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At least 415 records · Page 23Linked to original sources
PubMed2004

Identification of a purine-rich intronic enhancer element in the mouse eosinophil-associated ribonuclease 2 (mEar 2) gene.

The Mus musculus eosinophil-associated ribonuclease (mEar) gene cluster includes multiple distinct coding sequences that are highly divergent orthologs of the human eosinophil ribonucleases, eosinophil-derived neurotoxin (EDN/RNase 2) and eosinophil cationic protein (ECP/RNase 3). We present a transcriptional analysis of the gene encoding mEar 2, the only member of this cluster with a well-defined expression profile. In this work, we demonstrate that the presence of non-coding exon 1 and the intron in tandem with a 361-bp 5' promoter of mEar 2 results in enhanced reporter gene expression, as much as 6-to 10-fold over the activity observed with the 5' promoter alone. We have identified a conserved purine-rich element in the intron of the mEar 2 gene that is necessary for maximum transcription and that interacts specifically with NFAT-binding proteins in nuclear extracts derived from the mouse LA4 epithelial cell line. Similar intronic enhancers have been described as regulating transcription of the human EDN gene, suggesting an overall conservation of an important regulatory strategy.

Animals↗
PubMed2003

Gene structure of the human metabotropic glutamate receptor 5 and functional analysis of its multiple promoters in neuroblastoma and astroglioma cells.

The metabotropic glutamate receptor 5 (mGluR5) has a discrete tissue expression mainly limited to neural cells. Expression of mGluR5 is developmentally regulated and undergoes dramatic changes in association with neuropathological disorders. We report the complete genomic structure of the mGluR5 gene, which is composed of 11 exons and encompasses approximately 563 kbp. Three clusters of multiple transcription initiation sites located on three distinct exons (IA, IB, and II), which undergo alternative splicing, have been identified. The 5'-flanking regions of these exons were isolated and, using a luciferase reporter gene assay, shown to possess active promoter elements in SKN-MC neuroblastoma and U178-MG astroglioma cells. Promoter IA was characterized by a CpG island; promoter IB contained a TATA box, and promoter II possessed three active Oct-1-binding sites. Preferential luciferase activity was observed in SKN-MC concomitant with differential DNA binding activity to several responsive elements, including CREB, Oct-1, C/EBP, and Brn-2. Exposure to growth factors produced enhanced expression of promoters IB and II in astroglioma cells and activation of NF-kappa B. These results suggest that alternative 5'-splicing and usage of multiple promoters may contribute regulatory mechanisms for tissue- and context-specific expression of the mGluR5 gene.

5' Untranslated Regions↗
PubMed2004

Spatial growth of real-world networks.

Many real-world networks have properties of small-world networks, with clustered local neighborhoods and low average-shortest path. They may also show a scale-free degree distribution, which can be generated by growth and preferential attachment to highly connected nodes, or hubs. However, many real-world networks consist of multiple, interconnected clusters not normally seen in systems grown by preferential attachment, and there also exist real-world networks with a scale-free degree distribution that do not contain highly connected hubs. We describe spatial-growth mechanisms, not using preferential attachment, that address both aspects.

Journal Article↗
PubMed2001

Modularity in the gain and loss of genes: applications for function prediction.

Genes that are clustered on multiple genomes and are likely to functionally interact tend to be gained or lost together during genome evolution. Here, we demonstrate that exceptions to this pattern indicate relatively distant functional interactions between the encoded proteins. Hence, this can be used to divide predicted clusters of functionally interacting proteins into sub-clusters, and as such, to refine the prediction of their function and functional interactions.

Bacterial Proteins↗
PubMed2005

Vulnerability and unmet health care needs. The influence of multiple risk factors.

