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Genome organization in Arabidopsis thaliana: a survey for genes involved in isoprenoid and chlorophyll metabolism.

The isoprenoid biosynthetic pathway provides intermediates for the synthesis of a multitude of natural products which serve numerous biochemical functions in plants: sterols (isoprenoids with a C30 backbone) are essential components of membranes; carotenoids (C40) and chlorophylls (which contain a C20 isoprenoid side-chain) act as photosynthetic pigments; plastoquinone, phylloquinone and ubiquinone (all of which contain long isoprenoid side-chains) participate in electron transport chains; gibberellins (C20), brassinosteroids (C30) and abscisic acid (C15) are phytohormones derived from isoprenoid intermediates; prenylation of proteins (with C15 or C20 isoprenoid moieties) may mediate subcellular targeting and regulation of activity; and several monoterpenes (C10), sesquiterpenes (C15) and diterpenes (C20) have been demonstrated to be involved in plant defense. Here we present a comprehensive analysis of genes coding for enzymes involved in the metabolism of isoprenoid-derived compounds in Arabidopsis thaliana. By combining homology and sequence motif searches with knowledge regarding the phylogenetic distribution of pathways of isoprenoid metabolism across species, candidate genes for these pathways in A. thaliana were obtained. A detailed analysis of the vicinity of chromosome loci for genes of isoprenoid metabolism in A. thaliana provided evidence for the clustering of genes involved in common pathways. Multiple sequence alignments were used to estimate the number of genes in gene families and sequence relationship trees were utilized to classify their individual members. The integration of all these datasets allows the generation of a knowledge-based metabolic map of isoprenoid metabolic pathways in A. thaliana and provides a substantial improvement of the currently available gene annotation.

Abscisic Acid↗

Random walks with thin filaments: application of in vitro motility assay to the study of actomyosin regulation.

The in vitro motility devised by Kron and Spudich (Kron and Spudich, 1986; Kron et al., 1991) has proved a very valuable technique for studying the motor properties of myosin of all kinds but it is equally useful for the study of the thin filaments of muscle and their regulation. The movement of a population of thin filaments over immobilised myosin appears to be random but it does in fact yield a large amount of information about contractility and its regulation. The key to extracting useful information from in vitro motility assay experiments is the logical and comprehensive analysis of filament movements.

Actin Cytoskeleton↗

Control methods and the performance of the robotic testing system for human musculoskeletal joints.

Biomechanical testing of human musculoskeletal joints not only requires qualified testing machines and devices, but also needs an excellent control method to obtain better experimental results. In this paper, we take the human functional spinal unit (FSU) as an example to study how to improve the performance of the robotic testing system. First, the mechanical characteristics of FSU are described and the simplified model (rigid body-spring system) for the specimen is given. Because the location of the center of rotation (COR) of the specimen affects the performance of the system, a comprehensive analysis on the location of COR is carried out. The performance of the robotic testing system can also be improved through the improvement of the control method. Two control methods have been proposed in this paper: one is the improved hybrid control, the other is fuzzy logic control.

Algorithms↗

Gender differences in economic support and well-being of older Asians.

This report provides a comprehensive analysis of gender differences in economic support and well-being in eight countries in Southern and Eastern Asia (Bangladesh, Malaysia, Indonesia, Singapore, Thailand, Vietnam, Philippines, and Taiwan). We examine multiple economic indicators, including sources of income, receipt of financial and material support, income levels, ownership of assets, and subjective well-being. Results show substantial variation in gender differences across indicators and provide an important qualification to widely held views concerning the globally disadvantaged position of older women. Whereas men tend to report higher levels of income than women, there is generally little gender difference in housing characteristics, asset ownership, or reports of subjective economic well-being. Unmarried women are economically advantaged compared to unmarried men in some respects, in part because they are more likely to be embedded in multigenerational households and receive both direct and indirect forms of support from family members.

