RESUMO
Infrared spectra of Tutton compounds, M'2M''(SeO4)2â 6H2O (M'=K, NH4âº; M''=Mg, Co, Ni, Cu, Zn; X=S, Se), as well as those of SO4²â» guest ions included in selenate host lattices and of NH4(+) guest ions included in potassium host lattices are presented and discussed in the regions of ν3 and ν1 of SO4²â» guest ions, ν4 of NH4⺠guest ions and water librations. The SO4²â» guest ions matrix-isolated in selenate matrices (approximately 2 mol%) exhibit three bands corresponding to ν3 and one band corresponding to ν1 in good agreement with the low site symmetry C1 of the host selenate ions. When the larger SO4²â» ions are replaced by the smaller SO4²â» ions the mean values of the asymmetric stretching modes ν3 of the included SO4²â» ions are slightly shifted to lower frequencies as compared to those of the same ions in the neat sulfate compounds due to the smaller repulsion potential of the selenate matrices (larger unit-cell volumes of the selenates). It has been established that the extent of energetic distortion of the sulfate ions matrix-isolated in the ammonium selenates as deduced from the values of Δν3 and Δν3/νc is stronger than that of the same ions matrix-isolated in the potassium selenates due to the formation of hydrogen bonds between the SO4²â» guest ions with both the water molecules in the host compounds and the NH4⺠host ions (for example, Δν3 of the sulfate guest ions have values of 30 and 51 cm(-1) in the nickel potassium and ammonium compounds, and 33 and 49 cm(-1) in the zinc potassium and ammonium compounds, respectively). The infrared spectra of ammonium doped potassium sulfate matrices show three bands corresponding to Δν4 of the included ammonium ions in agreement with the low site symmetry C1 of the host potassium ions. However, the inclusion of ammonium ions in selenate matrices (with exception of the magnesium compound) leads to the appearance of four bands in the region of ν4. At that stage of our knowledge we assume that some kind of disorder of the ammonium ions included in selenate lattices occurs due to the different proton acceptor capability of the SO4²â» and SO4²â» ions. The latter ions are known to exhibit stronger proton acceptor abilities. This fact will facilitate the formation of polyfurcate hydrogen bonds of the ammonium ions in the selenate matrices, thus leading to increasing in the coordination number of these ions, i.e. to a disorder of the ammonium guest ions. The strength of the hydrogen bonds formed in the title Tutton compounds as well as that of the hydrogen bonds in potassium compounds containing isomorphously included ammonium ions as deduced from the wavenumbers of the water librations are also discussed. The bands corresponding to water librations in the spectra of the mixed crystals K1.8(NH4)0.2M(XO4)2â 6H2O (M=Mg, Co, Ni, Cu, Zn; X=S, Se) broaden and shift to lower frequencies as compared to those of the potassium host compounds, thus indicating that weaker hydrogen bonds are formed in the mixed crystals. These spectroscopic findings are owing to the decrease in the proton acceptor capacity of the SO4²â» and SO4²â» ions due to the formation of hydrogen bonds between the host anions and the guest ammonium cations additionally to water molecules (anti-cooperative or proton acceptor competitive effect). Furthermore, the band shifts in the spectra of the selenate matrices are generally larger than those observed in the spectra of the respective sulfates due to the stronger proton acceptor ability of the selenate ions.
Assuntos
Compostos de Amônio/química , Metais/química , Ácido Selênico/química , Sulfatos/química , Modelos Moleculares , Espectrofotometria Infravermelho , Água/químicaRESUMO
PURPOSE: Two genes for adult-onset primary open-angle glaucoma have been mapped to chromosomes 2cen-q13 and 3q21-q24. We studied a family with adult-onset primary open-angle glaucoma in which the disease did not map to these two chromosomal regions. METHODS: We ascertained a four-generation family with adult-onset primary open-angle glaucoma in which the disease status of individuals was objectively assigned using defined criteria. Complete ophthalmologic examinations, visual field testing, optic nerve head photographs, and venous blood samples were obtained. Family members were genotyped using polymerase chain reaction amplification of microsatellite polymorphic markers. Linkage analysis was performed and lod scores were calculated. Haplotype transmission data were analyzed. RESULTS: A total of 20 subjects in three successive generations agreed to participate in the study. This included samples from eight affected subjects, one glaucoma suspect, one normal individual, and two spouses in generations II and III, and an additional eight individuals in generation IV. The phenotype in this family appears to be variable, with onset of visual field loss in middle age, followed by modest elevation of intraocular pressure and progression of the disease in older individuals. Linkage was established with a group of DNA markers located in the 8q23 region. A lod score value of 3.61 was obtained using marker D8S1471. Three other markers from the same region gave lod score values of over 3.0. Haplotype transmission data identified two recombination events that placed the gene in a 6.3-cM region flanked by D8S1830 and D8S592. The disease-bearing haplotype was inherited by eight affected subjects and three glaucoma suspects. CONCLUSION: We present evidence for a third adult-onset primary open-angle glaucoma locus (GLC1D) on chromosome 8q23. The genetic heterogeneity of adult-onset glaucoma is evident from the multiplicity of chromosomal loci associated with this disease.
