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1.
Phys Chem Chem Phys ; 23(1): 470-486, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33320120

RESUMO

In the present study, solid-state nuclear magnetic resonance (NMR) spectra under magic angle spinning conditions of the rhombohedral structures α-B and B12P2 are reported together with the corresponding parameter sets from first principles calculations on α-B B12X2 (X = P, As, O). With the combination of density functional theory (DFT) and the gauge-including projector-augmented wave (GIPAW) approach as the theoretical tools at hand the computed 11B parameters lead to unambiguous explanation of the measurements. Thereby, we overcome common obstacles of processing recorded NMR spectra of solid-state compounds with several crystallographic positions, in particular non-trivial signal assignments and parameter determination due to peak overlap or even unexpected intensity/area ratios. In fact, we find very good agreement between the theoretical results and measured spectra without applying fitting procedures. Using the Perdew-Burke-Ernzerhof (PBE) functional, the results of the common construction types for pseudopotentials and referencing methods for the chemical shift determination are compared. Suggestions and conclusions from experimental 11B NMR studies on parameters according to the icosahedral positions are critically discussed, for instance the early suspected correlation to chemical shifts is not confirmed. Regarding the electric field gradient (EFG) a detailed explanation for obtaining small deviations amongst all investigated structures of the icosahedral polar sites compared to the equatorial sites is given. Our results show an important link between the exohedral bonding situation of compounds with icosahedral structure elements and the main axis of the EFG and therefore, also measurable quadrupole coupling constants if certain geometrical conditions are fulfilled. Finally, this work also contributes to establishing the number of unique sites measured by solid-state NMR methods within the modification of ß-B.

2.
Phys Chem Chem Phys ; 23(6): 3883-3897, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33539490

RESUMO

Based on the work on referencing 11B nuclear magnetic resonance (NMR) spectra for molecular icosahedral boranes and the subsequent transfer to the rhombohedral boron-rich borides of the α-rB12 type, we show that the magic angle spinning (MAS) NMR spectra of boron-rich borides with four or five symmetry-independent boron atoms can also be calculated. The calculations are performed on the level of density functional theory (DFT) using the gauge-including projector-augmented wave (GIPAW) approach. As model compounds o-MgB12C2 and MgB7 are used, for which the experimental spectra could be calculated in excellent agreement with a deviation of 1 to 2 ppm. Based on the calculations, the different B atoms can be assigned to the respective signals, taking into account the quadrupolar coupling constants Cq from computation of the electric field gradient (EFG) with its main axis Vzz. It is shown that due to the specific geometric conditions of icosahedra, the magnitudes of Vzz for the boron atoms involved in exohedral B-B bonds to neighbouring icosahedra depend only on the valence electron density of the bond critical point and the distance. This also applies to the bonds to the interstitial B2 unit in MgB7, but not to bonds to the heteroatom of the C2 dumbbell in o-MgB12C2. Both results are in line with our previous observations for the rhombohedral species (α-rB12; B12X2 with X = P, As, O). Finally, the spectrum of γ-B28 was calculated, whose structure also contains B12 icosahedra and interstitial B2 dumbbells. Here, a very similar bonding situation is found for the icosahedron, but the calculations show that the situation for the B2 unit is clearly different. In general, the only parameter that needs to be varied to fit calculated and measured spectra is the linewidth, as this cannot be calculated. For the cases of o-MgB12C2 and MgB7 signal areas are related to corresponding site multiplicities. A prerequisite for the successful application of the chosen method seems to be the presence of a semiconductor with a sufficiently large band gap, which is the case for the compounds investigated.

