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1.
Res Sq ; 2023 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-37292678

RESUMEN

The ancestral gamete fusion protein, HAP2, catalyzes sperm-egg fusion in a broad range of taxa dating to the last eukaryotic common ancestor. Remarkably, HAP2 orthologs are structurally related to the class II fusogens of modern-day viruses, and recent studies make clear that these proteins utilize similar mechanisms to achieve membrane merger. To identify factors that may regulate HAP2 activity, we screened mutants of the ciliate Tetrahymena thermophila for behaviors that mimic Δhap2 knockout phenotypes in this species. Using this approach, we identified two new genes, GFU1 and GFU2, whose products are necessary for the formation of membrane pores during fertilization and show that the product of a third gene, namely ZFR1, may be involved in pore maintenance and/or expansion. Finally, we propose a model that explains cooperativity between the fusion machinery on apposed membranes of mating cells and accounts for successful fertilization in T. thermophila's multiple mating type system.

2.
Genome Med ; 10(1): 15, 2018 02 26.
Artículo en Inglés | MEDLINE | ID: mdl-29482619

RESUMEN

BACKGROUND: Chlamydia trachomatis (Ct) is the most common infectious cause of blindness and bacterial sexually transmitted infection worldwide. Ct strain-specific differences in clinical trachoma suggest that genetic polymorphisms in Ct may contribute to the observed variability in severity of clinical disease. METHODS: Using Ct whole genome sequences obtained directly from conjunctival swabs, we studied Ct genomic diversity and associations between Ct genetic polymorphisms with ocular localization and disease severity in a treatment-naïve trachoma-endemic population in Guinea-Bissau, West Africa. RESULTS: All Ct sequences fall within the T2 ocular clade phylogenetically. This is consistent with the presence of the characteristic deletion in trpA resulting in a truncated non-functional protein and the ocular tyrosine repeat regions present in tarP associated with ocular tissue localization. We have identified 21 Ct non-synonymous single nucleotide polymorphisms (SNPs) associated with ocular localization, including SNPs within pmpD (odds ratio, OR = 4.07, p* = 0.001) and tarP (OR = 0.34, p* = 0.009). Eight synonymous SNPs associated with disease severity were found in yjfH (rlmB) (OR = 0.13, p* = 0.037), CTA0273 (OR = 0.12, p* = 0.027), trmD (OR = 0.12, p* = 0.032), CTA0744 (OR = 0.12, p* = 0.041), glgA (OR = 0.10, p* = 0.026), alaS (OR = 0.10, p* = 0.032), pmpE (OR = 0.08, p* = 0.001) and the intergenic region CTA0744-CTA0745 (OR = 0.13, p* = 0.043). CONCLUSIONS: This study demonstrates the extent of genomic diversity within a naturally circulating population of ocular Ct and is the first to describe novel genomic associations with disease severity. These findings direct investigation of host-pathogen interactions that may be important in ocular Ct pathogenesis and disease transmission.


Asunto(s)
Chlamydia trachomatis/genética , Genoma Bacteriano , Índice de Severidad de la Enfermedad , Tracoma/microbiología , Conjuntiva/patología , Enfermedades Endémicas , Marcadores Genéticos , Guinea Bissau , Humanos , Funciones de Verosimilitud , Fenotipo , Filogenia , Polimorfismo de Nucleótido Simple/genética , Tracoma/patología , Secuenciación Completa del Genoma
3.
J Clin Microbiol ; 53(10): 3141-7, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26179308

RESUMEN

Clostridium difficile remains the leading cause of nosocomial diarrhea worldwide, which is largely considered to be due to the production of two potent toxins: TcdA and TcdB. However, PCR ribotype (RT) 017, one of five clonal lineages of human virulent C. difficile, lacks TcdA expression but causes widespread disease. Whole-genome sequencing was applied to 35 isolates from hospitalized patients with C. difficile infection (CDI) and two environmental ward isolates in London, England. The phylogenetic analysis of single nucleotide polymorphisms (SNPs) revealed a clonal cluster of temporally variable isolates from a single hospital ward at University Hospital Lewisham (UHL) that were distinct from other London hospital isolates. De novo assembled genomes revealed a 49-kbp putative conjugative transposon exclusive to this hospital clonal cluster which would not be revealed by current typing methodologies. This study identified three sublineages of C. difficile RT017 that are circulating in London. Similar to the notorious RT027 lineage, which has caused global outbreaks of CDI since 2001, the lineage of toxin-defective RT017 strains appears to be continually evolving. By utilization of WGS technologies to identify SNPs and the evolution of clonal strains, the transmission of outbreaks caused by near-identical isolates can be retraced and identified.


