bluuebunny/crossref_metadata_2025_split huggingface dataset:
GxySBA ABC Transporter of Agrobacterium tumefaciens and Its Role in Sugar Utilization and
vir
Gene Expression
Authors: Zhao Jinlei , Binns Andrew N. 
Published: June 2014

ABSTRACT

Monosaccharides available in the extracellular milieu of
Agrobacterium tumefaciens
can be transported into the cytoplasm, or via the periplasmic sugar binding protein, ChvE, play a critical role in controlling virulence gene expression. The ChvE-MmsAB ABC transporter is involved in the utilization of a wide range of monosaccharide substrates but redundant transporters are likely given the ability of a
chvE-mmsAB
deletion strain to grow, albeit more slowly, in the presence of particular monosaccharides. In this study, a putative ABC transporter encoded by the
gxySBA
operon is identified and shown to be involved in the utilization of glucose, xylose, fucose, and arabinose, which are also substrates for the ChvE-MmsAB ABC transporter. Significantly, GxySBA is also shown to be the first characterized glucosamine ABC transporter. The divergently transcribed gene
gxyR
encodes a repressor of the
gxySBA
operon, the function of which can be relieved by a subset of the transported sugars, including glucose, xylose, and glucosamine, and this substrate-induced expression can be repressed by glycerol. Furthermore, deletion of the transporter can increase the sensitivity of the virulence gene expression system to certain sugars that regulate it. Collectively, the results reveal a remarkably diverse set of substrates for the GxySBA transporter and its contribution to the repression of sugar sensitivity by the virulence-controlling system, thereby facilitating the capacity of the bacterium to distinguish between the soil and plant environments.
Analysis of Salmonella enterica Serovar Typhimurium Variable-Number Tandem-Repeat Data for Public Health Investigation Based on Measured Mutation Rates and Whole-Genome Sequence Comparisons
Authors: Dimovski Karolina , Cao Hanwei , Wijburg Odilia L. C. , Strugnell Richard A. , Mantena Radha K. , Whipp Margaret , Hogg Geoff , Holt Kathryn E. 
Published: June 2014

ABSTRACT

Variable-number tandem repeats (VNTRs) mutate rapidly and can be useful markers for genotyping. While multilocus VNTR analysis (MLVA) is increasingly used in the detection and investigation of food-borne outbreaks caused by
Salmonella enterica
serovar Typhimurium (
S
. Typhimurium) and other bacterial pathogens, MLVA data analysis usually relies on simple clustering approaches that may lead to incorrect interpretations. Here, we estimated the rates of copy number change at each of the five loci commonly used for
S
. Typhimurium MLVA, during
in vitro
and
in vivo
passage. We found that loci STTR5, STTR6, and STTR10 changed during passage but STTR3 and STTR9 did not. Relative rates of change were consistent across
in vitro
and
in vivo
growth and could be accurately estimated from diversity measures of natural variation observed during large outbreaks. Using a set of 203 isolates from a series of linked outbreaks and whole-genome sequencing of 12 representative isolates, we assessed the accuracy and utility of several alternative methods for analyzing and interpreting
S
. Typhimurium MLVA data. We show that eBURST analysis was accurate and informative. For construction of MLVA-based trees, a novel distance metric, based on the geometric model of VNTR evolution coupled with locus-specific weights, performed better than the commonly used simple or categorical distance metrics. The data suggest that, for the purpose of identifying potential transmission clusters for further investigation, isolates whose profiles differ at one of the rapidly changing STTR5, STTR6, and STTR10 loci should be collapsed into the same cluster.
Chemosensory Regulation of a HEAT-Repeat Protein Couples Aggregation and Sporulation in Myxococcus xanthus
Authors: Darnell Cynthia L. , Wilson Janet M. , Tiwari Nitija , Fuentes Ernesto J. , Kirby John R. 
Published: June 2014

ABSTRACT

Chemosensory systems are complex, highly modified two-component systems (TCS) used by bacteria to control various biological functions ranging from motility to sporulation. Chemosensory systems and TCS both modulate phosphorelays comprised of histidine kinases and response regulators, some of which are single-domain response regulators (SD-RRs) such as CheY. In this study, we have identified and characterized the Che7 chemosensory system of
Myxococcus xanthus
, a common soil bacterium which displays multicellular development in response to stress. Both genetic and biochemical analyses indicate that the Che7 system regulates development via a direct interaction between the SD-RR CheY7 and a HEAT repeat domain-containing protein, Cpc7. Phosphorylation of the SD-RR affects the interaction with its target, and residues within the α4-β5-α5 fold of the REC domain govern this interaction. The identification of the Cpc7 interaction with CheY7 extends the diversity of known targets for SD-RRs in biological systems.
Accumulation of Phosphatidic Acid Increases Vancomycin Resistance in Escherichia coli
Authors: Sutterlin Holly A. , Zhang Sisi , Silhavy Thomas J. 
Published: June 2014

