J Thompson
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Publication
Journal: Nucleic Acids Research
January/2/1995
Abstract
The sensitivity of the commonly used progressive multiple sequence alignment method has been greatly improved for the alignment of divergent protein sequences. Firstly, individual weights are assigned to each sequence in a partial alignment in order to down-weight near-duplicate sequences and up-weight the most divergent ones. Secondly, amino acid substitution matrices are varied at different alignment stages according to the divergence of the sequences to be aligned. Thirdly, residue-specific gap penalties and locally reduced gap penalties in hydrophilic regions encourage new gaps in potential loop regions rather than regular secondary structure. Fourthly, positions in early alignments where gaps have been opened receive locally reduced gap penalties to encourage the opening up of new gaps at these positions. These modifications are incorporated into a new program, CLUSTAL W which is freely available.
Publication
Journal: Bioinformatics
December/20/2007
Abstract
CONCLUSIONS
The Clustal W and Clustal X multiple sequence alignment programs have been completely rewritten in C++. This will facilitate the further development of the alignment algorithms in the future and has allowed proper porting of the programs to the latest versions of Linux, Macintosh and Windows operating systems.
BACKGROUND
The programs can be run on-line from the EBI web server: http://www.ebi.ac.uk/tools/clustalw2. The source code and executables for Windows, Linux and Macintosh computers are available from the EBI ftp site ftp://ftp.ebi.ac.uk/pub/software/clustalw2/
Publication
Journal: Nucleic Acids Research
February/23/1998
Abstract
CLUSTAL X is a new windows interface for the widely-used progressive multiple sequence alignment program CLUSTAL W. The new system is easy to use, providing an integrated system for performing multiple sequence and profile alignments and analysing the results. CLUSTAL X displays the sequence alignment in a window on the screen. A versatile sequence colouring scheme allows the user to highlight conserved features in the alignment. Pull-down menus provide all the options required for traditional multiple sequence and profile alignment. New features include: the ability to cut-and-paste sequences to change the order of the alignment, selection of a subset of the sequences to be realigned, and selection of a sub-range of the alignment to be realigned and inserted back into the original alignment. Alignment quality analysis can be performed and low-scoring segments or exceptional residues can be highlighted. Quality analysis and realignment of selected residue ranges provide the user with a powerful tool to improve and refine difficult alignments and to trap errors in input sequences. CLUSTAL X has been compiled on SUN Solaris, IRIX5.3 on Silicon Graphics, Digital UNIX on DECstations, Microsoft Windows (32 bit) for PCs, Linux ELF for x86 PCs, and Macintosh PowerMac.
Publication
Journal: Trends in Biochemical Sciences
December/3/1998
Publication
Journal: Methods in enzymology
October/9/1996
Abstract
We have tested CLUSTAL W in a wide variety of situations, and it is capable of handling some very difficult protein alignment problems. If the data set consists of enough closely related sequences so that the first alignments are accurate, then CLUSTAL W will usually find an alignment that is very close to ideal. Problems can still occur if the data set includes sequences of greatly different lengths or if some sequences include long regions that are impossible to align with the rest of the data set. Trying to balance the need for long insertions and deletions in some alignments with the need to avoid them in others is still a problem. The default values for our parameters were tested empirically using test cases of sets of globular proteins where some information as to the correct alignment was available. The parameter values may not be very appropriate with nonglobular proteins. We have argued that using one weight matrix and two gap penalties is too simplistic to be of general use in the most difficult cases. We have replaced these parameters with a large number of new parameters designed primarily to help encourage gaps in loop regions. Although these new parameters are largely heuristic in nature, they perform surprisingly well and are simple to implement. The underlying speed of the progressive alignment approach is not adversely affected. The disadvantage is that the parameter space is now huge; the number of possible combinations of parameters is more than can easily be examined by hand. We justify this by asking the user to treat CLUSTAL W as a data exploration tool rather than as a definitive analysis method. It is not sensible to automatically derive multiple alignments and to trust particular algorithms as being capable of always getting the correct answer. One