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Biomedical subjects

N Larsen

Publications and source records attributed to N Larsen.

At least 19 recordsLinked to original sources

NAST: a multiple sequence alignment server for comparative analysis of 16S rRNA genes.

Microbiologists conducting surveys of bacterial and archaeal diversity often require comparative alignments of thousands of 16S rRNA genes collected from a sample. The computational resources and bioinformatics expertise required to construct such an alignment has inhibited high-throughput analysis. It was hypothesized that an online tool could be developed to efficiently align thousands of 16S rRNA genes via the NAST (Nearest Alignment Space Termination) algorithm for creating multiple sequence alignments (MSA). The tool was implemented with a web-interface at http://greengenes.lbl.gov/NAST. Each user-submitted sequence is compared with Greengenes' 'Core Set', comprising approximately 10,000 aligned non-chimeric sequences representative of the currently recognized diversity among bacteria and archaea. User sequences are oriented and paired with their closest match in the Core Set to serve as a template for inserting gap characters. Non-16S data (sequence from vector or surrounding genomic regions) are conveniently removed in the returned alignment. From the resulting MSA, distance matrices can be calculated for diversity estimates and organisms can be classified by taxonomy. The ability to align and categorize large sequence sets using a simple interface has enabled researchers with various experience levels to obtain bacterial and archaeal community profiles.

Algorithms↗

Dynamic role of kallikrein 6 in traumatic spinal cord injury.

Kallikrein 6 (K6) is a member of the kallikrein gene family that comprises 15 structurally and functionally related serine proteases. In prior studies we showed that, while this trypsin-like enzyme is preferentially expressed in neurons and oligodendroglia of the adult central nervous system (CNS), it is up-regulated at sites of injury due to expression by infiltrating immune and resident CNS cells. Given this background we hypothesized that K6 is a key contributor to the pathophysiology of traumatic spinal cord injury (SCI), influencing neural repair and regeneration. Examination of K6 expression following contusion injury to the adult rat cord, and in cases of human traumatic SCI, indicated significant elevations at acute and chronic time points, not only at the injury site but also in cord segments above and below. Elevations in K6 were particularly prominent in macrophages, microglia and reactive astrocytes. To determine potential effects of elevated K6 on the regeneration environment, the ability of neurons to adhere to and extend processes on substrata which had been exposed to recombinant K6 was examined. Limited (1 h) or excess (24 h) K6-mediated proteolytic digestion of a growth-facilitatory substrate, laminin, significantly decreased neurite outgrowth. By contrast, similar hydrolysis of a growth-inhibitory substrate, aggrecan, significantly increased neurite extension and cell adherence. These data support the hypothesis that K6 enzymatic cascades mediate events secondary to spinal cord trauma, including dynamic modification of the capacity for axon outgrowth.

Adolescent↗

Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB.

A 16S rRNA gene database (http://greengenes.lbl.gov) addresses limitations of public repositories by providing chimera screening, standard alignment, and taxonomic classification using multiple published taxonomies. It was found that there is incongruent taxonomic nomenclature among curators even at the phylum level. Putative chimeras were identified in 3% of environmental sequences and in 0.2% of records derived from isolates. Environmental sequences were classified into 100 phylum-level lineages in the Archaea and Bacteria.

Archaea↗

Thiopurine methyltransferase genotype distribution in patients with Crohn's disease.

BACKGROUND: Inter-individual response to azathioprine is partly due to inter-individual variation in the thiopurine methyltransferase (TPMT) activity. The TPMT genotype, which reflects the TPMT activity, has previously been studied in healthy Caucasians, with the most common variant allele being TPMT*3A. TPMT genotyping in adult patients with Crohn's disease has never been performed systematically. AIM: To determine the TPMT genotype distribution in adult patients with Crohn's disease. METHODS: One hundred and twenty randomly selected Danish patients (64 females and 56 males) with azathioprine-dependent Crohn's disease were included, and a polymerase chain reaction assay was used for TPMT genotyping. The patients were genotyped for the low-level genotype G460-->A and A719-->G transitions. RESULTS: One hundred and nine patients (90.3%; 95% confidence interval, 84.1-95.3) had a wild-type/ wild-type genotype, whereas 10 patients (8.3%; 95% confidence interval, 4.1-14.8) had one non-functional mutant allele and one patient (0.8%; 95% confidence interval, 0.02-4.6) had two non-functional mutant alleles. Only the TPMT*3A variant allele was found. CONCLUSIONS: The study showed a TPMT genotype distribution amongst adult Danish patients with Crohn's disease which was similar to the distribution of TPMT variant alleles normally found in healthy Caucasians.

Adolescent↗

Diabetic macular oedema: a comparison of vitreous fluorometry, angiography, and retinopathy.

