-hydrid generation (AAS-HG). Only the results of arsenic are discussed in this paper although the survey was extended to all analysed chemical elements. The purpose of this study was to make a risk probability mapping for arsenic that would allow better knowledge about the vulnerability of the soil to arsenic contamination. To achieve this purpose, the initial variable was transformed into an indicator variable using as thresholds the risk-based standards (intervention values) for soils, as proposed by [Swartjes 1999. Risk based assessment of soil and groundwater quality in the Netherlands: Standards and remediation. J. Geochem. Explor.73 1-10]. To account for spatial structure, sample variograms were computed for the main directions of the sampling grid and a spherical model was fitted to each sample variogram (arsenic variable and indicator variables). The parameters of the spherical model fitted to the arsenic variable were used to predict arsenic concentrations at unsampled locations. A risk probability mapping was also done to assess the vulnerability of the soil towards the mining works. The parameters of the spherical model fitted to each indicator variable were used to estimate probabilities of exceeding the corresponding threshold. The use of indicator kriging as an alternative to ordinary kriging for the soil data of Cova dos Mouros produced unbiased probability maps that allowed assessment of the quality of the soil.

  9. GenePRIMP: A GENE PRediction IMprovement Pipeline for Prokaryotic genomes

    SciTech Connect

    Pati, Amrita; Ivanova, Natalia N.; Mikhailova, Natalia; Ovchinnikova, Galina; Hooper, Sean D.; Lykidis, Athanasios; Kyrpides, Nikos C.

    2010-04-01

    We present 'gene prediction improvement pipeline' (GenePRIMP; http://geneprimp.jgi-psf.org/), a computational process that performs evidence-based evaluation of gene models in prokaryotic genomes and reports anomalies including inconsistent start sites, missed genes and split genes. We found that manual curation of gene models using the anomaly reports generated by GenePRIMP improved their quality, and demonstrate the applicability of GenePRIMP in improving finishing quality and comparing different genome-sequencing and annotation technologies.

  10. [Gene doping: gene transfer and possible molecular detection].

    PubMed

    Argüelles, Carlos Francisco; Hernández-Zamora, Edgar

    2007-01-01

    The use of illegal substances in sports to enhance athletic performance during competition has caused international sports organizations such as the COI and WADA to take anti doping measures. A new doping method know as gene doping is defined as "the non-therapeutic use of genes, genetic elements and/or cells that have the capacity to enhance athletic performance". However, gene doping in sports is not easily identified and can cause serious consequences. Molecular biology techniques are needed in order to distinguish the difference between a "normal" and an "altered" genome. Further, we need to develop new analytic methods and biological molecular techniques in anti-doping laboratories, and design programs that avoid the non therapeutic use of genes.

  11. BRCA1 and BRCA2 gene testing

    MedlinePlus

    ... gov/ency/patientinstructions/000690.htm BRCA1 and BRCA2 gene testing To use the sharing features on this ... br east ca ncer. What is the BRCA Gene Mutation? BRCA1 and BRCA2 are genes that suppress ...

  12. [Pathogenicity and pneumococcal capsular genes].

    PubMed

    García, E; García, P; López, R

    1994-01-01

    Pneumococci remain to be one of the most prominent human pathogens. Increasing efforts are being dedicated to the development of improved vaccines with wider specificity. Since a clear understanding of the genetics of capsular types in Streptococcus pneumoniae is missing, our efforts are oriented to characterize, at the molecular level, the genes involved in capsular polysaccharide biosynthesis. We have cloned and sequenced a chromosomal DNA fragment of a clinical isolate of type 3 pneumococcus and showed that it contains a type 3 specific gene as well as genes common to other serotypes.

  13. The design of synthetic genes.

    PubMed Central

    Presnell, S R; Benner, S A

    1988-01-01

    Computer programs are described that aid in the design of synthetic genes coding for proteins that are targets of a research program in site directed mutagenesis. These programs "reverse-translate" protein sequences into general nucleic acid sequences (those where codons have not yet been selected), map restriction sites into general DNA sequences, identify points in the synthetic gene where unique restriction sites can be introduced, and assist in the design of genes coding for hybrids and evolutionary intermediates between homologous proteins. Application of these programs therefore facilitates the use of modular mutagenesis to create variants of proteins, and the implementation of evolutionary guidance as a strategy for selecting mutants. PMID:2451218

  14. The hunt for gene dopers.

    PubMed

    Mansour, Mai M H; Azzazy, Hassan M E

    2009-07-01

    Gene doping, the abuse of gene therapy for illicit athletic enhancement, is perceived as a coming threat and is a prime concern to the anti-doping community. This doping technique represents a significant ethical challenge and there are concerns regarding its safety for athletes. This article presents the basics of gene doping, potential strategies for its detection and the role of promising new technologies in aiding detection efforts. These include the use of lab-on-a-chip techniques as well as nanoparticles to enhance the performance of current analytical methods and to develop new doping detection strategies. PMID:20355209

  15. Gene expression and fractionation resistance

    PubMed Central

    2014-01-01

    Background Previous work on whole genome doubling in plants established the importance of gene functional category in provoking or suppressing duplicate gene loss, or fractionation. Other studies, particularly in Paramecium have correlated levels of gene expression with vulnerability or resistance to duplicate loss. Results Here we analyze the simultaneous effect of function category and expression in two plant data sets, rosids and asterids. Conclusion We demonstrate function category and expression level have independent effects, though expression does not play the dominant role it does in Paramecium. PMID:25573431

  16. The Ensembl gene annotation system.

    PubMed

    Aken, Bronwen L; Ayling, Sarah; Barrell, Daniel; Clarke, Laura; Curwen, Valery; Fairley, Susan; Fernandez Banet, Julio; Billis, Konstantinos; García Girón, Carlos; Hourlier, Thibaut; Howe, Kevin; Kähäri, Andreas; Kokocinski, Felix; Martin, Fergal J; Murphy, Daniel N; Nag, Rishi; Ruffier, Magali; Schuster, Michael; Tang, Y Amy; Vogel, Jan-Hinnerk; White, Simon; Zadissa, Amonida; Flicek, Paul; Searle, Stephen M J

    2016-01-01

    The Ensembl gene annotation system has been used to annotate over 70 different vertebrate species across a wide range of genome projects. Furthermore, it generates the automatic alignment-based annotation for the human and mouse GENCODE gene sets. The system is based on the alignment of biological sequences, including cDNAs, proteins and RNA-seq reads, to the target genome in order to construct candidate transcript models. Careful assessment and filtering of these candidate transcripts ultimately leads to the final gene set, which is made available on the Ensembl website. Here, we describe the annotation process in detail.Database URL: http://www.ensembl.org/index.html. PMID:27337980

  17. Gene therapy: proceed with caution.

    PubMed

    Grobstein, C; Flower, M

    1984-04-01

    On 6 February 1984 the Recombinant DNA Advisory Committee of the National Institutes of Health approved a recommendation that the committee provide prior review of research protocols involving human gene therapy. Grobstein and Flower trace the development of public policy in response to concerns about the dangers of gene therapy, especially as it applies to germ line alteration. They offer guidelines and propose principles for an oversight body to confront the immediate and long term technical, social, and ethical implications of human genetic modification. An accompanying article presents a plea for the development of gene therapy by the mother of three children who have sickle cell anemia.

