Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “multiple clustering”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,423 records · Page 79Linked to original sources
PubMed1993

Splicing mutants and their second-site suppressors at the dihydrofolate reductase locus in Chinese hamster ovary cells.

Point mutants induced with a variety of mutagens at the dihydrofolate reductase (dhfr) locus in Chinese hamster ovary (CHO) cells were screened for aberrantly spliced dhfr mRNA by RNase protection and/or reverse transcriptase coupled with cDNA amplification by the polymerase chain reaction (PCR). Of 115 mutants screened, 28 were found to be affected in splicing. All exhibited less than 1% correct splicing, probably because the selection procedure was stringent. All 26 unique mutations were located within the consensus splice sequences; changes were found at 9 of 10 possible sites in this 25-kb six-exon gene. Mutations at the sites flanking the first and last exons resulted in the efficient recruitment of a cryptic site within each exon. In contrast, mutations bordering internal exons caused predominantly exon skipping. In many cases, multiple exons were skipped, suggesting the clustering of adjacent exons prior to actual splicing. Six mutations fell outside the well-conserved GU and AG dinucleotides. All but one were donor site single-base substitutions that decreased the agreement with the consensus and resulted in little or no correct splicing. Starting with five of these donor site mutants, we isolated 31 DHFR+ revertants. Most revertants carried a single-base substitution at a site other than that of the original mutation, and most had only partially regained the ability to splice correctly. The second-site suppression occurred through a variety of mechanisms: (i) a second change within the consensus sequence that produced a better agreement with the consensus; (ii) a change close to but beyond the consensus boundaries, as far as 8 bases upstream in the exon or 28 bases downstream in the intron; (iii) mutations in an apparent pseudo 5' site in the intron, 84 and 88 bases downstream of a donor site; and (iv) mutations that improved the upstream acceptor site of the affected exon. Taken together, these second-site suppressor mutations extend the definition of a splice site beyond the consensus sequence.

Alternative Splicing↗
PubMed1995

p53 inhibits DNA replication in vitro in a DNA-binding-dependent manner.

The p53 tumor suppressor gene product is a sequence-specific DNA-binding protein that is necessary for the G1 arrest of many cell types. Consistent with its role as a cell cycle checkpoint factor, p53 has been shown to be capable of both transcriptional activation and repression. Here we show a new potential role for p53 as a DNA-binding-dependent regulator of DNA replication. Constructs containing multiple copies of the ribosomal gene cluster (RGC) p53 binding site cloned on the late side of the polyomavirus origin were used in in vitro replication assays. In the presence of p53, the replication of these constructs was strongly inhibited, while the replication of constructs containing a mutant version of the RGC site was not affected by p53. Several tumor-derived mutant p53 proteins were unable to inhibit replication of the construct with wild-type RGC sites. Additionally, the transactivator GAL4-VP16 was unable to inhibit replication of a construct containing GAL4 binding sites adjacent to the polyomavirus origin. We also show that the inhibition by p53 can occur from sites cloned as far as 600 bp from the origin. Preincubation experiments suggest that p53 inhibits replication at a step mediated by ATP, possibly by inhibiting the binding of polyomavirus T antigen to the core origin. The presence of an endogenous p53 binding site in the polyomavirus origin suggests potential mechanisms for the observed inhibition.

Amino Acid Sequence↗
PubMed1997

Regulation of the myeloid-cell-expressed human gp91-phox gene as studied by transfer of yeast artificial chromosome clones into embryonic stem cells: suppression of a variegated cellular pattern of expression requires a full complement of distant cis elements.

Identifying the full repertoire of cis elements required for gene expression in mammalian cells (or animals) is challenging, given the moderate sizes of many loci. To study how the human gp91-phox gene is expressed specifically in myeloid hematopoietic cells, we introduced yeast artificial chromosome (YAC) clones and derivatives generated in yeast into mouse embryonic stem cells competent to differentiate to myeloid cells in vitro or into mouse chimeras. Fully appropriate regulation was recapitulated with a 130-kb YAC containing 60 and 30 kb of 5' and 3' flanking sequences, respectively. Immunodetection of human gp91-phox protein revealed uniform expression in individual myeloid cells. The removal of upstream sequences led to decreased overall expression which reflected largely a variegated pattern of expression, such that cells were either "on" or "off," rather than pancellular loss of expression. The proportion of clones displaying marked variegation increased with progressive deletion. DNase I mapping of chromatin identified two hypersensitive clusters, consistent with the presence of multiple regulatory elements. Our findings point to cooperative interactions of complex regulatory elements and suggest that the presence of an incomplete set of elements reduces the probability that an open chromatin domain (or active transcriptional complex) may form or be maintained in the face of repressive influences of neighboring chromatin.