3.
J Phys Chem A ; 124(11): 2173-2185, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-31999459

RESUMO

In this work, we perform first-principle density functional theory calculations with the Perdew-Burke-Ernzerhof (PBE) exchange correlation functional to compare the results of the gauge-including atomic orbital (GIAO) method with the gauge-including projector-augmented wave (GIPAW) approach for isotropic 11B nuclear magnetic resonance shifts. GIPAW had been used successfully for the theoretical calculation of nuclear magnetic parameters of 11B species in strong ionic solid-phase compounds such as borates but had been applied very rarely to structures where boron is mainly involved in complex covalent bonding situations, for example, in icosahedra of boron-rich borides. Thus, we investigate the accuracy of both well-known methods and reliability of the effective treatment of core electrons on a test set containing 16 experimentally known closo-(hetero)dodecaboranes. In general, we find very good agreement between GIAO and GIPAW when compared to experimental observations. However, accidental degeneracies of the shift values are better predicted by GIPAW. The optimized molecular geometries on the PBE level agree well with gaseous electron diffraction data and lead to theoretical isotropic chemical 11B shifts with root-mean-square errors of 2.1 and 1.0 ppm depending on the used model of converting absolute shieldings to chemical shifts. The comparison with results from hybrid functionals (B3LYP, B3LYP-D2, and PBE0) shows a minor improvement in accuracy, which is in agreement with 13C shifts of sp3-hybridized species. In order to prove the reliability of the conversion parameters obtained by PBE, we report the calculated 11B shifts of 1,2-, 1,7-, and 1,12-PCB10H11 with GIAO and GIPAW to our knowledge for the first time. Additionally, Bader's analysis is carried out on the converged electron density for all boron species within the molecular test set, yielding no simple direct relation between charge and isotropic shifts.

4.
J Chem Phys ; 147(2): 024101, 2017 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-28711065

RESUMO

An efficient implementation of energy gradients and of hyperfine coupling constants in second-order Møller-Plesset perturbation theory (MP2) is presented based on our fully atomic orbital (AO)-based approach. For the latter, an unrestricted AO-based MP2 formulation is introduced. A reduction in the dependency of the computational efficiency on the size of the basis set is achieved by a Cholesky decomposition and the prefactor is reduced by the resolution-of-the-identity approximation. Significant integral contributions are selected based on distance-including integral estimates (denoted as QQR-screening) and its reliability as a fully controlled screening procedure is demonstrated. The rate-determining steps are shown via model computations to scale cubically in the computation of energy gradients and quadratically in the case of hyperfine coupling constants. Furthermore, a significant speed-up of the computational time with respect to the canonical formulation is demonstrated.

5.
Oecologia ; 179(2): 455-66, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26025575

RESUMO

Plant size is a major predictor of ecological functioning. We tested the hypothesis that feeding damage to plants increases with plant size, as the conspicuousness of large plants makes resource finding and colonisation easier. Further, large plants can be attractive to herbivores, as they offer greater amounts and ranges of resources and niches, but direct evidence from experiments testing size effects on feeding damage and consequently on plant fitness is so far missing. We established a common garden experiment with a plant size gradient (10-130 cm height) using 21 annual Brassicaceae species, and quantified plant size, biomass and number of all aboveground components (flowers, fruits, leaves, stems) and their proportional feeding damage. Plant reproductive fitness was measured using seed number, 1000 seed weight and total seed weight. Feeding damage to the different plant components increased with plant size or component biomass, with mean damage levels being approximately 30 % for flowers, 5 % for fruits and 1 % for leaves and stems. Feeding damage affected plant reproductive fitness depending on feeding damage type, with flower damage having the strongest effect, shown by greatly reduced seed number, 1000 seed weight and total seed weight. Finally, we found an overall negative effect of plant size on 1000 seed weight, but not on seed number and total seed weight. In conclusion, being conspicuous and attractive to herbivores causes greater flower damage leading to higher fitness costs for large plants, which might be partly counterbalanced by benefits such as enhanced competitive/compensatory abilities or more mutualistic pollinator visits.


Assuntos
Brassicaceae/fisiologia , Herbivoria , Biomassa , Brassicaceae/anatomia & histologia , Brassicaceae/crescimento & desenvolvimento , Flores/anatomia & histologia , Flores/crescimento & desenvolvimento , Flores/fisiologia , Folhas de Planta/anatomia & histologia , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/fisiologia , Polinização , Sementes/anatomia & histologia , Sementes/crescimento & desenvolvimento , Sementes/fisiologia , Simbiose
6.
Audiol Neurootol ; 19(3): 203-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24801666

RESUMO

Norrie disease is a rare, X-linked genetic syndrome characterized by combined congenital blindness and progressive hearing impairment. Norrie disease is caused by alterations in the NDP gene encoding the growth factor norrin that plays a key role in vascular development and stabilization of the eye, inner ear and brain. We identified a family with 3 affected deafblind males and a single female carrier presenting with a serous retinal detachment but normal hearing. Genetic analysis revealed a novel c.277T>C missense mutation causing the substitution of a hydrophobic cysteine to a hydrophilic arginine [p.(Cys93Arg)] within the highly conserved cysteine knot domain of the norrin protein. These results should expand the scope for amniocentesis and genetic testing for Norrie disease which is gaining in importance due to novel postnatal therapeutic concepts to alleviate the devastating retinal symptoms of Norrie disease.


