bluuebunny/crossref_metadata_2025_split huggingface dataset:
The DtxR protein acting as dual transcriptional regulator directs a global regulatory network involved in iron metabolism of Corynebacterium glutamicum
Authors: Brune Iris , Werner Hendrikje , Hüser Andrea T , Kalinowski Jörn , Pühler Alfred , Tauch Andreas 
Published: February 2006

Abstract

Background
The knowledge about complete bacterial genome sequences opens the way to reconstruct the qualitative topology and global connectivity of transcriptional regulatory networks. Since iron is essential for a variety of cellular processes but also poses problems in biological systems due to its high toxicity, bacteria have evolved complex transcriptional regulatory networks to achieve an effective iron homeostasis. Here, we apply a combination of transcriptomics, bioinformatics, in vitro assays, and comparative genomics to decipher the regulatory network of the iron-dependent transcriptional regulator DtxR of Corynebacterium glutamicum.

Results
A deletion of the dtxR gene of C. glutamicum ATCC 13032 led to the mutant strain C. glutamicum IB2103 that was able to grow in minimal medium only under low-iron conditions. By performing genome-wide DNA microarray hybridizations, differentially expressed genes involved in iron metabolism of C. glutamicum were detected in the dtxR mutant. Bioinformatics analysis of the genome sequence identified a common 19-bp motif within the upstream region of 31 genes, whose differential expression in C. glutamicum IB2103 was verified by real-time reverse transcription PCR. Binding of a His-tagged DtxR protein to oligonucleotides containing the 19-bp motifs was demonstrated in vitro by DNA band shift assays. At least 64 genes encoding a variety of physiological functions in iron transport and utilization, in central carbohydrate metabolism and in transcriptional regulation are controlled directly by the DtxR protein. A comparison with the bioinformatically predicted networks of C. efficiens, C. diphtheriae and C. jeikeium identified evolutionary conserved elements of the DtxR network.

Conclusion
This work adds considerably to our currrent understanding of the transcriptional regulatory network of C. glutamicum genes that are controlled by DtxR. The DtxR protein has a major role in controlling the expression of genes involved in iron metabolism and exerts a dual regulatory function as repressor of genes participating in iron uptake and utilization and as activator of genes responsible for iron storage and DNA protection. The data suggest that the DtxR protein acts as global regulator by controlling the expression of other regulatory proteins that might take care of an iron-dependent regulation of a broader transcriptional network of C. glutamicum genes.
Evaluation and selection of tandem repeat loci for a Brucella MLVA typing assay
Authors: Le Flèche Philippe , Jacques Isabelle , Grayon Maggy , Al Dahouk Sascha , Bouchon Patrick , Denoeud France , Nöckler Karsten , Neubauer Heinrich , Guilloteau Laurence A , Vergnaud Gilles 
Published: February 2006

Abstract

Background
The classification of Brucella into species and biovars relies on phenotypic characteristics and sometimes raises difficulties in the interpretation of the results due to an absence of standardization of the typing reagents. In addition, the resolution of this biotyping is moderate and requires the manipulation of the living agent. More efficient DNA-based methods are needed, and this work explores the suitability of multiple locus variable number tandem repeats analysis (MLVA) for both typing and species identification.

Results
Eighty tandem repeat loci predicted to be polymorphic by genome sequence analysis of three available Brucella genome sequences were tested for polymorphism by genotyping 21 Brucella strains (18 reference strains representing the six 'classical' species and all biovars as well as 3 marine mammal strains currently recognized as members of two new species). The MLVA data efficiently cluster the strains as expected according to their species and biovar. For practical use, a subset of 15 loci preserving this clustering was selected and applied to the typing of 236 isolates. Using this MLVA-15 assay, the clusters generated correspond to the classical biotyping scheme of Brucella spp. The 15 markers have been divided into two groups, one comprising 8 user-friendly minisatellite markers with a good species identification capability (panel 1) and another complementary group of 7 microsatellite markers with higher discriminatory power (panel 2).