Animals↗
PubMed2004

The cellulosomes: multienzyme machines for degradation of plant cell wall polysaccharides.

The discrete multicomponent, multienzyme cellulosome complex of anaerobic cellulolytic bacteria provides enhanced synergistic activity among the different resident enzymes to efficiently hydrolyze intractable cellulosic and hemicellulosic substrates of the plant cell wall. A pivotal noncatalytic subunit called scaffoldin secures the various enzymatic subunits into the complex via the cohesin-dockerin interaction. The specificity characteristics and tenacious binding between the scaffoldin-based cohesin modules and the enzyme-borne dockerin domains dictate the supramolecular architecture of the cellulosome. The diversity in cellulosome architecture among the known cellulosome-producing bacteria is manifest in the arrangement of their genes in either multiple-scaffoldin or enzyme-linked clusters on the genome. The recently described three-dimensional crystal structure of the cohesin-dockerin heterodimer sheds light on the critical amino acids that contribute to this high-affinity protein-protein interaction. In addition, new information regarding the regulation of cellulosome-related genes, budding genetic tools, and emerging genomics of cellulosome-producing bacteria promises new insight into the assembly and consequences of the multienzyme complex.

Amino Acid Sequence↗
PubMed2004

Screening anti-inflammatory compounds in injured spinal cord with microarrays: a comparison of bioinformatics analysis approaches.

Inflammatory responses contribute to secondary tissue damage following spinal cord injury (SCI). A potent anti-inflammatory glucocorticoid, methylprednisolone (MP), is the only currently accepted therapy for acute SCI but its efficacy has been questioned. To search for additional anti-inflammatory compounds, we combined microarray analysis with an explanted spinal cord slice culture injury model. We compared gene expression profiles after treatment with MP, acetaminophen, indomethacin, NS398, and combined cytokine inhibitors (IL-1ra and soluble TNFR). Multiple gene filtering methods and statistical clustering analyses were applied to the multi-dimensional data set and results were compared. Our analysis showed a consistent and unique gene expression profile associated with NS398, the selective cyclooxygenase-2 (COX-2) inhibitor, in which the overall effect of these upregulated genes could be interpreted as neuroprotective. In vivo testing demonstrated that NS398 reduced lesion volumes, unlike MP or acetaminophen, consistent with a predicted physiological effect in spinal cord. Combining explanted spinal cultures, microarrays, and flexible clustering algorithms allows us to accelerate selection of compounds for in vivo testing.

Algorithms↗
PubMed1998

Various statistical methods in use for evaluating human malignant gastric specimens.

This paper presents the use of certain statistical methods (comparison of means - independent samples t-test, multiple linear regression analysis, multiple logistic regression analysis, analysis of clusters, etc.) included in the SPSS Statistical Package used to classify the patients quantitatively evaluated after a subtotal resection of their stomachs. The group consisted of 40 patients subdivided into two groups: primary neoplasia of the stomach (20 patients), and corresponding lymphogenic deposits in the abdominal perigastric lymph nodes (20 patients). Paraffin-embedded tissue sections (thickness 4-5 microm) prepared as consecutive hematoxylin-eosin-stained slides were morphometrically measured by a rotation of a graduated eyepiece-micrometer; thus, we obtained the minor and major axes' lengths of the elliptic nuclear profiles and the minor and major caliper diameters of the corresponding cellular profiles. These four variables were used to determine the dynamic changes in quantitative features of human gastric lesions when passing from normal histological structures, through hyperplastic processes (chronic gastritis), gastric precancer (ulcers and polyps with or without malignancy) till the development of primary carcinomas and their corresponding lymphogeneous metastases. Besides the increased cytomorphometrical measures, we also noted an opportunity to classify the patients according to these data as well as to add to the knowledge of our consultation system for clinical aid and use, recently published in the literature.

