bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural Homology between the C-Terminal Domain of the PapC Usher and Its Plug
Authors: Ford Bradley , Rêgo Ana Toste , Ragan Timothy J. , Pinkner Jerome , Dodson Karen , Driscoll Paul C. , Hultgren Scott , Waksman Gabriel 
Published: January 2010

ABSTRACT

P pili are extracellular appendages responsible for the targeting of uropathogenic
Escherichia coli
to the kidney. They are assembled by the chaperone-usher (CU) pathway of pilus biogenesis involving two proteins, the periplasmic chaperone PapD and the outer membrane assembly platform, PapC. Many aspects of the structural biology of the Pap CU pathway have been elucidated, except for the C-terminal domain of the PapC usher, the structure of which is unknown. In this report, we identify a stable and folded fragment of the C-terminal region of the PapC usher and determine its structure using both X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy. These structures reveal a β-sandwich fold very similar to that of the plug domain, a domain of PapC obstructing its translocation domain. This structural similarity suggests similar functions in usher-mediated pilus biogenesis, playing out at different stages of the process. This structure paves the way for further functional analysis targeting surfaces common to both the plug and the C-terminal domain of PapC.
Role of Decreased Levels of Fis Histone-Like Protein in Crohn's Disease-Associated Adherent Invasive
E
scherichia coli
LF82 Bacteria Interacting with Intestinal Epithelial Cells
Authors: Miquel Sylvie , Claret Laurent , Bonnet Richard , Dorboz Imen , Barnich Nicolas , Darfeuille-Michaud Arlette 
Published: January 2010

ABSTRACT

The interaction of Crohn's disease (CD)-associated adherent-invasive
Escherichia coli
(AIEC) strain LF82 with intestinal epithelial cells depends on surface appendages, such as type 1 pili and flagella. Histone-like proteins operate as global regulators to control the expression of these virulence factors. We evaluated the role of histone-like proteins in AIEC reference strain LF82 during infection of intestinal epithelial cells, Intestine-407, and observed that the
fis
mRNA level was decreased. The role of Fis in AIEC LF82 was determined by studying the phenotype of an LF82
fis
::Km mutant. This was the first mutant of strain LF82 that has been described thus far that is unable to express flagellin but still able to produce type 1 pili. The cyclic-di-GMP pathway linking flagella and type 1 pilus expression is not involved in Fis-mediated regulation, and we identified in the present study Fis-binding sites located upstream of the
fimE
gene and in the intergenic region between
fimB
and
nanC
of the
fim
operon encoding type 1 pili. The major consequence of decreased Fis expression in AIEC bacteria in contact with host cells is a direct downregulation of
fimE
expression, leading to the preferential ON phase of the
fimS
element. Thus, by maintaining type 1 pilus expression, AIEC bacteria, which interact with the gut mucosa, have greater ability to colonize and to induce inflammation in CD patients.
The Physiological Stimulus for the BarA Sensor Kinase
Authors: Gonzalez Chavez Ricardo , Alvarez Adrian F. , Romeo Tony , Georgellis Dimitris 
Published: January 2010

ABSTRACT
The two-component signal transduction system (TCS) BarA/UvrY activates transcription of CsrB and CsrC noncoding RNAs, which act by sequestering the RNA-binding global regulatory protein CsrA. Here, we show that the metabolic end products formate and acetate provide a physiological stimulus for this TCS and thus link posttranscriptional regulation by the Csr system to the metabolic state of the cell.
Early strength gain of mortar with prehydration of the cements
Authors: Topçu İlker Bekir , Şengel Hasan Selim 
Published: February 2010

In this study, early hardening and strength gain of mortar samples with prehydration have been studied and effects of prehydrated cement amount and duration on the compressive strength of the mortar have been examined. The compressive strengths and ultrasound pulse velocities, resonance frequencies, bending strengths, and setting times of prepared samples have been determined by conducting tests on 4 cm × 4 cm × 16 cm samples prepared for this purpose at 2, 7, and 28 d. When the setting times are evaluated, the heat released as a result of hydration declines, and the initial heat is reduced. A significant increase in the early compressive strength as an effect of prehydration method has been observed. It is evaluated that prehydration is an economical and practical method that can be enhanced and used in the production of the ready-mix concrete and prefabricated construction materials.
Look-alike, sound-alike drugs in oncology
Authors: Kovacic Laurel , Chambers Carole 
Published: January 2010

