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Fine mapping of a gene responsible for regulating dietary cholesterol absorption; founder effects underlie cases of phytosterolaemia in multiple communities.

Sitosterolaemia (also known as phytosterolaemia, MIM 210250) is a rare recessive autosomal inherited disorder, characterised by the presence of tendon and tuberous xanthomas, accelerated atherosclerosis and premature coronary artery disease. The defective gene is hypothesised to play an important role in regulating dietary sterol absorption and biliary secretion, thus defining a molecular mechanism whereby this physiological process is carried out. The disease locus was localised previously to chromosome 2p21, in a 15 cM interval between microsatellite markers D2S1788 and D2S1352 (based upon 10 families, maximum lodscore 4.49). In this study, we have extended these studies to include 30 families assembled from around the world. A maximum multipoint lodscore of 11.49 was obtained for marker D2S2998. Homozygosity and haplotype sharing was identified in probands from non-consanguineous marriages from a number of families, strongly supporting the existence of a founder effect among various populations. Additionally, based upon both genealogies, as well as genotyping, two Amish/Mennonite families, that were previously thought not to be related, appear to indicate a founder effect in this population as well. Using both homozygosity mapping, as well as informative recombination events, the sitosterolaemia gene is located at a region defined by markers D2S2294 and Afm210xe9, a distance of less than 2 cM.

Arteriosclerosis↗

Tobacco and oral health--the role of the world health organization.

In addition to several other chronic diseases, tobacco use is a primary cause of many oral diseases and adverse oral conditions. For example, tobacco is a risk factor for oral cancer, periodontal disease, and congenital defects in children whose mothers smoke during pregnancy. The epidemic of tobacco use is one of the greatest threats to global health; sadly the future appears worse because of the globalization of marketing. The World Health Organization (WHO) has strengthened the work for effective control of tobacco use. At the World Health Assembly in May 2003 the Member States agreed on a groundbreaking public health treaty to control tobacco supply and consumption. The treaty covers tobacco taxation, smoking prevention and treatment, illicit trade, advertising, sponsorship and promotion, and product regulation. Oral health professionals and dental associations worldwide should consider this platform for their future work for tobacco prevention since in several countries they play an important role in communication with patients and communities. The WHO Oral Health Programme gives priority to tobacco control in many ways through the development of national and community programmes which incorporates oral health and tobacco issues, tobacco prevention through schools, tobacco risk assessment in countries, and design of modern surveillance systems on risk factors and oral health. Systematic evaluation of coordinated efforts should be carried out at country and inter-country levels.

Advertising↗

Interrupting the transmission of wild polioviruses with vaccines: immunological considerations.

In 1988 the World Health Assembly set the goal of global poliomyelitis eradication by the year 2000. Substantial progress has been made, and 143 countries reported no poliomyelitis cases associated with the wild virus in 1993. This article reviews the immunological considerations relevant to interrupting the transmission of wild polioviruses with vaccines. Although serum immunity prevents poliomyelitis in the individual, it is local immunity that is important in preventing the transmission of polioviruses in the community. Natural infection and vaccination with oral polioviruses vaccine (OPV) produce local immunity in the intestine and the nasopharynx in about 70-80% of individuals. In contrast, inactivated poliovirus vaccine (IPV) produces local intestinal immunity in only 20-30% of the individuals. With either vaccine, however, a substantial proportion of the immunized population can transmit the wild virus. Moreover, although serum immunity is long-lasting, limited data suggest that local immunity may not be as persistent. To interrupt the transmission of wild polioviruses efforts should be made to achieve and sustain high levels of poliovirus vaccine coverage. Recent outbreaks show that wild poliovirus poses a risk for unimmunized individuals, even when overall coverage levels are high. Delivery of poliovirus vaccine to hard-to-reach populations will be of increasing importance as countries progress toward the final stages of poliomyelitis eradication. The immunization status of persons from poliomyelitis-free countries should be updated prior to travel to poliomyelitis-endemic areas.

Antibodies, Viral↗

Transcriptional analysis of biofilm formation processes in the anaerobic, hyperthermophilic bacterium Thermotoga maritima.

