bluuebunny/crossref_metadata_2025 huggingface dataset:
MPI-LIT: a literature-curated dataset of microbial binary protein--protein interactions
Authors: Rajagopala Seesandra V. , Goll Johannes , Gowda N.D. Deve , Sunil Kumar C. , Titz Björn , Mukherjee Arnab , Mary Sharmila S. , Raviswaran Naresh , Poojari Chetan S. , Ramachandra Srinivas , Shtivelband Svetlana , Blazie Stephen M. , Hofmann Julia , Uetz Peter
Published: September 2008

Prokaryotic protein–protein interactions are underrepresented in currently available databases. Here, we describe a ‘gold standard’ dataset (MPI-LIT) focusing on microbial binary protein–protein interactions and associated experimental evidence that we have manually curated from 813 abstracts and full texts that were selected from an initial set of 36 852 abstracts. The MPI-LIT dataset comprises 1237 experimental descriptions that describe a non-redundant set of 746 interactions of which 659 (88%) are not reported in public databases. To estimate the curation quality, we compared our dataset with a union of microbial interaction data from IntAct, DIP, BIND and MINT. Among common abstracts, we achieve a sensitivity of up to 66% for interactions and 75% for experimental methods. Compared with these other datasets, MPI-LIT has the lowest fraction of interaction experiments per abstract (0.9) and the highest coverage of strains (92) and scientific articles (813). We compared methods that evaluate functional interactions among proteins (such as genomic context or co-expression) which are implemented in the STRING database. Most of these methods discriminate well between functionally relevant protein interactions (MPI-LIT) and high-throughput data.

Availability:  http://www.jcvi.org/mpidb/interaction.php?dbsource=MPI-LIT.

Contact:  raja@jcvi.org

Supplementary information:  Supplementary data are available at Bioinformatics online.
A Pictorial Disease Severity Key and the Relationship Between Severity and Incidence for Black Root Rot of Pansy Caused by Thielaviopsis basicola
Authors: Copes Warren E. , Stevenson Katherine L.
Published: September 2008

A pictorial key was developed and the relationship between disease severity (S) and incidence (I) was examined to aid in the assessment of black root rot of pansy caused by Thielaviopsis basicola. The key consisted of photographs of root segments that represented nine disease severity levels ranging from 1 to 91%. Pansies that had received different fertility treatments, as part of seven separate experiments, were inoculated with T. basicola. Four weeks after inoculation, roots were washed, and incidence and severity of black root rot were visually assessed using a grid-line-intersect method. Disease incidence ranged from 1.3 to 100%, and severity ranged from 0.1 to 21.4% per plant. Four different mathematical models were compared to quantitatively describe the I-S relationship for the combined data from all seven experiments. Although all models provided an adequate fit, the model that is analogous to the Kono-Sugino equation provided the most reliable estimate of severity over the entire range of disease incidence values. The predictive ability and accuracy of this model across data sets was verified by jackknife and cross-validation techniques. We concluded that incidence of black root rot in pansy can be assessed more objectively and with greater precision than disease severity and can be used to provide reliable estimates of disease severity based on derived regression equations that quantify the I-S relationship for black root rot.
Canker and Twig Dieback of Blueberry Caused by Pestalotiopsis spp. and a Truncatella sp. in Chile
Authors: Espinoza José G. , Briceño Erika X. , Keith Lisa M. , Latorre Bernardo A.
Published: September 2008

Blueberry (Vaccinium spp.) has great economic importance in Chile, which currently has about 8,500 ha being cultivated. Recently, the presence of canker and dieback symptoms has been observed along the productive blueberry zone of Chile. Species of Pestalotiopsis and Truncatella were consistently isolated from diseased samples in 22 different locations. Therefore, the objective of this study was to identify and characterize the species of Pestalotiopsis and Truncatella associated with canker and twig dieback symptoms on blueberry. Forty-nine isolates were obtained on acidified potato dextrose agar in 2006 and 2007. These isolates were identified as Pestalotiopsis clavispora, P. neglecta, and Truncatella (=Pestalotia) angustata on the basis of colony characteristics and conidial morphology. This identification was verified by internal transcribed spacer analysis of DNA. Isolates of P. clavispora, P. neglecta, and T. angustata were pathogenic on apple, kiwifruit, and blueberry fruit. Similarly, isolates of P. clavispora were pathogenic on detached blueberry twigs of cv. O'Neal. Additionally, three selected isolates of P. clavispora induced light-brown canker lesions, surrounded by a reddish halo, and shoot dieback after twig inoculations on 2-year-old twigs of blueberry cvs. O'Neal, Bluecrop, Brightwell, Brigitta, Duke, Elliot, and Misty. Among blueberry cultivars, Brightwell and O'Neal were the most susceptible and Bluecrop and Misty the least susceptible, while Elliot, Brigitta, and Duke were moderately susceptible to P. clavispora. These pathogens were isolated consistently from inoculated plants, confirming Koch's postulates. P. clavispora was highly sensitive to fludioxonil and pyraclostrobin with a median effective concentration of 0.06 to 0.08 and 0.04 to 0.8 μg/ml, respectively. Therefore, the results of this study indicate that P. clavispora, P. neglecta, and T. angustata are primary pathogens that can cause canker lesions and dieback symptoms on blueberry not previously described in Chile. However, these results do not exclude that other species of these genera or other plant-pathogenic fungi (e.g., Botryosphaeria, Pestalotia, and Phomopsis spp.) may eventually be involved in this syndrome of blueberry.
First Report of Pea enation mosaic virus Infecting Pea and Broad Bean in Spain
Authors: Tornos T. , Cebrián M. C. , Córdoba-Sellés M. C. , Alfaro-Fernández A. , Herrera-Vásquez J. A. , Font M. I. , Jorda M. C.
Published: September 2008

