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MINRMS: an efficient algorithm for determining protein structure similarity using root-mean-squared-distance.

MOTIVATION: Existing algorithms for automated protein structure alignment generate contradictory results and are difficult to interpret. An algorithm which can provide a context for interpreting the alignment and uses a simple method to characterize protein structure similarity is needed. RESULTS: We describe a heuristic for limiting the search space for structure alignment comparisons between two proteins, and an algorithm for finding minimal root-mean-squared-distance (RMSD) alignments as a function of the number of matching residue pairs within this limited search space. Our alignment algorithm uses coordinates of alpha-carbon atoms to represent each amino acid residue and requires a total computation time of O(m(3) n(2)), where m and n denote the lengths of the protein sequences. This makes our method fast enough for comparisons of moderate-size proteins (fewer than approximately 800 residues) on current workstation-class computers and therefore addresses the need for a systematic analysis of multiple plausible shape similarities between two proteins using a widely accepted comparison metric.

Algorithms↗

EpoDB: a prototype database for the analysis of genes expressed during vertebrate erythropoiesis.

EpoDB is a database of genes expressed in vertebrate red blood cells. It is also a prototype for the creation of cell and tissue-specific databases from multiple external sources. The information in EpoDB obtained from GenBank, SWISS-PROT, Transfac, TRRD and GERD is curated to provide high quality data for sequence analysis aimed at understanding gene regulation during erythropoiesis. New protocols have been developed for data integration and updating entries. Using a BLAST-based algorithm, we have grouped GenBank entries representing the same gene together. This sequence similarity protocol was also used to identify new entries to be included in EpoDB. We have recently implemented our database in Sybase (relational tables) in addition to SICStus Prolog to provide us with greater flexibility in asking complex queries that utilize information from multiple sources. New additions to the public web site (http://www.cbil.upenn.edu/epodb) for accessing EpoDB are the ability to retrieve groups of entries representing different variants of the same gene and to retrieve gene expression data. The BLAST query has been enhanced by incorporating BLASTView, an interactive and graphical display of BLAST results. We have also enhanced the queries for retrieving sequence from specified genes by the addition of MEME, a motif discovery tool, to the integrated analysis tools which include CLUSTALW and TESS.

Animals↗

FrameD: A flexible program for quality check and gene prediction in prokaryotic genomes and noisy matured eukaryotic sequences.

We describe FrameD, a program that predicts coding regions in prokaryotic and matured eukaryotic sequences. Initially targeted at gene prediction in bacterial GC rich genomes, the gene model used in FrameD also allows to predict genes in the presence of frameshifts and partially undetermined sequences which makes it also very suitable for gene prediction and frameshift correction in unfinished sequences such as EST and EST cluster sequences. Like recent eukaryotic gene prediction programs, FrameD also includes the ability to take into account protein similarity information both in its prediction and its graphical output. Its performances are evaluated on different bacterial genomes. The web site (http://genopole.toulouse.inra.fr/bioinfo/FrameD/FD) allows direct prediction, sequence correction and translation and the ability to learn new models for new organisms.

Computer Graphics↗

FELINES: a utility for extracting and examining EST-defined introns and exons.

FELINES (Finding and Examining Lots of Intron 'N' Exon Sequences) is a utility written to automate construction and analysis of high quality intron and exon sequence databases produced from EST (expressed sequence tag) to genomic sequence alignments. We demonstrated the various programs of the FELINES utility by creating intron and exon sequence databases for the fungal organism Schizosaccharomyces pombe from alignments of EST to genomic sequences. In addition, we analyzed our constructed S.pombe sequence databases and the well-established Saccharomyces cerevisiae intron database from Manuel Ares' Laboratory for conserved sequence motifs. FELINES was shown to be useful for characterizing branchsites, polypyrimidine tracts and 5' and 3' splice sites in the intron databases and exonic splicing enhancers (ESEs) in S.pombe exons. FELINES is available at http://www.genome.ou.edu/informatics.html.

Base Sequence↗

MRI is nondiagnostic in cervical spine imaging of the helmeted football player with shoulder pads.

