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Results for “multiple clustering”

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PubMed2005

Distinct gene expression profiles and reduced JNK signaling in retinitis pigmentosa caused by RP1 mutations.

To understand the mechanisms underlying autosomal dominant progressive retinitis pigmentosa (RP) caused by the mutations of the RP1 gene and to identify molecules that play roles in the early disease process, we used Affymetrix U74Av2 microarrays to compare the gene expression profiles of retinas from Rp1-/- and Rp1+/+ mice at postnatal days (P) 7, 10, 14, 18 and 21. These profiles were independently verified by comparison with results of retinal serial analysis of gene expression, U74Av2 array studies of mouse retinas, real-time PCR and in situ hybridization. We found that the disruption of Rp1 significantly affected the expression of multiple clusters of genes whose products were involved in diverse biological pathways. The molecular responses to the disruption of Rp1 changed dramatically during development and were distinct from responses to the disruption of photoreceptor transcription factors (Crx-/- or Nrl-/-) and a phototransduction molecule (Pde6brd1). We found specific alterations of gene expression in the c-Jun N-terminal kinase (JNK) signaling cascades. Western analysis confirmed that the phosphorylation of key members in the JNK signaling cascades (i.e. JNK1, JNK2, MAP2, MKK4 and c-Jun) is reduced, whereas phospho-ERK and phospho-p38 are unchanged, in Rp1-/- retinas at P18-21. Immunostaining demonstrated that, like Rp1, phospho-JNKs and phospho-MAP2 are present in outer segments of photoreceptors. Our studies reveal unique molecular phenotypes in multiple biological pathways and the specific reduction of JNK signaling cascades in RP1 diseases, and suggest that RP1, a doublecortin-containing microtubule associated protein, and JNK signaling cascades play integral roles in photoreceptor development and maintenance. Our studies further suggest JNK-related therapeutic strategies for RP1 diseases.

Animals↗

PubMed2006

UniFrac--an online tool for comparing microbial community diversity in a phylogenetic context.

BACKGROUND: Moving beyond pairwise significance tests to compare many microbial communities simultaneously is critical for understanding large-scale trends in microbial ecology and community assembly. Techniques that allow microbial communities to be compared in a phylogenetic context are rapidly gaining acceptance, but the widespread application of these techniques has been hindered by the difficulty of performing the analyses. RESULTS: We introduce UniFrac, a web application available at http://bmf.colorado.edu/unifrac, that allows several phylogenetic tests for differences among communities to be easily applied and interpreted. We demonstrate the use of UniFrac to cluster multiple environments, and to test which environments are significantly different. We show that analysis of previously published sequences from the Columbia river, its estuary, and the adjacent coastal ocean using the UniFrac interface provided insights that were not apparent from the initial data analysis, which used other commonly employed techniques to compare the communities. CONCLUSION: UniFrac provides easy access to powerful multivariate techniques for comparing microbial communities in a phylogenetic context. We thus expect that it will provide a completely new picture of many microbial interactions and processes in both environmental and medical contexts.

Bacteria↗

PubMed2004

Selection and validation of differentially expressed genes in head and neck cancer.

We applied a robust combinatorial (multi-test) approach to microarray data to identify genes consistently up- or down-regulated in head and neck squamous cell carcinoma (HNSCC). RNA was extracted from 22 paired samples of HNSCC and normal tissue from the same donors and hybridized to the Affymetrix U95A chip. Forty-two differentially expressed probe sets (representing 38 genes and one expressed sequence tag) satisfied all statistical tests of significance and were selected for further validation. Selected probe sets were validated by hierarchical clustering, multiple probe set concordance, and target-subunit agreement. In addition, real-time PCR analysis of 8 representative (randomly selected from 38) genes performed on both microarray-tested and independently obtained samples correlated well with the microarray data. The genes identified and validated by this method were in comparatively good agreement with other rigorous HNSCC microarray studies. From this study, we conclude that combinatorial analysis of microarray data is a promising technique for identifying differentially expressed genes with few false positives.

Algorithms↗

PubMed1993

Neural encoding of single-formant stimuli in the cat. I. Responses of auditory nerve fibers.