ABSTRACT

In Gram-negative bacteria, lipopolysaccharide (LPS) contributes to the robust permeability barrier of the outer membrane, preventing entry of toxic molecules such as antibiotics. Mutations in
lptD
, the beta-barrel component of the LPS transport and assembly machinery, compromise LPS assembly and result in increased antibiotic sensitivity. Here, we report rare vancomycin-resistant suppressors that improve barrier function of a subset of
lptD
mutations. We find that all seven suppressors analyzed mapped to the essential gene
cdsA
, which is responsible for the conversion of phosphatidic acid to CDP-diacylglycerol in phospholipid biosynthesis. These
cdsA
mutations cause a partial loss of function and, as expected, accumulate phosphatidic acid. We show that this suppression is not confined to mutations that cause defects in outer membrane biogenesis but rather that these
cdsA
mutations confer a general increase in vancomycin resistance, even in a wild-type cell. We use genetics and quadrupole time of flight (Q-TOF) liquid chromatography-mass spectrometry (LC-MS) to show that accumulation of phosphatidic acid by means other than
cdsA
mutations also increases resistance to vancomycin. We suggest that increased levels of phosphatidic acid change the physical properties of the outer membrane to impede entry of vancomycin into the periplasm, hindering access to its target, an intermediate required for the synthesis of the peptidoglycan cell wall.
Challenges of Using Molecular Serotyping for Surveillance of Pneumococcal Disease
Authors: Magomani Victoria , Wolter Nicole , Tempia Stefano , du Plessis Mignon , de Gouveia Linda , von Gottberg Anne 
Published: June 2014

ABSTRACT

Recent advances in the molecular identification and serotyping of
Streptococcus pneumoniae
are useful for culture-negative samples; however, there are limitations associated with these methods. We aimed to assess the value of molecular assays for invasive pneumococcal disease (IPD) surveillance in South Africa from 2010 through 2012. Nonviable isolates and culture-negative clinical specimens were tested for the
lytA
gene and, if positive, were serotyped, using real-time PCRs. Multinomial regression analysis was used to determine the maximum
lytA
cycle threshold (

C
T

) value useful for predicting the ability to detect a serotype for the sample. The χ
2
test was used to compare the prevalence of serotypes between viable/nonviable isolates and culture-negative clinical specimens. Of 11,224 IPD cases reported, 1,091 (10%) were culture-negative samples and 981 (90%) of these were
lytA
positive. Samples with a

lytA C
T

value of ≥35 were significantly less likely to be serotyped. A serotype/group was determined for 87% (737/844) of samples with a

lytA C
T

value of <35, of which 60% (443/737) were identified as individual serotypes. The serotype prevalence did not differ significantly between isolates and culture-negative specimens. Although molecular serotyping added 7% (737/11,224) serotyping data, the inability to resolve 40% of samples to single serotypes remains a challenge for serotype-specific data analysis.
Hand and Nasal Carriage of Discordant Staphylococcus aureus Isolates among Urban Jail Detainees
Authors: David Michael Z. , Siegel Jane D. , Henderson Janet , Leos Greg , Lo Kaming , Iwuora Jerry , Taylor Alexis R. , Zychowski Diana L. , Porsa Esmaeil , Boyle-Vavra Susan , Daum Robert S. 
Published: June 2014

ABSTRACT

In 928 Dallas County Jail detainees, nasal carriage of
Staphylococcus aureus
was found in 32.8% (26.5% methicillin-susceptible
Staphylococcus aureus
[MSSA] and 6.3% methicillin-resistant
S. aureus
[MRSA]), and hand carriage was found in 24.9% (20.7% MSSA and 4.1% MRSA). Among MRSA nasal carriers, 41% had hand MRSA carriage; 29% with hand MRSA carriage had no nasal
S. aureus
carriage. The prevalence of carriage was not associated with duration of the jail stay up to 180 days.
Prevalence of dysglycemia in Calabar: a cross-sectional observational study among residents of Calabar, Nigeria
Authors: Enang O E , Otu A A , Essien O E , Okpara H , Fasanmade O A , Ohwovoriole A E , Searle J 
Published: June 2014