  18. Panspermia and horizontal gene transfer

    NASA Astrophysics Data System (ADS)

    Klyce, Brig

    2009-08-01

    Evidence that extremophiles are hardy and ubiquitous is helping to make panspermia a respectable theory. But even if life on Earth originally came from space, biologists assume that the subsequent evolution of life is still governed by the darwinian paradigm. In this review we show how panspermia could amend darwinism and point to a cosmic source for, not only extremophiles but, all of life. This version of panspermia can be called "strong panspermia." To support this theory we will discuss recent evidence pertaining to horizontal gene transfer, viruses, genes apparently older than the Earthly evolution of the features they encode, and primate-specific genes without identifiable precursors.

  19. The Ensembl gene annotation system

    PubMed Central

    Aken, Bronwen L.; Ayling, Sarah; Barrell, Daniel; Clarke, Laura; Curwen, Valery; Fairley, Susan; Fernandez Banet, Julio; Billis, Konstantinos; García Girón, Carlos; Hourlier, Thibaut; Howe, Kevin; Kähäri, Andreas; Kokocinski, Felix; Martin, Fergal J.; Murphy, Daniel N.; Nag, Rishi; Ruffier, Magali; Schuster, Michael; Tang, Y. Amy; Vogel, Jan-Hinnerk; White, Simon; Zadissa, Amonida; Flicek, Paul

    2016-01-01

    The Ensembl gene annotation system has been used to annotate over 70 different vertebrate species across a wide range of genome projects. Furthermore, it generates the automatic alignment-based annotation for the human and mouse GENCODE gene sets. The system is based on the alignment of biological sequences, including cDNAs, proteins and RNA-seq reads, to the target genome in order to construct candidate transcript models. Careful assessment and filtering of these candidate transcripts ultimately leads to the final gene set, which is made available on the Ensembl website. Here, we describe the annotation process in detail. Database URL: http://www.ensembl.org/index.html PMID:27337980

  20. Saporin as a novel suicide gene in anticancer gene therapy.

    PubMed

    Zarovni, N; Vago, R; Soldà, T; Monaco, L; Fabbrini, M S

    2007-02-01

    We used a non-viral gene delivery approach to explore the potential of the plant saporin (SAP) gene as an alternative to the currently employed suicide genes in cancer therapy. Plasmids expressing cytosolic SAP were generated by placing the region encoding the mature plant ribosome-inactivating protein under the control of cytomegalovirus (CMV) or simian virus 40 (SV40) promoters. Their ability to inhibit protein synthesis was first tested in cultured tumor cells co-transfected with a luciferase reporter gene. In particular, SAP expression driven by CMV promoter (pCI-SAP) demonstrated that only 10 ng of plasmid per 1.6 x 10(4) B16 cells drastically reduced luciferase activity to 18% of that in control cells. Direct intratumoral injection of pCI-SAP complexed with either lipofectamine or N-(2,3-dioleoyloxy-1-propyl) trimethylammonium methyl sulfate (DOTAP) in B16 melanoma-bearing mice resulted in a noteworthy attenuation of tumor growth. This antitumor effect was increased in mice that received repeated intratumoral injections. A SAP catalytic inactive mutant (SAP-KQ) failed to exert any antitumor effect demonstrating that this was specifically owing to the SAP N-glycosidase activity. Our overall data strongly suggest that the gene encoding SAP, owing to its rapid and effective action and its independence from the proliferative state of target cells might become a suitable candidate suicide gene for oncologic applications. PMID:17008932

  1. Gene amplification and insecticide resistance.

    PubMed

    Bass, Chris; Field, Linda M

    2011-08-01

    Pesticide resistance in arthropods has been shown to evolve by two main mechanisms, the enhanced production of metabolic enzymes, which bind to and/or detoxify the pesticide, and mutation of the target protein, which makes it less sensitive to the pesticide. One route that leads to enhanced metabolism is the duplication or amplification of the structural gene(s) encoding the detoxifying enzyme, and this has now been described for the three main families (esterases, glutathione S-transferases and cytochrome P450 monooxygenases) implicated in resistance. More recently, a direct or indirect role for gene duplication or amplification has been described for target-site resistance in several arthropod species. This mini-review summarises the involvement of gene duplication/amplification in the insecticide/acaricide resistance of insect and mite pests and highlights recent developments in this area in relation to P450-mediated and target-site resistance.

  2. Gene Cernan on Apollo 17

    NASA Video Gallery

    Apollo 17 Commander Gene Cernan recalls fixing a lunar rover problem with duct tape during his December 1972 mission. Cernan's interview was part of the commemoration of NASA's 50th anniversary in ...

  3. Autophagy Genes as Tumor Suppressors

    PubMed Central

    Liang, Chengyu; Jung, Jae U.

    2009-01-01

    Autophagy, originally described as a universal lysosome-dependent bulk degradation of cytoplasmic components upon nutrient deprivation, has since been shown to influence diverse aspects of homeostasis and is implicated in a wide variety of pathological conditions, including cancer. The list of autophagy-related (Atg) genes associated with the initiation and progression of human cancer as well as with responses to cancer therapy continues to grow as these genes are being discovered. However, whether Atg genes work through their expected mechanisms of autophagy regulation and/or through as-yet-undefined functions in the development of cancer remains to be further clarified. Here we review recent advances in the knowledge of the molecular basis of autophagy genes and their biological outputs during tumor development. A better understanding of the mechanistic link between cellular autophagy and tumor growth control may ultimately better human cancer treatments. PMID:19945837

  4. Gene flow and population differentiation.

    PubMed

    Endler, J A

    1973-01-19

    There are many possible spatial patterns of selection and gene flow that can produce a given cline structure; the actual geography of natural selection and gene flow must be worked out before an attempt is made to explain a given natural cline in terms of a model. The results of experimental and theoretical models show that it is possible for local differentiation to evolve parapatrically in spite of considerable gene flow if the selection gradients are relatively uniform. Irregularities in environmental gradients increase the sensitivity of clines to the effects of gene flow in proportion to the increase in the differences in gene frequencies between the emigrants and the demes receiving the immigrants. It is not necessary for a sharp spatial environmental change to be present for distinct differentiation to occur. In some cases even a gentle environmental gradient can give rise to marked spatial differentiation along a genetically continuous series of demes; such environmental differences may be below the practical limits of resolution in field studies. Any asymmetry in gene flow does not lead to dedifferentiation if the environmental gradient is smooth; it merely shifts the position of the transition zone between the differentiated areas from that which would be expected if there were no asymmetry. Abrupt geographic differences in gene, genotype, or morph frequencies should not, therefore, be interpreted as evidence for environmental changes in the immediate vicinity of the steepest part of the cline; neither should they be interpreted as evidence for geographic barriers, sharp environmental differences, or sexual isolation among the differentiated groups of populations when there are no other sources of evidence for these phenomena. Gene flow may be unimportant in the differentiation of populations along environmental gradients.

