bluuebunny/crossref_metadata_2025_split huggingface dataset:
Classification based upon gene expression data: bias and precision of error rates
Authors: Wood Ian A. , Visscher Peter M. , Mengersen Kerrie L. 
Published: March 2007

AbstractMotivation: Gene expression data offer a large number of potentially useful predictors for the classification of tissue samples into classes, such as diseased and non-diseased. The predictive error rate of classifiers can be estimated using methods such as cross-validation. We have investigated issues of interpretation and potential bias in the reporting of error rate estimates. The issues considered here are optimization and selection biases, sampling effects, measures of misclassification rate, baseline error rates, two-level external cross-validation and a novel proposal for detection of bias using the permutation mean.Results: Reporting an optimal estimated error rate incurs an optimization bias. Downward bias of 3–5% was found in an existing study of classification based on gene expression data and may be endemic in similar studies. Using a simulated non-informative dataset and two example datasets from existing studies, we show how bias can be detected through the use of label permutations and avoided using two-level external cross-validation. Some studies avoid optimization bias by using single-level cross-validation and a test set, but error rates can be more accurately estimated via two-level cross-validation. In addition to estimating the simple overall error rate, we recommend reporting class error rates plus where possible the conditional risk incorporating prior class probabilities and a misclassification cost matrix. We also describe baseline error rates derived from three trivial classifiers which ignore the predictors.Availability: R code which implements two-level external cross-validation with the PAMR package, experiment code, dataset details and additional figures are freely available for non-commercial use from http://www.maths.qut.edu.au/profiles/wood/permr.jspContact: i.wood@qut.edu.auSupplementary information: Supplementary data are available at Bioinformatics online.
Lesions attributed to vaccination of sheep with Gudair™ for the control of ovine paratuberculosis: post farm economic impacts at slaughter
Authors: Eppleston J , Windsor PA 
Published: March 2007

Objective   To determine i) the prevalence of lesions at the site of vaccination with Gudair™, and ii) the incidence of discounting of slaughtered sheep carcasses due to the presence of these lesions.Design   A survey of the prevalence of injection lesions and actual discounts applied to 20 consignments of vaccinates slaughtered in abattoirs in New South Wales.Procedure   Consignments of sheep previously vaccinated against ovine Johne's disease (OJD) were assessed on the slaughter chain for the prevalence of vaccination site lesions and any costs associated with carcass trimming were estimated. In addition a telephone survey was conducted to determine the experiences and risk attitudes of 8 abattoirs in south east New South Wales likely to have previously processed vaccinates.Results   The prevalence of lesions observed was 18% for adult (mutton) and 65% for lamb carcasses. The value of the trim removed was insignificant, the labour cost of its removal was nil and no carcass was downgraded to a lower value grade.Conclusion   Under the market conditions existing at the time the study was conducted, in sheep vaccinated at the recommended site high on the neck, it is unlikely that OJD vaccination site lesions will be a significant cost to producers or the processing industry and will represent only a very small proportion of the total cost of OJD control by vaccination.
The tightly regulated promoter of the xanA gene of Aspergillus nidulans is included in a helitron
Authors: Cultrone Antonietta , Domínguez Yazmid Reyes , Drevet Christine , Scazzocchio Claudio , Fernández‐Martín Rafael 
Published: March 2007

SummaryIn Aspergillus nidulans the xanA gene codes for a xanthine α‐ketoglutarate‐dependent dioxygenase, an enzyme only present in the fungal kingdom. The 5′ region of this gene, including its putative promoter and the first 54 codons of the open reading frame, together with the first intron is duplicated in the genome. This duplication corresponds to a helitron, a eukaryotic element proposed to transpose replicatively by the rolling circle mechanism. We show that the regulation of xanA conforms to that of other genes of the purine degradation pathway, necessitating the specific UaY transcription factor and the AreA GATA factor. The promoter of the duplicated region is active ectopically and the difficulty in detecting an mRNA from the duplicated region is at least partially due to nonsense‐mediated decay. Comparative genomic data are only consistent with the hypothesis that the 5′ region of xanA pre‐existed the helitron insertion, and that a ‘secondary helitron’ was generated from an insertion 5′ to it and a pre‐existing 3′ consensus sequence within the open reading frame. It is possible to propose a role of helitrons in promoter shuffling and thus in recruiting new genes into specific regulatory circuits.
Chromosomal toxin–antitoxin loci can diminish large‐scale genome reductions in the absence of selection
Authors: Szekeres Silvia , Dauti Mira , Wilde Caroline , Mazel Didier , Rowe‐Magnus Dean A. 
Published: March 2007