CONTEXT: Previous studies have demonstrated a strong association between minority race, low socioeconomic status (SES), and lack of potential access to care (e.g., no insurance coverage and no regular source of care) and poor receipt of health care services. Most studies have examined the independent effects of these risk factors for poor access, but more practical models are needed to account for the clustering of multiple risks. OBJECTIVE: To present a profile of risk factors for poor access based on income, insurance coverage, and having a regular source of care, and examine the association of the profiles with unmet health care needs due to cost. Relationships are examined by race/ethnicity. DESIGN: Analysis of 32,374 adults from the 2000 National Health Interview Survey. MAIN OUTCOME MEASURES: Reported unmet needs due to cost: missing/delaying needed medical care, and delaying obtaining prescriptions, mental health care, or dental care. RESULTS: Controlling for personal demographic and community factors, individuals who were low income, uninsured, and had no regular source of care were more likely to miss or delay needed health care services due to cost. After controlling for these risk factors, whites were more likely than other racial/ethnic groups to report unmet needs. When presented as a risk profile, a clear gradient existed in the likelihood of having an unmet need according to the number of risk factors, regardless of racial/ethnic group. CONCLUSION: Unmet health care needs due to cost increased with higher risk profiles for each racial and ethnic group. Without attention to these co-occurring risk factors for poor access, it is unlikely that substantial reductions in disparities will be made in assuring access to needed health care services among vulnerable populations.

Adult↗
PubMed1995

Integrin-mediated cell adhesion promotes tyrosine phosphorylation of p130Cas, a Src homology 3-containing molecule having multiple Src homology 2-binding motifs.

p130Cas (Cas) has been recently identified as a 130-kDa protein that is highly phosphorylated on tyrosine residues and is stably associated with p47v-crk (v-Crk) and p60v-src (v-Src) oncogene products in cells transformed by the respective genes. Cas is a novel signaling molecule having a single Src homology (SH) 3 domain and a cluster of multiple SH2-binding motifs. While the tight association of Cas with v-Crk and v-Src is strongly suggestive of a significant role in regulating cellular transformation, the function of Cas in normal untransformed cells is totally unknown. We report here that cell adhesion to fibronectin rapidly promotes tyrosine phosphorylation of Cas in human and rat fibroblast cell lines. The response was equally induced by cell adhesion to plates coated with vitronectin, laminin, and collagen but not by cell attachment to nonspecific substrate poly-L-lysine. The kinetic profile of Cas phosphorylation was almost identical with that of tyrosine phosphorylation of focal adhesion kinase pp125FAK (Fak), which is well known to be activated subsequent to integrin-mediated cell adhesion. Adhesion-dependent Cas phosphorylation was completely inhibited by treating cells with cytochalasin D, an agent that disrupts polymerization of actin stress fibers. These results suggest that tyrosine phosphorylation of Cas is stimulated by normal cell adhesion in close association with Fak phosphorylation and the formation of actin stress fibers. In v-Src- or v-Crk-transformed cells, however, the tyrosine phosphorylation of Cas is markedly increased in an adhesion-independent manner that is insensitive to treatment with cytochalasin D. Thus, Cas plays a role in signaling pathways mediated by cell adhesion as well as by transformation. We propose that Cas may amplify and propagate integrin-mediated signals by interacting with SH2-containing molecule(s).

Animals↗
PubMed2004

DNA diversity of human populations from Eastern Europe and Siberia studied by multilocus DNA fingerprinting.

We used DNA fingerprinting with M13 phage DNA as a probe to estimate the degree of genomic variability and genetic relationships in a heterogeneous group of 13 populations from Eastern Europe and Siberia. The popultaions belong to three language families: Indo-European (Slavonic: Russians, Byelorussians), Uralic (Finno-Ugric: Maris, Mordvinians, Udmurts), and Altaic (Turkic: Bashkirs, Tatars, Chuvashes, Yakuts). Multivariate statistical analyses were used (multidimensional scaling, cluster, and multiple correspondence analyses), and coefficients of gene differentiation ( Gst') were evaluated. The level of interpopulation subdivision in the various ethnic groups appeared to be different: the Byelorussian populations revealed no regional differences, in contrast to the Bashkir populations, which formed a heterogeneous group. The populations subdivided into three general clusters: Slavonic populations formed a separate tight cluster characterized by a minimal level of interpopulation diversity, Bashkir and Yakut populations formed the second cluster, and the Finno-Ugric and several populations of the Turkic linguistic groups formed the third cluster. The robustness of these results obtained by different statistical data treatments reveals that multilocus DNA fingerprinting can be reliably used for population studies.

Bacteriophage M13↗
PubMed2006

Energy pooling in multiple ionization and Coulomb explosion of clusters by nanosecond-long, megawatt laser pulses.

