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1.
J Cardiol ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38964712

RESUMO

BACKGROUND: Lower limb artery disease (LEAD) is accompanied by multiple comorbidities; however, the effect of hyperpolypharmacy on patients with LEAD has not been established. This study investigated the associations between hyperpolypharmacy, medication class, and adverse clinical outcomes in patients with LEAD. METHODS: This study used data from a prospective multicenter observational Japanese registry. A total of 366 patients who underwent endovascular treatment (EVT) for LEAD were enrolled in this study. The primary endpoints were major adverse cardiac events (MACE), including myocardial infarction, stroke, and all-cause death. RESULTS: Of 366 patients with LEAD, 12 with missing medication information were excluded. Of the 354 remaining patients, 166 had hyperpolypharmacy (≥10 medications, 46.9 %), 162 had polypharmacy (5-9 medications, 45.8 %), and 26 had nonpolypharmacy (<5 medications, 7.3 %). Over a 4.7-year median follow-up period, patients in the hyperpolypharmacy group showed worse outcomes than those in the other two groups (log-rank test, p < 0.001). Multivariate analysis revealed that the total number of medications was significantly associated with an increased risk of MACE (hazard ratio per medication increase 1.078, 95 % confidence interval 1.02-1.13 p = 0.012). Although an increased number of non-cardiovascular medications was associated with an elevated risk of MACE, the increase in cardiovascular medications was not statistically significant (log-rank test, p = 0.002 and 0.35, respectively). CONCLUSIONS: Hyperpolypharmacy due to non-cardiovascular medications was significantly associated with adverse outcomes in patients with LEAD who underwent EVT, suggesting the importance of medication reviews, including non-cardiovascular medications.

3.
Angiology ; 73(8): 753-763, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35077237

RESUMO

We investigated the prognostic effects of hyperuricemia and high or low body mass index (BMI) in peripheral artery disease (PAD) after endovascular therapy (EVT). Between July 2015-2016, 357 consecutive patients with PAD who underwent EVT were enrolled. Patients were divided into 2 groups: BMI < 25 kg/m2 (low BMI) and ≥ 25 kg/m2 (high BMI); they were also divided into 2 more groups based on the presence/absence of hyperuricemia. The primary and secondary endpoints were major adverse cardiovascular and limb events (MACLE), and all-cause death at 3 years post-EVT. Patients with hyperuricemia had significantly lower freedom from MACLE than patients without hyperuricemia at 3 years (57.0 vs 71.9%, p = .0068). The overall survival of patients with hyperuricemia was significantly lower than that of patients without hyperuricemia (63.9 vs 81.7%, p = .0012). Patients with hyperuricemia who had low BMI experienced significantly lower freedom from MACLE than those without hyperuricemia who had low BMI (48.2 vs 69.9%, p = .002). The overall survival of patients with hyperuricemia who had low BMI was significantly lower than that of patients without hyperuricemia who had low BMI (55.2 vs 77.1%, p = .003). Patients with hyperuricemia had significantly more MACLE and a lower survival at 3 years than patients without hyperuricemia, even if they had a low BMI.


Assuntos
Procedimentos Endovasculares , Hiperuricemia , Doença Arterial Periférica , Índice de Massa Corporal , Procedimentos Endovasculares/efeitos adversos , Humanos , Sistema de Registros , Fatores de Risco , Resultado do Tratamento , Redução de Peso
4.
J Endovasc Ther ; 29(6): 845-854, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-34969317

