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PubMed1987

Development of cysteamine-induced ultrastructural surface changes on duodenal mucosa.

Duodenal ulcers were induced acutely in female rats by a single oral administration of cysteamine, 70 mg/100 gm, in order to study morphologic progression of lesion development from the perspective of cellular surface changes by scanning electron microscopy. Thick sections of resin-embedded specimens were also studied by light microscopy, and animals were sacrificed at intervals of 30 minutes, 1, 2, 4, 8, 12, 20, and 24 hours post-treatment. Earliest evidence of cytologic lesions was apparent at 2 hours and data confirmed earlier reports that alterations began at villous tips. Both cellular sloughing and in situ cellular injury were evident, the latter phenomenon constituting the principal mode of cysteamine-induced erosion. In situ change began, from surface perspective, as a minute cavitation on the apical aspect of an isolated, single epithelial cell which was surrounded by normal cells. These early lesions progressed to in situ necrosis either of isolated cells or of small clusters of adjacent cells. This phenomenon occurred concurrently on multiple villi, all within the localized site at which cysteamine-induced duodenal ulcers are known to develop. An additional early morphologic change was the occasional appearance of a background of pleomorphic cellular apices of variable size on the villous ridges. By 8 to 12 hours, cellular damage advanced to erosions with some cells in the preulcer area still showing initial stages of in situ cellular injury. Precipitated mucus on the surface was increased in the preulcer area, and by 20 to 24 hours typical duodenal ulcers were evident. These scanning electron microscopic data confirm the significance of surface damage at villous tips very early in the cysteamine-induced ulcerogenesis. The present higher resolution findings demonstrated that earliest cellular damage, principally in situ cell injury, occurred simultaneously at multiple sites in the preulcer zone rather than at a single cluster of cellular damage which enlarges peripherally.

Animals↗
PubMed1993

An examination of cluster-based classification schemes for DUI offenders.

This study examines the utility of cluster-based classification schemes for DUI offenders. Variables from previous empirical typologies and multiple domains were used in a series of cluster analyses in order to examine replicability across independent samples, across clustering algorithms and across sets of psychometric indicators. The arbitrary nature of cluster solutions and the external validity of cluster-based schemes, with respect to an outcome criterion constructed synthetically from earlier research, was examined. Only three of eight cluster techniques (Ward's, K means, and complete linkage) yielded meaningful results. For these techniques, replicability was poor across samples, algorithms and sets of psychometric indicators. Results indicated that identified clusters were arbitrary. Although external validity analysis yielded positive results, the possibility that external validity was a function of underlying dimensions was discussed, as were other implications of the findings.

Adult↗
PubMed2005

A hybrid genetic algorithm and expectation maximization method for global gene trajectory clustering.

Clustering time-course gene expression data (gene trajectories) is an important step towards solving the complex problem of gene regulatory network modeling and discovery as it significantly reduces the dimensionality of the gene space required for analysis. Traditional clustering methods that perform hill-climbing from randomly initialized cluster centers are prone to produce inconsistent and sub-optimal cluster solutions over different runs. This paper introduces a novel method that hybridizes genetic algorithm (GA) and expectation maximization algorithms (EM) for clustering gene trajectories with the mixtures of multiple linear regression models (MLRs), with the objective of improving the global optimality and consistency of the clustering performance. The proposed method is applied to cluster the human fibroblasts and the yeast time-course gene expression data based on their trajectory similarities. It outperforms the standard EM method significantly in terms of both clustering accuracy and consistency. The biological implications of the improved clustering performance are demonstrated.

Algorithms↗
PubMed1996

Cytology of hepatocellular carcinoma in serous fluids: a report of three cases.

Three cases of hepatocellular carcinoma (HCC) detected in serous fluids are reported. Two cases were detected in ascitic fluid and one case was identified in pleural fluid of a patient with widespread disease. The cytopathologic findings correlated well with the histologic type in each case. One case each of moderately differentiated, poorly differentiated, and fibrolamellar HCC were seen. In general, the fluids contained large polygonal cells, singly and in small clusters with large vesicular, occasionally multiple nuclei and prominent nucleoli. The current literature describing HCC in serous fluids is sparse. The identification of this tumor in serous fluids would allow diagnosis of new or recurrent disease and have implications for therapy.

