bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of theCorynebacterium diphtheriaeDtxR Regulon: Identification of a Putative Siderophore Synthesis and Transport System That Is Similar to theYersiniaHigh-Pathogenicity Island-Encoded Yersiniabactin Synthesis and Uptake System
Authors: Kunkle Carey A. , Schmitt Michael P. 
Published: November 2003

ABSTRACTThe diphtheria toxin repressor, DtxR, is a global iron-dependent regulatory protein inCorynebacterium diphtheriaethat controls gene expression by binding to 19-bp operator sequences. To further define the DtxR regulon inC. diphtheriae, a DtxR repressor titration assay (DRTA) was developed and used to identify 10 previously unknown DtxR binding sites. Open reading frames downstream from seven of the newly identified DtxR binding sites are predicted to encode proteins associated with iron or heme transport. Electrophoretic mobility shift assays indicated that DtxR was able to bind to DNA fragments carrying the 19-bp operator regions, and transcriptional analysis of putative promoter elements adjacent to the binding site sequences revealed that most of these regions displayed iron- and DtxR-regulated activity. A putative siderophore biosynthesis and transport operon located downstream from one of the DtxR binding sites, designatedsid, is similar to the yersiniabactin synthesis and uptake genes encoded on theYersinia pestishigh pathogenicity island. The siderophore biosynthetic genes in thesidoperon contained a large deletion in theC. diphtheriaeC7 strain, but thesidgenes were unaffected in four clinical isolates that are representative of the dominant strains from the recent diphtheria epidemic in the former Soviet Union. Mutations in the siderophore biosynthetic genes in a clinical strain had no effect on siderophore synthesis or growth in low-iron conditions; however, a mutation in one of the putative transport proteins,cdtP, resulted in reduced growth in iron-depleted media, which suggests that this system may have a role in iron uptake. The findings from this study indicate thatC. diphtheriaecontains at least 18 DtxR binding sites and that DtxR may affect the expression of as many as 40 genes.
Subtractive Hybridization Reveals a Type I Polyketide Synthase Locus Specific to
Mycobacterium ulcerans
Authors: Jenkin Grant A. , Stinear Timothy P. , Johnson Paul D. R. , Davies John K. 
Published: November 2003

ABSTRACT

Mycobacterium ulcerans
causes Buruli ulcer, the third most prevalent mycobacterial infection of immunocompetent humans after tuberculosis and leprosy. Recent work has shown that the production by
M. ulcerans
of mycolactone, a novel polyketide, may partly explain the pathogenesis of Buruli ulcer. To search for the genetic basis of virulence in
M. ulcerans
, we took advantage of the close genetic relationship between
M. ulcerans
and
Mycobacterium marinum
by performing genomic suppressive subtractive hybridization of
M. ulcerans
with
M. marinum
. We identified several DNA fragments specific to
M. ulcerans
, in particular, a type I polyketide synthase locus with a highly repetitive modular arrangement. We postulate that this locus is responsible for the synthesis of mycolactone in
M. ulcerans
.
Quinolone Resistance Due to Reduced Target Enzyme Expression
Authors: Ince Dilek , Hooper David C. 
Published: November 2003

ABSTRACT

We report for the first time low-level quinolone resistance mediated by decreased expression of topoisomerase IV in
Staphylococcus aureus
. A single-step mutant of wild-type
S. aureus
strain ISP794, P18 selected by using twice the MIC of premafloxacin, had four- and four- to eightfold greater MICs of premafloxacin and ciprofloxacin, respectively, than the wild type. Sequencing of
parEC
and
gyrBA
with their promoter regions revealed a point mutation (G→A) 13 bp upstream of the start codon of
parE
. Genetic linkage studies showed that there was a high level of correlation between the mutation and the resistance phenotype, and allelic exchange confirmed the contribution of the mutation to resistance. Decreased expression of ParE and decreased steady-state levels of
parEC
transcripts in P18 and in resistant allelic exchange mutants were observed. The steady-state levels of
gyrBA
and
topB
transcripts were increased in P18 but not in two resistant allelic exchange mutants, and sequencing upstream of either gene did not reveal a difference between ISP794 and P18. The steady-state levels of
topA
transcripts were similar in the various strains. Growth competition experiments performed at 30, 37, and 41°C with a susceptible allelic exchange strain and a resistant allelic exchange strain suggested that loss of fitness was associated with reduced levels of ParE at 41°C. However, P18 had a growth advantage over ISP794 at all temperatures, suggesting that a compensatory mechanism was associated with the increased levels of
gyrBA
and
topB
transcripts. Thus, reduced levels of ParE appear to be compatible with cell survival, although there may be a fitness cost during rapid cell multiplication, which might be overcome by compensatory mechanisms without reversion of the resistance phenotype.
Role of the Stationary Growth Phase Sigma Factor RpoS of
Burkholderia pseudomallei
in Response to Physiological Stress Conditions
Authors: Subsin Benchamas , Thomas Mark S. , Katzenmeier Gerd , Shaw Jonathan G. , Tungpradabkul Sumalee , Kunakorn Mongkol 
Published: November 2003