1. We have studied auditory responses to a set of speech-related narrowband sounds, single-formant stimuli (SFSs), in populations of auditory nerve fibers (ANFs). An analytic method was developed to extract the envelope of temporal discharge patterns of the ANF responses to nonsinusoidally modulated stimuli, whose spectra have multiple clusters of components. Such responses are often encountered in the auditory system when complex stimuli are used and have traditionally been studied by analyzing the fundamental component of the responses. 2. The envelope modulation in the SFSs is shown to be represented by the response patterns of ANFs. When the whole ANF population is considered, the information on modulation in stimulus envelope does not disappear at the highest sound level tested at all best frequencies (BFs) we studied (1-10 kHz). The representation is the best at medium sound levels and degrades at high sound levels. Low/medium-spontaneous rate (SR) ANFs showed greater envelope modulation in their responses at high sound levels than do high-SR ANFs. The quality of the representation at high sound levels is, on average, proportional to BF threshold of an ANF. On the basis of populations of ANFs with all SRs, the envelope modulation in the SFSs is represented over a wide range of sound levels. 3. We found that low-BF ANFs differ from high-BF ANFs in representing envelope modulation in the SFSs. For ANFs with BFs less than approximately 6 kHz, information on stimulus envelope is not only contained in spectral components near direct current but also in components at the vicinities of frequencies equal to BF and its multiples. In fact, for ANFs with BFs < 3 kHz, the contribution from spectral components centered at BF to overall response modulation is greater than that from spectral components near direct current. These findings indicate that, by using measures solely based on the fundamental component, the amount of modulation in the responses to narrowband stimuli is underestimated for low-BF ANFs. 4. Off-BF stimulation of ANFs with SFSs was found to result in increased envelope modulation in responses at high sound levels. The further away the stimulus is centered relative to unit BF, the greater the modulation it induces, provided that the stimulus is capable of exciting the unit. An SFS centered as close as 15% off unit BF can produce a significant increase in the modulation of responses at very high sound levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1998

Low incidence of BRCA1 mutations among Italian families with breast and ovarian cancer.

Most familial breast or ovarian cancers are thought to be due to highly penetrant mutations in the predisposing genes BRCA1 and BRCA2. The cloning of these genes has opened a new era for the genetic counseling of women with a family history of breast or ovarian cancer. To estimate the incidence of detectable BRCA1 mutations and to define the eligibility criteria for genetic testing in the Italian population, a total of 53 patients belonging to 46 families clustering multiple cases of breast and/or ovarian cancer were investigated. Seven families presented with ovarian cancer only, 16 had both ovarian and breast cancers, and 23 were characterized by breast cancer only. Using a combination of protein truncation test (PTT) and single strand conformational polymorphism (SSCP) analysis followed, when necessary, by direct sequencing, we found 8 distinct mutations, 2 of these not reported before. Five frameshift and 2 nonsense mutations led to a truncated protein. One mutation was a missense substitution involving a cysteine in the zinc finger domain. One variant creating an ETS binding site in intron I was found but its role was not defined. The percentage of families carrying mutations was 17%. Among the families characterized by ovarian cancer only and by breast and ovarian cancer, the percentage of BRCA1 mutations was 57% and 12.5%, respectively. In contrast, the percentage of altered BRCA1 in families with only breast cancers was 9%. In the 46 Italian families studied, BRCA1 mutations were detected in fewer kindreds than those previously hypothesized based on linkage analysis, especially when these were characterized by breast cancers only. Our results indicate that families with a low number of cancer patients should be referred for BRCA1 genetic testing mainly when ovarian cancer is present.

Adult↗

PubMed1989

Differences between IQ and school achievement in anorexia nervosa.

Anorexia nervosa is a multidimensional syndrome in which perfectionistic striving appears as a common component of the symptom cluster. Multiple studies have linked this character trait to attempts to achieve a "perfect" weight. In contrast, no empirical data are available that document perfectionistic striving outside of food and weight themes. The present study (N = 20) looked for evidence of perfectionistic striving in school behavior by comparing school achievement and IQ scores. School achievement was found to be significantly greater than would be predicted by IQ scores. This finding and directions for future research are discussed.

Achievement↗

PubMed2001

Gene expression profiling in postmortem Rett Syndrome brain: differential gene expression and patient classification.