must examine the alignments closely, especially in conjunction with the underlying phylogenetic tree (or estimate of it) and try varying some of the parameters. Outliers (sequences that have no close relatives) should be aligned carefully, as should fragments of sequences. The program will automatically delay the alignment of any sequences that are less than 40% identical to any others until all other sequences are aligned, but this can be set from a menu by the user. It may be useful to build up an alignment of closely related sequences first and to then add in the more distant relatives one at a time or in batches, using the profile alignments and weighting scheme described earlier and perhaps using a variety of parameter settings. We give one example using SH2 domains. SH2 domains are widespread in eukaryotic signalling proteins where they function in the recognition of phosphotyrosine-containing peptides. In the chapter by Bork and Gibson ([11], this volume), Blast and pattern/profile searches were used to extract the set of known SH2 domains and to search for new members. (Profiles used in database searches are conceptually very similar to the profiles used in CLUSTAL W: see the chapters [11] and [13] for profile search methods.) The profile searches detected SH2 domains in the JAK family of protein tyrosine kinases, which were thought not to contain SH2 domains. Although the JAK family SH2 domains are rather divergent, they have the necessary core structural residues as well as the critical positively charged residue that binds phosphotyrosine, leaving no doubt that they are bona fide SH2 domains. The five new JAK family SH2 domains were added sequentially to the existing alignment of 65 SH2 domains using the CLUSTAL W profile alignment option. Figure 6 shows part of the resulting alignment. Despite their divergent sequences, the new SH2 domains have been aligned nearly perfectly with the old set. No insertions were placed in the original SH2 domains. In this example, the profile alignment procedure has produced better results than a one-step full alignment of all 70 SH2 domains, and in considerably less time. (ABSTRACT TRUNCATED)
Publication
Journal: Nucleic Acids Research
September/2/1999
Abstract
In recent years improvements to existing programs and the introduction of new iterative algorithms have changed the state-of-the-art in protein sequence alignment. This paper presents the first systematic study of the most commonly used alignment programs using BAliBASE benchmark alignments as test cases. Even below the 'twilight zone' at 10-20% residue identity, the best programs were capable of correctly aligning on average 47% of the residues. We show that iterative algorithms often offer improved alignment accuracy though at the expense of computation time. A notable exception was the effect of introducing a single divergent sequence into a set of closely related sequences, causing the iteration to diverge away from the best alignment. Global alignment programs generally performed better than local methods, except in the presence of large N/C-terminal extensions and internal insertions. In these cases, a local algorithm was more successful in identifying the most conserved motifs. This study enables us to propose appropriate alignment strategies, depending on the nature of a particular set of sequences. The employment of more than one program based on different alignment techniques should significantly improve the quality of automatic protein sequence alignment methods. The results also indicate guidelines for improvement of alignment algorithms.
Publication
Journal: Medical Care
April/25/1980
Publication
Journal: Computer applications in the biosciences : CABIOS
June/29/1994
Abstract
Position-specific substitution matrices, known as profiles, derived from multiple sequence alignments are currently used to search sequence databases for distantly related members of protein families. The performance of the database searches is enhanced by using (i) a sequence weighting scheme which assigns higher weights to more distantly related sequences based on branch lengths derived from phylogenetic trees, (ii) exclusion of positions with mainly padding characters at sites of insertions or deletions and (iii) the BLOSUM62 residue comparison matrix. A natural consequence of these modifications is an improvement in the alignment of new sequences to the profiles. However, the accuracy of the alignments can be further increased by employing a similarity residue comparison matrix. These developments are implemented in a program called PROFILEWEIGHT which runs on Unix and Vax computers. The only input required by the program is the multiple sequence alignment. The output from PROFILEWEIGHT is a profile designed to be used by existing searching and alignment programs. Test results from database searches with four different families of proteins show the improved sensitivity of the weighted profiles.
