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W Gilbert

Publications and source records attributed to W Gilbert.

At least 19 recordsLinked to original sources
PubMed2005

An evaluation of information dissemination during the severe acute respiratory syndrome (SARS) outbreak among selected rural communities in Kuala Kangsar.

To assess the level of knowledge, attitude and practice (KAP) on SARS and its preventive measures among the rural population of Kuala Kangsar district. This KAP study was also done to identify the expectation and preference of rural population upon obtaining health information. This is a cross-sectional study of 201 households from four villages in Kuala Kangsar. Face-to-face interview was done regarding knowledge, attitude and practice on SARS and its preventive measures. Statistical analyses were performed with SPSS (Version 10.0). A scoring system was used to assess the level of knowledge, attitude and practice towards SARS. Ninety one percent of the study population was aware of SARS. Majority of them have good attitude towards SARS based on the formulated scoring system. Television was found to be the first hand information about SARS and most preferred source of information by the rural population. Knowledge and attitude of respondents concerning SARS were good. Television was found to be the preference among the rural population in obtaining health information.

Adult↗
PubMed2001

Intron distribution difference for 276 ancient and 131 modern genes suggests the existence of ancient introns.

o introns delineate elements of protein tertiary structure? This issue is crucial to the debate about the role and origin of introns. We present an analysis of the full set of proteins with known three-dimensional structures that have homologs with intron positions recorded in GenBank. A computer program was generated that maps on a reference sequence the positions of all introns in homologous genes. We have applied this program to a set of 665 nonredundant protein sequences with defined three-dimensional structures in the Protein Data Bank (PDB), which yielded 8,217 introns in 407 proteins. For the subset of proteins corresponding to ancient conserved regions (ACR), we find that there is a correlation of phase-zero introns with the boundary regions of modules and no correlation for the phase-one and phase-two positions. However, for a subset of proteins without prokaryotic counterparts (131 non-ACR proteins), a set of presumably modern proteins (or proteins that have diverged extremely far from any ancestral form), we do not find any correlation of phase-zero intron positions with three-dimensional structure. Furthermore, we find an anticorrelation of phase-one intron positions with module boundaries: they actually have a preference for the interior of modules. This finding is explicable as a preference for phase-one introns to lie in glycines, between G/G sequences, the preference for glycines being anticorrelated with the three-dimensional modules. We interpret this anticorrelation as a sign that a number of phase-one introns, and hence many modern introns, have been inserted into G/G "protosplice" sequences.

Evolution, Molecular↗
PubMed2001

Phosphorylation by Sky1p promotes Npl3p shuttling and mRNA dissociation.

Mammalian SR proteins are currently thought to function in mRNA export as well as splicing. They contain multiple phosphorylated serine/arginine (RS/SR) dipeptides. Although SR domains can be phosphorylated by many kinases in vitro, the physiologically relevant kinase(s), and the role(s) of these modifications in vivo have remained unclear. Npl3 is a shuttling protein in budding yeast that we showed previously to be a substrate for the mammalian SR protein kinase, SRPK1, as well as the related yeast kinase, Sky1. Here we demonstrate that Sky1p phosphorylates only one of Npl3p's eight SR/RS dipeptides. Mutation of the C-terminal RS to RA, or deletion of SKY1, results in the cytoplasmic accumulation of Npl3p. The redistribution of Npl3p is accompanied by its increased association with poly(A)+ RNA and decreased association with its import receptor, Mtr10p, in vivo. We propose that phosphorylation of Npl3p by the cytoplasmically localized Sky1p is required for efficient release of mRNA upon termination of export.

Arginine↗
PubMed2001

Evaluation of a microwave and infrared human-presence sensing system for agricultural equipment.

The potential use of electronic safety sensors to protect operators from agricultural equipment with rotating hazards has been identified and discussed as a possible means to prevent traumatic entanglement injury. A multi-sensor human-presence sensing system to protect persons approaching a rotating PTO shaft powering a stationary implement was developed using commercially available, passive infrared and microwave sensors. A control and data acquisition system was designed and constructed to evaluate sensor performance and response. The sensor system performed well during 822 warm weather test passes in which a person approached the potentially hazardous area near the drawbar and PTO/IID located between an IH 986 test tractor and a self-unloading forage wagon. During the 822 test passes, there were no false alarms and no misses. Operators approached the hazard space walking from 92 to 227 cm/second. During tests, the sensing system yielded warning times generally between 0.5 and 1.0 seconds, providing an estimate of the time available to accomplish machine shutdown or operator warnings. Additional cold weather tests caused the control and data acquisition hardware to function erratically. This work suggests that multi-sensor human detection systems have the potential to reduce false alarms through redundancy when more than one sensor is required to detect a person before the system signals a "detect" condition. However, the use of multiple, redundant sensors also increases the potential for a "miss." Further work is needed to determine whether these types of sensor can yield timely enough information to prevent injury via mechanical shutdown or operator warnings.