Adult↗
PubMed1997

A proposed test battery and constellations of specific behavioral paradigms to investigate the behavioral phenotypes of transgenic and knockout mice.

Behavioral phenotyping of transgenic and knockout mice requires rigorous, formal analyses. Well-characterized paradigms can be chosen from the established behavioral neuroscience literature. This review describes (1) a series of neurological and neuropsychological tests which are effectively used as a first screen for behavioral abnormalities in mutant mice, and (2) a series of specific behavioral paradigms, clustered by category. Included are multiple paradigms for each category, including learning and memory, feeding, analgesia, aggression, anxiety, depression, schizophrenia, and drug abuse models. Examples are given from the experiences of the authors, in applying these experimental designs to transgenic and knockout mice. Extensive references for each behavioral paradigm are provided, to allow new investigators to access the relevant literature on behavioral methodology.

Animals↗
PubMed2002

Quality of life in young people: ratings and factor structure of the Quality of Life Profile-Adolescent Version.

The purpose of the study was to provide British data relating to the 54-item Quality of Life Profile Adolescent Version (QOLPAV; Raphael et al., 1996, Journal of Adolescent Health, 19, 366-375) and to explore the underlying factor structure of the questionnaire. The relationship between demographic variables (such as social economic status, gender and ethnicity) and quality of life (QOL) were investigated. Eight hundred and ninety-nine young people aged 12-16 were recruited from secondary schools in the south of England to participate in the study. Factor analysis highlighted eight dimensions embedded within the scale, which were largely consistent with the QOL model proposed by Raphael et al. (1996, Journal of Adolescent Health, 19, 366-375). A notable exception concerned items from the subdomain of "spiritual being", which did not cluster together but dispersed across multiple factors. Exclusion of complex items and those with low loadings on subdomains resulted in a briefer scale consisting of 32 items. Of the demographic variables examined, only age was significantly associated with quality of life scores.

Adolescent↗
PubMed1983

Evolution of epitopes on human and nonhuman primate lymphocyte cell surface antigens.

The T- and B-cell surface polypeptides detected by an international workshop panel of 100 mouse monoclonal antibodies (M.Ab) were biochemically defined by radioimmunoprecipitation. Eight T-cell-associated molecules and eight B-cell-associated molecules were identified by multiple antibodies in the panel. Clusters of antibodies specific for the same polypeptide were then compared for their reactivity against peripheral blood mononuclear cells (PBMC) from 11 nonhuman primate species. All the major T- and B-cell antigens present in humans were also expressed in some nonhuman primates. M.Ab to the same antigen were found to react with distinct epitope groups that differed in their phylogenetic distribution. Some epitopes were highly conserved, while other epitopes on the same molecule were only expressed in hominoids and were not detected in old world and new world monkeys. Our detailed analysis of the phylogeny of 37 T-cell antigen epitopes on ten different molecules revealed there was no clear correspondence between the number of epitopes shared and evolutionary distance. Rather the data suggest that parallelism with back mutation may be a common mechanism in the evolution of T-cell antigens. The data also show that the tissue distribution of T-cell antigens can differ between primate species; for example, M.Ab to human Tp45 Tla-Qa-like antigens that did not react with human PBMC did react with PBMC from new world monkeys.

Animals↗
PubMed2003

In vitro regulation of rat derived microglia.