We report the results of experiments that establish the possibility of bringing about multiple ionization and Coulomb explosion of molecular clusters with nanosecond laser pulses at intensities as small as 10(9) W cm(-2). We demonstrate several new facets of the laser-cluster interaction in the low-intensity, long-pulse domain: (i) The choice of laser wavelength for a given cluster species is very crucial. (ii) Excited electronic states play a very important role in the ionization dynamics. (iii) When field ionization is insignificant and ponderomotive energies are very small, it is energy pooling rather than inverse bremsstrahlung that determines how clusters absorb energy from the optical field.

Journal Article↗
PubMed1993

Cooperative binding of an Ultrabithorax homeodomain protein to nearby and distant DNA sites.

Cooperativity in binding of regulatory proteins to multiple DNA sites can heighten the sensitivity and specificity of the transcriptional response. We report here the cooperative DNA-binding properties of a developmentally active regulatory protein encoded by the Drosophila homeotic gene Ultrabithorax (Ubx). We show that naturally occurring binding sites for the Ubx-encoded protein contain clusters of multiple individual binding site sequences. Such sites can form complexes containing a dozen or more Ubx-encoded protein molecules, with simultaneous cooperative interactions between adjacent and distant DNA sites. The distant mode of interaction involves a DNA looping mechanism; both modes appear to enhance transcriptional activation in a simple yeast assay system. We found that cooperative binding is dependent on sequences outside the homeodomain, and we have identified regions predicted to form coiled coils carboxy terminal to the homeodomains of the Ubx-encoded protein and several other homeotic proteins. On the basis of our findings, we propose a multisite integrative model of homeotic protein action in which functional regulatory elements can be built from a few high-affinity sites, from many lower-affinity sites, or from sites of some intermediate number and affinity. An important corollary of this model is that even small differences in binding of homeotic proteins to individual sites could be summed to yield large overall differences in binding to multiple sites. This model is consistent with reports that homeodomain protein targets contain multiple individual binding site sequences distributed throughout sizable DNA regions. Also consistent is a recent report that sequences carboxy terminal to the Ubx homeodomain can contribute to segmental specificity.

Animals↗
PubMed2006

Geographic patterns of microsatellite variation in Boechera stricta, a close relative of Arabidopsis.

The genus Boechera is a widespread North American group with great potential for studies of ecology and evolution: Boechera is closely related to Arabidopsis and exhibits different ecological and reproductive strategies. Boechera stricta (previously Arabis drummondii) is a morphologically and genetically well-defined, perennial crucifer species. Fifteen natural populations of diploid individuals from the Rocky Mountains were analysed using 21 microsatellite loci. In accordance with our expectation for this predominately inbreeding species, a high F IS value (0.89) was observed. Furthermore, populations of B. stricta were highly differentiated, as indicated by F ST = 0.56. Three clusters were identified using structure- the majority of populations belonged to either the Northern or Southern cluster. Together, the north-south partitioning and evenness of genetic variation across the two clusters suggested multiple refugia for this perennial herb in the Rocky Mountains. Pleistocene glaciation, together with the topographically and climatologically heterogeneous cordillera, has profoundly influenced the genetic architecture of B. stricta. Genetic population structure was also influenced by relatively recent genome admixture at two levels: within species (involving individuals from the Northern and Southern clusters) and between species (with the hybridization of B. stricta and Boechera holboellii). This complexity of population structure at presumably neutral microsatellite loci located throughout the genome in B. stricta provides a baseline against which to test whether functional genetic variation is undergoing local adaptive evolution throughout the natural species range.

Brassicaceae↗
PubMed1999

Molecular mechanism of metabolic syndrome X: contribution of adipocytokines adipocyte-derived bioactive substances.

Syndrome X is a clinical syndrome in which multiple risks cluster in an individual, and it is a common basis of vascular disease in the industrial countries. The molecular basis of Syndrome X, however, has not been elucidated. We have analyzed body fat distribution using CT scan and have shown that people who have accumulated intra-abdominal visceral fat frequently have multiple risks and vascular diseases. Thus, "visceral fat syndrome" is a clinical entity compatible with Syndrome X. To clarify the molecular mechanism of the disorders in visceral fat syndrome, we analyzed the expressed genes in adipose tissue by a large-scale random sequencing. Unexpectedly, visceral fat expressed a variety of the genes for secretory proteins including various bioactive substances; we designated them adipocytokines. One of them, plasminogen activator inhibitor-1, was overproduced in accumulated visceral fat and might contribute to the development of vascular disease. We have also cloned a novel adipose-specific gene named adiponectin. Adiponectin is a collagen-like plasma protein which has an inhibitory effect on proliferation of vascular smooth muscle cells; its plasma levels are paradoxically decreased in obesity. Adipocytokines may play important roles in the development of the disorders in Syndrome X.

