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1.
Science ; 365(6455): 817-820, 2019 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-31439797

RESUMO

The near-Earth asteroid (162173) Ryugu is a 900-m-diameter dark object expected to contain primordial material from the solar nebula. The Mobile Asteroid Surface Scout (MASCOT) landed on Ryugu's surface on 3 October 2018. We present images from the MASCOT camera (MASCam) taken during the descent and while on the surface. The surface is covered by decimeter- to meter-sized rocks, with no deposits of fine-grained material. Rocks appear either bright, with smooth faces and sharp edges, or dark, with a cauliflower-like, crumbly surface. Close-up images of a rock of the latter type reveal a dark matrix with small, bright, spectrally different inclusions, implying that it did not experience extensive aqueous alteration. The inclusions appear similar to those in carbonaceous chondrite meteorites.

2.
Mol Psychiatry ; 23(5): 1356-1367, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28416808

RESUMO

Synapse development and neuronal activity represent fundamental processes for the establishment of cognitive function. Structural organization as well as signalling pathways from receptor stimulation to gene expression regulation are mediated by synaptic activity and misregulated in neurodevelopmental disorders such as autism spectrum disorder (ASD) and intellectual disability (ID). Deleterious mutations in the PTCHD1 (Patched domain containing 1) gene have been described in male patients with X-linked ID and/or ASD. The structure of PTCHD1 protein is similar to the Patched (PTCH1) receptor; however, the cellular mechanisms and pathways associated with PTCHD1 in the developing brain are poorly determined. Here we show that PTCHD1 displays a C-terminal PDZ-binding motif that binds to the postsynaptic proteins PSD95 and SAP102. We also report that PTCHD1 is unable to rescue the canonical sonic hedgehog (SHH) pathway in cells depleted of PTCH1, suggesting that both proteins are involved in distinct cellular signalling pathways. We find that Ptchd1 deficiency in male mice (Ptchd1-/y) induces global changes in synaptic gene expression, affects the expression of the immediate-early expression genes Egr1 and Npas4 and finally impairs excitatory synaptic structure and neuronal excitatory activity in the hippocampus, leading to cognitive dysfunction, motor disabilities and hyperactivity. Thus our results support that PTCHD1 deficiency induces a neurodevelopmental disorder causing excitatory synaptic dysfunction.

3.
Mol Psychiatry ; 23(4): 973-984, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28397838

RESUMO

Approximately 1% of the global population is affected by intellectual disability (ID), and the majority receive no molecular diagnosis. Previous studies have indicated high levels of genetic heterogeneity, with estimates of more than 2500 autosomal ID genes, the majority of which are autosomal recessive (AR). Here, we combined microarray genotyping, homozygosity-by-descent (HBD) mapping, copy number variation (CNV) analysis, and whole exome sequencing (WES) to identify disease genes/mutations in 192 multiplex Pakistani and Iranian consanguineous families with non-syndromic ID. We identified definite or candidate mutations (or CNVs) in 51% of families in 72 different genes, including 26 not previously reported for ARID. The new ARID genes include nine with loss-of-function mutations (ABI2, MAPK8, MPDZ, PIDD1, SLAIN1, TBC1D23, TRAPPC6B, UBA7 and USP44), and missense mutations include the first reports of variants in BDNF or TET1 associated with ID. The genes identified also showed overlap with de novo gene sets for other neuropsychiatric disorders. Transcriptional studies showed prominent expression in the prenatal brain. The high yield of AR mutations for ID indicated that this approach has excellent clinical potential and should inform clinical diagnostics, including clinical whole exome and genome sequencing, for populations in which consanguinity is common. As with other AR disorders, the relevance will also apply to outbred populations.

4.
Science ; 355(6332): 1392-1395, 2017 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-28325842

RESUMO

The Rosetta spacecraft spent ~2 years orbiting comet 67P/Churyumov-Gerasimenko, most of it at distances that allowed surface characterization and monitoring at submeter scales. From December 2014 to June 2016, numerous localized changes were observed, which we attribute to cometary-specific weathering, erosion, and transient events driven by exposure to sunlight and other processes. While the localized changes suggest compositional or physical heterogeneity, their scale has not resulted in substantial alterations to the comet's landscape. This suggests that most of the major landforms were created early in the comet's current orbital configuration. They may even date from earlier if the comet had a larger volatile inventory, particularly of CO or CO2 ices, or contained amorphous ice, which could have triggered activity at greater distances from the Sun.