Asunto(s)
Clostridioides difficile/clasificación , Infecciones por Clostridium/epidemiología , Infección Hospitalaria/epidemiología , Diarrea/epidemiología , Brotes de Enfermedades , Enterotoxinas/deficiencia , Ribotipificación , Toxinas Bacterianas , Clostridioides difficile/genética , Clostridioides difficile/aislamiento & purificación , Infecciones por Clostridium/microbiología , Análisis por Conglomerados , Infección Hospitalaria/microbiología , Diarrea/microbiología , Genoma Bacteriano , Humanos , Londres/epidemiología , Epidemiología Molecular , Filogenia , Reacción en Cadena de la Polimerasa , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADN
4.
Elife ; 42015 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-25732036

RESUMEN

To improve understanding of the factors influencing tuberculosis transmission and the role of pathogen variation, we sequenced all available specimens from patients diagnosed over 15 years in a whole district in Malawi. Mycobacterium tuberculosis lineages were assigned and transmission networks constructed, allowing ≤10 single nucleotide polymorphisms (SNPs) difference. We defined disease as due to recent infection if the network-determined source was within 5 years, and assessed transmissibility from forward transmissions resulting in disease. High-quality sequences were available for 1687 disease episodes (72% of all culture-positive episodes): 66% of patients linked to at least one other patient. The between-patient mutation rate was 0.26 SNPs/year (95% CI 0.21-0.31). We showed striking differences by lineage in the proportion of disease due to recent transmission and in transmissibility (highest for lineage-2 and lowest for lineage-1) that were not confounded by immigration, HIV status or drug resistance. Transmissions resulting in disease decreased markedly over time.


Asunto(s)
Genoma Bacteriano , Mycobacterium tuberculosis/genética , Tuberculosis/transmisión , Humanos , Malaui/epidemiología , Mutación , Mycobacterium tuberculosis/clasificación , Filogenia , Polimorfismo de Nucleótido Simple , Prevalencia , Tuberculosis/epidemiología
5.
Scand J Immunol ; 79(1): 43-50, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24117665

RESUMEN

It has been previously shown that there are some interethnic differences in susceptibility to malaria between two sympatric ethnic groups of Mali, the Fulani and the Dogon. The lower susceptibility to Plasmodium falciparum malaria seen in the Fulani has not been fully explained by genetic polymorphisms previously known to be associated with malaria resistance, including haemoglobin S (HbS), haemoglobin C (HbC), alpha-thalassaemia and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Given the observed differences in the distribution of FcγRIIa allotypes among different ethnic groups and with malaria susceptibility that have been reported, we analysed the rs1801274-R131H polymorphism in the FcγRIIa gene in a study of Dogon and Fulani in Mali (n = 939). We confirm that the Fulani have less parasite densities, less parasite prevalence, more spleen enlargement and higher levels of total IgG antibodies (anti-CSP, anti-AMA1, anti-MSP1 and anti-MSP2) and more total IgE (P < 0.05) compared with the Dogon ethnic group. Furthermore, the Fulani exhibit higher frequencies of the blood group O (56.5%) compared with the Dogon (43.5%) (P < 0.001). With regard to the FcγRIIa polymorphism and allele frequency, the Fulani group have a higher frequency of the H allele (Fulani 0.474, Dogon 0.341, P < 0.0001), which was associated with greater total IgE production (P = 0.004). Our findings show that the FcγRIIa polymorphism might have an implication in the relative protection seen in the Fulani tribe, with confirmatory studies required in other malaria endemic settings.


