bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk factors that predict the requirement of aggressive therapy among Chinese patients with Crohn's disease
Authors: YANG Chuan Hua , DING Juan , GAO Yan , CHEN Xiang , YANG Zhao Bin , XIAO Shu Dong
Published: January 2011

OBJECTIVES:  Crohn's disease is now increasingly considered as a disabling disease. Conventionally, the disease is managed by step‐up therapy. In recent years, the top‐down strategy has been proposed and is thought to benefit the patients in whom the condition is likely to rapidly deteriorate toward disabling. However, this strategy has severe adverse effects which have to be weighed against its benefits. The aim of this study is to identify the risk factors that can predict the requirement of top‐down therapy among Chinese patients.

METHODS:  We included 207 Chinese patients who had histories of Crohn's disease for ≥5 years, or those who had Crohn's disease for <5 years and at least one criterion of disabling disease. The risk factors related to the 5‐year disabling course and the 2‐year disabling course of Crohn's disease were separately analyzed in the same cohort by logistic regression.

RESULTS:  Among the 207 patients, the rate of disabling disease was 80.19% for 5‐year, and 71.01% for 2‐year. The risk factors of age <40 years at diagnosis, steroids requirement for treating acute exacerbation, and presence of perianal disease at diagnosis were significantly associated with a 5‐year disabling course. In the same cohort, the risk factors related to 2‐year disabling course were likewise steroids requirement for treating acute exacerbation and presence of perianal disease at diagnosis.

CONCLUSION:  The risk factors associated with disabling Crohn's disease, which entails the requirement of top‐down therapy in Chinese patients, are requirement of steroids for treating acute exacerbation and the presence of perianal disease at diagnosis.
Relationship between nonalcoholic fatty liver disease and metabolic syndrome
Authors: CHEN Shao Hua , HE Fan , ZHOU Hua Li , WU Hong Ru , XIA Chen , LI You Ming
Published: January 2011

OBJECTIVE:  The aim of this study was to investigate the prevalence of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) in subjects who underwent a routine health checkup. We intended to establish a clinical association between NAFLD and MS as well as to compare the diagnostic criteria of MS based on the definitions set forth by the International Diabetes Federation (IDF), the US National Cholesterol Education Program Adult Treatment Panel III (2001) (NCEP/ATP‐III) and the Metabolic Syndrome Study Group of Chinese Diabetes Society (CDS).

METHODS:  Weight, height, waist circumference, hip circumference, percentage of body fat, blood pressure and ultrasound of liver were performed on subjects undergoing routine health checkup. Serum triglyceride, total cholesterol, high density lipoprotein cholesterol and fasting plasma glucose level were measured.

RESULTS:  A total of 2394 subjects were included in this analysis and 437 had NAFLD. The prevalence of MS in the whole sample according to IDF, NCEP/ATP‐III and CDS definitions was 11.11%, 8.48% and 5.30%, respectively. The total degree of agreement between IDF, NCEP/ATP‐III and CDS definition was 87.76%. The prevalence of MS in NAFLD subjects is much higher than that in non‐NAFLD subjects. The prevalence of NAFLD in MS subjects is also much higher than that in non‐MS subjects.

CONCLUSION:  The prevalence of MS varied depending on the diagnostic criteria used. NAFLD was strongly associated with the MS, although it remains unknown whether NAFLD is a cause or effect of MS.
Serum DJ‐1 as a diagnostic marker and prognostic factor for pancreatic cancer
Authors: HE Xiang Yi , LIU Bing Ya , YAO Wei Yan , ZHAO Xiao Jiao , ZHENG Zhong , LI Jian Fang , YU Bei Qin , YUAN Yao Zong
Published: January 2011

OBJECTIVE:  DJ‐1 is an oncoprotein secreted by cancer cells. Therefore, it might be a diagnostic or prognostic biomarker for pancreatic cancer (PC).

METHODS:  The study involved 47 patients with PC, 43 with chronic pancreatitis, and 40 healthy subjects. We assayed the serum level of DJ‐1 and the conventional tumor marker carbohydrate antigen 19‐9 (CA 19‐9) to define the diagnostic and prognostic value of DJ‐1 for PC.

RESULTS:  Serum DJ‐1 level was elevated in patients with PC compared with those with chronic pancreatitis and healthy individuals. The area under the curve (AUC) of serum DJ‐1 was higher than CA 19‐9 (DJ‐1 vs. CA19‐9, 0.8735 ± 0.0356 vs. 0.6647 ± 0.0572 ng/mL), and an 87.5% sensitivity was reached with a combination of serum DJ‐1 and CA19‐9. No association of serum DJ‐1 level with tumor node metastasis (TNM) classification or tumor resectability was found. However, after resection, the median serum DJ‐1 level was decreased from 2.00 to 0.78 ng/mL. In addition, higher serum DJ‐1 was correlated with shorter overall survival as analyzed by both Kaplan–Meier test (P = 0.018) and COX regression analysis (P = 0.013). The median overall survival time of PC patients with serum DJ‐1 level greater than or equal to 2.06 ng/mL was 7.00 ± 1.11 months, whereas that of patients with lower DJ‐1 levels was 13.0 ± 2.5 months.