5.
Clin Genet ; 90(6): 563-565, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27747863

RESUMO

(a) Homozygosity-mapping-by-descent of four Bhakkar congenital indifference/insensitivity to pain (CIP) families. (b) Identification of mutation Met1190* in SCN9A. (c) SCN9A/NaV1.7 2D structure (as predicted by CCTOP and SMART) and approximate position of known nonsense (*) and missense (M) mutations ( www.hgmd.cf.ac.uk), as well as the Bhakkar mutation (this study) in red.


Assuntos
Mutação , Canal de Sódio Disparado por Voltagem NAV1.7/genética , Insensibilidade Congênita à Dor/genética , Análise Mutacional de DNA , Feminino , Homozigoto , Humanos , Masculino , Canal de Sódio Disparado por Voltagem NAV1.7/química , Insensibilidade Congênita à Dor/fisiopatologia , Paquistão , Linhagem , Conformação Proteica
6.
Mol Ecol ; 25(3): 825-41, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26661903

RESUMO

Processes shaping the distribution of foliar fungal endophyte species remain poorly understood. Despite increasing evidence that these cryptic fungal symbionts of plants mediate interactions with pathogens and herbivores, there remain basic questions regarding the extent to which dispersal limitation and host specificity might shape fungal endophyte community composition in rainforests. To assess the relative importance of spatial pattern and host specificity, we isolated fungi from a sample of mapped trees in lowland Papua New Guinea. Sequences of the internal transcribed spacer (ITS) region were obtained for 2079 fungal endophytes from three sites and clustered into molecular operational taxonomic units (MOTUs) at 95% similarity. Multivariate analyses suggest that host affinity plays a significant role in structuring endophyte community composition whereas there was no evidence of endophyte spatial pattern at the scale of tens to hundreds of metres. Differences in endophyte communities between sampled trees were weakly correlated with variation in foliar traits but not with tree species relatedness. The dominance of relatively few generalist endophytes and the presence of a large number of rare MOTUs was a consistent observation at three sites separated by hundreds of kilometres and regional turnover was low. Host specificity appears to play a relatively weak but more important role than dispersal limitation in shaping the distribution of fungal endophyte communities in New Guinea forests. Our results suggest that in the absence of strong ecological gradients and host turnover, beta diversity of endophyte communities could be low in large areas of contiguous forest.


Assuntos
Biodiversidade , Endófitos/classificação , Fungos/classificação , Floresta Úmida , Árvores/microbiologia , DNA Fúngico , DNA Espaçador Ribossômico/genética , Endófitos/genética , Fungos/genética , Dados de Sequência Molecular , Nova Guiné , Filogenia , Folhas de Planta/microbiologia , Análise Espacial
7.
Nature ; 528(7581): 237-40, 2015 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-26659183

RESUMO

The dwarf planet (1) Ceres, the largest object in the main asteroid belt with a mean diameter of about 950 kilometres, is located at a mean distance from the Sun of about 2.8 astronomical units (one astronomical unit is the Earth-Sun distance). Thermal evolution models suggest that it is a differentiated body with potential geological activity. Unlike on the icy satellites of Jupiter and Saturn, where tidal forces are responsible for spewing briny water into space, no tidal forces are acting on Ceres. In the absence of such forces, most objects in the main asteroid belt are expected to be geologically inert. The recent discovery of water vapour absorption near Ceres and previous detection of bound water and OH near and on Ceres (refs 5-7) have raised interest in the possible presence of surface ice. Here we report the presence of localized bright areas on Ceres from an orbiting imager. These unusual areas are consistent with hydrated magnesium sulfates mixed with dark background material, although other compositions are possible. Of particular interest is a bright pit on the floor of crater Occator that exhibits probable sublimation of water ice, producing haze clouds inside the crater that appear and disappear with a diurnal rhythm. Slow-moving condensed-ice or dust particles may explain this haze. We conclude that Ceres must have accreted material from beyond the 'snow line', which is the distance from the Sun at which water molecules condense.