Asunto(s)
Predisposición Genética a la Enfermedad/genética , Malaria Falciparum/genética , Polimorfismo de Nucleótido Simple , Receptores de IgG/genética , Adolescente , Anticuerpos Antiprotozoarios/inmunología , Niño , Preescolar , Etnicidad/genética , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad/etnología , Genotipo , Interacciones Huésped-Parásitos , Humanos , Inmunoglobulina E/inmunología , Inmunoglobulina G/inmunología , Lactante , Recién Nacido , Malaria Falciparum/etnología , Malaria Falciparum/inmunología , Masculino , Malí/epidemiología , Plasmodium falciparum/inmunología , Plasmodium falciparum/fisiología , Prevalencia , Esplenomegalia/genética , Esplenomegalia/inmunología , Esplenomegalia/parasitología
6.
Genes Immun ; 13(6): 503-8, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22673309

RESUMEN

The genetic basis for susceptibility to malaria has been studied widely in African populations but less is known of the contribution of specific genetic variants in Asian populations. We genotyped 67 single-nucleotide polymorphisms (SNPs) in 1030 severe malaria cases and 2840 controls from Vietnam. After data quality control, genotyping data of 956 cases and 2350 controls were analysed for 65 SNPs (3 gender confirmation, 62 positioned in/near 42 malarial candidate genes). A total of 14 SNPs were monomorphic and 2 (rs8078340 and rs33950507) were not in Hardy-Weinberg equilibrium in controls (P<0.01). In all, 7/46 SNPs in 6 genes (ICAM1, IL1A, IL17RC, IL13, LTA and TNF) were associated with severe malaria, with 3/7 SNPs in the TNF/LTA region. Genotype-phenotype correlations between SNPs and clinical parameters revealed that genotypes of rs708567 (IL17RC) correlate with parasitemia (P=0.028, r(2)=0.0086), with GG homozygotes having the lowest parasite burden. Additionally, rs708567 GG homozygotes had a decreased risk of severe malaria (P=0.007, OR=0.78 (95% CI; 0.65-0.93)) and death (P=0.028, OR=0.58 (95% CI; 0.37-0.93)) than those with AA and AG genotypes. In summary, variants in six genes encoding adhesion and proinflammatory molecules are associated with severe malaria in the Vietnamese. Further replicative studies in independent populations will be necessary to confirm these findings.


Asunto(s)
Moléculas de Adhesión Celular/genética , Mediadores de Inflamación/inmunología , Malaria Falciparum/genética , Malaria Falciparum/inmunología , Adulto , Pueblo Asiatico/genética , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Variación Genética , Humanos , Molécula 1 de Adhesión Intercelular/genética , Interleucina-13/genética , Interleucina-1alfa/genética , Masculino , Parasitemia/genética , Parasitemia/inmunología , Polimorfismo de Nucleótido Simple , Receptores de Interleucina/genética , Factor de Necrosis Tumoral alfa/genética , Vietnam , Adulto Joven
7.
Appl Environ Microbiol ; 75(23): 7445-52, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19820157

RESUMEN

Endosymbiotic bacteria were identified in the parasitic ciliate Ichthyophthirius multifiliis, a common pathogen of freshwater fish. PCR amplification of DNA prepared from two isolates of I. multifiliis, using primers that bind conserved sequences in bacterial 16S rRNA genes, generated an approximately 1,460-bp DNA product, which was cloned and sequenced. Sequence analysis demonstrated that 16S rRNA gene sequences from three classes of bacteria were present in the PCR product. These included Alphaproteobacteria (Rickettsiales), Sphingobacteria, and Flavobacterium columnare. DAPI (4',6-diamidino-2-phenylindole) staining showed endosymbionts dispersed throughout the cytoplasm of trophonts and, in most, but not all theronts. Endosymbionts were observed by transmission electron microscopy in the cytoplasm, surrounded by a prominent, electron-translucent halo characteristic of Rickettsia. Fluorescence in situ hybridization demonstrated that bacteria from the Rickettsiales and Sphingobacteriales classes are endosymbionts of I. multifiliis, found in the cytoplasm, but not in the macronucleus or micronucleus. In contrast, F. columnare was not detected by fluorescence in situ hybridization. It likely adheres to I. multifiliis through association with cilia. The role that endosymbiotic bacteria play in the life history of I. multifiliis is not known.