BACKGROUND: It is currently recommended that helmet and shoulder pads remain in place during the initial clinical and radiographic evaluation of the helmeted athlete with a potential cervical spine injury. The objective of this prospectively designed, single-subject study was to determine whether MRI may play a role in the initial evaluation and management of the helmeted football player with a cervical spine injury. METHODS: One male athlete was fitted using equipment (football helmet [Riddell], shoulder pads [Douglas]) worn during the collegiate season at Lehigh University. Standard MRI using a routine clinical 0.7 T high field open MRI scanner (GE Signa System, Milwaukee, WI) was employed for the evaluation using standard clinical parameters (sagittal T1, fast spin echo [FSE] T2, STIR, and axial FSE T2 series). A single board-certified, fellowship-trained neuroradiologist reviewed all series. Studies were evaluated for image clarity and diagnostic capability in this clinical setting. RESULTS: All standard MRI series were of extremely limited quality, even using sequences and slice selection designed to minimize artifact associated with metals (FSE T2-weighted series). When all MRI series were reviewed as a whole, sufficient evidence was not available to allow clinical decision making. CONCLUSIONS: The amount and type of metal within the standard football helmet and shoulder pads result in sufficient field inhomogeneity and SKEW artifact to preclude adequate evaluation of the cervical structures, rendering MRI evaluation in this setting not clinically useful. This study shows that current MRI techniques play no role in the clearance of the cervical spine (with currently available brands of helmet and shoulder pads in place) without prior equipment removal or manipulation.

Artifacts↗

Psychiatric and medical comorbidities of bipolar disorder.

OBJECTIVES: This review summarizes the literature on psychiatric and medical comorbidities in bipolar disorder. The coexistence of other Axis I disorders with bipolar disorder complicates psychiatric diagnosis and treatment. Conversely, symptom overlap in DSM-IV diagnoses hinders definition and recognition of true comorbidity. Psychiatric comorbidity is often associated with earlier onset of bipolar symptoms, more severe course, poorer treatment compliance, and worse outcomes related to suicide and other complications. Medical comorbidity may be exacerbated or caused by pharmacotherapy of bipolar symptoms. METHODS: Articles were obtained by searching MEDLINE from 1970 to present with the following search words: bipolar disorder AND, comorbidity, anxiety disorders, eating disorder, alcohol abuse, substance abuse, ADHD, personality disorders, borderline personality disorder, medical disorders, hypothyroidism, obesity, diabetes mellitus, multiple sclerosis, lithium, valproate, lamotrigine, carbamazepine, atypical antipsychotics. Articles were prioritized for inclusion based on the following considerations: sample size, use of standardized diagnostic criteria and validated methods of assessment, sequencing of disorders, quality of presentation. RESULTS: Although the literature establishes a strong association between bipolar disorder and substance abuse, the direction of causality is uncertain. An association is also seen with anxiety disorders, attention-deficit/hyperactivity disorder, and eating disorders, as well as cyclothymia and other axis II personality disorders. Medical disorders accompany bipolar disorder at rates greater than predicted by chance. However, it is often unclear whether a medical disorder is truly comorbid, a consequence of treatment, or a combination of both. CONCLUSION: To ensure prompt, appropriate intervention while avoiding iatrogenic complications, the clinician must evaluate and monitor patients with bipolar disorder for the presence and the development of comorbid psychiatric and medical conditions. Conversely, physicians should have a high index of suspicion for underlying bipolar disorder when evaluating individuals with other psychiatric diagnoses (not just unipolar depression) that often coexist with bipolar disorder, such as alcohol and substance abuse or anxiety disorders. Anticonvulsants and other mood stabilizers may be especially helpful in treating bipolar disorder with significant comorbidity.

Anticonvulsants↗

Monte Carlo advice.

The generation of long, high quality random number sequences for Monte Carlo simulations using minicomputers is considered. The importance of the thorough testing of Monte Carlo random number generators is emphasized. A recommendation is given to authors of Monte Carlo papers to specify their random number generator and to describe the randomness testing which that generator has undergone.

Computers↗

Microeukaryote community patterns along an O2/H2S gradient in a supersulfidic anoxic fjord (Framvaren, Norway).