RESUMO

PURPOSE: Information on the relationship between frailty and the outcome of endovascular therapy (EVT) in elderly patients with lower extremity peripheral artery disease (PAD) is scarce. This study aimed to reveal the impact of frailty on the prognosis of super-elderly patients who underwent EVT. MATERIALS AND METHODS: From August 2015 to August 2016, 335 consecutive patients who underwent EVT were enrolled in the I-PAD registry from 7 institutes in Nagano prefecture. Among them, we categorized 323 patients into 4 groups according to age and the presence or absence of frailty as follows: elderly with frailty (age ≥ 75, Clinical Frailty Scale [CFS] ≥ 5), elderly without frailty (age ≥ 75, CFS ≤ 4), young with frailty (age < 75, CFS ≥ 5), and young without frailty (age < 75, CFS ≤ 4); we analyzed them accordingly. The primary endpoints were major adverse cardiovascular and limb events (MACLE), defined as a composite of cardiovascular death, myocardial infarction, stroke, admission for heart failure, major amputation, and revascularization. The secondary endpoint was cardiovascular death. RESULTS: The median follow-up period was 2.7 years. In the elderly with frailty, elderly without frailty, young with frailty, and young without frailty groups, the freedom rates from MACLE were 34.9%, 55.7%, 35.4%, and 63.0%, respectively (p<0.001) and from all-cause death were 43.5%, 73.4%, 50.7%, and 90.9%, respectively (p<0.001). The freedom rates from MACLE were significantly higher among elderly patients with frailty than among young patients without frailty (55.7% vs 35.4%, p=0.01). In multivariate analysis, frailty was independently associated with MACLE incidence. CONCLUSION: Frailty as defined by CFS might be a predictor of MACLE incidence in patients with PAD who underwent EVT. By considering treatment indications for patients with PAD by focusing on frailty rather than age, we may examine whether EVT policies are appropriate and manage patient and caregiver expectations for potential improvement in functional outcomes. Further studies are expected to investigate whether changes in frailty after EVT change prognosis.


Assuntos
Procedimentos Endovasculares , Fragilidade , Doença Arterial Periférica , Humanos , Idoso , Fragilidade/diagnóstico , Fragilidade/complicações , Procedimentos Endovasculares/efeitos adversos , Resultado do Tratamento , Fatores de Risco , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/terapia , Doença Arterial Periférica/complicações , Estudos Retrospectivos
5.
Biophys Rev ; 10(2): 667-676, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29468522

RESUMO

Conrad H. Waddington discovered the phenomenon of genetic assimilation through a series of experiments on fruit flies. In those experiments, artificially exerted environmental stress induced plastic phenotypic changes in the fruit flies, but after some generations, the same phenotypic variant started to appear without the environmental stress. Both the initial state (where the phenotypic changes were environmentally induced and plastic) and the final state (where the phenotypic changes were genetically fixed and constitutive) are experimental facts. However, it remains unclear how the environmentally induced phenotypic change in the first generation becomes genetically fixed in the central process of genetic assimilation itself. We have argued that the key to understanding the mechanism of genetic assimilation lies in epigenetics, and proposed the "cooperative model" in which the evolutionary process depends on both genetic and epigenetic factors. Evolutionary simulations based on the cooperative model reproduced the process of genetic assimilation. Detailed analysis of the trajectories has revealed genetic assimilation is a process in which epigenetically induced phenotypic changes are incrementally and statistically replaced with multiple minor genetic mutations through natural selection. In this scenario, epigenetic and genetic changes may be considered as mutually independent but equivalent in terms of their effects on phenotypic changes. This finding rejects the common (and confused) hypothesis that epigenetically induced phenotypic changes depend on genetic mutations. Furthermore, we argue that transgenerational epigenetic inheritance is not required for evolution by genetic assimilation.