SummarySuperintegrons (SIs) are chromosomal genetic elements containing assemblies of genes, each flanked by a recombination sequence (attC site) targeted by the integron integrase. SIs may contain hundreds of attC sites and intrinsic instability is anticipated; yet SIs are remarkably stable. This implies that either selective pressure maintains the genes or mechanisms exist which favour their persistence in the absence of selection. Toxin/antitoxin (TA) systems encode a stable toxin and a specific, unstable antitoxin. Once activated, the continued synthesis of the unstable antitoxin is necessary for cell survival. A bioinformatic search of accessible microbial genomes for SIs and TA systems revealed that large SIs harboured TA gene cassettes while smaller SIs did not. We demonstrated the function of TA loci in different genomic contexts where large‐scale deletions can occur; in SIs and in a 165 kb dispensable region of the Escherichia coli genome. When devoid of TA loci, large‐scale genome loss was evident in both environments. The inclusion of two TA loci, relBE1 and parDE1, which we identified in the Vibrio vulnificus SI rendered these environments refractory to gene loss. Thus, chromosomal TA loci can stabilize massive SI arrays and limit the extensive gene loss that is a hallmark of reductive evolution.
Control of IS911 target selection: how OrfA may ensure IS dispersion
Authors: Rousseau Philippe , Loot Céline , Guynet Catherine , Ah‐Seng Yoan , Ton‐Hoang Bao , Chandler Mick 
Published: March 2007

SummaryIS911 transposition involves a closed circular insertion sequence intermediate (IS‐circle) and two IS‐encoded proteins: the transposase OrfAB and OrfA which regulates IS911 insertion. OrfAB alone promotes insertion preferentially next to DNA sequences resembling IS911 ends while the addition of OrfA strongly stimulates insertion principally into DNA targets devoid of the IS911 end sequences. OrfAB shares its N‐terminal region with OrfA. This includes a helix–turn–helix (HTH) motif and the first three of four heptads of a leucine zipper (LZ). OrfAB binds specifically to IS911 ends via its HTH whereas OrfA does not. We show here: that OrfA binds DNA non‐specifically and that this requires the HTH; that OrfA LZ is required for its multimerization; and that both motifs are essential for OrfA activity. We propose that these OrfA properties are required to assemble a nucleoprotein complex committed to random IS911 insertion. This control of IS911 insertion activity by OrfA in this way would assure its dispersion.
The telomere system of the Streptomyces linear plasmid SCP1 represents a novel class
Authors: Huang Chih‐Hung , Tsai Hsiu‐Hui , Tsay Yeou‐Guang , Chien Yu‐Nien , Wang Shan‐Li , Cheng Ming‐Yuan , Ke Chia‐Hui , Chen Carton W. 
Published: March 2007

SummaryLinear plasmids and chromosomes of Streptomyces carry terminal proteins (TPs) covalently attached to the 5′ ends of the DNA. Most known telomeres are conserved in primary sequence and in the potential secondary structures formed during replication. The TP that caps these telomeres is also highly conserved and its coding gene, tpg, is present in all Streptomyces chromosomes and some linear plasmids. Linear plasmid SCP1 contains atypical telomere sequences and no tpg homologue, and can replicate in the absence of tpg, suggesting that it carries a novel TP gene. To isolate the TP on the SCP1 telomeres, we constructed a multicopy mini‐SCP1 plasmid. The TP capping the plasmid was isolated and subjected to tryptic digestion and mass spectrometric analysis, and the results indicated that the TP was encoded by an open reading frame (ORF), SCP1.127 (tpc), on SCP1. Of the two ORFs upstream of tpc, SCP1.125 (tac) but not SCP1.126 was essential for replication of mini‐SCP1. The Tac–Tpc system of SCP1 represents a convergently evolved novel telomere‐capping system of Streptomyces linear replicons.
Cell cycle‐regulated vesicular trafficking of Toxoplasma APT1, a protein localized to multiple apicoplast membranes
Authors: Karnataki Anuradha , DeRocher Amy , Coppens Isabelle , Nash Coral , Feagin Jean E. , Parsons Marilyn 
Published: March 2007