To resolve the fine-scale architecture of anoxic protistan communities, we conducted a cultivation-independent 18S rRNA survey in the superanoxic Framvaren Fjord in Norway. We generated three clone libraries along the steep O(2)/H(2)S gradient, using the multiple-primer approach. Of 1,100 clones analyzed, 753 proved to be high-quality protistan target sequences. These sequences were grouped into 92 phylotypes, which displayed high protistan diversity in the fjord (17 major eukaryotic phyla). Only a few were closely related to known taxa. Several sequences were dissimilar to all previously described sequences and occupied a basal position in the inferred phylogenies, suggesting that the sequences recovered were derived from novel, deeply divergent eukaryotes. We detected sequence clades with evolutionary importance (for example, clades in the euglenozoa) and clades that seem to be specifically adapted to anoxic environments, challenging the hypothesis that the global dispersal of protists is uniform. Moreover, with the detection of clones affiliated with jakobid flagellates, we present evidence that primitive descendants of early eukaryotes are present in this anoxic environment. To estimate sample coverage and phylotype richness, we used parametric and nonparametric statistical methods. The results show that although our data set is one of the largest published inventories, our sample missed a substantial proportion of the protistan diversity. Nevertheless, statistical and phylogenetic analyses of the three libraries revealed the fine-scale architecture of anoxic protistan communities, which may exhibit adaptation to different environmental conditions along the O(2)/H(2)S gradient.

Anaerobiosis↗

Mot1 associates with transcriptionally active promoters and inhibits association of NC2 in Saccharomyces cerevisiae.

Mot1 stably associates with the TATA-binding protein (TBP), and it can dissociate TBP from DNA in an ATP-dependent manner. Mot1 acts as a negative regulator of TBP function in vitro, but genome-wide transcriptional profiling suggests that Mot1 positively affects about 10% of yeast genes and negatively affects about 5%. Unexpectedly, Mot1 associates with active RNA polymerase (Pol) II and III promoters, and it is rapidly recruited in response to activator proteins. At Pol II promoters, Mot1 association requires TBP and is strongly correlated with the level of TBP occupancy. However, the Mot1/TBP occupancy ratio at both Mot1-stimulated and Mot1-inhibited promoters is high relative to that at typical promoters, strongly suggesting that Mot1 directly affects transcriptional activity in a positive or negative manner, depending on the gene. The effect of Mot1 at the HIS3 promoter region depends on the functional quality and DNA sequence of the TATA element. Unlike TBP, Mot1 association is largely independent of the Srb4 component of Pol II holoenzyme, and it also can occur downstream of the promoter region. Mot1 removes TBP, but not TBP complexes or preinitiation complexes, from inappropriate genomic locations. Mot1 inhibits the association of NC2 with promoters, suggesting that the TBP-Mot1 and TBP-NC2 complexes compete for promoter occupancy in vivo. We speculate that Mot1 does not form transcriptionally active TBP complexes but rather regulates transcription in vivo by modulating the activity of free TBP and/or by affecting promoter DNA structure.

Adenosine Triphosphatases↗

A modified block matching method for real-time freehand strain imaging.

This manuscript reports a technical innovation that has been developed for real-time, freehand strain imaging. This work is based on a well-known block-matching algorithm with two significant modifications. First, since displacements are estimated row-by-row, displacement estimates from the previous row are used to predict the displacement estimates in the current row, thereby drastically reducing the search-region size and increasing computational efficiency. Second, a displacement error detection and correction method is developed to overcome the local tracking errors that may be more severe with freehand scanning and thereby improve the robustness of the algorithm. This algorithm has been implemented on a clinical ultrasound imaging system, and with real-time imaging feedback, long sequences of high quality strain images are observed using freehand compression. Displacement estimation errors with this method are experimentally measured and compared with results from simulation. We report only a specific implementation, with no comparison to other displacement estimators in the literature and no optimization of this specific technique. Images of tissue-mimicking phantoms with small spherical targets are used to test the ability to detect small lesions using the strain imaging technique. In vivo strain images of breast and thyroid are also shown.

Algorithms↗

Graphical representation of ribosomal RNA probe accessibility data using ARB software package.