  5. Gene therapy and nasopharyngeal carcinoma.

    PubMed

    Hughes, J; Alusi, G; Wang, Y

    2012-06-01

    In 2003, a non-replicating adenoviral gene therapy product received the world`s first government licence for the treatment of head and neck cancer. Two years later approval was granted to a replication-selective adenovirus for the treatment of nasopharyngeal carcinoma in combination with chemotherapy. This review introduces the reader to gene therapy as an emerging treatment modality, and outlines its application to the management of nasopharyngeal carcinoma by examining recent pre-clinical and clinical research.

  6. Gene Transfer into Cardiac Myocytes

    PubMed Central

    Lang, Sarah E.; Westfall, Margaret V.

    2016-01-01

    Traditional methods for DNA transfection are often inefficient and toxic for terminally differentiated cells, such as cardiac myocytes. Vector-based gene transfer is an efficient approach for introducing exogenous cDNA into these types of primary cell cultures. In this chapter, separate protocols for adult rat cardiac myocyte isolation and gene transfer with recombinant adenovirus are provided and are routinely utilized for studying the effects of sarcomeric proteins on myofilament function. PMID:25836585

  7. Transgenic Arabidopsis Gene Expression System

    NASA Technical Reports Server (NTRS)

    Ferl, Robert; Paul, Anna-Lisa

    2009-01-01

    The Transgenic Arabidopsis Gene Expression System (TAGES) investigation is one in a pair of investigations that use the Advanced Biological Research System (ABRS) facility. TAGES uses Arabidopsis thaliana, thale cress, with sensor promoter-reporter gene constructs that render the plants as biomonitors (an organism used to determine the quality of the surrounding environment) of their environment using real-time nondestructive Green Fluorescent Protein (GFP) imagery and traditional postflight analyses.

  8. Gene-culture coevolution between cattle milk protein genes and human lactase genes.

    PubMed

    Beja-Pereira, Albano; Luikart, Gordon; England, Phillip R; Bradley, Daniel G; Jann, Oliver C; Bertorelle, Giorgio; Chamberlain, Andrew T; Nunes, Telmo P; Metodiev, Stoitcho; Ferrand, Nuno; Erhardt, Georg

    2003-12-01

    Milk from domestic cows has been a valuable food source for over 8,000 years, especially in lactose-tolerant human societies that exploit dairy breeds. We studied geographic patterns of variation in genes encoding the six most important milk proteins in 70 native European cattle breeds. We found substantial geographic coincidence between high diversity in cattle milk genes, locations of the European Neolithic cattle farming sites (>5,000 years ago) and present-day lactose tolerance in Europeans. This suggests a gene-culture coevolution between cattle and humans.

  9. Nutritional regulation of gene expression.

    PubMed

    Cousins, R J

    1999-01-25

    Genes are regulated by complex arrays of response elements that influence the rate of transcription. Nutrients and hormones either act directly to influence these rates or act indirectly through specialized signaling pathways. Metabolites of vitamins A and D, fatty acids, some sterols, and zinc are among the nutrients that influence transcription directly. Components of dietary fiber may influence gene expression indirectly through changes in hormonal signaling, mechanical stimuli, and metabolites produced by the intestinal microflora. In addition, consumption of water-soluble fibers may lead to changes in gene expression mediated through indirect mechanisms that influence transcription rates. In the large intestine, short-chain fatty acids, including butyric acid, are produced by microflora. Butyric acid can indirectly influence gene expression. Some sources of fiber limit nutrient absorption, particularly of trace elements. This could have direct or indirect effects on gene expression. Identification of genes in colonic epithelial cells that are differentially regulated by dietary fiber will be an important step toward understanding the role of dietary factors in colorectal cancer progression.

  10. Homologous gene replacement in Physarum

    SciTech Connect

    Burland, T.G.; Pallotta, D.

    1995-01-01

    The protist Physarum polycephalum is useful for analysis of several aspects of cellular and developmental biology. To expand the opportunities for experimental analysis of this organism, we have developed a method for gene replacement. We transformed Physarum amoebae with plasmid DNA carrying a mutant allele, ardD{Delta}1, of the ardD actin gene; ardD{Delta}1 mutates the critical carboxy-terminal region of the gene product. Because ardD is not expressed in the amoeba, replacement of ardD{sup +} with ardD{Delta}1 should not be lethal for this cell type. Transformants were obtained only when linear plasmid DNA was used. Most transformants carried one copy of ardD{Delta}1 in addition to ardD{sup +}, but in two (5%), ardD{sup +} was replaced by a single copy of ardD{Delta}1. This is the first example of homologous gene replacement in Physarum. ardD{Delta}1 was stably maintained in the genome through growth, development and meiosis. We found no effect of ardD{Delta}l on viability, growth, or development of any of the various cell types of Physarum. Thus, the carboxy-terminal region of the ardD product appears not to perform a unique essential role in growth or development. Nevertheless, this method for homologous gene replacement can be applied to analyze the function of any cloned gene. 38 refs., 6 figs., 1 tab.

  11. Gene Polymorphisms in Chronic Periodontitis

    PubMed Central

    Laine, Marja L.; Loos, Bruno G.; Crielaard, W.

    2010-01-01

    We aimed to conduct a review of the literature for gene polymorphisms associated with chronic periodontitis (CP) susceptibility. A comprehensive search of the literature in English was performed using the keywords: periodontitis, periodontal disease, combined with the words genes, mutation, or polymorphism. Candidate gene polymorphism studies with a case-control design and reported genotype frequencies in CP patients were searched and reviewed. There is growing evidence that polymorphisms in the IL1, IL6, IL10, vitamin D receptor, and CD14 genes may be associated with CP in certain populations. However, carriage rates of the rare (R)-allele of any polymorphism varied considerably among studies and most of the studies appeared under-powered and did not correct for other risk factors. Larger cohorts, well-defined phenotypes, control for other risk factors, and analysis of multiple genes and polymorphisms within the same pathway are needed to get a more comprehensive insight into the contribution of gene polymorphisms in CP. PMID:20339487

  12. Cationic Bolaamphiphiles for Gene Delivery

    NASA Astrophysics Data System (ADS)

    Tan, Amelia Li Min; Lim, Alisa Xue Ling; Zhu, Yiting; Yang, Yi Yan; Khan, Majad

    2014-05-01

    Advances in medical research have shed light on the genetic cause of many human diseases. Gene therapy is a promising approach which can be used to deliver therapeutic genes to treat genetic diseases at its most fundamental level. In general, nonviral vectors are preferred due to reduced risk of immune response, but they are also commonly associated with low transfection efficiency and high cytotoxicity. In contrast to viral vectors, nonviral vectors do not have a natural mechanism to overcome extra- and intracellular barriers when delivering the therapeutic gene into cell. Hence, its design has been increasingly complex to meet challenges faced in targeting of, penetration of and expression in a specific host cell in achieving more satisfactory transfection efficiency. Flexibility in design of the vector is desirable, to enable a careful and controlled manipulation of its properties and functions. This can be met by the use of bolaamphiphile, a special class of lipid. Unlike conventional lipids, bolaamphiphiles can form asymmetric complexes with the therapeutic gene. The advantage of having an asymmetric complex lies in the different purposes served by the interior and exterior of the complex. More effective gene encapsulation within the interior of the complex can be achieved without triggering greater aggregation of serum proteins with the exterior, potentially overcoming one of the great hurdles faced by conventional single-head cationic lipids. In this review, we will look into the physiochemical considerations as well as the biological aspects of a bolaamphiphile-based gene delivery system.