Thermotoga maritima, a fermentative, anaerobic, hyperthermophilic bacterium, was found to attach to bioreactor glass walls, nylon mesh, and polycarbonate filters during chemostat cultivation on maltose-based media at 80 degrees C. A whole-genome cDNA microarray was used to examine differential expression patterns between biofilm and planktonic populations. Mixed-model statistical analysis revealed differential expression (twofold or more) of 114 open reading frames in sessile cells (6% of the genome), over a third of which were initially annotated as hypothetical proteins in the T. maritima genome. Among the previously annotated genes in the T. maritima genome, which showed expression changes during biofilm growth, were several that corresponded to biofilm formation genes identified in mesophilic bacteria (i.e., Pseudomonas species, Escherichia coli, and Staphylococcus epidermidis). Most notably, T. maritima biofilm-bound cells exhibited increased transcription of genes involved in iron and sulfur transport, as well as in biosynthesis of cysteine, thiamine, NAD, and isoprenoid side chains of quinones. These findings were all consistent with the up-regulation of iron-sulfur cluster assembly and repair functions in biofilm cells. Significant up-regulation of several beta-specific glycosidases was also noted in biofilm cells, despite the fact that maltose was the primary carbon source fed to the chemostat. The reasons for increased beta-glycosidase levels are unclear but are likely related to the processing of biofilm-based polysaccharides. In addition to revealing insights into the phenotype of sessile T. maritima communities, the methodology developed here can be extended to study other anaerobic biofilm formation processes as well as to examine aspects of microbial ecology in hydrothermal environments.

ATP-Binding Cassette Transporters↗

The chaperone/usher pathways of Pseudomonas aeruginosa: identification of fimbrial gene clusters (cup) and their involvement in biofilm formation.

Pseudomonas aeruginosa, an important opportunistic human pathogen, persists in certain tissues in the form of specialized bacterial communities, referred to as biofilm. The biofilm is formed through series of interactions between cells and adherence to surfaces, resulting in an organized structure. By screening a library of Tn5 insertions in a nonpiliated P. aeruginosa strain, we identified genes involved in early stages of biofilm formation. One class of mutations identified in this study mapped in a cluster of genes specifying the components of a chaperone/usher pathway that is involved in assembly of fimbrial subunits in other microorganisms. These genes, not previously described in P. aeruginosa, were named cupA1-A5. Additional chaperone/usher systems (CupB and CupC) have been also identified in the genome of P. aeruginosa PAO1; however, they do not appear to play a role in adhesion under the conditions where the CupA system is expressed and functions in surface adherence. The identification of these putative adhesins on the cell surface of P. aeruginosa suggests that this organism possess a wide range of factors that function in biofilm formation. These structures appear to be differentially regulated and may function at distinct stages of biofilm formation, or in specific environments colonized by this organism.

Adhesins, Bacterial↗

CholeraSeq: a comprehensive genomic pipeline for cholera surveillance and near real-time outbreak investigation.

SUMMARY: Next Generation Sequencing is widely deployed in cholera-endemic regions, yet an end-to-end reproducible pipeline that unifies read QC, filtering, reference mapping, variant calling/annotation, recombination screening, and extraction of parsimony informative sites/variant codons, phylogenetic inference for downstream phylodynamic and epidemiological analyses have been lacking, slowing outbreak investigation and public health response. CholeraSeq is a high-throughput genomics pipeline for cholera genomic surveillance. It ingests consensus genomes, short read sequence data, draft assemblies, and scales seamlessly from local to cloud environments. To accelerate epidemiological context placement of new outbreak strains, we provide a curated ready-to-use core genome alignment compiled from public data, enabling flexible, fast, integration of new samples for outbreak investigations. AVAILABILITY AND IMPLEMENTATION: CholeraSeq is freely available on the GitHub platform https://github.com/CERI-KRISP/CholeraSeq. CholeraSeq is implemented in Nextflow with a modular design building upon the nf-core community standards.

Cholera↗

The Venturi Fluoride Saturator project.

This study was conducted to determine whether Venturi Fluoride Saturator (VFS) systems could be used to fluoridate small community and school water supply systems with an acceptable level of maintenance. VFS systems were installed and operated at four school and six community well sites according to state and federal regulations and recommendations. School VFS systems were unable to maintain optimum fluoride residuals even with substantial maintenance. All six community well site VFS systems performed acceptably, with only a few short lapses. VFS system maintenance was labor intensive. Recurring problems were caused by lengthy equipment delivery delays, the unavailability of timely technical assistance to support the VFS system, and the inadequate quality of VFS equipment and design. Based upon these findings, further expansion of the use of VFS systems either for community or school fluoridation cannot be recommended. Additional study of and improvements in the VFS system are indicated. Three major recommendations appear appropriate: (1) extensive laboratory testing of the VFS system concept under controlled conditions should be performed to determine the functioning parameters of this equipment under different hydrodynamic conditions; (2) additional research and development of the VFS unit to improve the quality of operations and the quality control of manufacturing and assembly should be undertaken; and (3) a VFS equipment distribution network should be developed, with sufficient logistical and technical support to supply equipment parts and expertise for installation, monitoring, and maintenance in a timely and efficient manner.