Publication
Journal: Bioinformatics
May/3/1999
Abstract
CONCLUSIONS
BAliBASE is a database of manually refined multiple sequence alignments categorized by core blocks of conservation sequence length, similarity, and the presence of insertions and N/C-terminal extensions.
BACKGROUND
From http://www-igbmc. u-strasbg.fr/BioInfo/BAliBASE/index.html
Publication
Journal: FEBS Letters
November/22/1993
Abstract
New findings are presented for the approximately 50 residue KH motif, a domain recently discovered in RNA-binding proteins. The conserved sequence is approximately 10 residues larger than previously reported. Profile searches have revealed new members of this family, including two, E. coli NusA and human GAP-associated p62 phosphoprotein, for which RNA-binding data exists. A nusA homolog was detected in the RNA polymerase gene complex of six archaebacterial species and may encode an antiterminator. All KH-containing proteins are linked with RNA and the KH motif most probably functions as a nucleic acid binding domain.
Publication
Journal: New England Journal of Medicine
January/25/1996
Abstract
BACKGROUND
Inherited mutations in the BRCA1 gene are associated with a high risk of breast and ovarian cancer in some families. However, little is known about the contribution of BRCA1 mutations to breast cancer in the general population. We analyzed DNA samples from women enrolled in a population-based study of early-onset breast cancer to assess the spectrum and frequency of germ-line BRCA1 mutations in young women with breast cancer.
METHODS
We studied 80 women in whom breast cancer was diagnosed before the age of 35, and who were not selected on the basis of family history. Genomic DNA was studied for BRCA1 mutations by analysis involving single-strand conformation polymorphisms and with allele-specific assays. Alterations were defined by DNA sequencing.
RESULTS
Germ-line BRCA1 mutations were identified in 6 of the 80 women. Four additional rare sequence variants of unknown functional importance were also identified. Two of the mutations and three of the rare sequence variants were found among the 39 women who reported no family history of breast or ovarian cancer. None of the mutations and only one of the rare variants was identified in a reference population of 73 unrelated subjects.
CONCLUSIONS
Alterations in BRCA1 were identified in approximately 10 percent of this cohort of young women with breast cancer. The risk of harboring a mutation was not limited to women with family histories of breast or ovarian cancer. These results represent a minimal estimate of the frequency of BRCA1 mutations in this population. Comprehensive methods of identifying BRCA1 mutations and understanding their importance will be needed before testing of women in the general population can be undertaken.
Publication
Journal: Nucleic Acids Research
October/4/2000
Abstract
DbClustal addresses the important problem of the automatic multiple alignment of the top scoring full-length sequences detected by a database homology search. By combining the advantages of both local and global alignment algorithms into a single system, DbClustal is able to provide accurate global alignments of highly divergent, complex sequence sets. Local alignment information is incorporated into a ClustalW global alignment in the form of a list of anchor points between pairs of sequences. The method is demonstrated using anchors supplied by the Blast post-processing program, Ballast. The rapidity and reliability of DbClustal have been demonstrated using the recently annotated Pyrococcus abyssi proteome where the number of alignments with totally misaligned sequences was reduced from 20% to <2%. A web site has been implemented proposing BlastP database searches with automatic alignment of the top hits by DbClustal.
Publication
Journal: Cancer
April/26/2000
Abstract
BACKGROUND
There is a clear and growing need for data regarding BRCA1 and BRCA2 mutation frequencies among breast carcinoma cases not specifically ascertained on the basis of extreme family history profiles. Toward this end, the authors previously reported results with regard to BRCA1 in breast carcinoma patients drawn from a population-based study. In the current study the authors present new findings concerning BRCA2 mutation frequency in this same population, as well as summary data regarding the combined contribution of these two genes.