Adipocytes↗
PubMed2006

Setting the stage for equity-sensitive monitoring of the maternal and child health Millennium Development Goals.

OBJECTIVE: This analysis seeks to set the stage for equity-sensitive monitoring of the health-related Millennium Development Goals (MDGs). METHODS: We use data from international household-level surveys (Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS)) to demonstrate that establishing an equity baseline is necessary and feasible, even in low-income and data-poor countries. We assess data from six countries using 11 health indicators and six social stratifiers. Simple bivariate stratification is complemented by simultaneous stratification to expose the compound effect of multiple forms of vulnerability. FINDINGS: The data reveal that inequities are complex and interactive: inferences cannot be drawn about the nature or extent of inequities in health outcomes from a single stratifier or indicator. CONCLUSION: The MDGs and other development initiatives must become more comprehensive and explicit in their analysis and tracking of inequities. The design of policies to narrow health gaps must take into account country-specific inequities.

Data Collection↗
PubMed1988

Distinctive charge configurations in proteins of the Epstein-Barr virus and possible functions.

The protein products of several open reading frames (ORFs) of the Epstein-Barr virus (EBV) are remarkable in their distribution of charged residues. The nuclear antigen proteins EBNA1-EBNA4 of the EBV latent state contain separate significant clusters of charge of each sign. They (excepting EBNA4) also feature distinctive periodic charge patterns [e.g., (+, O)8, (O, -, -)7] and significant tandem repeats. None of the other ORFs (about 80) of the genome possess the conjunction of these properties. Only the protein encoded from BMLF1, the first immediate early transactivator protein, contains significant multiple charge clusters and periodic charge patterns. All proteins that contain significant repeats also contain at least one significant charge cluster of a single sign. These include EBNA5 and LYDMA produced during latency and BZLF1, whose expression terminates latency and initiates productive growth. It is reasonable to conclude that these aggregate significant charge configurations and repeats are important functionally for the latent existence and for the initiation of the lytic cycle and may be characteristic of these conditions. We discuss how large multimeric protein structures bound together by clusters of unlike charge may provide a mechanism for regulation of the expression of these proteins.

Amino Acid Sequence↗
PubMed2001

A multiple imputation approach to linear regression with clustered censored data.

We extend Wei and Tanner's (1991) multiple imputation approach in semi-parametric linear regression for univariate censored data to clustered censored data. The main idea is to iterate the following two steps: 1) using the data augmentation to impute for censored failure times; 2) fitting a linear model with imputed complete data, which takes into consideration of clustering among failure times. In particular, we propose using the generalized estimating equations (GEE) or a linear mixed-effects model to implement the second step. Through simulation studies our proposal compares favorably to the independence approach (Lee et al., 1993), which ignores the within-cluster correlation in estimating the regression coefficient. Our proposal is easy to implement by using existing softwares.

Algorithms↗
PubMed2001

Genomic analysis of orthologous mouse and human olfactory receptor loci.

Olfactory receptor (OR) genes represent approximately 1% of genomic coding sequence in mammals, and these genes are clustered on multiple chromosomes in both the mouse and human genomes. We have taken a comparative genomics approach to identify features that may be involved in the dynamic evolution of this gene family and in the transcriptional control that results in a single OR gene expressed per olfactory neuron. We sequenced approximately 350 kb of the murine P2 OR cluster and used synteny, gene linkage, and phylogenetic analysis to identify and sequence approximately 111 kb of an orthologous cluster in the human genome. In total, 18 mouse and 8 human OR genes were identified, including 7 orthologs that appear to be functional in both species. Noncoding homology is evident between orthologs and generally is confined within the transcriptional unit. We find no evidence for common regulatory features shared among paralogs, and promoter regions generally do not contain strong promoter motifs. We discuss these observations, as well as OR clustering, in the context of evolutionary expansion and transcriptional regulation of OR repertoires.

5' Untranslated Regions↗
PubMed1986

Cerebral amyloid angiopathy: the vascular pathology and complications.