CONCLUSIONS:  These findings indicate the potential clinical significance for serum DJ‐1 level to be used for the diagnosis and prognosis prediction of patients with PC.
Haemoglobin (Hb) G‐Philadelphia, Hb Stanleyville‐II, Hb G‐Norfolk, Hb Matsue‐Oki and Hb Mizushi can form a panel of α‐chain variants that overlap in their phenotype: the novel use of StyI to screen for Hb G‐Philadelphia
Authors: KHALIL M. S. M. , TIMBS A. , HENDERSON S. , SCHUH A. , HUSSEIN M. R. A. , OLD J.
Published: January 2011

Introduction:  Haemoglobin (Hb) G‐Philadelphia mutation is a common alpha‐globin chain variant [α68(E17)Asn > Lys]. Combined high performance liquid chromatography (HPLC) and isoelectric focusing (IEF) can be used in a presumptive diagnosis of Hb G‐Philadelphia, but there are other α‐chain variants with a similar phenotype that cannot be excluded. Our aim was to develop a novel StyI restriction enzyme assay to diagnose the common Hb G‐Philadelphia mutation and to identify any other variants with a similar phenotype by DNA sequencing.

Methods:  Thirty‐one cases given a presumptive diagnosis as Hb G‐Philadelphia by HPLC and IEF were subjected to DNA analysis by restriction enzyme digestion using StyI. Negative cases were then subjected to DNA sequencing.

Results:  Twenty‐two cases (78.6%) of 28 cases amplified were tested positive for Hb G‐Philadelphia by StyI restriction digestion. Sequencing of the six negative cases revealed two cases of Hb G‐Philadelphia with C→A mutation in codon 68 in α2 globin gene, plus one case each of Hb G‐Norfolk Hb Stanleyville‐II, Hb Matsue‐Oki and Hb Mizushi.

Conclusion:  A novel StyI restriction enzyme can be used to confirm the commonest type of Hb G‐Philadelphia. DNA sequencing identified four other α‐chain variants with a similar HPLC and IEF phenotype.
Three novel alternative splicing mutations in BCR‐ABL1 detected in CML patients with resistance to kinase inhibitors
Authors: MA W. , GILES F. , ZHANG X. , WANG X. , ZHANG Z. , LEE T.‐S. , YEH C.‐H. , ALBITAR M.
Published: January 2011

Introduction:  Multiple types of mutations in the BCR‐ABL1 kinase domain have been reported. We previously reported a common alternatively spliced BCR‐ABL mRNA with a 35‐nucleotide insertion (35INS). We report three novel alternative splicing mutants expressed as the dominant transcripts in patient with chronic myelogenous leukemia and resistance to kinase inhibitors.

Methods:  We screened RNA from more than 200 patients with resistance to more than one of the three kinase inhibitors for ABL1 kinase domain mutations by direct sequencing.

Results:  We found three not previously described splice mutants. All three showed >90% mutant transcript. The first resulted from the insertion of 79 nucleotides into the ABL1 exon 8–9 junction. The inserted sequence contained a sequence from regions of intron 8, located 120 bp apart: the 35‐nucleotide sequence previously described, and an additional 44‐nucleotide segment downstream from 35INS. The combined 79‐nucleotide insertion splice mutant showed the same protein change as 35INS (p C475YfsX11). The second splice mutation comprised an 84‐nucleotide sequence from intron 7 inserted into the ABL1 exon7–8 junction, also causing a frameshift and protein truncation (p A424EfsX18). The third splice derived from a 231‐nucleotide sequence from intron 4 retained in the ABL1 exon 4–5 junction adding 40 intron‐encoded amino acids and leading to a frameshift and early termination (p E275LfsX41).

Conclusion:  These findings, when combined with the data on 35INS, support the concept that loss of the C‐terminus of BCR‐ABL1 is associated with significant resistance to kinase inhibitors; this mechanism appears to be a major source of resistance to kinase inhibitors.
Hyperkalemia Associated with Use of Angiotensin‐Converting Enzyme Inhibitors and Angiotensin Receptor Blockers
Authors: Raebel Marsha A.
Published: January 2011

The aims of this article are to review the current understanding of hyperkalemia associated with angiotensin‐converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) therapy. This includes reviewing the pathophysiology of how these agents affect potassium handling within the kidney, risk factors for developing hyperkalemia, incidence, clinical signs and symptoms, and providing a practical approach to treatment of the patient who is either at risk of, or experiencing, hyperkalemia. ACEi and ARB are effective therapeutic agents used in a variety of clinical scenarios. However, related to their effects on the renin–angiotensin–aldosterone system, their use can be associated with hyperkalemia, particularly in patients who have chronic renal insufficiency. Published incidence estimates of hyperkalemia associated with ACEi or ARB vary, but up to 10% of patients may experience at least mild hyperkalemia. Important considerations when initiating ACEi or ARB therapy include obtaining an estimate of glomerular filtration rate and a baseline serum potassium concentration, as well as assessing whether the patient has excessive potassium intake from diet, supplements, or drugs that can also increase serum potassium. Serum potassium monitoring shortly after initiation of therapy can assist in preventing hyperkalemia. If hyperkalemia does develop, prompt recognition of cardiac dysrhythmias and effective treatment to antagonize the cardiac effects of potassium, redistribute potassium into cells, and remove excess potassium from the body is important.Understanding the mechanism of action of ACEi and ARB coupled with judicious drug use and clinical vigilance can minimize the risk to the patient of developing hyperkalemia. Should hyperkalemia occur, prompt recognition and management can optimize clinical outcome.
Every session counts: The differential impact of previous programmes and current programme dosage on offender recidivism
Authors: Kroner Daryl G. , Takahashi Masaru
Published: January 2011

Purpose. The present study examined the impact of current treatment dosage on recidivism among offenders.