6.
Biophys Rev ; 9(2): 73-77, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28424740

RESUMO

The epigenome, i.e., the whole of chromatin modifications, is transferred from mother to daughter cells during cell differentiation. When de novo chromatin modifications (establishment or erasure of, respectively, new or pre-existing DNA methylations and/or histone modifications) are made in a daughter cell, however, it has a different epigenome than its mother cell. Although de novo chromatin modification is an important event that comprises elementary processes of cell differentiation, its molecular mechanism remains poorly understood. We argue, in this letter, that a key to solving this problem lies in understanding the role of long non-coding RNAs (lncRNAs), a type of RNA that is becoming increasingly prominent in epigenetic studies. Many studies show that lncRNAs form ribonucleoprotein complexes in the nucleus and are involved in chromatin modifications. However, chromatin-modifying enzymes lack the information about genomic positions on which they act. It is known, on the other hand, that a single-stranded RNA in general can bind to a double-stranded DNA to form a triple helix. If each lncRNA forms a ribonucleoprotein complex with chromatin-modifying enzymes on one hand and, at the same time, a triple helix with a genomic region based on its specific nucleotide sequence on the other hand, it can induce de novo chromatin modifications at specific sites. Thus, the great variety of lncRNAs can be explained by the requirement for the diversity of "genomic address codes" specific to their cognate genomic regions where de novo chromatin modifications take place.

7.
Biophysics (Nagoya-shi) ; 10: 99-108, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-27493504

RESUMO

We propose the cooperative model of phenotype-driven evolution, in which natural selection operates on a phenotype caused by both genetic and epigenetic factors. The conventional theory of evolutionary synthesis assumes that a phenotypic value (P) is the sum of genotypic value (G) and environmental deviation (E), P=G+E, where E is the fluctuations of the phenotype among individuals in the absence of environmental changes. In contrast, the cooperative model assumes that an evolution is triggered by an environmental change and individuals respond to the change by phenotypic plasticity (epigenetic changes). The phenotypic plasticity, while essentially qualitative, is denoted by a quantitative value F which is modeled as a normal random variable like E, but with a much larger variance. Thus, the fundamental equation of the cooperative model is given as P=G+F where F includes the effect of E. Computer simulations using a genetic algorithm demonstrated that the cooperative model realized much faster evolution than the evolutionary synthesis. This accelerated evolution was found to be due to the cumulative evolution made possible by a ratchet mechanism due to the epigenetic contribution to the phenotypic value. The cooperative model can well account for the phenomenon of genetic assimilation, which, in turn, suggests the mechanism of cumulative selection. The cooperative model may also serve as a theoretical basis to understand various ideas and phenomena of the phenotype-driven evolution such as genetic assimilation, the theory of facilitated phenotypic variation, and epigenetic inheritance over generations.

8.
J Acoust Soc Am ; 134(2): 1283-94, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23927126

RESUMO

To date, the intonation of infant-directed speech (IDS) has been analyzed without reference to its phonological structure. Intonational phonology should, however, inform IDS research, discovering important properties that have previously been overlooked. The present study investigated "intonational exaggeration" in Japanese IDS using the intonational phonological framework. Although intonational exaggeration, which is most often measured by pitch-range expansion, is one of the best-known characteristics of IDS, Japanese has been reported to lack such exaggeration. The present results demonstrated that intonational exaggeration is in fact present and observed most notably at the location of boundary pitch movements, and that the effects of lexical pitch accents in the remainder of the utterances superficially mask the exaggeration. These results not only reveal dynamic aspects of Japanese IDS, but also in turn contribute to the theory of intonational phonology, suggesting that paralinguistic pitch-range modifications most clearly emerge where the intonation system of a language allows maximum flexibility in varying intonational contours.


Assuntos
Relações Mãe-Filho , Fonética , Acústica da Fala , Comportamento Verbal , Qualidade da Voz , Adulto , Análise de Variância , Pré-Escolar , Feminino , Humanos , Lactente , Comportamento do Lactente , Japão , Masculino , Percepção da Altura Sonora , Espectrografia do Som , Medida da Produção da Fala , Fatores de Tempo
9.
Intrinsically Disord Proteins ; 1(1): e24157, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-28516007

RESUMO

"What's in a name? That which we call a rose By any other name would smell as sweet." From "Romeo and Juliet", William Shakespeare (1594) This article opens a series of publications on disambiguation of the basic terms used in the field of intrinsically disordered proteins. We start from the beginning, namely from the explanation of what the expression "intrinsically disordered protein" actually means and why this particular term has been chosen as the common denominator for this class of proteins characterized by broad structural, dynamic and functional characteristics.

