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PubMed2003

Saccharomyces Genome Database (SGD) provides biochemical and structural information for budding yeast proteins.

The Saccharomyces Genome Database (SGD: http://genome-www.stanford.edu/Saccharomyces/) has recently developed new resources to provide more complete information about proteins from the budding yeast Saccharomyces cerevisiae. The PDB Homologs page provides structural information from the Protein Data Bank (PDB) about yeast proteins and/or their homologs. SGD has also created a resource that utilizes the eMOTIF database for motif information about a given protein. A third new resource is the Protein Information page, which contains protein physical and chemical properties, such as molecular weight and hydropathicity scores, predicted from the translated ORF sequence.

Amino Acid Motifs↗
PubMed2004

e-Quantum chemistry free resources.

Among computational chemistry methods, quantum mechanics calculates geometries and electronic structures with accuracy especially for systems with electronic delocalization. The use of a multiconfigurational approach is able to treat highly degenerated states such as those occurring at the transition state in some chemical reactions. Moreover, an accurate description of potential energy surfaces can be obtained with the evaluation of the dynamic electron correlation effects by this approach. Molecular properties range from simple dipole moments, vibrational frequencies or IR intensities to frequency dependent hyperpolarizabilities. Quantum chemical calculations are thus an attractive source of molecular descriptors which can be used in QSAR/QSPR studies and which can express all electronic and geometric properties of molecules. A survey and a comparison of the performance of free e-resources for semi-empirical and ab initio calculations is provided.

Data Collection↗
PubMed2005

SpliceInfo: an information repository for mRNA alternative splicing in human genome.

We have developed an information repository named SpliceInfo to collect the occurrences of the four major alternative-splicing (AS) modes in human genome; these include exon skipping, 5'-alternative splicing, 3'-alternative splicing and intron retention. The dataset is derived by comparing the nucleotide and protein sequences available for a given gene for evidence of AS. Additional features such as the tissue specificity of the mRNA, the protein domain contained by exons, the GC-ratio of exons, the repeats contained within the exons, and the Gene Ontology are annotated computationally for each exonic region that is alternatively spliced. Motivated by a previous investigation of AS-related motifs such as exonic splicing enhancer and exonic splicing silencer, this resource also provides a means of identifying motifs candidates and this should help to identify potential regulatory mechanisms within a particular exonic sequence set and its two flanking intronic sequence sets. This is carried out using motif discovery tools to identify motif candidates related to alternative splicing regulation and together with a secondary structure prediction tool, will help in the identification of the structural properties of such regulatory motifs. The integrated resource is now available on http://SpliceInfo.mbc.NCTU.edu.tw/.

Alternative Splicing↗
PubMed2005

The crystal structure of polyhydroxybutyrate depolymerase from Penicillium funiculosum provides insights into the recognition and degradation of biopolyesters.

Polyhydroxybutyrate is a microbial polyester that can be produced from renewable resources, and is degraded by the enzyme polyhydroxybutyrate depolymerase. The crystal structures of polyhydroxybutyrate depolymerase from Penicillium funiculosum and its S39 A mutant complexed with the methyl ester of a trimer substrate of (R)-3-hydroxybutyrate have been determined at resolutions of 1.71 A and 1.66 A, respectively. The enzyme is comprised of a single domain, which represents a circularly permuted variant of the alpha/beta hydrolase fold. The catalytic residues Ser39, Asp121, and His155 are located at topologically conserved positions. The main chain amide groups of Ser40 and Cys250 form an oxyanion hole. A crevice is formed on the surface of the enzyme, to which a single polymer chain can be bound by predominantly hydrophobic interactions with several hydrophobic residues. The structure of the S39A mutant-trimeric substrate complex reveals that Trp307 is responsible for the recognition of the ester group adjacent to the scissile group. It is also revealed that the substrate-binding site includes at least three, and possibly four, subsites for binding monomer units of polyester substrates. Thirteen hydrophobic residues, which are exposed to solvent, are aligned around the mouth of the crevice, forming a putative adsorption site for the polymer surface. These residues may contribute to the sufficient binding affinity of the enzyme for PHB granules without a distinct substrate-binding domain.

Amino Acid Sequence↗
PubMedDate not supplied

The Shanghai case: A qualitative evaluation of community health reform in response to the challenge of population ageing.