Assuntos
Cegueira/congênito , Proteínas do Olho/genética , Mutação de Sentido Incorreto , Proteínas do Tecido Nervoso/genética , Doenças do Sistema Nervoso/genética , Espasmos Infantis/genética , Cegueira/genética , Família , Feminino , Doenças Genéticas Ligadas ao Cromossomo X , Testes Genéticos , Humanos , Masculino , Linhagem , Degeneração Retiniana
7.
Respir Res ; 14: 124, 2013 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-24219370

RESUMO

BACKGROUND: The common cold is the most widespread viral infection in humans. Iota-carrageenan has previously shown antiviral effectiveness against cold viruses in clinical trials. This study investigated the efficacy of a carrageenan-containing nasal spray on the duration of the common cold and nasal fluid viral load in adult patients. METHODS: In a randomized, double-blind, placebo-controlled trial, 211 patients suffering from early symptoms of the common cold were treated for seven days. Application was performed three times daily with either a carrageenan-supplemented nasal spray or saline solution as placebo with an overall observation period of 21 days. The primary endpoint was the duration of disease defined as the time until the last day with symptoms followed by all other days in the study period without symptoms. During the study, but prior unblinding, the definition of disease duration was adapted from the original protocol that defines disease duration as the time period of symptoms followed by 48 hours without symptoms. RESULTS: In patients showing a laboratory-confirmed cold virus infection and adherence to the protocol, alleviation of symptoms was 2.1 days faster in the carrageenan group in comparison to placebo (p = 0.037). The primary endpoint that had been prespecified but was changed before unblinding was not met. Viral titers in nasal fluids showed a significantly greater decrease in carrageenan patients in the intention-to-treat population (p = 0.024) and in the per protocol population (p = 0.018) between days 1 and 3/4. CONCLUSIONS: In adults with common cold virus infections, direct local administration of carrageenan with nasal sprays reduced the duration of cold symptoms. A significant reduction of viral load in the nasal wash fluids of patients confirmed similar findings from earlier trials in children and adults. TRIAL REGISTRATION: Current Controlled Trials ISRCTN80148028.


Assuntos
Antivirais/uso terapêutico , Carragenina/uso terapêutico , Resfriado Comum/tratamento farmacológico , Resfriado Comum/virologia , Sprays Nasais , Administração Intranasal , Adulto , Antivirais/administração & dosagem , Antivirais/farmacologia , Carragenina/administração & dosagem , Carragenina/farmacologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Líquido da Lavagem Nasal/virologia , Rhinovirus/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento , Carga Viral/efeitos dos fármacos
8.
Phys Chem Chem Phys ; 15(44): 19253-61, 2013 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-24113576

RESUMO

A proof of principle is presented for the rational design of metal clusters functionalized with hydrophilic, chiral ligands. A colloidal method is used to prepare "unprotected" metal clusters of well-defined size that are subsequently functionalized in a separate step with hydrophilic, chiral ligands. As clusters from the same batch are functionalized with different organic molecules while the cluster size is maintained, the approach allows for systematic investigations and the differences in the observed properties to be related to the influence of the functionalizing ligand. Within this work cysteine and two cysteine derivatives (glutathione and N-acetyl-cysteine) are used as functionalizing ligands for Pt clusters. The materials are characterized using various methods allowing for the determination of ligand coverage, binding mode and chiro-optical properties. Finally, 2-butanone hydrogenation is used as a simple model reaction to demonstrate that these systems exhibit the potential to be used as asymmetric, heterogeneous catalysts. The observed differences in selectivity and reactivity are discussed based on the knowledge gained from the characterization.