Assuntos
Mapeamento Cromossômico , Cromossomos Humanos Par 8 , Ligação Genética , Glaucoma de Ângulo Aberto/genética , Idoso , Doença Crônica , DNA/análise , Feminino , Marcadores Genéticos , Glaucoma de Ângulo Aberto/patologia , Haplótipos , Humanos , Escore Lod , Masculino , Pessoa de Meia-Idade , Disco Óptico/patologia , Linhagem , Reação em Cadeia da Polimerase , Sequências Repetitivas de Ácido Nucleico , Campos VisuaisRESUMO
Juvenile optic atrophy (Kjer type; OPA1) is an autosomal dominant trait with an insidious onset in the first decade of life. The condition is characterized by a progressive loss of visual acuity that usually occurs with severe defects in color vision and visual fields. Genetic linkage analysis of a number of families has already assigned the OPA1 locus to the 3q28-qter region, within an estimated region of about 8 cM that is flanked by D3S1601 and D3S1265. Our study of a four-generation English family also supported tight linkage between the OPA1 locus and a group of DNA markers from the reported region. Of the 13 markers genotyped in this family, D3S2305 provided the maximum LOD score of 3.91 at theta = 0.00. Inspection of the haplotype transmission in this family identified critical recombinant individuals that refined the location of the OPA1 locus to an estimated region of about 2cM that is flanked by two DNA markers of D3S1601 and D3S2748. This refinement should facilitate the molecular cloning of the OPA1 gene and the determination of its defective product.
Assuntos
Mapeamento Cromossômico , Cromossomos Humanos Par 3/genética , DNA/análise , Atrofias Ópticas Hereditárias/genética , Alelos , Feminino , Marcadores Genéticos , Genótipo , Haplótipos , Humanos , Escore Lod , Masculino , Pessoa de Meia-Idade , Linhagem , Reação em Cadeia da Polimerase , Sequências Repetitivas de Ácido Nucleico , Acuidade VisualRESUMO
Positional mapping of families segregating for juvenile-onset primary open angle glaucoma (JOAG) has previously identified a locus (GLCIA) for this condition on the long arm of chromosome I. Recently, three mutations in the TIGR gene (Trabecular meshwork Inducible Gluco-corticoid Response protein) have been described in a total of ten familial, three sporadic, and one normal subject. One of the familial cases has also been indicated to be of an adult-onset type. Herein, we report the identification of a new mutation in the TIGR gene in a six generation well-documented Edinburgh family with JOAG. We have sampled and screened the living affected members of this family and identified an 'A'-to-'G' transition at amino acid 337 that has changed the glutamine (Gln) to arginine (Arg). This newly identified mutation resides 27 amino acids 5-prime from the previously reported mutation of Gly-to-Val. This mutation created a new MspI restriction site that has co-segregated perfectly with inherited affected haplotype of the pedigree and, furthermore, it has not been observed in 142 chromosomes of randomly selected subjects of the same population. This report, therefore, confirms the role of the TIGR gene in the etiology of JOAG and adds a new mutation to the three reported previously.