Conclusion
The MLVA-15 assay can be applied to large collections of Brucella strains with automated or manual procedures, and can be proposed as a complement, or even a substitute, of classical biotyping methods. This is facilitated by the fact that MLVA is based on non-infectious material (DNA) whereas the biotyping procedure itself requires the manipulation of the living agent. The data produced can be queried on a dedicated MLVA web service site.
Are osteoporotic fractures being adequately investigated?: A questionnaire of GP & orthopaedic surgeons
Authors: Chami George , Jeys Lee , Freudmann Mathew , Connor Louise , Siddiqi Mashood 
Published: February 2006

Abstract

Background
To investigate the current practice of Orthopaedic Surgeons & General Practitioners (GP) when presented with patients who have a fracture, with possible underlying Osteoporosis.

Methods
Questionnaires were sent to 140 GPs and 140 Orthopaedic Surgeons. The participants were asked their routine clinical practice with regard to investigation of underlying osteoporosis in 3 clinical scenarios.
55 year old lady with a low trauma Colles fracture
60 year old lady with a vertebral wedge fracture
70 year old lady with a low trauma neck of femur fracture.

Results
Most doctors agreed that patients over 50 years old with low trauma fractures required investigation for osteoporosis, however, most surgeons (56%, n = 66) would discharge patients with low trauma Colles fracture without requesting or initiating investigation for osteoporosis. Most GPs (67%, n = 76) would not investigate a similar patient for osteoporosis, unless prompted by the Orthopaedic Surgeon or patient.
More surgeons (71%, n= 83) and GPs (64%, n = 72) would initiate investigations for osteoporosis in a vertebral wedge fracture, but few surgeons (35%, n = 23) would investigate a neck of femur fracture patient after orthopaedic treatment.

Conclusion
Most doctors know that fragility fractures in patients over 50 years old require investigation for Osteoporosis; however, a large population of patients with osteoporotic fractures are not being given the advantages of secondary prevention.
Gene expression profiles in developing nephrons using Lim1 metanephric mesenchyme-specific conditional mutant mice
Authors: Chen You-Tzung , Kobayashi Akio , Kwan Kin Ming , Johnson Randy L , Behringer Richard R 
Published: February 2006

Abstract

Background

Lim1 is a homeobox gene that is essential for nephrogenesis. During metanephric kidney development, Lim1 is expressed in the nephric duct, ureteric buds, and the induced metanephric mesenchyme. Conditional ablation of Lim1 in the metanephric mesenchyme blocks the formation of nephrons at the nephric vesicle stage, leading to the production of small, non-functional kidneys that lack nephrons.

Methods
In the present study, we used Affymetrix probe arrays to screen for nephron-specific genes by comparing the expression profiles of control and Lim1 conditional mutant kidneys. Kidneys from two developmental stages, embryonic day 14.5 (E14.5) and 18.5 (E18.5), were examined.

Results
Comparison of E18.5 kidney expression profiles generated a list of 465 nephron-specific gene candidates that showed a more than 2-fold increase in their expression level in control kidney versus the Lim1 conditional mutant kidney. Computational analysis confirmed that this screen enriched for kidney-specific genes. Furthermore, at least twenty-eight of the top fifty (56%) candidates (or their vertebrate orthologs) were previously reported to have a nephron-specific expression pattern. Our analysis of E14.5 expression data yielded 41 candidate genes that are up-regulated in the control kidneys compared to the conditional mutants. Three of them are related to the Notch signaling pathway that is known to be important in cell fate determination and nephron patterning.

Conclusion
Therefore, we demonstrate that Lim1 conditional mutant kidneys serve as a novel tissue source for comprehensive expression studies and provide a means to identify nephron-specific genes.
Study protocol to investigate the effect of a lifestyle intervention on body weight, psychological health status and risk factors associated with disease recurrence in women recovering from breast cancer treatment [ISRCTN08045231]
Authors: Saxton John M , Daley Amanda , Woodroofe Nicola , Coleman Robert , Powers Hilary , Mutrie Nanette , Siddall Vanessa , Crank Helen 
Published: February 2006