Background. Medication errors with oncology drugs can place cancer patients at risk for adverse events or death. Look-alike, sound-alike (LASA) drug names may increase the risk for errors. Published lists of LASA drug names are generally a result of voluntarily reported medication incidents. This study performed a proactive review of the oncology drug formulary from the Cancer Services of the Alberta Health Services for LASA drug pairs. Methods. The Levenshtein Distance and Bigram Similarity algorithms, same first and last letters, and Lexi-CompR on-line alerts were used to review the outpatient oncology formulary to identify potential LASA generic drug name pairs. Results. Results indicate there are more potential LASA generic drug name pairs in the oncology formulary than are published in the literature. The risk detection methods used in this study identified unique and common LASA drug pairs. The Bigram Similarity algorithm identified 186 LASA drug pairs from 3320 possible pairs. The Levenshtein Distance algorithm, same first and last letters, and Lexi-CompR methods identified 42, 75, and 38 LASA drug pairs, respectively. Five generic LASA drug pairs were identified in common by all four of the risk determination methods. Discussion. LASA drug pairs identified by three or four methods were considered to provide the highest risk for errors. A step-wise approach to risk reduction, dependent on the number of detection methods identifying a pair, is presented. Conclusion. For specialty areas of practice, a proactive system of reviewing LASA drug name pairs may be warranted for increasing medication safety. J Oncol Pharm Practice (2011) 17: 104— 118.
Abnormal VWF modifies megakaryocytopoiesis: studies of platelets and megakaryocyte cultures from patients with von Willebrand disease type 2B
Authors: Nurden Paquita , Gobbi Giuliana , Nurden Alan , Enouf Jocelyne , Youlyouz-Marfak Ibtissam , Carubbi Cecilia , La Marca Silvia , Punzo Margherita , Baronciani Luciano , De Marco Luigi , Vitale Marco , Federici Augusto B. 
Published: January 2010

Abstractvon Willebrand factor (VWF) is an essential mediator of platelet adhesion to the vessel wall, but little is known about its role in megakaryocytopoiesis. VWF and its platelet receptor, glycoprotein Ibα (GPIbα), are both expressed during megakaryocyte (MK) maturation. This study was designed to evaluate whether the enhanced VWF-GPIbα interactions typical of patients with von Willebrand disease type 2B (VWD2B) modify platelet production. Platelets from 9 patients with VWD2B with 7 different gain-of-function mutations were examined by electron microscopy (EM) and immunofluorescence labeling. For the patients with VWD2B, EM characteristically showed variable numbers of structurally abnormal giant platelets, sometimes in agglutinates. Cultures of MKs from controls performed with or without purified VWF confirmed a positive influence of VWF on platelet production with specific inhibition by an antibody blocking VWF binding to GPIbα. VWD2B MK cultures examined by EM showed a disorganized demarcation membrane system and abnormal granule distribution. They produced platelets with structural abnormalities typical of VWD2B. Confocal examination of MK revealed limited extension of pseudopods with few large proplatelets. These results confirm that megakaryocytopoiesis is modified by the enhanced VWF-GPIbα interactions. These data obtained for controls and patients with VWD2B suggest a novel regulatory role of VWF-GPIbα interactions in platelet production.
A temporal precedence based clustering method for gene expression microarray data
Authors: Krishna Ritesh , Li Chang-Tsun , Buchanan-Wollaston Vicky 
Published: January 2010

AbstractBackgroundTime-course microarray experiments can produce useful data which can help in understanding the underlying dynamics of the system. Clustering is an important stage in microarray data analysis where the data is grouped together according to certain characteristics. The majority of clustering techniques are based on distance or visual similarity measures which may not be suitable for clustering of temporal microarray data where the sequential nature of time is important. We present a Granger causality based technique to cluster temporal microarray gene expression data, which measures the interdependence between two time-series by statistically testing if one time-series can be used for forecasting the other time-series or not.ResultsA gene-association matrix is constructed by testing temporal relationships between pairs of genes using the Granger causality test. The association matrix is further analyzed using a graph-theoretic technique to detect highly connected components representing interesting biological modules. We test our approach on synthesized datasets and real biological datasets obtained for Arabidopsis thaliana. We show the effectiveness of our approach by analyzing the results using the existing biological literature. We also report interesting structural properties of the association network commonly desired in any biological system.ConclusionsOur experiments on synthesized and real microarray datasets show that our approach produces encouraging results. The method is simple in implementation and is statistically traceable at each step. The method can produce sets of functionally related genes which can be further used for reverse-engineering of gene circuits.
Global transcriptomic response of Leptospira interrogans serovar Copenhageni upon exposure to serum
Authors: Patarakul Kanitha , Lo Miranda , Adler Ben 
Published: January 2010