9.
Clin Genet ; 88(3): 224-33, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25131214

RESUMO

Studies of genomic copy number variants (CNVs) have identified genes associated with autism spectrum disorder (ASD) and intellectual disability (ID) such as NRXN1, SHANK2, SHANK3 and PTCHD1. Deletions have been reported in PTCHD1 however there has been little information available regarding the clinical presentation of these individuals. Herein we present 23 individuals with PTCHD1 deletions or truncating mutations with detailed phenotypic descriptions. The results suggest that individuals with disruption of the PTCHD1 coding region may have subtle dysmorphic features including a long face, prominent forehead, puffy eyelids and a thin upper lip. They do not have a consistent pattern of associated congenital anomalies or growth abnormalities. They have mild to moderate global developmental delay, variable degrees of ID, and many have prominent behavioral issues. Over 40% of subjects have ASD or ASD-like behaviors. The only consistent neurological findings in our cohort are orofacial hypotonia and mild motor incoordination. Our findings suggest that hemizygous PTCHD1 loss of function causes an X-linked neurodevelopmental disorder with a strong propensity to autistic behaviors. Detailed neuropsychological studies are required to better define the cognitive and behavioral phenotype.


Assuntos
Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/genética , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Proteínas de Membrana/genética , Mutação , Fenótipo , Deleção de Sequência , Adolescente , Adulto , Criança , Pré-Escolar , Éxons , Facies , Feminino , Humanos , Lactente , Masculino , Adulto Jovem
11.
South Med J ; 107(12): 780-7, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25502159

RESUMO

Aging is progressively deteriorating physiological function that leads to increasing risks of illness and death. Increases in life expectancy and the aging of a large segment of the population have made age-related disability and morbidity increasingly important issues. Supplements such as α-lipoic acid may have antiaging effects by positively affecting oxidative stress, cognitive function, and cardiovascular function.


Assuntos
Envelhecimento/efeitos dos fármacos , Antioxidantes/farmacologia , Suplementos Nutricionais , Estresse Oxidativo/efeitos dos fármacos , Ácido Tióctico/farmacologia , Envelhecimento/fisiologia , Humanos
12.
Am J Med Sci ; 348(5): 366-70, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24841419

RESUMO

BACKGROUND: Mental stress (MS) reduces diastolic function (DF) and may lead to congestive heart failure with preserved systolic function. Whether brain natriuretic hormone (brain natriuretic peptide [BNP]) mediates the relationship of MS with DF is unknown. METHODS: One hundred sixty individuals aged 30 to 50 years underwent 2-hour protocol of 40-minute rest, videogame stressor and recovery. Hemodynamics, pro-BNP samples and DF indices were obtained throughout the protocol. Separate regression analyses were conducted using rest and stress E/A, E' and E/E' as dependent variables. Predictor variables were entered into the stepwise regression models in a hierarchical fashion. At the first level, age, sex, race, height, body mass index, pro-BNP and left ventricular mass (LVM) were permitted to enter the models. The second level consisted of systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR). The final level contained cross-product terms of race by SBP, DBP and HR. RESULTS: E/A ratio was lower during stress compared to rest and recovery (P < 0.01). Resting E/A ratio was predicted by a regression model of age (-0.31), pro-BNP (0.16), HR (-0.40) and DBP (-0.23) with an R² = 0.33. Stress E/A ratio was predicted by age (-0.24), pro-BNP (0.08), HR (-0.38) and SBP (-0.21) with total R² = 0.22. Resting E' model consisted of age (-0.22), pro-BNP (0.26), DBP (-0.27) and LVM (-0.15) with an R² = 0.29. Stress E' was predicted by age (-0.18), pro-BNP (0.35) and LVM (-0.18) with an R² = 0.18. Resting E/E' was predicted by race (0.17, B > W) and DBP (0.24) with an R² = 0.10. Stress E/E' consisted of pro-BNP (-0.36), height (-0.26) and HR (-0.21) with an R² = 0.15. CONCLUSIONS: pro-BNP predicts both resting and stress DF, suggesting that lower BNP during MS may be a marker of diastolic dysfunction in apparently healthy individuals.