METHODS
Subjects were drawn from two population-based, case-control studies of breast carcinoma in young women conducted in western Washington State and focused on 1) women diagnosed with breast carcinoma before age 35 years (n = 203); and 2) women with a first-degree family history of breast carcinoma who were diagnosed before age 45 years (n = 225). Similarities and differences between BRCA2 carriers and BRCA1 carriers were analyzed in terms of age at diagnosis, family history status, and disease features.
RESULTS
Of cases diagnosed before age 35 years, all of whom were unselected for family history, 9.4% carried germline mutations (3.4% for BRCA2 and 5.9% for BRCA1). Of cases diagnosed before age 45 years who had a first-degree family history of breast carcinoma, 12.0% carried germline mutations (4.9% for BRCA2 and 7.1% for BRCA1). Increased frequencies of mutations were observed in cases with a personal or family history of early age at diagnosis and in those with four or more family members affected with breast carcinoma. BRCA2 mutations were less common than BRCA1 mutations in families with any history of ovarian carcinoma.
CONCLUSIONS
Overall, given current constraints on health care resources, these data suggest that screening for germline mutations in these breast carcinoma susceptibility genes may have the greatest impact on overall health care if it is prioritized toward high and moderate risk populations.
Publication
Journal: Nature
April/8/2008
Abstract
Macroscopic mechanical objects and electromagnetic degrees of freedom can couple to each other through radiation pressure. Optomechanical systems in which this coupling is sufficiently strong are predicted to show quantum effects and are a topic of considerable interest. Devices in this regime would offer new types of control over the quantum state of both light and matter, and would provide a new arena in which to explore the boundary between quantum and classical physics. Experiments so far have achieved sufficient optomechanical coupling to laser-cool mechanical devices, but have not yet reached the quantum regime. The outstanding technical challenge in this field is integrating sensitive micromechanical elements (which must be small, light and flexible) into high-finesse cavities (which are typically rigid and massive) without compromising the mechanical or optical properties of either. A second, and more fundamental, challenge is to read out the mechanical element's energy eigenstate. Displacement measurements (no matter how sensitive) cannot determine an oscillator's energy eigenstate, and measurements coupling to quantities other than displacement have been difficult to realize in practice. Here we present an optomechanical system that has the potential to resolve both of these challenges. We demonstrate a cavity which is detuned by the motion of a 50-nm-thick dielectric membrane placed between two macroscopic, rigid, high-finesse mirrors. This approach segregates optical and mechanical functionality to physically distinct structures and avoids compromising either. It also allows for direct measurement of the square of the membrane's displacement, and thus in principle the membrane's energy eigenstate. We estimate that it should be practical to use this scheme to observe quantum jumps of a mechanical system, an important goal in the field of quantum measurement.
Publication
Journal: Bioinformatics
March/16/2004
Abstract
BACKGROUND
Most multiple sequence alignment programs use heuristics that sometimes introduce errors into the alignment. The most commonly used methods to correct these errors use iterative techniques to maximize an objective function. We present here an alternative, knowledge-based approach that combines a number of recently developed methods into a two-step refinement process. The alignment is divided horizontally and vertically to form a 'lattice' in which well aligned regions can be differentiated. Alignment correction is then restricted to the less reliable regions, leading to a more reliable and efficient refinement strategy.
RESULTS
The accuracy and reliability of RASCAL is demonstrated using: (i) alignments from the BAliBASE benchmark database, where significant improvements were often observed, with no deterioration of the existing high-quality regions, (ii) a large scale study involving 946 alignments from the ProDom protein domain database, where alignment quality was increased in 68% of the cases; and (iii) an automatic pipeline to obtain a high-quality alignment of 695 full-length nuclear receptor proteins, which took 11 min on a DEC Alpha 6100 computer
BACKGROUND
RASCAL is available at ftp://ftp-igbmc.u-strasbg.fr/pub/RASCAL.