The cell culture approach to the study of the nervous system attempts to reduce cellular complexity to various extents and to characterize the influences of extrinsic molecules on the cell population under study. To date, the main source of culture model systems to explore CNS function and dysfunction is fetal brain material from experimental animals, typically rodents. We have developed primary microglial cell cultures and focused on the concentration-dependent effects of different amino acids and growth promoting additives on microglial morphology and function. We used Basal Medium Eagle (BME) with 1g/L of glucose instead of Dulbecco's modified Eagle medium (DMEM) as serum-free condition, since BME does not contain L-Glycine (Gly) and L-Serine (Ser), and investigated the effects of these two amino acids on microglial morphology and functions by adding various concentrations of the amino acids to BME and different concentrations of ascorbic acid (10-75 micro g/ ml), hydrocortisone (1-7.5 nM) and DL-alpha-tocopherol (0.01-0.5 micro g/ml) as growth promoters. Under Gly/Ser-free, serum-free condition, and growth promoters-free conditions, the majority of rat microglial cells displayed round morphology, whereas in the presence of 5 micro M Gly and 25 micro M Ser, which correspond to the concentrations of Gly and Ser in the cerebrospinal fluid, they extended multiple branched processes and formed clusters of rough endoplasmic reticulum. Ascorbic acid (25 micro g/ml), 2.5 nM hydrocortisone and 0.05 micro g/ml of DL-alpha-tocopherol elicited the highest level of microglial activation as measured by an increased expression of MHC class-I and MHC class-II antigens. Neuron culture experiments using the conditioned medium obtained from the different microglial culture conditions indicate neurotoxic and neurotrophic effects depending on the concentrations of amino acids as well as on the concentration of the growth promoters. These findings suggest that resting ramified microglial cells with neurotrophic activity can be induced with the combination of BME medium and small amounts of extracellular matrix growth promoters.

Animals↗
PubMed1999

Poisson-Boltzmann model studies of molecular electrostatic properties of the cAMP-dependent protein kinase.

Protonation equilibria of residues important in the catalytic mechanism of a protein kinase were analyzed on the basis of the Poisson-Boltzmann electrostatic model along with a cluster-based treatment of the multiple titration state problem. Calculations were based upon crystallographic structures of the mammalian cAMP-dependent protein kinase, one representing the so called closed form of the enzyme and the other representing an open conformation. It was predicted that at pH 7 the preferred form of the phosphate group at the catalytically essential threonine 197 (P-Thr197) in the closed form is dianionic, whereas in the open form a monoanionic ionization state is preferred. This dianionic state of P-Thr197, in the closed form, is stabilized by interactions with ionizable residues His87, Arg165, and Lys189. Our calculations predict that the hydroxyl of the Ser residue in the peptide substrate is very difficult to ionize, both in the closed and open structures of the complex. Also, the supposed catalytic base, Asp166, does not seem to have a pK(a) appropriate to remove the hydroxyl group proton of the peptide substrate. However, when Ser of the peptide substrate is forced to remain ionized, the predicted pK(a) of Asp166 increases strongly, which suggests that the Asp residue is a likely candidate to attract the proton if the Ser residue becomes deprotonated, possibly during some structural change preceding formation of the transition state. Finally, in accord with suggestions made on the basis of the pH-dependence of kinase kinetics, our calculations predict that Glu230 and His87 are the residues responsible for the molecular pK(a) values of 6.2 and 8.5, observed in the experiment.

Adenosine Triphosphate↗
PubMed1999

Acclimation of Arabidopsis thaliana to the light environment: the role of photoreceptors.

The regulation by light of the composition of the photosynthetic apparatus was investigated in photomorphogenic mutants of Arabidopsis thaliana (L.) Heynh. cv. Landsberg erecta. Leaf chlorophyll, photosynthesis, photosystem II function, and ribulose-1, 5-bisphosphate carboxylase-oxygenase and photosystem II contents were determined for plants grown under high- or low-irradiance growth regimes. Although certain mutant lines had altered chloroplast composition compared to the wild type, all photoreceptor mutants tested were capable of light-dependent changes in chloroplast composition and photosynthetic function, indicating that photoreceptors do not play a central role in the regulation of acclimation at the level of the chloroplast. However, the clear acclimation defect in a det1 signal transduction mutant indicates that photoreceptor-controlled responses either share regulatory components with acclimation, or are important in the expression of components which in turn regulate acclimation. We suggest that the COP/DET/FUS regulatory cluster is a focus for multiple signal transduction pathways, including some of the metabolic signals which form the basis for the acclimatory response.

Arabidopsis↗
PubMed1989

Spectral characteristics of the responses of primary auditory-nerve fibers to frequency-modulated signals.