  13. PET genes of Saccharomyces cerevisiae.

    PubMed Central

    Tzagoloff, A; Dieckmann, C L

    1990-01-01

    We describe a collection of nuclear respiratory-defective mutants (pet mutants) of Saccharomyces cerevisiae consisting of 215 complementation groups. This set of mutants probably represents a substantial fraction of the total genetic information of the nucleus required for the maintenance of functional mitochondria in S. cerevisiae. The biochemical lesions of mutants in approximately 50 complementation groups have been related to single enzymes or biosynthetic pathways, and the corresponding wild-type genes have been cloned and their structures have been determined. The genes defined by an additional 20 complementation groups were identified by allelism tests with mutants characterized in other laboratories. Mutants representative of the remaining complementation groups have been assigned to one of the following five phenotypic classes: (i) deficiency in cytochrome oxidase, (ii) deficiency in coenzyme QH2-cytochrome c reductase, (iii) deficiency in mitochondrial ATPase, (iv) absence of mitochondrial protein synthesis, and (v) normal composition of respiratory-chain complexes and of oligomycin-sensitive ATPase. In addition to the genes identified through biochemical and genetic analyses of the pet mutants, we have cataloged PET genes not matched to complementation groups in the mutant collection and other genes whose products function in the mitochondria but are not necessary for respiration. Together, this information provides an up-to-date list of the known genes coding for mitochondrial constituents and for proteins whose expression is vital for the respiratory competence of S. cerevisiae. PMID:2215420

  14. Gene-gene, gene-environment, gene-nutrient interactions and single nucleotide polymorphisms of inflammatory cytokines.

    PubMed

    Nadeem, Amina; Mumtaz, Sadaf; Naveed, Abdul Khaliq; Aslam, Muhammad; Siddiqui, Arif; Lodhi, Ghulam Mustafa; Ahmad, Tausif

    2015-05-15

    Inflammation plays a significant role in the etiology of type 2 diabetes mellitus (T2DM). The rise in the pro-inflammatory cytokines is the essential step in glucotoxicity and lipotoxicity induced mitochondrial injury, oxidative stress and beta cell apoptosis in T2DM. Among the recognized markers are interleukin (IL)-6, IL-1, IL-10, IL-18, tissue necrosis factor-alpha (TNF-α), C-reactive protein, resistin, adiponectin, tissue plasminogen activator, fibrinogen and heptoglobins. Diabetes mellitus has firm genetic and very strong environmental influence; exhibiting a polygenic mode of inheritance. Many single nucleotide polymorphisms (SNPs) in various genes including those of pro and anti-inflammatory cytokines have been reported as a risk for T2DM. Not all the SNPs have been confirmed by unifying results in different studies and wide variations have been reported in various ethnic groups. The inter-ethnic variations can be explained by the fact that gene expression may be regulated by gene-gene, gene-environment and gene-nutrient interactions. This review highlights the impact of these interactions on determining the role of single nucleotide polymorphism of IL-6, TNF-α, resistin and adiponectin in pathogenesis of T2DM. PMID:25987962

  15. Immunoglobulin genes of the turtles.

    PubMed

    Magadán-Mompó, Susana; Sánchez-Espinel, Christian; Gambón-Deza, Francisco

    2013-03-01

    The availability of reptile genomes for the use of the scientific community is an exceptional opportunity to study the evolution of immunoglobulin genes. The genome of Chrysemys picta bellii and Pelodiscus sinensis is the first one that has been reported for turtles. The scanning for immunoglobulin genes resulted in the presence of a complex locus for the immunoglobulin heavy chain (IGH). This IGH locus in both turtles contains genes for 13 isotypes in C. picta bellii and 17 in P. sinensis. These correspond with one immunoglobulin M, one immunoglobulin D, several immunoglobulins Y (six in C. picta bellii and eight in P. sinensis), and several immunoglobulins that are similar to immunoglobulin D2 (five in C. picta belli and seven in P. sinensis) that was previously described in Eublepharis macularius. It is worthy to note that IGHD2 are placed in an inverted transcriptional orientation and present sequences for two immunoglobulin domains that are similar to bird IgA domains. Furthermore, its phylogenetic analysis allows us to consider about the presence of IGHA gene in a primitive reptile, so we would be dealing with the memory of the gene that originated from the bird IGHA. In summary, we provide a clear picture of the immunoglobulins present in a turtle, whose analysis supports the idea that turtles emerged from the evolutionary line from the differentiation of birds and the presence of the IGHA gene present in a common ancestor.

  16. Gene therapy for paediatric leukaemia.

    PubMed

    Rousseau, R F; Bollard, C M; Heslop, H E

    2001-07-01

    Improvements in the chemotherapeutic and transplant regimens have had a significant impact in improving survival rates for paediatric leukaemia. However, there are still important problems to address including what options are available for patients with chemoresistant disease and what strategies are available to avoid the concerns regarding the toxicity associated with highly cytotoxic treatment regimens. Gene therapy and immunotherapy protocols hold great promise. Using gene transfer of a marker gene, a number of biological issues in the therapy of leukaemia have been addressed. For example, by gene marking autologous bone marrow grafts it has been possible to demonstrate that infused marrow contributes to relapse in acute and chronic myeloid leukaemias. In the allogeneic transplant setting, genetically modified T-cells have proven valuable for the prophylaxis and treatment of viral diseases and may have an important role in preventing or treating disease relapse. Gene transfer is also being used to modify tumour function, enhance immunogenicity, and confer drug-resistance to normal haematopoietic stem cells. With the continued scientific advancements in this field, gene therapy will almost certainly have a major impact on the treatment of paediatric leukaemia in the future. PMID:11727502

  17. New gene evolution: little did we know.

    PubMed

    Long, Manyuan; VanKuren, Nicholas W; Chen, Sidi; Vibranovski, Maria D

    2013-01-01

    Genes are perpetually added to and deleted from genomes during evolution. Thus, it is important to understand how new genes are formed and how they evolve to be critical components of the genetic systems that determine the biological diversity of life. Two decades of effort have shed light on the process of new gene origination and have contributed to an emerging comprehensive picture of how new genes are added to genomes, ranging from the mechanisms that generate new gene structures to the presence of new genes in different organisms to the rates and patterns of new gene origination and the roles of new genes in phenotypic evolution. We review each of these aspects of new gene evolution, summarizing the main evidence for the origination and importance of new genes in evolution. We highlight findings showing that new genes rapidly change existing genetic systems that govern various molecular, cellular, and phenotypic functions.