ABSTRACT

The
Burkholderia pseudomallei rpoS
gene was identified, and an
rpoS
null mutant was constructed. The mutant was shown to have an increased sensitivity to carbon starvation and oxidative stress. By using
rpoS-lacZ
fusions, transcription of
rpoS
was shown to be growth phase regulated, reaching a peak upon entry into stationary phase.
Unexpected patterns of mitochondrial DNA variation among Native Americans from the Southeastern United States
Authors: (Weiss) Bolnick Deborah A. , Smith David Glenn 
Published: November 2003

AbstractMitochondrial DNA (mtDNA) haplogroups were determined by restriction fragment length polymorphism‐typing for 66 individuals from four southeastern North American populations, and the HVS I portion of the mtDNA control region was sequenced in 48 of these individuals. Although populations from the same geographic region usually exhibit similar haplogroup frequency distributions (Lorenz and Smith [1996] Am. J. Phys. Anthropol.101:307–323; Malhi et al. [2001] Hum. Biol.73:17–55), those from the Southeast instead exhibit haplogroup frequency distributions that differ significantly from one another. Such divergent haplogroup frequency distributions are unexpected for the Muskogean‐speaking southeastern populations, which share many sociocultural traits, speak closely related languages, and have experienced extensive admixture both with each other and with other eastern North American populations. Independent origins, genetic isolation from other Native American populations due to matrilocality, differential admixture, or a genetic bottleneck could be responsible for this heterogeneous distribution of haplogroup frequencies. Within a given haplogroup, however, the HVS I sequences from the four Muskogean‐speaking populations appear relatively similar to one another, providing evidence for close relationships among them and for reduced diversity within haplogroups in the Southeast. Given additional archaeological, linguistic, and ethnographic evidence, these results suggest that a genetic bottleneck associated with the historical population decline is the most plausible explanation for such patterns of mtDNA variation. Am J Phys Anthropol, 2003. © 2003 Wiley‐Liss, Inc.
Sedimentation rates in the lower Yellow River over the past 2300 years as influenced by human activities and climate change
Authors: Xu Jiongxin 
Published: November 2003

AbstractAnalysis of the sedimentary record has been used to determine the historical sedimentation rate in the lower Yellow River and the historical literature has been studied to obtain information on climate change and human activities. Based on the data obtained, the temporal variation in the sedimentation rate in the lower Yellow River over the past 2300 years has been studied in relation to climate change and the impact of human activities. The results indicate that the response of the sedimentation zone of Yellow River system to changes in the erosion zone are consistent with existing understanding. Changes in vegetation and land use, both related to climate change and human activities, are two major controls responsible for the increase in sedimentation rates. Additionally, the changing strategies for harnessing of the lower Yellow River are also responsible for such acceleration. With the trend of accelerated sedimentation in the past 2300 years, the period from the 7th to 10th centuries and the period since the mid‐19th century have been identified as two periods in which abrupt changes occurred. Copyright © 2003 John Wiley & Sons, Ltd.
Bisphosphonate treatment affects trabecular bone apparent modulus through micro‐architecture rather than matrix properties
Authors: Day J. S. , Ding M. , Bednarz P. , van der Linden J. C. , Mashiba T. , Hirano T. , Johnston C. C. , Burr D. B. , Hvid I. , Sumner D. R. , Weinans H. 
Published: November 2003

AbstractBisphosphonates are emerging as an important treatment for osteoporosis. But whether the reduced fracture risk associated with bisphosphonate treatment is due to increased bone mass, improved trabecular architecture and/or increased secondary mineralization of the calcified matrix remains unclear. We examined the effects of bisphosphonates on both the trabecular architecture and matrix properties of canine trabecular bone. Thirty‐six beagles were divided into a control group and two treatment groups, one receiving risedronate and the other alendronate at 5–6 times the clinical dose for osteoporosis treatment. After one year, the dogs were killed, and samples from the first lumbar vertebrae were examined using a combination of micro‐computed tomography, finite element modeling, and mechanical testing. By combining these methods, we examined the treatment effects on the calcified matrix and trabecular architecture independently. Conventional histomorphometry and microdamage data were obtained from the second and third lumbar vertebrae of the same dogs [Bone 28 (2001) 524]. Bisphosphonate treatment resulted in an increased apparent Young's modulus, decreased bone turnover, increased calcified matrix density, and increased microdamage. We could not detect any change in the effective Young's modulus of the calcified matrix in the bisphosphonate treated groups. The observed increase in apparent Young's modulus was due to increased bone mass and altered trabecular architecture rather than changes in the calcified matrix modulus. We hypothesize that the expected increase in the Young's modulus of the calcified matrix due to the increased calcified matrix density was counteracted by the accumulation of microdamage. © 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
Predicting stress fractures using a probabilistic model of damage, repair and adaptation
Authors: Taylor David , Casolari Edoardo , Bignardi Cristina 
Published: November 2003