Methods. Using a sample of dropouts from a community treatment programme, current treatment dosage and past completed programmes were used to predict criminal recidivism.

Results. After statistically controlling for risk levels, only current dosage was predictive of recidivism.

Conclusions. Offenders’ current direction, indicated by current dosage, is central to reducing recidivism. Strategies for offenders completing treatment sessions are discussed.
The linking of burglary crimes using offender behaviour: Testing research cross‐nationally and exploring methodology
Authors: Tonkin M. , Santtila P. , Bull R.
Published: January 2011

Purpose. The current study tests whether existing behavioural case linkage findings from the United Kingdom (UK) will replicate abroad with a sample of residential burglaries committed in Finland. In addition, a previously discussed methodological issue is empirically explored.

Methods. Seven measures of behavioural similarity, geographical proximity, and temporal proximity are calculated for pairs of burglary crimes committed by 117 serial burglars in Finland. The ability of these seven measures to distinguish between pairs of crimes committed by the same offender (linked pairs) and different offenders (unlinked pairs) is tested using logistic regression and receiver operating characteristic (ROC) analysis. Two methodologies for forming the unlinked pairs are compared; one representing the ‘traditional’ approach used by research and, the other, a new approach that represents a potentially more realistic and statistically sound approach to testing case linkage.

Results. A wider range of offender behaviours were able to distinguish between linked and unlinked crime pairs in the current Finnish sample than in previous UK‐based research. The most successful features were the kilometre‐distance between crimes (the intercrime distance), the number of days separating offences (temporal proximity), and a combination of target, entry, internal, and property behaviours (the combined domain). There were no statistically significant differences between the two methodological approaches.

Conclusions. The current findings demonstrate that a wider range of offender behaviours can be used to discriminate between linked and unlinked residential burglary crimes committed in Finland than in the UK. The use of a more realistic and statistically sound methodology does not lead to substantial changes in case linkage findings.
Surface activated bonding of copper through silicon vias and gold stud bumps at room temperature
Authors: Howlader M. M. R. , Zhang F. , Deen M. J. , Suga T. , Yamauchi A.
Published: January 2011

A comprehensive investigation of the surfaces of copper through silicon vias (Cu-TSVs) and gold stud bumps is presented. These vias and stud bumps were bonded at room temperature using a nanobonding and interconnection equipment. The influence of heating on the bonded interface was also studied. In order to achieve an intimate contact between the Au-stud bumps and Cu-TSVs, the stud bumps were flattened under an external force of 20 N before bonding. The surface roughness of the flattened area was improved due to deformation of the bumps. Specimens with high deformation provided better alignment accuracy than those with low deformation. The Cu-TSV surface showed inhomogeneous behavior due to the influence of electroplating and chemical mechanical polishing. Tensile pulling test of the bonded interfaces showed three fractures modes in the bulk of the Au bump and the Au pad. The electrical resistance of the bonded interface was dependent on the surface morphology of the bumps and TSVs, the distance between the bumps and TSVs, the locations of the bumps and TSV with respect to the argon fast atom beams, and the distribution of external force during bonding. Heating at 200 °C for 60 h in air increased the electrical resistance of the bonded interface. This investigation shows that the vertical integration of Au/Cu at room temperature and low bonding force can be applied to three-dimensional interconnections for low cost miniaturized systems.
Photocapacitance spectroscopy study of deep-level defects in freestanding n-GaN substrates using transparent conductive polymer Schottky contacts
Authors: Nakano Yoshitaka , Lozac’h Mickael , Matsuki Nobuyuki , Sakoda Kazuaki , Sumiya Masatomo
Published: January 2011

We have investigated electronic deep levels in freestanding n-GaN substrates grown by hydride vapor phase epitaxy (HVPE) by means of a steady-state photocapacitance spectroscopy technique using transparent conductive polyaniline Schottky contacts. Two specific deep levels located at ∼1.7 and ∼3.1 eV below the conduction band were revealed to be significantly reduced compared to those in n-GaN layers grown by metal-organic chemical vapor deposition. This difference between them is probably due to extremely low concentrations of threading dislocations and residual C impurities in the HVPE-grown n-GaN substrates.
Manipulating the Bioenergetics of Alloreactive T Cells Causes Their Selective Apoptosis and Arrests Graft-Versus-Host Disease
Authors: Gatza Erin , Wahl Daniel R. , Opipari Anthony W. , Sundberg Thomas B. , Reddy Pavan , Liu Chen , Glick Gary D. , Ferrara James L. M.
Published: January 2011

Bioenergetic properties differentiate alloreactive T cells from other proliferating cells and can be exploited to arrest GVHD in mice.
Yet Another Reason Rats Don’t Take Day Jobs
Authors: Bentley-Lewis Rhonda
Published: January 2011

Feeding rats during the day rather than during their normal night pattern promotes obesity.
Thermococcus kodakarensis
as a Host for Gene Expression and Protein Secretion
Authors: Takemasa Ryo , Yokooji Yuusuke , Yamatsu Atsushi , Atomi Haruyuki , Imanaka Tadayuki
Published: January 2011