Twenty-five cases with cerebral amyloid angiopathy (CAA) were studied. Senile plaques (SP) were present in all cases. In only eight cases which also displayed either SP (two cases), or both SP and Alzheimer's neurofibrillary tangles (NFT) (six cases), was there a history of dementia. In five cases, SP and NFT were observed without a history of dementia. Seven cases had significant cerebral hemorrhage, single or multiple, which could be related to CAA. Ten cases had cerebral infarcts, but only in seven of these cases could the infarcts be related to CAA. In five cases, with moderate to severe CAA and no history of dementia other distinctive vascular changes were also noted in the brain. These CAA-associated vasculopathies (CAA-AV) consisted of: clusters of multiple arteriolar lumina, the so-called "glomerular" formations, with various degrees of amyloid infiltration; aneurysmal vessels with amyloid infiltration; obliterative intimal changes; "double barreling", chronic inflammatory perivascular or transmural infiltrates; hyaline (nonamyloid) arteriolar degeneration, with or without aneurysmal dilatation; and fibrinoid necrotizing vascular change. In all five cases with CAA-AV, there were cerebral infarcts or hemorrhages which were considered to be direct complications of amyloid angiopathy, or of the vasculopathies developing secondary to the amyloid infiltration of vessel walls. It is possible that the associated vasculopathies represented secondary vascular changes that followed amyloid deposition in the blood vessel walls.

Aged↗
PubMed1996

Trinucleotide repeats and long homopeptides in genes and proteins associated with nervous system disease and development.

Several human neurological disorders are associated with proteins containing abnormally long runs of glutamine residues. Strikingly, most of these proteins contain two or more additional long runs of amino acids other than glutamine. We screened the current human, mouse, Drosophila, yeast, and Escherichia coli protein sequence data bases and identified all proteins containing multiple long homopeptides. This search found multiple long homopeptides in about 12% of Drosophila proteins but in only about 1.7% of human, mouse, and yeast proteins and none among E. coli proteins. Most of these sequences show other unusual sequence features, including multiple charge clusters and excessive counts of homopeptides of length > or = two amino acid residues. Intriguingly, a large majority of the identified Drosophila proteins are essential developmental proteins and, in particular, most play a role in central nervous system development. Almost half of the human and mouse proteins identified are homeotic homologs. The role of long homopeptides in fine-tuning protein conformation for multiple functional activities is discussed. The relative contributions of strand slippage and of dynamic mutation are also addressed. Several new experiments are proposed.

Amino Acid Sequence↗
PubMed2004

Renal defects and limb deficiencies in 197 infants: is it possible to define the "acrorenal syndrome"?

Dieker and Opitz in 1969 described the simultaneous occurrence of limb deficiencies (LDs) and renal anomalies (RAs) in three patients. Curran and Curran introduced in 1972 the term "acrorenal syndrome." Since then, the term "acrorenal syndrome" is used occasionally, but a well-circumscribed definition has never been established. On the other hand, the concept of an acrorenal polytopic developmental field defect was postulated by Opitz and others to explain the association between RAs and LDs. We undertook this study to investigate whether this acrorenal "syndrome" could be identified in a large group of cases with congenital RAs and a limb deficiency. Eleven birth defect registries that are part of the International Clearinghouse for Birth Defects Monitoring (i.e., registries of ICBDMS in Finland, France [Paris and Strasbourg], Israel, Italy [IPIMC and Emilia Romagna], Mexico, Northern Netherlands, South America, Spain, and the United States [Atlanta]) provided data on 815 infants who had a LD and at least one other major congenital anomaly. These 815 cases were ascertained among 5,163,958 births. We selected the 197 cases who had both a limb deficiency and a renal or urinary tract anomaly. In about 50% of these cases a diagnosis or a recognized phenotype was reported, with chromosomal aberrations and VACTERL being most frequent. In the group with no diagnosis or recognized phenotype (95 cases), we looked for (a) clustering of specific types of LDs and RAs, and (b) for clustering of associated anomalies, in order to find evidence for and be able to define better the term "acrorenal syndrome." Our data suggest that an association exists between LDs and RAs, possibly explained by the concept of the acrorenal polytopic developmental field defect. However, our dataset does not yield evidence for the existence of one distinct "syndrome," defined as a pattern of causally related multiple anomalies. Therefore, use of the term "acrorenal syndrome" should be avoided.

Abnormalities, Multiple↗