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A database of recombinant viruses and recombinant viral vectors available from the RIKEN DNA bank.

BACKGROUND: Viral vectors are required as gene-delivery systems for gene therapy and basic research. Recombinant adenoviruses (rAds) expressing genes of interest are being developed as research tools and many studies in vitro and in vivo have already been performed with such rAds. METHODS: Shuttle vectors for rAds were constructed with full-length cDNAs and rAds were generated in HEK293 cells by the COS-TPC method. The rAds and shuttle vectors were developed by the Japanese research community and deposited in the RIKEN DNA Bank (RDB; http://www.brc.riken.jp/lab/dna/en/) for distribution to the scientific community. The Recombinant Virus Database (RVD; http://www.brc.riken.jp/lab/dna/rvd/) was established at the RIKEN BioResource Center (BRC) in Japan as the source of information about and distribution of the various resources. RESULTS: The RIKEN BRC is releasing more than 300 recombinant viruses (RVs) and 500 shuttle vectors, as well as all related information, which is included in a newly established database, the RVD. The RVD consists of (i) information about the RVs, the inserted cDNAs and the shuttle vectors; (ii) data about sequence-tagged sites (STSs) that are markers of viral DNAs; and (iii) experimental protocols for the use of RVs. CONCLUSIONS: The new database and available resources should be very useful to scientists who are studying human gene therapy and performing related basic research. It is a web-interfaced flat-file database that can be accessed through the internet. Moreover, all of the resources deposited in the RDB, which is a public facility in Japan, are available to researchers around the world.

Adenoviridae↗

Distribution and speciation of metals in annual rings of black willow.

Information on the spatial distribution and speciation of metals in nonhyperaccumulator plants is lacking. This study used synchrotron X-ray fluorescence (SXRF) compositional imaging to investigate the spatial distribution of Ni, Mn, Cu, Zn, and Fe in annual rings of black willow (Salix nigra L.) collected from a metal-contaminated area, and used X-ray absorption spectroscopy (XAS) to investigate Ni and Mn speciation in regions of the annual rings with elevated Ni concentrations. Annual rings were recollected in early 2003 from an individual known to be enriched with Ni from previous studies. Compositional imaging showed Ni and associated co-contaminants conservatively located in an annual ring. When compared with a corresponding photomicrograph, SXRF compositional images showed that metals were sharply constrained by the boundaries of the annual ring, indicating a sudden onset and cessation of uptake, and a lack of post-growth mobility of the metals. There was a particularly strong correlation between Ni and Mn in the metal-enriched annual ring (r = 0.8822), which suggested similar transport and binding behavior of these elements. X-ray absorption spectroscopy showed Ni and Mn to be present in the 2+ oxidation state. X-ray absorption near edge structure spectroscopy (XANES) fingerprinting of localized, highly Ni-enriched regions within the lumen of willow xylem vessels found similarities with Ni-pectic acid complexes, Ni-histidine, and NiSO4.

Environmental Monitoring↗

Spatial and seasonal distribution of Culicoides imicola in Iberia in relation to the transmission of African horse sickness virus.

Collections of biting midges were made over 24 months from sixty sites spread across Iberia. Information on the distribution of the vector of African horse sickness virus, Culicoides imicola, from these 3119 samples showed that this species was annually present across south-western Spain as far as 3 degrees 53'W and throughout most of Portugal, up to 41 degrees 5'N. C. imicola was found in all areas where African horse sickness epizootics had occurred in 1987-90 and also in areas outside the epizootic zones. Seasonal patterns of capture success of C. imicola, from seventeen frequently sampled sites where the vector was present, usually showed a late summer-early autumn peak. At the sites furthest south there was a discrete peak, mostly in September or October, before and after which the numbers captured increased or decreased steadily. At higher latitudes peak abundances occurred as early as May or as late as November, population build up was less uniform and numbers often declined rapidly after the peak was reached. Both the distribution and seasonal abundance patterns closely matched transmission patterns of African horse sickness virus, which rose during late summer and caused most cases during the autumn months.

African Horse Sickness↗

Distribution of lamellae in human femoral shafts deformed by bending with inferences on mechanical properties.

On the basis of previous investigations indicating that the distribution of osteonic and interstitial lamellae in a normal femur depends on its mechanical properties, a procedure has been devised to provide information on the distribution of lamellae in human femora diaphyses deformed by bending. To achieve this, exactly plane parallel cross sections, 100 micron thick, were prepared from the portion of maximum bending, using an annular blade microtome. An index of the distribution of longitudinal lamellae (whose fiber bundles and crystallites have a longitudinal course and withstand loading by tension) and transverse lamellae (whose fiber bundles and crystallites have a transverse course and withstand loading by compression) was determined using circularly polarized light as illuminating source and a Quantimet 720 image analyzing computer. The results show that, even in a pathologically deformed bone, both the microscopic structure of sections at the level of osteonic and interstitial lamellae, and their macroscopic shape may be governed by the distribution of the forces active in bone.