Taking advantage of the gene manipulation system developed in
Thermococcus kodakarensis
, here, we developed a system for gene expression and efficient protein secretion using this hyperthermophilic archaeon as a host cell. DNA fragments encoding the C-terminal domain of chitinase (ChiAΔ4), which exhibits endochitinase activity, and the putative signal sequence of a subtilisin-like protease (TK1675) were fused and positioned under the control of the strong constitutive promoter of the cell surface glycoprotein gene. This gene cassette was introduced into
T. kodakarensis
, and secretion of the ChiAΔ4 protein was examined. ChiAΔ4 was found exclusively in the culture supernatant and was not detected in the soluble and membrane fractions of the cell extract. The signal peptide was specifically cleaved at the C-terminal peptide bond following the Ala-Ser-Ala sequence. Efficient secretion of the orotidine-5′-monophosphate decarboxylase protein was also achieved with the same strategy. We next individually overexpressed two genes (TK1675 and TK1689) encoding proteases with putative signal sequences. By comparing protein degradation activities in the host cells and transformants in both solid and liquid media, as well as measuring peptidase activity using synthetic peptide substrates, we observed dramatic increases in protein degradation activity in the two transformants. This study displays an initial demonstration of cell engineering in hyperthermophiles.
Poly-α-Glutamic Acid Synthesis Using a Novel Catalytic Activity of RimK from
Escherichia coli
K-12
Authors: Kino Kuniki , Arai Toshinobu , Arimura Yasuhiro
Published: January 2011

Poly-
l
-α-amino acids have various applications because of their biodegradable properties and biocompatibility. Microorganisms contain several enzymes that catalyze the polymerization of
l
-amino acids in an ATP-dependent manner, but the products from these reactions contain amide linkages at the side residues of amino acids: e.g., poly-γ-glutamic acid, poly-ε-lysine, and cyanophycin. In this study, we found a novel catalytic activity of RimK, a ribosomal protein S6-modifying enzyme derived from
Escherichia coli
K-12. This enzyme catalyzed poly-α-glutamic acid synthesis from unprotected
l
-glutamic acid (Glu) by hydrolyzing ATP to ADP and phosphate. RimK synthesized poly-α-glutamic acid of various lengths; matrix-assisted laser desorption ionization-time of flight-mass spectrometry showed that a 46-mer of Glu (maximum length) was synthesized at pH 9. Interestingly, the lengths of polymers changed with changing pH. RimK also exhibited 86% activity after incubation at 55°C for 15 min, thus showing thermal stability. Furthermore, peptide elongation seemed to be catalyzed at the C terminus in a stepwise manner. Although RimK showed strict substrate specificity toward Glu, it also used, to a small extent, other amino acids as C-terminal substrates and synthesized heteropeptides. In addition, RimK-catalyzed modification of ribosomal protein S6 was confirmed. The number of Glu residues added to the protein varied with pH and was largest at pH 9.5.
Antifungal Activity Displayed by Cereulide, the Emetic Toxin Produced by
Bacillus cereus
Authors: Ladeuze Sandy , Lentz Nathalie , Delbrassinne Laurence , Hu Xiaomin , Mahillon Jacques
Published: January 2011

In this study, the fungistatic activity of
Bacillus cereus
cereulide-producing strains was demonstrated against nine fungal species. The role of cereulide was confirmed using plasmid-cured derivatives and
ces
knockout mutants. The fungistatic spectra of cereulide and valinomycin, a chemically related cyclododecadepsipeptide, were also compared and found to be similar but distinct.
Correlation of Quantitative PCR for a Poultry-Specific
Brevibacterium
Marker Gene with Bacterial and Chemical Indicators of Water Pollution in a Watershed Impacted by Land Application of Poultry Litter
Authors: Weidhaas Jennifer L. , Macbeth Tamzen W. , Olsen Roger L. , Harwood Valerie J.
Published: January 2011

The impact of fecal contamination from human and agricultural animal waste on water quality is a major public health concern. Identification of the dominant source(s) of fecal pollution in a watershed is necessary for assessing the safety of recreational water and protecting water resources. A field study was conducted using quantitative PCR (qPCR) for the 16S rRNA gene of
Brevibacterium
sp. LA35 to track feces-contaminated poultry litter in environmental samples. Based on sensitivity and specificity characteristics of the qPCR method, the Bayesian conditional probability that detection of the LA35 marker gene in a water sample represented a true-positive result was 93%. The marker's covariance with fecal indicator bacteria (FIB) and metals associated with poultry litter was also assessed in litter, runoff, surface water, and groundwater samples. LA35 was detected in water and soil samples collected throughout the watershed, and its concentration covaried with concentrations of
Escherichia coli
, enterococci, As, Cu, P, and Zn. Significantly greater concentrations of FIB, As, Cu, P, and Zn were observed in edge-of-field runoff samples in which LA35 was detected, compared to samples in which it was not detected. Furthermore, As, Cu, P, and Zn concentrations covaried in environmental samples in which LA35 was detected and typically did not in samples in which the marker gene was not detected. The covariance of the poultry-specific LA35 marker gene with these known contaminants from poultry feces provides further evidence that it is a useful tool for assessing the impact of poultry-derived fecal pollution in environmental waters.
Novel Virulence Gene and Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) Multilocus Sequence Typing Scheme for Subtyping of the Major Serovars of
Salmonella enterica
subsp.
enterica
Authors: Liu Fenyun , Barrangou Rodolphe , Gerner-Smidt Peter , Ribot Efrain M. , Knabel Stephen J. , Dudley Edward G.
Published: January 2011

