bluuebunny/crossref_metadata_2025_split huggingface dataset:
SKPDB: a structural database of shikimate pathway enzymes
Authors: Arcuri Helen A , Zafalon Geraldo FD , Marucci Evandro A , Bonalumi Carlos E , da Silveira Nelson JF , Machado José M , de Azevedo Walter F , Palma Mário S 
Published: January 2010

Abstract

Background
The functional and s tructural characterisation of enzymes that belong to microbial metabolic pathways is very important for structure-based drug design. The main interest in studying shikimate pathway enzymes involves the fact that they are essential for bacteria but do not occur in humans, making them selective targets for design of drugs that do not directly impact humans.

Description
The ShiKimate Pathway DataBase (SKPDB) is a relational database applied to the study of shikimate pathway enzymes in microorganisms and plants. The current database is updated regularly with the addition of new data; there are currently 8902 enzymes of the shikimate pathway from different sources. The database contains extensive information on each enzyme, including detailed descriptions about sequence, references, and structural and functional studies. All files (primary sequence, atomic coordinates and quality scores) are available for downloading. The modeled structures can be viewed using the Jmol program.

Conclusions
The SKPDB provides a large number of structural models to be used in docking simulations, virtual screening initiatives and drug design. It is freely accessible at http://lsbzix.rc.unesp.br/skpdb/.
The Zur regulon of Corynebacterium glutamicum ATCC 13032
Authors: Schröder Jasmin , Jochmann Nina , Rodionov Dmitry A , Tauch Andreas 
Published: January 2010

Abstract

Background
Zinc is considered as an essential element for all living organisms, but it can be toxic at large concentrations. Bacteria therefore tightly regulate zinc metabolism. The Cg2502 protein of Corynebacterium glutamicum was a candidate to control zinc metabolism in this species, since it was classified as metalloregulator of the zinc uptake regulator (Zur) subgroup of the ferric uptake regulator (Fur) family of DNA-binding transcription regulators.

Results
The cg2502 (zur) gene was deleted in the chromosome of C. glutamicum ATCC 13032 by an allelic exchange procedure to generate the zur-deficient mutant C. glutamicum JS2502. Whole-genome DNA microarray hybridizations and real-time RT-PCR assays comparing the gene expression in C. glutamicum JS2502 with that of the wild-type strain detected 18 genes with enhanced expression in the zur mutant. The expression data were combined with results from cross-genome comparisons of shared regulatory sites, revealing the presence of candidate Zur-binding sites in the mapped promoter regions of five transcription units encoding components of potential zinc ABC-type transporters (cg0041-cg0042/cg0043; cg2911-cg2912-cg2913), a putative secreted protein (cg0040), a putative oxidoreductase (cg0795), and a putative P-loop GTPase of the COG0523 protein family (cg0794). Enhanced transcript levels of the respective genes in C. glutamicum JS2502 were verified by real-time RT-PCR, and complementation of the mutant with a wild-type zur gene reversed the effect of differential gene expression. The zinc-dependent expression of the putative cg0042 and cg2911 operons was detected in vivo with a gfp reporter system. Moreover, the zinc-dependent binding of purified Zur protein to double-stranded 40-mer oligonucleotides containing candidate Zur-binding sites was demonstrated in vitro by DNA band shift assays.

Conclusion
Whole-genome expression profiling and DNA band shift assays demonstrated that Zur directly represses in a zinc-dependent manner the expression of nine genes organized in five transcription units. Accordingly, the Zur (Cg2502) protein is the key transcription regulator for genes involved in zinc homeostasis in C. glutamicum.
Sex-dimorphic gene expression and ineffective dosage compensation of Z-linked genes in gastrulating chicken embryos
Authors: Zhang Shaobing O , Mathur Sachin , Hattem Gaye , Tassy Olivier , Pourquié Olivier 
Published: January 2010

Abstract

Background
Considerable progress has been made in our understanding of sex determination and dosage compensation mechanisms in model organisms such as C. elegans, Drosophila and M. musculus. Strikingly, the mechanism involved in sex determination and dosage compensation are very different among these three model organisms. Birds present yet another situation where the heterogametic sex is the female. Sex determination is still poorly understood in birds and few key determinants have so far been identified. In contrast to most other species, dosage compensation of bird sex chromosomal genes appears rather ineffective.