Humans↗
PubMed1993

An assessment of survival rates and within-patient clustering of failures for endosseous oral implants.

This study examined endosseous cylinder implant survival, defined as the unqualified presence of the implant in the mouth at the end of the observation period, in 598 consecutive VA patients, with a total of 2098 implants. Data were taken from the Department of Veterans Affairs (VA) Dental Implant Registry, which has maintained longitudinal data on the survival of individual dental implants in VA patients since 1987. The maximum time of observation in any one patient was 2040 days (5.6 yr). Survival analysis by use of life-table methods was carried out on both an implant- and a patient-specific basis. Implant cases were accrued randomly, and therefore a random censoring model was used. A correlated binomial model was used for assessment of the degree of within-patient clustering of implant removals. Results showed that the implant-specific survival rate during the longest time interval (5.6 yr) was 89.9%; the patient-specific implant survival rate during the same time was 78.2%. Among implants which were removed, the mean time to removal was 292 days. The hazard function, which describes the probability of implant loss as a function of time, decreased steadily throughout the observation period. The correlated binomial model suggested a clustering of removals within patients with multiple implants (rho = 0.11, p = 0.0001). The odds of having a second implant removed were 1.3 times greater if the patient had already had one implant removed. This study suggests that when implants fail, they do so soon after placement, and the likelihood of failure decreases steadily from implantation through the first five years post-surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2004

Eph receptors, ephrins, and synaptic function.

Compelling new findings have revealed that receptor tyrosine kinases of the Eph family, along with their ephrin ligands, play an essential role in regulating the properties of developing mature excitatory synapses in the central nervous system. The cell surface localization of both the Eph receptors and the ephrins enables these proteins to signal bidirectionally at sites of cell-to-cell contact, such as synapses. Eph receptors and ephrins have indeed been implicated in multiple aspects of synaptic function, including clustering and modulating N-methyl-D-aspartate receptors, modifying the geometry of postsynaptic terminals, and influencing long-term synaptic plasticity and memory. In this review, we discuss how Eph receptors and ephrins are integrated into the molecular machinery that supports synaptic function.

Animals↗
PubMed2002

False lateralization of language cortex on functional MRI after a cluster of focal seizures.

fMRI can define language cortex but its limitations are not yet fully understood. This article describes a child in whom fMRI falsely lateralized language cortex when performed after a cluster of left temporal lobe seizures. Multiple language tasks revealed no activation over the left temporal lobe despite a normal neurologic exam at the time of the study. A second fMRI performed 2 weeks later activated sites predominantly over the left, which were confirmed by extra-operative functional language mapping. fMRI may be unhelpful after frequent seizures.

Adolescent↗
PubMed2005

Preparedness for taking care of elderly parents:"first, you get ready to cry".

The results reported in this article are from a larger, mixed-methods study of the factors influencing the preparedness of adult daughters for taking care of elderly parents. This article focuses on findings surfacing in unstructured interviews with daughters revealing an area of caregiving not addressed in survey items, that of daughters' emotional reactions to multiple losses. Actual and anticipatory losses clustered into two categories: loss of the parent and loss of one's own youth. Implications for health care providers are detailed, including: recognizing each daughter's unique life situation; providing anticipatory and long-term emotional support and counseling; and assisting with problem solving, grief work, and making meaning of losses.

Activities of Daily Living↗
PubMed2003

Evolutionary course of CsRn1 long-terminal-repeat retrotransposon and its heterogeneous integrations into the genome of the liver fluke, Clonorchis sinensis.

The evolutionary course of the CsRn1 long-terminal-repeat (LTR) retrotransposon was predicted by conducting a phylogenetic analysis with its paralog LTR sequences. Based on the clustering patterns in the phylogenetic tree, multiple CsRn1 copies could be grouped into four subsets, which were shown to have different integration times. Their differential sequence divergences and heterogeneous integration patterns strongly suggested that these subsets appeared sequentially in the genome of C. sinensis. Members of recently expanding subset showed the lowest level of divergence in their LTR and reverse transcriptase gene sequences. They were also shown to be highly polymorphic among individual genomes of the trematode. The CsRn1 element exhibited a preference for repetitive, agenic chromosomal regions in terms of selecting integration targets. Our results suggested that CsRn1 might induce a considerable degree of intergenomic variation and, thereby, have influenced the evolution of the C. sinensis genome.