The spectral responses of cat single primary auditory nerve fibers to sinusoidal frequency-modulated acoustic signals applied to the ear are examined. Period histograms were constructed from the neural spike-train data, and the frequency spectrum was determined by Fourier transforming these histograms. Several clusters of spectral components were present. The lowest-frequency cluster consists of components at DC, at the modulation frequency, and at its harmonics. In the next cluster, components surround the carrier frequency and are separated from it by the modulation frequency and its harmonics. Higher-frequency clusters surround frequencies that are twice and three times the carrier frequency. The components in each cluster are separated from the multiples of the carrier frequency by the modulation frequency and its harmonics. The magnitudes of the spectral components were investigated for carrier frequencies located below, at, and above the unit characteristic frequency, and for different signal levels, modulation frequencies, and modulation indices. The components at the modulation frequency and its harmonics were strong and present over a wide range of signal levels, carrier frequencies, modulation frequencies, and nerve-fiber characteristics. The presence of components at the modulation frequency indicates that a demodulation process is occurring. This process may be significant for speech recognition.

Acoustic Stimulation↗
PubMed2005

Electron energy loss spectra near structural defects in TiN and TiC.

In this study, we use first principles multiple scattering calculations on atomic clusters to show how the carbon and nitrogen K-edge fine structures are modified in the vicinity of structural defects in TiN and TiC. Changes in the electron energy loss spectra are due to changes in the atomic structure of the first atomic shells around the absorbing atom. Two different kinds of defects, which both modify the structure of these atomic shells, are investigated here. In a first part, we describe a method which correctly takes into account the statistical spatial distribution of nitrogen vacancies in a TiN cluster. We study the influence of vacancy concentration on the shape of the nitrogen K-edge spectra and we find that vacancies mainly affect the height of the second peak of the spectra. This peak decreases when the number of vacancies in the second nitrogen shell increases. In a second part, we study the carbon K-edge spectrum modification near stacking faults in TiC. Two different stacking faults are studied. These two-dimensional defects are responsible for changes in the position of the carbon as well as titanium atoms of the atomic shells centered on the absorbing carbon atom. The shape of the spectra is strongly modified near the stacking faults and several peaks are affected by these modifications. We show that these fine structure modifications only concern the very first carbon atomic layers near the two-dimensional defects.

Journal Article↗
PubMed2026

The domestication-associated WHP10 tandem cluster of amino acid transporter genes enhances whole-plant protein accumulation in maize.

Improving protein accumulation in maize is essential for sustainable agriculture, yet the regulatory mechanisms governing the intermediate "flow" of organic nitrogen remain elusive. Here, we show that the maize stem acts as a regulatory node for nitrogen allocation. By integrating spatial transcriptomics and metabolomics with quantitative genetics, we demonstrate that a transport-oriented stem program orchestrates the high-protein phenotype of the wild maize accession Ames21814. We identified a major locus, Whole-plant High Protein 10 (WHP10), that encodes a tandemly duplicated cluster of amino acid transporter genes. WHP10 exhibits strong vascular-biased expression, driven by promoter divergence that enhances the wild allele's activity. Functional assays and genetic validation support a model in which the WHP10 cluster facilitates the transport of multiple nitrogen-rich amino acids, thereby contributing to vascular-associated amino acid transport and post-uptake organic-nitrogen partitioning. Our findings establish stem flow as a regulatory layer for protein accumulation and identify WHP10 as a high-value target for precision breeding to enhance whole-plant protein accumulation without compromising grain yield.

Zea mays↗
PubMed2005

Grouping of streptomycetes using 16S-ITS RFLP fingerprinting.

A total of 463 Streptomyces and Kitasatospora type strains were screened using 16S-ITS RFLP fingerprinting (combined restriction digest using enzymes BstUI and HaeIII). In total, 59 clusters could be delineated, each comprising multiple strains with nearly identical patterns. Good correlation was found in general with phylogeny, as revealed by 16S rDNA sequencing. Most strains assigned to a particular 16S-ITS RFLP cluster were classified into the corresponding 16S sequencing cluster whether a 16S similarity cut-off value of 97 or 98% was used. We conclude that the taxonomic resolution of 16S-ITS RFLP fingerprinting is higher than that of 16S rDNA sequencing; this may provide a tool for reducing the number of laborious DNA-DNA hybridizations necessary for discovering potentially new species within Streptomyces.

Cluster Analysis↗
PubMed2005

Dynamics of multiple quantum coherences in dipole-coupling spins in solid.