Results
By comparing microarrays from microdissected primitive streak from single chicken embryos, we identified a large number of genes differentially expressed between male and female embryos at a very early stage (Hamburger and Hamilton stage 4), long before any sexual differentiation occurs. Most of these genes are located on the Z chromosome, which indicates that dosage compensation is ineffective in early chicken embryos. Gene ontology analyses, using an enhanced annotation tool for Affymetrix probesets of the chicken genome developed in our laboratory (called Manteia), show that among these male-biased genes found on the Z chromosome, more than 20 genes play a role in sex differentiation.

Conclusions
These results corroborate previous studies demonstrating the rather inefficient dosage compensation for Z chromosome in birds and show that this sexual dimorphism in gene regulation is observed long before the onset of sexual differentiation. These data also suggest a potential role of non-compensated Z-linked genes in somatic sex differentiation in birds.
Antinociceptive effect of geranylgeraniol and 6α,7β-dihydroxyvouacapan-17β-oate methyl ester isolated from Pterodon pubescens Benth
Authors: Spindola Humberto M , Servat Leila , Denny Carina , Rodrigues Rodney AF , Eberlin Marcos N , Cabral Elaine , Sousa Ilza MO , Tamashiro Jorge Y , Carvalho João E , Foglio Mary A 
Published: January 2010

AbstractBackgroundPterodon pubescensBenth seeds are commercially available in the Brazilian medicinal plant street market. The crude alcoholic extracts of this plant are used in folk medicine as anti-inflammatory, analgesic, and anti-rheumatic preparations. The aim of this study was to evaluate the contribution of geranylgeraniol (C1) and 6α, 7β-dihydroxyvouacapan-17β-oate methyl ester (C2) isolated fromPterodon pubescensBenth. to the antinociceptive activity of the crude extract.ResultsCompounds C1 and C2 demonstrated activity against writhing with intraperitoneal (i.p.) and oral (p.o.) routes, capsaicin (i.p. and p.o.), glutamate (i.p.), and in the hot-plate (p.o.) tests, demonstrating their contribution to the antinociceptive activity of crudePterodon pubescensBenth extracts. The observed activity of compounds C1 and C2 may be related to vanilloid receptors VR1, and/or glutamate peripheral receptors. In hot-plate model, the antinociceptive activity was maintained when naloxone chloride (opioid antagonist) was administered prior to treatment with compounds suggesting that C1 and C2 (p.o.) do not exert their antinociceptive effects in the hot-plate test via opioid receptors. The findings presented herein also suggest that compounds within the crudePterodon pubescensBenth. extract may exert a synergistic interactive effect, since the crude extract (300 mg.kg-1) containing lower concentrations of compounds C1 (11.5%- 34.6 mg. kg-1) and C2 (1.5% - 4.7 mg.kg-1) gave statistically the same effect to the pure compounds when tested separately (C1 = C2 = 300 mg.kg-1) in writhing experimental model with p.o. administration. Further studies will be undertaken to establish more specifically the mechanisms of action for compounds C1 and C2. Possible synergistic interactions will be evaluated employing the Isobole method.ConclusionThese results allowed us to establish a relationship between the popular use ofPterodon pubescensseeds for pain relief and the activity of two major compounds isolated from this species which demonstrated antinociceptive activity. Various "in vivo"experimental models corroborate the folk use of this species for different pain and inflammation disorders.
Inhibition of receptor tyrosine kinase signalling by small molecule agonist of T-cell protein tyrosine phosphatase
Authors: Mattila Elina , Marttila Heidi , Sahlberg Niko , Kohonen Pekka , Tähtinen Siri , Halonen Pasi , Perälä Merja , Ivaska Johanna 
Published: January 2010

Abstract

Background
T-cell protein tyrosine phosphatase (TCPTP/TC45) is a ubiquitously expressed intra-cellular non-receptor protein tyrosine phosphatase involved in the negative regulation of several cancer relevant cellular signalling pathways. We have previously shown that interaction between the α-cytoplasmic tail of α1β1 integrin and TCPTP activates TCPTP by disrupting an inhibitory intra-molecular bond in TCPTP. Thus, inhibition of the regulatory interaction in TCPTP is a desirable strategy for TCPTP activation and attenuation of oncogenic RTK signalling. However, this is challenging with low molecular weight compounds.