Biomechanical Phenomena↗

The distribution of follicular units in the Chinese scalp: implications for reconstruction of natural-appearing hairlines in Orientals.

BACKGROUND: Follicular transplantation using hair in its naturally occurring groups, called follicular units (FUs), has become the most popular technique in hair restoration surgery. Recently follicular transplantation was performed with a qualitative and quantitative concept to achieve the best clinical result. The characteristics and distribution of FUs are well studied in Caucasians and widely applied in hair transplantation surgery. OBJECTIVE: In order to understand the normal distribution of FUs in the Chinese scalp, we counted the number of hairs and FUs in normal Chinese scalp to provide general information for surgical planning and design in bald Chinese patients. METHODS: A total of 50 normal and 50 bald Chinese adults were enrolled to count the hairs on their scalp. One hundred bald patients receiving hairline reconstruction were also prospectively quantitatively evaluated. RESULTS: In normal Chinese scalp, an average 71.78 FUs/cm(2) and 137.08 hairs/cm(2) were calculated with a follicular density of 1.91 hairs/FU. Two-hair FUs are the predominate group (50.29%). In bald patients, an average of 68.07 FUs/cm(2) was found, which was less than that of the occipital scalp in normal nonbald patients. In reconstruction of the frontal hairline, a total of 700-1000 FUs were implanted with an average density of 30 FUs/cm(2). CONCLUSION: We found the average number of FUs (0.72 FU/mm(2)) was less than that in Caucasian patients (1 FU/mm(2)). The average density of 30 FUs/cm(2) implanted was suitable to reconstruct a natural frontal hairline in bald Chinese patients, which can achieve about 40% of normal hair density. Our results could provide the hair surgeon with general information about hair distribution on the Chinese scalp for surgical planning and design in their patients.

Adult↗

Multicenter surveillance of invasive meningococcal infections in children.

OBJECTIVES: Meningococcal disease continues to result in substantial morbidity and mortality in children, but there is limited recent surveillance information regarding serogroup distribution and outcome in children in the United States. The objective of this study was to collect demographic, clinical, laboratory, and outcome information for infants and children who had Neisseria meningitidis infections of various serogroups and were cared for in 10 pediatric hospitals. METHODS: Investigators at each of the participating hospitals identified children with meningococcal infections and collected demographic and clinical information using a standard data form. Meningococcal isolates were sent to a central laboratory for serogrouping by slide agglutination and penicillin susceptibility. RESULTS: From January 1, 2001, through March 15, 2005, 159 episodes of systemic meningococcal infections were detected. The greatest numbers of children were younger than 12 months (n = 41) or were 12 to 24 months of age (n = 22). Meningitis was the most common clinical manifestation of disease accounting for 112 (70%) cases; 43 (27%) children had bacteremia only. Children who were younger than 5 years (17 of 102) were significantly less likely to require mechanical ventilation than children who were 5 to 10 years of age (12 of 24) or children who were older than 10 years (13 of 33). Overall, 55 (44%) isolates were serogroup B, 32 (26%) were serogroup C, and 27 (22%) were serogroup Y. All but 1 isolate (intermediate) were susceptible to penicillin. The overall mortality rate was 8% (13 of 159) but was greater for children who were > or = 11 years of age (7 [21.2%] of 33) than for children who were younger than 11 years (6 [4.8%] of 126). Unilateral or bilateral hearing loss occurred in 14 (12.5%) of 112 children with meningitis. CONCLUSIONS: The morbidity and the mortality of meningococcal infections are substantial. With the recent licensure of meningococcal conjugate vaccines, our baseline trends in meningococcal disease can be compared with those seen after widespread vaccination to assess the success of routine immunization.

Adolescent↗

Realization of real-time clinical data integration using advanced database technology.

As information & communication technologies have advanced, interest in mobile health care systems has grown. In order to obtain information seamlessly from distributed and fragmented clinical data from heterogeneous institutions, we need solutions that integrate data. In this article, we introduce a method for information integration based on real-time message communication using trigger and advanced database technologies. Messages were devised to conform to HL7, a standard for electronic data exchange in healthcare environments. The HL7 based system provides us with an integrated environment in which we are able to manage the complexities of medical data. We developed this message communication interface to generate and parse HL7 messages automatically from the database point of view. We discuss how easily real time data exchange is performed in the clinical information system, given the requirement for minimum loading of the database system.

