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PubMed1995

Ecologic studies in epidemiology: concepts, principles, and methods.

An ecologic study focuses on the comparison of groups, rather than individuals; thus, individual-level data are missing on the joint distribution of variables within groups. Variables in an ecologic analysis may be aggregate measures, environmental measures, or global measures. The purpose of an ecologic analysis may be to make biologic inferences about effects on individual risks or to make ecologic inferences about effects on group rates. Ecologic study designs may be classified on two dimensions: (a) whether the primary group is measured (exploratory vs analytic study); and (b) whether subjects are grouped by place (multiple-group study), by time (time-trend study), or by place and time (mixed study). Despite several practical advantages of ecologic studies, there are many methodologic problems that severely limit causal inference, including ecologic and cross-level bias, problems of confounder control, within-group misclassification, lack of adequate data, temporal ambiguity, collinearity, and migration across groups.

Data Interpretation, Statistical↗

PubMed2026

Assembly and comparative analysis of the mitochondrial genome of Pleione yunnanensis: genome structure and evolutionary insights.

BACKGROUND: Pleione yunnanensis a terrestrial or semi-epiphytic herbaceous plant belonging to the Orchidaceae family, is valued for both its medicinal uses and ornamental appeal. Although its chloroplast genomes have been sequenced, its complete mt genome had not previously been resolved, limiting genetic and evolutionary studies of the species. RESULTS: In this work, we assembled and characterized the first complete mt genome of P. yunnanensis, revealing a structurally complex, multibranched system composed of 14 circular-mapping molecules totaling 468,176 bp with a GC content of 44.32%. The genome encodes 44 annotated genes, including 28 protein-coding genes (PCGs), 15 tRNAs, and one rRNA. The multibranched architecture provides new evidence supporting the dynamic and recombinational nature of plant mt genomes. Repeat analysis uncovered 29 simple sequence repeats (SSRs), 19 tandem repeats, and 118 dispersed repeats, indicating a comparatively lower repeat abundance than that found in closely related orchids with similar mt genome sizes. Codon-usage profiling of PCGs showed a marked bias toward A/T-ending codons. Prediction of RNA editing sites identified 4,708 putative edits across mitochondrial PCGs. Most mitochondrial genes displayed Ka/Ks ratios close to 1.0, suggesting relaxed selective constraints or lineage-specific evolutionary patterns rather than strong positive selection. Moreover, we detected 69 chloroplast-derived homologous fragments, including 15 intact genes, suggesting ongoing plastid-mitochondrial DNA transfer. Phylogenetic reconstruction and collinearity comparisons demonstrated that P. yunnanensis clustered closely with Dendrobium species, including D. amplum and D. hancockii, within the Orchidaceae clade. CONCLUSIONS: This study provides the first complete mt genome of P. yunnanensis, providing a foundational genomic resource for the genus Pleione. The results not only improve our understanding of mt genome structure and evolution in Orchidaceae, but also offer valuable molecular evidence for phylogenetic inference, germplasm identification, and conservation of this endangered medicinal species.

Orchidaceae↗

PubMed2003

Modeling the integration of motion signals across space.

Experiments by Loffler and Orbach on the integration of motion signals across space [J. Opt. Soc. Am. A 20, 1461 (2003)] revealed that both three-dimensional analysis and object interpretation play a much smaller role than previously assumed. These results motivated the quantitative description of a low-level, bottom-up model presented here. Motion is computed in parallel at different spatial sites, and excitatory interactions operate between sites. The strength of these interactions is determined mainly by distance. Simulations correctly predict behavior for a variety of manipulations on multi-aperture stimuli: aligned and skewed lines, different presentation times, different inter-aperture gaps, and different spatial frequencies. However, strictly distance-dependent mechanisms are too simplistic to account for all experimental data. Mismatches for grossly misoriented lines suggest collinear facilitation as a promising extension. Once incorporated, collinear facilitation not only correctly predicts results for misoriented patterns but also accounts for the lack of motion integration between heterogeneous stimuli such as lines and dots.