Assuntos
Pressão Sanguínea/fisiologia , Peptídeo Natriurético Encefálico/sangue , Descanso/fisiologia , Estresse Psicológico/sangue , Adulto , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Descanso/psicologia , Estresse Psicológico/psicologia , Jogos de Vídeo/psicologia
13.
J Investig Med High Impact Case Rep ; 2(4): 2324709614560907, 2014 Oct-Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26425631

RESUMO

We report a case of cerebrovascular accident with thromboembolic stroke etiology in a patient who had atrial flutter and negative transesophageal echocardiography (TEE) results. The increased D-dimer levels (1877 ng/mL) initiated referral for magnetic resonance imaging and magnetic resonance angiography of the brain that showed classic recanalization of an embolic thrombus in the angular branch of the left middle cerebral distribution. The D-dimer level of this patient was normalized after 3 months of anticoagulation therapy. Although TEE is considered the gold standard for evaluation of cardiac source of embolism, exclusion of intracardiac thrombus with TEE alone does not eliminate the risk of thromboembolic events. This case highlights the utility of D-dimer as a potential adjunct in the decision-making process to guide investigation of thromboembolism, determine subsequent therapy, and hence reduce the risk of embolic stroke recurrence.

14.
PLoS One ; 8(5): e64040, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23737964

RESUMO

BACKGROUND: The 16 kDa heat shock protein (HSP) is an immuno-dominant antigen, used in diagnosis of infectious Mycobacterium tuberculosis (M.tb.) causing tuberculosis (TB). Its use in serum-based diagnostics is limited, but for the direct identification of M.tb. bacteria in sputum or cultures it may represent a useful tool. Recently, a broad set of twelve 16 kDa specific heavy chain llama antibodies (VHH) has been isolated, and their utility for diagnostic applications was explored. METHODOLOGY/PRINCIPAL FINDINGS: To identify the epitopes recognized by the nine (randomly selected from a set of twelve 16 kDa specific VHH antibodies) distinct VHH antibodies, 14 overlapping linear epitopes (each 20 amino acid long) were characterized using direct and sandwich ELISA techniques. Seven out of 14 epitopes were recognized by 8 out of 9 VHH antibodies. The two highest affinity binders B-F10 and A-23 were found to bind distinct epitopes. Sandwich ELISA and SPR experiments showed that only B-F10 was suitable as secondary antibody with both B-F10 and A-23 as anchoring antibodies. To explain this behavior, the epitopes were matched to the putative 3D structure model. Electrospray ionization time-of-flight mass spectrometry and size exclusion chromatography were used to determine the higher order conformation. A homodimer model best explained the differential immunological reactivity of A-23 and B-F10 against heat-treated M.tb. lysates. CONCLUSIONS/SIGNIFICANCE: The concentrations of secreted antigens of M.tb. in sputum are too low for immunological detection and existing kits are only used for identifying M.tb. in cultures. Here we describe how specific combinations of VHH domains could be used to detect the intracellular HSP antigen. Linked to methods of pre-concentrating M.tb. cells prior to lysis, HSP detection may enable the development of protein-based diagnostics of sputum samples and earlier diagnosis of diseases.


Assuntos
Proteínas de Bactérias/metabolismo , Camelídeos Americanos , Proteínas de Choque Térmico/metabolismo , Temperatura Alta , Cadeias Pesadas de Imunoglobulinas/imunologia , Mycobacterium tuberculosis/isolamento & purificação , Multimerização Proteica , Sequência de Aminoácidos , Animais , Especificidade de Anticorpos , Proteínas de Bactérias/química , Proteínas de Bactérias/imunologia , Mapeamento de Epitopos , Proteínas de Choque Térmico/química , Proteínas de Choque Térmico/imunologia , Modelos Moleculares , Dados de Sequência Molecular , Peso Molecular , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/metabolismo , Mycobacterium tuberculosis/fisiologia , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/imunologia , Estrutura Quaternária de Proteína , Escarro/microbiologia , Tuberculose/diagnóstico
15.
Nucleic Acids Res ; 41(10): e111, 2013 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-23571753