During the spring of 2007, pea plants (Pisum sativum L.) (cvs. Utrillo and Floreta) showing virus-like symptoms were observed in several commercial fields in the southern and eastern regions of Catalonia, Spain. Incidence of symptomatic plants ranged from 5 to 15% and was distributed in both small and large patches. Infected plants exhibited yellow mosaic leaf symptoms that later became translucent. Leaves gradually curled and in some cases developed enations near the veins on the abaxial surface. Plants were “bushy” and had shortened internodes. Infection prior to pod formation resulted in pods that were distorted and stunted (1). The infected leaves and pods were tested by indirect-ELISA with a potyvirus-specific antibody (Agdia, Elkhart, IN) and double-antibody sandwich (DAS)-ELISA with antibodies specific to Pea enation mosaic virus (PEMV), Broad bean wilt virus 1 (BBWV-1), Beet western yellow virus (BWYV), Bean yellow mosaic virus (BYMV), Alfalfa mosaic virus (AMV), and Tomato spotted wilt virus (TSWV) (Loewe Biochemica GmbH, Sauerlach, Germany). PEMV was detected in all 24 symptomatic samples that were collected from 10 locations between March 2007 and March 2008. Thirteen of these samples also tested positive for BWYV, but no differences in symptom expression were observed in plants infected with both viruses or PEMV alone. PEMV was also identified in seven broad bean plants (Vicia faba L.) from three additional locations. These plants expressed interveinal yellow mosaic on leaves and deformed pods. The genomic sequence of PEMV-1 (GenBank Accession No. L04573) was used to design primers to amplify a 451-nt segment of the polymerase gene by reverse transcription (RT)-PCR; PEMV-D (5′-TGACCATGAGTCCACTGAGG-3′), PEMV-R (5′-AGTATCTTCCAACAACCACAT-3′). One ELISA-positive sample was analyzed and the expected size amplicon was generated. Direct sequencing (GenBank Accession No. EU652339) revealed that PEMV-1 and our pea isolate have nucleotide sequence identities of 95%. To our knowledge, this is the first report of PEMV in Spain, which might cause important economical losses since PEMV is an important viral disease of pea and other legumes worldwide.

Reference: (1) J. S. Skaf and G. A. Zoeten. No. 372 (No. 257 revised) in: Description of Plant Viruses. AAB, Kew, Surrey, England, 2000.
First Report of White Mold Caused by Sclerotinia sclerotiorum on Sweet Basil in Turkey
Authors: Tok F. M.
Published: September 2008

In February of 2008, wilt and collapse of sweet basil (Ocimum basilicum L.) was observed on approximately 20% of the plants in a commercial greenhouse in Demre, Antalya, Turkey. Crown and stems of infected plants were necrotic; leaves turned brown and wilted. Profuse, white mycelia and occasionally black sclerotia were found inside and outside of affected stems. Sclerotinia sclerotiorum (Lib). de Bary, identified based on morphological characteristics was isolated from sclerotia and symptomatic stems on potato dextrose agar amended with tetracycline. To conduct pathogenicity tests, sclerotia produced on carrot discs were surface disinfested in 70% ethanol and dried on sterilized filter papers. Ten sclerotia were placed in 9-cm-diameter glass petri plates containing 15 ml of sterilized distilled water. Plates were wrapped with Parafilm and incubated at 4°C for 5 to 6 weeks in the dark. Plates were then incubated at 15°C in 12 h of dark and 12 h of light. Apothecia developed after 2 weeks. Ascospores were harvested from apothecia with distilled water by crushing and shaking the apothecia in centrifuge tubes. Thirty basil plants sprayed with ascospores (106 spores per ml) were maintained in a growth chamber at 22°C and 90% humidity. After 2 weeks, necrotic leaves and stems were observed on all inoculated plants. S. sclerotiorum was recovered from symptomatic tissues. No symptoms developed on the 30 basil plants sprayed with sterile distilled water. The pathogenicity test was repeated with similar results. S. sclerotiorum on basil has been reported in Canada (4), the United States, (2,3), and Italy (1). To our knowledge, this is the first report of S. sclerotiorum on basil in Turkey.

References: (1) A. Garibaldi et al. Plant Dis. 81:124, 1997. (2) G. E. Holcomb and M. J. Reed. Plant Dis. 78:924, 1994. (3) S. T. Koike. Plant Dis. 84:1342, 2000. (4) T. C. Paulitz. Plant Dis. 81:229, 1997.
First Report of Soybean Rust Caused by Phakopsora pachyrhizi on Erythrina herbacea (Coral Bean)
Authors: Gevens A. J. , Nequi N. , Vitoreli A. , Marois J. J. , Wright D. L. , Harmon C. L. , Harmon P. F.
Published: September 2008