Animals↗
PubMed2006

The field dependence/independence cognitive style does not control the spatial perception of elevation.

Earlier work described the presence of a significant connection between an individual's ability to disregard distracting aspects of a visual field in the classical rod-and-frame test (RFT), in which a subject is required to set a rod so that it will appear vertical in the presence of a square frame that is roll tilted from vertical, and in paper-and-pencil tests, in which the subject is required to find a hidden figure embedded in a more complex figure (the Embedded Figures Test [EFT]; see, e.g., Witkin, Dyk, Faterson, Goodenough, & Karp, 1962; Witkin et al., 1954; Witkin, Oltman, Raskin, & Karp, 1971). This has led to a belief in the existence of a bipolar dimension of cognitive style that is utilized in such disembedding tasks--namely, the extent to which an individual is dependent on or independent from the influence of a distracting visual field. The influence of an inducing visual field on the perception of elevation measured by the setting of a visual target to appear at eye level (the visually perceived eye level [VPEL] discrimination) has also been found to be correlated with the RFT. We have thus explored the possible involvement of the dependence/independence cognitive style on the VPEL discrimination. Measurements were made on each of 18 subjects (9 of them female, 9 male) setting a small target to the VPEL in the presence of a pitched visual field across a range of six pitches from -30 degrees (topbackward) to +20 degrees (topforward) and on each of three tests generally recognized as tests of cognitive spatial abilities: the EFT, the Gestalt Completion Test, and the Snowy Pictures Test (SPT). Although there were significant pairwise correlations relating performance on the three cognitive tests (+.73, +.48, and +.71), the correlation of each of these three with the slope of the VPEL-versus-pitch function was not significant, as it was with the slope of the perception of visual pitch of the field (PVP)-versus-pitch function. VPEL, PVP, and a cognitive factor separated into three essentially independent factors in a multiple-factor analysis, with the three cognitive tests clustering at the cognitive factor, and with no significant loading on either of the other two factors. From the above considerations and a multiple-factor analytic treatment including additional results from this and other laboratories, we conclude that the cognitive-processing style held to be involved in the performance on the EFT and the perception of vertical as measured by the RFT is not general for egocentric space perception; it does not involve the perception of elevation.

Adolescent↗
PubMed2000

Current health behaviors and readiness to pursue life-style changes among men and women diagnosed with early stage prostate and breast carcinomas.

BACKGROUND: Cancer survivors are at increased risk for developing secondary tumors, diabetes, osteoporosis, and cardiovascular disease, thus making them an important target population for health-related interventions. However, little is known regarding cancer survivors' behaviors and their interest in pursuing healthier diets, exercise, and smoking cessation. METHODS: A 65-item survey was mailed to 1667 patients diagnosed with early stage carcinoma of the breast or prostate that requested data regarding demographics, health behaviors, stage of readiness for smoking cessation, exercise, increased fruit and vegetable (F&V) consumption, and decreased fat intake, as well as interest in specific health programs and when, relative to diagnosis, these programs should be offered. RESULTS: Responses from 978 cancer survivors suggested that the overwhelming majority (85%) reported their health as good to excellent. The majority of respondents (55%) ate fewer than 5 daily servings of F&Vs, with prostate carcinoma patients reporting eating significantly fewer servings than patients with breast carcinoma (P < 0.001). In contrast, 69% of respondents reported adherence to a low fat diet, again with lower practice rates among prostate carcinoma patients than patients with breast carcinoma (P = 0.006). The majority of respondents (58%) reported routine exercise and 8% were current smokers. Significantly more breast carcinoma patients than prostate carcinoma patients were current smokers (P = 0.03). There was strong interest in health promotion programs across behaviors, and a fair amount of concordance between low fat dietary behaviors and exercise, as well as consumption of five daily servings of F&Vs. The majority of patients expressed a preference for programs that could be delivered via mailed brochure, with 57% of respondents indicating that programs should be initiated at the time of diagnosis or soon after (within 6 months). CONCLUSIONS: The results of the current study suggest that although many cancer survivors already practice healthy life-style behaviors, there is a substantial proportion who do not. Interventions especially are needed to increase daily F&V intake; however, given the fair degree of clustering between dietary and exercise behaviors, multiple risk factor interventions also may be warranted. Among cancer survivors, receptivity is high for health promotion programs, especially those that can be delivered by mail and soon after diagnosis.