Methods
We developed a high-throughput compatible assay to analyse activity of recombinant TCPTP in vitro. Using this assay we have screened 64280 small molecules to identify novel agonists for TCPTP. Dose-dependent response to TCPTP agonist was performed using the in vitro assay. Inhibition effects and specificity of TCPTP agonists were evaluated using TCPTP expressing and null mouse embryonic fibroblasts. Western blot analysis was used to evaluate attenuation of PDGFRβ and EGFR phosphorylation. Inhibition of VEGF signalling was analysed with VEGF-induced endothelial cell sprouting assays.

Results
From the screen we identified six TCPTP agonists. Two compounds competed with α1-cytoplasmic domain for binding to TCPTP, suggesting that they activate TCPTP similar to α1-cyt by disrupting the intra-molecular bond in TCPTP. Importantly, one of the compounds (spermidine) displayed specificity towards TCPTP in cells, since TCPTP -/- cells were 43-fold more resistant to the compound than TCPTP expressing cells. This compound attenuates PDGFRβ and VEGFR2 signalling in cells in a TCPTP-dependent manner and functions as a negative regulator of EGFR phosphorylation in cancer cells.

Conclusions
In this study we showed that small molecules mimicking TCPTP-α1 interaction can be used as TCPTP agonists. These data provide the first proof-of-concept description of the use of high-throughput screening to identify small molecule PTP activators that could function as RTK antagonists in cells.
Forefoot disease activity in rheumatoid arthritis patients in remission: results of a cohort study
Authors: van der Leeden Marike , Steultjens Martijn PM , van Schaardenburg Dirkjan , Dekker Joost 
Published: January 2010

Abstract
Introduction
The aim of our study was to investigate the presence of disease activity in the metatarsophalangeal (MTP) joints of the forefoot in rheumatoid arthritis (RA) patients in remission according to the Disease Activity Score based on 28 joints (DAS28) remission criterion.

Methods
A total of 848 patients with recent-onset RA were included from 1995 through 2007. The DAS28 and pain and swelling of the MTP joints were assessed annually. The data were analyzed using descriptive techniques.

Results
On average, 35% of the patients fulfilled the remission criterion of DAS28 <2.6 during the first eight years of RA. On average, 29% of these patients had at least one painful MTP joint and, on average, 31% had at least one swollen MTP joint during follow-up. Forty percent, on average, had at least one involved MTP joint (pain and/or swelling).

Conclusions
Painful and/or swollen MTP joints were detected in a substantial proportion of patients classified as being in remission. Therefore, examination of the foot joints - irrespective of the patient's state of remission - seems indicated in order to provide optimal foot care.
Ventilation with lower tidal volumes as compared with conventional tidal volumes for patients without acute lung injury: a preventive randomized controlled trial
Authors: Determann Rogier M , Royakkers Annick , Wolthuis Esther K , Vlaar Alexander P , Choi Goda , Paulus Frederique , Hofstra Jorrit-Jan , de Graaff Mart J , Korevaar Johanna C , Schultz Marcus J 
Published: January 2010

Abstract
Introduction
Recent cohort studies have identified the use of large tidal volumes as a major risk factor for development of lung injury in mechanically ventilated patients without acute lung injury (ALI). We compared the effect of conventional with lower tidal volumes on pulmonary inflammation and development of lung injury in critically ill patients without ALI at the onset of mechanical ventilation.

Methods
We performed a randomized controlled nonblinded preventive trial comparing mechanical ventilation with tidal volumes of 10 ml versus 6 ml per kilogram of predicted body weight in critically ill patients without ALI at the onset of mechanical ventilation. The primary end point was cytokine levels in bronchoalveolar lavage fluid and plasma during mechanical ventilation. The secondary end point was the development of lung injury, as determined by consensus criteria for ALI, duration of mechanical ventilation, and mortality.