10.
PLoS One ; 7(11): e50445, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23189203

RESUMO

The relationship between sequence polymorphisms and human disease has been studied mostly in terms of effects of single nucleotide polymorphisms (SNPs) leading to single amino acid substitutions that change protein structure and function. However, less attention has been paid to more drastic sequence polymorphisms which cause premature termination of a protein's sequence or large changes, insertions, or deletions in the sequence. We have analyzed a large set (n = 512) of insertions and deletions (indels) and single nucleotide polymorphisms causing premature termination of translation in disease-related genes. Prediction of protein-destabilization effects was performed by graphical presentation of the locations of polymorphisms in the protein structure, using the Genomes TO Protein (GTOP) database, and manual annotation with a set of specific criteria. Protein-destabilization was predicted for 44.4% of the nonsense SNPs, 32.4% of the frameshifting indels, and 9.1% of the non-frameshifting indels. A prediction of nonsense-mediated decay allowed to infer which truncated proteins would actually be translated as defective proteins. These cases included the proteins linked to diseases inherited dominantly, suggesting a relation between these diseases and toxic aggregation. Our approach would be useful in identifying potentially aggregation-inducing polymorphisms that may have pathological effects.


Assuntos
Polimorfismo de Nucleotídeo Único , Proteínas/química , Proteínas/genética , Bases de Dados de Proteínas , Predisposição Genética para Doença , Humanos , Interações Hidrofóbicas e Hidrofílicas , Mutação INDEL , Modelos Moleculares , Conformação Proteica , Estabilidade Proteica
11.
Genes Cells ; 17(10): 817-25, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22908957

RESUMO

Intrinsically disordered (ID) proteins (IDPs) are abundant in eukaryotes but are scarce in prokaryotes. Mitochondria, cellular organelles that descended from Rickettsia-like α-proteobacteria, are at the intersection between prokaryotes and eukaryotes. Although IDPs are reportedly as rare in mitochondria as in bacteria, these details remained to be clarified. Human mitochondrial proteins (n = 706) were obtained from the UniProt database, and information on ID regions of all human proteins was extracted from the DICHOT database. A BLAST search carried out against all α-proteobacterial proteins identified two types of mitochondrial proteins: those with (B) and without (E) bacterial homologues. The B-type proteins (n = 387) descended from a bacterial ancestor, whereas the E-type proteins (n = 319) were more recently added to the mitochondria via the host cell during the early evolution of eukaryotes. The average ID ratios of B-type/E-type proteins are 10.3% and 21.4%, respectively. The 706 proteins were further classified into four groups based on the mitochondrial subcompartment, namely, the matrix, intermembrane space, inner membrane, or outer membrane. The ID ratios in these different locations suggest that the frequency of IDPs in mitochondria might be due to the evolutionary origin (B-type/E-type) of the protein, rather than differences in its functional environment.


Assuntos
Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Biologia Computacional/métodos , Bases de Dados de Proteínas , Enzimas/química , Enzimas/metabolismo , Humanos , Proteínas Mitocondriais/química , Proteínas Mitocondriais/classificação , Sinais Direcionadores de Proteínas , Transporte Proteico
12.
Mol Biosyst ; 8(1): 247-55, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21866296