RESUMO

Proteins that recognize and bind specific sites in DNA are essential for regulation of numerous biological functions. Such proteins often require a negative supercoiled DNA topology to function correctly. In current research, short linear DNA is often used to study DNA-protein interactions. Although linear DNA can easily be modified, for capture on a surface, its relaxed topology does not accurately resemble the natural situation in which DNA is generally negatively supercoiled. Moreover, specific binding sequences are flanked by large stretches of non-target sequence in vivo. Here, we present a straightforward method for capturing negatively supercoiled plasmid DNA on a streptavidin surface. It relies on the formation of a temporary parallel triplex, using a triple helix forming oligonucleotide containing locked nucleic acid nucleotides. All materials required for this method are commercially available. Lac repressor binding to its operator was used as model system. Although the dissociation constants for both the linear and plasmid-based operator are in the range of 4 nM, the association and dissociation rates of Lac repressor binding to the plasmid-based operator are ~18 times slower than on a linear fragment. This difference underscores the importance of using a physiologically relevant DNA topology for studying DNA-protein interactions.


Assuntos
DNA Super-Helicoidal/química , DNA/química , Plasmídeos/genética , DNA Super-Helicoidal/metabolismo , Repressores Lac/metabolismo , Oligonucleotídeos/química , Regiões Operadoras Genéticas
16.
Biosens Bioelectron ; 40(1): 219-26, 2013 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-22878083

RESUMO

Uniform orientation of capture molecules on biosensors has been reported to increase sensitivity. Here it is investigated which analyte properties contribute to sensitivity by orientation. Orientation of capture molecules on biosensors was investigated using variable domains of llama heavy-chain antibodies (VHHs) as capture molecule, and a surface plasmon resonance (SPR) chip as biosensor. Two VHHs were tested in this study: one recognizing foot-and-mouth disease virus (FMDV) and another recognizing the 16 kDa heat-shock protein of Mycobacterium tuberculosis. SPR chips with randomly immobilized biotinylated VHHs were compared to streptavidin-coated SPR chips, on which similar quantities of oriented biotinylated VHHs were non-covalently immobilized. Analytes that differ in molecular weight, epitope number and epitope affinity were compared using the FMDV-recognizing VHH. When binding of intact FMDV particles (146 S; 8200 kDa) or pentameric FMDV coat protein aggregates (12 S; 282 kDa) was detected, a modest (1-2-fold) increase in sensitivity was observed. When a 26-residue peptide (3 kDa) containing the epitope for VHH recognition was tested, much larger effects of capture molecule orientation (14-fold) on signal were observed. A 20-227-fold improvement was also observed when the epitope peptide was covalently linked to bovine serum albumin (67 kDa) or R-phycoerythrin (240 kDa). The results indicate that orientation of the capture molecule hardly affects high-affinity interactions, while it leads to strong improvements in sensitivity for lower-affinity interactions.


Assuntos
Antígenos/análise , Antígenos/química , Técnicas Biossensoriais/instrumentação , Imunoensaio/instrumentação , Desenho de Equipamento , Análise de Falha de Equipamento , Conformação Proteica , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
17.
Psychol Med ; 43(9): 1965-71, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23237013

RESUMO

BACKGROUND: Although usually thought of as external environmental stressors, a significant heritable component has been reported for measures of stressful life events (SLEs) in twin studies. Method We examined the variance in SLEs captured by common genetic variants from a genome-wide association study (GWAS) of 2578 individuals. Genome-wide complex trait analysis (GCTA) was used to estimate the phenotypic variance tagged by single nucleotide polymorphisms (SNPs). We also performed a GWAS on the number of SLEs, and looked at correlations between siblings. RESULTS: A significant proportion of variance in SLEs was captured by SNPs (30%, p = 0.04). When events were divided into those considered to be dependent or independent, an equal amount of variance was explained for both. This 'heritability' was in part confounded by personality measures of neuroticism and psychoticism. A GWAS for the total number of SLEs revealed one SNP that reached genome-wide significance (p = 4 × 10-8), although this association was not replicated in separate samples. Using available sibling data for 744 individuals, we also found a significant positive correlation of R 2 = 0.08 in SLEs (p = 0.03). CONCLUSIONS: These results provide independent validation from molecular data for the heritability of reporting environmental measures, and show that this heritability is in part due to both common variants and the confounding effect of personality.