BACKGROUND
http://bioinfo-igbmc.u-strasbourg.fr/BioInfo/RASCAL/paper/rascal_supp.html
Publication
Journal: Trends in Ecology and Evolution
October/1/2012
Abstract
The role of polyploidy in the origin of evolutionary novelty and the maintenance of diversity in plant populations has come to be recognized as an integral component of the ecological and evolutionary dynamics of plant species populations. Recent attempts to examine the evolutionary significance of polyploidy have focused on the processes responsible for the origin of polyploid plants and the conditions that favour their establishment and persistence. The importance of these issues is not simply limited to the evolutionary dynamics of polyploidy but is, in fact, central to our understanding of the population biology processes that act on the establishment of new 'types' and the maintenance of biotic diversity at both the inter- and intraspecific levels.
Publication
Journal: Nucleic Acids Research
September/16/1996
Abstract
DNA translation frames can be disrupted for several reasons, including: (i) errors in sequence determination; (ii) RNA processing, such as intron removal and guide RNA editing; (iii) less commonly, polymerase frameshifting during transcription or ribosomal frameshifting during translation. Frameshifts frequently confound computational activities involving homologous sequences, such as database searches and inferences on structure, function or phylogeny made from multiple alignments. A dynamic alignment algorithm is reported here which compares a protein profile (a residue scoring matrix for one or more aligned sequences) against the three translation frames of a DNA strand, allowing frameshifting. The algorithm has been incorporated into a new package, WiseTools, for comparison of biological sequences. A protein profile can be compared against either a DNA sequence or a protein sequence. The program PairWise may be used interactively for alignment of any two sequence inputs. SearchWise can perform combinations of searches through DNA or protein databases by a protein profile or DNA sequence. Routine application of the programs has revealed a set of database entries with frameshifts caused by errors in sequence determination.
Publication
Journal: JAMA - Journal of the American Medical Association
April/14/1998
Abstract
BACKGROUND
Studies of high-risk families with multiple early-onset cases of breast cancer have been useful for assessing the type and spectrum of germline mutations on the BRCA1 gene, but do not provide guidance to women with modest family history profiles. Thus, studies of women from the general population are needed to determine the BRCA1 mutation frequency in women perceived to be at high risk, and to develop profiles of those most likely to be carriers.
OBJECTIVE
To characterize frequency and spectrum of germline BRCA1 mutations in 2 categories of women identified via population-based studies hypothesized to be at increased risk of carrying such mutations: those diagnosed as having breast cancer before age 35 years and those diagnosed before age 45 years who have first-degree breast cancer family history.
METHODS
Study subjects were drawn from 2 population-based case-control studies of breast cancer in young women on the basis of their family history or their age of diagnosis. Cases were younger than 35 years or were younger than 45 years with first-degree family history at the time of breast cancer diagnosis and were ascertained via a population-based cancer registry, and controls (women without breast cancer) were identified via random-digit dialing.
METHODS
Three counties in western Washington State.
METHODS
BRCA1 germline mutations in study subjects identified in DNA from peripheral blood lymphocytes by single-strand conformation polymorphism analysis using primer pairs that span the BRCA1 coding region and intron-exon boundaries.
RESULTS
Of 193 women diagnosed as having breast cancer before age 35 years, none of whom were selected on the basis of family history status, 12 (6.2%, 95% confidence interval [CI], 3.2%-10.6%) had germline BRCA1 mutations. In 208 women diagnosed before age 45 years who had first-degree breast cancer family history, 15 (7.2%, 95% CI,4.1%-11.6%) had germline mutations in BRCA1. In both groups, there were variations in mutation frequency noted by age and by family history. Mutation frequency decreased with increasing age of diagnosis. Higher proportions of mutations were seen in cases with at least 1 relative diagnosed as having breast cancer before age 45 years, in cases with greater numbers of affected relatives, and those with ovarian cancer family history. Mutation frequency did not vary by bilateral breast cancer family history. No frameshift or nonsense mutations were observed in 71 control women with a first-degree family history, although missense changes of unknown significance were seen in cases and controls.