AbstractBackgroundBreast cancer survivors often encounter physiological and psychological problems related to their diagnosis and treatment that can influence long-term prognosis. The aim of this research is to investigate the effects of a lifestyle intervention on body weight and psychological well-being in women recovering from breast cancer treatment, and to determine the relationship between changes in these variables and biomarkers associated with disease recurrence and survival.Methods/designFollowing ethical approval, a total of 100 patients will be randomly assigned to a lifestyle intervention (incorporating dietary energy restriction in conjunction with aerobic exercise training) or normal care control group. Patients randomised to the dietary and exercise intervention will be given individualised healthy eating dietary advice and written information and attend moderate intensity aerobic exercise sessions on three to five days per week for a period of 24 weeks. The aim of this strategy is to induce a steady weight loss of up to 0.5 Kg each week. In addition, the overall quality of the diet will be examined with a view to (i) reducing the dietary intake of fat to ~25% of the total calories, (ii) eating at least 5 portions of fruit and vegetables a day, (iii) increasing the intake of fibre and reducing refined carbohydrates, and (iv) taking moderate amounts of alcohol. Outcome measures will include body weight and body composition, psychological health status (stress and depression), cardiorespiratory fitness and quality of life. In addition, biomarkers associated with disease recurrence, including stress hormones, estrogen status, inflammatory markers and indices of innate and adaptive immune function will be monitored.DiscussionThis research will provide valuable information on the effectiveness of a practical, easily implemented lifestyle intervention for evoking positive effects on body weight and psychological well-being, two important factors that can influence long-term prognosis in breast cancer survivors. However, the added value of the study is that it will also evaluate the effects of the lifestyle intervention on a range of biomarkers associated with disease recurrence and survival. Considered together, the results should improve our understanding of the potential role that lifestyle-modifiable factors could play in saving or prolonging lives.
Signs of positive selection of somatic mutations in human cancers detected by EST sequence analysis
Authors: Babenko Vladimir N , Basu Malay K , Kondrashov Fyodor A , Rogozin Igor B , Koonin Eugene V 
Published: February 2006

Abstract

Background
Carcinogenesis typically involves multiple somatic mutations in caretaker (DNA repair) and gatekeeper (tumor suppressors and oncogenes) genes. Analysis of mutation spectra of the tumor suppressor that is most commonly mutated in human cancers, p53, unexpectedly suggested that somatic evolution of the p53 gene during tumorigenesis is dominated by positive selection for gain of function. This conclusion is supported by accumulating experimental evidence of evolution of new functions of p53 in tumors. These findings prompted a genome-wide analysis of possible positive selection during tumor evolution.

Methods
A comprehensive analysis of probable somatic mutations in the sequences of Expressed Sequence Tags (ESTs) from malignant tumors and normal tissues was performed in order to access the prevalence of positive selection in cancer evolution. For each EST, the numbers of synonymous and non-synonymous substitutions were calculated. In order to identify genes with a signature of positive selection in cancers, these numbers were compared to: i) expected numbers and ii) the numbers for the respective genes in the ESTs from normal tissues.

Results
We identified 112 genes with a signature of positive selection in cancers, i.e., a significantly elevated ratio of non-synonymous to synonymous substitutions, in tumors as compared to 37 such genes in an approximately equal-sized EST collection from normal tissues. A substantial fraction of the tumor-specific positive-selection candidates have experimentally demonstrated or strongly predicted links to cancer.

Conclusion
The results of EST analysis should be interpreted with extreme caution given the noise introduced by sequencing errors and undetected polymorphisms. Furthermore, an inherent limitation of EST analysis is that multiple mutations amenable to statistical analysis can be detected only in relatively highly expressed genes. Nevertheless, the present results suggest that positive selection might affect a substantial number of genes during tumorigenic somatic evolution.
Inflammation and enhanced nociceptive responses to bladder distension produced by intravesical zymosan in the rat
Authors: Randich Alan , Uzzell Tyler , Cannon Ronda , Ness Timothy J 
Published: February 2006

Abstract

Background
Mycotic infections of the bladder produce pain and inflammatory changes. The present study examined the inflammatory and nociceptive effects of the yeast cell wall component, zymosan, when admininstered into the urinary bladder in order to characterize this form of bladder sensitization.