Abstract

Background
Leptospirosis is a zoonosis of worldwide distribution caused by infection with pathogenic serovars of Leptospira spp. The most common species, L. interrogans, can survive in the environment for lengthy periods of time in between infection of mammalian hosts. Transmission of pathogenic Leptospira to humans mostly occurs through abraded skin or mucosal surfaces after direct or indirect contact with infected animals or contaminated soil or water. The spirochete then spreads hematogenously, resulting in multi-organ failure and death in severe cases. Previous DNA microarray studies have identified differentially expressed genes required for adaptation to temperature and osmolarity conditions inside the host compared to those of the environment.

Results
In order to identify genes involved in survival in the early spirochetemic phase of infection, we performed a transcriptional analysis of L. interrogans serovar Copenhageni upon exposure to serum in comparison with EMJH medium. One hundred and sixty-eight genes were found to be differentially expressed, of which 55 were up-regulated and 113 were down-regulated. Genes of known or predicted function accounted for 54.5 and 45.1% of up- and down-regulated genes, respectively. Most of the differentially expressed genes were predicted to be involved in transcriptional regulation, translational process, two-component signal transduction systems, cell or membrane biogenesis, and metabolic pathways.

Conclusions
Our study showed global transcriptional changes of pathogenic Leptospira upon exposure to serum, representing a specific host environmental cue present in the bloodstream. The presence of serum led to a distinct pattern of gene expression in comparison to those of previous single-stimulus microarray studies on the effect of temperature and osmolarity upshift. The results provide insights into the pathogenesis of leptospirosis during the early bacteremic phase of infection.
Genetic Diversity of Salmonella enteric serovar Typhi and Paratyphi in Shenzhen, China from 2002 through 2007
Authors: Wu Weiyuan , Wang Hui , Lu Jian , Wu Jinsong , Chen Minjun , Xu Yingchun , Lu Yuemei 
Published: January 2010

Abstract

Background
Typhoid and paratyphoid fever are endemic in China. The objective of this investigation was to determine the molecular features of nalidixic acid-resistant Salmonella enteric serovar Typhi (S. typhi) and Paratyphi (S. paratyphi) from blood isolates in Shenzhen, China.

Results
Twenty-five S. typhi and 66 S. paratyphi were isolated from 91 bacteriemic patients between 2002 and 2007 at a hospital in Shenzhen, Southern China. Fifty-two percent (13/25) of S. typhi and 95.3% (61/64) of S. paratyphi A were resistant to nalidixic acid. Sixty-seven isolates of nalidixic acid-resistant Salmonella (NARS) showed decreased susceptibility to ciprofloxacin (MICs of 0.125-1 μg/mL). All 75 NARS isolates had a single substitution in the quinolone resistance-determining region (QRDR) of GyrA (Ser83→Phe/Pro/Tyr, or Asp87→Gly/Asn), and 90.7% of these isolates carried the substitution Ser83Phe in GyrA. No mutation was found in the QRDR of gyrB, parC, or parE. Plasmid mediated quinolone resistance genes including qnr and aac(6')-Ib-cr were not detected in any isolate. Twenty-two distinct pulsed field gel electrophoresis (PFGE) patterns were observed among S. typhi. Sixty-four isolates of S. paratyphi A belonged to one clone. Eighty-seven investigated inpatients were infected in the community. Six patients infected by S. paratyphi A had a travel history before infection.