Shanghai's health care system is facing a serious challenge of an ageing population, as 14% of its 17 million residents are 65 or older. In 2000, a community health reform was implemented to provide comprehensive and continuous primary care to community residents with a focus on seniors. The study employed the theoretical framework of examining primary care in terms of the constellation of its four unique elements (first contact, comprehensiveness, longitudinality and coordination) and three healthcare components (structure, process and outcome). The study aimed to evaluate the extent to which the reform has achieved its process goals and how the organizational context influenced the level of implementation. In-depth interviews with 25 health providers, 15 seniors and four community leaders were carried out. The study found that the Shanghai community health reform has improved the structure and process of primary care regarding first contact, comprehensiveness and longitunality. However, the reform is constrained by structural barriers on seniors' financial access to resources and the capacity of primary care providers. The previous organization system also constrains the reform in CHCs financing and administration. The Shanghai case illustrates that a broad societal view has to be taken when analysing health reforms, which requires the involvement of multiple sectors including the government, health providers and health consumers.

Aged↗
PubMed2000

Comparative sequence analysis of 634 kb of the mouse chromosome 16 region of conserved synteny with the human velocardiofacial syndrome region on chromosome 22q11.2.

Mouse genomic DNA sequence extending 634 kb on proximal mouse chromosome 16 was compared to the corresponding human sequence from chromosome 22q11.2. Haploinsufficiency for this region results in velocardiofacial syndrome (VCFS) in humans. The mouse region is rearranged into three conserved blocks relative to human, but gene content and position are highly conserved within these blocks. Examination of the boundaries of one of these blocks suggested that the evolutionary chromosomal rearrangement occurred in the mouse lineage, resulting in inactivation of the mouse orthologue of ZNF74. Sequence analysis identified 21 genes and 15 ESTs. These include 2 novel genes, Srec2 and Cals2, and previously undescribed splice variants of several other genes. Exon discovery was carried out using GRAIL2, MZEF, or comparative analysis across 491 kb of conserved mouse and human sequence. Sequence comparison was highly effective, identifying every gene and nearly every exon without the high frequency of false-positive predictions seen when algorithmic methods were used alone. In combination, these procedures identified every gene with no false-positive predictions. Comparative sequence analysis also revealed regions of extensive conservation among noncoding sequences, accounting for 6% of the sequence. A library of such sequences has been established to form a resource for generalized studies of regulatory and structural elements.

Abnormalities, Multiple↗
PubMed1978

Environmental adaptation of the mental patient.

An ecological model suggests looking at the hospitalized mental patient in terms of how well the resources available in the environment fit his individual needs. This study explores the relationship between the environmental fit of patients while they are in the hospital and their adaptation to the community once they have left. Data on individual needs and evaluations of environmental resources were obtained through a series of structured interviews. Results indicate that the more a patient feels the hospital environment is a good fit, the longer he stays there. Hospital fit is positively related to fit in the community, but the latter is related only to the degree of symptomatology exhibited by the expatient in the community and not to how long he is able to remain out of the hospital. Implications of the findings and the model are discussed.

Adaptation, Psychological↗
PubMed1990

Toxicological information series, II. A survey of toxicology information.

The structure of toxicology information is outlined. Key resources, both print and electronic, are described and the role of organizations is discussed on national and world levels. The section on computerized information covers systems such as TOXNET, CIS, and the ANSWER workstation.

Dictionaries, Chemical as Topic↗
PubMed1983

Loss, stress and readjustment: the structure of coping with bereavement and disability.

On the basis of recent developments in the study of readjustment, a comprehensive formal theoretical framework was suggested, predicting the factors enhancing and impeding readjustment after a traumatic irrevocable loss (bereavement and disability) and empirically supported. Empirical investigation and application of multivariate techniques of data analysis revealed an identical structure of the content universe of readjustment for three groups: war widows, bereaved parents and disabled army veterans. The structure ascertained the hypothesized predominance of individual resources--and particularly those which facilitate affective interaction relationship--as well as of primary groups' emotional support in enhancing readjustment, compared to the limited efficacy of formal rehabilitation agencies. In the realm of instrumental coping assistance, data ascertained the efficacy of 'resource enhancing' support (e.g. vocational training) in advancing readjustment. Data also ascertained that the weight of individual resources and primary group support in facilitating readjustment is greater than the effect of the severity of the disability, and plays a greater role in readjustment than lapse of time since the loss. The significance of the study is in the development and empirical verification of a formal comprehensive and testable framework of readjustment to change following a traumatic loss. Though the universal validity of the framework needs further proof, there seems to be sufficient basis for assuming such validity until empirically verified. It is suggested to view this study as a first step toward a general model of readjustment. The study seems particularly contributing to the body of knowledge in the realm of stress and coping in light of the difficulties in arriving at a valid empirical verification of the stressful life events leads to coping leads to homeostasis relationship.