Aged↗

ATM and genome maintenance: defining its role in breast cancer susceptibility.

The ATM gene is mutated in ataxia-telangiectasia (A-T), a genetic instability syndrome characterized by increased cancer risk, as well as other features. Recent studies have shown that the ATM protein kinase plays a critical role in maintaining genome integrity by activating a biochemical chain reaction that in turn leads to cell cycle checkpoint activation and repair of DNA damage. ATM targets include well-known tumor suppressor genes such as p53 and BRCA1, both of which play an important role in predisposition to breast cancer. Studies of A-T families have consistently reported an increased risk of breast cancer in women with one mutated ATM gene, but so far an increased frequency of ATM mutations has not been found in women with breast cancer. Some specific missense and protein truncating variants of ATM have been reported to confer increased breast cancer risk, but the magnitude of this risk remains uncertain. A more comprehensive analysis of ATM is needed in large case-control studies, and in multiple-case breast cancer families.

Ataxia Telangiectasia↗

NMR for structural proteomics of Thermotoga maritima: screening and structure determination.

This paper describes the NMR screening of 141 small (<15 kDa) recombinant Thermotoga maritima proteins for globular folding. The experimental data shows that approximately 25% of the screened proteins are folded under our screening conditions, which makes this procedure an important step for selecting those proteins that are suitable for structure determination. A comparison of screening based either on 1D 1H NMR with unlabeled proteins or on 2D [1H,15N]-COSY with uniformly 15N-labeled proteins is presented, and a comprehensive analysis of the 1D 1H NMR screening data is described. As an illustration of the utility of these methods to structural proteomics, the NMR structure determination of TM1492 (ribosomal protein L29) is presented. This 66-residue protein consists of a N-terminal 3(10)-helix and two long alpha-helices connected by a tight turn centered about glycine 35, where conserved leucine and isoleucine residues in the two alpha-helices form a small hydrophobic core.

Bacterial Proteins↗

Assessing population need for mental health care: a review of approaches and predictors.

This review aimed to clarify the concept of need, explore the different approaches used to assess need, and contribute to an improved understanding of predictor and intervening factors in assessing need for mental health services. Two population-based needs assessment approaches have been identified: modeling need for services and surveys of the general population. The most widely used model was that based on the Jarman-8 index of social deprivation. The population-based epidemiological surveys addressed perceived need by seeking direct, self-reported measures of individuals' perceptions of their needs for care. Although many studies have reported correlates of service use, few have attempted to identify correlates of perceived need. The fact that two-thirds to three-quarters of people were identified as meeting criteria for a mental health disorder, but did not report receiving treatment, highlighted a gap between epidemiology and service use. This gap could be explained by a number of intervening factors such as the discordance between diagnosis and disability, the determinants of and barriers to help-seeking behavior, the belief systems concerning appropriate treatments, and choice of health professionals. This review has thus identified the predictor variables which are important for a comprehensive analysis of need for mental health care. Suggestions and challenges have been put forward to address the identified gaps in assessing population need.

Developed Countries↗

Base usage and dinucleotide frequency of infectious bursal disease virus.

Base usage and dinucleotide frequency have been extensively studied in many eukaryotic organisms and bacteria, but not for viruses. In this paper, a comprehensive analysis of these aspects for infectious bursal disease virus (IBDV) was presented. The analysis of base usage indicated that all of the IBDV genes possess equivalent overall nucleotide distributions. However when the base usage at each codon positions was analysed by using cluster analysis, the VP5 open reading frame (ORF) formed a different cluster isolated from the other genes. The unusual base usage of VP5 ORF may indicate that the gene was originated by the virus "overprinting strategy", a strategy in which virus may create novel gene by utilizing the unused reading frames of its existing genes. Meanwhile, the GC content of the IBDV genes and the chicken's coding sequences was comparable; suggesting the virus imitation of the host to increase its translational efficiency. The analysis of dinucleotide frequency indicated that IBDV genome had dinucleotide bias: the frequencies of CpG and TpA were lower and the TpG was higher than the expected. Classical methylation pathway, a process where CpG converted to TpG, may explain the significant correlation between the CpG deficiency and TpG abundance. "Principal component analysis of the dinucleotide frequencies" (DF-PCA) was used to analyse the overall dinucleotide frequencies of IBDV genome. DF-PCA on the hypervariable region and polyprotein (VPX-VP4-VP3) gene showed that the very virulent IBDV (vvIBDV) was segregated from other strains; which meant vvIBDV had a unique dinucleotide pattern. In summary, the study of base usage and dinucleotide frequency had unravelled many overlooked genomic properties of the virus.