CONCLUSIONS
Women with BRCA1 germline mutations lacked a common family history profile. Also, a large proportion of the women with a first-degree breast cancer family history and women diagnosed as having breast cancer before age 35 years did not carry germline BRCA1 mutations. Hence, while early-onset disease and a strong breast cancer family history may be useful guidelines for checking BRCA1 status, these findings on women drawn from the general population suggest that it may be difficult to develop BRCA1 mutation screening criteria among women with modest family history profiles.
Publication
Journal: Journal of Molecular Biology
February/13/2002
Abstract
Multiple sequence alignment is a fundamental tool in a number of different domains in modern molecular biology, including functional and evolutionary studies of a protein family. Multiple alignments also play an essential role in the new integrated systems for genome annotation and analysis. Thus, the development of new multiple alignment scores and statistics is essential, in the spirit of the work dedicated to the evaluation of pairwise sequence alignments for database searching techniques. We present here norMD, a new objective scoring function for multiple sequence alignments. NorMD combines the advantages of the column-scoring techniques with the sensitivity of methods incorporating residue similarity scores. In addition, norMD incorporates ab initio sequence information, such as the number, length and similarity of the sequences to be aligned. The sensitivity and reliability of the norMD objective function is demonstrated using structural alignments in the SCOP and BAliBASE databases. The norMD scores are then applied to the multiple alignments of the complete sequences (MACS) detected by BlastP with E-value<10, for a set of 734 hypothetical proteins encoded by the Vibrio cholerae genome. Unrelated or badly aligned sequences were automatically removed from the MACS, leaving a high-quality multiple alignment which could be reliably exploited in a subsequent functional and/or structural annotation process. After removal of unreliable sequences, 176 (24 %) of the alignments contained at least one sequence with a functional annotation. 103 of these new matches were supported by significant hits to the Interpro domain and motif database.
Publication
Journal: Nature
April/13/2004
Abstract
Diamond is an electrical insulator well known for its exceptional hardness. It also conducts heat even more effectively than copper, and can withstand very high electric fields. With these physical properties, diamond is attractive for electronic applications, particularly when charge carriers are introduced (by chemical doping) into the system. Boron has one less electron than carbon and, because of its small atomic radius, boron is relatively easily incorporated into diamond; as boron acts as a charge acceptor, the resulting diamond is effectively hole-doped. Here we report the discovery of superconductivity in boron-doped diamond synthesized at high pressure (nearly 100,000 atmospheres) and temperature (2,500-2,800 K). Electrical resistivity, magnetic susceptibility, specific heat and field-dependent resistance measurements show that boron-doped diamond is a bulk, type-II superconductor below the superconducting transition temperature T(c) approximately 4 K; superconductivity survives in a magnetic field up to Hc2(0)>> or = 3.5 T. The discovery of superconductivity in diamond-structured carbon suggests that Si and Ge, which also form in the diamond structure, may similarly exhibit superconductivity under the appropriate conditions.
Publication
Journal: Nature
May/13/2014
Abstract
By analogy to transistors in classical electronic circuits, quantum optical switches are important elements of quantum circuits and quantum networks. Operated at the fundamental limit where a single quantum of light or matter controls another field or material system, such a switch may enable applications such as long-distance quantum communication, distributed quantum information processing and metrology, and the exploration of novel quantum states of matter. Here, by strongly coupling a photon to a single atom trapped in the near field of a nanoscale photonic crystal cavity, we realize a system in which a single atom switches the phase of a photon and a single photon modifies the atom's phase. We experimentally demonstrate an atom-induced optical phase shift that is nonlinear at the two-photon level, a photon number router that separates individual photons and photon pairs into different output modes, and a single-photon switch in which a single 'gate' photon controls the propagation of a subsequent probe field. These techniques pave the way to integrated quantum nanophotonic networks involving multiple atomic nodes connected by guided light.