SummaryThe apicoplast is a relict plastid essential for viability of the apicomplexan parasites Toxoplasma and Plasmodium. It is surrounded by multiple membranes that proteins, substrates and metabolites must traverse. Little is known about apicoplast membrane proteins, much less their sorting mechanisms. We have identified two sets of apicomplexan proteins that are homologous to plastid membrane proteins that transport phosphosugars or their derivatives. Members of the first set bear N‐terminal extensions similar to those that target proteins to the apicoplast lumen. While Toxoplasma gondii lacks this type of translocator, the N‐terminal extension from the Plasmodium falciparum sequence was shown to be functional in T. gondii. The second set of translocators lacks an N‐terminal targeting sequence. This translocator, TgAPT1, when tagged with HA, localized to multiple apicoplast membranes in T. gondii. Contrasting with the constitutive targeting of luminal proteins, the localization of the translocator varied during the cell cycle. Early‐stage parasites showed circumplastid distribution, but as the plastid elongated in preparation for division, vesicles bearing TgAPT1 appeared adjacent to the plastid. After plastid division, the protein resumes a circumplastid colocalization. These studies demonstrate for the first time that vesicular trafficking likely plays a role in the apicoplast biogenesis.
The type III secretion system needle tip complex mediates host cell sensing and translocon insertion
Authors: Veenendaal Andreas K. J. , Hodgkinson Julie L. , Schwarzer Lynn , Stabat David , Zenk Sebastian F. , Blocker Ariel J. 
Published: March 2007

SummaryType III secretion systems (T3SSs) are essential virulence determinants of many Gram‐negative bacterial pathogens. The Shigella T3SS consists of a cytoplasmic bulb, a transmembrane region and a hollow ‘needle’ protruding from the bacterial surface. Physical contact with host cells initiates secretion and leads to assembly of a pore, formed by IpaB and IpaC, in the host cell membrane, through which proteins that facilitate host cell invasion are translocated. As the needle is implicated in host cell sensing and secretion regulation, its tip should contain components that initiate host cell contact. Through biochemical and immunological studies of wild‐type and mutant Shigella T3SS needles, we reveal tip complexes of differing compositions and functional states, which appear to represent the molecular events surrounding host cell sensing and pore formation. Our studies indicate that the interaction between IpaB and IpaD at needle tips is key to host cell sensing, orchestration of IpaC secretion and its subsequent assembly at needle tips. This allows insertion into the host cell membrane of a translocation pore that is continuous with the needle.
Transposition and target specificity of the typical IS30 family element IS1655 from Neisseria meningitidis
Authors: Kiss János , Nagy Zita , Tóth Gábor , Kiss György Botond , Jakab Júlia , Chandler Michael , Olasz Ferenc 
Published: March 2007

SummaryWe have analysed the transposition and target selection strategy of IS1655, a typical IS30 family member resident in Neisseria meningitidis. We have redefined IS1655 as a 1080 bp long element with 25 bp imperfect inverted repeats (IRs), which generates a 3 bp target duplication and have shown that it transposes using an intermediate with abutted IRs separated by 2 bp. IS1655 exhibits bipartite target specificity inserting preferentially either next to sequences similar to its IRs or into an unrelated but well defined sequence. IR‐targeting leads to the formation of a new junction in which the targeted IR and one of the donor IRs are separated by 2 bp. The non‐IR targets were characterized as an imperfect 19 bp palindrome in which the central five positions show slight GC excess and the distal region is AT‐rich. Artificial targets designed according to the consensus were recognized by the element as hot spots for insertion. The organization of IS1655 is similar to that of other IS30 family members. Moreover, it shows striking similarity to IS30 in transposition strategy even though their transposases differ in their N‐terminal regions, which, for IS30, appears to determine target specificity. Comparative analysis of the transposases and the evolutionary aspects of sequence variants are also briefly discussed.
Enteropathogenic Escherichia coli Tir is an SH2/3 ligand that recruits and activates tyrosine kinases required for pedestal formation
Authors: Bommarius Bettina , Maxwell David , Swimm Alyson , Leung Sara , Corbett Anita , Bornmann William , Kalman Daniel 
Published: March 2007