Salmonella enterica
subsp.
enterica
is the leading cause of bacterial food-borne disease in the United States. Molecular subtyping methods are powerful tools for tracking the farm-to-fork spread of food-borne pathogens during outbreaks. In order to develop a novel multilocus sequence typing (MLST) scheme for subtyping the major serovars of
S. enterica
subsp.
enterica
, the virulence genes
sseL
and
fimH
and clustered regularly interspaced short palindromic repeat (CRISPR) loci were sequenced from 171 clinical isolates from nine
Salmonella
serovars,
Salmonella
serovars Typhimurium, Enteritidis, Newport, Heidelberg, Javiana, I 4,[5],12:i:−, Montevideo, Muenchen, and Saintpaul. The MLST scheme using only virulence genes was congruent with serotyping and identified epidemic clones but could not differentiate outbreaks. The addition of CRISPR sequences dramatically improved discriminatory power by differentiating individual outbreak strains/clones. Of particular note, the present MLST scheme provided better discrimination of
Salmonella
serovar Enteritidis strains than pulsed-field gel electrophoresis (PFGE). This method showed high epidemiologic concordance for all serovars screened except for
Salmonella
serovar Muenchen. In conclusion, the novel MLST scheme described in the present study accurately differentiated outbreak strains/clones of the major serovars of
Salmonella
, and therefore, it shows promise for subtyping this important food-borne pathogen during investigations of outbreaks.
Regulatory Control of the
Escherichia coli
O157:H7
lpf1
Operon by H-NS and Ler
Authors: Rojas-López Maricarmen , Arenas-Hernández Margarita M. P. , Medrano-López Abraham , Martínez de la Peña Claudia F. , Puente José Luis , Martínez-Laguna Ygnacio , Torres Alfredo G.
Published: January 2011

Long polar fimbriae 1 (Lpf1) of
Escherichia coli
O157:H7 is a tightly regulated adhesin, with H-NS silencing the transcriptional expression of the
lpf1
operon while Ler (locus of enterocyte effacement-encoded regulator) acts as an antisilencer. We mapped the minimal regulatory region of
lpf1
required for H-NS- and Ler-mediated regulation and found that it is 79% AT rich. Three putative sites for H-NS binding were identified. Two of them, named silencer regulatory sequence 1 (SRS1) and SRS2, are located on a region that covers both of the
lpf1
promoters (P1 and P2). The third putative H-NS binding site is located within the
lpfA1
gene in a region extending from +258 bp to +545 bp downstream of ATG; however, this site does not seem to play a role in
lpfA1
regulation under the conditions tested in this work. Ler was also found to interact with Ler binding sites (LBSs). Ler binding site 1 (LBS1) and LBS2 are located upstream of the two promoters. LBS1 overlaps SRS1, while LBS3 overlaps the P1 promoter and SRS2. Based on the experimental data, we propose that H-NS silences
lpf1
expression by binding to both of the SRSs on the promoter region, forming an SRS-H-NS complex that prevents RNA polymerase-mediated transcription. A model of the regulation of the
lpfA1
operon of
E. coli
O157:H7 by H-NS and Ler is discussed.
Legionella pneumophila
LbtU Acts as a Novel, TonB-Independent Receptor for the Legiobactin Siderophore
Authors: Chatfield Christa H. , Mulhern Brendan J. , Burnside Denise M. , Cianciotto Nicholas P.
Published: January 2011

Gram-negative
Legionella pneumophila
produces a siderophore (legiobactin) that promotes lung infection. We previously determined that
lbtA
and
lbtB
are required for the synthesis and secretion of legiobactin. DNA sequence and reverse transcription-PCR (RT-PCR) analyses now reveal the presence of an iron-repressed gene (
lbtU
) directly upstream of the
lbtAB
-containing operon.
In silico
analysis predicted that LbtU is an outer membrane protein consisting of a 16-stranded transmembrane β-barrel, multiple extracellular domains, and short periplasmic tails. Immunoblot analysis of cell fractions confirmed an outer membrane location for LbtU. Although replicating normally in standard media,
lbtU
mutants, like
lbtA
mutants, were impaired for growth on iron-depleted agar media. While producing typical levels of legiobactin,
lbtU
mutants were unable to use supplied legiobactin to stimulate growth on iron-depleted media and displayed an inability to take up iron. Complemented
lbtU
mutants behaved as the wild type did. The
lbtU
mutants were also impaired for infection in a legiobactin-dependent manner. Together, these data indicate that LbtU is involved in the uptake of legiobactin and, based upon its location, is most likely the
Legionella
siderophore receptor. The sequence and predicted two-dimensional (2D) and 3D structures of LbtU were distinct from those of all known siderophore receptors, which generally contain a 22-stranded β-barrel and an extended N terminus that binds TonB in order to transduce energy from the inner membrane. This observation coupled with the fact that
L. pneumophila
does not encode TonB suggests that LbtU is a new type of receptor that participates in a form of iron uptake that is mechanistically distinct from the existing paradigm.
Identification of Genes Essential for Prey-Independent Growth of
Bdellovibrio bacteriovorus
HD100
Authors: Roschanski Nicole , Klages Sven , Reinhardt Richard , Linscheid Michael , Strauch Eckhard
Published: January 2011