ObjectivePopulation data on dysglycemia are scarce in West Africa. This study aimed to determine the pattern of dysglycemia in Calabar city in South East Nigeria.DesignThis was a cross-sectional observational study.Methods1134 adults in Calabar were recruited. A multistage sampling method randomly selected 4 out of 22 wards, and 50 households from each ward. All adults within each household were recruited and an oral glucose tolerance test was performed. Dysglycemia was defined as any form of glucose intolerance, including: impaired fasting glucose (blood glucose level 110–125 mg/dL), impaired glucose tolerance (blood glucose level ≥140 mg/dL 2 h after consuming 75 g of glucose), or diabetes mellitus (DM), as defined by fasting glucose level ≥126 mg/dL, or a blood glucose level ≥200 mg/dL, 2 h after a 75 g glucose load.ResultsMean values of fasting plasma glucose were 95 mg/dL (95% CI 92.1 to 97.5) for men and 96 mg/dL (95% CI 93.2 to 98.6) for women. The overall prevalence of dysglycemia was 24%. The prevalence of impaired fasting glucose was 9%, the prevalence of impaired glucose tolerance 20%, and the prevalence of undiagnosed DM 7%. All values were a few percentage points higher for men than women.ConclusionsThe prevalence of undiagnosed DM among residents of Calabar is similar to studies elsewhere in Nigeria but much higher than the previous national prevalence survey, with close to a quarter of the adults having dysglycemia and 7% having undiagnosed DM. This is a serious public health problem requiring a programme of mass education and case identification and management in all health facilities.Trial registration numberCRS/MH/CR-HREC/020/Vol.8/43
Birth cohort study on the effects of desert dust exposure on children's health: protocol of an adjunct study of the Japan Environment & Children’s Study
Authors: Kanatani Kumiko T , Adachi Yuichi , Sugimoto Nobuo , Noma Hisashi , Onishi Kazunari , Hamazaki Kei , Takahashi Yoshimitsu , Ito Isao , Egawa Miho , Sato Keiko , Go Tohshin , Kurozawa Youichi , Inadera Hidekuni , Konishi Ikuo , Nakayama Takeo ,   Japan Environment & Children's Study Group
Published: June 2014

IntroductionDesert dust is estimated to constitute about 35% of aerosol in the troposphere. Desertification, climatic variability and global warming all can contribute to increased dust formation. This study aims to examine possible health effects of desert dust exposure on pregnant women and their children. The purpose of this report was to present the study protocol.Methods and analysisThis 4-year birth cohort study began in 2011 as an adjunct study of the Japan Environment & Children’s Study (JECS) involving three regions: Kyoto, Toyama and Tottori. The JECS participants of the three regions above who also agreed to participate in this adjunct study were enrolled prior to delivery. Light Detecting and Ranging (LIDAR) with a polarisation analyser, which can distinguish mineral dust particles from other particles, is used for exposure measurements. Outcomes are allergic symptoms for mothers and development of asthma and other allergic or respiratory diseases for their children. Data are acquired in a timely manner by connecting local LIDAR equipment to an online questionnaire system. Participants answer the online questionnaire using mobile phones or personal computers.Ethics and disseminationThe study protocol was approved by the ethics committees of Kyoto University, University of Toyama and Tottori University. All participants provided written informed consent. The results of this study will be published in peer-reviewed journals and disseminated to the scientific community and general public.Trial Registration numberUMIN000010826.
Diagnostic and prognostic significance of CD200 expression and its stability in plasma cell myeloma
Authors: Douds Jonathan J , Long Daniel J , Kim Annette S , Li Shaoying 
Published: June 2014