Methods
Parametric analyses of the time-course (0–48 hr) and concentration (0–2% solutions) variables associated with intravesical zymosan-induced bladder inflammation were performed in female rats. Plasma extravasation of Evan's Blue dye was used as a measure of tissue inflammation. Cardiovascular and visceromotor responses to urinary bladder distension were used as measures of nociception.

Results
Zymosan-induced bladder inflammation, as indexed by plasma extravasation of Evan's Blue, was significantly greater in rats treated with either 1 or 2% solutions as compared to either 0.1 or 0.5% zymosan solutions. In time-course studies (1 – 48 hr post-treatment), 1% zymosan-induced inflammation progressively increased with time following administration, was greatest at 24 hr and began to normalize by 48 hr. In the studies of inflammation-induced changes in nociception, arterial blood pressure (ABP) and visceromotor responses to graded distension of the urinary bladder were significantly increased relative to controls 24 hr after zymosan administration.

Conclusion
These studies provide important time-course and solution concentration parameters for studies of zymosan-induced inflammation of the bladder and suggest utility of this model for the study of bladder-related pain.
Uncharged isocoumarin-based inhibitors of urokinase-type plasminogen activator
Authors: Heynekamp Justin J , Hunsaker Lucy A , Vander Jagt Thomas A , Deck Lorraine M , Vander Jagt David L 
Published: February 2006

Abstract

Background
Urokinase-type plasminogen activator (uPA) plays a major role in extracellular proteolytic events associated with tumor cell growth, migration and angiogenesis. Consequently, uPA is an attractive target for the development of small molecule active site inhibitors. Most of the recent drug development programs aimed at nonpeptidic inhibitors targeted at uPA have focused on arginino mimetics containing amidine or guanidine functional groups attached to aromatic or heterocyclic scaffolds. There is a general problem of limited bioavailability of these charged inhibitors. In the present study, uPA inhibitors were designed on an isocoumarin scaffold containing uncharged substituents.

Results
4-Chloro-3-alkoxyisocoumarins were synthesized in which the 3-alkoxy group contained a terminal bromine; these were compared with similar inhibitors that contained a charged terminal functional group. Additional variations included functional groups attached to the seven position of the isocoumarin scaffold. N- [3-(3-Bromopropoxy)-4-chloro-1-oxo-1H-isochromen-7-yl]benzamide was identified as an uncharged lead inhibitor of uPA, Ki = 0.034 μM. Molecular modeling of human uPA with these uncharged inhibitors suggests that the bromine occupies the same position as positively charged arginino mimetic groups.

Conclusion
This study demonstrates that potent uncharged inhibitors of uPA can be developed based upon the isocoumarin scaffold. A tethered bromine in the three position and an aromatic group in the seven position are important contributors to binding. Although the aim was to develop compounds that act as mechanism-based inactivators, these inhibitors are competitive reversible inhibitors.
Nurses' perceptions and experiences of communication in the operating theatre: a focus group interview
Authors: Nestel Debra , Kidd Jane 
Published: February 2006

AbstractNurses' perceptions and experiences of communication in the operating theatre: a focus group interviewBackgroundCommunication programmes are well established in nurse education. The focus of programmes is most often on communicating with patients with less attention paid to inter-professional communication or skills essential for working in specialised settings. Although there are many anecdotal reports of communication within the operating theatre, there are few empirical studies. This paper explores communication behaviours for effective practice in the operating theatre as perceived by nurses and serves as a basis for developing training.MethodsA focus group interview was conducted with seven experienced theatre nurses from a large London teaching hospital. The interview explored their perceptions of the key as well as unique features of effective communication skills in the operating theatre. Data was transcribed and thematically analysed until agreement was achieved by the two authors.ResultsThere was largely consensus on the skills deemed necessary for effective practice including listening, clarity of speech and being polite. Significant influences on the nature of communication included conflict in role perception and organisational issues. Nurses were often expected to work outside of their role which either directly or indirectly created barriers for effective communication. Perceptions of a lack of collaborative team effort also influenced communication.ConclusionAlthough fundamental communication skills were identified for effective practice in the operating theatre, there were significant barriers to their use because of confusion over clarity of roles (especially nurses' roles) and the implications for teamwork. Nurses were dissatisfied with several aspects of communication. Future studies should explore the breadth and depth of this dissatisfaction in other operating theatres, its impact on morale and importantly on patient safety. Interprofessional communication training for operating theatre staff based in part on the key issues identified in this study may help to create clarity in roles and focus attention on effective teamwork and promote clinical safety.
Influence of head models on EEG simulations and inverse source localizations
Authors: Ramon Ceon , Schimpf Paul H , Haueisen Jens 
Published: February 2006