The identification of mutations in the transcriptional repressor methyl-CpG-binding protein 2 (MECP2) gene in Rett Syndrome (RTT) suggests that an inappropriate release of transcriptional silencing may give rise to RTT neuropathology. Despite this progress, the molecular basis of RTT neuropathogenesis remains unclear. Using multiple cDNA microarray technologies, subtractive hybridization, and conventional biochemistry, we generated comprehensive gene expression profiles of postmortem brain tissue from RTT patients and matched controls. Many glial transcripts involved in known neuropathological mechanisms were found to have increased expression in RTT brain, while decreases were observed in the expression of multiple neuron-specific mRNAs. Dramatic and consistent decreases in transcripts encoding presynaptic markers indicated a specific deficit in presynaptic development. Employing multiple clustering algorithms, it was possible to accurately segregate RTT from control brain tissue samples based solely on gene expression profile. Although previously achieved in cancers, our results constitute the first report of human disease classification using gene expression profiling in a complex tissue source such as brain.

Adolescent↗

PubMed1995

Mapping of a human rRNA gene in the YAC contig surrounding the SMA candidate gene.

Using the yeast artificial chromosome (YAC) 116 flanking the autosomal recessive spinal muscular atrophy (SMA) gene region, we have screened a human fetal brain cDNA library and isolated the cDNA clone 14-3/9 with an insert size of 2.5 kb. The cDNA clone could be identified as part of the human rRNA gene coding for 28S rRNA with a total size of 5025 bp. The human 28S rRNA is involved in the organization of the 60S ribosomal subparticle and is arranged in a 13-kb pre-rRNA transcription unit that occurs in tandem repeat clusters. Multiple copies of the rRNA gene have been mapped by pulsed field blot hybridization in the YAC contig between YAC 66 and YAC 116, which encompasses the SMA candidate gene, and additionally in the distally localized YAC 153.

Adult↗

PubMed1992

Patterns of projections from area 2 of the sensory cortex to area 3a and to the motor cortex in cats.

Peripheral information reaches the motor cortex partly through corticocortical pathways that arise from two functional subdivisions, area 2 and area 3a, of the sensory cortex. These sensory areas are synaptically linked with one another. The patterns of connectivity and the different submodality input that each area receives suggest that they send different efferent signals to the motor cortex. The projections from area 2 to area 3a and to the motor cortex were studied with retrogradely transported fluorescent tracers. The pattern and distribution of neuronal labeling in area 2 was determined following injections of different tracers into the forelimb regions of area 3a and the motor cortex. The results showed that the projections from area 2 to the two target regions were topographically and somatotopically related. Multiple clusters of motor cortex projection neurons were found in area 2, and these clusters overlapped extensively with clusters of area 3a projection neurons. Although cells labeled with one of the dyes were often in close proximity to cells labeled with the other dye, no double-labeled cells were found. Two different laminar patterns were seen for the two populations of neurons. The projection to area 3a originated from cells located in layers II-III and layers V-VI. The projection to the motor cortex originated from cells spread throughout layers II-IV, but predominantly in layer III. Differences in laminar arrangement of the two populations of cells suggest a directional flow of information processing in the sensorimotor cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Local connections in transplanted and normal cerebral cortex of rats.

Injections of the fluorescent tracer Fluoro-Gold were made in transplanted and normal cerebral cortex of rats in order to investigate and compare the local connectivities of both. In the normal somatosensory cortex, small injections in superficial layers (I to III) produced retrograde cell labeling below the injection site in two bands: in layer V and in the deep part of layer VI. Pieces of embryonic rat neocortical tissue were transplanted into a cavity made in the somatosensory cortex of young adult rats. After a survival period of 2-3 months, small injections of Fluoro-Gold were made in the superficial part of the grafts. These injections revealed multiple clusters of intratransplant-projecting cells. No callosal or thalamic neurons were labeled in these experiments. On occasion, a bilaminated pattern of retrograde cell labeling was observed inside the transplants. In both transplanted and normal cortices, pyramidal and non-pyramidal cells were retrograde-labeled. We conclude that in the neocortical transplants there is a pattern of local connectivity that is reminiscent of the pattern of intracortical connectivity in the normal neocortex in at least two aspects: first, the retrograde-labeled cells tended to form clusters or bands; second, both pyramidal and non-pyramidal cells were labeled.

Animals↗

PubMed1985

The HLA-AW24 gene: sequence, surroundings and comparison with the HLA-A2 and HLA-A3 genes.

