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At least 1,279 records · Page 71Linked to original sources
PubMed1999

The neuropsychological signature of primary progressive aphasia.

An effect size analysis incorporating meta-analytic principles was used to review neuropsychological findings in patients with primary progressive aphasia (PPA). Studies dating back to 1982 were gathered and the neuropsychological test results from a total of 55 patients with PPA and 162 healthy controls were synthesized using effect size analyses. The results indicate that patients with PPA are most deficient on tests of verbal skill, followed by performance on measures of delayed recall, cognitive flexibility and abstraction, memory acquisition, attention/concentration, and, finally, performance skill. A rank-order list of specific neuropsychological tasks and test variables in order of sensitivity to PPA is also provided to aid in the interpretation of the quantitative results and in the differentiation of PPA from other disorders with prominent features of dementia such as Alzheimer's disease.

Aphasia↗
PubMed1998

Lead concentrations and isotopic signatures in vintages of French wine between 1950 and 1991.

Vintages of French wine from 1950 to 1991 were analyzed for lead isotopes and concentrations to investigate whether they might be used to archive the isotopic composition of the anthropogenic lead in aerosols to which the vineyard was exposed. Early vintages (1950-1980) contained 78-227 ng/g of lead with 206Pb/207Pb ratios between 1.152 and 1.173, while the later vintages displayed significantly lower concentrations and a smaller range of isotopic ratios. The concentration of trimethyl lead, which is associated with automobile emissions, was found to be poorly correlated with total lead in the wines, suggesting that automobile aerosols were not a significant source of the lead. This result was supported by lead isotope data which showed a poor correlation with the available petrol and aerosol data. To identify its origin lead isotopes were measured in vineyard aerosols, soil particles, bottle caps, corks, and brass components used to dispense the wine. Although a dominant source could not be identified there was some evidence to suggest that brass which had a high lead concentration was a significant contributor. Because the lead contribution from the processing of wine was probably relatively high in the past it is unlikely that old vintages of wine will be a suitable archive for lead isotopes in aerosols.

Aerosols↗
PubMed2002

Mycobacterium bovis BCG cell wall and lipopolysaccharide induce a novel gene, BIGM103, encoding a 7-TM protein: identification of a new protein family having Zn-transporter and Zn-metalloprotease signatures.

To identify novel genes induced during innate immune activation, we screened a cDNA library prepared from monocytes stimulated with Mycobacterium bovis BCG cell wall. A novel transcript with three-protein coding potential was identified, and the expressed proteins from individual frames showed distinct intracellular localization. Live and heat-killed Mycobacterium, bacterial cell wall, and inflammatory cytokines like TNFalpha were found to be potent inducers of the transcript. Expression of this gene is very low or undetectable in unstimulated monocytes, while a steady expression level was observed during differentiation of monocytes to dendritic cells and macrophages. The entire gene consisted of eight major exons and was localized on chromosome 4q22-q24, spanning approximately 84 kb. The main open reading frame of the transcript encoded a putative seven-transmembrane (TM) protein that showed homology with a number of functionally unknown proteins in the database. Further analysis revealed that all of these proteins have detectable similarity with the ZIP family of metal transporters. In fact, increased accumulation of intracellular Zn(2+) was observed due to the expression of BIGM103 in CHO cells. However, the identified proteins are structurally unique compared to known ZIP members and they also possess the hallmark of Zn-metalloproteases, suggesting a new class of multi-TM protein with dual features. Here we present a collection of these proteins and discuss the functional aspects of BIGM103, based on our results and current findings on two members of the family, Drosophila Catsup and Arabidopsis IAR1.

Amino Acid Sequence↗
PubMed1997

Global self-organization of all known protein sequences reveals inherent biological signatures.

A global classification of all currently known protein sequences is performed. Every protein sequence is partitioned into segments of 50 amino acid residues and a dynamic programming distance is calculated between each pair of segments. This space of segments is initially embedded into Euclidean space. The algorithm that we apply embeds every finite metric space into Euclidean space so that (1) the dimension of the host space is small, (2) the metric distortion is small. A novel self-organized, cross-validated clustering algorithm is then applied to the embedded space with Euclidean distances. We monitor the validity of our clustering by randomly splitting the data into two parts and performing an hierarchical clustering algorithm independently on each part. At every level of the hierarchy we cross-validate the clusters in one part with the clusters in the other. The resulting hierarchical tree of clusters offers a new representation of protein sequences and families, which compares favorably with the most updated classifications based on functional and structural data about proteins. Some of the known families clustered into well distinct clusters. Motifs and domains such as the zinc finger, EF hand, homeobox, EGF-like and others are automatically correctly identified, and relations between protein families are revealed by examining the splits along the tree. This clustering leads to a novel representation of protein families, from which functional biological kinship of protein families can be deduced, as demonstrated for the transporter family. Finally, we introduce a new concise representation for complete proteins that is very useful in presenting multiple alignments, and in searching for close relatives in the database. The self-organization method presented is very general and applies to any data with a consistent and computable measure of similarity between data items.