RESUMO

Proteins in general consist not only of globular structural domains (SDs), but also of intrinsically disordered regions (IDRs), i.e. those that do not assume unique three-dimensional structures by themselves. Although IDRs are especially prevalent in eukaryotic proteins, the functions are mostly unknown. To elucidate the functions of IDRs, we first divided eukaryotic proteins into subcellular localizations, identified IDRs by the DICHOT system that accurately divides entire proteins into SDs and IDRs, and examined charge and hydropathy characteristics. On average, mitochondrial proteins have IDRs more positively charged than SDs. Comparison of mitochondrial proteins with orthologous prokaryotic proteins showed that mitochondrial proteins tend to have segments attached at both N and C termini, high fractions of which are IDRs. Segments added to the N-terminus of mitochondrial proteins contain not only signal sequences but also mature proteins and exhibit a positive charge gradient, with the magnitude increasing toward the N-terminus. This finding is consistent with the notion that positively charged residues are added to the N-terminus of proteobacterial proteins so that the extended proteins can be chromosomally encoded and efficiently transported to mitochondria after translation. By contrast, nuclear proteins generally have positively charged SDs and negatively charged IDRs. Among nuclear proteins, DNA-binding proteins have enhanced charge tendencies. We propose that SDs in nuclear proteins tend to be positively charged because of the need to bind to negatively charged nucleotides, while IDRs tend to be negatively charged to interact with other proteins or other regions of the same proteins to avoid premature proteasomal degradation.


Assuntos
Proteínas Mitocondriais/química , Proteínas Mitocondriais/metabolismo , Proteínas Nucleares/química , Proteínas Nucleares/metabolismo , Dobramento de Proteína , Animais , Humanos , Interações Hidrofóbicas e Hidrofílicas , Conformação Proteica , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/metabolismo
13.
BMC Struct Biol ; 11: 29, 2011 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-21693062

RESUMO

BACKGROUND: Although structural domains in proteins (SDs) are important, half of the regions in the human proteome are currently left with no SD assignments. These unassigned regions consist not only of novel SDs, but also of intrinsically disordered (ID) regions since proteins, especially those in eukaryotes, generally contain a significant fraction of ID regions. As ID regions can be inferred from amino acid sequences, a method that combines SD and ID region assignments can determine the fractions of SDs and ID regions in any proteome. RESULTS: In contrast to other available ID prediction programs that merely identify likely ID regions, the DICHOT system we previously developed classifies the entire protein sequence into SDs and ID regions. Application of DICHOT to the human proteome revealed that residue-wise ID regions constitute 35%, SDs with similarity to PDB structures comprise 52%, while SDs with no similarity to PDB structures account for the remaining 13%. The last group consists of novel structural domains, termed cryptic domains, which serve as good targets of structural genomics. The DICHOT method applied to the proteomes of other model organisms indicated that eukaryotes generally have high ID contents, while prokaryotes do not. In human proteins, ID contents differ among subcellular localizations: nuclear proteins had the highest residue-wise ID fraction (47%), while mitochondrial proteins exhibited the lowest (13%). Phosphorylation and O-linked glycosylation sites were found to be located preferentially in ID regions. As O-linked glycans are attached to residues in the extracellular regions of proteins, the modification is likely to protect the ID regions from proteolytic cleavage in the extracellular environment. Alternative splicing events tend to occur more frequently in ID regions. We interpret this as evidence that natural selection is operating at the protein level in alternative splicing. CONCLUSIONS: We classified entire regions of proteins into the two categories, SDs and ID regions and thereby obtained various kinds of complete genome-wide statistics. The results of the present study are important basic information for understanding protein structural architectures and have been made publicly available at http://spock.genes.nig.ac.jp/~genome/DICHOT.


Assuntos
Biologia Computacional/métodos , Proteínas/química , Processamento Alternativo , Bases de Dados de Proteínas , Genoma , Fosforilação , Proteoma/química
14.
Calcif Tissue Int ; 88(5): 432-41, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21359625