Assuntos
Acontecimentos que Mudam a Vida , Personalidade/genética , Irmãos/psicologia , Transtornos de Ansiedade , Interação Gene-Ambiente , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Modelos Genéticos , Neuroticismo , Fenótipo , Polimorfismo de Nucleotídeo Único , Meio Social
18.
Mol Psychiatry ; 18(2): 195-205, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22182935

RESUMO

Meta-analyses of bipolar disorder (BD) genome-wide association studies (GWAS) have identified several genome-wide significant signals in European-ancestry samples, but so far account for little of the inherited risk. We performed a meta-analysis of ∼750,000 high-quality genetic markers on a combined sample of ∼14,000 subjects of European and Asian-ancestry (phase I). The most significant findings were further tested in an extended sample of ∼17,700 cases and controls (phase II). The results suggest novel association findings near the genes TRANK1 (LBA1), LMAN2L and PTGFR. In phase I, the most significant single nucleotide polymorphism (SNP), rs9834970 near TRANK1, was significant at the P=2.4 × 10(-11) level, with no heterogeneity. Supportive evidence for prior association findings near ANK3 and a locus on chromosome 3p21.1 was also observed. The phase II results were similar, although the heterogeneity test became significant for several SNPs. On the basis of these results and other established risk loci, we used the method developed by Park et al. to estimate the number, and the effect size distribution, of BD risk loci that could still be found by GWAS methods. We estimate that >63,000 case-control samples would be needed to identify the ∼105 BD risk loci discoverable by GWAS, and that these will together explain <6% of the inherited risk. These results support previous GWAS findings and identify three new candidate genes for BD. Further studies are needed to replicate these findings and may potentially lead to identification of functional variants. Sample size will remain a limiting factor in the discovery of common alleles associated with BD.


Assuntos
Transtorno Bipolar/etnologia , Transtorno Bipolar/genética , Predisposição Genética para Doença , Metanálise como Assunto , Polimorfismo de Nucleotídeo Único , Anquirinas/genética , Anquirinas/metabolismo , Antidepressivos/farmacologia , Grupo com Ancestrais do Continente Asiático/genética , Linhagem Celular Transformada , Citocinas/genética , Relação Dose-Resposta a Droga , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Frequência do Gene , Estudo de Associação Genômica Ampla , Humanos , Lectinas/genética , Lectinas/metabolismo , Cloreto de Lítio/farmacologia , Masculino , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , RNA Mensageiro/metabolismo , Receptores de Prostaglandina/genética , Receptores de Prostaglandina/metabolismo , Fatores de Tempo , Ácido Valproico/farmacologia
19.
Int J Mol Sci ; 13(8): 10537-52, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22949878

RESUMO

Aptamers are oligonucleotide ligands, either RNA or ssDNA, selected for high-affinity binding to molecular targets, such as small organic molecules, proteins or whole microorganisms. While reports of new aptamers are numerous, characterization of their specific interaction is often restricted to the affinity of binding (K(D)). Over the years, crystal structures of aptamer-protein complexes have only scarcely become available. Here we describe some relevant technical issues about the process of crystallizing aptamer-protein complexes and highlight some biochemical details on the molecular basis of selected aptamer-protein interactions. In addition, alternative experimental and computational approaches are discussed to study aptamer-protein interactions.


Assuntos
Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/metabolismo , Proteínas/química , Proteínas/metabolismo , Animais , Cristalografia por Raios X , Humanos , Modelos Moleculares , Conformação de Ácido Nucleico , Conformação Proteica
20.
Science ; 336(6082): 687-90, 2012 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-22582254

RESUMO

Vesta's surface is characterized by abundant impact craters, some with preserved ejecta blankets, large troughs extending around the equatorial region, enigmatic dark material, and widespread mass wasting, but as yet an absence of volcanic features. Abundant steep slopes indicate that impact-generated surface regolith is underlain by bedrock. Dawn observations confirm the large impact basin (Rheasilvia) at Vesta's south pole and reveal evidence for an earlier, underlying large basin (Veneneia). Vesta's geology displays morphological features characteristic of the Moon and terrestrial planets as well as those of other asteroids, underscoring Vesta's unique role as a transitional solar system body.

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