Soybean rust (SBR), caused by the obligate fungus Phakopsora pachyrhizi Syd. & P. Syd., was initially reported on soybean (Glycine max L.) in Louisiana in 2004 and has since been reported on soybean and/or kudzu (Pueraria lobata (Willd.) Ohwi) in 9 states in 2005, 15 states in 2006, and 19 states in 2007 (1). The host range of P. pachyrhizi includes plants that are all in the Fabaceae or legume family. Six plant species in the United States have been reported as hosts of P. pachyrhizi: soybean, kudzu, Florida beggarweed (Desmodium tortuosum (Sw) DC.), dry bean (Phaseolus vulgaris L.), lima bean (P. lunatus L.), and scarlet runner bean (P. coccineus L.) (4). On 17 April 2008, a rust disease was observed on a weedy legume host with red showy flowers that was growing with kudzu in an overgrown vacant lot in the understory of live oak trees (Quercus virginiana Mill.) in Citra, FL. The discovery was made during routine scouting of this Integrated Pest Management Pest Information Platform for Extension and Education (IPM PIPE) mobile sentinel plot (3). The plant was confirmed by University of Florida botanists to be Erythrina herbaceae L., commonly known as coral bean. Coral bean is native to the southeastern United States and also is planted as a perennial ornamental. A sample of leaves exhibiting rust pustules characteristic of P. pachyrhizi uredinia was collected and examined with a microscope. Brown-to-brick red, angular lesions that were 3 to 11 mm in diameter (average 6.75 mm) were observed on the undersides of the leaves of two trifoliates. Within these lesions, there were several uredinia, some exuding hyaline, echinulate urediniospores (20 × 25 μm). The visual diagnosis and the species of the rust fungus were confirmed to be P. pachyrizi by a real-time PCR protocol (2). The diagnosis on this new host was verified by a USDA, APHIS National Mycologist in Beltsville, MD. Coral bean may serve as an additional overwintering host for P. pachyrhizi in the southeast. To our knowledge, this is the first report of soybean rust caused by P. pachyrhizi on E. herbaceae.

References: (1) R. S. C. Christiano and H. Scherm, Phytopathology 97:1428, 2007. (2) R. D. Frederick et al. Phytopathology 92:217, 2002. (3) S. A. Isard et al. Online publication. doi:10.1094/PHP-2006-0915-01-RV. Plant Health Progress, 2006. (4) T. L. Slaminko et al. Plant Dis. 92:767, 2008.
First Report of Oilseed Rape Stem Rot Caused by Sclerotinia sclerotiorum in Greece
Authors: Tziros G. T. , Bardas G. A. , Tsialtas J. T. , Karaoglanidis G. S.
Published: September 2008

Oilseed rape (Brassica napus L.) was recently introduced into Greece for the production of biofuels. During May of 2007, symptoms typical of stem rot were observed on oilseed rape plants in three commercial fields in the area of Galatades-Pella, Central Macedonia, Greece. Approximately 30% of the plants were affected. Symptoms began as a chlorotic wilt on the foliage and developed into necrosis of basal stems. In the advanced stages of the disease, stems and branches became bleached and eventually died. White, as well as black, mycelium and irregularly shaped sclerotia (2 to 5 mm in diameter) were produced abundantly on and inside the affected stems. To isolate the pathogen, 20 symptomatic 6-month-old plants were collected from each field. Sclerotia were dipped in 70% ethanol, surface sterilized in 1% sodium hypochlorite for 1 min, and rinsed in sterile water. Sclerotia placed on potato dextrose agar (PDA) were incubated in the dark at 25°C for 10 days. Sclerotinia sclerotiorum (Lib.) de Bary was identified on the basis of morphological characteristics (2). To conduct pathogenicity tests, 10 6-week-old oilseed rape plants (cv. Titan) were each inoculated with a 5-mm-diameter colonized PDA disk placed in wounds made in the basal stem with a sterile scalpel. Five control plants were treated similarly except that the agar disk did not contain mycelium. Plants were then covered with a plastic bag to maintain high humidity. After 72 h, the bags were removed and the plants were maintained in a growth chamber at 23 to 25°C with a 12-h photoperiod and 75% relative humidity. Pathogenicity tests were repeated three times. Symptoms identical to those observed in the field developed within 12 days after inoculation; control plants remained healthy. The fungus was reisolated from all inoculated plants, confirming Koch's postulates. S. sclerotiorum has been reported on oilseed rape in Argentina, Australia, Brazil, Canada, the United States, and New Zealand (1). To our knowledge, this is the first report of Sclerotinia stem rot of oilseed rape in Greece.

References: (1) D. F. Farr et al. Fungal Databases. Systematic Botany and Mycology Laboratory. Online publication. ARS, USDA, 2008. (2) L. M. Kohn. Phytopathology 69:881, 1979.
A New ‘Candidatus Liberibacter’ Species in Solanum tuberosum in New Zealand
Authors: Liefting L. W. , Perez-Egusquiza Z. C. , Clover G. R. G. , Anderson J. A. D.
Published: September 2008

Symptoms resembling “zebra chip” disease (3) were observed in potato (Solanum tuberosum) tubers harvested from a breeding trial in South Auckland, New Zealand in May 2008. The tubers had necrotic flecking and streaking that became marked when the potatoes were fried. Affected plants generally senesced early, at the beginning of April. The mean yield was approximately 60% less than expected and harvested tubers had less dry matter (13%) than normal (19%). Large numbers of the psyllid Bactericera cockerelli were observed on the crop during the summer. Total DNA was extracted from the vascular tissue of five symptomatic tubers and seven volunteers collected from the affected field with a DNeasy Plant Mini Kit (Qiagen, Valencia, CA). Samples were tested by PCR using primers OA2 (GenBank Accession No. EU834130) and OI2c (2). These primers amplify a 1,160-bp fragment of the 16S rRNA sequence of a ‘Candidatus Liberibacter’ species identified in tomato and capsicum in New Zealand. No fragment was amplified from healthy plants, but amplicons of the expected size were obtained from all symptomatic tubers and one plant. A 650-bp fragment of the β operon was also amplified from symptomatic tubers. The amplicons were directly sequenced (GenBank Accession Nos. EU849020 and EU919514). BLAST analysis showed 100% identity to the tomato/capsicum liberibacter (GenBank Accession Nos. EU834130 and EU834131). From a commercial potato field adjoining the breeding trial, groundkeeper tubers were collected and separated into those that were asymptomatic and those that exhibited a range of symptoms. Total DNA was extracted and tested by PCR using the OA2/OI2c primers. In the first category, 6 of 10 tubers tested positive, whereas the 10 tubers in the second category tested negative. Two phytoplasmas seem to be involved in the “zebra chip” disease complex (4) but were not detected in the samples in this study. To our knowledge, this is the first report of a liberibacter associated with disease in potato. From transmission electron microscope observations, previous researchers have hypothesized that a bacterium-like organism may cause “zebra chip” (1) and B. cockerelli is associated with the disease (3). “Zebra chip” was first reported in Mexico in 1994, since then it has caused significant economic damage in Guatemala, Mexico, and the southwestern United States. The economic impact of the disease in New Zealand is yet to be determined.