Assuntos
Proteínas do Olho/genética , Glaucoma de Ângulo Aberto/genética , Glicoproteínas , Mutação Puntual , Cromossomos Humanos Par 1/genética , Proteínas do Citoesqueleto , Análise Mutacional de DNA , Feminino , Marcadores Genéticos , Genótipo , Humanos , Masculino , Linhagem , Reação em Cadeia da Polimerase , Malha TrabecularRESUMO
The infrared (IR) spectra of Co(HCOO)2 x 2H2O, Ni(HCOO)2 x 2H2O and Cu2Co(Ni)1-x (HCOO)2 x 2H2O mixed crystals (0 < x < or = 0.5) have been recorded and the internal modes of the formate groups and the water molecules are discussed. The analysis of the spectra of the mixed crystals reveals that when copper ions replace cobalt and nickel ions in Co(HCOO) x 2H2O and Ni(HCOO)2 x 2H2O, the Cu2+ ions are localized at the two available positions. However, the occupancy degree of the Me(1) and Me(2) sites by the different cations needs X-ray diffraction (XRD) studies of the single crystals. The new crystal phase Co0.17Cu0.83(HCOO)2 x 2H2O obtained from the Co(HCOO)2 x 2H2O-Cu(HCOO)2 x 2H2O-H2O system at 50 degrees C crystallizes in the monoclinic system with lattice parameters: a = 12.329(4); b = 7.241(2); c = 8.707(5) A and beta = 103.13(3) degrees (SG probably P2/c). The number of the bands corresponding to the uncoupled OD vibrations and the water librations shows that probably more than two water molecules are expected to exist in the structure. Furthermore, it is assumed that the water molecules bonded to the copper ions form stronger hydrogen bonds (stronger Cu-OH2 interaction) than those bonded to the cobalt ions.
Assuntos
Cobalto/química , Cobre/química , Formiatos/química , Níquel/química , Cátions , Espectrofotometria Infravermelho/métodosRESUMO
Synthetic malachite, hydrozincite and five monophasic mixed copper-zinc hydroxycarbonates have been studied by Fourier transform infrared (FTIR) spectroscopy at ambient and liquid nitrogen temperature in the region of 4000-400 cm(-1). The analysis of the spectra reveals that the samples containing up to 20% zinc retain the malachite lattice, thus forming solid solutions. The inclusion of zinc ions in malachite reflects on the positions and intensity of the bands corresponding to the internal modes of the carbonate ion, to the OH librations and to the Me-O interactions. For example, the higher and the lower frequency components of v3 shift to higher and lower frequencies, respectively. The intensity of the bands corresponding to v2 decreases with the zinc content increase. The spectrum of the sample Cu1.31Zn0.69(OH)2CO3 become diffuse and ill-resolved in the region of the Me-O interactions (region below 600 cm(-1)) and the corresponding bands are shifted to lower frequencies due to the weaker Zn-O interactions as compared with those of the copper ions. The internal modes of the carbonate ions in hydrozincite and aurichalcite are assigned and discussed taking into account the site symmetry and factor group symmetry. The OH and OD stretches (matrix-isolated HDO molecules) and the hydrogen bond strengths are interpreted in terms of Me-O interactions (synergetic effect), hydrogen bond angles and different hydrogen bond acceptor strengths of the oxygen atoms from the carbonate ions. It proves that the hydrogen bonds in hydrozincite are stronger as compared with those in malachite, irrespective of both the larger hydrogen bond lengths and the weaker Zn-O interactions in hydrozincite due to the higher hydrogen bond acceptor strength of the non-coordinated oxygen atom and the formation of bifurcated hydrogen bonds.
Assuntos
Compostos de Zinco/química , Carbonatos/química , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
gp96 is a residential heat shock protein of the endoplasmic reticulum that has been implicated in the activation of dendritic cells (DCs) for the initiation of adaptive immunity. By genetic targeting of gp96 onto the cell surface, we demonstrate that direct access of gp96 to DCs induces their maturation, resulting in secretion of proinflammatory cytokines IL-1beta, IL-12, and chemokine monocyte chemoattractant protein-1 and up-regulation of the expression of MHC class I, MHC class II, CD80, CD86, and CD40. Furthermore, surface expression of gp96 on tumor cells renders them regressive via a T lymphocyte-dependent mechanism. This work reinforces the notion that gp96 is an endogenous DC activator and unveils that the context in which Ag is delivered to the immune system, in this case surface expression of gp96, has profound influence on immunity. It also establishes a principle of bridging innate and adaptive immunity for cancer immunotherapy by surface targeting of an intracellular heat shock protein.