AIM: To evaluate the relation between the quantitative measurement of vitreous fluorescein with fluorescein angiography and retinopathy in diabetic patients with and without clinically significant macular oedema (CSMO). METHODS: In a prospective cross sectional study, passive permeability and active, outward transport of fluorescein across the blood-retinal barrier were quantitated with vitreous fluorometry in 61 eyes from 48 patients with CSMO and 22 fellow eyes without CSMO, after exclusion of eyes with previous macular laser treatment and vitreous liquification. All patients were recruited from the university hospital's outpatient clinic. Retinopathy and fluorescein angiograms were evaluated on 60 degree photographs. RESULTS: The passive permeability in CSMO was significantly correlated with the severity of leakage on fluorescein angiograms (r=0.73), the level of retinopathy (r=0.61), and visual acuity (r=0.45). Significant differences between eyes with CSMO and eyes without CSMO were found for passive permeability (p<0.001), fluorescein leakage (p<0.001), visual acuity (p=0.02), and retinopathy (p=0.002). CONCLUSION: Passive permeability of fluorescein quantitated with vitreous fluorometry was correlated both with semiquantitative fluorescein angiography and retinopathy, and a significant increase in passive permeability was found when comparing eyes with CSMO to eyes without CSMO. No such pattern was found for the active transport indicating that passive and not the outward, active transport is the factor of most importance in the development of CSMO.

Adult↗

Nitric acid trihydrate (NAT) in polar stratospheric clouds.

A comprehensive investigation of polar stratospheric clouds was performed on 25 January 2000 with instruments onboard a balloon gondola flown from Kiruna, Sweden. Cloud layers were repeatedly encountered at altitudes between 20 and 24 kilometers over a wide range of atmospheric temperatures (185 to 197 kelvin). Particle composition analysis showed that a large fraction of the cloud layers was composed of nitric acid trihydrate (NAT) particles, containing water and nitric acid at a molar ratio of 3:1; this confirmed that these long-sought solid crystals exist well above ice formation temperatures. The presence of NAT particles enhances the potential for chlorine activation with subsequent ozone destruction in polar regions, particularly in early and late winter.

Journal Article↗

WIT: integrated system for high-throughput genome sequence analysis and metabolic reconstruction.

The WIT (What Is There) (http://wit.mcs.anl.gov/WIT2/) system has been designed to support comparative analysis of sequenced genomes and to generate metabolic reconstructions based on chromosomal sequences and metabolic modules from the EMP/MPW family of databases. This system contains data derived from about 40 completed or nearly completed genomes. Sequence homologies, various ORF-clustering algorithms, relative gene positions on the chromosome and placement of gene products in metabolic pathways (metabolic reconstruction) can be used for the assignment of gene functions and for development of overviews of genomes within WIT. The integration of a large number of phylogenetically diverse genomes in WIT facilitates the understanding of the physiology of different organisms.

Databases, Factual↗

A missense variant of the porcine melanocortin-4 receptor (MC4R) gene is associated with fatness, growth, and feed intake traits.

Our knowledge of the genetic factors affecting obesity is increasing, but information about the individual gene effects remains limited in humans as well as in animal models. The melanocortin-4 receptor gene (MC4R) has been implicated in the regulation of feeding behavior and body weight in humans and mice. We have studied MC4R as a candidate gene for the control of economically important growth and performance traits in the pig. A missense mutation was identified in a region highly conserved among melanocortin receptor (MCR) genes. To determine whether there was an association of this MC4R polymorphism with phenotypic variation, we tested the mutation in a large number of individual animals from several different pig lines. Analyses of growth and performance test records showed significant associations of MC4R genotypes with backfat and growth rate in a number of lines as well as feed intake overall. It is probable that the variant amino acid residue of the MC4R mutation (or a closely linked mutation) causes a significant change of the MC4R function. These results support the functional significance of a pig MC4R missense mutation and suggest that comparative genomics based on model species may be equally important for application to farm animals as they are for human medicine.

Adipose Tissue↗

Screening and prevention of diabetic blindness.

Diabetic eye disease remains a major cause of blindness in the world. Laser treatment for proliferative diabetic retinopathy and diabetic macular edema became available more than two decades ago. The outcome of treatment depends on the timing of laser treatment. The laser treatment is optimally delivered when high-risk characteristics have developed in proliferative retinopathy or diabetic macular edema and before this has significantly affected vision. Laser treatment is usually successful if applied during this optimal period whereas the treatment benefit falls sharply if the treatment is applied too late. In order to optimize the timing of laser treatment in diabetic eye disease screening programs have been established. The oldest screening program is 20 years old and several programs have been established during the last decade. In this paper the organisation and methods of screening programs are described including direct and photographic screening. The incidence and prevalence of blindness is much lower in populations where screening for diabetic eye disease has been established compared to diabetic populations without screening. Technical advantages may allow increased efficiency and telescreening. From a public health standpoint screening for diabetic eye disease is one of the most cost effective health procedures available. Diabetic eye disease can be prevented using existing technology and the cost involved is many times less than the cost of diabetic blindness.