Animals↗

Energy, volatile production, and climatic effects of the Chicxulub Cretaceous/Tertiary impact.

A comprehensive analysis of volatiles in the Chicxulub impact strongly supports the hypothesis that impact-generated sulfate aerosols caused over a decade of global cooling, acid rain, and disruption of ocean circulation, which contributed to the mass extinction at the Cretaceous/Tertiary (K/T) boundary. The crater size, meteoritic content of the K/T boundary clay, and impact models indicate that the Chicxulub crater was formed by a short period comet or an asteroid impact that released 0.7-3.4 x 10(31) ergs of energy. Impact models and experiments combined with estimates of volatiles in the projectile and target rocks predict that over 200 gigatons (Gt) each of SO2 and water vapor, and over 500 Gt of CO2, were globally distributed in the stratosphere by the impact. Additional volatiles may have been produced on a global or regional scale that formed sulfate aerosols rapidly in cooler parts of the vapor plume, causing an early, intense pulse of sulfuric acid rain. Estimates of the conversion rate of stratospheric SO2 and water vapor to sulfate aerosol, based on volcanic production of sulfate aerosols, coupled with calculations of diffusion, coagulation, and sedimentation, demonstrate that the 200 Gt stratospheric SO2 and water vapor reservoir would produce sulfate aerosols for 12 years. These sulfate aerosols caused a second pulse of acid rain that was global. Radiative transfer modeling of the aerosol clouds demonstrates (1) that if the initial rapid pulse of sulfate aerosols was global, photosynthesis may have been shut down for 6 months and (2) that for the second prolonged aerosol cloud, solar transmission dropped 80% by the end of first year and remained 50% below normal for 9 years. As a result, global average surface temperatures probably dropped between 5 degrees and 31 degrees K, suggesting that global near-freezing conditions may have been reached. Impact-generated CO2 caused less than 1 degree K greenhouse warming and therefore was insignificant compare to the sulfate cooling. The magnitude of sulfate cooling depends largely upon the rate of ocean mixing as surface waters cool, sink, and are replaced by upwelling of deep ocean water. This upwelling apparently drastically altered ocean stratification and circulation, which may explain the global collapse of the delta 13C gradient between surface and deep ocean waters at the K/T boundary.

Acid Rain↗

Conformational properties of a cyclic peptide bradykinin B2 receptor antagonist using experimental and theoretical methods.

The solution conformation of the cyclic peptide J324 (cyclo0,6-[Lys0,Glu6,D-Phe7]BK), an antagonist targeted at the bradykinin (BK) B2 receptor, has been investigated using experimental and theoretical methods. In order to gain insight into the structural requirements essential for BK antagonism, we carried out molecular dynamics (MD) simulations using simulated annealing as the sampling protocol. Following a free MD simulation we performed simulations using nuclear Overhauser enhancement (NOE) distance constraints determined by NMR experiments. The low-energy structures obtained were compared with each other, grouped into families and analyzed with respect to the presence of secondary structural elements in their backbone. We also introduced new ways of plotting structural data for a more comprehensive analysis of large conformational sets. Finally, the relationship between characteristic backbone conformations and the spatial arrangement of specific pharmacophore centers was investigated.