A cosmid clone containing two class I sequences was found to cause expression of the HLA-AW24 protein after transfection into mouse L cells. The restriction map of this cosmid shows extensive homology over 26 kb with the map of the HLA-A3 region obtained from cosmids of the same library, constructed with DNA from an HLA-A3/HLA-AW24 heterozygote, but diverges over the remaining 14 kb. The HLA-AW24 gene was subcloned from this cosmid and its nucleotide sequence was determined. Amino acid and, more strikingly, nucleotide sequence comparisons with other HLA alleles indicate that the A locus alleles are more closely related to each other than to alleles from other HLA loci. A very skewed distribution of silent substitutions is apparent, and the occurrence of clustered multiple substitutions hints at gene-conversion-like events.

Alleles↗

PubMed1975

Benign lymphoid polyps of the rectum.

Benign lymphoid polyps are a rare histologic entity and should not be confused with malignant disease of the colon and rectum. Although retention polyps are the single most common type of colonic polyp in children, the presence of multiple clustered polyps in the rectum should alert the radiologist to the possibility of benign lymphoid polyps. A representative case is described and a review of the pediatric experience with this entity is discussed.

Child↗

PubMed1994

Isolation of two contigs of overlapping cosmids derived from human chromosomal band 3p21.1 and identification of 5 new 3p21.1 genes.

Consistent loss of DNA sequences from several regions on the short arm of human chromosome 3 has suggested that multiple tumor suppressor genes reside on chromosome 3p in various types of cancer cells. We have focused our efforts on an analysis of chromosomal band 3p21.1 since aminoacylase-1 (ACY1), which is localized to this band, has been shown to have lower levels of expression in several small cell and non-small cell lung cancer cell lines. Starting with two cosmids within 3p21.1, D3S92 and D3S93, we have isolated two separate contigs of overlapping cosmids within 3p21.1, by screening a library of 5700 chromosome 3-specific cosmid clones. Detailed restriction maps for these two contigs show that they contain multiple clusters of rare cutting restriction endonuclease sites. One contig extends for 100 kb and encompassed both ACY1 and D3S92, and the other extends about 80 kb around the D3S93 locus. Many different restriction fragments derived from these two contigs were found to be evolutionarily conserved and hybridized to distinct message transcripts. These fragments were used to identify homologous cDNAs from an adenogastric cDNA library, and several of these cDNAs were partially sequenced. We have identified five new genes from these two contigs and there is evidence to suggest that several additional genes reside within these cosmid contigs. The genes identified from 3p21.1 were then hybridized to DNA, isolated from a series of lung cancer cell lines and matched normal and tumor DNA from lung cancer patients. No alterations were detected with any of these probes, both at the DNA or RNA levels. A similar analysis with DNA fragments derived from these two genomic regions also failed to detect any alterations.

Animals↗

PubMed2000

Transcriptional enhancers of immunoglobulin light chain genes in Atlantic cod (Gadus morhua).

The organization of immunoglobulin heavy (H) chain genes in teleosts resembles that of mammals and amphibians, whereas light (L) chain genes are arranged in multiple clusters of variable (VL), joining (JL), and constant (CL) region segments. Sequence analysis of two Atlantic cod genomic clones (14,966 and 13,116 bp in length) revealed a very compact IgL chain locus with the VL genes in opposite transcriptional orientation to the JL and the CL genes. This suggests the possibility of rearrangements between clusters by inversion. Each cluster spans approximately 2.1 kb and distances between clusters vary between 2.1 and 4.8 kb. To gain insight into the transcriptional regulation of this complex, multiclustered locus, chloramphenicol acetyl transferase reporter constructs containing 14 different DNA segments from the two genomic clones were transfected into channel catfish B and non-B-cell lines, as well as into mouse B-cell lines. These studies showed strong enhancer activity downstream of the CL region in three out of six L chain gene clusters when assayed in fish, but not in mouse B cells. Interestingly, both mouse and human lambda enhancers exhibited strong activity in the fish B cells, while the mouse 3' kappa enhancer did not. This suggests that transcription factors similar to those involved in mammalian lambda expression are present in B cells from teleosts.

Animals↗

PubMed2006

Alveolar echinococcosis of the liver in a Tokyo resident with an unknown route of infection: report of a case.