Amino Acid Sequence↗
PubMed2002

Signature Tagged Mutagenesis of Haemophilus influenzae identifies genes required for in vivo survival.

The pathogenic bacterium Haemophilus influenzae causes meningitis, epiglottitis, pneumonia, otitis media and other infections. To further understand the genetic basis of invasive disease and to inform about the bacterium's requirements in an in vivo environment, we analysed a library of 1632 insertional Tn1545 -Delta3 transposon mutants for their capacity to cause systemic infection in an animal model. We identified 25 genes that are potentially essential for H. influenzae invasive disease, and are candidates for further exploratory research. Seven of the genes encode hypothetical proteins, the function of six of which could be tentatively assigned on the basis of functional motifs and low homology to other bacterial genes. Eleven genes encode central metabolic enzymes or transporters; eight encode proteins that interact with DNA or modify other proteins; and four encode enzymes involved in the elaboration of classical virulence determinants. Two genes have no known function. Independent mutagenesis of six of the 25 genes and determination of the competitive index confirmed that these genes are important or essential to the organism in an in vivo environment. This genome-wide analysis has identified metabolic and other genes required during invasive disease, and the findings may lead to new interventions to prevent and treat H. influenzae infections.

Animals↗
PubMed2027

Systematic Dissection of Key Driver Perturbation Signatures in Single Cells via ECCITE-seq.

CRISPR screens, such as expanded CRISPR-compatible cellular indexing of transcriptomes and epitopes by sequencing (ECCITE-seq), enable the simultaneous measurement of transcriptomes, gRNA identity, and cell-surface protein expression at single-cell resolution to systematically interrogate gene function. This platform provides a powerful and scalable experimental approach for validating disease-associated regulators identified by large-scale association studies and other computational methods, including network-based analyses of multi-omics data. Here, as an example application, we describe an ECCITE-seq framework to characterize the transcriptomic consequences of perturbing multiple neuronal key driver genes associated with Alzheimer's disease (AD) in human-induced pluripotent stem cell (hiPSC)-derived neurons. More broadly, by integrating customized pooled gRNA libraries with different CRISPR effectors across multiple cell types, this approach allows for the assessment of the regulatory impact of candidate genes implicated in development and disease processes.

Humans↗
PubMed2001

High-resolution analysis of Y-chromosomal polymorphisms reveals signatures of population movements from Central Asia and West Asia into India.

Linguistic evidence suggests that West Asia and Central Asia have been the two major geographical sources of genes in the contemporary Indian gene pool. To test the nature and extent of similarities in the gene pools of these regions we have collected DNA samples from four ethnic populations of northern India, and have screened these samples for a set of 18 Y-chromosome polymorphic markers (12 unique event polymorphisms and six short tandem repeats). These data from Indian populations have been analysed in conjunction with published data from several West Asian and Central Asian populations. Our analyses have revealed traces of population movement from Central Asia and West Asia into India. Two haplogrops, HG-3 and HG-9, which are known to have arisen in the Central Asian region, are found in reasonably high frequencies (41.7% and 14.3% respectively) in the study populations. The ages estimated for these two haplogroups are less in the Indian populations than those estimated from data on Middle Eastern populations. A neighbour-joining tree based on Y-haplogroup frequencies shows that the North Indians are genetically placed between the West Asian and Central Asian populations. This is consistent with gene flow from West Asia and Central Asia into India.

Alleles↗
PubMedDate not supplied

Identifying sources of groundwater pollution using trace element signatures.

A simple receptor modeling approach has been applied to groundwater pollution studies and has shown that marker trace elements can be used effectively in source identification and apportionment. Groundwater and source materials from one coal-fired and five oil-fired power plants, and one coal-tar deposit site have been analyzed by instrumental neutron activation analysis for more than 20 minor and trace elements. In one of the oil-fired power plants, trace element patterns indicated a leak from the hazardous waste surface impoundments owing to the failure of a hypolon liner. Also, the extent and spatial distribution of groundwater contamination have been determined in a coal-tar deposit site.