Adult↗
PubMed1994

Forming and reforming the market for third-party purchasing of health care: a German perspective.

Germany is known for its comprehensive health care coverage by sickness funds and private health insurers and its successful cost containment policy. The stabilization of health care expenditures as a percentage of GNP was enforced by five cost containment laws since 1977. The last one became effective in 1993 and the next ones are planned for 1996 and 2000. The 1993 law has initiated drastic changes of the system. Office based physicians will be paid by a mixture of capitation, fee-for-service and fees for combined service packages. The hospital financing will be transformed from the current per diem remuneration to a payment system where per diems are combined with payments based on diagnostic related groups and patient management categories. Up till now many restrictions exist for insurees to switch sickness funds. These limitations were removed by the 1993 law. To allow unbiased competition between sickness funds, a risk compensation pool, some kind of statutory reinsurance, will transfer financial resources from sickness funds with good risk structure to those with many bad risks. In many respects health policy has imposed what health economists have recommended for a long time. However, there is some doubt whether increased competition will really increase efficiency of providing medical care because it takes place in a highly regulated market.

Cost Control↗
PubMed2004

Toward consistent assignment of structural domains in proteins.

The assignment of protein domains from three-dimensional structure is critically important in understanding protein evolution and function, yet little quality assurance has been performed. Here, the differences in the assignment of structural domains are evaluated using six common assignment methods. Three human expert methods (AUTHORS (authors' annotation), CATH and SCOP) and three fully automated methods (DALI, DomainParser and PDP) are investigated by analysis of individual methods against the author's assignment as well as analysis based on the consensus among groups of methods (only expert, only automatic, combined). The results demonstrate that caution is recommended in using current domain assignments, and indicates where additional work is needed. Specifically, the major factors responsible for conflicting domain assignments between methods, both experts and automatic, are: (1) the definition of very small domains; (2) splitting secondary structures between domains; (3) the size and number of discontinuous domains; (4) closely packed or convoluted domain-domain interfaces; (5) structures with large and complex architectures; and (6) the level of significance placed upon structural, functional and evolutionary concepts in considering structural domain definitions. A web-based resource that focuses on the results of benchmarking and the analysis of domain assignments is available at

Algorithms↗
PubMedDate not supplied

[Awareness of deficits and anosognosia in Alzheimer's disease].