AbstractThis paper is concerned with the theoretical prediction of stress fractures in the bones of athletes, soldiers and others during periods of intensive exercise. Previously [J. Orthop. Res. 19 (2001) 919] we showed that test data on the fatigue strength of bone in vitro could be described using Weibull's probabilistic model, allowing predictions to be made of the probability of failure as a function of time under cyclic loading. This paper extends the earlier argument by including two living processes which act to reduce the incidence of failure: (i) repair of damage, and; (ii) adaptation by bone deposition. Having incorporated these aspects into the mathematical model, we applied the theory to a specific case: the human second metatarsal. We predicted a 17% incidence of stress fractures, all occurring within 6 weeks of commencement of the training programme. These predictions agreed well with clinical findings. Interestingly, we concluded that the major effect in preventing stress fractures comes from repair rather than from adaptation, which has a relatively minor role because it acts more slowly. © 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
Tibio‐femoral loading during human gait and stair climbing
Authors: Taylor William R. , Heller Markus O. , Bergmann Georg , Duda Georg N. 
Published: November 2003

AbstractSurgical intervention of the knee joint routinely endeavors to recreate a physiologically normal joint loading environment. The loading conditions resulting from osteotomies, fracture treatment, ligament replacements, and arthroplasties of the knee are considered to have an impact on the long term clinical outcome; however, knowledge regarding in vivo loading conditions is limited. Using a previously validated musculoskeletal lower limb model, we predicted the tibio‐femoral joint contact forces that occur in the human knee during the common daily activities of walking and stair climbing. The average resultant peak force during walking was 3.1 times body weight (BW) across four total hip arthroplasty patients. Inter‐individual variations proved larger than the variation of forces for each patient repeating the same task. Forces through the knee were considerably larger during stair climbing than during walking: the average resultant peak force during stair climbing was 5.4 BW although peaks of up to 6.2 BW were calculated for one particular patient. Average anteroposterior peak shear components of 0.6 BW were determined during walking and 1.3 BW during stair climbing. These results confirm both the joint contact forces reported in the literature and the importance of muscular activity in creating high forces across the joint. The magnitudes of these forces, specifically in shear, have implications for all forms of surgical intervention in the knee. The data demonstrate that high contact and shear forces are generated during weight bearing combined with knee flexion angles greater than approximately 15°. Clinically, the conditions that produce these larger contact forces should be avoided during post‐operative rehabilitation. © 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
Bone sialoprotein‐coated femoral implants are osteoinductive but mechanically compromised
Authors: O'Toole Gary C. , Salih E. , Gallagher C. , FitzPatrick D. , O'Higgins N. , O'Rourke S. K. 
Published: November 2003

AbstractAseptic loosening of femoral implants in total hip replacement remains an unsolved orthopaedic problem. This paper investigates the potential role of bone sialoprotein (BSP) in enhancing bone‐implant adherence. As BSP is osteoinductive in rat calvarial models, we investigated whether BSP is similarly osteoinductive when coated onto intramedullary femoral implants.BSP‐coated titanium implants were implanted into the femur of female “Wistar” rats (average weight 215 g) that were sacrificed at days 10, 20 and 30. Harvested femoral implants were subjected to pullout testing and then examined histologically.BSP‐coated implants demonstrate osteoinduction when examined histologically. Plugging the femoral canal with BSP prior to inserting the implant neither increased implant pullout strengths nor further increased osteoblastic activity.This study has demonstrated for the first time that BSP is osteoinductive when coated onto femoral implants and inserted into bones subjected to mechanical loading. However, we found that pullout strengths are a function of implant surface topographical characteristics and are not affected by BSP coating or histological osteoinduction. © 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
Relative biological effectiveness (RBE), quality factor (Q), and radiation weighting factor (wR)
Authors: Valentin J. 
Published: November 2003