We report the case of a 45-year-old Tokyo man who developed alveolar echinococcosis of the liver, which is an extremely rare disorder in Japan, except for Hokkaido, Japan's northernmost island. The findings of multiple clustered cysts on computed tomography were unlike those of any hepatic tumors we had previously encountered. T2-weighted magnetic resonance imaging revealed the characteristic findings of small cysts with a very high signal intensity. The tumors were successfully removed by a hepatic resection. The patient lives in Tokyo, but has visited Hokkaido many times. The exact route of infection in this patient remains unclear. Sliced raw venison, which he reported eating on every visit to Sapporo in Hokkaido, represented the only potential route of infection we could identify. This meat may have somehow become contaminated with embryonated eggs. Nowadays, even city inhabitants are at risk of developing rare diseases due to the rapid development of transportation systems.

Diet↗

PubMed1982

Participation of precentral neurons in somatically and visually triggered movements in primates.

Monkeys were trained to perform somatically and visually triggered wrist flexion-extension (F-E) movements. Extracellular unit recordings were made in the contralateral precentral forelimb area. These neurons were identified as being best related to particular single forelimb joints by their responses to passive somatosensory stimulation and to the determining effects of local intracortical microstimulation. It was found that almost 60% of single-joint related cells participated in both somatically and visually triggered movements. All wrist (F-E) neurons responded reciprocally while non-wrist (F-E) neurons had reciprocal as well as bidirectional responses to the oppositely directed visual and somatic perturbations. Somatically related responses and visually related responses were both uniformly distributed throughout the vertical layers of precentral cortex. With respect to horizontal spatial arrangements, multiple clusters of reciprocally and bidirectionally responsive neurons were intermingled. This latter finding supports the concept of a context-sensitive organization for motor control within precentral cortex.

Animals↗

PubMed1993

Cloning and characterization of the human t(3;6)(p14;p11) translocation breakpoint associated with hematologic malignancies.

The t(3;6)(p14;p11) chromosome translocation was identified in a family in which three members developed hematologic malignancies. To help characterize the region on chromosome 3 surrounding this translocation breakpoint, two flanking lambda clones, MS156 and MJ1525, were linked by pulsed-field gel electrophoresis to the same 510-kb NotI fragment on chromosome 3. MS156 was localized to a region proximal to the breakpoint of a der(3) chromosome somatic cell hybrid (derived from the t(3;6) cell line), and MJ1525 localized distal to the breakpoint. MJ1525 was used to screen the CEPH yeast artificial chromosome (YAC) library, which revealed a YAC, 195F3, that spanned the breakpoint. Subcloning into Lambda DASH II and production of a contiguous array of overlapping lambda clones revealed a clone, L17, that spanned the breakpoint. A rare restriction endonuclease map for the YAC 195F3 was constructed, and multiple clusters of rare restriction sites within the YAC were identified, possibly indicating the disruption of a gene by the t(3;6) translocation breakpoint.

Animals↗

PubMed1990

The atrial myocardial cells of mouse heart: a structural and stereological study.

Structural and stereological studies of mouse atrial myocardial cells, carried out in the same fashion as our previous investigations on mouse ventricle, demonstrate an extremely well-developed sarcoplasmic reticulum (SR) in atrial cells. The volume fraction (Vv) of the SR exceeds 12% in mouse atrial cells; perimyofibrillar network SR constitutes the major portion. We have confirmed the findings of Bossen et al. (1981, Tissue Cell 13, 71-77) of a difference between atria in terms of coupling density, the right atrium having a significantly lower incidence of interior junctional SR than the left. The SR of mouse atrium comprises a rich variety of specialized segments, including the IJSR, peripheral junctional SR, corbular SR, cisternal SR (including regions similar to fenestrated collars of striated skeletal muscle SR), as well as a peculiar form of extended junctional SR (EJSR). Although less frequent in occurrence than corbular SR, the EJSR seems closely related, since it occurs in multiple clusters at or near the Z-line regions, contains internal granular densities, and bears surface-connected structures resembling junctional processes. Seen in thin sections, mouse atrial EJSR elements are more complex than corbular SR, being larger in diameter and frequently circular in profile. Thick-section and serial-section analyses reveal that bodies of EJSR are in fact hollow spheroids. The transverse-axial tubular system of mouse atrium is rather poorly developed in comparison to its ventricular counterpart. The Golgi apparatus and associated specific atrial granules are prominent cell components. "Focal ellipsoidal deposits" (FEDs) previously described by Page and co-workers (1986, Amer. J. Physiol.) are consistently located adjacent to the Golgi region, but immunocytochemical staining for two different segments of atrial natriuretic peptide reveals no specific reaction in FEDs, whereas the SAGs are densely labeled for both antibodies.

Animals↗