This article reviews studies concerning unawareness of deficits in Alzheimer's disease. Unawareness of the deficits associated with dementia has frequently been reported in clinical descriptions of the later stages of the disease. Consistent with the literature, we shall use the expressions impaired awareness, unawareness of deficits, anosognosia, and lack of insight interchangeably. Anosognosia can be defined as an impaired ability to recognize the presence or appreciate the severity of deficits in sensory, perceptual, motor, affective, or cognitive functioning. Unawareness has been operationally defined in a variety of ways. Unawareness can be measured as the discrepancy between the patient's self-report and the report of a natural caregiver or the clinical rating of a health care professional. The reports generally concern with several domains, most often memory domain. Discrepancy between subjective ratings and neuropsychological performance during clinical assessment has also been used to measure anosognosia. Advantages, limits and equivalence of these different methods are discussed. The impact of family burden has to be considered as a systematic methodological bias if the natural caregiver is implicated in the assessment. The psychometric properties of the clinical assessment have also to be discussed. The psychological nature of the discrepancy between patient's self-report and cognitive performances has to be analyzed and the necessity of ecological protocols, longitudinal assessment is discussed. The major results concerning prevalence, nature of anosognosia and the associated disorders are analyzed. In particular, the notion of heterogeneity of anosognosia and the correlates with depression, severity of dementia and executive dysfunction are developed. Prevalence is largely function of methodological choices and conceptual definition of anosognosia. Three major researches are compared and the contrast between their results (prevalence from 23% to 75% in AD) is analyzed. Particularly, the hypotheses about anosognosia play a great role in the findings. At first time of research, anosognosia was considered as a general symptom and so, studies were centered on the unawareness related to only one cognitive function. But the 90's findings suggest that patients with AD have impaired awareness for some types of deficits (affective or cognitive functions) but can more accurately appraise other deficits. Currently anosognosia cannot be considered as a unitary entity. It may be that patients with AD are unaware of some types of deficits, but are aware of others, and that nature and intensity of their anosognosia may change during the course of the dementia. It has been proposed that depression is more common when disease is mild and awareness of deficits is retained, and that depression becomes less common when disease increases and awareness declines. Depression is conceived as a psychological reaction. However, the correlations between anosognosia level and depression scores reveal either weak relationships or no relationships. Alternative hypothesis is that anosognosia is related to overall dementia severity and to memory impairment. However, correlations of unawareness of deficits, i.e. the difference between self-report and relative's -rating, with a measure of dementia and with patient's performance on objective memory tasks did not reveal strong, consistent relationships between degree of anosognosia and severity of dementia or of memory impairment. On the other hand, the best neuropsychological predictors of impaired insight are Trail Making Test or Wisconsin Card Sorting Test, i.e. tests that have been shown to be sensitive to a frontal lobe dysfunction. SPECT measures of regional cerebral blood flow have been used in the study of anosognosia. The main findings are that unawareness in AD is associated with hypoperfusion of the right dorsolateral frontal lobe. Anosognosia may result from the disruption of broader cognitive process that is subsumed by the frontal lobes. The mechanisms of unawareness are not well known and studies are essentially descriptive works and try to give information about pre-valence or clinical associated disorders of anosognosia. Several authors have proposed that unawareness is part of a defensive mechanism that would protect demented patients from depressive feelings. Other authors have proposed that anosognosia may result from dysfunction in specific brain areas. It is suggested that anosognosia in AD may result from greater impairment of a central executive system, which is a metacognitive structure that is involved in planning, cognitive resource allocation, and set shifting. The main problem with those both major hypotheses is their incapacity to explain the heterogeneous impairment of awareness. Other authors speculate that the impaired insight of Alzheimer's disease has several components, psychological and neuropsychological. This view doesn't seem convincing and new components have to be taken in account in order to propose a theoretical framework about anosognosia in AD. Environmental and dispositional components and an interactional view could be interesting. Those possible directions for future research and solutions concerning methodological and conceptual problems are outlined. In particular, a neuro-psycho-social view of unawareness is introduced.

Aged↗
PubMed2003

Data use and information creation: challenges for marine scientists and for managers.

In the coastal waters of European countries and in the offshore waters of the north-east Atlantic, there is an increasing need for scientists to meet challenging objectives, such as to identify meaningful measures of 'quality', and to recommend 'indicators' to underpin implementation of directives, conventions, statutes and other more informal national and international initiatives. Those indicators may relate to particular species or habitats, to changes in physical and chemical characteristics, and even to the use to which the system is put. The problems to be overcome are difficult, but new and developing approaches will make a significant contribution. The approaches include: criteria to identify 'sensitivity' and 'importance', structures to organise information and electronic information resources to access data. The real challenge is to make the results of the various scientific initiatives relevant to and understandable by a wide range of customers with similar overlapping requirements, and thus make a genuine contribution to protecting the marine environment. Above and beyond that is the need for scientists to drive the agenda to enable real and lasting progress to be made towards ecosystem-based management of our seas and a proper consideration of what 'sustainability' may mean in the marine environment and how we utilise its resources.

Conservation of Natural Resources↗
PubMedDate not supplied

The role of prosody in discourse processing.

The influence of prosody and its visual analog, punctuation, in text comprehension was investigated in two experiments. In the first experiment 20 subjects listened to three taped passages of equal length and difficulty varying in intonation (normal, monotonous, or altered) and were tested on tasks of text comprehension and word recognition. In the second experiment 20 new subjects read the same passages but with varying punctuation (appropriate, no punctuation, or altered) and were also tested on text comprehension and word recognition. Subjects' reading time was also recorded. ANOVA results revealed that altered prosody and punctuation affect performance in a similar fashion and seriously impair text comprehension and word recognition. This sensitivity to altered intonation suggests that linguistic prosody not only supplies redundant cues for judging sentence structure but that it also manages attentional resources to help with semantic encoding of lexical units and with the organization of linguistic information in long term memory.