Conclusions
Nalidixic acid-resistant S. typhi and S. paratyphi A blood isolates were highly prevalent in Shenzhen, China. PFGE showed the variable genetic diversity of nalidixic acid-resistant S. typhi and limited genetic diversity of nalidixic acid -resistant S. paratyphi A.
Toll-like receptor 2 gene polymorphisms, pulmonary tuberculosis, and natural killer cell counts
Authors: Chen Yung-Che , Hsiao Chang-Chun , Chen Chung-Jen , Chin Chien-Hung , Liu Shih-Feng , Wu Chao-Chien , Eng Hock-Liew , Chao Tung-Ying , Tsen Chia-Cheng , Wang Yi-Hsi , Lin Meng-Chih 
Published: January 2010

AbstractBackgroundTo investigate whether the toll-like receptor 2 polymorphisms could influence susceptibility to pulmonary TB, its phenotypes, and blood lymphocyte subsets.MethodsA total of 368 subjects, including 184 patients with pulmonary TB and 184 healthy controls, were examined for TLR2 polymorphisms over locus -100 (microsatellite guanine-thymine repeats), -16934 (T>A), -15607 (A>G), -196 to -174 (insertion>deletion), and 1350 (T>C). Eighty-six TB patients were examined to determine the peripheral blood lymphocyte subpopulations.ResultsWe newly identified an association between the haplotype [A-G-(insertion)-T] and susceptibility to pulmonary TB (p = 0.006, false discovery rate q = 0.072). TB patients with systemic symptoms had a lower -196 to -174 deletion/deletion genotype frequency than those without systemic symptoms (5.7% vs. 17.7%; p = 0.01). TB patients with the deletion/deletion genotype had higher blood NK cell counts than those carrying the insertion allele (526 vs. 243.5 cells/μl, p = 0.009). TB patients with pleuritis had a higher 1350 CC genotype frequency than those without pleuritis (12.5% vs. 2.1%; p = 0.004). TB patients with the 1350 CC genotype had higher blood NK cell counts than those carrying the T allele (641 vs. 250 cells/μl, p = 0.004). TB patients carrying homozygous short alleles for GT repeats had higher blood NK cell counts than those carrying one or no short allele (641 vs. 250 cells/μl, p = 0.004).ConclusionsTLR2 genetic polymorphisms influence susceptibility to pulmonary TB. TLR2 variants play a role in the development of TB phenotypes, probably by controlling the expansion of NK cells.
The association between farming activities, precipitation, and the risk of acute gastrointestinal illness in rural municipalities of Quebec, Canada: a cross-sectional study
Authors: Febriani Yossi , Levallois Patrick , Gingras Suzanne , Gosselin Pierre , Majowicz Shannon E , Fleury Manon D 
Published: January 2010

Abstract

Background
Increasing livestock density and animal manure spreading, along with climate factors such as heavy rainfall, may increase the risk of acute gastrointestinal illness (AGI). In this study we evaluated the association between farming activities, precipitation and AGI.

Methods
A cross-sectional telephone survey of randomly selected residents (n = 7006) of 54 rural municipalities in Quebec, Canada, was conducted between April 2007 and April 2008. AGI symptoms and several risk factors were investigated using a phone questionnaire. We calculated the monthly prevalence of AGI, and used multivariate logistic regression, adjusting for several demographic and risk factors, to evaluate the associations between AGI and both intensive farming activities and cumulative weekly precipitation. Cumulative precipitation over each week, from the first to sixth week prior to the onset of AGI, was analyzed to account for both the delayed effect of precipitation on AGI, and the incubation period of causal pathogens. Cumulative precipitation was treated as a four-category variable: high (≥90th percentile), moderate (50th to <90th percentile), low (10th to <50th percentile), and very low (<10th percentile) precipitation.

Results
The overall monthly prevalence of AGI was 5.6% (95% CI 5.0%-6.1%), peaking in winter and spring, and in children 0-4 years old. Living in a territory with intensive farming was negatively associated with AGI: adjusted odds ratio (OR) = 0.70 (95% CI 0.51-0.96). Compared to low precipitation periods, high precipitation periods in the fall (September, October, November) increased the risk of AGI three weeks later (OR = 2.20; 95% CI 1.09-4.44) while very low precipitation periods in the summer (June, July, August) increased the risk of AGI four weeks later (OR = 2.19; 95% CI 1.02-4.71). Further analysis supports the role of water source on the risk of AGI.

Conclusions
AGI poses a significant burden in Quebec rural municipalities with a peak in winter. Intensive farming activities were found to be negatively associated with AGI. However, high and very low precipitation levels were positively associated with the occurrence of AGI, especially during summer and fall. Thus, preventive public health actions during such climate events may be warranted.
Expression of epithelial calcium transport system in rat cochlea and vestibular labyrinth
Authors: Yamauchi Daisuke , Nakaya Kazuhiro , Raveendran Nithya N , Harbidge Donald G , Singh Ruchira , Wangemann Philine , Marcus Daniel C 
Published: January 2010

Abstract

Background
The low luminal Ca2+ concentration of mammalian endolymph in the inner ear is required for normal hearing and balance. We recently reported the expression of mRNA for a Ca2+-absorptive transport system in primary cultures of semicircular canal duct (SCCD) epithelium.