Bdellovibrio bacteriovorus
HD100 is an obligate predatory bacterium that attacks and invades Gram-negative bacteria. The predator requires living bacteria to survive as growth and replication take place inside the bacterial prey. It is possible to isolate mutants that grow and replicate outside prey bacteria. Such mutants are designated host or prey independent, and their nutritional requirements vary. Some mutants are saprophytic and require prey extracts for extracellular growth, whereas other mutants grow axenically, which denotes the formation of colonies on complete medium in the absence of any prey components. The initial events leading to prey-independent growth are still under debate, and several genes may be involved. We selected new mutants by three different methods: spontaneous mutation, transposon mutagenesis, and targeted gene knockout. By all approaches we isolated mutants of the
hit
(host interaction) locus. As the relevance of this locus for the development of prey independence has been questioned, we performed whole-genome sequencing of five prey-independent mutants. Three mutants were saprophytic, and two mutants could grow axenically. Whole-genome analysis revealed that the mutation of a small open reading frame of the
hit
locus is sufficient for the conversion from predatory to saprophytic growth. Complementation experiments were performed by introduction of a plasmid carrying the wild-type
hit
gene into saprophytic mutants, and predatory growth could be restored. Whole-genome sequencing of two axenic mutants demonstrated that in addition to the
hit
mutation the colony formation on complete medium was shown to be influenced by the mutations of two genes involved in RNA processing. Complementation experiments with a wild-type gene encoding an RNA helicase, RhlB, abolished the ability to form colonies on complete medium, indicating that stability of RNA influences axenic growth.
Accessibility and Evolutionary Conservation Mark Bacterial Small-RNA Target-Binding Regions
Authors: Peer Asaf , Margalit Hanah
Published: January 2011

Bacterial small noncoding RNAs have attracted much interest in recent years as posttranscriptional regulators of genes involved in diverse pathways. Small RNAs (sRNAs) are 50 to 400 nucleotides long and exert their regulatory function by directly base pairing with mRNA targets to alter their stability and/or affect their translation. This base pairing is achieved through a region of about 10 to 25 nucleotides, which may be located at various positions along different sRNAs. By compiling a data set of experimentally determined target-binding regions of sRNAs and systematically analyzing their properties, we reveal that they are both more evolutionarily conserved and more accessible than random regions. We demonstrate the use of these properties for computational identification of sRNA target-binding regions with high specificity and sensitivity. Our results show that these predicted regions are likely to base pair with known targets of an sRNA, suggesting that pointing out these regions in a specific sRNA can help in searching for its targets.
Ethical issues related to the access to orphan drugs in Brazil: the case of mucopolysaccharidosis type I
Authors: Boy Raquel , Schwartz Ida V D , Krug Bárbara C , Santana-da-Silva Luiz C , Steiner Carlos E , Acosta Angelina X , Ribeiro Erlane M , Galera Marcial F , Leivas Paulo G C , Braz Marlene
Published: January 2011

Background/Aims

Mucopolysaccharidosis type I (MPS I) is a rare lysosomal storage disorder treated with bone marrow transplantation or enzyme replacement therapy with laronidase, a high-cost orphan drug. Laronidase was approved by the US Food and Drug Administration and the European Medicines Agency in 2003 and by the Brazilian National Health Surveillance Agency in 2005. Many Brazilian MPS I patients have been receiving laronidase despite the absence of a governmental policy regulating access to the drug. Epidemiological and treatment data concerning MPS I are scarce. This study aims to present a demographic profile of Brazilian patients with MPS I, describe the routes of access to laronidase in Brazil, and discuss associated ethical issues relating to public funding of orphan drugs.

Methods

In this cross-sectional observational study, data were collected nationwide between January and September 2008 from physicians, public institutions and non-governmental organisations involved with diagnosis and treatment of MPS I, using two data collection instruments specifically designed for this purpose.

Results

The minimum prevalence of MPS I in Brazil was estimated at 1/2 700 000. Most patients (69.8%) were younger than 15 years; 60 (88.2%) received laronidase. The most common route of access to the drug was through lawsuits (86.6%).

Conclusions

In Brazil, MPS I is predominantly a paediatric illness. Even though the cost of laronidase treatment is not officially covered by the Brazilian government, most MPS I patients receive the drug, usually through litigation. This gives rise to major ethical conflicts concerning drug access in a low-resource context. The Brazilian health policy framework lacks evidence-based clinical protocols for the distribution of orphan drugs.
Rethinking scientific responsibility: Figure 1
Authors: Forssén Annika , Meland Eivind , Hetlevik Irene , Strand Roger
Published: January 2011

Researchers should be made co-responsible for the wider consequences of their research focus and the application of their findings. This paper describes a meta-reflection procedure that can be used as a tool to enhance scientific responsibility and reflective practice. The point of departure is that scientific practice is situated in power relations, has direction and, consequently, power implications. The contextual preconditions and implications of research should be stated and discussed openly. The reflection method aims at revealing both upstream elements, such as for instance preconceptions, and downstream elements, for example, public consequences of research. The validity of research might improve from such discussions. Validity should preferably be understood as a broader concept than the methodological concerns in science.
Parents' experiences of newborn screening for genetic susceptibility to type 1 diabetes
Authors: Kerruish Nikki J
Published: January 2011