SummaryEnteropathogenic Escherichia coli (EPEC) cause intestinal inflammation, severe diarrhoea and mortality, particularly among children in developing nations. Upon attachment to intestinal epithelial cells, EPEC induces actin‐filled membrane protrusions called ‘pedestals’ and disrupts microvilli to form attaching and effacing (A/E) lesions. EPEC also disrupts epithelial barrier function and causes colitis. Here we have investigated how virulence factors which orchestrate formation of actin pedestals interface with host tyrosine kinases. We show that Tec‐family tyrosine kinases localize beneath EPEC and, with Abl‐family kinases, comprise a set of redundant host kinases utilized by EPEC to form actin pedestals. We also show that Tir, a virulence factor required for pathogenesis, contains a polyproline region (PPR) that interacts with SH3 domains of redundant kinases, and a phosphorylation site (Y474) that interacts with kinase SH2 domains. These interactions are essential for pedestal formation, and mimic activation of kinases by cellular ligands. Our results suggest that a positive feedback loop exists in which initial phosphorylation of Tir on Y474 by tyrosine kinases causes recruitment of additional redundant kinases via PPR–SH3 interactions and PO3–Y474–SH2 interactions, which in turn phosphorylate other Tir molecules as well as proteins that catalyse formation of actin pedestals.
Cellulosomes: microbial nanomachines that display plasticity in quaternary structure
Authors: Gilbert Harry J. 
Published: March 2007

SummaryThe assembly of proteins that display complementary activities into supramolecular intra‐ and extracellular complexes is central to cellular function. One such nanomachine of considerable biological and industrial significance is the plant cell wall degrading apparatus of anaerobic bacteria termed the cellulosome. The Clostridium thermocellum cellulosome assembles through the interaction of a type I dockerin module in the catalytic entities with one of several type I cohesin modules in the non‐catalytic scaffolding protein. Recent structural studies have provided the molecular details of how dockerin–cohesin interactions mediate both cellulosome assembly and the retention of the protein complex on the bacterial cell surface. The type I dockerin, which displays near‐perfect sequence and structural symmetry, interacts with its cohesin partner through a dual binding mode in which either the N‐ or C‐terminal helix dominate heterodimer formation. The biological significance of this dual binding mode is discussed with respect to the plasticity of the orientation of the catalytic subunits within this supramolecular assembly. The flexibility in the quaternary structure of the cellulosome may reflect the challenges presented by the degradation of a heterogenous recalcitrant insoluble substrate by an intricate macromolecular complex, in which the essential synergy between the catalytic subunits is a key feature of cellulosome function.
Analysis of resistance to Xylella fastidiosa within a hybrid population of Pera sweet orange × Murcott tangor
Authors: Coletta‐Filho H. D. , Pereira E. O. , Souza A. A. , Takita M. A. , Cristofani‐Yale M. , Machado M. A. 
Published: March 2007

Resistance to Xylella fastidiosa was evaluated within a population of 20 interspecific hybrids of Pera sweet orange and Murcott tangor under greenhouse conditions. Efficiency of inoculation, multiplication of bacteria within the plants, xylem vessel morphology, and symptom expression were analysed. The rate of infection ranged from 40 to 100% (average 70%) for all genotypes analysed. Xylella fastidiosa populations ranged from log 0·59 to log 2·13 cells mg−1 tissue for the resistant hybrids. These values were significantly different (P = 0·05) from those obtained for the tolerant (no symptoms but bacteria recovered) or susceptible (symptoms and bacteria recovered) hybrids (log 3·02 to log 4·06 cells mg−1). Xylella fastidiosa was recovered from all hybrids (log 2·31 to 5·03 CFU mg−1 tissue) except the resistant ones. The first foliar symptoms appeared at least 90 days post‐inoculation, the time varying according to genotype. No correlation between xylem vessel morphology and disease expression was observed, indicating that the resistance was the result of a genetic response of the host. According to this hypothesis, a high broad‐based heritability index for resistance was obtained (0·96) at 210 days from X. fastidiosa inoculations, using bacterial quantification by real‐time PCR, which indicated that the influence of the number of bacteria was the result of genetic rather than environmental variations.
Acitretin‐induced subungual hemorrhage
Authors: Aydogan Kenan , Karadogan Serap Koran , Tunali Sukran 
Published: March 2007