Equipment Design↗

A whole-genome assembly of Drosophila.

We report on the quality of a whole-genome assembly of Drosophila melanogaster and the nature of the computer algorithms that accomplished it. Three independent external data sources essentially agree with and support the assembly's sequence and ordering of contigs across the euchromatic portion of the genome. In addition, there are isolated contigs that we believe represent nonrepetitive pockets within the heterochromatin of the centromeres. Comparison with a previously sequenced 2.9- megabase region indicates that sequencing accuracy within nonrepetitive segments is greater than 99. 99% without manual curation. As such, this initial reconstruction of the Drosophila sequence should be of substantial value to the scientific community.

Algorithms↗

Floral gene resources from basal angiosperms for comparative genomics research.

BACKGROUND: The Floral Genome Project was initiated to bridge the genomic gap between the most broadly studied plant model systems. Arabidopsis and rice, although now completely sequenced and under intensive comparative genomic investigation, are separated by at least 125 million years of evolutionary time, and cannot in isolation provide a comprehensive perspective on structural and functional aspects of flowering plant genome dynamics. Here we discuss new genomic resources available to the scientific community, comprising cDNA libraries and Expressed Sequence Tag (EST) sequences for a suite of phylogenetically basal angiosperms specifically selected to bridge the evolutionary gaps between model plants and provide insights into gene content and genome structure in the earliest flowering plants. RESULTS: Random sequencing of cDNAs from representatives of phylogenetically important eudicot, non-grass monocot, and gymnosperm lineages has so far (as of 12/1/04) generated 70,514 ESTs and 48,170 assembled unigenes. Efficient sorting of EST sequences into putative gene families based on whole Arabidopsis/rice proteome comparison has permitted ready identification of cDNA clones for finished sequencing. Preliminarily, (i) proportions of functional categories among sequenced floral genes seem representative of the entire Arabidopsis transcriptome, (ii) many known floral gene homologues have been captured, and (iii) phylogenetic analyses of ESTs are providing new insights into the process of gene family evolution in relation to the origin and diversification of the angiosperms. CONCLUSION: Initial comparisons illustrate the utility of the EST data sets toward discovery of the basic floral transcriptome. These first findings also afford the opportunity to address a number of conspicuous evolutionary genomic questions, including reproductive organ transcriptome overlap between angiosperms and gymnosperms, genome-wide duplication history, lineage-specific gene duplication and functional divergence, and analyses of adaptive molecular evolution. Since not all genes in the floral transcriptome will be associated with flowering, these EST resources will also be of interest to plant scientists working on other functions, such as photosynthesis, signal transduction, and metabolic pathways.

Biodiversity↗

[Maquiladoras and women on the US-Mexican border: a benefit or a detriment to occupational health?].

This article examines the impact of work conditions on the health of women working in assembly plants known as "maquiladoras". A sample of 480 women residing in Tijuana and with similar low socioeconomic conditions was studied. The sample included 120 electronics workers, 120 textile workers, 120 service workers and 120 women with no history of labor-force participation. These groups were compared on physical and psychosocial health outcomes, including depression, nervousness, functional impediments and sense of control over life. Data were obtained from interviews conducted in the communities where workers reside. Although high levels of depression and a low sense of control over life was observed, maquiladora workers--particularly in the electronics industry--suffered less functional impediments and nervousness than service workers. However, maquiladora workers were at higher risk of delivering infants of low birthweight.

Adolescent↗

Future vision of the GDB human genome database.

In 1973, scientists assembled at the first Human Gene Mapping Workshop to discuss the 64 human genes mapped at that time. In 1989, the GDB Human Genome Database was created to store information on 1, 700 mapped human genes. Ten years later, as the human genome project closes in on the release of the complete DNA sequence holding as many as 100,000 human genes, GDB is evolving to continue to meet the needs of the scientific community. Well known as a resource for data which has been stringently reviewed as part of the curation process, GDB prepares to continue to provide a compilation of the human genome including maps, map objects, polymorphisms, and mutations. As more sites across the Internet are established to share biological information, it becomes increasingly burdensome for the scientist to collect data from all sources of a particular domain. In an attempt to reduce this burden, GDB continues to load data from large genome centres and accept submissions from researchers around the world. Moreover, GDB looks to provide a mechanism to link gene-related information to the human reference sequence. In doing this, GDB plans to establish federated linkages with "boutique" databases around the world that could contain enormous amounts of valuable information about specific genes or chromosomes.