References: (1) S. H. De Boer et al. Page 30 in: New and Old Pathogens of Potato in Changing Climate. A. Hannukkala and M. Segerstedt, eds. Online publication. Agrifood Research Working Paper 142, 2007. (2) S. Jagoueix et al. Mol. Cell. Probes 10:43, 1996. (3) J. E. Munyaneza et al. J. Econ. Entomol. 100:656, 2007. (4) G. A. Secor et al. Plant Dis. 90:377, 2006.
Reconstruction of the genome origins and evolution of the hybrid lager yeast Saccharomyces pastorianus
Authors: Dunn Barbara , Sherlock Gavin
Published: September 2008

Inter-specific hybridization leading to abrupt speciation is a well-known, common mechanism in angiosperm evolution; only recently, however, have similar hybridization and speciation mechanisms been documented to occur frequently among the closely related group of sensu stricto Saccharomyces yeasts. The economically important lager beer yeast Saccharomyces pastorianus is such a hybrid, formed by the union of Saccharomyces cerevisiae and Saccharomyces bayanus-related yeasts; efforts to understand its complex genome, searching for both biological and brewing-related insights, have been underway since its hybrid nature was first discovered. It had been generally thought that a single hybridization event resulted in a unique S. pastorianus species, but it has been recently postulated that there have been two or more hybridization events. Here, we show that there may have been two independent origins of S. pastorianus strains, and that each independent group—defined by characteristic genome rearrangements, copy number variations, ploidy differences, and DNA sequence polymorphisms—is correlated with specific breweries and/or geographic locations. Finally, by reconstructing common ancestral genomes via array-CGH data analysis and by comparing representative DNA sequences of the S. pastorianus strains with those of many different S. cerevisiae isolates, we have determined that the most likely S. cerevisiae ancestral parent for each of the independent S. pastorianus groups was an ale yeast, with different, but closely related ale strains contributing to each group’s parentage.
Genome-wide relationship between histone H3 lysine 4 mono- and tri-methylation and transcription factor binding
Authors: Robertson A. Gordon , Bilenky Mikhail , Tam Angela , Zhao Yongjun , Zeng Thomas , Thiessen Nina , Cezard Timothee , Fejes Anthony P. , Wederell Elizabeth D. , Cullum Rebecca , Euskirchen Ghia , Krzywinski Martin , Birol Inanc , Snyder Michael , Hoodless Pamela A. , Hirst Martin , Marra Marco A. , Jones Steven J.M.
Published: September 2008

We characterized the relationship of H3K4me1 and H3K4me3 at distal and proximal regulatory elements by comparing ChIP-seq profiles for these histone modifications and for two functionally different transcription factors: STAT1 in the immortalized HeLa S3 cell line, with and without interferon-gamma (IFNG) stimulation; and FOXA2 in mouse adult liver tissue. In unstimulated and stimulated HeLa cells, respectively, we determined ∼270,000 and ∼301,000 H3K4me1-enriched regions, and ∼54,500 and ∼76,100 H3K4me3-enriched regions. In mouse adult liver, we determined ∼227,000 and ∼34,800 H3K4me1 and H3K4me3 regions. Seventy-five percent of the ∼70,300 STAT1 binding sites in stimulated HeLa cells and 87% of the ∼11,000 FOXA2 sites in mouse liver were distal to known gene TSS; in both cell types, ∼83% of these distal sites were associated with at least one of the two histone modifications, and H3K4me1 was associated with over 96% of marked distal sites. After filtering against predicted transcription start sites, 50% of ∼26,800 marked distal IFNG-stimulated STAT1 binding sites, but 95% of ∼5800 marked distal FOXA2 sites, were associated with H3K4me1 only. Results for HeLa cells generated additional insights into transcriptional regulation involving STAT1. STAT1 binding was associated with 25% of all H3K4me1 regions in stimulated HeLa cells, suggesting that a single transcription factor can interact with an unexpectedly large fraction of regulatory regions. Strikingly, for a large majority of the locations of stimulated STAT1 binding, the dominant H3K4me1/me3 combinations were established before activation, suggesting mechanisms independent of IFNG stimulation and high-affinity STAT1 binding.
Analysis of spin-echo small-angle neutron scattering measurements
Authors: Andersson Robert , van Heijkamp Léon F. , de Schepper Ignatz M. , Bouwman Wim G.
Published: September 2008

Spin-echo small-angle neutron scattering (SESANS) is, in contrast to conventional small-angle neutron scattering (SANS), a real-space technique. SESANS measures the projection of the density–density correlation function of a sample, rather than, as in SANS, its Fourier transform. This paper introduces a toolkit for interpretion and analysis of a SESANS measurement. Models that are used in SANS are discussed and translated into a SESANS formalism. These models can be used to analyse and fit the data obtained by SESANS. Dilute, concentrated, random, fractal and anisotropic density distributions are considered. Numerical methods used to calculate the projection from numerical data are presented, either by using Fourier transformation orviathe real-space pair correlation function.
Novel affinity tag system using structurally defined antibody‐tag interaction: Application to single‐step protein purification
Authors: Nogi Terukazu , Sangawa Takeshi , Tabata Sanae , Nagae Masamichi , Tamura‐Kawakami Keiko , Beppu Ayako , Hattori Mitsuharu , Yasui Norihisa , Takagi Junichi
Published: September 2008