RESUMO

We demonstrated the capability of in vivo synchrotron radiation CT (SRCT) in analyzing short-term changes in trabecular bone architecture (TBA) and the degree of bone mineralization (DBM) in small animals. Mice underwent unilateral sciatic neurectomy (SN) and sham operation on the contralateral side (SO) at 13 weeks of age. In vivo SRCT scans (11.7-µm cubic voxel) were made of both knees 7 and 17 days (group 1, n = 7) or only 17 days (group 2, n = 6) after surgery. In three mice in group 2, one knee was scanned twice on the same day in different orientations for reproducibility testing. Two scan data sets of the tibial proximal metaphysis acquired at different time points (group 1) or at the same time point (group 2) were registered for detecting differences in volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), connectivity density (Conn.D), and mean DBM (mDBM). The reproducibility test showed small errors of <2.5% in the TBA indexes and <3.0% in mDBM, while mismatched bone regions amounted to >25%. In group 1, Tb.Th increased but Tb.N and Conn.D decreased in both SN and SO; BV/TV and mDBM increased only in SO; accordingly, BV/TV, Tb.Th, and mDBM became lower in SN than in SO. No significant interaction between SN and irradiation was found; the SN effects on TBA and DBM were similar between groups 1 and 2, although synchrotron irradiation led to higher Tb.Th and lower Tb.N in group 1. In conclusion, in vivo SRCT has potential use for detecting short-term bone dynamics of small animals.


Assuntos
Densidade Óssea/fisiologia , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/fisiologia , Calcificação Fisiológica/fisiologia , Nervo Isquiático/cirurgia , Síncrotrons , Tomografia Computadorizada por Raios X/métodos , Animais , Densidade Óssea/efeitos da radiação , Osso e Ossos/efeitos da radiação , Calcificação Fisiológica/efeitos da radiação , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/fisiologia , Articulação do Joelho/efeitos da radiação , Masculino , Camundongos , Camundongos Endogâmicos ICR , Modelos Animais , Modelos Biológicos , Reprodutibilidade dos Testes , Nervo Isquiático/fisiologia
15.
Int J Mol Sci ; 11(12): 4991-5008, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21614187

RESUMO

O-glycosylation of mammalian proteins is one of the important posttranslational modifications. We applied a support vector machine (SVM) to predict whether Ser or Thr is glycosylated, in order to elucidate the O-glycosylation mechanism. O-glycosylated sites were often found clustered along the sequence, whereas other sites were located sporadically. Therefore, we developed two types of SVMs for predicting clustered and isolated sites separately. We found that the amino acid composition was effective for predicting the clustered type, whereas the site-specific algorithm was effective for the isolated type. The highest prediction accuracy for the clustered type was 74%, while that for the isolated type was 79%. The existence frequency of amino acids around the O-glycosylation sites was different in the two types: namely, Pro, Val and Ala had high existence probabilities at each specific position relative to a glycosylation site, especially for the isolated type. Independent component analyses for the amino acid sequences around O-glycosylation sites showed the position-specific existences of the identified amino acids as independent components. The O-glycosylation sites were preferentially located within intrinsically disordered regions of extracellular proteins: particularly, more than 90% of the clustered O-GalNAc glycosylation sites were observed in intrinsically disordered regions. This feature could be the key for understanding the non-conservation property of O-glycosylation, and its role in functional diversity and structural stability.


Assuntos
Simulação por Computador , Redes Neurais de Computação , Proteínas/genética , Análise de Sequência de Proteína/métodos , Glicosilação , Conformação Proteica
16.
BMC Struct Biol ; 9: 26, 2009 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-19402914