Advances in genomic medicine have lead to debate about the potential inclusion of genetic tests for susceptibility to common complex disorders in newborn screening programmes. Empirical evidence concerning psychosocial reactions to genetic testing is a crucial component of both ethical debate and policy development, but while there has been much speculation concerning the possible psychosocial impact of screening newborns for genetic susceptibilities, there remains a paucity of data. The aim of the study reported here is to provide some of this missing empirical evidence, using type 1 diabetes as an example of a common disorder with multiple significant genetic contributors to its aetiology. Semi-structured interviews were conducted with 11 parents of babies who had received increased risk results in a study that involved newborn screening for genetic susceptibility to type 1 diabetes. Interpretative phenomenological analysis was used to evaluate the data. The interview data suggest that the probabilistic nature of results of genetic susceptibility tests impacts upon all aspects of parents' psychosocial reactions, resulting in a complex and dynamic process quite different to that described in relation to current newborn screening programmes. While parents generally reported fairly minor levels of concern in response to news of their child's increased genetic risk, these worries frequently recurred, and perception of risk also varied and fluctuated over time. Both individual and contextual factors appeared to interact with the inherent uncertainty of the test result to contribute to the dynamic nature of parental reactions, and their behavioural responses. The implications of these findings for future research and for the debate concerning potential expansion of newborn screening are discussed.
Authorship policies of bioethics journals: Table 1
Authors: Resnik David B , Master Zubin
Published: January 2011

Inappropriate authorship is a common problem in biomedical research and may be becoming one in bioethics, due to the increase in multiple authorship. This paper investigates the authorship policies of bioethics journals to determine whether they provide adequate guidance for researchers who submit articles for publication, which can help deter inappropriate authorship. It was found that 63.3% of bioethics journals provide no guidance on authorship; 36.7% provide guidance on which contributions merit authorship, 23.3% provide guidance on which contributions do not merit authorship, 23.3% require authors to take responsibility for their contributions or for the article as a whole, 20% provide guidance on which contributions merit an acknowledgement but not authorship, 6.7% require authors to describe their contributions, and only 3.3% distinguish between authorship in empirical and conceptual research. To provide authors with effective guidance and promote integrity in bioethics research, bioethics journals should adopt authorship policies that address several important topics, such as the qualifications for authorship, describing authorship contributions, taking responsibility for the research and the difference between authorship in empirical and conceptual research.
Novel non-occlusive temporary endoluminal neck protection device to assist in the treatment of aneurysms in a canine model
Authors: Turner Raymond D , Chaudry M Imran , Turk Aquilla S
Published: January 2011

Introduction

Current models for the endovascular treatment of aneurysms often require the use of adjuvant devices. Balloon-assisted techniques require temporary occlusion of the parent vessel. Intravascular stents require the use of antiplatelet medication. A novel device that achieves temporary neck protection without parent vessel occlusion or antiplatelet medication is examined in a canine model.

Method

20 sidewall wide-necked aneurysms were created in 10 canines, one in each carotid artery, using a vein graft technique, and allowed to mature. In each canine, one aneurysm was catheterized with a microcatheter while the neck protection device (NPD) was unsheathed across the neck of the aneurysm and the aneurysm was coiled. The second aneurysm in each canine was coiled without an adjunctive device. The NPD was assessed for coil herniation, coil entrapment within the device, deployability and retrievability. Five animals were killed immediately and five were killed at 28 days and the carotid artery was explanted and sent for necropsy to assess for injury to the endothelium.

Results

All aneurysms were successfully treated with no adverse events. The NPD was well visualized and unsheathed and resheathed successfully in all cases. There was no coil entrapment within the device, and there were no cases of coil herniation. There was no evidence of endothelial injury or dissection.

Conclusion

The device was technically successful in all devices and further development of this device may be of benefit in endovascular treatment of aneurysms.
Biological monitoring of low-level 2-butoxyethanol exposure in decal transfer workers in bicycle manufacturing factories
Authors: Hung Po-Chen , Cheng Shu-Fang , Liou Saou-Hsing , Tsai Shih-Wei
Published: January 2011

Objectives

In this study, exposures to ethylene glycol monobutyl ether (or 2-butoxyethanol, 2-BE) in decal transfer workers in the bicycle manufacturing industry were investigated. Personal air sampling and biological monitoring were used to assess total uptake through inhalation and dermal exposure. Haemoglobin was also analysed to evaluate the effects of exposure on the haematopoietic system.

Methods

80 workers in two bicycle factories completed a questionnaire. NIOSH method 1403 was adopted for air sampling and analysis of 2-BE. Prework and postwork urine samples were also collected for determination of total 2-butoxyacetic acid (BAA) after hydrolysis. Haemoglobin tests were performed using an automated haemoglobin analysis system.

Results

The 31 decal transfer workers whose hands were in direct contact with a dilute aqueous solution of 2-BE, were exposed to an average of 1.7 ppm (8.1 mg/m3) of 2-BE in air. Correlation of 2-BE in air and postshift urinary BAA levels (after hydrolysis) was poor. Postshift total BAA levels in urine on Monday and Friday (446.8 and 619.4 mg/g creatinine) were around 223% and 310% of the ACGIH proposed Biological Exposure Index (BEI; 200 mg/g creatinine). Higher levels of total BAA were observed in the urine of subjects exposed to low-level 2-BE in air, presumably because of direct dermal contact.