Bradykinin Receptor Antagonists↗

A direct in vivo measurement of the three-dimensional orientation of the occlusal plane and of the sagittal discrepancy of the jaws.

The aim of the present investigation was to three dimensionally assess craniofacial relationships in vivo. Specifically, by using a non-invasive direct technique, the following measurements were made: 1) natural head position relative to the ground; 2) orientation of the occlusal plane relative to the subject's intrinsic facial planes; and 3) anteroposterior discrepancy of the dental bases, taking into consideration all the facial hard- and soft-tissue structures. Several dental and soft-tissue facial landmarks were directly digitized from 24 adult healthy volunteers with Angle Class I occlusions by means of an electromagnetic three-dimensional computerized digitizer. In natural head position, the three-dimensional orientation of Camper's, occlusal, and mandibular planes were measured along with the anteroposterior maxillo-mandibular discrepancies. In the frontal plane projection, all the measured planes appeared about horizontal. In the lateral plane projection, on average, Camper's plane deviated from the true horizontal by approximately 18 degrees (in a 'head flexed' direction). The occlusal plane deviated from the same horizontal by about 14 degrees, while the mandibular plane had a steeper inclination (about 30 degrees ); both planes were significantly correlated to Camper's plane. The measurements of anteroposterior jaw discrepancy revealed a wide range of sagittal relationships in the analyzed subjects. The method was found to be repeatable and fast. This direct three-dimensional in vivo assessment of the orientation of occlusal plane relative to the other facial planes could allow for a more comprehensive analysis of maxillo-mandibular sagittal discrepancies.

Journal Article↗

Development and validation of a brief form of the Multidimensional Personality Questionnaire.

The Multidimensional Personality Questionnaire (MPQ; A. Tellegen, 1982, in press) provides for a comprehensive analysis of personality at both the lower order trait and broader structural levels. Its higher order dimensions of Positive Emotionality, Negative Emotionality, and Constraint embody affect and temperament constructs, which have been conceptualized in psychobiological terms. The MPQ thus holds considerable potential as a structural framework for investigating personality across varying levels of analysis, and this potential would be enhanced by the availability of an abbreviated version. This article describes efforts to develop and validate a brief (155-item) form, the MPQ-BF. Success was evidenced by uniformly high correlations between the brief- and full-form trait scales and consistency of higher order structures. The MPQ-BF is recommended as a tool for investigating the genetic, neurobiological, and psychological substrates of personality.

Adolescent↗

Examining culturally based variables associated with ethnicity: influences on credibility perceptions of empirically supported interventions.

Treatment rationales for 2 widely used and empirically supported interventions, cognitive therapy (CT) and time-limited dynamic psychotherapy (TLDP), were examined for their perceived credibility among 136 Asian American college students. This study conducted a comprehensive analysis of culturally based variables (often assumed to underlie ethnicity) and their related effects on credibility perceptions. Variables assessed included cultural identity, self-construals, values, and mental health beliefs. Participants were randomly assigned to read either a CT or TLDP treatment rationale for depression and then rated the credibility of the interventions. Results indicated that cultural identity and self-construals moderated credibility ratings across CT and TLDP rationales. Findings underscore the importance of moving beyond ethnic group analyses to the examination of specific culturally based variables.

Adolescent↗

Cultures in chimpanzees.

As an increasing number of field studies of chimpanzees (Pan troglodytes) have achieved long-term status across Africa, differences in the behavioural repertoires described have become apparent that suggest there is significant cultural variation. Here we present a systematic synthesis of this information from the seven most long-term studies, which together have accumulated 151 years of chimpanzee observation. This comprehensive analysis reveals patterns of variation that are far more extensive than have previously been documented for any animal species except humans. We find that 39 different behaviour patterns, including tool usage, grooming and courtship behaviours, are customary or habitual in some communities but are absent in others where ecological explanations have been discounted. Among mammalian and avian species, cultural variation has previously been identified only for single behaviour patterns, such as the local dialects of song-birds. The extensive, multiple variations now documented for chimpanzees are thus without parallel. Moreover, the combined repertoire of these behaviour patterns in each chimpanzee community is itself highly distinctive, a phenomenon characteristic of human cultures but previously unrecognised in non-human species.