  18. Homology-dependent Gene Silencing in Paramecium

    PubMed Central

    Ruiz, Françoise; Vayssié, Laurence; Klotz, Catherine; Sperling, Linda; Madeddu, Luisa

    1998-01-01

    Microinjection at high copy number of plasmids containing only the coding region of a gene into the Paramecium somatic macronucleus led to a marked reduction in the expression of the corresponding endogenous gene(s). The silencing effect, which is stably maintained throughout vegetative growth, has been observed for all Paramecium genes examined so far: a single-copy gene (ND7), as well as members of multigene families (centrin genes and trichocyst matrix protein genes) in which all closely related paralogous genes appeared to be affected. This phenomenon may be related to posttranscriptional gene silencing in transgenic plants and quelling in Neurospora and allows the efficient creation of specific mutant phenotypes thus providing a potentially powerful tool to study gene function in Paramecium. For the two multigene families that encode proteins that coassemble to build up complex subcellular structures the analysis presented herein provides the first experimental evidence that the members of these gene families are not functionally redundant. PMID:9529389

  19. OGEE: an online gene essentiality database.

    PubMed

    Chen, Wei-Hua; Minguez, Pablo; Lercher, Martin J; Bork, Peer

    2012-01-01

    OGEE is an Online GEne Essentiality database. Its main purpose is to enhance our understanding of the essentiality of genes. This is achieved by collecting not only experimentally tested essential and non-essential genes, but also associated gene features such as expression profiles, duplication status, conservation across species, evolutionary origins and involvement in embryonic development. We focus on large-scale experiments and complement our data with text-mining results. Genes are organized into data sets according to their sources. Genes with variable essentiality status across data sets are tagged as conditionally essential, highlighting the complex interplay between gene functions and environments. Linked tools allow the user to compare gene essentiality among different gene groups, or compare features of essential genes to non-essential genes, and visualize the results. OGEE is freely available at http://ogeedb.embl.de.

  20. PoplarGene: poplar gene network and resource for mining functional information for genes from woody plants.

    PubMed

    Liu, Qi; Ding, Changjun; Chu, Yanguang; Chen, Jiafei; Zhang, Weixi; Zhang, Bingyu; Huang, Qinjun; Su, Xiaohua

    2016-01-01

    Poplar is not only an important resource for the production of paper, timber and other wood-based products, but it has also emerged as an ideal model system for studying woody plants. To better understand the biological processes underlying various traits in poplar, e.g., wood development, a comprehensive functional gene interaction network is highly needed. Here, we constructed a genome-wide functional gene network for poplar (covering ~70% of the 41,335 poplar genes) and created the network web service PoplarGene, offering comprehensive functional interactions and extensive poplar gene functional annotations. PoplarGene incorporates two network-based gene prioritization algorithms, neighborhood-based prioritization and context-based prioritization, which can be used to perform gene prioritization in a complementary manner. Furthermore, the co-functional information in PoplarGene can be applied to other woody plant proteomes with high efficiency via orthology transfer. In addition to poplar gene sequences, the webserver also accepts Arabidopsis reference gene as input to guide the search for novel candidate functional genes in PoplarGene. We believe that PoplarGene (http://bioinformatics.caf.ac.cn/PoplarGene and http://124.127.201.25/PoplarGene) will greatly benefit the research community, facilitating studies of poplar and other woody plants. PMID:27515999

  1. PoplarGene: poplar gene network and resource for mining functional information for genes from woody plants

    PubMed Central

    Liu, Qi; Ding, Changjun; Chu, Yanguang; Chen, Jiafei; Zhang, Weixi; Zhang, Bingyu; Huang, Qinjun; Su, Xiaohua

    2016-01-01

    Poplar is not only an important resource for the production of paper, timber and other wood-based products, but it has also emerged as an ideal model system for studying woody plants. To better understand the biological processes underlying various traits in poplar, e.g., wood development, a comprehensive functional gene interaction network is highly needed. Here, we constructed a genome-wide functional gene network for poplar (covering ~70% of the 41,335 poplar genes) and created the network web service PoplarGene, offering comprehensive functional interactions and extensive poplar gene functional annotations. PoplarGene incorporates two network-based gene prioritization algorithms, neighborhood-based prioritization and context-based prioritization, which can be used to perform gene prioritization in a complementary manner. Furthermore, the co-functional information in PoplarGene can be applied to other woody plant proteomes with high efficiency via orthology transfer. In addition to poplar gene sequences, the webserver also accepts Arabidopsis reference gene as input to guide the search for novel candidate functional genes in PoplarGene. We believe that PoplarGene (http://bioinformatics.caf.ac.cn/PoplarGene and http://124.127.201.25/PoplarGene) will greatly benefit the research community, facilitating studies of poplar and other woody plants. PMID:27515999

  2. Murine erythropoietin gene: cloning, expression, and human gene homology.

    PubMed Central

    Shoemaker, C B; Mitsock, L D

    1986-01-01

    The gene for murine erythropoietin (EPO) was isolated from a mouse genomic library with a human EPO cDNA probe. Nucleotide sequence analysis permitted the identification of the murine EPO coding sequence and the prediction of the encoded amino acid sequence based on sequence conservation between the mouse and human EPO genes. Both the coding DNA and the amino acid sequences were 80% conserved between the two species. Transformation of COS-1 cells with a mammalian cell expression vector containing the murine EPO coding region resulted in secretion of murine EPO with biological activity on both murine and human erythroid progenitor cells. The transcription start site for the murine EPO gene in kidneys was determined. This permitted tentative identification of the transcription control region. The region included 140 base pairs upstream of the cap site which was over 90% conserved between the murine and human genes. Surprisingly, the first intron and much of the 5'- and 3'-untranslated sequences were also substantially conserved between the genes of the two species. Images PMID:3773894

  3. Newer gene editing technologies toward HIV gene therapy.

    PubMed

    Manjunath, N; Yi, Guohua; Dang, Ying; Shankar, Premlata

    2013-11-01

    Despite the great success of highly active antiretroviral therapy (HAART) in ameliorating the course of HIV infection, alternative therapeutic approaches are being pursued because of practical problems associated with life-long therapy. The eradication of HIV in the so-called "Berlin patient" who received a bone marrow transplant from a CCR5-negative donor has rekindled interest in genome engineering strategies to achieve the same effect. Precise gene editing within the cells is now a realistic possibility with recent advances in understanding the DNA repair mechanisms, DNA interaction with transcription factors and bacterial defense mechanisms. Within the past few years, four novel technologies have emerged that can be engineered for recognition of specific DNA target sequences to enable site-specific gene editing: Homing Endonuclease, ZFN, TALEN, and CRISPR/Cas9 system. The most recent CRISPR/Cas9 system uses a short stretch of complementary RNA bound to Cas9 nuclease to recognize and cleave target DNA, as opposed to the previous technologies that use DNA binding motifs of either zinc finger proteins or transcription activator-like effector molecules fused to an endonuclease to mediate sequence-specific DNA cleavage. Unlike RNA interference, which requires the continued presence of effector moieties to maintain gene silencing, the newer technologies allow permanent disruption of the targeted gene after a single treatment. Here, we review the applications, limitations and future prospects of novel gene-editing strategies for use as HIV therapy.

  4. Noninvasive Tracking of Gene Transcript and Neuroprotection after Gene Therapy

    PubMed Central

    Ren, Jiaqian; Chen, Y. Iris; Liu, Christina H.; Chen, Po-Chih; Prentice, Howard; Wu, Jang-Yen; Liu, Philip K.