Conclusions

The mean preshift BAA on Friday was significantly higher than that on Monday, implying that the more days of exposures, the higher the accumulation. Since accumulation occurred with low-level exposure to 2-BE, it is recommended that urine samples be collected at the end of the working week.
Designing clinical trials in canine spinal cord injury as a model to translate successful laboratory interventions into clinical practice
Authors: Jeffery N. D. , Hamilton L. , Granger N.
Published: January 2011

Many interventions have been shown to improve outcome after experimental spinal cord injury in laboratory animals. The challenge now is to determine whether any of these can be translated to become an efficacious therapy for clinical lesions – a process that is often difficult and frequently fails. Here, we discuss the steps that are required to make this transition and the need for rigorous clinical trials. A key component is an outcome measure that is amenable to statistical analysis; we describe methods that we have developed to accurately measure function after spinal cord injury in dogs. The general methodology may have parallels in the development of veterinary models to test putative therapies for other diseases of humans and animals.
Investigating Barriers to Knowledge Management Success: A Conceptual Model and a Comparative Case Analysis
Authors: BenMoussa Chihab
Published: January 2011

What barriers obstruct the success of knowledge management programs? This paper has integrated studies on the barriers to knowledge management (KM) into a theoretical framework. Based on this framework, five cases documenting failed KM initiatives were analysed. The analysis gives a clear picture about why certain KM projects fail. The high failure rate of KM can be explained by the supply-IT based approach many organisations adopt when it comes to their KM programs. To increase the success rate of KM projects, companies should go beyond the one-dimensional thinking, e.g. technology, and adopt an approach where all the ingredients of KM operate in a synchronised way.
Technology Transfer Mediations of Technical Writers: Perspectives from the Philippine Software Industry
Authors: Calbay Francis Raymond
Published: January 2011

In their attempts to communicate innovation, technical writers produce what Everett Rogers calls "technology-embodied information," per the Diffusion of Innovations theory. This study focuses on technical writers working for multinational software firms in the Philippines and seeks to explain their function as gatekeepers in the information traffic between development centres and software users. The practices of technical writers — representative of eight software companies — are collected, described, and analysed according to qualitative design. The study uses the focus group discussion as its primary research tool, triangulated by portfolio and process documentation analyses. Key themes are presented in step-flow. The study illustrates technical communication tasks such as user profiling, knowledge capture, and information delivery within the framework of technology transfer.
KM Modules: An Analysis of Coursework
Authors: Rehman Sajjad ur , Sumait Haya
Published: January 2011

Knowledge management is a growing discipline and its structure and boundaries have been examined using different perspectives. This study is based on the KM curricula of 13 graduate degree programmes for producing a KM framework, based on the collective wisdom of curriculum designers of these programmes. Analysis of curricula was conducted at two levels of course titles and course descriptions. Keywords and phrases were identified and listed, then reduced into relevant categories in three successive exercises of subtraction. Each identified term was treated as a module. If a module was offered in more than one programme or course, the number was provided for the occurrence in order to indicate the emphasis it received in different curricula. Thus, we have been able to identify major categories of KM curricula in these schools. There is a need for academics and experts in the field to further validate these results in subsequent research.
DAMAGE ASSESSMENT OF BURIED PIPES DUE TO THE 2007 NIIGATA CHUETSU-OKI EARTHQUAKE IN JAPAN
Authors: MARUYAMA YOSHIHISA , KIMISHIMA KOTA , YAMAZAKI FUMIO
Published: January 2011

This study investigated the damage distribution of buried pipes due to the 2007 Niigata Chuetsu-Oki earthquake in Japan. Various damage datasets — e.g. water pipes, low-pressure gas pipes, mid-pressure gas pipes, sewage lines, collapsed houses, and liquefaction occurrences — were integrated into a geographic information system. Using the datasets, the spatial distribution of damage was investigated with respect to geomorphological land classification and altitude. The minimum distances between the damaged locations were measured, and the spatial correlations of damage incidents to lifeline systems were evaluated. In addition, the damage ratios of water distribution pipes were compared with different fragility curves constructed from the damage datasets for the 1995 Kobe earthquake and other recent earthquakes in Japan.
ACCURATE EVALUATION OF BUILDING DAMAGE IN THE 2003 BOUMERDES, ALGERIA EARTHQUAKE FROM QUICKBIRD SATELLITE IMAGES
Authors: MESLEM ABDELGHANI , YAMAZAKI FUMIO , MARUYAMA YOSHIHISA
Published: January 2011

Using QuickBird satellite images of Boumerdes city obtained following the 21 May 2003 Algeria earthquake, our study examined the applicability of high-resolution optical imagery for the visual detection of building damage grade based on the ground-truth data on the urban nature, typology of a total of 2,794 buildings, and the real damage observed. The results are presented as geographical information system (GIS) damage mapping of buildings obtained from field surveys and QuickBird images. In general, totally collapsed buildings, partially collapsed buildings, and buildings surrounded by debris can be identified by using only post-event pan-sharpened images. However, due to the nature of the damage observed, some buildings may be judged incorrectly even if preevent images are employed as a reference to evaluate the damage status. Hence, in this study, we clarify the limitations regarding the applicability of high-resolution optical satellite imagery in building damage-level mapping.
NUMERICAL ANALYSIS OF AN EXISTING RC FRAME BY USING 3D ELEMENTS
Authors: QIAN J. , ZHAO G. , LEI T. , LU X.
Published: January 2011

In view of the fact that there are no suitable 1D elements that may adequately predict brittle shear failure, a refined finite element (FE) model using full 3D elements has been established for a existing frame structure. Numerical computation is performed to study the seismic damage and failure patterns of existing buildings. Emphases are focused on shear failure of beams and columns and additional stiffness effects of slabs and brick walls. The simulation results agree well with the in situ test and the general damage pattern observed in the 2008 Sichuan earthquake.