RESUMO

BACKGROUND: In addition to structural domains, most eukaryotic proteins possess intrinsically disordered (ID) regions. Although ID regions often play important functional roles, their accurate identification is difficult. As human transcription factors (TFs) constitute a typical group of proteins with long ID regions, we regarded them as a model of all proteins and attempted to accurately classify TFs into structural domains and ID regions. Although an extremely high fraction of ID regions besides DNA binding and/or other domains was detected in human TFs in our previous investigation, 20% of the residues were left unassigned. In this report, we exploit the generally higher sequence divergence in ID regions than in structural regions to completely divide proteins into structural domains and ID regions. RESULTS: The new dichotomic system first identifies domains of known structures, followed by assignment of structural domains and ID regions with a combination of pre-existing tools and a newly developed program based on sequence divergence, taking un-aligned regions into consideration. The system was found to be highly accurate: its application to a set of proteins with experimentally verified ID regions had an error rate as low as 2%. Application of this system to human TFs (401 proteins) showed that 38% of the residues were in structural domains, while 62% were in ID regions. The preponderance of ID regions makes a sharp contrast to TFs of Escherichia coli (229 proteins), in which only 5% fell in ID regions. The method also revealed that 4.0% and 11.8% of the total length in human and E. coli TFs, respectively, are comprised of structural domains whose structures have not been determined. CONCLUSION: The present system verifies that sequence divergence including information of unaligned regions is a good indicator of ID regions. The system for the first time estimates the complete fractioning of structured/un-structured regions in human TFs, also revealing structural domains without homology to known structures. These predicted novel structural domains are good targets of structural genomics. When applied to other proteins, the system is expected to uncover more novel structural domains.


Assuntos
Proteínas de Bactérias , Bases de Dados de Proteínas/classificação , Dobramento de Proteína , Análise de Sequência de Proteína , Relação Estrutura-Atividade , Fatores de Transcrição/química , Inteligência Artificial , Biologia Computacional , Humanos , Reconhecimento Automatizado de Padrão , Ligação Proteica , Conformação Proteica , Estrutura Terciária de Proteína , Software , Fatores de Transcrição/genética
17.
Nucleic Acids Res ; 37(Database issue): D333-7, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18987007

RESUMO

The Genomes TO Protein Structures and Functions (GTOP) database (http://spock.genes.nig.ac.jp/~genome/gtop.html) freely provides an extensive collection of information on protein structures and functions obtained by application of various computational tools to the amino acid sequences of entirely sequenced genomes. GTOP contains annotations of 3D structures, protein families, functions, and other useful data of a protein of interest in user-friendly ways to give a deep insight into the protein structure. From the initial 1999 version, GTOP has been continually updated to reap the fruits of genome projects and augmented to supply novel information, in particular intrinsically disordered regions. As intrinsically disordered regions constitute a considerable fraction of proteins and often play crucial roles especially in eukaryotes, their assignments give important additional clues to the functionality of proteins. Additionally, we have incorporated the following features into GTOP: a platform independent structural viewer, results of HMM searches against SCOP and Pfam, secondary structure predictions, color display of exon boundaries in eukaryotic proteins, assignments of gene ontology terms, search tools, and master files.


Assuntos
Bases de Dados de Proteínas , Conformação Proteica , Proteínas/genética , Éxons , Genômica , Proteínas/química , Proteínas/fisiologia , Análise de Sequência de Proteína , Software
18.
Biophysics (Nagoya-shi) ; 5: 53-58, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-27857579

RESUMO

Proteins with wholly or partly denatured structures in vivo are called intrinsically disordered or natively unfolded proteins (NUPs). Functional importance of NUPs was revealed by NMR studies as first reviewed by P. Wright in 1999. Since then, computational analyses on NUPs have also been intensively carried out to predict that approximately one third of eukaryotic proteins are NUPs. I will start this overview with the question why it took so long to identify NUPs as an important subject of protein science, and then move on to several issues such as, whether or not NUPs are specific to eukaryotes, what a particularly higher fraction of NUPs existing in the nucleus means, and what evolutionary implications NUPs have.