Blindness↗

Chemical analysis of polar stratospheric cloud particles

A balloon-borne gondola carrying a particle analysis system, a backscatter sonde, and pressure and temperature sensors was launched from Kiruna, Sweden, on 25 January 1998. Measurements within polar stratospheric cloud layers inside the Arctic polar vortex show a close correlation between large backscatter ratios and enhanced particle-related water and nitric acid signals at low temperatures. Periodic structures in the data indicate the presence of lee waves. The H2O/HNO3 molar ratios are consistently found to be above 10 at atmospheric temperatures between 189 and 192 kelvin. Such high ratios indicate ternary solution particles of H2O, HNO3, and H2SO4 rather than the presence of solid hydrates.

Journal Article↗

A new version of the RDP (Ribosomal Database Project).

The Ribosomal Database Project (RDP-II), previously described by Maidak et al. [ Nucleic Acids Res. (1997), 25, 109-111], is now hosted by the Center for Microbial Ecology at Michigan State University. RDP-II is a curated database that offers ribosomal RNA (rRNA) nucleotide sequence data in aligned and unaligned forms, analysis services, and associated computer programs. During the past two years, data alignments have been updated and now include >9700 small subunit rRNA sequences. The recent development of an ObjectStore database will provide more rapid updating of data, better data accuracy and increased user access. RDP-II includes phylogenetically ordered alignments of rRNA sequences, derived phylogenetic trees, rRNA secondary structure diagrams, and various software programs for handling, analyzing and displaying alignments and trees. The data are available via anonymous ftp (ftp.cme.msu. edu) and WWW (http://www.cme.msu.edu/RDP). The WWW server provides ribosomal probe checking, approximate phylogenetic placement of user-submitted sequences, screening for possible chimeric rRNA sequences, automated alignment, and a suggested placement of an unknown sequence on an existing phylogenetic tree. Additional utilities also exist at RDP-II, including distance matrix, T-RFLP, and a Java-based viewer of the phylogenetic trees that can be used to create subtrees.

Base Sequence↗

The tmRNA database (tmRDB).

This first release of the tmRNA database (tmRDB) contains 19 tmRNA sequences, a tmRNA sequence alignment with emphasis of base pairs that are supported by comparative sequence analysis, and a tabulation of tmRNA-encoded tag peptides. The tmRNADB also offers an RNA secondary structure diagram of the Escherichia coli tmRNA, as well as PDB-formatted coordinates for three-dimensional modeling. The data are available on the World Wide Web at http://www.uthct. edu/tmRDB/tmRDB.html

Computer Communication Networks↗

The Signal Recognition Particle Database (SRPDB).

This release of the SRPDB (signal recognition particle database, http://pegasus.uthct.edu/SRPDB/SRPDB . html ) adds four SRP RNA sequences (a total of 99 SRP RNA sequences), 23 SRP protein sequences (a total of 63 protein sequences from SRP9, SRP14, SRP19, SRP21, SRP54, SRP68 or SRP72), and, for the first time, sequences of the alpha subunit of the eukaryotic SRP receptor and its homologous bacterial proteins (a total of 21 sequences). Sequences are offered phylogenetically ordered, annotated with links to the primary databases, and in aligned form. Also downloadable are sample SRP RNA secondary structure diagrams, three-dimensional models of representative SRP RNAs, and search motifs.

Amino Acid Sequence↗

The Signal Recognition Particle Database (SRPDB).

The SRPDB (Signal Recognition Particle Database) offers aligned SRP RNA and SRP protein sequences, phylogenetically ordered and annotated. This release adds three SRP RNA sequences (totaling 96 SRP RNA sequences) and 11 SRP protein sequences (a total of 39 protein sequences from SRP9, SRP14, SRP19, SRP21, SRP54, SRP68 or SRP72). Also downloadable are sample SRP RNA secondary structure diagrams, a three-dimensional model of the human SRP RNA, search motifs and software.

Amino Acid Sequence↗

The RDP (Ribosomal Database Project).

The Ribosomal Database Project (RDP) is a curated database that offers ribosome-related data, analysis services and associated computer programs. The offerings include phylogenetically ordered alignments of ribosomal RNA (rRNA) sequences, derived phylogenetic trees, rRNA secondary structure diagrams, and various software for handling, analyzing and displaying alignments and trees. The data are available via anonymous FTP (rdp.life.uiuc.edu), electronic mail (server@rdp.life.uiuc.edu), gopher (rdpgopher.life.uiuc.edu) and WWW (http://rdpwww.life.uiuc.edu/ ). The electronic mail and WWW servers provide ribosomal probe checking, approximate phylogenetic placement of user-submitted sequences, screening for possible chimeric rRNA sequences, automated alignment, and a suggested placement of an unknown sequence on an existing phylogenetic tree.

Animals↗

The Signal Recognition Particle Database (SRPDB).

The Signal Recognition Particle Database (SRPDB) provides aligned SRP RNA and SRP protein sequences, annotated and phylogenetically ordered. The current release included 93 RNAs and 29 proteins representing SRP9, SRP14, SRP19, SRP21, SRP54, SRP68 and SRP72. The SRPDB can be downloaded and is accessible via the World Wide Web.

Computer Communication Networks↗