Adult↗
PubMed2000

Prevalence of selected cardiovascular disease risk factors among American Indians and Alaska Natives--United States, 1997.

Heart disease and stroke, the principal causes of cardiovascular disease (CVD), are the first and fifth leading causes of death among American Indians and Alaska Natives (AI/AN) (1,2). Risk factors for CVD frequently cluster, which may increase CVD risk multiplicatively (3). To characterize the prevalence of risk factors for CVD (i.e., hypertension, current cigarette smoking, high cholesterol, obesity, and diabetes) among AI/AN, CDC analyzed data from the 1997 Behavioral Risk Factor Surveillance System (BRFSS). This report summarizes the results of that analysis, which indicated that 63.7% of AI/AN men and 61.4% of AI/AN women who participated in the survey had one or more CVD risk factors.

Adult↗
PubMed2002

Motherhood and dental disease.

OBJECTIVE: To investigate whether motherhood is associated with tooth mortality, dental caries or destructive periodontal disease. DESIGN: An analytical cross-sectional study. SETTING: The Magomeni mother and child health clinic in Dar es Salaam, Tanzania. PARTICIPANTS: An age stratified total sample consisting of 500 mothers and pregnant women. Outcome measures Loss of a tooth, caries in a tooth or loss of periodontal attachment on a tooth. RESULTS: Controlling for current age and age at first child birth using multiple logistic regression and fitting cluster-specific models, no association was found between the number of children a woman had and loss of teeth [OR: 0.7-0.8 (95% CI: 0.3, 1.5)]. Nor was there any association with caries [OR: 1.0-1.1 (95% CI: 0.4, 1.9)]. Attachment loss among women having given birth to four or more children was, however more common than among women with fewer children [OR: 1.5-1.7 (95% CI: 1.0, 2.7)]. CONCLUSIONS: No evidence supporting the hypothesis that the more children a woman has the more teeth she loses was found. Nor was an association between the number of children and caries found. There may, however, be an association between motherhood and periodontal destruction.

Adult↗
PubMed1992

Syndrome--a changing concept.

Syndrome is one of the oldest terms in the medical vocabulary. Traditionally, the term has been used mainly as a designation for complex medical entities, such as multiple abnormalities, that are characterized by clusters of concurring symptoms, usually three or more. During the mid-twentieth century, the meaning and the use of the term were altered. First to take place was an attempt to eliminate physicians' names from syndrome nomenclature, resulting in a significant increase in the use of descriptive designations in proportion to eponyms. But the trend was counterbalanced by the creation of new classes of eponyms. Eponymous syndrome nomenclature now includes the names of literary characters, patients' surnames, subjects of famous paintings, famous persons, geographic locations, institutions, biblical figures, and mythological characters. This was followed by a relaxation in the scope of the definition of syndrome, wherein the term could also be used as a modifier indicating a special (sometimes unspecified) complexity of an already named pathological condition. Eventually syndrome changed from its original use as an exclusively medical term and came to mean anything unusual, abnormal, bizarre, or humorous, whether medical, social, behavioral, or cultural. This unrestrained use of the term is the principal cause of an enormous volume of the sometimes irrelevant syndrome literature cluttering databases in the MEDLARS system and of the deterioration of "SYNDROME" as a specific MeSH term and a useful search parameter.

Abstracting and Indexing↗
PubMed2005

Modulefinder: a tool for computational discovery of cis regulatory modules.

Regulation of gene expression occurs largely through the binding of sequence-specific transcription factors (TFs) to genomic binding sites (BSs). We present a rigorous scoring scheme, implemented as a C program termed "ModuleFinder", that evaluates the likelihood that a given genomic region is a cis regulatory module (CRM) for an input set of TFs according to its degree of: (1) homotypic site clustering; (2) heterotypic site clustering; and (3) evolutionary conservation across multiple genomes. Importantly, ModuleFinder obtains all parameters needed to appropriately weight the relative contributions of these sequence features directly from the input sequences and TFBS motifs, and does not need to first be trained. Using two previously described collections of experimentally verified CRMs in mammals and in fly as validation datasets, we show that ModuleFinder is able to identify CRMs with great sensitivity and specificity.

Amino Acid Sequence↗