Publication
Journal: American Journal of Epidemiology
September/23/1997
Abstract
Head injury and apolipoprotein E (APOE)-epsilon 4 (e4) genotype have each been associated with increased risk of Alzheimer's disease. If APOE-e4 affects neuronal viability and branching, and if response to head injury differs in e4 patients, then the association between head injury and Alzheimer's disease may vary with the presence of the e4 allele. The authors examined this association in a case-control study conducted between 1987 and 1995 among enrollees of the Group Health Cooperative of Puget Sound, a health maintenance organization in Seattle, Washington. Proxy informants reported prior head injury with loss of consciousness for 32 of 349 patients with probable Alzheimer's disease and for 16 of 342 control subjects of similar age and sex who had been randomly selected from the same population (odds ratio (OR) = 2.1, 95% confidence interval (CI) 1.1-3.8). Elevated risk was observed among men (OR = 4.2, 95% CI 1.5-11.5) but not among women (OR = 1.1, 95% CI 0.5-2.6). No significant variation in the head injury-Alzheimer's disease risk relation by APOE-e4 genotype was found among 230 cases and 309 controls (OR = 3.1 (95% CI 0.7-14.6) for persons with at least one e4 allele and OR = 2.0 (95% CI 0.8-5.2) for those without e4). Neither age, education, race, type of proxy informant, nor duration of relationship with the proxy confounded the association. Head injury with loss of consciousness, although uncommon in this sample, was associated with increased risk of Alzheimer's disease. APOE-e4 was an independent risk factor which neither modified nor confounded the association. Susceptibility to Alzheimer's disease as conferred by APOE-e4 does not appear to increase the risk associated with head injury.
Publication
Journal: Epidemiology
November/8/1995
Abstract
Research regarding the possible association between Alzheimer's disease and a history of depression has been inconclusive. Using a case-control design, we assessed the strength of the association between reported history of depression and onset of Alzheimer's disease. We enrolled probable Alzheimer's disease cases (N = 294), who were ascertained and diagnosed by our Alzheimer's Disease Patient Registry, and randomly selected nondemented controls (N = 300) of similar age and gender from the same base population. The mean age (for cases) was 78.5 years. Informants provided data regarding history of depression. "Treated depression" was defined as depression for which a physician/psychologist consultation, medication, or hospitalization had occurred. Restricting treated depression to exclude primary loss or grief reactions, we found a modest association with Alzheimer's disease [odds ratio (OR) = 1.8; 95% confidence interval (CI) = 0.9-3.5] after adjusting for gender, age, education, and type of informant. When these data were stratified by depression onset year, we observed an odds ratio of 2.0 (95% CI = 0.9-4.6) for depression occurring more than 10 years before the onset of dementia symptoms, and an OR of 0.9 (95% CI = 0.2-3.0) for depression onset within 10 years of the onset of dementia symptoms. Thus, depressive episodes occurring well before dementia symptom onset appear to increase the risk of Alzheimer's disease.
Publication
Journal: Nucleic Acids Research
August/23/1994
Abstract
Searches with dsRNA-binding domain profiles detected two copies of the domain in each of RNA helicase A, Drosophila maleless and C. elegans ORF T20G5-11 (of unknown function). RNA helicase A is unusual in being one of the few characterised DEAD/DExH helicases that are active as monomers. Other monomeric DEAD/DExH RNA helicases (p68, NPH-II) have domains that match another RNA-binding motif, the RGG repeat. The DEAD/DExH domain appears to be insufficient on its own to promote helicase activity and additional RNA-binding capacity must be supplied either as domains adjacent to the DEAD/DExH-box or by bound partners as in the eIF-4AB dimer. The presence or absence of extra RNA-binding domains should allow classification of DEAD/DExH proteins as monomeric or multimeric helicases.
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