A perturbation method deals with dipolar coupling spins in solids is presented. As example of application the method, the multiple-quantum coherence dynamics in clusters of a linear chain of four nuclear spins and a ring of six spins coupled by dipole-dipole interaction are considered. The calculated 0Q and 2Q intensities in a linear chain of four nuclear spins and 6Q intensity in a ring of six spins vs. the duration of the preparation period agree well with the exact solutions (for linear chain of four nuclear spins) and simulation data (for linear chain of four nuclear spins and a ring of six spin).

Journal Article↗
PubMed2002

Ductal carcinoma in situ of the breast: a new phenotype classification system and its relation to prognosis.

In a study of invasive breast cancer, multiple correspondence analysis (MCA) revealed clustering of eight pathobiological variables. Two different phenotypes were distinguished by an index calculated on the basis of the variables (histologic grade, necrosis, lymphoid infiltration, number of mitosis and expression of c-erbB-2, p53, progesterone receptor and Bcl-2). Phenotype A lesions share most of the features of normal breast tissue. Phenotype B looks more malignant, has a higher early recurrence rate and is more frequently seen in younger patients. Our aim was to see if ductal breast carcinoma in situ (DCIS) could be divided into the same phenotypes. One hundred and eighty DCIS were investigated. Association between the eight variables was studied in 2 x 2 models. The phenotype index was calculated by summing weights for the variables in the MCA. All variables were associated, except Bcl-2. DCIS was divided in two phenotypes. Thirty-three tumours were Phenotype A and 147 Phenotype B. The mean age at diagnosis was 65.5 and 58.4 years for Phenotypes A and B, respectively (p = 0.0012). No difference regarding local relapse free survival was seen. Two phenotypes were distinguished in DCIS, similar to invasive breast cancer. In an earlier study, 45% of the invasive cancers were classified as Phenotype B. In this study, 82% of DCIS were Phenotype B. This may indicate that invasive breast cancer of Phenotype B is derived from DCIS of Phenotype B. The distribution of DCIS phenotypes with a small proportion of Phenotype A DCIS may be due to that Phenotype A DCIS is less likely to be detected by mammography, or that some invasive breast cancers of Phenotype A progress to invasiveness without passing the in situ phase.

Adult↗
PubMed2006

Genome-wide scan for visceral leishmaniasis susceptibility genes in Brazil.

A genome-wide scan was conducted for visceral leishmaniasis (VL) in Brazil. Initially, 405 markers were typed in 22 multicase pedigrees (28 nuclear families; 174 individuals; 66 affected). Non-parametric multipoint analysis detected nine chromosomal regions with provisional evidence (logarithm of the odds (LOD) scores 0.95-1.66; 0.003<P<0.018) for linkage. To confirm linkage, 132 individuals (43 affected) from 19 independently ascertained families were genotyped across these regions. Three regions (6q27, 7q11.22 and 17q11.2-q21.3) retained evidence (LOD scores 1.08, 1.34, 1.14; P=0.013, 0.007, 0.011) for linkage. To determine which genes contribute to linkage at 17q11.2-q21.3, 80 single nucleotide polymorphisms were genotyped in 98 nuclear families with 183 affected individuals. Family-based association test analysis indicated associations at two chemokine genes, CCL1 and CCL16, that lie 1.6 Mb apart, show some extended linkage disequilibrium with each other, but each lie within different clusters of candidate CCL genes. Multiple genes may therefore contribute to the linkage peak for VL at 17q12.

Brazil↗
PubMed2004

Does making newborn follow-up appointments from the hospital improve compliance?

OBJECTIVE: To test a system of arranging the first newborn follow-up appointments made from the hospital prior to discharge. METHODS: Prospective randomized study of 328 term healthy newborns divided into control and intervention groups. As there were multiple practices, we checked for clustering in the two groups and then compared them for patient compliance with the first newborn appointment. We also compared the control and intervention groups for compliance with regard to insurance status. RESULTS: There was difference between the control and intervention group in timeliness for the first appointment (control, 84.9%, intervention group, 94.2%, p=0.0062). There was also improvement in privately insured patients (control 89.1%, intervention 96.5%, p=0.0263), as well as in Medicaid+noninsured patients (control 64.7%, intervention 90.2%, p=0.0245). DISCUSSION: We conclude that arranging for follow-up appointments from the hospital is a worthwhile inexpensive intervention that could significantly improve patient compliance with the first newborn visit.

Aftercare↗