Biologically important human proteins often require mammalian cell expression for structural studies, presenting technical and economical problems in the production/purification processes. We introduce a novel affinity peptide tagging system that uses a low affinity anti‐peptide monoclonal antibody. Concatenation of the short recognition sequence enabled the successful engineering of an 18‐residue affinity tag with ideal solution binding kinetics, providing a low‐cost purification means when combined with nondenaturing elution by water‐miscible organic solvents. Three‐dimensional information provides a firm structural basis for the antibody–peptide interaction, opening opportunities for further improvements/modifications.
Locational Equilibria in Weberian Agglomeration
Authors: Hanink Dean M. , Cromley Robert G.
Published: September 2008

A simple Weberian agglomeration is developed and then extended as an innovative fixed‐charged, colocation model over a large set of locational possibilities. The model is applied to cases in which external economies (EE) arise due to colocation alone and also cases in which EE arise due to city size. Solutions to the model are interpreted in the context of contemporary equilibrium analysis, which allows Weberian agglomeration to be interpreted in a more general way than in previous analyses. Within that context, the Nash points and Pareto efficient points in the location patterns derived in the model are shown to rarely coincide. The applications consider agglomeration from two perspectives: one is the colocation behavior of producers as the agents of agglomeration and the other is the interaction between government and those agents in the interest of agglomeration policy. Extending the analysis to games, potential Pareto efficiency and Hicks optimality are considered with respect to side payments between producers and with respect to appropriate government incentives toward agglomeration.
Pre‐gravid physical activity and reduced risk of glucose intolerance in pregnancy: the role of insulin sensitivity
Authors: Retnakaran Ravi , Qi Ying , Sermer Mathew , Connelly Philip W. , Zinman Bernard , Hanley Anthony J. G.
Published: September 2008

Objective  Pre‐gravid physical activity has been associated with a reduced risk of gestational diabetes mellitus (GDM), although neither the types of exercise nor the physiologic mechanisms underlying this protective effect have been well‐studied. Thus, we sought to study the relationships between types of pre‐gravid physical activity and metabolic parameters in pregnancy, including glucose tolerance, insulin sensitivity and β‐cell function.

Design/patients/measurements  A total of 851 women underwent a glucose challenge test (GCT) and a 3‐h oral glucose tolerance test (OGTT) in late pregnancy, yielding four glucose tolerance groups: (i) GDM; (ii) gestational impaired glucose tolerance (GIGT); (iii) abnormal GCT with normal glucose tolerance on OGTT (abnormal GCT NGT); and (iv) normal GCT with NGT on OGTT (normal GCT NGT). Pre‐gravid physical activity was assessed using the Baecke questionnaire, which measures (i) total physical activity and (ii) its three component domains: work, nonsport leisure‐time, and vigorous/sports activity.

Results  Glucose tolerance status improved across increasing quartiles of pre‐gravid total physical activity (P = 0·0244). Whereas neither work nor nonsport leisure‐time activity differed between glucose tolerance groups, pre‐gravid vigorous/sports activity was significantly higher in women with normal GCT NGT compared to women with (i) abnormal GCT NGT (P = 0·0018) (ii) GIGT (P = 0·0025), and (iii) GDM (P = 0·0044). In particular, vigorous/sports activity correlated with insulin sensitivity (measured by ISOGTT) (r = 0·21, P < 0·0001). Furthermore, on multiple linear regression analysis, pre‐gravid vigorous/sports activity emerged as a significant independent predictor of ISOGTT in pregnancy (t = 4·97, P < 0·0001).

Conclusions  Pre‐gravid vigorous/sports activity is associated with a reduced risk of glucose intolerance in pregnancy, an effect likely mediated by enhanced insulin sensitivity.
Common exon 3 polymorphism of the GH receptor (GHR) gene and effect of GH therapy on growth in Korean children with idiopathic short stature (ISS)
Authors: Ko Jung Min , Park Jung Young , Yoo Han‐Wook
Published: September 2008

Objective  A human GH receptor (GHR) gene exon 3 polymorphism (d3‐GHR) has been reported to be associated with responsiveness to GH therapy. We assessed the frequencies of this polymorphism in Korean control and idiopathic short stature (ISS) populations, and analysed short‐term growth response to GH therapy according to GHR‐exon 3 genotypes in Korean children with ISS.

Design and patients  This was a retrospective study in 158 ISS children. Auxological and endocrine parameters were measured, and the GHR‐exon 3 genotype was analysed. Allelic frequencies of GHR‐exon 3 genotype were compared between the ISS group and a control group. GH had been administered for 62 patients, 52 of whom remained prepubertal after the first follow‐up year. Changes in height velocity (HV) and IGF‐1 and IGFBP‐3 concentrations following GH therapy were compared in patients with these genotypes.

Results  There was no difference in GHR‐exon 3 genotype frequency between ISS and control groups of Koreans. However, the fl/fl genotype was more frequent in Koreans than in Caucasians. ISS children with d3‐GHR showed a significantly higher increment in HV (P = 0·002) and a marginally significant increment in IGF‐1 concentration (P = 0·064) at the first year of GH therapy.

Conclusion  fl‐GHR was more frequently detected in a Korean population than in Caucasians. The growth promotion efficacy of GH therapy differed significantly between ISS patients with and without the d3‐GHR allele. These findings indicate that the GHR‐exon 3 polymorphism can affect the growth promoting efficacy of short‐term GH therapy in Korean children with ISS.
Hyperthyroidism in a population with Down syndrome (DS)
Authors: Goday‐Arno Alberto , Cerda‐Esteva Mariaina , Flores‐Le‐Roux Juana Antonia , Chillaron‐Jordan Juan José , Corretger Josep Maria , Cano‐Pérez Juan Francisco
Published: September 2008

Background  Thyroid disorders are frequent in patients with Down syndrome (DS). It is well‐known that the prevalence of hypothyroidism is high but data on hyperthyroidism are scarce.