BACKGROUND: Taxon specific hybridization probes in combination with a variety of commonly used hybridization formats nowadays are standard tools in microbial identification. A frequently applied technology, fluorescence in situ hybridization (FISH), besides single cell identification, allows the localization and functional studies of the microbial community composition. Careful in silico design and evaluation of potential oligonucleotide probe targets is therefore crucial for performing successful hybridization experiments. RESULTS: The PROBE Design tools of the ARB software package take into consideration several criteria such as number, position and quality of diagnostic sequence differences while designing oligonucleotide probes. Additionally, new visualization tools were developed to enable the user to easily examine further sequence associated criteria such as higher order structure, conservation, G+C content, transition-transversion profiles and in situ target accessibility patterns. The different types of sequence associated information (SAI) can be visualized by user defined background colors within the ARB primary and secondary structure editors as well as in the PROBE Match tool. CONCLUSION: Using this tool, in silico probe design and evaluation can be performed with respect to in situ probe accessibility data. The evaluation of proposed probe targets with respect to higher-order rRNA structure is of importance for successful design and performance of in situ hybridization experiments. The entire ARB software package along with the probe accessibility data is available from the ARB home page http://www.arb-home.de

Algorithms↗

Transcriptomic analysis of eggs, rediae and cercariae reveal stage-specific adaptations in the rumen fluke Calicophoron daubneyi.

Rumen flukes, particularly the trematode Calicophoron daubneyi, are emerging parasites of livestock in Europe, yet transcriptomic insights into their environmental and intermediate host stages remain limited. Here, we present a comprehensive transcriptomic analysis of eggs at three distinct developmental stages (freshly excreted, early developmental and eye-spot stages), as well as rediae and cercariae, of C. daubneyi. High-quality RNA-sequencing (RNA-seq) datasets revealed both shared and stage-specific transcriptional profiles with each developmental stage exhibiting its own distinct expression pattern. Subsequent GO-Term enrichment analyses revealed that fully embryonated eggs in eye-spot-stage especially upregulated genes related to cilia assembly, movement and motility, reflecting preparation for miracidial hatching and host-seeking behavior. Rediae showed enhanced transcription of genes involved in diverse metabolic and biosynthetic processes, supporting rapid asexual proliferation within the snail intermediate host. Cercariae exhibited predominant upregulation of genes associated with signal transduction and energy metabolism, indicating the adaptation to its changing environmental conditions. These findings provide the first transcriptomic insights into the biology of C. daubneyi outside the definitive host, reveal molecular mechanisms underlying development, transmission and adaptation to a changing environment and identify stage-specific genes as potential targets for interventions aimed at disrupting the parasites life cycle and controlling rumen flukes in the future.

Animals↗

[The epileptic crises of the Lennox-Gastaut syndrome. I. Convulsive forms].

Clinical and electroensephalographic aspects of twenty seven (27) patients with Lennox-Gastaut syndrome were studied (20 without previous West syndrome, group A, and 7 with this antecedent, group B). The epileptic seizures were characterized through descriptions made by relatives who were in close contact with the patients, and also by direct observation by the author in the clinic. The direct observation was possible due to high frequency of the seizures. Denominations were given to the manifestations not previously mentioned in the literature, according to the quality and eventual sequence of observable phenomena, in agreement with the terminology used by the Clinical and EEG Classification of Epileptic Seizures. The incidence, prognostic, clinical and evolutive aspects of elementary forms of epileptic seizures were discussed. Great variability of the convulsive seizures was verified, permitting their division into simple, complex and mixed forms.

Child, Preschool↗

[Epileptic crises of the Lennox-Gastaut syndrome. II. Partial and nonconvulsive forms].

Clinical and electroencephalographic aspects of partial and non convulsive forms of epileptic seizures of twenty seven (27) patients with Lennox-Gastaut syndrome were studied (20 without previous West syndrome, Group A, and 7 with this antecedent, group B). The epileptic seizures were characterized through descriptions made by relatives who were in close contact with the patients, and also by direct observation by the author in the clinic. The direct observation was possible due to high frequency rates of the seizures. Denominations were given to the manifestations not previously mentioned in the literature, according to the quality and eventual sequence of observable phenomena, in agreement with the terminology used by the Clinical and EEG Classification of Epileptic Seizures. The incidence and clinical aspects of elementary partial and non-convulsive forms of epileptic seizures were discussed. Great variability of the non-convulsive seizures was verified permiting their division into simple, complex and mixed forms, similarly to the absences. Unilateral forms of atonic seizures were identified.

Electroencephalography↗

The human biological resource centres network. A key infrastructure for biomedical research in Europe.