19.
Acta Crystallogr D Biol Crystallogr ; 64(Pt 11): 1138-45, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19020352

RESUMO

F-spondin is a secreted and extracellular matrix-attached protein that has been implicated in axonal pathfinding during neural development as well as in vascular remodelling in adult tissues. F-spondin is composed of a reeler, a spondin and six thrombospondin type 1 repeat domains. The reeler domain shares homology with the amino-terminal domain of reelin, a large secreted glycoprotein that guides migrating neurons during cortical development. Crystal structures of the F-spondin reeler domain were determined at 1.45 and 2.70 A resolution. The structure revealed a nine-stranded antiparallel beta-sandwich fold similar to the immunoglobulin or fibronectin type III domains, but with a unique extra beta-hairpin. Moreover, an amino-terminal extension which is anchored at its beginning via a conserved disulfide bond loosely packs against one face of the beta-sandwich, making a major contribution to the surface features of the domain. Structural comparison among the different molecules contained in two different crystals reveals an unusual conformational plasticity of the amino-terminal loop, suggesting its role in molecular interactions.


Assuntos
Moléculas de Adesão Celular Neuronais/química , Dissulfetos/química , Proteínas da Matriz Extracelular/química , Sequências Repetidas Invertidas/genética , Proteínas do Tecido Nervoso/química , Estrutura Secundária de Proteína/genética , Estrutura Terciária de Proteína/genética , Serina Endopeptidases/química , Sequência de Aminoácidos , Animais , Moléculas de Adesão Celular Neuronais/metabolismo , Cristalização , Dissulfetos/metabolismo , Matriz Extracelular/metabolismo , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Humanos , Dados de Sequência Molecular , Proteínas do Tecido Nervoso/metabolismo , Proteína Reelina , Alinhamento de Sequência , Serina Endopeptidases/metabolismo , Transgenes/genética
20.
Rinsho Byori ; 56(8): 678-83, 2008 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-18800623

RESUMO

Nine clones of non-pathogenic streptococci were isolated from the pharynges of seven healthy subjects, and grown on sheep blood agar plates with a hemolysis or gamma hemolysis, then cultured in LB broth for 16 hrs. Purified streptolysin O (SLO) purchased from Sigma Chemical Co. (Sigma-SLO), SLO antigen as a latex agglutination reagent from A company (A-SLO) and supernatants from four culture media were electrophoresed on 12% SDS-polyacrylamide gel and transferred to PVDF membranes. Immunological analyses of antibodies against SLO in healthy sera and proteins in culture medium demonstrated that healthy sera contained an antibody recognizing Sigma-SLO, A-SLO and a protein of the same size as SLO (SLO-like protein) in culture medium. These findings suggest that healthy subjects develop an antibody directed against SLO-like protein produced by non-pathogenic streptococci, and that this antibody cross-reacts with Sigma-SLO and A-SLO. Using DNA from Streptococcus pyogenes and non-pathogenic streptococci, the SLO gene and SLO-like protein gene were analyzed by direct sequencing with oligonucleotide primers designed to cover no. 74 to approximately 1900 of the SLO gene. There were three different bases resulting in amino acid substitution between the SLO gene and SLO-like protein gene, namely 101Lys (AAA) of SLO to Asn (AAT), 175Met (ATG) to Arg (AGG) and 185Asp (GAT) to Asn (AAT). Remaining 560 residues of 563 amino acids constituting SLO-like protein were homologous to SLO. Non-pathogenic streptococci on the pharynges of healthy subjects produce an SLO-like protein composed of amino acids similar to those of SLO, which induces an antibody against this SLO-like protein in serum. It is likely that an antibody against SLO-like protein in healthy sera cross-reacts with SLO and causes a pseudo-positive reaction on ASO measurement by the latex agglutination method using SLO antigen.


Assuntos
Anticorpos/imunologia , Streptococcus pyogenes/metabolismo , Streptococcus/metabolismo , Estreptolisinas/química , Estreptolisinas/imunologia , Adulto , Proteínas de Bactérias/biossíntese , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/imunologia , Western Blotting , Reações Cruzadas , DNA Bacteriano , Eletroforese em Gel de Poliacrilamida , Humanos , Faringe/microbiologia , Estreptolisinas/biossíntese , Estreptolisinas/genética
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