The effect of ionising radiation is influenced by the dose, the dose rate, and the quality of the radiation. Before 1990, dose-equivalent quantities were defined in terms of a quality factor, Q( L), that was applied to the absorbed dose at a point in order to take into account the differences in the effects of different types of radiation. In its 1990 recommendations, the ICRP introduced a modified concept. For radiological protection purposes, the absorbed dose is averaged over an organ or tissue, T, and this absorbed dose average is weighted for the radiation quality in terms of the radiation weighting factor, w R, for the type and energy of radiation incident on the body. The resulting weighted dose is designated as the organ- or tissue-equivalent dose, H T. The sum of the organ-equivalent doses weighted by the ICRP organ-weighting factors, w T, is termed the effective dose, E. Measurements can be performed in terms of the operational quantities, ambient dose equivalent, and personal dose equivalent. These quantities continue to be defined in terms of the absorbed dose at the reference point weighted by Q( L). The values for w R and Q( L) in the 1990 recommendations were based on a review of the biological and other information available, but the underlying relative biological effectiveness (RBE) values and the choice of w R values were not elaborated in detail. Since 1990, there have been substantial developments in biological and dosimetric knowledge that justify a re-appraisal of w R values and how they may be derived. This re-appraisal is the principal objective of the present report. The report discusses in some detail the values of RBE with regard to stochastic effects, which are central to the selection of w R and Q( L). Those factors and the dose-equivalent quantities are restricted to the dose range of interest to radiation protection, i.e. to the general magnitude of the dose limits. In special circumstances where one deals with higher doses that can cause deterministic effects, the relevant RBE values are applied to obtain a weighted dose. The question of RBE values for deterministic effects and how they should be used is also treated in the report, but it is an issue that will demand further investigations. This report is one of a set of documents being developed by ICRP Committees in order to advise the ICRP on the formulation of its next Recommendations for Radiological Protection. Thus, while the report suggests some future modifications, the w R values given in the 1990 recommendations are still valid at this time. The report provides a scientific background and suggests how the ICRP might proceed with the derivation of w R values ahead of its forthcoming recommendations.
Evaluating Alcohol Access and the Alcohol Environment in Neighborhood Areas
Authors: Freisthler Bridget , Gruenewald Paul J. , Treno Andrew J. , Lee Juliet 
Published: November 2003

Background:This paper examines neighborhood, outlet, and server characteristics related to successful purchases of alcohol by intoxicated patrons and underage drinkers at alcohol establishments. It is hypothesized that outlets in commercial areas near to other premises, with poor exterior maintenance, much advertising, and inexperienced youthful servers will be more likely to sell alcohol to intoxicated and underage patrons.Methods:Data were collected using pseudo‐intoxicated patron and apparent minor surveys of randomly selected alcohol establishments in a metropolitan area of northern California. Data collection operations included independent surveillance of these drinking places to establish neighborhood and premise characteristics and pseudo‐intoxicated patron and apparent minor stings to assess rates of these forms of illegal alcohol sales. Male actors feigning intoxication and female of‐age youth identified as appearing to be 20 years or younger attempted to purchase alcohol at on‐ and off‐premise establishments, respectively. Rates of sales (off‐premise) and service (on‐premise) were the primary outcomes.Results:Apparent minors purchased alcohol in 39% of attempts (95% CI, 34–45%) while pseudo‐intoxicated patrons were served alcohol in 58% of attempts (95% CI, 50–67%). Sales to apparent minors were significantly related to percentage of Hispanic residents and areas with greater population density. Sales to pseudo‐intoxicated patrons were more frequent when the server was male and appeared to be under the age of 30. These sales were also more frequent in Hispanic neighborhoods with high population density and high numbers of on‐premise outlets but were less frequent in African American neighborhoods.Conclusion:The findings suggest that underage and intoxicated patron sales differ by areas. Both forms of illegal sales of alcohol are more likely in highly populated areas of communities. The findings also suggest that server characteristics are strongly related to sales to intoxicated patrons, suggesting some leverage for responsible beverage service programs in these environments.
Reproductive modes, ontogenies, and the evolution of body form
Authors: Wake Marvalee 
Published: November 2003

AbstractThe evolution and development of complex morphological structures, and of body form, can now be addressed hierarchically, using diverse techniques from multiple theoretical perspectives. Such an 'integrative' or 'holistic' approach is likely to provide more complete insight into the origin of patterns and processes of evolution than the more traditional reductionist mode. Current work on the implications of reproductive mode on the ontogenies of amphibians and the evolution of their body form is an example of that approach. Genome size, egg and clutch size, and a number of other life history traits are involved with developmental rate and pattern (including loss of larval features, ontogenetic repatterning, and modified patterns of organogenesis), and reproductive mode (the presumed ancestral egg-laying vs. direct development and viviparity) is correlated and potentially causal for certain patterns. Such correlations are being explored using a variety of approaches, and examples of this work-in-progress are provided.