Results
One hundred fifty patients (74 conventional versus 76 lower tidal volume) were enrolled and analyzed. No differences were observed in lavage fluid cytokine levels at baseline between the randomization groups. Plasma interleukin-6 (IL-6) levels decreased significantly more strongly in the lower-tidal-volume group ((from 51 (20 to 182) ng/ml to 11 (5 to 20) ng/ml versus 50 (21 to 122) ng/ml to 21 (20 to 77) ng/ml; P = 0.01)). The trial was stopped prematurely for safety reasons because the development of lung injury was higher in the conventional tidal-volume group as compared with the lower tidal-volume group (13.5% versus 2.6%; P = 0.01). Univariate analysis showed statistical relations between baseline lung-injury score, randomization group, level of positive end-expiratory pressure (PEEP), the number of transfused blood products, the presence of a risk factor for ALI, and baseline IL-6 lavage fluid levels and the development of lung injury. Multivariate analysis revealed the randomization group and the level of PEEP as independent predictors of the development of lung injury.

Conclusions
Mechanical ventilation with conventional tidal volumes is associated with sustained cytokine production, as measured in plasma. Our data suggest that mechanical ventilation with conventional tidal volumes contributes to the development of lung injury in patients without ALI at the onset of mechanical ventilation.

Trial registration
ISRCTN82533884
Macrophages: do they impact AIDS progression more than CD4 T cells?
Authors: Kuroda Marcelo J 
Published: January 2010

Abstract
Data review of the hypothesis that damage in the monocyte/macrophage arm of innate immunity is a key component predicting AIDS progression.
Destruction of CD4+ T cells is considered to be the main cause of immunodeficiency manifested by opportunistic infections in HIV-1-infected humans, as well as in SIV-infected macaques. We propose that monocyte/macrophage lineage cells also play an important role in the pathogenesis of AIDS, based on our recent work with the SIV/rhesus macaque animal model. We propose that damage to CD4+ T cells is important and readily apparent, but damage to monocyte/macrophage lineage cells, although less obvious, may provide the missing link to predict the onset of opportunistic infections and progression to AIDS.
Perceived barriers to flexible sigmoidoscopy screening for colorectal cancer among UK ethnic minority groups: a qualitative study
Authors: Austin K L , Power E , Solarin I , Atkin W S , Wardle J , Robb K A 
Published: January 2010

Objectives Evidence from existing UK screening programmes indicates disparities in uptake rates between UK ethnic minorities and the white majority population. The aim of this study was to explore barriers to the uptake of flexible sigmoidoscopy (FS) screening among UK ethnic minority populations. Specifically, beliefs about bowel cancer, perceived barriers to the test and ideas about ways to increase uptake were investigated. Methods Nine focus groups were conducted with a total of 53 participants from African-Caribbean, Gujarati Indian, Pakistani and white British communities. The topic guide was based on the Health Belief Model. Discussions were subject to framework analysis. Results Most participants expressed limited awareness of bowel cancer and cited this as a barrier to screening attendance. Anxiety regarding the invasiveness of the test, the bowel preparation and fear of a cancer diagnosis were common barriers across all ethnic groups. Language difficulties, failure to meet religious sensitivities and the expression of culturally influenced health beliefs were all discussed as specific barriers to uptake. Ethnically tailored health promotion and general practitioner involvement were recommended as ways of overcoming such barriers. Conclusions The study was the first attempt to qualitatively explore barriers to FS bowel cancer screening in UK ethnic minorities. Most barriers were shared by all ethnic groups but health educators should supplement approaches designed for the majority to incorporate the specific needs of individual minority groups to ensure equitable access.
Career destinations, views and future plans of the UK medical qualifiers of 1988
Authors: Taylor Kathryn , Lambert Trevor , Goldacre Michael 
Published: January 2010

Summary Objectives To report the career destinations, views and future plans of a cohort of senior doctors who qualified in the 1980s. Methods Postal questionnaire survey of all doctors who qualified from all UK medical schools in 1988. Results The response rate was 69%. We estimated that 81% of the total cohort was working in the NHS, 16 years after qualification; and that at least 94% of graduates who, when students, were from UK homes, were working in medicine. Of NHS doctors, 30% worked part-time. NHS doctors rated their job satisfaction highly (median score 19.9, scale 5–25) but were less satisfied with the amount of leisure time available to them (median score 5.4, scale 1–10). NHS doctors were very positive about their careers, but were less positive about working hours and some other aspects of the NHS. Women were more positive than men about working conditions; general practitioners were more positive than hospital doctors. Twenty-five percent reported unmet needs for further training or career-related advice, particularly about career development. Twenty-nine percent intended to reduce their hours in future, while 6%, mainly part-time women, planned to increase their hours. Overall, 10% of NHS doctors planned to do more service work in future and 24% planned to do less; among part-time women, 18% planned to do more and only 14% less. Conclusions These NHS doctors, now in their 40s, had a high level of satisfaction with their jobs and their careers but were less satisfied with some other aspects of their working environment. A substantial percentage had expectations about future career development and change.
Collecting 3D electron diffraction data by the rotation method
Authors: Zhang Daliang , Oleynikov Peter , Hovmöller Sven , Zou Xiaodong 
Published: January 2010