Objectives  To assess the prevalence, aetiology, clinical characteristics, evolution and treatment of hyperthyroidism in a population with DS attending a specialized medical centre.

Methods  Data were gathered by systematic review of 1832 medical records from the Catalan DS Foundation, in Spain, registered between January 1991 and February 2006. Patients with the diagnosis of hyperthyroidism were identified and data on clinical features, physical examination, laboratory and imaging tests, treatment and evolution were collected.

Results  Twelve patients with hyperthyroidism were recorded (6·5 cases/1000 patients with DS). There were 5 males and 7 females, with a mean age at diagnosis of 16·8 years. The most common presenting symptoms were decreased heat tolerance, sweating, increased irritability and weight loss. All patients had diffuse goitre at physical examination and two patients presented with exophthalmia. Clinical diagnosis was confirmed biochemically. Thyroid‐stimulating immunoglobulin levels were raised (mean 128·1 U/l) and imaging tests confirmed the diagnosis of Graves’ disease in all cases. Patients started treatment with carbimazole at diagnosis and after a mean period of 40 months without clinical remission, they required definitive therapy with radioactive iodine. Subjects developed hypothyroidism after radio‐iodine therapy and replacement therapy with levothyroxine was necessary.

Conclusions  Hyperthyroidism is more prevalent in patients with DS than in the general population and has no gender predominance. It is caused mainly by Graves’ disease. Anti‐thyroid drugs were not effective in achieving remission and radioactive iodine as a definitive treatment was required in all cases.
The effect of genetic variation in the type 1 deiodinase gene on the interindividual variation in serum thyroid hormone levels: an investigation in healthy Danish twins
Authors: Van Der Deure Wendy M. , Hansen Pia Skov , Peeters Robin P. , Uitterlinden André G. , Fenger Mogens , Kyvik Kirsten Ohm , Hegedüs Laszlo , Visser Theo J.
Published: September 2008

Introduction  Genetic factors have a considerable influence on serum thyroid hormone levels. The C785T and A1814G polymorphisms, located in the 3′ untranslated region of the type 1 deiodinase (D1) gene have been associated with serum FT4 and rT3 levels.

Objective  In healthy Danish twins, we examined the association of these polymorphisms with serum thyroid hormone levels and determined the proportion of genetic influence explained by these variants. We analysed the underlying functional mechanism by performing mRNA stability measurements and analysed the effect of these variants on D1 activity.

Methods  Serum thyroid measurements and genotypes of the D1‐C785T and D1‐A1814G polymorphisms were determined in 1192 twins. Structural equation modelling was used to determine heritability estimates. Functional analyses were carried out in D1‐transfected JEG3 cells.

Results  Carriers of the D1‐785T allele had 3·8% higher FT4 and 14·3% higher rT3 levels, resulting in a lower T3/T4 and T3/rT3 ratio and a higher rT3/T4 ratio. This polymorphism explained 0·87% and 1·79%, respectively, of the variation in serum FT4 and rT3. The D1‐A1814G polymorphism was not associated with serum thyroid hormone levels. No differences in D1 mRNA decay rate or D1 activity were observed between wild‐type D1 and the two variants.

Conclusion  The D1‐C785T polymorphism is consistently and significantly associated with serum thyroid hormone levels. However, the proportion of genetic influence explained by this particular polymorphism is small. No effect of the polymorphism on D1 mRNA decay rate or D1 activity was observed. The underlying functional mechanism needs to be elucidated.
Alterations in thyroid function tests in aged hospitalized patients: prevalence, aetiology and clinical outcome
Authors: Iglesias P. , Muñoz A. , Prado F. , Guerrero M. T. , Macías M. C , Ridruejo E. , Tajada P. , Díez J. J
Published: September 2008

Background  Thyroid dysfunction is common in aged people and has recently been associated to mortality.

Aims Our aims have been (1) to assess the prevalence of alterations in thyroid function tests in hospitalized patients over age 60 years and (2) to study the relationship between thyroid functional status and mortality during hospitalization.

Methods  We studied a group of 447 patients (62% women), aged 61–101 year, hospitalized during 2005. Thyroid dysfunction was assessed by measuring serum concentrations of thyrotrophin (TSH), free thyroxine (FT4), and free thriiodothyronine (FT3). Thyroid autoimmune status was evaluated through thyroid peroxidase (TPO) and thyroglobulin (TG) antibodies quantification.

Results  Twenty‐one patients (4·7%, 19 women) showed previously known thyroid dysfunction. 332 patients (74·3%) showed alterations in thyroid function tests. Euthyroid sick syndrome (ESS) was the derangement more frequently found (n = 278, 62·2%). After excluding ESS patients, 60 patients (13·4%) showed thyroid dysfunction: overt hypothyroidism, 14 (3·1%); subclinical hypothyroidism, 25 (5·6%); overt hyperthyroidism, 11 (2·5%), and subclinical hyperthyroidism, 10 patients (2·2%). Thyroid autoimmunity was positive in only 4·0% and 2·3% of patients, for TPOAb and TgAb, respectively. The presence of alterations in thyroid function tests was positively associated with the age of the patients and mortality during hospital stay (P < 0·001). Serum levels of FT3 were negatively related to death during hospitalization (OR 0·56; CI 95%, 0·38–0·81; P < 0·01).