Clinical Laboratory Information Systems↗

The information encrypted in accurate peptide masses-improved protein identification and assistance in glycopeptide identification and characterization.

Analytically useful information from accurate mass data for peptides with an error of </=20 ppm is discussed. The deltamass (= mass value following the decimal point) distribution of natural peptides is extracted from a protein database. Compared with the random peptide data, the natural data show a higher average deltamass value and a smaller width of the mass distribution. This deviation can be ascribed to the non-random abundances of the standard amino acids. In particular, accurate mass data for peptides located near the edges of the natural mass distribution contain analytical information. Mass data near the edges generate very few hits in a protein database search and are therefore highly specific for protein identification. Mass signals near the low-mass edge indicate either a high probability that the peptide contains one or several cysteine sites, or that the peptide is highly acidic due to the presence of several D and/or E residues or that it is a glycopeptide. Mass data near the high-mass edge indicate a non-polar peptide with a high abundance of the non-polar amino acids leucine, isoleucine and valine. An Internet page is introduced that analyzes the deviation of a peptide mass from the average deltamass value and that supports the characterization of glycopeptides found near the low-mass edge of the mass distribution.

Amino Acid Sequence↗

Direct measurement of aluminum uptake and distribution in single cells of Chara corallina.

Quantitative information on the uptake and distribution of Al at the cellular level is required to understand mechanisms of Al toxicity, but direct measurement of uptake across the plasma membrane has remained elusive. We measured rates of Al transport across membranes in single cells of Chara corallina using the rare (26)Al isotope, an emerging technology (accelerator mass spectrometry), and a surgical technique for isolating subcellular compartments. Accumulation of Al in the cell wall dominated total uptake (71-318 microgram m(-2) min(-1)), although transport across the plasma membrane was detectable (71-540 ng m(-2) min(-1)) within 30 min of exposure. Transport across the tonoplast was initially negligible, but accelerated to rates approximating uptake across the plasma membrane. The avacuolate protoplasm showed signs of saturation after 60 min, but continued movement across the plasma membrane was supported by sequestration in the vacuole. Saturation of all compartments was observed after 12 to 24 h. Accumulation of Al in the cell wall reflected variation in [Al(3+)] induced by changes in Al supply or complexing ligands, but was unaffected by pH. In contrast, transport across the plasma membrane peaked at pH 4.3 and increased when [Al(3+)] was reduced by complexing ligands. Cold temperature (4 degrees C) reduced accumulation in the cell wall and protoplasm, whereas 2,4-dinitrophenol and m-chlorocarbonylcyanidephenyl hydrazone increased membrane transport by 12- to 13-fold. Our data suggest that the cell wall is the major site of Al accumulation. Nonetheless, membrane transport occurs within minutes of exposure and is supported by subsequent sequestration in the vacuole. The rapid delivery of Al to the protoplasm suggests that intracellular lesions may be possible.

2,4-Dinitrophenol↗

Of jugglers, mechanics, communities, and the thyroid gland: how do we achieve good quality data to improve public health?

Our knowledge about the distribution of exposures to toxic chemicals in various communities is limited. Only about 6% of approximately 1,400 toxic chemicals have been identified in surveys. Even for those chemicals that are measured, information is often insufficient to identify smaller populations at high risk. The question is whether information about the distribution of diseases in communities can help identify environmental risks, indicate areas of concern, and thus substitute exposure information. Thyroid disorders represent a large group of diseases that cannot be recorded into registries because of the lack of clear caseness; community-based monitoring of subtle health effects is needed. Thus, to identify potential health risks in communities, epidemiologic studies including effect and human exposure monitoring are necessary. However, to overcome the limitation of nonsystematic case studies, the development of a network of exposed communities concerned about exposures is proposed. A network would provide assessments of exposures and health outcomes, with different communities mutually serving as exposed and control groups. Such a network would foster communication and prevention measures within communities often left out of the dissemination of information about risks identified in studies conducted with residents of these communities.

Communication↗

(13)C-NMR isotopomer distribution analysis: a method for measuring metabolic fluxes in condensation biosynthesis.