    2015-01-01

    Gene therapy holds exceptional potential for translational medicine by improving the products of defective genes in diseases and/or providing necessary biologics from endogenous sources during recovery processes. However, validating methods for the delivery, distribution and expression of the exogenous genes from such therapy can generally not be applicable to monitor effects over the long term because they are invasive. We report here that human granulocyte colony-stimulating factor (hG-CSF) cDNA encoded in scAAV-type 2 adeno-associated virus, as delivered through eye drops at multiple time points after cerebral ischemia using bilateral carotid occlusion for 60 min (BCAO-60) led to significant reduction in mortality rates, cerebral atrophy, and neurological deficits in C57black6 mice. Most importantly, we validated hG-CSF cDNA expression using translatable magnetic resonance imaging (MRI) in living brains. This noninvasive approach for monitoring exogenous gene expression in the brains has potential for great impact in the area of experimental gene therapy in animal models of heart attack, stroke, Alzheimer’s dementia, Parkinson’s disorder and amyotrophic lateral sclerosis, and the translation of such techniques to emergency medicine. PMID:26207935

  5. [Developments in gene delivery vectors for ocular gene therapy].

    PubMed

    Khabou, Hanen; Dalkara, Deniz

    2015-05-01

    Gene therapy is quickly becoming a reality applicable in the clinic for inherited retinal diseases. Its remarkable success in safety and efficacy, in clinical trials for Leber's congenital amaurosis (LCA) type II generated significant interest and opened up possibilities for a new era of retinal gene therapies. Success in these clinical trials was mainly due to the favorable characteristics of the retina as a target organ. The eye offers several advantages as it is readily accessible and has some degree of immune privilege making it suitable for application of viral vectors. The viral vectors most frequently used for retinal gene delivery are lentivirus, adenovirus and adeno-associated virus (AAV). Here we will discuss the use of these viral vectors in retinal gene delivery with a strong focus on favorable properties of AAV. Thanks to its small size, AAV diffuses well in the inter-neural matrix making it suitable for applications in neural retina. Building on this initial clinical success with LCA II, we have now many opportunities to extend this proof-of-concept to other retinal diseases using AAV as a vector. This article will discuss what are some of the most imminent cellular targets for such therapies and the AAV toolkit that has been built to target these cells successfully. We will also discuss some of the challenges that we face in translating AAV-based gene therapies to the clinic.

  6. The biology of novel animal genes: Mouse APEX gene knockout

    SciTech Connect

    MacInnes, M.; Altherr, M.R.; Ludwig, D.; Pedersen, R.; Mold, C.

    1997-07-01

    This is the final report of a one-year, Laboratory Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The controlled breeding of novel genes into mice, including the gene knockout (KO), or conversely by adding back transgenes provide powerful genetic technologies that together suffice to determine in large part the biological role(s) of novel genes. Inbred mouse remains the best understood and most useful mammalian experimental system available for tackling the biology of novel genes. The major mammalian apurinic/apyrimidinic (AP) endonuclease (APE), is involved in a key step in the repair of spontaneous and induced AP sites in DNA. Efficient repair of these lesions is imperative to prevent the stable incorporation of mutations into the cellular genome which may lead to cell death or transformation. Loss or modulation of base excison repair activity in vivo may elevate the spontaneous mutation rate in cells, and may lead to a substantial increase in the incidence of cancer. Despite extensive biochemical analysis, however, the significance of these individual APE functions in vivo has not been elucidated. Mouse embryonic stem (ES) cells heterozygous for a deletion mutation in APE have been generated and whole animals containing the APE mutation have been derived from these ES cells. Animals homozygous for the APE null mutation die early in gestation, underscoring the biological significance of this DNA repair gene.

  7. Newer Gene Editing Technologies toward HIV Gene Therapy

    PubMed Central

    Manjunath, N.; Yi, Guohua; Dang, Ying; Shankar, Premlata

    2013-01-01

    Despite the great success of highly active antiretroviral therapy (HAART) in ameliorating the course of HIV infection, alternative therapeutic approaches are being pursued because of practical problems associated with life-long therapy. The eradication of HIV in the so-called “Berlin patient” who received a bone marrow transplant from a CCR5-negative donor has rekindled interest in genome engineering strategies to achieve the same effect. Precise gene editing within the cells is now a realistic possibility with recent advances in understanding the DNA repair mechanisms, DNA interaction with transcription factors and bacterial defense mechanisms. Within the past few years, four novel technologies have emerged that can be engineered for recognition of specific DNA target sequences to enable site-specific gene editing: Homing Endonuclease, ZFN, TALEN, and CRISPR/Cas9 system. The most recent CRISPR/Cas9 system uses a short stretch of complementary RNA bound to Cas9 nuclease to recognize and cleave target DNA, as opposed to the previous technologies that use DNA binding motifs of either zinc finger proteins or transcription activator-like effector molecules fused to an endonuclease to mediate sequence-specific DNA cleavage. Unlike RNA interference, which requires the continued presence of effector moieties to maintain gene silencing, the newer technologies allow permanent disruption of the targeted gene after a single treatment. Here, we review the applications, limitations and future prospects of novel gene-editing strategies for use as HIV therapy. PMID:24284874

  8. Combining Hierarchical and Associative Gene Ontology Relations with Textual Evidence in Estimating Gene and Gene Product Similarity

    SciTech Connect

    Sanfilippo, Antonio P.; Posse, Christian; Gopalan, Banu; Riensche, Roderick M.; Beagley, Nathaniel; Baddeley, Bob L.; Tratz, Stephen C.; Gregory, Michelle L.

    2007-03-01

    Gene and gene product similarity is a fundamental diagnostic measure in analyzing biological data and constructing predictive models for functional genomics. With the rising influence of the Gene Ontology, two complementary approaches have emerged where the similarity between two genes or gene products is obtained by comparing Gene Ontology (GO) annotations associated with the genes or gene products. One approach captures GO-based similarity in terms of hierarchical relations within each gene subontology. The other approach identifies GO-based similarity in terms of associative relations across the three gene subontologies. We propose a novel methodology where the two approaches can be merged with ensuing benefits in coverage and accuracy, and demonstrate that further improvements can be obtained by integrating textual evidence extracted from relevant biomedical literature.

  9. Dynamics of the T cell response to Mycobacterium tuberculosis DosR and Rpf antigens in a Colombian population of household contacts of recently diagnosed pulmonary tuberculosis patients.