Assuntos
Ligantes , Metais/química , Acetilcisteína/química , Butanonas/química , Catálise , Cisteína/química , Glutationa/química , Hidrogenação , Interações Hidrofóbicas e Hidrofílicas , Platina/química , Estereoisomerismo
9.
Electrophoresis ; 30(16): 2765-72, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19653233

RESUMO

Advances in microfluidic chips for chiral separations from 2003 to early 2009 are discussed. Microchip-based separation techniques promise higher speed, throughput, portability, less sample and reagent consumption, better environmental compatibility, reduced cost and the prospect of system integration. Microchip electrophoresis is the most promising technique for miniaturized enantioseparations and has been performed with a variety of designs and analytes, however, other formats such as microchip electrochromatography are also gaining in popularity. Microchip fabrication, chemistry and detection issues are critically discussed and highlighted. Integration of enantioseparation techniques into multifunctional microchips are currently a rapidly advancing area of research and methods are discussed that may eventually enable enantioseparations to be the part of a holistic chemical microchip.


Assuntos
Eletroforese em Microchip/métodos , Eletrocromatografia Capilar , Miniaturização , Estereoisomerismo , Temperatura
10.
Electrophoresis ; 29(24): 4894-9, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19025868

RESUMO

A high intensity 266 nm continuous wave (cw-) laser developed for material processing was utilised as an excitation source for sensitive native fluorescence detection of unlabelled compounds in MCE. This 120 mW laser was attached via an optical fibre into a commercial epifluorescence microscope. With this MCE set-up we evaluated the impact of laser power on the S/N of aromatic compounds as well as of proteins. Compared with a previous work which used a 4 mW pulsed laser for excitation, improved S/N for small aromatics and to a lesser extent for proteins could be attained. The LOD of the system was determined down to 24 ng/mL for serotonin (113 nM), 24 ng/mL for propranolol (81 nM), 80 ng/mL for tryptophan (392 nM) and 80 ng/mL for an aromatic diol (475 nM). Sensitive protein detection was obtained at concentrations of 5 microg/mL for lysocyme, trypsinogen and chymotrypsinogen (340, 208 and 195 nM, respectively). Finally, a comparison of the cw- with a pulsed 266 nm laser, operating at the same average power, showed a higher attainable sensitivity of the cw-laser. This can be attributed to fluorescence saturation and photobleaching effects of the pulsed laser at high pulse energies.


Assuntos
Eletroforese em Microchip/instrumentação , Lasers , Proteínas/análise , Espectrometria de Fluorescência/instrumentação , Raios Ultravioleta , Eletroforese em Microchip/métodos , Sensibilidade e Especificidade , Espectrometria de Fluorescência/métodos
11.
J Chem Theory Comput ; 14(6): 3014-3024, 2018 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-29762028

RESUMO

We introduce a new ansatz to compute hyperfine coupling constants of selected nuclei at the level of second-order Møller-Plesset perturbation (MP2) and double-hybrid density functional theory with reduced computational effort, opening the route to the analyis of hyperfine coupling constants of large molecular structures. Our approach is based on a reformulation of the canonical MP2 term in atomic orbitals, thus exploiting the locality of electron correlation. We show that a perturbation-including integral screening reduces the scaling behavior of the number of significant two-electron integrals to sublinear. This selected-nuclei approach allows for an efficient computation within scaled-opposite spin (SOS) RI-MP2 on massively parallelized architectures such as graphical processor units (GPUs), thus enabling studies on the influence of the environment on hyperfine coupling constants.

12.
Otol Neurotol ; 28(7): 884-6, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17955603

RESUMO

OBJECTIVE: To analyze the prevalence and importance of the maternally inherited A1555G mutation in the 12S rRNA gene in the Austrian population. STUDY DESIGN: Investigation for mutations of genetically affected familial and sporadic cases of hearing impairment (HI), including analyses of audiometric data. SETTING: Teaching hospital, tertiary referral center. PATIENTS: Forty-five familial and 77 sporadic cases of nonsyndromic HI in an Austrian Caucasian ethnic group. MAIN OUTCOME MEASURE(S): Pure-tone audiometric data and screening by restriction fragment length polymorphism analysis after exclusion of GJB2 (Connexin 26) caused hearing loss. RESULTS: In the investigated hearing-impaired population, the mutation A1555G in the mitochondrial 12S rRNA gene was not detected. CONCLUSION: The A1555G mutation in the mitochondrial DNA 12S rRNA is not a major cause of HI in the Austrian Caucasian population.