Conclusions  About three quarters of patients admitted in our geriatric unit exhibited alterations in thyroid function tests. This finding was associated with elevated age and poor prognosis. The reduction of FT3 values was a powerful predictor for mortality during hospitalization in elderly patients.
A ceramide‐1‐phosphate analogue, PCERA‐1, simultaneously suppresses tumour necrosis factor‐α and induces interleukin‐10 production in activated macrophages
Authors: Goldsmith Meir , Avni Dorit , Levy‐Rimler Galit , Mashiach Roi , Ernst Orna , Levi Maya , Webb Bill , Meijler Michael M. , Gray Nathanael S. , Rosen Hugh , Zor Tsaffrir
Published: September 2008

Tight regulation of the production of the key pro‐inflammatory cytokine tumour necrosis factor‐α (TNF‐α) is essential for the prevention of chronic inflammatory diseases. In vivo administration of a synthetic phospholipid, named hereafter phospho‐ceramide analogue‐1 (PCERA‐1), was previously found to suppress lipopolysaccharide (LPS)‐induced TNF‐α blood levels. We therefore investigated the in vitro anti‐inflammatory effects of PCERA‐1. Here, we show that extracellular PCERA‐1 potently suppresses production of the pro‐inflammatory cytokine TNF‐α in RAW264.7 macrophages, and in addition, independently and reciprocally regulates the production of the anti‐inflammatory cytokine interleukin‐10 (IL‐10). Specificity is demonstrated by the inability of the phospholipids ceramide‐1‐phosphate (C1P), sphingosine‐1‐phosphate (S1P) and lysophosphatidic acid (LPA) to perform these activities. Similar TNF‐α suppression and IL‐10 induction by PCERA‐1 were observed in macrophages when activated by Toll‐like receptor 4 (TLR4), TLR2 and TLR7 agonists. Regulation of cytokine production is demonstrated at the mRNA and protein levels. Finally, we show that, while PCERA‐1 does not block activation of nuclear factor (NF)‐κB and mitogen‐activated protein kinases by LPS, it elevates the intracellular cAMP level. In conclusion, the anti‐inflammatory activity of PCERA‐1 seems to be mediated by a cell membrane receptor, upstream of cAMP production, and eventually TNF‐α suppression and IL‐10 induction. Thus, identification of the PCERA‐1 receptor may provide new pharmacological means to block inflammation.
The molecular analysis of Trypanosoma cruzi metallocarboxypeptidase 1 provides insight into fold and substrate specificity
Authors: Niemirowicz Gabriela , Fernández Daniel , Solà Maria , Cazzulo Juan J. , Avilés Francesc X. , Gomis‐Rüth F. Xavier
Published: September 2008

Trypanosoma cruzi is the aetiological agent of Chagas' disease, a chronic infection that affects millions in Central and South America. Proteolytic enzymes are involved in the development and progression of this disease and two metallocarboxypeptidases, isolated from T. cruzi CL Brener clone, have recently been characterized: TcMCP‐1 and TcMCP‐2. Although both are cytosolic and closely related in sequence, they display different temporary expression patterns and substrate preferences. TcMCP‐1 removes basic C‐terminal residues, whereas TcMCP‐2 prefers hydrophobic/aromatic residues. Here we report the three‐dimensional structure of TcMCP‐1. It resembles an elongated cowry, with a long, deep, narrow active‐site cleft mimicking the aperture. It has an N‐terminal dimerization subdomain, involved in a homodimeric catalytically active quaternary structure arrangement, and a proteolytic subdomain partitioned by the cleft into an upper and a lower moiety. The cleft accommodates a catalytic metal ion, most likely a cobalt, which is co‐ordinated by residues included in a characteristic zinc‐binding sequence, HEXXH and a downstream glutamate. The structure of TcMCP‐1 shows strong topological similarity with archaeal, bacterial and mammalian metallopeptidases including angiotensin‐converting enzyme, neurolysin and thimet oligopeptidase. A crucial residue for shaping the S1′ pocket in TcMCP‐1, Met‐304, was mutated to the respective residue in TcMCP‐2, an arginine, leading to a TcMCP‐1 variant with TcMCP‐2 specificity. The present studies pave the way for a better understanding of a potential target in Chagas' disease at the molecular level and provide a template for the design of novel therapeutic approaches.
Rga2 is a Rho2 GAP that regulates morphogenesis and cell integrity in S. pombe
Authors: Villar‐Tajadura Ma Antonia , Coll Pedro M. , Madrid Marisa , Cansado Jose , Santos Beatriz , Pérez Pilar
Published: September 2008

Schizosaccharomyces pombe Rho2 GTPase regulates α‐D‐glucan synthesis and acts upstream of Pck2 to activate the MAP kinase pathway for cell integrity. However, little is known about its regulation. Here we describe Rga2 as a Rho2 GTPase‐activating protein (GAP) that regulates cell morphology. rga2+ gene is not essential for growth but its deletion causes longer and thinner cells whereas rga2+ overexpression causes shorter and broader cells. rga2+ overexpression also causes abnormal accumulation of Calcofluor‐stained material and cell lysis, suggesting that it also participates in cell wall integrity. Rga2 localizes to growth tips and septum region. The N‐terminal region of the protein is required for its correct localization whereas the PH domain is necessary exclusively for Rga2 localization to the division area. Also, Rga2 localization depends on polarity markers and on actin polymerization. Rga2 interacts with Rho2 and possesses in vitro and in vivo GAP activity for this GTPase. Accordingly, rga2Δ cells contain more α‐D‐glucan and therefore partially suppress the thermosensitivity of mok1–664 cells, which have a defective α‐D‐glucan synthase. Additionally, genetic interactions and biochemical analysis suggest that Rga2 regulates Rho2–Pck2 interaction and might participate in the regulation of the MAPK cell integrity pathway.
Commonly affected body sites in 92 Japanese combat sports participants with Trichophyton tonsurans infection
Authors: Shiraki Yumi , Hiruma Masataro , Hirose Nobuyoshi , Ikeda Shigaku
Published: September 2008