Asunto(s)
Cilióforos/microbiología , Flavobacterium/aislamiento & purificación , Rickettsia/aislamiento & purificación , Sphingobacterium/aislamiento & purificación , Simbiosis , Animales , Cilióforos/fisiología , Análisis por Conglomerados , Citoplasma/microbiología , ADN Bacteriano/química , ADN Bacteriano/genética , ADN Ribosómico/química , ADN Ribosómico/genética , Microscopía Electrónica de Transmisión , Datos de Secuencia Molecular , Filogenia , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN
8.
Nature ; 455(7214): 799-803, 2008 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-18843368

RESUMEN

Plasmodium knowlesi is an intracellular malaria parasite whose natural vertebrate host is Macaca fascicularis (the 'kra' monkey); however, it is now increasingly recognized as a significant cause of human malaria, particularly in southeast Asia. Plasmodium knowlesi was the first malaria parasite species in which antigenic variation was demonstrated, and it has a close phylogenetic relationship to Plasmodium vivax, the second most important species of human malaria parasite (reviewed in ref. 4). Despite their relatedness, there are important phenotypic differences between them, such as host blood cell preference, absence of a dormant liver stage or 'hypnozoite' in P. knowlesi, and length of the asexual cycle (reviewed in ref. 4). Here we present an analysis of the P. knowlesi (H strain, Pk1(A+) clone) nuclear genome sequence. This is the first monkey malaria parasite genome to be described, and it provides an opportunity for comparison with the recently completed P. vivax genome and other sequenced Plasmodium genomes. In contrast to other Plasmodium genomes, putative variant antigen families are dispersed throughout the genome and are associated with intrachromosomal telomere repeats. One of these families, the KIRs, contains sequences that collectively match over one-half of the host CD99 extracellular domain, which may represent an unusual form of molecular mimicry.


Asunto(s)
Genoma de Protozoos/genética , Genómica , Macaca mulatta/parasitología , Malaria/parasitología , Plasmodium knowlesi/genética , Secuencia de Aminoácidos , Animales , Antígenos CD/química , Antígenos CD/genética , Cromosomas/genética , Secuencia Conservada , Genes Protozoarios/genética , Humanos , Datos de Secuencia Molecular , Plasmodium knowlesi/clasificación , Plasmodium knowlesi/fisiología , Estructura Terciaria de Proteína , Proteínas Protozoarias/química , Proteínas Protozoarias/genética , Análisis de Secuencia de ADN , Telómero/genética
9.
Ann Hum Genet ; 72(Pt 3): 368-74, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-18261185

RESUMEN

We introduce a simple and yet scientifically objective criterion for identifying SNPs with genotyping errors due to poor clustering. This yields a metric for assessing the stability of the assigned genotypes by evaluating the extent of discordance between the calls made with the unperturbed and perturbed intensities. The efficacy of the metric is evaluated by: (1) estimating the extent of over-dispersion of the Hardy-Weinberg equilibrium chi-square test statistics; (2) an interim case-control study, where we investigated the efficacy of the introduced metric and standard quality control filters in reducing the number of SNPs with evidence of phenotypic association which are attributed to genotyping errors; (3) investigating the call and concordance rates of SNPs identified by perturbation analysis which have been genotyped on both Affymetrix and Illumina platforms. Removing SNPs identified by the extent of discordance can reduce the degree of over-dispersion of the HWE test statistic. Sensible use of perturbation analysis in an association study can correctly identify SNPs with problematic genotyping, reducing the number required for visual inspection. SNPs identified by perturbation analysis had lower call and concordance rates, and removal of these SNPs significantly improved the performance for the remaining SNPs.