Assuntos
Antígenos de Neoplasias/metabolismo , Antígenos de Neoplasias/fisiologia , Células Dendríticas/imunologia , Neoplasias Experimentais/imunologia , Animais , Apresentação de Antígeno , Antígenos CD/biossíntese , Antígenos de Neoplasias/genética , Antígenos de Superfície/genética , Antígenos de Superfície/metabolismo , Antígenos de Superfície/fisiologia , Diferenciação Celular , Células Cultivadas , Citocinas/biossíntese , Marcação de Genes , Células-Tronco Hematopoéticas/imunologia , Antígenos de Histocompatibilidade/biossíntese , Camundongos , Modelos Biológicos , Transporte Proteico , Linfócitos T Citotóxicos/imunologia , Células Tumorais Cultivadas , Regulação para CimaRESUMO
Primary open angle glaucoma (GLC1) is a common ocular disorder with a characteristic degeneration of the optic nerve and visual field defects that is often associated with an elevated intraocular pressure. The severe but rare juvenile-onset type has previously been mapped to 1q21-q31, and its genetic heterogeneity has been established. Herein, we present a new locus (GLC1B) for one form of GLC1 on chromosome 2cen-q13 with a clinical presentation of low to moderate intraocular pressure, onset in late 40s, and a good response to medical treatment. Two-point and haplotype analyses of affected and unaffected meioses in six families provided maximum linkage information with D2S417, GATA112EO3, D2S113, D2S373, and D2S274 (lod scores ranging from 3.11 to 6.48) within a region of 8.5 cM that is flanked by D2S2161 and D2S2264. Analysis of affected meioses alone revealed no recombination with an additional two markers (D2S2264 and D2S135) in a region of 11.2 cM that is flanked by D2S2161 and D2S176. Analysis of unaffected meioses identified only one healthy 86-year-old male who has inherited the entire affected haplotype and, hence, is a gene carrier for this condition. Eight additional families with similar and/or different clinical presentation did not show any linkage to this region and, therefore, provided evidence for genetic heterogeneity of adult-onset primary open angle glaucoma.
Assuntos
Mapeamento Cromossômico/métodos , Cromossomos Humanos Par 2/genética , Glaucoma de Ângulo Aberto/genética , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Centrômero/genética , Feminino , Triagem de Portadores Genéticos , Heterogeneidade Genética , Glaucoma de Ângulo Aberto/fisiopatologia , Haplótipos , Humanos , Escore Lod , Masculino , Repetições de Microssatélites/genética , Pessoa de Meia-Idade , Linhagem , Polimorfismo GenéticoRESUMO
One of the major causes of blindness is primary open-angle glaucoma, which affects millions of elderly people worldwide. Genetic studies have so far mapped three loci for the adult-onset form of this condition to the 2cen-q13, 3q21-q24, and 8q23 regions. Herein, we report the localization of a fourth locus, to the 10p15-p14 region, in one large British family with a classical form of normal-tension open-angle glaucoma. Of the 42 meioses genotyped in this pedigree, 39 subjects (16 affected) inherited a haplotype compatible with their prior clinical designation, whereas the remaining 3 were classified as unknown. Although a maximum LOD score of 10.00 at a recombination fraction of straight theta=.00 was obtained with D10S1216, 21 other markers provided significant values, varying between 3.77 and 9.70. When only the affected meioses of this kindred were analyzed, LOD scores remained statistically significant, ranging from 3.16 (D10S527) to 3.57 (D10S506). Two critical recombinational events in the affected subjects positioned this new locus to a region of approximately 21 cM, flanked by D10S1729 and D10S1664. However, an additional recombination in a 59-year-old unaffected female suggests that this locus resides between D10S585 (or D10S1172) and D10S1664, within a genetic distance of 5-11 cM. However, the latter minimum region must be taken cautiously, because the incomplete penetrance has previously been documented for this group of eye conditions. A partial list of genes that positionally are considered as candidates includes NET1, PRKCT, ITIH2, IL2RA, IL15RA, IT1H2, hGATA3, the mRNA for open reading frame KIAA0019, and the gene for D123 protein.
Assuntos
Cromossomos Humanos Par 10 , Glaucoma de Ângulo Aberto/genética , Adulto , Idade de Início , Idoso , Mapeamento Cromossômico , Feminino , Ligação Genética , Marcadores Genéticos , Genótipo , Haplótipos , Humanos , Escore Lod , Masculino , Pessoa de Meia-Idade , Fenótipo , Recombinação GenéticaRESUMO
Mutations in the trabecular meshwork induced glucocorticoid response protein (TIGR) or myocilin (MYOC) has recently been shown to cause juvenile onset primary open angle glaucoma (JOAG). In this study, we identified two new mutations (Asp380Ala and Ser502Pro) in two British families and another (Pro370Leu) in a French-Canadian family. These mutations were not present in a total of 106 normal chromosomes. In another Turkish family with JOAG, we also detected a sequence variant that was proven to be an amino acid polymorphism (Arg76Lys). No other sequence changes were found in the entire coding region and splice junctions of the TIGR/MYOC gene in this family. However, it is still possible that mutations either in the TIGR promoter or in another neighbouring gene could cause glaucoma in this JOAG family. Our results confirm the role of the TIGR/MYOC gene in the aetiology of the JOAG phenotype.