Coal↗
PubMed2005

Gene signatures of testicular seminoma with emphasis on expression of ets variant gene 4.

Gene expression patterns of testicular seminoma were analysed applying oligonucleotide microarrays in 40 specimens of different tumour stages (pT1, pT2, pT3) and in normal testes. Transcripts of maternally expressed 3 transcripts were expressed in seminoma without correlation with delta-like 1 homologue expression indicating an impaired imprinting status in seminoma. Interestingly, the transcripts of bromodomain-containing 2 and nuclear autoantigenic sperm protein associated with spermatogenesis were significantly upregulated in progressing tumour stages. Transcription factors TEA domain family member 4 and ETS variant gene 4 (ETV4), weakly expressed in normal testis, were strongly augmented during tumourigenesis. For ETV4 expression, a significant correlation with the increased expression of matrix metalloproteinase 2 and a disintegrin and metalloproteinase domain 15 was determined. The ETV4 protein was localised to nuclei of spermatogonia and revealed an intense staining in seminoma cells. Taken together, we characterised additional transcription factors and spermatogenesis-associated genes involved in the progression of seminoma.

Adenovirus E1A Proteins↗
PubMed2006

Three clinical variants of gastroesophageal reflux disease form two distinct gene expression signatures.

It has been proposed recently that gastroesophageal reflux disease (GERD) patients may be categorized into three distinct groups exhibiting non-erosive reflux disease (NERD), erosive reflux disease (ERD), and Barrett's esophagus (BE). Measurement of relative gene expression levels was undertaken to identify distinct molecular subclasses in different variants of gastroesophageal disease. The measurements were made with Affymetrix U133A 2.0 GeneChips and RNA isolated from mucosal samples of normal squamous esophageal epithelium from 24, 28, and 26 patients with NERD, ERD and BE, respectively. Statistical testing of microarray data showed that gene expression profiles are discriminative for BE and NERD, but not for combinations of BE and ERD or NERD and ERD. In addition, women developing NERD exhibited transcriptional patterns that differed from those of men with BE. In clustering analyses, we did not observe correlations between sex and assignment of gene expression profile of ERD patients to either the NERD or the BE group. Although the biological significance of the identified genes remains uncertain, we hypothesize that GERD is a monophyletic disease that develops with the onset of gastroesophageal reflux and represents two main molecular classes, which may result in different progressions to inflammatory process within esophageal epithelium modulated by sexual dimorphism. While normal epithelium samples from NERD and BE patients are molecularly homogeneous, esophageal mucosa from ERD patients is molecularly similar to either NERD or BE. These findings may be useful for defining molecular markers which could predict potential progression to Barrett's metaplasia among patients with reflux disease.

Adult↗
PubMed1997

[Strategy for securing medical documents by electronic signature and encryption].

The paper presents a survey of security strategies for the protection of medical documents which are generated, stored, and exchanged electronically. It is not meant to provide a precise technical background but to give a guideline for interested medical professionals. A systematic approach for the definition of appropriate security requirements is outlined, and generally accepted security functions (services) are described. The major part of the paper is dedicated to a technical introduction to state-of-the-art security mechanisms based on cryptographic methods. Finally, actual implementation problems and perspectives are discussed from a German/European viewpoint.

Computer Communication Networks↗
PubMed1996

Electrorotation of erythrocytes treated with dipicrylamine: mobile charges within the membrane show their "signature" in rotational spectra.

In this study, electrorotation spectra of individual cells (that is, frequency dependence of cell rotation speed) have been proved to yield information not only about the passive electric properties of cell constituents, but also about the presence of mobile charges within the plasma membrane being part of ion carrier transport systems. Experiments on human erythrocytes pretreated with the lipophilic anion dipicrylamine (DPA) gave convincing evidence that these artificial mobile charges adsorbed to the plasma membrane contributed significantly to the rotational spectrum at relatively low conductivity of the external medium (2-5 mS m-1). Theoretical integration of the mobile charge concept into the single-shell model (viewing the cell as a homogenous sphere surrounded by a membrane) led to a set of equations which predicted electrorotational behavior of DPA-treated cells in dependence on medium conductivity. The quantitative data on the partition and the transmembrane translocation rate of the DPA anion extracted from the experimental rotational spectra agreed well with the corresponding literature values.