Abstract
A new method for collecting complete three-dimensional electron diffraction data is described. Diffraction data is collected by combining electron beam tilt at many very small steps, with rotation of the crystal in a few but large steps. A number of practical considerations are discussed, as well as advantages and disadvantages compared to other methods of collecting electron diffraction data.
Structure determination of the zeolite IM-5 using electron crystallography
Authors: Sun Junliang , He Zhanbing , Hovmöller Sven , Zou Xiaodong , Gramm Fabian , Baerlocher Christian , McCusker Lynne B. 
Published: January 2010

Abstract
The structure of the complex zeolite IM-5 (Cmcm, a = 14.33(4) Å, b = 56.9(2) Å, c = 20.32(7) Å) was determined by combining selected area electron diffraction (SAED), 3D reconstruction of high resolution transmission electron microscopy (HRTEM) images from different zone axes and distance least squares (DLS) refinement. The unit cell parameters were determined from SAED. The space group was determined from extinctions in the SAED patterns and projection symmetries of HRTEM images. Using the structure factor amplitudes and phases of 144 independent reflections obtained from HRTEM images along the [100], [010] and [001] directions, a 3D electrostatic potential map was calculated by inverse Fourier transformation. From this 3D potential map, all 24 unique Si positions could be determined. Oxygen atoms were added between each Si–Si pair and further refined together with the Si positions by distance-least-squares. The final structure model deviates on average 0.16 Å for Si and 0.31 Å for O from the structure refined using X-ray powder diffraction data. This method is general and offers a new possibility for determining the structures of zeolites and other materials with complex structures.
Automated nanocrystal orientation and phase mapping in the transmission electron microscope on the basis of precession electron diffraction
Authors: Rauch Edgar F. , Portillo Joaquin , Nicolopoulos Stavros , Bultreys Daniel , Rouvimov Sergei , Moeck Peter 
Published: January 2010

Abstract
An automated technique for the mapping of nanocrystal phases and orientations in a transmission electron microscope is described. It is primarily based on the projected reciprocal lattice geometry that is extracted from electron diffraction spot patterns. Precession electron diffraction patterns are especially useful for this purpose. The required hardware allows for a scanning-precession movement of the primary electron beam on the crystalline sample and can be interfaced to any older or newer mid-voltage transmission electron microscope (TEM). Experimentally obtained crystal phase and orientation maps are shown for a variety of samples. Comprehensive commercial and open-access crystallographic databases may be used in support of the nanocrystal phase identification process and are briefly mentioned.
The strong phase object approximation may allow extending crystallographic phases of dynamical electron diffraction patterns of 3D protein nano-crystals
Authors: Abrahams Jan Pieter 
Published: January 2010

Abstract
Simulations suggest that the strong phase object approximation of dynamical scattering may allow extracting crystallographic phase information from single 2D electron diffraction patterns of 3D protein crystals using probabilitistic procedures. Unlike other phasing methods, the procedure does not requires any additional knowledge – like real space images, atomicity, non-crystallographic symmetry, the presence or location of disordered solvent or the availability of a support with a known structure. In specific cases, the availability of precession electron diffraction data can further improve the phases.
Esthesioneuroblastoma (Olfactory Neuroblastoma) with Ectopic ACTH Syndrome: A Multidisciplinary Case Presentation from the Joan Karnell Cancer Center of Pennsylvania Hospital
Authors: Mintzer David M. , Zheng Sarah , Nagamine Michiko , Newman Jason , Benito Maria 
Published: January 2010

Abstract
The case of a patient with recurrent esthesioneuroblastoma complicated by ectopic adrenocorticotropic hormone production is presented, including the workup and management of this uncommon complication of an uncommon disease.