Asunto(s)
Predisposición Genética a la Enfermedad , Técnicas Genéticas , Genoma Humano/genética , Polimorfismo de Nucleótido Simple/genética , Alelos , Cromosomas Humanos/genética , Humanos , Hibridación Genética , Fenotipo , Proyectos de Investigación
10.
Genes Immun ; 9(2): 122-9, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18200030

RESUMEN

We describe the haplotypic structure of the interferon regulatory factor-1 (IRF-1) locus in two West African ethnic groups, Fulani and Mossi, that differ in their susceptibility and immune response to Plasmodium falciparum malaria. Both populations showed significant associations between IRF-1 polymorphisms and carriage of P. falciparum infection, with different patterns of association that may reflect their different haplotypic architecture. Genetic variation at this locus does not therefore account for the Fulani-specific resistance to malaria while it could contribute to parasite clearance's ability in populations living in endemic areas. We then conducted a case-control study of three haplotype-tagging single nucleotide polymorphisms (htSNPs) in 370 hospitalised malaria patients (160 severe and 210 uncomplicated) and 410 healthy population controls, all from the Mossi ethnic group. All three htSNPs showed correlation with blood infection levels in malaria patients, and the rs10065633 polymorphism was associated with severe disease (P=0.02). These findings provide the first evidence of the involvement in malaria susceptibility of a specific locus within the 5q31 region, previously shown to be linked with P. falciparum infection levels.


Asunto(s)
Factor 1 Regulador del Interferón/genética , Malaria Falciparum/genética , Plasmodium falciparum/genética , Polimorfismo Genético/genética , Adolescente , Adulto , Animales , Burkina Faso/epidemiología , Burkina Faso/etnología , Estudios de Casos y Controles , Niño , Estudios Transversales , Predisposición Genética a la Enfermedad , Haplotipos/genética , Humanos , Malaria Falciparum/epidemiología , Malaria Falciparum/etnología , Plasmodium falciparum/aislamiento & purificación
11.
Mol Psychiatry ; 11(6): 539-46, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16520822

RESUMEN

We investigated the association of the NRG1 gene and schizophrenia using meta-analytic techniques, combining all published data while restricting our analysis to studies investigating the most commonly reported single marker (SNP8NRG221533). We also investigated whether ancestry (European vs East Asian) and study design (family-based vs case-control) moderated any association. We found no evidence for an association of SNP8NRG221533 with schizophrenia, and significant between-study heterogeneity, which persisted when family-based studies were combined separately. However, when haplotype-based P-values were combined, there was evidence in support of an association of NRG1 with schizophrenia, and no evidence of between-study heterogeneity. Our meta-analysis provides support for the association of NRG1 with schizophrenia, but indicates that firmly establishing the role of NRG1 gene in schizophrenia by genetic association requires much larger sample sizes than have hitherto been reported. Association analyses and replications should take place at the level of the gene, rather than at the level of SNP, haplotype, or functional variant. Meta-analysis would then be carried out on the basis of the combination of P-values.


Asunto(s)
Haplotipos/genética , Neurregulina-1/genética , Esquizofrenia/genética , Pueblo Asiatico/genética , Asia Oriental , Marcadores Genéticos/genética , Humanos , Linaje , Polimorfismo de Nucleótido Simple/genética , Tamaño de la Muestra , Población Blanca/genética
12.
Cerebrovasc Dis ; 21(5-6): 323-8, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16490941

RESUMEN

BACKGROUND: Weak associations between total and LDL cholesterol and ischaemic stroke compared with coronary heart disease (CHD) are at odds with the similar effectiveness of statin drugs in preventing ischaemic stroke and CHD, suggesting that other lipid sub-fractions that are affected by statins might be better predictors of ischaemic stroke. Apolipoprotein B levels are reduced by statins and are a stronger predictor of CHD than total and LDL cholesterol in patients both on and off statins. However, there are very few published data on apolipoproteins and stroke risk and no studies in patients with previous transient ischaemic attack (TIA). METHODS: We performed a prospective cohort study of the associations of baseline total cholesterol, LDL, HDL, apolipoproteins A1 and B (apo A1; apo B) and risk of ischaemic stroke in 261 patients with previous TIA. Cox proportional hazards models were used to determine crude and multivariate-adjusted hazard ratios (HR) above versus below median values at 10-years follow-up. RESULTS: The apo B/apo A1 ratio was the strongest independent predictor of ischaemic stroke (HR=2.94, 95% CI 1.43-5.88, p=0.003) followed by apo B (HR=2.26, 95% CI 1.16-4.38, p=0.02). The associations between total cholesterol, LDL, HDL, LDL/HDL ratio and apo A1 and ischaemic stroke risk did not reach statistical significance. CONCLUSIONS: Apo B and the apo B/apo A1 ratio are predictive of ischaemic stroke in patients with previous TIA. Further studies are required to determine whether the prognostic value of apolipoprotein levels is maintained in patients on statins.