Electrophysiology↗
PubMed2002

Divergent intron conservation in the mitochondrial nad2 gene: signatures for the three bryophyte classes (mosses, liverworts, and hornworts) and the lycophytes.

The slow-evolving mitochondrial DNAs of plants have potentially conserved information on the phylogenetic branching of the earliest land plants. We present the nad2 gene structures in hornworts and liverworts and in the presumptive earliest-branching vascular land plant clade, the Lycopodiopsida. Taken together with the recently obtained nad2 data for mosses, each class of bryophytes presents another pattern of angiosperm-type introns conserved in nad2: intron nad2i1 in mosses; intron nad2i3 in liverworts; and both introns, nad2i3 and nad2i4, in hornworts. The lycopods Isoetes and Lycopodium show diverging intron conservation and feature a unique novel intron, termed nad2i3b. Hence, mitochondrial introns in general are positionally stable in the bryophytes and provide significant intraclade phylogenetic information, but the nad2 introns, in particular, cannot resolve the interclade relationships of the bryophyte classes and to the tracheophytes. The necessity for RNA editing to reconstitute conserved codon entities in nad2 is obvious for all clades except the marchantiid liverworts. Finally, we find that particularly small group II introns appear as a general feature of the Isoetes chondriome. Plant mitochondrial peculiarities such as RNA editing frequency, U-to-C type of RNA editing, and small group II introns appear to be genus-specific rather than gene-specific features.

Amino Acid Sequence↗
PubMed2002

Persistent organochlorine contaminants and enantiomeric signatures of chiral pollutants in ringed seals (Phoca hispida) collected on the east and west side of the Northwater Polynya, Canadian Arctic.

To examine the influence of diet and age on organochlorine contaminant (OC) concentrations in two closely related ringed seal (Phoca hispida) populations enantiomeric fractions (EFs) of chiral contaminants and stable isotopes of nitrogen (delta15N) and carbon (delta13C) were measured along with OCs in ringed seals collected from the east and west side of the Northwater Polynya. Seals from these two locations were feeding at the same trophic level based on delta15N values in muscle but had slightly different sources of carbon based on delta13C measurements in muscle. After removing the influence of age, sex, and blubber thickness, OC concentrations did not vary between ringed seals from the east and west side of the polynya. SigmaPCB, SigmaDDT, and Sigmachlordane were found to increase with age for both male and female seals. The inclusion of older (>20 years) female seals, which may have a reduced reproductive effort, may influence the relationships in females. Stable isotopes failed to describe OC concentrations in ringed seals suggesting that diet was not a major factor in variation of OC concentrations within this ringed seal population. Cis- and trans-chlordane, oxychlordane, and heptachlor epoxide were all nonracemic in the ringed seal blubber but did not vary with age, sex, or collection site. Alpha-HCH appeared racemic (enantiomeric fraction = 0.50 +/- 0.01) in the seals, although this EF is different than those previously observed in their prey species, and was found to vary significantly with age. EF values in the ringed seals varied considerably from other Arctic marine mammals and seabirds, providing addition evidence that the type(s) and characteristic(s) of the enzymes involved in biotransformation of chiral OCs vary between these organisms.

Adipose Tissue↗
PubMed2002

Simulations of NMR-detected diffusion in suspensions of red cells: the "signatures" in q-space plots of various lattice arrangements.

Coherence effects from pulsed field-gradient spin-echo (PGSE) nuclear magnetic resonance diffusion experiments have been observed and characterized for diffusants in many heterogeneous systems, ranging from porous materials to cell suspensions. The resulting coherence patterns appear in plots of the normalized PGSE signal intensities as a function of the spatial wave vector Q in a so-called q-space plot. The origin of these phenomena and their mathematical and physical underpinnings are now well established. We have conducted a number of studies of diffusion-coherence phenomena in suspensions of red blood cells and have made extensive use of computer simulations of molecular diffusion in virtual lattices of cells to aid in the interpretation and analysis of experimental data. In the current work we extended the canonical model used in these studies to investigate the effect that varying the packing arrangement of cells in the suspension has on the coherence patterns, as seen in q-space plots. We show that changes in the packing arrangement of cells are reflected in the q-space plots and in the results of diffusion tensor analysis and thus we speculate upon the possible clinical importance of these findings.

Anisotropy↗