Computer Simulation↗

PubMed1998

Simulation of S2-state multiline EPR signal in oriented photosystem II membranes: structural implications for the manganese cluster in an oxygen-evolving complex.

High-quality angular-dependent spectra of multiline electron paramagnetic resonance (EPR) signals from the S2-state Mn cluster in a photosynthetic oxygen-evolving complex (OEC) were obtained for partially oriented photosystem (PS) II membranes, and the magnetic structure of the Mn cluster has been studied by simulation analysis. The angular-dependent multiline spectra were simulated by taking into account the anisotropic properties of both hyperfine tensors of intrinsic Mn ions and g-tensor of the cluster in a tetranuclear model. The best-fit parameters for the simulation indicate that (a) the oxidation state of the S2-state Mn cluster is Mn(III, IV, IV, IV), (b) the electronic orbital configuration of the Mn(III) ion is (dpi)3[dz2(sigma))]1, (c) the effective g-tensor of the Mn cluster and the hyperfine tensor of the Mn(III) ion are axially symmetric, and their principal z-axes are nearly collinear each other, and (d) the z-axis of the dz2 orbital of the Mn(III) ion and the normal of the thylakoid membrane are at an angle of 50.1 +/- 1.8 degrees. The results are compatible with those of the oriented XAFS study [Mukerji, I., et al. (1994) Biochemistry 33, 9712-9721], and indicate that the O-O vector of the putative di-mu-oxo bridged Mn(III)-Mn(IV) dimer unit in the Mn cluster tilts by 43-56 degrees with respect to the normal of thylakoid membrane. A model of the arrangement of the di-mu-oxo bridged Mn(III)-Mn(IV) unit with respect to the thylakoid membrane is proposed.

Absorptiometry, Photon↗

PubMedDate not supplied

Structural interpretation of the topological index. 2. The molecular connectivity index, the Kappa index, and the atom-type E-State index.

The structural interpretation is extended to the topological indices describing cyclic structures. Three representatives of the topological index, such as the molecular connectivity index, the Kappa index, and the atom-type E-State index, are interpreted by mining out, through projection pursuit combining with a number theory method generating uniformly distributed directions on unit sphere, the structural features hidden in the spaces spanned by the three series of indices individually. Some interesting results, which can hardly be found by individual index, are obtained from the multidimensional spaces by several topological indices. The results support quantitatively the former studies on the topological indices, and some new insights are obtained during the analysis. The combinations of several molecular connectivity indices describe mainly three general categories of molecular structure information, which include degree of branching, size, and degree of cyclicity. The cyclicity can also be coded by the combination of chi cluster and path/cluster indices. The Kappa shape indices encode, in combination, significant information on size, the degree of cyclicity, and the degree of centralization/separation in branching. The size, branch number, and cyclicity information has also been mined out to interpret atom-type E-State indices. The structural feature such as the number of quaternary atoms is searched out to be an important factor. The results indicate that the collinearity might be a serious problem in the applications of the topological indices.

Journal Article↗

PubMed1999

Use of a clustered model to identify factors affecting hospital length of stay.

Predictive models have been used to identify factors that may prolong hospital length of stay (LOS). However, because predictors of LOS are collinear, the proportion of variance associated with each factor in a multivariate stepwise regression model may not reflect its mathematical contribution in explaining LOS. In an attempt to model factor contribution to LOS more realistically, we evaluated a clinically based clustered model. This model uses classes of candidate predictors, that is, patient attributes, adverse events, treatment modality, and health provider identity. Clusters of variables are permitted to enter into the model in a theoretically based predetermined sequence, so that the additional contribution of each cluster of factors can be assessed while the contribution of preceding factors is preserved. The clustered model was tested and compared with a free stepwise multivariate analysis in a cohort of patients undergoing prostatectomy for benign prostatic hypertrophy. We found that both models explained a similar proportion of the variance in LOS (56%-57%). However, some important differences were evident. Prostate size, associated with 12% of the variance in the clustered model, was not an independent predictor in the free model. A higher proportion of variance was associated with process variables, such as treatment modality in the free model. We conclude that use of a clustered model may facilitate more realistic assessment of the relative contribution of factors to LOS.