Continuing advances in life sciences and medical research are the result of the remarkable achievements of cell and molecular biology. In the post-sequencing era, the quality of the huge amount of data continuously generated by biotechnology, i.e. genomics, proteomics and high-throughput screening, depends on the quality assurance and the traceability of the original biological materials, including the annotations linked to these materials. Thus, biological resource centres are key infrastructures supporting biotechnology, bioprocessing and the development of new approaches in the prevention, diagnosis and treatment of diseases.

Biomedical Research↗

Metagenomic insights into antibiotic resistance genes and virulence factors in sediments of river Yamuna.

Riverine sediments serve as critical reservoirs of microbial diversity and functional genes, reflecting both natural ecological processes and anthropogenic impacts. In the present study, we employed a shotgun metagenomic approach to investigate microbial community composition, antimicrobial resistance (AMR) genes, and virulence factors in sediments collected from three environmentally distinct locations of the Yamuna River near Agra, India, representing BSA, TGY, and YEA. The sediment DNA was subjected to high-throughput Illumina sequencing, followed by quality control, assembly, and open reading frame prediction. Taxonomic classification and diversity analyses were performed using MEGAN6 and R-based statistical tools, while AMR genes were identified from predicted metagenomic proteins using the Resistance Gene Identifier (RGI) against the CARD database, with high-confidence perfect and strict hits retained; ARGs were interpreted independently of species-level host assignment. Virulence factors were assessed through presence-absence profiling of functionally relevant gene categories. The results revealed pronounced spatial heterogeneity in microbial communities, with increasing taxonomic diversity, functional complexity, and evenness from BSA to TGY and YEA. TGY and YEA composite samples showed greater observed representation of high-confidence AMR gene predictions spanning multiple drug classes and resistance mechanisms, alongside a diverse repertoire of virulence-associated genes linked to motility, adhesion, and secretion systems. In contrast, the BSA site harbored a comparatively simpler resistome and virulome. Overall, this study highlights Yamuna River sediments as important reservoirs of resistance and virulence determinants and underscores the need for long-term genomic surveillance to inform risk assessment, pollution control, and sustainable river management strategies.

AMR↗

The statistical distribution of the intensity of pixels within spots of DNA microarrays: what is the appropriate single-value representative?

This paper opens a discussion about an important issue in the analysis of data from spotted DNA microarrays: how to summarise into a single value the distribution for the intensity values of the pixels within a spot. Although the most popular statistic used is the median, there is no clear study demonstrating why it is more appropriate than other measures of central tendency such as the mean or the mode. Here, we argue that the median intensity is not the most appropriate measure for many common cases and discuss a frequently encountered case of a 'doughnut'-shaped spot for which the mode is closest to the 'expected' spot intensity. For an 'ideal' spot with a clear boundary and uniformly hybridised, the intensity of its pixels should approximately be normally distributed. In practical situations, these two requirements are often not met due to the physical properties of pins and the particularities of the printing and hybridisation processes. As a consequence, the distribution of the intensity of the pixels is usually negatively skewed. This asymmetry results in a larger displacement for the mean and median than for the mode from the ideal situation mentioned above.

Algorithms↗

[Quality assurance in food production in Europe according to ISO 90000 and HACCP (Hazard Analysis and Critical Control Points)].

HACCP is intended to make food protection programs evolve from a mainly retrospective quality control toward a preventative quality assurance approach and to provide an increased confidence in food safety. In parallel, the continuous evolution of quality concepts in the food industry resulted in the development of quality systems and quality assurance techniques with regard to the EN 29,000 (ISO 9000) series of standards. Specific to the food industry, HACCP can be seen as a very effective method to prepare specific Safety Assurance Plans (cf. the quality assurance plan concept) within a quality systems approach (Jouve, 1993). By reference to ISO 8402, a Quality Assurance Plan (QAP) basically sets out "the specific quality practices, resources and sequence of activities relevant to a particular product, service, contract or project". Quality assurance plans are more particularly useful for projects relating to new products or processes and/or comprising inter-related tasks whose interaction may be complex. In addition, in contractual or regulatory situations, such plans can be used to demonstrate the supplier's capability to meet identified objectives, specification or standards. In the food industry, the management of safety is a critical and complex issue which fits very well in the scope of application of a specific QAP; it is also where the use of HACCP is otherwise recommended by priority.

Food Contamination↗