AimPrevious studies showed that CD200 expression is a prognostic factor for plasma cell myeloma (PCM), but the prognostic effect is conflicting between studies. We studied CD200 protein expression and the stability of expression in PCM to clarify its potential utility in diagnosis, prognosis and monitoring of disease.MethodCD200 expression was studied in 77 cases of PCM by immunohistochemistry on paraffin sections from decalcified bone marrow biopsies.ResultThere were 16 newly diagnosed cases and 61 post-treatment cases from 54 patients: 37 men and 17 women, with a median age of 62 years (range, 41–88 years). CD200 demonstrated moderate to strong membrane expression in positive cases. Fifty-six of 77 cases (73%) showed CD200 expression. Twenty of the 22 (91%) patients with serial specimens demonstrated stable CD200 expression (n=15) or lack of CD200 expression (n=5). One patient lost CD200 expression, while another one gained CD200 expression during treatment. The clinical, pathologic and cytogenetic features between the CD200+ group and the CD200− group were similar in most instances. However, CD200 expression was associated with lower serum β2-microglobulin (p=0.03). There was no significant difference in overall survival and progression-free survival between the CD200+ and CD200− patients (p>0.05).ConclusionsCD200 is expressed in a majority of PCM cases, and the expression is stable during the treatment process. Therefore, immunohistochemical expression of CD200 is a useful marker for the diagnosis and follow-up of PCM.
Antimicrobial susceptibility and genetic characterisation of oxytetracycline‐resistant Edwardsiella tarda isolated from diseased eels
Authors: Lo D. Y. , Lee Y. J. , Wang J. H. , Kuo H. C. 
Published: June 2014

Edwardsiellosis is one of the most important bacterial diseases in eels. Edwardsiella tarda (E. tarda) isolates (n=94) from diseased eels were screened against the eight most commonly used antimicrobial agents in aquaculture in Taiwan. These isolates were highly susceptible to ampicillin, amoxicillin, florfenicol, oxolinic acid and flumequine. In total, 20 of the 94 (21.3 per cent) isolates tested were resistant to oxytetracycline (OTC). Among the 20 tetracycline‐resistant E. tarda isolates, tet (A) was the predominant resistance determinant and was detected in 100 per cent of the isolates, whereas 90 per cent of these isolates carried the tet (M) determinant. The efflux pump inhibitor omeprazole reduced the minimum inhibitory concentrations (MICs) of OTC for these isolates by twofold to eightfold, suggesting that an intact efflux pump, presumably encoded by tet (A), is required for high‐level tetracycline resistance. Real‐time PCR experiments showed that increased expression levels of tet (A) and tet (R) could contribute to OTC resistance. Southern blot hybridisation also confirmed that the 20 OTC‐resistant E. tarda isolates all carried the TetA determinant on a plasmid that is approximately 50 or 70 kb in size, and restriction fragment length polymorphisms (RFLP) showed that the tet (A) gene was located on an 8–10 kb Eco RI fragment in all of these plasmids. The same plasmid type and RFLP patterns were detected across different farms in the same region, but differences in their pulsed‐field gel electrophoresis (PFGE) patterns were observed. This suggests a possible role for horizontal spreading and local transmission of the plasmid in the OTC‐resistant E. tarda population of eels from two different geographic origins.
Challenges to global mineral resource security and options for future supply
Authors: Lusty P. A. J. , Gunn A. G. 
Published: June 2014

Abstract
Minerals are vital to support economic growth and the functioning of modern society. Demand for minerals is increasing as global population expands and minerals are used in a greater range of applications, particularly associated with the deployment of new technologies. While concerns about future mineral scarcity have been expressed, these are generally unfounded and based on over-simplistic analysis. This paper considers recent debate around security of mineral supply and technical, geosciences-based options to improve utilization of the resource base and contribute to replenishing reserves. History suggests that increasing demand for minerals and higher prices will generally lead to technological and scientific innovation that results in new or alternative sources of supply. Recent assessments of global mineral endowment suggest that society should be optimistic about its ability to meet future demand for minerals, provided that there is continued innovation and investment in science and technology. Reducing energy consumption and breaking the current link between metal production and greenhouse gas emissions are among the greatest challenges to secure a sustainable mineral supply. However, widespread adoption of low-carbon mineral extraction technologies, underpinned by multidisciplinary research, and increased global utilization of low-carbon energy sources will allow these challenges to be met.
Evaluating the impact of a late-burial corrosion model on reservoir permeability and performance in a mature carbonate field using near-wellbore upscaling
Authors: Chandra Viswasanthi , Wright Paul , Barnett Andrew , Steele Richard , Milroy Paul , Corbett Patrick , Geiger Sebastian , Mangione Alessandro 
Published: June 2014