Assuntos
Perda Auditiva/epidemiologia , Perda Auditiva/genética , RNA Ribossômico/genética , Audiometria de Tons Puros , Áustria/epidemiologia , Conexina 26 , Conexina 30 , Conexinas/genética , DNA/genética , DNA Mitocondrial/genética , Frequência do Gene , Humanos , Mutação/fisiologia , Polimorfismo de Fragmento de Restrição
13.
Int J Oncol ; 27(2): 307-15, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16010410

RESUMO

The human prostate gland is a well known source of H1 and H2 relaxin but information is lacking on the expression and potential role of the INSL3 peptide hormone within the prostate gland. In the present study we have investigated the expression of human INSL3 in patients with benign prostate hyperplasia (BPH), prostate intraepithelial neoplasia (PIN) and prostate carcinoma tissues. Of the prostate epithelial cells, strongest INSL3 expression was detected in the basal epithelial cell compartment. Weaker INSL3 mRNA expression and immunoreactive INSL3 production were observed in secretory epithelial cells and in interstitial smooth muscle cells. Prostate epithelial cells were also a source for transcripts encoding the INSL3 receptor LGR8 suggesting the presence of an autocrine/paracrine INSL3-LGR8 ligand-receptor system within the human prostate. Three human prostate carcinoma cell lines displayed differential gene activity for INSL3 and LGR8. While LNCaP was devoid of INSL3, the androgen-insensitive PC-3 and the stromal prostate cell line hPCP co-expressed INSL3 and LGR8 transcripts. In addition to expressing INSL3 mRNA, the LGR8-negative DU-145 also expressed an INSL3 splice form formerly demonstrated in thyroid carcinoma cells. When incubated with recombinant INSL3, PC-3 cells showed significantly increased intracellular cAMP levels indicating functional LGR8 receptors. INSL3 did not alter the proliferative or metabolic activity of PC-3 carcinoma cells. Instead, PC-3 responded to INSL3 with significantly enhanced tumor cell motility and a transcriptional down-regulation of ErbB receptors and EGF. All-trans-retinoic acid was demonstrated in PC-3 to up-regulate LGR8 gene activity in a dose- and time-dependent manner while having no effect on INSL3 gene activity. In conclusion, we have identified a functional INSL3-LGR8 ligand-receptor system in human prostate carcinoma cells.


Assuntos
Insulina/genética , Hiperplasia Prostática/patologia , Neoplasia Prostática Intraepitelial/patologia , Neoplasias da Próstata/patologia , Proteínas/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , AMP Cíclico/metabolismo , Relação Dose-Resposta a Droga , Fator de Crescimento Epidérmico/farmacologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Expressão Gênica/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Hibridização In Situ , Insulina/análise , Insulina/farmacologia , Masculino , Hiperplasia Prostática/genética , Hiperplasia Prostática/metabolismo , Neoplasia Prostática Intraepitelial/genética , Neoplasia Prostática Intraepitelial/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Proteínas/análise , Proteínas/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Acoplados a Proteínas G/análise , Receptores Acoplados a Proteínas G/genética , Proteínas Recombinantes/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Tretinoína/farmacologia
14.
PLoS One ; 10(8): e0135928, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26291614

RESUMO

Large plants are often more conspicuous and more attractive for associated animals than small plants, e.g. due to their wider range of resources. Therefore, plant size can positively affect species richness of associated animals, as shown for single groups of herbivores, but studies usually consider intraspecific size differences of plants in unstandardised environments. As comprehensive tests of interspecific plant size differences under standardised conditions are missing so far, we investigated effects of plant size on species richness of all associated arthropods using a common garden experiment with 21 Brassicaceae species covering a broad interspecific plant size gradient from 10 to 130 cm height. We recorded plant associated ecto- and endophagous herbivores, their natural enemies and pollinators on and in each aboveground plant organ, i.e. flowers, fruits, leaves and stems. Plant size (measured as height from the ground), the number of different plant organ entities and their biomass were assessed. Increasing plant size led to increased species richness of associated herbivores, natural enemies and pollinating insects. This pattern was found for ectophagous and endophagous herbivores, their natural enemies, as well as for herbivores associated with leaves and fruits and their natural enemies, independently of the additional positive effects of resource availability (i.e. organ biomass or number of entities and, regarding natural enemies, herbivore species richness). We found a lower R2 for pollinators compared to herbivores and natural enemies, probably caused by the high importance of flower characteristics for pollinator species richness besides plant size. Overall, the increase in plant height from 10 to 130 cm led to a 2.7-fold increase in predicted total arthropod species richness. In conclusion, plant size is a comprehensive driver of species richness of the plant associated arthropods, including pollinators, herbivores and their natural enemies, whether they are endophagous or ectophagous or associated with leaves or fruits.