    PubMed

    Arroyo, Leonar; Rojas, Mauricio; Ortíz, Blanca L; Franken, Kees L M C; García, Luis F; Ottenhoff, Tom H M; Barrera, Luis F

    2016-03-01

    Immune response to DosR and Rpf antigens from Mycobacterium tuberculosis (Mtb) seems to be important for latency maintenance. Little is known about the dynamics of the immune response to these antigens in an endemic community. Thus, the IFNγ response and cytokine production in response to PPD, Esat6-Cfp10 (E6-C10), DosR and Rpf antigens in healthy HHC of tuberculosis (TB) patients over a 12 (T12) months period (short-term, stLTBI) was investigated. This response was compared with a group of LTBI, who have remained healthy for 5-7 years (long-term, ltLTBI). According to the IFNγ response, two groups of HHCs were identified in stLTBI in response to E6-C10. At T12, E6-C10(+) HHCs displayed a decrease in the IFNγ levels and a generalized decrease in cytokines production. The E6-C10(-) HHC showed an increase in the IFNγ response and cytokine levels. In stLTBI, the responses to E6-C10, DosR, and Rpf may be interpreted as a protective immune response controlling Mtb infection and may be leading to a state of latent infection. Comparing the response of stLTBI and ltLTBI, we observed significant changes in the proportions of CD45RO(+)CD27(+) T cells to specific DosR and Rpf, which may indicate a persistent immune response to Mtb antigens in ltLTBI.

  10. Genes and Abdominal Aortic Aneurysm

    PubMed Central

    Hinterseher, Irene; Tromp, Gerard; Kuivaniemi, Helena

    2010-01-01

    Abdominal aortic aneurysm (AAA) is a multifactorial disease with a strong genetic component. Since first candidate gene studies were published 20 years ago, nearly 100 genetic association studies using single nucleotide polymorphisms (SNPs) in biologically relevant genes have been reported on AAA. The studies investigated SNPs in genes of the extracellular matrix, the cardiovascular system, the immune system, and signaling pathways. Very few studies were large enough to draw firm conclusions and very few results could be replicated in another sample set. The more recent unbiased approaches are family-based DNA linkage studies and genome-wide genetic association studies, which have the potential of identifying the genetic basis for AAA, if appropriately powered and well-characterized large AAA cohorts are used. SNPs associated with AAA have already been identified in these large multicenter studies. One significant association was of a variant in a gene called CNTN3 which is located on chromosome 3p12.3. Two follow-up studies, however, could not replicate the association. Two other SNPs, which are located on chromosome 9p21 and 9q33 were replicated in other samples. The two genes with the strongest supporting evidence of contribution to the genetic risk for AAA are the CDKN2BAS gene, also known as ANRIL, which encodes an antisense RNA that regulates expression of the cyclin-dependent kinase inhibitors CDKN2A and CDKN2B, and DAB2IP, which encodes an inhibitor of cell growth and survival. Functional studies are now needed to establish the mechanisms by which these genes contribute to AAA pathogenesis. PMID:21146954

  11. A hybrid approach of gene sets and single genes for the prediction of survival risks with gene expression data.

    PubMed

    Seok, Junhee; Davis, Ronald W; Xiao, Wenzhong

    2015-01-01

    Accumulated biological knowledge is often encoded as gene sets, collections of genes associated with similar biological functions or pathways. The use of gene sets in the analyses of high-throughput gene expression data has been intensively studied and applied in clinical research. However, the main interest remains in finding modules of biological knowledge, or corresponding gene sets, significantly associated with disease conditions. Risk prediction from censored survival times using gene sets hasn't been well studied. In this work, we propose a hybrid method that uses both single gene and gene set information together to predict patient survival risks from gene expression profiles. In the proposed method, gene sets provide context-level information that is poorly reflected by single genes. Complementarily, single genes help to supplement incomplete information of gene sets due to our imperfect biomedical knowledge. Through the tests over multiple data sets of cancer and trauma injury, the proposed method showed robust and improved performance compared with the conventional approaches with only single genes or gene sets solely. Additionally, we examined the prediction result in the trauma injury data, and showed that the modules of biological knowledge used in the prediction by the proposed method were highly interpretable in biology. A wide range of survival prediction problems in clinical genomics is expected to benefit from the use of biological knowledge.

  12. Clock Genes in Glia Cells

    PubMed Central

    Chi-Castañeda, Donají

    2016-01-01

    Circadian rhythms are periodic patterns in biological processes that allow the organisms to anticipate changes in the environment. These rhythms are driven by the suprachiasmatic nucleus (SCN), the master circadian clock in vertebrates. At a molecular level, circadian rhythms are regulated by the so-called clock genes, which oscillate in a periodic manner. The protein products of clock genes are transcription factors that control their own and other genes’ transcription, collectively known as “clock-controlled genes.” Several brain regions other than the SCN express circadian rhythms of clock genes, including the amygdala, the olfactory bulb, the retina, and the cerebellum. Glia cells in these structures are expected to participate in rhythmicity. However, only certain types of glia cells may be called “glial clocks,” since they express PER-based circadian oscillators, which depend of the SCN for their synchronization. This contribution summarizes the current information about clock genes in glia cells, their plausible role as oscillators and their medical implications. PMID:27666286

  13. Gene therapy for metachromatic leukodystrophy.

    PubMed

    Rosenberg, Jonathan B; Kaminsky, Stephen M; Aubourg, Patrick; Crystal, Ronald G; Sondhi, Dolan

    2016-11-01

    Leukodystrophies (LDs) are rare, often devastating genetic disorders with neurologic symptoms. There are currently no disease-specific therapeutic approaches for these diseases. In this review we use metachromatic leukodystrophy as an example to outline in the brief the therapeutic approaches to MLD that have been tested in animal models and in clinical trials, such as enzyme-replacement therapy, bone marrow/umbilical cord blood transplants, ex vivo transplantation of genetically modified hematopoietic stem cells, and gene therapy. These studies suggest that to be successful the ideal therapy for MLD must provide persistent and high level expression of the deficient gene, arylsulfatase A in the CNS. Gene therapy using adeno-associated viruses is therefore the ideal choice for clinical development as it provides the best balance of potential for efficacy with reduced safety risk. Here we have summarized the published preclinical data from our group and from others that support the use of a gene therapy with AAVrh.10 serotype for clinical development as a treatment for MLD, and as an example of the potential of gene therapy for LDs especially for Krabbe disease, which is the focus of this special issue. © 2016 Wiley Periodicals, Inc. PMID:27638601

  14. Gene Therapy for Pituitary Tumors

    PubMed Central

    Seilicovich, Adriana; Pisera, Daniel; Sciascia, Sandra A.; Candolfi, Marianela; Puntel, Mariana; Xiong, Weidong; Jaita, Gabriela; Castro, Maria G.