Computer Simulation↗

How can a proposed Cochrane diet and nutrition field work effectively?

The Cochrane Database currently provides relatively little evidence-based guidance about nutrition relevant to general practitioners. This situation could be improved by the establishment of a new Cochrane Field to identify relevant studies, prioritize topics to include nutrition, work with Cochrane methodologists on the inclusion of observational studies, and disseminate results of Cochrane reviews to general practitioners and their patients. A Diet and Nutrition Field could be established as a separate entity or as a Subgroup of the existing Primary Health Care (PHC) Field. The Field would be appropriate if the intent is to immediately cover nutritional interventions of all sorts, in all settings. However, if the focus is nutritional evidence for use by primary care clinicians, organization as a subField would provide a simpler registration process, allow Cochrane activities to begin sooner, and would allow members to focus on primary-care-relevant nutritional issues, conserving their resources and energy. A mechanism exists for conversion to a freestanding Field if the scope later expands. Of the core Field functions, identification and assembly of relevant trials into a specialized register would be among the most important. Special registers are generated by focused literature searches augmented by hand-searching of key journals. Given the importance of studies with observational designs, a nutrition field register will require some additional work on search strategies and inclusion criteria. Other key functions would include ensuring effective communication both with members of other Cochrane entities and with the scientific and clinical community with interests in diet and nutrition.

Communication↗

Hemoptysis: clinicians' perspectives.

Clinicians who were interested and considerably experienced in assessing patients with hemoptysis were surveyed during a computer-assisted interactive presentation at the 1988 ACCP Annual Scientific Assembly. The approach to ambulatory patients with minor bleeding was consistent with recently published guidelines: fiberoptic bronchoscopy has a central role, with a less apparent impact of other new technologies. Although specific diagnostic results were significantly more useful (p less than 0.01), even nonspecific bronchoscopy findings were though to have clinical value. External factors such as medicolegal concerns and obligations to provide service were acknowledged to influence selection of patients for bronchoscopy, and community-based clinicians cited such effects more often than academicians (p less than 0.02). Approaches to patients with massive hemoptysis reflected caution essential to acute management. Bronchoscopy was performed earlier (p less than 0.01) than in patients with minor bleeding, but opinions differed regarding instrument selection, the best method of airway support, and the roles of interventional angiography. This survey suggests that real-world settings are addressed incompletely by published experiences accumulated in tertiary centers. Clarification of optimum approaches to patients with hemoptysis requires further input from practicing clinicians.

Ambulatory Care↗

Population-based mortality outcome of rheumatoid arthritis in females.

UNLABELLED: Rheumatoid arthritis (RA) is a systemic disease whose morbidity exceeds its mortality. This abstract quantifies the mortality of RA in a general population over a 30-year period in females. The generic, across the spectrum of disease, mortality ratio is 136%; the excess death rate is 12. The mortality impact on males is minimal; the source publication noted a mortality ratio of 107%. Many selected cases of RA can be underwritten very favorably. PURPOSE: To quantify the excess mortality in females diagnosed with rheumatoid arthritis (RA) between 1955 to 1985. SUBJECTS AND METHODS: Medical records of all residents age 35 and over of Rochester, Minnesota, who met the American College of Rheumatology 1987 diagnostic criteria for RA were reviewed. Based on the comprehensive statistical base for residents in Rochester, virtually complete ascertainment of all clinically recognized cases of RA were identified. An incidence cohort identifying the same residents with new cases of RA occurring between January 1, 1955, and January 1, 1985, was created. Three, 10-year prevalence cohorts were assembled as of July 1, 1965, 1975 and 1985. Patients in each cohort were followed longitudinally until death or migration from Rochester. Data of disease characteristics, course, co-morbidity and death were collected. During the follow-up period, 6.9% moved out of the county, and 5.1% moved into the county after the diagnosis of RA had been made elsewhere. Expected survival was based on age and sex adjusted survival from the same community in the same time period. Mortality was described using the Kaplan-Meier product-limit method. Cox proportional hazards modeling was used to examine the effects of age, sex and rheumatoid factor on survival. DATA: In the 1965, 1975 and 1985 prevalence cohorts, there were 163, 235 and 272 cases of RA, respectively. Some individuals were present in more than one. Deaths in each cohort were 54, 93 and 111, respectively. Median follow-up was 12.7 years for the entire group with the earlier groups being longer. Mean follow-up was 15.1 years. Seventy-three percent of patients were females. The average age at diagnosis was 60.2 years.