Animals↗

Conservation and rearrangement of mitochondrial structural gene sequences.

Mitochondria contain the simplest DNA molecules that are present in eukaryotes. Mitochondrial DNA (mtDNA) is easily purified, and is an important model system for studying eukaryote gene structure and basic molecular processes. The protein sequences of mitochondrial gene products have been shown to be conserved from yeast to man, and there are definite similarities at the DNA sequence level. In contrast, the overall organization of the mitochondrial genome is drastically different in these organisms. To understand this, we need to extend work on mtDNA to a wider range of species. We have chosen to study the mtDNA of Aspergillus nidulans because a particularly comprehensive analysis of this system can be achieved using genetics as well as biochemistry, and like most eukaryotes it is an obligate aerobe, whereas Saccharomyces cerevisiae is not. We have investigated whether defined pieces of particular yeast mitochondrial genes show enough homology to Aspergillus mtDNA fragments to enable the corresponding Aspergillus genes to be located on the physical map. The results reported here show that this is the case for all five genes tested, and present the first data on the physical organization of the structural genes in the mitochondrial genome of A. nidulans.

Adenosine Triphosphatases↗

Transmission dynamics and epidemiology of BSE in British cattle.

A comprehensive analysis of the bovine spongiform encephalopathy (BSE) epidemic in cattle in Great Britain assesses past, present and future patterns in the incidence of infection and disease, and allows a critical appraisal of different culling policies for eradication of the disease.

Age Factors↗

High-fidelity mRNA amplification for gene profiling.

The completion of the Human Genome Project has made possible the comprehensive analysis of gene expression, and cDNA microarrays are now being employed for expression analysis in cancer cell lines or excised surgical specimens. However, broader application of cDNA microarrays is limited by the amount of RNA required: 50-200 microg of total RNA (T-RNA) and 2-5 microg poly(A) RNA. To broaden the use of cDNA microarrays, some methods aiming at intensifying fluorescence signal have resulted in modest improvement. Methods devoted to amplifying starting poly(A) RNA or cDNA show promise, in that detection can be increased by orders of magnitude. However, despite the common use of these amplification procedures, no systematic assessment of their limits and biases has been documented. We devised a procedure that optimizes amplification of low-abundance RNA samples by combining antisense RNA (aRNA) amplification with a template-switching effect (Clonetech, Palo Alto, CA). The fidelity of aRNA amplified from 1:10,000 to 1:100,000 of commonly used input RNA was comparable to expression profiles observed with conventional poly(A) RNA- or T-RNA-based arrays.

Gene Amplification↗

Kinetics of unfolding and folding from amide hydrogen exchange in native ubiquitin.

Amide hydrogen (NH) exchange is one of the few experimental techniques with the potential for determining the thermodynamics and kinetics of conformational motions at nearly every residue in native proteins. Quantitative interpretation of NH exchange in terms of molecular motions relies on a simple two-state kinetic model: at any given slowly exchanging NH, a closed or exchange-incompetent conformation is in equilibrium with an open or exchange-competent conformation. Previous studies have demonstrated the accuracy of this model in measuring conformational equilibria by comparing exchange data with the thermodynamics of protein unfolding. We report here a test of the accuracy of the model in determining the kinetics of conformational changes in native proteins. The kinetics of folding and unfolding for ubiquitin have been measured by conventional methods and compared with those derived from a comprehensive analysis of the pH dependence of exchange in native ubiquitin. Rate constants for folding and unfolding from these two very different types of experiments show good agreement. The simple model for NH exchange thus appears to be a robust framework for obtaining quantitative information about molecular motions in native proteins.

Deuterium↗