    2009-01-01

    Pituitary tumors are the most common primary intracranial neoplasms. Although most pituitary tumors are considered typically benign, others can cause severe and progressive disease. The principal aims of pituitary tumor treatment are the elimination or reduction of the tumor mass, normalization of hormone secretion and preservation of remaining pituitary function. In spite of major advances in the therapy of pituitary tumors, for some of the most difficult tumors, current therapies that include medical, surgical and radiotherapeutic methods are often unsatisfactory and there is a need to develop new treatment strategies. Gene therapy, which uses nucleic acids as drugs, has emerged as an attractive therapeutic option for the treatment of pituitary tumors that do not respond to classical treatment strategies if the patients become intolerant to the therapy. The development of animal models for pituitary tumors and hormone hypersecretion has proven to be critical for the implementation of novel treatment strategies and gene therapy approaches. Preclinical trials using several gene therapy approaches for the treatment of anterior pituitary diseases have been successfully implemented. Several issues need to be addressed before clinical implementation becomes a reality, including the development of more effective and safer viral vectors, uncovering novel therapeutic targets and development of targeted expression of therapeutic transgenes. With the development of efficient gene delivery vectors allowing long-term transgene expression with minimal toxicity, gene therapy will become one of the most promising approaches for treating pituitary adenomas. PMID:16457646

  15. Melatonin Receptor Genes in Vertebrates

    PubMed Central

    Li, Di Yan; Smith, David Glenn; Hardeland, Rüdiger; Yang, Ming Yao; Xu, Huai Liang; Zhang, Long; Yin, Hua Dong; Zhu, Qing

    2013-01-01

    Melatonin receptors are members of the G protein-coupled receptor (GPCR) family. Three genes for melatonin receptors have been cloned. The MT1 (or Mel1a or MTNR1A) and MT2 (or Mel1b or MTNR1B) receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype, Mel1c (or MTNR1C), has been identified in fish, amphibians and birds. Another melatonin related orphan receptor, GPR50, which does not bind melatonin, is found exclusively in mammals. The hormone melatonin is secreted primarily by the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone acts systemically in numerous organs. In the brain, it is involved in the regulation of various neural and endocrine processes, and it readjusts the circadian pacemaker, the suprachiasmatic nucleus. This article reviews recent studies of gene organization, expression, evolution and mutations of melatonin receptor genes of vertebrates. Gene polymorphisms reveal that numerous mutations are associated with diseases and disorders. The phylogenetic analysis of receptor genes indicates that GPR50 is an outgroup to all other melatonin receptor sequences. GPR50 may have separated from a melatonin receptor ancestor before the split between MTNR1C and the MTNR1A/B ancestor. PMID:23712359

  16. Metazoan Gene Families from Metazome

    DOE Data Explorer

    Metazome is a joint project of the Department of Energy's Joint Genome Institute and the Center for Integrative Genomics to facilitate comparative genomic studies amongst metazoans. Clusters of orthologous and paralogous genes that represent the modern descendents of ancestral gene sets are constructed at key phylogenetic nodes. These clusters allow easy access to clade specific orthology/paralogy relationships as well as clade specific genes and gene expansions. As of version 2.0.4, Metazome provides access to twenty-four sequenced and annotated metazoan genomes, clustered at nine evolutionarily significant nodes. Where possible, each gene has been annotated with PFAM, KOG, KEGG, and PANTHER assignments, and publicly available annotations from RefSeq, UniProt, Ensembl, and JGI are hyper-linked and searchable. The included organisms (by common name) are: Human, Mouse, Rat, Dog, Opossum, Chicken, Frog, Stickleback, Medaka, Fugu pufferfish; Zebrafish, Seasquirt - savignyi, Seasquirt - intestinalis, Amphioxus, Sea Urchin, Fruitfly, Mosquite, Yellow Fever Mosquito, Silkworm, Red Flour Beetle, Worm, Briggsae Worm, Owl limpet (snail), and Sea anemone. [Copied from Metazome Overview at http://www.metazome.net/Metazome_info.php

  17. Systems Biophysics of Gene Expression

    PubMed Central

    Vilar, Jose M.G.; Saiz, Leonor

    2013-01-01

    Gene expression is a process central to any form of life. It involves multiple temporal and functional scales that extend from specific protein-DNA interactions to the coordinated regulation of multiple genes in response to intracellular and extracellular changes. This diversity in scales poses fundamental challenges to the use of traditional approaches to fully understand even the simplest gene expression systems. Recent advances in computational systems biophysics have provided promising avenues to reliably integrate the molecular detail of biophysical process into the system behavior. Here, we review recent advances in the description of gene regulation as a system of biophysical processes that extend from specific protein-DNA interactions to the combinatorial assembly of nucleoprotein complexes. There is now basic mechanistic understanding on how promoters controlled by multiple, local and distal, DNA binding sites for transcription factors can actively control transcriptional noise, cell-to-cell variability, and other properties of gene regulation, including precision and flexibility of the transcriptional responses. PMID:23790365

  18. Gene Ontology Consortium: going forward

    PubMed Central

    2015-01-01

    The Gene Ontology (GO; http://www.geneontology.org) is a community-based bioinformatics resource that supplies information about gene product function using ontologies to represent biological knowledge. Here we describe improvements and expansions to several branches of the ontology, as well as updates that have allowed us to more efficiently disseminate the GO and capture feedback from the research community. The Gene Ontology Consortium (GOC) has expanded areas of the ontology such as cilia-related terms, cell-cycle terms and multicellular organism processes. We have also implemented new tools for generating ontology terms based on a set of logical rules making use of templates, and we have made efforts to increase our use of logical definitions. The GOC has a new and improved web site summarizing new developments and documentation, serving as a portal to GO data. Users can perform GO enrichment analysis, and search the GO for terms, annotations to gene products, and associated metadata across multiple species using the all-new AmiGO 2 browser. We encourage and welcome the input of the research community in all biological areas in our continued effort to improve the Gene Ontology. PMID:25428369

  19. Gene Chips and Functional Genomics

    NASA Astrophysics Data System (ADS)

    Hamadeh, Hisham; Afshari, Cynthia

    2000-11-01

    These past few years of scientific discovery will undoubtedly be remembered as the "genomics era," the period in which biologists succeeded in enumerating the sequence of nucleotides making up all, or at least most, of human DNA. And while this achievement has been heralded as a technological feat equal to the moon landing, it is only the first of many advances in DNA technology. Scientists are now faced with the task of understanding the meaning of the DNA sequence. Specifically, they want to learn how the DNA code relates to protein function. An important tool in the study of "functional genomics," is the cDNA microarray—also known as the gene chip. Inspired by computer microchips, gene chips allow scientists to monitor the expression of hundreds, even thousands, of genes in a fraction of the time it used to take to monitor the expression of a single one. By altering the conditions under which a particular tissue expresses genes—say, by exposing it to toxins or growth factors—scientists can determine the suite of genes expressed in different situations and hence start to get a handle on the function of these genes. The authors discuss this important new technology and some of its practical applications.

  20. Hox gene dysregulation in acute myeloid leukemia.

    PubMed

    De Braekeleer, Etienne; Douet-Guilbert, Nathalie; Basinko, Audrey; Le Bris, Marie-Josée; Morel, Frédéric; De Braekeleer, Marc

    2014-02-01

    In humans, class I homeobox genes (HOX genes) are distributed in four clusters. Upstream regulators include transcriptional activators and members of the CDX family of transcription factors. HOX genes encode proteins and need cofactor interactions, to increase their specificity and selectivity. HOX genes contribute to the organization and regulation of hematopoiesis by controlling the balance between proliferation and differentiation. Changes in HOX gene expression can be associated with chromosomal rearrangements generating fusion genes, such as those involving MLL and NUP98, or molecular defects, such as mutations in NPM1 and CEBPA for example. Several miRNAs are involved in the control of HOX gene expression and their expression correlates with HOX gene dysregulation. HOX genes dysregulation is a dominant mechanism of leukemic transformation. A better knowledge of their target genes and the mechanisms by which their dysregulated expression contributes to leukemogenesis could lead to the development of new drugs.