Assuntos
Brassicaceae/fisiologia , Comportamento Alimentar/fisiologia , Herbivoria/fisiologia , Componentes Aéreos da Planta/fisiologia , Polinização/fisiologia , Animais , Biomassa , Insetos/fisiologia , Dinâmica Populacional
15.
Otol Neurotol ; 34(4): 650-6, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23640091

RESUMO

HYPOTHESIS: Additional genetic changes in the regulatory region of the human GJB2 gene encoding the gap junction protein (Connexin 26) may contribute to sensorineural hearing loss. BACKGROUND: Mutations in GJB2 cause up to 50% of autosomal recessive nonsyndromic hearing impairment (NSHI). METHODS: In the present study, we screened the putative 5' GJB2 regulatory region for novel alterations. RESULTS: In idiopathic familial cases of NSHI lacking known pathogenic alterations in GJB2, we identified a T→C transition (refSNP: rs117685390) in a putative transcription factor binding sequence 228 bp proximal to the transcriptional start site at a homozygous frequency of 0.125 (n = 40), significantly overrepresented in comparison to the homozygous allele frequencies of 0.043 in the normal-hearing Caucasian population (n = 211; p < 0.001). In a NSHI family, inheritance of the rs117685390 C allele segregated on independent chromosomes with NSHI in conjunction with heterozygous inheritance of c.35delG, the most common Caucasian mutation in the GJB2 coding region. In a patient group (n = 32) bearing heterozygous pathogenic c.35delG mutations, - rs117685390 C allele homozygosity was also highly overrepresented (0.25; p < 0.001) and not exclusively linked to the c.35delG mutation in cis in patients homozygous for c.35delG. However, in the majority of NSHI homozygous c.35delG chromosomes examined (91/94), c.35delG homozygosity was linked to the rs117685390 C allele in cis. CONCLUSION: These results suggest that the rs117685390 C allele could represent a biomarker for the development of NSHI in Caucasian populations and may be included in risk assessment for the development of NSHI.


Assuntos
Conexinas/genética , Perda Auditiva/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Conexina 26 , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Perda Auditiva Neurossensorial/genética , Homozigoto , Humanos , Masculino , Mutação
16.
17.
Laryngoscope ; 120(2): 359-64, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19950373

RESUMO

OBJECTIVES/HYPOTHESIS: Analysis of association between genotype and phenotype. STUDY DESIGN: Prospective genetic study in a family. METHODS: Auditory investigations, computer tomography, and genetic sequencing of the fibroblast growth factor 3 (FGF3) gene were performed on a Somali family presenting with autosomal recessive, hearing impairment, microdontia, and outer ear morphologies ranging from normal auricle development to microtia assessed as type 1 Weerda dysplasia in affected individuals. RESULTS: Computed tomography imaging identified differential inter- and intraindividual malformations of the inner ear including labyrinth aplasia, development of a common cavity to the presence of a cochlear with 1.5 windings (Mondini malformation) in affected individuals, symptoms similar to those described as labyrinth aplasia, microtia, and microdontia (LAMM) syndrome, caused by mutations in FGF3. Genetic sequencing revealed the presence of a novel p.R95W missense mutation in FGF3 segregating with pathology. The p.R95W mutation substitutes a positively charged arginine for a polar tryptophan in the highly conserved RYLAM consensus of the beta 6 sheet of FGF3 that interacts with FGFR2. CONCLUSIONS: These findings describe, for the first time, variable inner ear malformations and outer ear dysplasia in the presence of constant microdontia, associated with homozygous inheritance of the p.R95W mutation in FGF3, mirroring phenotypes observed in mouse models ablating FGF3/FGFR2 signaling.