Adult↗
PubMed2001

Analyzing differences in the costs of treatment across centers within economic evaluations.

OBJECTIVES: Assessments of health technologies increasingly include economic evaluations conducted alongside clinical trials. One particular concern with economic evaluations conducted alongside clinical trials is the generalizability of results from one setting to another. Much of the focus relating to this topic has been on the generalizability of results between countries. However, the characteristics of clinical trial design require further consideration of the generalizability of cost data between centers within a single country, which could be important in decisions about adoption of the new technology. METHODS: We used data from a multicenter clinical trial conducted in the United Kingdom to assess the degree of variation in costs between patients and between treatment centers and the determinants of the degree of such variation. RESULTS: The variation between patients was statistically significant for both the experimental and conventional treatments. However, the degree of variation between centers was only statistically significant for the experimental treatment. Such variation appeared to be a result of hospital practice, such as payment mechanisms for staff and provision of hostel accommodation, rather than variations in physical resource use or substantive differences in cost structure. CONCLUSIONS: Multicenter economic evaluations are necessary for determining the variations in hospital practice and characteristics that can in turn determine the generalizability of study results to other settings. Such analyses can identify issues that may be important in adopting a new health technology. Analysis is required of similar large multicenter trials to confirm these conclusions.

Bronchial Neoplasms↗
PubMed2000

Isolation and biochemical characterization of peroxisomes from cultured rat glial cells.

Peroxisomes are now recognized to play important cellular functions and its dysfunction leads to a group of neurological disorders. This study reports peroxisomal enzyme activities in cultured glial cells and peroxisomes isolated from cultured oligodendrocytes and C6 glial cells. Peroxisomal enzyme activities were found to be higher in oligodendroglial cells than in astrocytes or mixed glial cells. We also developed a method for the isolation of peroxisomes from glial cells by a combination of differential and density gradient centrifugation techniques. Peroxisomes from oligodendrocytes in nycodenz gradient were isolated at a density of 1.165 g/ml +/- 0.011. Activities of dihydroxyacetone phosphate acyl transferase, beta-oxidation of lignoceric acid and alpha-oxidation of phytanic acid were almost exclusively associated with the distribution of catalase activity (a marker enzyme for peroxisomes) in the gradient. This protocol should be a resource for studies designed to investigate the structure and function of peroxisomes in brain cells.

Animals↗
PubMed2004

Contribution of frontal and temporal lobe function to memory interference from divided attention at retrieval.

On the basis of their scores on composite measures of frontal and temporal lobe function, derived from neuropsychological testing, seniors were divided preexperimentally into 4 groups. Participants studied a list of unrelated words under full attention and recalled them while concurrently performing an animacy decision task to words, an odd-digit identification task to numbers, or no distracting task. Large interference effects on memory were produced by the animacy but not by the odd-digit distracting task, and this pattern was not influenced by level of frontal or temporal lobe function. Results show associative retrieval is largely disrupted by competition for common representations, and it is not affected by a reduction in general processing resources, attentional capacity, or competition for memory structures in the temporal lobe.

Aged↗
PubMedDate not supplied

Anatomical, cellular and molecular analysis of 8,000-yr-old human brain tissue from the Windover archaeological site.

Recovery and analysis of ancient tissue and bone of human origin has long been extensively investigated. Only recently, however, has it been technically possible to recover genetic material from ancient human and animal samples. As both previous studies involved dried tissue, it is important to determine whether other conditions may also preserve ancient tissue and genetic material. We describe here an analysis of preserved human bone and soft matter discovered in 1984-85 buried in a small swampy pond in central Florida. The recovered skeletal material represented a minimum of 40 individuals of both sexes and various ages. Corrected radiocarbon dates directly from bone and from peat matrix gave consistent ages in the range of 7,790 to 8,290 yr before present (BP). Nine individuals with intracranial soft matter were recovered and, in five of these, material recognizable as preserved or replaced brain tissue was present. Further analysis demonstrated gross anatomical features, remnant cellular structure and human DNA. As this find appears to be the oldest-known example of preserved human cell structure and DNA, it represents a significant resource for both anthropological and genetic studies.

Adult↗