Aged↗

PubMed1998

Grass genomes.

For the most part, studies of grass genome structure have been limited to the generation of whole-genome genetic maps or the fine structure and sequence analysis of single genes or gene clusters. We have investigated large contiguous segments of the genomes of maize, sorghum, and rice, primarily focusing on intergenic spaces. Our data indicate that much (>50%) of the maize genome is composed of interspersed repetitive DNAs, primarily nested retrotransposons that insert between genes. These retroelements are less abundant in smaller genome plants, including rice and sorghum. Although 5- to 200-kb blocks of methylated, presumably heterochromatic, retrotransposons flank most maize genes, rice and sorghum genes are often adjacent. Similar genes are commonly found in the same relative chromosomal locations and orientations in each of these three species, although there are numerous exceptions to this collinearity (i.e., rearrangements) that can be detected at the levels of both the recombinational map and cloned DNA. Evolutionarily conserved sequences are largely confined to genes and their regulatory elements. Our results indicate that a knowledge of grass genome structure will be a useful tool for gene discovery and isolation, but the general rules and biological significance of grass genome organization remain to be determined. Moreover, the nature and frequency of exceptions to the general patterns of grass genome structure and collinearity are still largely unknown and will require extensive further investigation.

Journal Article↗

PubMed2005

Complete genome sequence of cercopithecine herpesvirus 2 (SA8) and comparison with other simplexviruses.

We have obtained the complete sequence of the herpesvirus simian agent 8 (SA8; cercopithecine herpesvirus 2) a baboon simplexvirus closely related to the monkey B virus and herpes simplex virus types 1 and 2. The genome of SA8 is 150,715 bp long, with an overall G/C content of 76%, the highest among the simplexviruses sequenced so far. The sequencing has confirmed that the genomic arrangement of SA8 is similar to that of other simplexviruses: unique long and unique short regions bordered by two sets of inverted repeats. All genes identified in SA8 are homologous and collinear with those of the monkey B virus, including the lack of the RL1 open reading frame, a gene responsible for neurovirulence in human herpes simplex viruses. This latter finding supports the hypothesis that a different pathogenetic mechanism may have developed in human simplexviruses, after their divergence from monkey simplexviruses.

Alphaherpesvirinae↗

PubMed1998

Genetic analysis of the rat leukemia virus: influence of viral sequences in transduction of the c-ras proto-oncogene and expression of its transforming activity.

The rat leukemia virus (RaLV) is an endogenous retrovirus that is spontaneously released by Sprague-Dawley rat embryo cells. The overall structure of the RaLV genome resembles that of other simple, replication-competent retroviruses, but the sequence of the long terminal repeats (LTR) is unique and unrelated to the known retroviruses. Phylogenetically, the RaLV genome appears to be more closely related to the feline leukemia virus group of retroviruses than to the murine leukemia virus group. A remarkable feature of RaLV is that it is capable of transducing a ras proto-oncogene from rat tumor cells in the form of an acutely transforming virus, designated the Rasheed strain of the rat sarcoma virus (RaSV). With the exception of the c-ras sequence, the genomes of both RaLV and RaSV are collinear. The RaSV-encoded oncogene v-Ra-ras expresses a fusion protein with a molecular mass of 29 kDa, and it exhibits a unique structure that has not been described previously for any known virus. The 5' end of this gene is derived from sequences encoding RaLV matrix followed by 20 bp derived from the U5 region of the RaLV LTR (RS-U5 element) which is joined at its 3' end to sequences derived from all six (coding and noncoding) exons of the c-ras proto-oncogene at the 3' end. This recombinational event represents a novel mechanism among the acutely transforming viruses that have been studied.

3T3 Cells↗

PubMed1997

Bias in diet assessment methods--consequences of collinearity and measurement errors on power and observed relative risks.