Asunto(s)
Apolipoproteína A-I/sangre , Apolipoproteínas B/sangre , Ataque Isquémico Transitorio/sangre , Accidente Cerebrovascular/etiología , Anciano , Biomarcadores/sangre , Colesterol/sangre , Estudios de Cohortes , Femenino , Humanos , Lipoproteínas HDL/sangre , Lipoproteínas LDL/sangre , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas
13.
Dev Biol (Basel) ; 121: 153-63, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-15962478

RESUMEN

Recombinant DNA techniques have enormous potential for the development of inexpensive, safe and efficacious vaccines for the aquaculture industry. Aside from rationally attenuated pathogens, two broad categories of recombinant vaccines have been described. The first are so-called "vectored" vaccines, which consist of either viral or plasmid expression vectors harbouring genes for protective antigens from a given pathogen. The second are recombinant subunit antigens produced using heterologous protein expression systems. Less onerous from a regulatory standpoint, recombinant subunit vaccines generate strong antibody responses in recipient animals when administered parenterally with adjuvant-containing formulations. This approach is nevertheless constrained by the fact that low-cost systems for protein expression (especially E. coli, but also yeast) often generate misfolded or incorrectly processed membrane antigens that fail to protect, while more complex insect and mammalian tissue culture cells are prohibitively expensive from a production standpoint. Furthermore, subunit antigens generate less than optimal mucosal and cytotoxic T-cell responses, the last two of which are especially important for the clearance of intracellular pathogens. Fortunately, these constraints are now being overcome through the use of new generation adjuvants and delivery systems that enhance immunogenicity, as well as new expression systems for the production of viral and protozoan membrane antigens.


Asunto(s)
Adyuvantes Inmunológicos/metabolismo , Formación de Anticuerpos/inmunología , Antígenos/metabolismo , Acuicultura/métodos , Linfocitos T/inmunología , Vacunas de ADN , Vacunas de Subunidad , Animales , Células Cultivadas , Escherichia coli , Linfocitos T/metabolismo , Levaduras
14.
Mol Psychiatry ; 10(8): 765-70, 2005 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-15824744

RESUMEN

There is strong evidence for a genetic contribution to schizophrenia, but the contribution of individual candidate genes remains uncertain. We attempted to replicate a recent meta-analysis that reported an association of the catechol O-methyltransferase (COMT) Val allele with schizophrenia, and suggested that this effect may be moderated by ancestry. We included reports published subsequent to the original meta-analysis, and included a formal test of the moderating effect of ancestry in order to test whether the association operates differently in populations of European ancestry compared to populations of Asian ancestry. A corrected P-value for the 5% significance threshold was employed where appropriate, using Bonferroni's method, and studies that demonstrated departure from Hardy-Weinberg equilibrium among controls were excluded. When all studies were included in a meta-regression, there was evidence for a significant association of COMT Val allele frequency with schizophrenia case status and a significant main effect of ancestry. The interaction of COMT Val allele frequency and ancestry was also significant. However, when only studies that reported allele frequencies that did not depart significantly from Hardy-Weinberg equilibrium among controls were included, these effects were no longer significant. The results of our meta-analysis do not support an association between the COMT Val allele and schizophrenia case status, and do not support recent claims that this association may be moderated by ancestry.