Assuntos
Anormalidades Múltiplas/genética , Orelha Externa/anormalidades , Orelha Interna/anormalidades , Fator 3 de Crescimento de Fibroblastos/genética , Mutação de Sentido Incorreto , Anormalidades Dentárias/genética , Feminino , Perda Auditiva Neurossensorial/congênito , Perda Auditiva Neurossensorial/genética , Humanos , Masculino , Linhagem
18.
Eur Urol ; 56(3): 544-51, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19524353

RESUMO

BACKGROUND: National Institutes of Health (NIH) category III prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent condition for which no standardised treatment exists. OBJECTIVES: To assess the safety and efficacy of a standardised pollen extract in men with inflammatory CP/CPPS. DESIGN, SETTING, AND PARTICIPANTS: We conducted a multicentre, prospective, randomised, double-blind, placebo-controlled phase 3 study comparing the pollen extract (Cernilton) to placebo in men with CP/CPPS (NIH IIIA) attending urologic centres. INTERVENTION: Participants were randomised to receive oral capsules of the pollen extract (two capsules q8h) or placebo for 12 wk. MEASUREMENTS: The primary endpoint of the study was symptomatic improvement in the pain domain of the NIH Chronic Prostatitis Symptom Index (NIH-CPSI). Participants were evaluated using the NIH-CPSI individual domains and total score, the number of leukocytes in post-prostatic massage urine (VB3), the International Prostate Symptom Score (IPSS), and the sexuality domain of a life satisfaction questionnaire at baseline and after 6 and 12 wk. RESULTS AND LIMITATIONS: In the intention-to-treat analysis, 139 men were randomly allocated to the pollen extract (n=70) or placebo (n=69). The individual domains pain (p=0.0086) and quality of life (QoL; p=0.0250) as well as the total NIH-CPSI score (p=0.0126) were significantly improved after 12 wk of treatment with pollen extract compared to placebo. Response, defined as a decrease of the NIH-CPSI total score by at least 25% or at least 6 points, was seen in the pollen extract versus placebo group in 70.6% and 50.0% (p=0.0141), respectively. Adverse events were minor in all patients studied. CONCLUSIONS: Compared to placebo, the pollen extract significantly improved total symptoms, pain, and QoL in patients with inflammatory CP/CPPS without severe side-effects.


Assuntos
Fitoterapia , Extratos Vegetais/uso terapêutico , Prostatite/tratamento farmacológico , Adolescente , Adulto , Método Duplo-Cego , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Secale , Adulto Jovem
19.
Otol Neurotol ; 28(7): 884-886, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17704703

RESUMO

OBJECTIVE:: To analyze the prevalence and importance of the maternally inherited A1555G mutation in the 12S rRNA gene in the Austrian population. STUDY DESIGN:: Investigation for mutations of genetically affected familial and sporadic cases of hearing impairment (HI), including analyses of audiometric data. SETTING:: Teaching hospital, tertiary referral center. PATIENTS:: Forty-five familial and 77 sporadic cases of nonsyndromic HI in an Austrian Caucasian ethnic group. MAIN OUTCOME MEASURE(S):: Pure-tone audiometric data and screening by restriction fragment length polymorphism analysis after exclusion of GJB2 (Connexin 26) caused hearing loss. RESULTS:: In the investigated hearing-impaired population, the mutation A1555G in the mitochondrial 12S rRNA gene was not detected. CONCLUSION:: The A1555G mutation in the mitochondrial DNA 12S rRNA is not a major cause of HI in the Austrian Caucasian population.

20.
Electrophoresis ; 27(16): 3277-83, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16858723

RESUMO

Channels in microfluidic glass chips manufactured with the alternative powder blasting technology were permanently coated with poly(vinyl alcohol) (PVA) in order to improve the performance in microchip electrophoresis. The performance of coated and uncoated powder-blasted (pb) devices as well as coated and uncoated wet chemical etched (wc) chips was compared in electrophoretic separations of fluorescently labeled test compounds. The limited electrophoretic resolution obtained in pb-chips could significantly be improved by coating the channels with PVA. The resolution of test compounds in such coated pb-devices was even higher than in uncoated wc-chips. PVA-coated pb-chips could also successfully be applied in chiral separations. While in an uncoated pb-chip using a cyclodextrins buffer only one broad signal was obtained, two well-resolved signals were obtained in a coated device.


Assuntos
Eletroforese em Microchip/instrumentação , Vidro , Técnicas Analíticas Microfluídicas , Álcool de Polivinil/química , Sensibilidade e Especificidade , Estereoisomerismo
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