BACKGROUND: If several risk factors for disease are considered in a regression model and these factors are affected by measurement errors, the observed relative risk will be attenuated. In nutritional epidemiology, several nutrient variables show strong correlation, described as collinearity. The observed relative risk will then depend not only on the validity of the chosen diet assessment method but also on collinearity between variables in the model. METHODS: The validity of different diet assessment methods are compared. The correlation coefficients between common nutrients and foods are given using data from the Malmö Food Study. Intake of nutrients and foods were assessed with a modified diet history method, combining a 2-week food record for beverages and lunch/dinner meals and a food frequency questionnaire for other foods. The study population comprised 165 men and women aged 50-65 years. A multivariate logistic regression model is used to illustrate the effect of collinearity on observed relative risk (RRo). RESULTS: A moderate to high correlation between risk factors will substantially influence RRo even when using diet assessment methods with high validity. Methods with low validity might even give inverse RRo. CONCLUSION: It is stressed that caution must be exercised and only a selected number of variables should be included in the model, especially when they are highly intercorrelated, since RRo might be severely biased.

Aged↗

PubMed1997

The abundant latency-associated transcripts of herpes simplex virus type 1 are bound to polyribosomes in cultured neuronal cells and during latent infection in mouse trigeminal ganglia.

During herpes simplex virus type 1 (HSV-1) latency, limited viral transcription takes place. This transcription has been linked to the ability of the HSV-1 genome to reactivate and consists of abundant 2.0- and 1.5-kb collinear latency-associated transcripts (LATs), spanned by minor hybridizing RNA (mLAT). The 1.5-kb LAT is derived from the 2.0-kb LAT by splicing, and both transcripts contain two large overlapping open reading frames. The molecular action mechanisms of the latency-associated gene expression are unknown, and no HSV-1 latency-encoded proteins have been convincingly demonstrated. We have cloned the entire latency-associated transcriptionally active HSV-1 DNA fragment (10.4 kb) under control of a constitutive promoter and generated a neuronal cell line (NA4) stably transfected with the viral LAT's region. NA4 cells produced the 2.0- and the 1.5-kb LATs. Northern blotting and reverse transcription-PCR analysis of RNA from NA4 cells and from trigeminal ganglia of mice latently infected with HSV-1 revealed that the two abundant LAT species were present in the polyribosomal RNA fractions. After addition of EDTA, which causes dissociation of mRNA-ribosome complexes, both LATs could be detected only in subpolyribosomal, but not in polyribosomal fractions. These results show that (i) HSV-1 LATs are bound to polyribosomes during latency in vivo, as well as in neuronal cells in vitro, and therefore might be translated, and that (ii) the NA4 cell line is a suitable tool with which to look for HSV-1 latency-encoded gene products.

Animals↗

PubMed1997

A comparative QSAR analysis of acetylcholinesterase inhibitors currently studied for the treatment of Alzheimer's disease.

Considering the relevance of acetylcholinesterase inhibitors as potential agents for the treatment of the Alzheimer's disease, we have undertaken a comparative QSAR analysis aimed at individuating the physico-chemical properties governing the inhibitory activity of such compounds. The QSAR equations for 13 series of derivatives have been calculated and discussed. The series studied are all those we found in the literature suitable for a QSAR analysis and represent the three main classes of acetylcholinesterase inhibitors currently investigated, namely, physostigmine analogues, 1,2,3,4-tetrahydroacridines and benzylamines. The equations we obtained show that, within each class, the main physico-chemical properties affecting the inhibitory activity are almost the same for all the series and can be individuated by the use of proper parameters. The conclusions of this study can be summarized as follows: (a) hydrophobicity plays a critical role in both the physostigmine- and the benzylamine-derived classes; (b) electronic effects are important for the interactions carried out by the variable portion of benzylamine derivatives; and (c) steric factors are also significant, but, as in other cases, the collinearity between steric and hydrophobic parameters does not allow one to draw any final conclusion.

Acetylcholinesterase↗

PubMed2004

Conservation of the microstructure of genome segments in Brassica napus and its diploid relatives.