(13)C NMR spectroscopy associated with the use of (13)C-enriched substrates is a powerful tool to investigate intracellular metabolism because of the wealth of information contained in the distribution of isotopes in key metabolites. A new method of using (13)C label distribution measurements in carbon skeletons of metabolites to estimate metabolic fluxes through biochemical reaction networks is presented here. This method can be applied to metabolite synthesis occurring by condensation reactions of the type nA --> B, where n is the number of precursor A molecules needed to synthesize one molecule of product B. NMR isotopomer distribution analysis (NMR-IDA) involves the introduction of a (13)C-enriched precursor, and measurements of the (13)C positional enrichments at just one carbon atom position of the product B via (13)C NMR spectroscopy. Information on isotopomer distribution is obtained, and data are analyzed according to a mathematical model based on multinomial probability expressions to obtain the best fit between theoretical and experimental (13)C label distribution. The use of the NMR-IDA method allows for estimation of two key parameters representing the fractional flux of (13)C-enriched tracer A molecules to total precursor A pool and the fraction of product B synthesized in the presence of a (13)C-enriched source, respectively. A practical example of NMR-IDA application to fatty acid synthesis from [(1,2 (13)C(2))acetyl]-L-carnitine in cultured primary astrocytes is also presented.

Animals↗

Gaps in policy-relevant information on burden of disease in children: a systematic review.

BACKGROUND: Valid information about cause-specific child mortality and morbidity is an essential foundation for national and international health policy. We undertook a systematic review to investigate the geographical dispersion of and time trends in publication for policy-relevant information about children's health and to assess associations between the availability of reliable data and poverty. METHODS: We identified data available on Jan 1, 2001, and published since 1980, for the major causes of morbidity and mortality in young children. Studies with relevant data were assessed against a set of inclusion criteria to identify those likely to provide unbiased estimates of the burden of childhood disease in the community. FINDINGS: Only 308 information units from more than 17,000 papers identified were regarded as possible unbiased sources for estimates of childhood disease burden. The geographical distribution of these information units revealed a pattern of small well-researched populations surrounded by large areas with little available information. No reliable population-based data were identified from many of the world's poorest countries, which account for about a third of all deaths of children worldwide. The number of new studies diminished over the last 10 years investigated. INTERPRETATION: The number of population-based studies yielding estimates of burden of childhood disease from less developed countries was low. The decreasing trend over time suggests reductions in research investment in this sphere. Data are especially sparse from the world's least developed countries with the highest child mortality. Guidelines are needed for the conduct of burden-of-disease studies together with an international research policy that gives increased emphasis to global equity and coverage so that knowledge can be generated from all regions of the world.

Acute Disease↗

Heterogeneity of endocytic proteins: distribution of clathrin adaptor proteins in neurons and glia.

Clathrin adaptor protein (AP)180 is a synaptic protein that regulates the assembly of clathrin-coated vesicles. Several endocytic proteins including AP2, CALM, and epsin 1 have functions or molecular structures similar to AP180. We determined if AP180 associates with functional synapses in cultured hippocampal neurons. We also compared the expression pattern of AP180 with the other endocytic proteins. The distribution of AP180 corresponded with the synaptic vesicle-associated protein synapsin I, and with functional presynaptic terminals labeled with the styryl dye FM1-43. Synaptic AP2 colocalized with AP180, but the distribution of AP2 was not limited to synapses of neurons and it was also expressed in glia. CLAM and epsin 1 immunoreactivities were also detected in both neurons and glia. Unlike AP180, the neuronal immunoreactivity of CALM was not intense in the synaptic puncta. Epsin 1 immunoreactivity was found in both synaptic and extrasynaptic sites, and its synaptic distribution only partially overlapped with that of AP180. These results support roles for AP180 in synaptic function in neurons. The findings also provide information on the distribution of AP2, CALM, and epsin 1 in cells of the nervous system that suggest different roles for these endocytic proteins in the biology of these cells.

Adaptor Proteins, Vesicular Transport↗

GeneNotes--a novel information management software for biologists.

BACKGROUND: Collecting and managing information is a challenging task in a genome-wide profiling research project. Most databases and online computational tools require a direct human involvement. Information and computational results are presented in various multimedia formats (e.g., text, image, PDF, word files, etc.), many of which cannot be automatically processed by computers in biologically meaningful ways. In addition, the quality of computational results is far from perfect and requires nontrivial manual examination. The timely selection, integration and interpretation of heterogeneous biological information still heavily rely on the sensibility of biologists. Biologists often feel overwhelmed by the huge amount of and the great diversity of distributed heterogeneous biological information. DESCRIPTION: We developed an information management application called GeneNotes. GeneNotes is the first application that allows users to collect and manage multimedia biological information about genes/ESTs. GeneNotes provides an integrated environment for users to surf the Internet, collect notes for genes/ESTs, and retrieve notes. GeneNotes is supported by a server that integrates gene annotations from many major databases (e.g., HGNC, MGI, etc.). GeneNotes uses the integrated gene annotations to (a) identify genes given various types of gene IDs (e.g., RefSeq ID, GenBank ID, etc.), and (b) provide quick views of genes. GeneNotes is free for academic usage. The program and the tutorials are available at: http://bayes.fas.harvard.edu/genenotes/. CONCLUSIONS: GeneNotes provides a novel human-computer interface to assist researchers to collect and manage biological information. It also provides a platform for studying how users behave when they manipulate biological information. The results of such study can lead to innovation of more intelligent human-computer interfaces that greatly shorten the cycle of biology research.