Accidents, Occupational↗
PubMed2000

EID: the Exon-Intron Database-an exhaustive database of protein-coding intron-containing genes.

To aid studies of molecular evolution and to assist in gene prediction research, we have constructed an Exon-Intron Database (EID) in FASTA format. Currently, the database is derived from GenBank release 112, and it contains 51 289 protein-coding genes (287 209 exons) that harbor introns, along with extensive descriptions of each gene and its DNA and protein sequences, as well as splice motif information. There is 17% redundancy inherited from GenBank-a purge at the 99% identity level reduced the database to 42 460 genes (243 589 exons). We have created subdatabases of genes whose intron positions have been experimentally determined. One such database, constructed by comparing genomic and mRNA sequences, contains 11 242 genes (62 474 exons). A larger database of 22 196 genes (105 595 exons) was constructed by selecting on keywords to eliminate computer-predicted genes. By examining the two nucleotides adjacent to the intron boundary, we infer that there is a 2% rate of errors or other deviations from the standard GTellipsisAG motif in nuclear genes. This criterion can be used to eliminate 4921 genes from the overall database. Various tools are provided to enable generation of user-specific subsets of the EID. The EID distribution can be obtained from http://mcb.harvard.edu/gilbert/EID

Base Sequence↗
PubMed2000

The genomic structure of c14orf1 is conserved across eukarya.

We have recently cloned the gene C14orf1, which is strongly expressed in normal testis and in several cancer cell lines and tumors. This gene maps to 14q24.3 and is interrupted by four introns. Two of them are also represented in the open reading frame of Schizosaccharomyces pombe in the same phase. In Arabidopsis taliana only the first of the two introns was found, in the same phase as the corresponding ones in S. pombe and human. Disruption of the ortholog in Saccharomyces cerevisiae (Yer044c) led to a severe growth defect, and C14orf1 failed to complement mutant yeast when put under the control of the natural Yer044c promoter. Further studies are needed to understand the causes underlying the high degree of conservation of the C14orf1 genomic structure.

Amino Acid Sequence↗
PubMed1999

Centripetal modules and ancient introns.

We have created an algorithm which instantiates the centripetal definition of modules, compact regions of protein structure, as introduced by Go and Nosaka (M. Go and M. Nosaka, 1987. Protein architecture and the origin of introns. Cold Spring Harbor Symp. Quant. Bio. 52, 915-924). That definition seeks the minima of a function that sums the squares of C-alpha carbon distances over a window around each amino acid residue in a three-dimensional protein structure and identifies such minima with module boundaries. We analyze a set of 44 ancient conserved proteins, with known three-dimensional structures, which have intronless homologues in bacteria and intron-containing homologues in the eukaryotes, with a corresponding set of 988 intron positions. We show that the phase zero intron positions are significantly correlated with the module boundaries (p = 0.0002), while the intron positions that lie within codons, in phase one and phase two, are not correlated with these 'centripetal' module boundaries. Furthermore, we analyze the phylogenetic distribution of intron positions and identify a subset of putatively 'ancient' intron positions: phase zero positions in one phylogenetic kingdom which have an associated intron either in an identical position or within three codons in another phylogenetic kingdom (a notion of intron sliding). This subset of 120 'ancient' introns lies closer to the module boundaries than does the full set of phase zero introns with high significance, a p-value of 0.008. We conclude that the behavior of this set of introns supports the prediction of a mixed theory: that some introns are very old and were used for exon shuffling in the progenote, while many introns have been lost and added since.

Algorithms↗
PubMed1998

Toward a resolution of the introns early/late debate: only phase zero introns are correlated with the structure of ancient proteins.

We present evidence that a well defined subset of intron positions shows a non-random distribution in ancient genes. We analyze a database of ancient conserved regions drawn from GenBank 101 to retest two predictions of the theory that the first genes were constructed by exon shuffling. These predictions are that there should be an excess of symmetric exons (and sets of exons) flanked by introns of the same phase (positions within the codon) and that intron positions in ancient proteins should correlate with the boundaries of compact protein modules. Both these predictions are supported by the data, with considerable statistical force (P values < 0.0001). Intron positions correlate to modules of diameters around 21, 27, and 33 A, and this correlation is due to phase zero introns. We suggest that 30-40% of present day intron positions in ancient genes correspond to phase zero introns originally present in the progenote, while almost all of the remaining intron positions correspond to introns added, or moved, appearing equally in all three intron phases. This proposal provides a resolution for many of the arguments of the introns-early/introns-late debate.