The cultivated Brassica species are the group of crops most closely related to Arabidopsis thaliana (Arabidopsis). They represent models for the application in crops of genomic information gained in Arabidopsis and provide an opportunity for the investigation of polyploid genome formation and evolution. The scientific literature contains contradictory evidence for the dynamics of the evolution of polyploid genomes. We aimed at overcoming the inherent complexity of Brassica genomes and clarify the effects of polyploidy on the evolution of genome microstructure in specific segments of the genome. To do this, we have constructed bacterial artificial chromosome (BAC) libraries from genomic DNA of B. rapa subspecies trilocularis (JBr) and B. napus var Tapidor (JBnB) to supplement an existing BAC library from B. oleracea. These allowed us to analyse both recent polyploidization (under 10,000 years in B. napus) and more ancient polyploidization events (ca. 20 Myr for B. rapa and B. oleracea relative to Arabidopsis), with an analysis of the events occurring on an intermediate time scale (over the ca. 4 Myr since the divergence of the B. rapa and B. oleracea lineages). Using the Arabidopsis genome sequence and clones from the JBr library, we have analysed aspects of gene conservation and microsynteny between six regions of the genome of B. rapa with the homoeologous regions of the genomes of B. oleracea and Arabidopsis. Extensive divergence of gene content was observed between the B. rapa paralogous segments and their homoeologous segments within the genome of Arabidopsis. A pattern of interspersed gene loss was identified that is similar, but not identical, to that observed in B. oleracea. The conserved genes show highly conserved collinearity with their orthologues across genomes, but a small number of species-specific rearrangements were identified. Thus the evolution of genome microstructure is an ongoing process. Brassica napus is a recently formed polyploid resulting from the hybridization of B. rapa (containing the Brassica A genome) and B. oleracea (containing the Brassica C genome). Using clones from the JBnB library, we have analysed the microstructure of the corresponding segments of the B. napus genome. The results show that there has been little or no change to the microstructure of the analysed segments of the Brassica A and C genomes as a consequence of the hybridization event forming natural B. napus. The observations indicate that, upon polyploid formation, these segments of the genome did not undergo a burst of evolution discernible at the scale of microstructure.

Brassica↗

PubMed2002

Mosaic organization of orthologous sequences in grass genomes.

Although comparative genetic mapping studies show extensive genome conservation among grasses, recent data provide many exceptions to gene collinearity at the DNA sequence level. Rice, sorghum, and maize are closely related grass species, once sharing a common ancestor. Because they diverged at different times during evolution, they provide an excellent model to investigate sequence divergence. We isolated, sequenced, and compared orthologous regions from two rice subspecies, sorghum, and maize to investigate the nature of their sequence differences. This study represents the most extensive sequence comparison among grasses, including the largest contiguous genomic sequences from sorghum (425 kb) and maize (435 kb) to date. Our results reveal a mosaic organization of the orthologous regions, with conserved sequences interspersed with nonconserved sequences. Gene amplification, gene movement, and retrotransposition account for the majority of the nonconserved sequences. Our analysis also shows that gene amplification is frequently linked with gene movement. Analyzing an additional 2.9 Mb of genomic sequence from rice not only corroborates our observations, but also suggests that a significant portion of grass genomes may consist of paralogous sequences derived from gene amplification. We propose that sequence divergence started from hotspots along chromosomes and expanded by accumulating small-scale genomic changes during evolution.

Chromosomes, Plant↗

PubMed1996

Identification and characterization of the pseudorabies virus UL3.5 protein, which is involved in virus egress.