Asunto(s)
Catecol O-Metiltransferasa/genética , Metionina , Esquizofrenia/genética , Valina , Sustitución de Aminoácidos , Estudios de Casos y Controles , Bases de Datos Factuales , Humanos , Esquizofrenia/enzimología , Programas Informáticos , Población Blanca/genética
15.
Parasitology ; 126 Suppl: S87-93, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-14667175

RESUMEN

We are developing Tetrahymena thermophila as a delivery system for recombinant vaccines against parasitic protozoa, including the common fish parasite, Ichthyophthirius multifiliis. T. thermophila cell lines expressing I. multifiliis genes under the control of a cadmium-inducible metallothionein gene promoter conferred strong protection against a lethal parasite challenge when administered parenterally to naive fish. Nevertheless, given that heavy metals can be toxic to parasites, a question arose as to whether protection resulted from Cd residues carried over with the vaccine, rather than acquired immunity per se. To address this issue, we examined the sensitivity of I. multifiliis to Cd in vitro and determined Cd concentrations in different host tissues following i.p. injection of juvenile channel catfish with the recombinant vaccine. We found that CdCl2 at concentrations > or = 50 ppb were lethal to I. multifiliis theronts in vitro. Furthermore, Cd concentrations were clearly elevated in fish tissues and reached levels equivalent to 74 ng/g wet weight (74 ppb) in the skin within 14 days of injection with recombinant T. thermophila. Nevertheless, fish injected with non-transformed Tetrahymena grown in the presence or absence of CdCl2 showed no significant difference in either relative survival or parasite load following direct challenge with I. multifiliis.


Asunto(s)
Cadmio/farmacología , Infecciones por Cilióforos/veterinaria , Cilióforos/efectos de los fármacos , Enfermedades de los Peces/prevención & control , Ictaluridae/metabolismo , Vacunas Antiprotozoos/administración & dosificación , Animales , Cadmio/farmacocinética , Cilióforos/inmunología , Cilióforos/metabolismo , Infecciones por Cilióforos/inmunología , Infecciones por Cilióforos/prevención & control , Relación Dosis-Respuesta a Droga , Enfermedades de los Peces/inmunología , Ictaluridae/parasitología , Riñón/metabolismo , Músculos/metabolismo , Piel/metabolismo , Tetrahymena thermophila/inmunología , Vacunas Sintéticas/administración & dosificación
16.
Biophys J ; 85(5): 3066-73, 2003 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-14581207

RESUMEN

We present a new method for creating patches of fluid lipid bilayers with conjugated biotin and other compounds down to 1 microm resolution using a photolithographically patterned polymer lift-off technique. The patterns are realized as the polymer is mechanically peeled away in one contiguous piece in solution. The functionality of these surfaces is verified with binding of antibodies and avidin on these uniform micron-scale platforms. The biomaterial patches, measuring 1 micro m-76 microm on edge, provide a synthetic biological substrate for biochemical analysis that is approximately 100x smaller in width than commercial printing technologies. 100 nm unilamellar lipid vesicles spread to form a supported fluid lipid bilayer on oxidized silicon surface as confirmed by fluorescence photobleaching recovery. Fluorescence photobleaching recovery measurements of DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiIC(18)(3))) stained bilayer patches yielded an average diffusion coefficient of 7.54 +/- 1.25 microm(2) s(-1), equal to or slightly faster than typically found in DiI stained cells. This diffusion rate is approximately 3x faster than previous values for bilayers on glass. This method provides a new means to form functionalized fluid lipid bilayers as micron-scale platforms to immobilize biomaterials, capture antibodies and biotinylated reagents from solution, and form antigenic stimuli for cell stimulation.


Asunto(s)
Avidina/química , Materiales Biomiméticos/química , Técnicas Biosensibles/instrumentación , Biotina/química , Materiales Biocompatibles Revestidos/química , Inmunoensayo/instrumentación , Membrana Dobles de Lípidos/química , Fosfatidiletanolaminas/química , Adsorción , Materiales Biomiméticos/síntesis química , Técnicas Biosensibles/métodos , Materiales Biocompatibles Revestidos/síntesis química , Enzimas Inmovilizadas , Recuperación de Fluorescencia tras Fotoblanqueo , Inmunoensayo/métodos , Membrana Dobles de Lípidos/síntesis química , Ensayo de Materiales , Membranas Artificiales , Nanotecnología/instrumentación , Nanotecnología/métodos , Fosfolípidos/química , Fotograbar/métodos , Silicio , Propiedades de Superficie
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