Outbreaks of Trichophyton tonsurans infection constitute one of the serious problems among combat sports practitioners in Japan. To facilitate the diagnosis of individuals at risk, we undertook a study to determine which body sites are most commonly infected. We reviewed medical data, hairbrush culture results and questionnaire information from patients with T. tonsurans infection who were admitted to the dermatology clinic of Juntendo University hospital from 2000 to 2004. The study included 92 patients (87 males), aged 6–38 years (mean age: 18.4 years old). Eighty‐nine patients were judo practitioners and three were wrestlers. Twenty‐eight patients (30.4%) were asymptomatic carriers. In 64 patients, 51 patients (55.4%) with tinea corporis, 27 patients (29.3%) with tinea capitis, and/or one patient (1.1%) with tinea manuum were seen. Tinea corporis was observed on the forehead, auricles, nape of the neck, bilateral shoulders, left side of the upper chest, both elbows, back of the left hand to the wrist and both knees. Tinea capitis was most common in the occipitonuchal region at the hairline and in the temporal and frontal regions, at both auricles. Initial screening of these sites might facilitate the identification of the infection especially in judo practitioners.
Fusarium species detected in onychomycosis in Colombia
Authors: Castro López Natalia , Casas Clemencia , Sopo Leticia , Rojas Alejandro , Del Portillo Patricia , Cepero de García María Caridad , Restrepo Silvia
Published: September 2008

Fusarium spp. have frequently been isolated from patients with onychomycosis. In Colombia, several studies have shown that Fusarium is the most common non‐dermatophyte mould causing onychomycosis and its spread has increased in the past years. In this study, samples were collected in 2003 and 2004 from 137 patients who were diagnosed with onychomycosis caused by Fusarium spp. Three species of Fusarium were identified: Fusarium solani (64.9%), Fusarium oxysporum (32.8%) and Fusarium verticillioides (2.3%). The diseases were more common in women (73%) than in men (27%) and occurred mainly among adults between 31 and 40 years old. The percentage of patients who had received previous treatments was 63.5%. In the last years, new and improved antifungal agents like echinocandins or new triazoles like voriconazole have been developed. For this reason, susceptibility testing using voriconazole was performed, by broth microdilution and disk diffusion. The results showed that F. solani had the highest minimum inhibitory concentration. Using the disk diffusion test, many of the isolates showed variable susceptibility. Genetic diversity of F. oxysporum isolates was determined by random amplified polymorphic DNA. Twenty isolates belonging to different haplotypes were selected for PCR amplification of a region of the gene encoding α‐l‐arabinofuranosidase B, a specific test to determine if the isolates were F. oxysporum f. sp. dianthi. On the basis of these PCR results, we found that five out of the 20 F. oxysporum isolates corresponded to f. sp. dianthi.
Preliminary study of activity of the thioredoxin inhibitor pleurotin against Trichophyton mentagrophytes: a novel anti‐dermatophyte possibility
Authors: Berdicevsky Israela , Kaufman Gil , Newman David J. , Horwitz Benjamin A.
Published: September 2008

Dermatophyte infections, while not life‐threatening, are very common, and there is great interest in developing new antifungal agents. Transcriptional profiling of Trichophyton on keratin has identified some antioxidant genes as induced on this host substrate, including a thioredoxin gene TmTRX1. If thioredoxin is a virulence factor, or necessary for the growth on keratin, thioredoxin inhibitors should act as antifungals. As a first evaluation of this hypothesis, we have tested the activity of a thioredoxin‐inhibitory natural product, pleurotin, against a clinical isolate of each of two fungal pathogens: the dermatophyte T. mentagrophytes and Candida albicans. Pleurotin inhibited the growth of the dermatophyte in vitro and in an ex vivo skin model, but had no effect on Candida. It may be possible to develop and optimise thioredoxin inhibitors, some of which are already under study in cancer chemotherapy, as antifungals.
Quality of life in patients suffering from seborrheic dermatitis: influence of age, gender and education level
Authors: Szepietowski Jacek C. , Reich Adam , Wesołowska‐Szepietowska Ewa , Baran Eugeniusz ,   for the National Quality of Life in Dermatology Group
Published: September 2008

Seborrheic dermatitis is a common inflammatory skin condition occurring mostly on the face, scalp and chest. Despite its high frequency, the impact of seborrheic dermatitis on patients’ quality of life (QoL) has not been studied well so far. The objectives of this study were to analyse how seborrheic dermatitis affects the patients’ QoL and which socio‐economic factors could modulate QoL in these patients. A total of 3000 patients with seborrheic dermatitis and/or dandruff were enrolled into the study. All participants were divided into subgroups according to gender, age and education level. A specially designed questionnaire with demographic and clinical details of patients as well as Dermatology Life Quality Index (DLQI) was completed during a patient visit in an outpatient clinic. Data were collected by local dermatologists who were instructed regarding the inclusion and exclusion criteria and the questionnaires were sent back to us upon completion. The mean DLQI score for all patients was 6.92 ± 5.34 points. Patients with dandruff had significantly better QoL than subjects with seborrheic dermatitis (5.34 ± 4.67 points vs. 7.73 ± 5.3 points, respectively; P < 0.001) or individuals with dandruff plus seborrheic dermatitis (7.54 ± 5.6 points, P < 0.001). In addition, women, younger patients and subjects with higher educational level were more affected than the rest of the patients. Seborrheic dermatitis had significant, negative influence on patients’ QoL. Observed discrepancies between subgroups could be explained by different roles played by different patient subgroups in the society. DLQI can be successfully used for the assessment of QoL in large populational studies.