Alphaherpesvirus genomes exhibit a generally collinear gene arrangement, and most of their genes are conserved among the different members of the subfamily. Among the exceptions is the UL3.5 gene of pseudorabies virus (PrV) for which positional homologs have been detected in the genomes of varicella-zoster virus, equine herpesvirus 1, and bovine herpesvirus 1 but not in the genomes of herpes simplex virus types 1 and 2. To identify and characterize the predicted 224 amino acid UL3.5 protein of PrV, a rabbit antiserum was prepared against a UL3.5 fusion protein expressed in Escherichia coli. In Western blot (immunoblot) analyses the antiserum detected a 30-kDa protein in the cytoplasm of PrV infected cells which was absent from purified virions. For functional analysis, UL3.5-expressing cell lines were established and virus mutants were isolated after the rescue of defective, glycoprotein B-negative PrV by insertion of the complementing glycoprotein B-encoding gene of bovine herpesvirus 1 at two sites within the UL3.5 locus. A PrV mutant carrying the insertion at codon 159 and expressing a truncated UL3.5 protein was still capable of efficient productive replication in noncomplementing cells. In contrast, a PrV mutant carrying the insertion at codon 10 of the UL3.5 gene did not express detectable UL3.5 protein and exhibited a dramatic growth deficiency on non-complementing cells with regard to plaque formation and one-step replication. Electron microscopical studies showed an accumulation of unenveloped capsids in the vicinity of the Golgi apparatus. This defect could be compensated by propagation on complementing UL3.5-expressing cell lines. Our results thus demonstrate that the PrV UL3.5 gene encodes a nonstructural protein which plays an important role in virus replication, presumably during virus egress. The functionally relevant domains appear to be located within the N-terminal part of the UL3.5 protein which also comprises the region exhibiting the highest level of homology between the predicted UL3.5 homologous proteins of other alphaherpesviruses.

Animals↗

PubMed2003

Electromagnetic actuator for generating variably oriented shear waves in MR elastography.

Magnetic resonance elastography (MRE) is a recently developed technique for determining the mechanical properties of biological tissue. In dynamic MRE, electromagnetic units (actuators) are widely used to generate shear waves in tissue. These actuators exploit the interaction between the static magnetic field B(0) and an annular coil supplied with alternating currents. Therefore, coil movements are restricted to selected orientations to B(0). Conventional actuators transfer this movement collinearly to B(0) into the tissue. In this study, an electromagnetic actuator was introduced that overcomes this limitation. It is demonstrated that different directions of mechanical excitation can be generated and monitored by MRE. Different spatial components of the propagation of the shear waves were determined using agarose phantoms. The technique allows maximum contrast for MRE images of objects with anisotropic strain components such as muscle tissue.

Anisotropy↗

PubMed2005

Physico-chemical properties of PCDD/PCDFs and phthalate esters.

QSPR models for water solubility (S), n-octanol/water partition coefficient (K(OW)), and Henry's law constant (H) for polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzo-p-furans (PCDFs) and phthalates have been established based on two different sets of parameters. Those parameters were topology based characteristic root index (CRI) and three semi-empirical molecular descriptors, namely--energies of the highest occupied and the lowest unoccupied molecular orbital (E(HOMO) and E(LUMO)), and dipole moment (mu). The best fit equation found by "forward multiple linear regression" showed that the topology based CRI was the most important parameter for the modelling of solubility and n-octanol/water partition coefficient. For n-octanol/water partition coefficient a two-parameter equation including the CRI and E(HOMO) with a correlation coefficient of r = 0.992 was obtained whereas a three-parameter equation for solubility and Henry's law constant including the CRI, E(LUMO) and mu with a correlation coefficient of r = 0.986 and r = 0.933 was obtained, respectively. E(HOMO) and mu didn't appear in the same model because of the collinearity. The results of modified jackknife tests indicated that the three models were statistically robust. Mean deviation of calculated values from experimental data amounted to 0.27, 0.17, and 0.28 log units for the three properties mentioned. The developed models have been used to predict the S, K(OW) and H of compounds not included in the training sets.

1-Octanol↗

PubMed2005

Localization of monocular stimuli in different depth planes.

We examined the phenomenon in which two physically aligned monocular stimuli appear to be non-collinear when each of them is located in binocular regions that are at different depth planes. Using monocular bars embedded in binocular random-dot areas that are at different depths, we manipulated properties of the binocular areas and examined their effect on the perceived direction and depth of the monocular stimuli. Results showed that (1) the relative visual direction and perceived depth of the monocular bars depended on the binocular disparity and the dot density of the binocular areas, and (2) the visual direction, but not the depth, depended on the width of the binocular regions. These results are consistent with the hypothesis that monocular stimuli are treated by the visual system as binocular stimuli that have acquired the properties of their binocular surrounds. Moreover, partial correlation analysis suggests that the visual system utilizes both the disparity information of the binocular areas and the perceived depth of the monocular bars in determining the relative visual direction of the bars.

Depth Perception↗