Biology↗

Operational and scientific notes.

Published information on the distribution of Aedes albopictus in South Carolina is limited and fragmentary. This paper draws on various published and unpublished sources and presents synoptic information on the occurrence of the mosquito in 17 counties. Additional surveys are required to establish the infestation status of the other 29 counties in the state.

Aedes↗

Comparison of three joint simulator wear debris isolation techniques: acid digestion, base digestion, and enzyme cleavage.

Quantification of ultrahigh molecular weight polyethylene (UHMWPE) wear debris remains a challenging task in orthopedic device analysis. Currently, the weight loss method is the only accepted practice for quantifying the amount of wear generated from a PE component. This technique utilizes loaded soak controls and weight differences to account for polymeric material lost through wear mechanisms. This method enables the determination of the amount of wear in the orthopedic device, but it provides no information about debris particulate size distribution. In order to shed light on wear mechanisms, information about the wear debris and its size distribution is necessary. To date, particulate isolation has been performed using the base digestion technique. The method uses a strong base, ultracentrifugation, and filtration to digest serum constituents and to isolate PE debris from sera. It should be noted that particulate isolation methods provide valuable information about particulate size distribution and may elucidate the mechanisms of wear associated with polymeric orthopedic implants; however, these techniques do not yet provide a direct measure of the amount of wear. The aim of this study is to present alternative approaches to wear particle isolation for analysis of polymer wear in total joint replacements without recourse to ultracentrifugation. Three polymer wear debris isolation techniques (the base method, an acid treatment, and an enzymatic digestion technique) are compared for effectiveness in simulator studies. A requirement of each technique is that the wear particulate must be completely devoid of serum proteins in order to effectively image and count these particles. In all methods the isolation is performed through filtration and chemical treatment. Subsequently, the isolated polymer particles are imaged using scanning electron microscopy and quantified with digital image analysis. The results from this study clearly show that isolation can be performed without the use of ultracentrifugation and that these methods provide a viable option for wear debris analysis.

Biocompatible Materials↗

Hierarchical models for probabilistic dose-response assessment.

Probabilistic risk assessment is gaining acceptance as the most appropriate way to characterize and communicate uncertainties in estimates of human health risk and/or reference levels of exposure such as benchmark doses. Although probabilistic techniques are well established in the exposure-assessment component of the National Research Council's risk-assessment paradigm, they are less well developed in the dose-response-assessment component. This paper proposes the use of hierarchical statistical models as tools for implementing probabilistic dose-response assessments, in that such models provide a natural connection between the pharmacokinetic (PK) and pharmacodynamic (PD) components of dose-response models. The results show that incorporating internal dose information into dose-response assessments via the coupling of PK and PD models in a hierarchical structure can reduce the uncertainty in the dose-response assessment of risk. However, information on the mean of the internal dose distribution is sufficient; having information on the variance of internal dose does not affect the uncertainty in the resulting estimates of excess risks or benchmark doses. In addition, the complexity of a PK model of internal dose does not affect how the variability in risk is measured via the ultimate endpoint.

Dose-Response Relationship, Drug↗

NMR, cloud-point measurements and enzymatic depolymerization: complementary tools to investigate substituent patterns in modified celluloses.

The substituent patterns of some chemically modified celluloses were characterized as a function of their size distribution, using size-exclusion chromatography coupled to both nuclear magnetic resonance spectroscopy (NMR) and cloud-point measurements. Intact and enzymatically hydrolyzed methyl cellulose (MC) was fractionated according to size, and the level of substitution of the fractions was measured off-line using NMR. Clouding behavior was also measured as a function of size. Clear differences between hydrolyzed and nonhydrolyzed samples were observed using both techniques. For samples that had been selectively hydrolyzed using cellulose-degrading enzymes, NMR data showed a direct link between the degree of degradation and the level of substitution. Differences in the clouding behavior highlighted changes in substituent levels and substituent patterns across the size distribution. The techniques gave valuable and somewhat complementary information on the substituent distributions of the samples before and after enzymatic hydrolysis.

Bacillus↗