Results
We now identify this system in native vestibular and cochlear tissues by qRT-PCR, immunoblots and confocal immunolocalization. Transcripts were found and quantified for several isoforms of epithelial calcium channels (TRPV5, TRPV6), calcium buffer proteins (calbindin-D9K, calbindin-D28K), sodium-calcium exchangers (NCX1, NCX2, NCX3) and plasma membrane Ca2+-ATPase (PMCA1, PMCA2, PMCA3, and PMCA4) in native SCCD, cochlear lateral wall (LW) and stria vascularis (SV) of adult rat as well as Ca2+ channels in neonatal SCCD. All components were expressed except TRPV6 in SV and PMCA2 in SCCD. 1,25-(OH)2vitamin D3 (VitD) significantly up-regulated transcripts of TRPV5 in SCCD, calbindin-D9K in SCCD and LW, NCX2 in LW, while PMCA4 in SCCD and PMCA3 in LW were down-regulated. The expression of TRPV5 relative to TRPV6 was in the sequence SV > Neonatal SCCD > Adult SCCD > LW > primary culture SCCD. Expression of TRPV5 protein from primary culture of SCCD did not increase significantly when cells were incubated with VitD (1.2 times control; P > 0.05). Immunolocalization showed the distribution of TRPV5 and TRPV6. TRPV5 was found near the apical membrane of strial marginal cells and both TRPV5 and TRPV6 in outer and inner sulcus cells of the cochlea and in the SCCD of the vestibular system.

Conclusions
These findings demonstrate for the first time the expression of a complete Ca2+ absorptive system in native cochlear and vestibular tissues. Regulation by vitamin D remains equivocal since the results support the regulation of this system at the transcript level but evidence for control of the TRPV5 channel protein was lacking.
Analysis of the role of PCNA-DNA contacts during clamp loading
Authors: McNally Randall , Bowman Gregory D , Goedken Eric R , O'Donnell Mike , Kuriyan John 
Published: January 2010

AbstractBackgroundSliding clamps, such as Proliferating Cell Nuclear Antigen (PCNA) in eukaryotes, are ring-shaped protein complexes that encircle DNA and enable highly processive DNA replication by serving as docking sites for DNA polymerases. In an ATP-dependent reaction, clamp loader complexes, such as the Replication Factor-C (RFC) complex in eukaryotes, open the clamp and load it around primer-template DNA.ResultsWe built a model of RFC bound to PCNA and DNA based on existing crystal structures of clamp loaders. This model suggests that DNA would enter the clamp at an angle during clamp loading, thereby interacting with positively charged residues in the center of PCNA. We show that simultaneous mutation of Lys 20, Lys 77, Arg 80, and Arg 149, which interact with DNA in the RFC-PCNA-DNA model, compromises the ability of yeast PCNA to stimulate the DNA-dependent ATPase activity of RFC when the DNA is long enough to extend through the clamp. Fluorescence anisotropy binding experiments show that the inability of the mutant clamp proteins to stimulate RFC ATPase activity is likely caused by reduction in the affinity of the RFC-PCNA complex for DNA. We obtained several crystal forms of yeast PCNA-DNA complexes, measuring X-ray diffraction data to 3.0 Å resolution for one such complex. The resulting electron density maps show that DNA is bound in a tilted orientation relative to PCNA, but makes different contacts than those implicated in clamp loading. Because of apparent partial disorder in the DNA, we restricted refinement of the DNA to a rigid body model. This result contrasts with previous analysis of a bacterial clamp bound to DNA, where the DNA was well resolved.ConclusionMutational analysis of PCNA suggests that positively charged residues in the center of the clamp create a binding surface that makes contact with DNA. Disruption of this positive surface, which had not previously been implicated in clamp loading function, reduces RFC ATPase activity in the presence of DNA, most likely by reducing the affinity of RFC and PCNA for DNA. The interaction of DNA is not, however, restricted to one orientation, as indicated by analysis of the PCNA-DNA co-crystals.