Abstract
Field X comprises a giant Palaeogene limestone reservoir with a long production history. An original geomodel used for history matching employed a permeability transform derived directly from core data. However, the resulting permeability model required major modifications, such as horizontal and vertical permeability multipliers, in order to match the historic data. The rationale behind these multipliers is not well understood and not based on geological constraints. Our study employs an integrated near-wellbore upscaling workflow to identify and evaluate the geological heterogeneities that enhanced reservoir permeability. Key among these heterogeneities are mechanically weak zones of solution-enhanced porosity, leached stylolites and associated tension-gashes, which were developed during late-stage diagenetic corrosion. The results of this investigation confirmed the key role of diagenetic corrosion in enhancing the permeability of the reservoir. Insights gained from the available production history, in conjunction with petrophysical data analysis, substantiated the characterization of this solution-enhanced permeability. This study provided valuable insights into the means by which a satisfactory field-level history match for a giant carbonate reservoir can be achieved. Instead of applying artificial permeability multipliers that do not necessarily capture the impacts of geological heterogeneities, our method incorporates representations of fine-scale heterogeneities. Improving the characterization of permeability distribution in the field provided an updated and geologically consistent permeability model that could contribute to the ongoing development plans to maximize incremental oil recovery.
Molecular Pathways: Targeting ETS Gene Fusions in Cancer
Authors: Feng Felix Y. , Brenner J. Chad , Hussain Maha , Chinnaiyan Arul M. 
Published: June 2014

Abstract
Rearrangements, or gene fusions, involving the ETS family of transcription factors are common driving events in both prostate cancer and Ewing sarcoma. These rearrangements result in pathogenic expression of the ETS genes and trigger activation of transcriptional programs enriched for invasion and other oncogenic features. Although ETS gene fusions represent intriguing therapeutic targets, transcription factors, such as those comprising the ETS family, have been notoriously difficult to target. Recently, preclinical studies have demonstrated an association between ETS gene fusions and components of the DNA damage response pathway, such as PARP1, the catalytic subunit of DNA protein kinase (DNAPK), and histone deactylase 1 (HDAC1), and have suggested that ETS fusions may confer sensitivity to inhibitors of these DNA repair proteins. In this review, we discuss the role of ETS fusions in cancer, the preclinical rationale for targeting ETS fusions with inhibitors of PARP1, DNAPK, and HDAC1, as well as ongoing clinical trials targeting ETS gene fusions. Clin Cancer Res; 20(17); 4442–8. ©2014 AACR.
Biomarkers of Bone Remodeling in Multiple Myeloma Patients to Tailor Bisphosphonate Therapy
Authors: Patel Chirayu G. , Yee Andrew J. , Scullen Tyler A. , Nemani Neeharika , Santo Loredana , Richardson Paul G. , Laubach Jacob P. , Ghobrial Irene M. , Schlossman Robert L. , Munshi Nikhil C. , Anderson Kenneth C. , Raje Noopur S. 
Published: June 2014

Abstract
Background: Patients with multiple myeloma may be susceptible to osteonecrosis of the jaw (ONJ) and stress fractures due to long-term aminobisphosphonate (aBP) therapy. However, it is unknown whether urinary N-telopeptide (NTX) or other bone biomarkers are predictive of skeletal-related events (SRE) or the impact of cessation of aBP therapy on bone remodeling.
Methods: We studied markers of bone turnover over a 6-month period after a single dose of zoledronic acid in 29 patients with multiple myeloma in remission who previously received 8 to 12 doses of pamidronate or zoledronate (NCT00577642). Our primary objective was to determine the duration of time urinary NTX levels remain suppressed after a single dose of zoledronate. A secondary objective was to identify and correlate other markers of bone remodeling with NTX changes. Thirty cytokines, based on their possible role in bone remodeling, were tested using cytokine arrays. Candidates were confirmed by ELISA.
Results: All patients had continued suppression of NTX levels, except 1 patient who had an increase in NTX levels associated with an SRE. GDF-15 and decorin were found to decrease, whereas bone-specific alkaline phosphatase (BSALP) increased. Although not significant in aggregate, osteopontin and osteoprotegerin levels increased in at least half of the patients.
Conclusion: Our data show that NTX levels continue to be suppressed after aBP therapy, and suggest that suppressed NTX levels may be predictive of freedom from SRE in this patient population. Furthermore, osteoblast suppression by aBP may be reversible in myeloma. These data provide the basis for less frequent dosing of aBPs. Clin Cancer Res; 20(15); 3955–61. ©2014 AACR.