A 20‐year‐old woman with a 2‐year history of histologically confirmed palmoplantar keratoderma due to psoriasis, resistant to several topical agents, was admitted to the Department of Dermatology, Uludag University, Bursa, Turkey. Therapy with oral acitretin (0.5 mg/kg/day, 35 mg/day) was initiated. A month after starting acitretin treatment, she noted slight reddening of the second left fingernail. Clinical examination revealed red–brown discoloration of the second fingernail associated with subungual hemorrhage involving the proximal nail bed (lunula region) (Fig. 1). The nail change was asymptomatic. The patient complained only of discoloration underneath the nail plate. No abnormalities were detected on the skin, mucous membranes, or toenails/other fingernails. The patient denied exposure to microtrauma or any other drugs. The erythrocyte sedimentation rate, full blood cell count, electrolytes, renal and hepatic tests, and serum lipids were normal. Coagulation tests, including blood clotting time, international normalized ratio, activated partial thromboplastin time, thrombin time, platelet number, and function tests, were within normal levels.Acitretin‐induced subungual hemorrhage involving the proximal portion (lunula region) of the second left fingernail bedimageTreatment with acitretin was discontinued, and the nail change resolved completely after 3 weeks. A similar episode of subungual hemorrhage recurred, however, within 48 h after re‐challenge with a lower dose of acitretin (25 mg/day). The drug was definitively stopped and the eruption faded again within a week. An objective causality assessment suggests that subungual hemorrhage was probably related to acitretin in this patient.
Sex‐specific ecomorphological variation and the evolution of sexual dimorphism in dwarf chameleons (Bradypodion spp.)
Authors: STUART‐FOX D. , MOUSSALLI A. 
Published: March 2007

AbstractNatural selection can influence the evolution of sexual dimorphism through selection for sex‐specific ecomorphological adaptations. The role of natural selection in the evolution of sexual dimorphism, however, has received much less attention than that of sexual selection. We examined the relationship between habitat structure and both male and female morphology, and sexual dimorphism in size and shape, across 21 populations of dwarf chameleon (genus Bradypodion). Morphological variation in dwarf chameleons was strongly associated with quantitative, multivariate aspects of habitat structure and, in most cases, relationships were congruent between the sexes. However, we also found consistent relationships between habitat and sexual dimorphism. These resulted from both differences in magnitude of ecomorphological relationships that were otherwise congruent between the sexes, as well as in sex‐specific ecomorphological adaptations. Our study provides evidence that natural selection plays an important role in the evolution of sexual dimorphism.
Genotypic selection in Daphnia populations consisting of inbred sibships
Authors: HAAG C. R. , EBERT D. 
Published: March 2007

AbstractThe genetic basis of fitness reduction associated with inbreeding is still poorly understood. Here we use associations between allozyme genotypes and fitness to investigate the genetic basis of inbreeding depression in experimental outdoor populations of the water flea, Daphnia magna. In Daphnia, a phase of clonal reproduction follows hatching from sexually produced resting eggs, and changes in genotype frequencies during the clonal phase can be used to estimate fitness. Our experiment resembles natural colonization of ponds in that single clones colonize an empty pool, expand asexually and produce sexual offspring by selfing (sisters mate with their clonal brothers). These offspring diapause and form populations consisting of selfed sibships in the following spring. In 12 of 13 experimental populations, genotypes of selfed hatchlings after diapause conformed to Mendelian expectations. During the subsequent ca. 10 asexual generations, however, genotype frequencies changed significantly at 19 of 27 single loci studied within populations, mostly in favour of heterozygotes, with heterozygosity at multiple loci affecting the change in genotype frequency multiplicatively. Because variance in heterozygosity among siblings at a given marker reflects only heterozygosity in the chromosomal region around this marker, our results suggest that selection at fitness‐associated loci in the chromosomal regions near the markers were responsible for these changes. The genotype frequency changes were more consistent with selection acting on linked loci than on the allozymes themselves. Taken together, the evidence for abundant selection in the chromosomal regions of the markers and the fact that changes in genotype frequencies became apparent only after several generations of clonal selection, point to a genetic load consisting of many alleles of small or intermediate effects, which is consistent with the strong genetic differentiation and repeated genetic bottlenecks in the metapopulation from which the animals for this study were obtained.