Animals↗
PubMed1998

Relationship between "proto-splice sites" and intron phases: evidence from dicodon analysis.

The coding sequence at the boundaries of exons flanking nuclear introns shows some degree of conservation. To the extent that such sequences might be recognized by the splicing machinery, this conservation may be a derived result of evolution for efficient splicing. Alternatively, such conserved sequences might be remnants of proto-splice sites, which might have existed early in eukaryotic genes and served as the targets for the insertion of introns, as has been proposed by the introns-late theory. The distribution of intron phases, the position of the intron within a codon, is biased with an over-representation of phase 0 introns. Could any distribution of proto-splice sites account for today's intron phase distribution? Here, we examine the dicodon usage in six model organisms, based on current sequences in the GenBank database, and predict the phase distribution that would be expected if introns had been inserted into proto-splice sites. However, these predictions differ between the various model organisms and disagree with the observed intron phase distributions. Thus, we reject the hypothesis that introns are inserted into hypothetical proto-splice sites. Finally, we analyze the sequences around the splice sites of introns in all six of the species to show that the actual conservation of sequence in exon regions near introns is very small and differs considerably between these species, which is inconsistent with a general proto-splice sites model.

Animals↗
PubMed1997

The correlation between introns and the three-dimensional structure of proteins.

We test the hypothesis that introns were used to construct the first genes from small exons, whose protein products represent compact elements of structure. For any three-dimensional structure, a computer program analyzes the structure into a set of modules, segments of the polypeptide chain bounded in space by a maximum diameter, separated by a set of 'boundary regions'. The 'boundary regions' are such that if the gene were divided by an intron in each 'boundary region', the protein would be divided into modules less than the specified diameter. Using a set of 32 ancient proteins, which have no introns in prokaryotes, we examine the intron positions in their eukaryotic homologs and show that the introns are correlated with modules of diameter 21, 28 and 33 A, with P values below 0.001.

Exons↗
PubMed1997

A novel zebrafish gene expressed specifically in the photoreceptor cells of the retina.

We have identified and characterized a novel protein from adult zebrafish retina, which we named ES1. Database search revealed that the ES1 gene has significant similarity to two genes with unknown functions: the Escherichia coli sigma cross-reacting protein 27a (scrp27a) and the human KNP-I/GT335. In situ hybridization and immunohistochemistry experiments showed that both ES1 mRNA and protein are expressed specifically in adult photoreceptor cells. ES1 seems to be a cytoplasmic protein. An ES1-like antigen was also detected in photoreceptor cells of goldfish with anti-ES1 antibodies. The retina specific expression and the evolutionary conservation suggest that ES1 protein may be important for maintaining normal retina structure and function.

Amino Acid Sequence↗
PubMed1997

Origin of genes.

We discuss two tests of the hypothesis that the first genes were assembled from exons. The hypothesis of exon shuffling in the progenote predicts that intron phases will be correlated so that exons will be an integer number of codons and predicts that the exons will be correlated with compact regions of polypeptide chain. These predictions have been tested on ancient conserved proteins (proteins without introns in prokaryotes but with introns in eukaryotes) and hold with high statistical significance. We conclude that introns are correlated with compact features of proteins 15-, 22-, or 30-amino acid residues long, as was predicted by "The Exon Theory of Genes."

Animals↗
PubMed1997

Ligands for ErbB-family receptors encoded by a neuregulin-like gene.

Neuregulins (also called ARIA, GGF, heregulin or NDF) are a group of polypeptide factors that arise from alternative RNA splicing of a single gene. Through their interaction with the ErbB family of receptors (ErbB2, ErbB3 and ErbB4), neuregulins help to regulate cell growth and differentiation in many tissues. Here we report the cloning of a second neuregulin-like gene, neuregulin-2. The encoded product of the neuregulin-2 gene has a motif structure similar to that of neuregulins and an alternative splicing site in the epidermal growth factor(EGF)-like domain gives rise to two isoforms (alpha and beta). Northern blot and in situ hybridization analysis of adult rat tissues indicate that expression of neuregulin-2 is highest in the cerebellum, and the expression pattern is different from that of neuregulins. Recombinant neuregulin-2beta induces the tyrosine-phosphorylation of ErbB2, ErbB3 and ErbB4 in cell lines expressing all of these ErbB-family receptors. However, in cell lines with defined combinations of ErbBs, neuregulin-2beta only activates those with ErbB3 and/or ErbB4, suggesting that signalling by neuregulin-2 is mediated by ErbB3 and/or ErbB4 receptors.

Amino Acid Sequence↗