Arthritis, Rheumatoid↗

The dental school's role in academic health centers: report of a study.

This paper highlights for the dental education community selected data from a recently completed study of the organization and governance of academic health centers, conducted under the auspices of the Association of Academic health Centers and funded by the W. K. Kellogg Foundation. It is hoped that the limited information presented here will stimulate interest in the larger study. Data derived from three questionnaires used in the study are presented and discussed. Top administrators in academic health centers were surveyed to assemble information on the structural components and hierarchical relationships in contemporary academic health centers, the processes by which decisions are made, the way in which conflicts are resolved, and the conditions that administrators envision for their institutions in the future. Dental school deans were part of the survey group, and their responses are examined along with those of deans of other health professional schools.

Academic Medical Centers↗

A BAC-based physical map of the Drosophila buzzatii genome.

Large-insert genomic libraries facilitate cloning of large genomic regions, allow the construction of clone-based physical maps, and provide useful resources for sequencing entire genomes. Drosophila buzzatii is a representative species of the repleta group in the Drosophila subgenus, which is being widely used as a model in studies of genome evolution, ecological adaptation, and speciation. We constructed a Bacterial Artificial Chromosome (BAC) genomic library of D. buzzatii using the shuttle vector pTARBAC2.1. The library comprises 18,353 clones with an average insert size of 152 kb and an approximately 18x expected representation of the D. buzzatii euchromatic genome. We screened the entire library with six euchromatic gene probes and estimated the actual genome representation to be approximately 23x. In addition, we fingerprinted by restriction digestion and agarose gel electrophoresis a sample of 9555 clones, and assembled them using FingerPrint Contigs (FPC) software and manual editing into 345 contigs (mean of 26 clones per contig) and 670 singletons. Finally, we anchored 181 large contigs (containing 7788 clones) to the D. buzzatii salivary gland polytene chromosomes by in situ hybridization of 427 representative clones. The BAC library and a database with all the information regarding the high coverage BAC-based physical map described in this paper are available to the research community.

Animals↗

Temporal dynamics and degradation activity of an bacterial inoculum for treating waste metal-working fluid.

In order for established bioreactors to be effective for treating chemically mixed wastes such as metal working fluids (MWF) it is essential that they harbour microbial populations that can maintain sufficient active biomass and degrade each of the chemical constituents present. In this study we investigated the effectiveness of a bacterial consortium composed of four species (Clavibacter michiganensis, Methylobacterium mesophilicum, Rhodococcus erythropolis and Pseudomonas putida), assembled on the basis of their apparent ubiquity in waste MWF, degradation ability and tolerance to fluctuating chemistry of the waste. The temporal dynamics of the inoculum and its effects on the fate of individual chemical components of the waste were studied, by regular sampling, over 400 h. Using a complementary approach of culture with chemotaxonomic (FAME) analysis and applying group specific probes (FISH), the inoculum was found to represent a significant component of the community in bioreactors with and without presence of indigenous MWF populations. In addition, the reduction in the COD by the consortium was approximately 85% of the total pollution load, and 30-40% more effectively than any other treatment (indigenous MWF community alone or activated sludge). Furthermore, all the chemical constituents, including the biocide (a formaldehyde release agent) demonstrated > 60% reduction. Many chemical components of the MWF proved to be recalcitrant in the other treatments. The results of this study confirm that assemblage of an inoculum, based on a comprehensive knowledge of the indigenous microbial community, in the target habitat, is a highly effective way of selecting microbial populations for bioaugmentation of bioreactors.

Actinomycetales↗

Automated metabolic reconstruction for Methanococcus jannaschii.

We present the computational prediction and synthesis of the metabolic pathways in Methanococcus jannaschii from its genomic sequence using the PathoLogic software. Metabolic reconstruction is based on a reference knowledge base of metabolic pathways and is performed with minimal manual intervention. We predict the existence of 609 metabolic reactions that are assembled in 113 metabolic pathways and an additional 17 super-pathways consisting of one or more component pathways. These assignments represent significantly improved enzyme and pathway predictions compared with previous metabolic reconstructions, and some key metabolic reactions, previously missing, have been identified. Our results, in the form of enzymatic assignments and metabolic pathway predictions, form a database (MJCyc) that is accessible over the World Wide Web for further dissemination among members of the scientific community.

Computational Biology↗