Abstract

Background
The structure of the anatomical surfaces, e.g., CSF and gray and white matter, could severely influence the flow of volume currents in a head model. This, in turn, will also influence the scalp potentials and the inverse source localizations. This was examined in detail with four different human head models.

Methods
Four finite element head models constructed from segmented MR images of an adult male subject were used for this study. These models were: (1) Model 1: full model with eleven tissues that included detailed structure of the scalp, hard and soft skull bone, CSF, gray and white matter and other prominent tissues, (2) the Model 2 was derived from the Model 1 in which the conductivity of gray matter was set equal to the white matter, i.e., a ten tissue-type model, (3) the Model 3 was derived from the Model 1 in which the conductivities of gray matter and CSF were set equal to the white matter, i.e., a nine tissue-type model, (4) the Model 4 consisted of scalp, hard skull bone, CSF, gray and white matter, i.e., a five tissue-type model. How model complexity influences the EEG source localizations was also studied with the above four finite element models of the head. The lead fields and scalp potentials due to dipolar sources in the motor cortex were computed for all four models. The inverse source localizations were performed with an exhaustive search pattern in the motor cortex area. The inverse analysis was performed by adding uncorrelated Gaussian noise to the scalp potentials to achieve a signal to noise ratio (SNR) of -10 to 30 dB. The Model 1 was used as a reference model.

Results
The reference model, as expected, performed the best. The Model 3, which did not have the CSF layer, performed the worst. The mean source localization errors (MLEs) of the Model 3 were larger than the Model 1 or 2. The scalp potentials were also most affected by the lack of CSF geometry in the Model 3. The MLEs for the Model 4 were also larger than the Model 1 and 2. The Model 4 and the Model 3 had similar MLEs in the SNR range of -10 dB to 0 dB. However, in the SNR range of 5 dB to 30 dB, the Model 4 has lower MLEs as compared with the Model 3.

Discussion
These results indicate that the complexity of head models strongly influences the scalp potentials and the inverse source localizations. A more complex head model performs better in inverse source localizations as compared to a model with lesser tissue surfaces. The CSF layer plays an important role in modifying the scalp potentials and also influences the inverse source localizations. In summary, for best results one needs to have highly heterogeneous models of the head for accurate simulations of scalp potentials and for inverse source localizations.
Electrical impedance tomography imaging using a priori ultrasound data
Authors: Soleimani Manuchehr 
Published: February 2006

Abstract

Background
Different imaging systems (e.g. electrical, magnetic, and ultrasound) rely on a wide variety of physical properties, and the datasets obtained from such systems provide only partial information about the unknown true state. One approach is to choose complementary imaging systems, and to combine the information to achieve a better representation.

Methods
This paper discusses the combination of ultrasound and electrical impedance tomography (EIT) information. Ultrasound reflection signals are good at locating sharp acoustic density changes associated with the boundaries of objects. Some boundaries, however, may be indeterminable due to masking from intermediate boundaries or because they are outside the ultrasound beam. Conversely, the EIT data contains relatively low-quality information, but it includes the whole region enclosed by the electrodes.

Results
Results are shown from a narrowband level-set method applied to 2D and 3D EIT incorporating limited angle ultrasound time of flight data.

Conclusion
The EIT reconstruction is shown to be faster and more accurate using the additional edge information from both one and four transducer ultrasound systems.