bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypervirulent Chlamydia trachomatis Clinical Strain Is a Recombinant between Lymphogranuloma Venereum (L
2
) and D Lineages
Authors: Somboonna Naraporn , Wan Raymond , Ojcius David M. , Pettengill Matthew A. , Joseph Sandeep J. , Chang Alexander , Hsu Ray , Read Timothy D. , Dean Deborah 
Published: May 2011

ABSTRACT

Chlamydia trachomatis
is an obligate intracellular bacterium that causes a diversity of severe and debilitating diseases worldwide. Sporadic and ongoing outbreaks of lymphogranuloma venereum (LGV) strains among men who have sex with men (MSM) support the need for research on virulence factors associated with these organisms. Previous analyses have been limited to single genes or genomes of laboratory-adapted reference strain L
2
/434 and outbreak strain L
2
b/UCH-1/proctitis. We characterized an unusual LGV strain, termed L
2
c, isolated from an MSM with severe hemorrhagic proctitis. L
2
c developed nonfusing, grape-like inclusions and a cytotoxic phenotype in culture, unlike the LGV strains described to date. Deep genome sequencing revealed that L
2
c was a recombinant of L
2
and D strains with conserved clustered regions of genetic exchange, including a 78-kb region and a partial, yet functional, toxin gene that was lost with prolonged culture. Indels (insertions/deletions) were discovered in an
ftsK
gene promoter and in the
tarp
and
hctB
genes, which encode key proteins involved in replication, inclusion formation, and histone H1-like protein activity, respectively. Analyses suggest that these indels affect gene and/or protein function, supporting the
in vitro
and disease phenotypes. While recombination has been known to occur for
C. trachomatis
based on gene sequence analyses, we provide the first whole-genome evidence for recombination between a virulent, invasive LGV strain and a noninvasive common urogenital strain. Given the lack of a genetic system for producing stable
C. trachomatis
mutants, identifying naturally occurring recombinants can clarify gene function and provide opportunities for discovering avenues for genomic manipulation.

IMPORTANCE
Lymphogranuloma venereum (LGV) is a prevalent and debilitating sexually transmitted disease in developing countries, although there are significant ongoing outbreaks in Australia, Europe, and the United States among men who have sex with men (MSM). Relatively little is known about LGV virulence factors, and only two LGV genomes have been sequenced to date. We isolated an LGV strain from an MSM with severe hemorrhagic proctitis that was morphologically unique in tissue culture compared with other LGV strains. Bioinformatic and statistical analyses identified the strain as a recombinant of L
2
and D strains with highly conserved clustered regions of genetic exchange. The unique culture morphology and, more importantly, disease phenotype could be traced to the genes involved in recombination. The findings have implications for bacterial species evolution and, in the case of ongoing LGV outbreaks, suggest that recombination is a mechanism for strain emergence that results in significant disease pathology.
Presence of Putative Repeat-in-Toxin Gene
tosA
in Escherichia coli Predicts Successful Colonization of the Urinary Tract
Authors: Vigil Patrick D. , Stapleton Ann E. , Johnson James R. , Hooton Thomas M. , Hodges Andrew P. , He Yongqun , Mobley Harry L. T. 
Published: May 2011

ABSTRACT

Uropathogenic
Escherichia coli
(UPEC) strains, which cause the majority of uncomplicated urinary tract infections (UTIs), carry a unique assortment of virulence or fitness genes. However, no single defining set of virulence or fitness genes has been found in all strains of UPEC, making the differentiation between UPEC and fecal commensal strains of
E. coli
difficult without the use of animal models of infection or phylogenetic grouping. In the present study, we consider three broad categories of virulence factors simultaneously to better define a combination of virulence factors that predicts success in the urinary tract. A total of 314 strains of
E. coli
, representing isolates from fecal samples, asymptomatic bacteriuria, complicated UTIs, and uncomplicated bladder and kidney infections, were assessed by multiplex PCR for the presence of 15 virulence or fitness genes encoding adhesins, toxins, and iron acquisition systems. The results confirm previous reports of gene prevalence among isolates from different clinical settings and identify several new patterns of gene associations. One gene,
tosA
, a putative repeat-in-toxin (RTX) homolog, is present in 11% of fecal strains but 25% of urinary isolates. Whereas
tosA
-positive strains carry an unusually high number (11.2) of the 15 virulence or fitness genes,
tosA
-negative strains have an average of only 5.4 virulence or fitness genes. The presence of
tosA
was predictive of successful colonization of a murine model of infection, even among fecal isolates, and can be used as a marker of pathogenic strains of UPEC within a distinct subset of the B2 lineage.

IMPORTANCE
Escherichia coli
is the primary cause of urinary tract infections, the most common bacterial infection of humans. Virulence of a uropathogenic strain is typically defined by the clinical source of the isolate, the ability to colonize the bladder and kidneys in a murine model, the phylogenetic group of the bacterium, and virulence gene content. Here we describe a novel single gene, the repeat-in-toxin gene
tosA
, the presence of which predicts virulence of
E. coli
isolates regardless of source. Rapid identification of uropathogenic strains of
E. coli
may aid in the development of therapeutic and preventive therapies.
Changes in anteroposterior patellar tendon diameter support a continuum of pathological changes
Authors: Malliaras Peter , Cook Jill 
Published: May 2011

ObjectivesA continuum of pathological ultrasound patellar tendon changes from normal tendons, followed by diffuse and then focal change in echogenicity has been proposed. The anteroposterior (AP) diameter of each pathological state and whether change in pathological state is accompanied by change in AP diameter are not known. The aims of this study were to (1) investigate the AP diameter of previously described patellar tendon ultrasound groups (normal, diffuse and focal change in echogenicity) and (2) investigate the change in AP diameter among active volleyball players during a season and whether this corresponds with change in ultrasound group.MethodsThe grey-scale ultrasound pathological groups (normal, diffuse, focal) and AP diameter were measured among 102 volleyball players at the beginning of a season and 58 volleyball players at 6 one-monthly intervals during a 5-month indoor season.ResultsThere was a significant ordinal relationship (analysis of variance, Student–Neuman–Keuls post hoc test, p < 0.05) between AP diameter and normal tendons, diffuse and focally abnormal tendons among men (3.4 ± 0.4, 4.9 ± 0.4, 6.5 ± 1.8 mm) and women (3.2 ± 0.4, 4.2 ± 0.4, 4.6 ± 0.7 mm). Tendons that stayed in the same group tended to have a smaller mean change than tendons that changed group.ConclusionsThese findings support the proposed continuum of tendon pathology. Mild patellar tendon thickening (>4.2 mm among men, >4 mm among women) may indicate pathology among active athletes.
Urinary trichlorophenol levels and increased risk of attention deficit hyperactivity disorder among US school-aged children
Authors: Xu Xiaohui , Nembhard Wendy N , Kan Haidong , Kearney Greg , Zhang Zhi-Jiang , Talbott Evelyn O 
Published: May 2011

BackgroundTrichlorophenols (TCPs) are organochlorine compounds which are ubiquitous in the environment and well known for their carcinogenic effects. However, little is known about their neurotoxicity in humans.ObjectivesOur goal was to examine the association between body burden of TCPs (ie, 2,4,5-TCP and 2,4,6-TCP) and attention deficit hyperactivity disorder (ADHD).MethodsWe calculated ORs and 95% CIs from logistic regression analyses using data from the 1999–2004 National Health and Nutrition Examination Survey (NHANES) to evaluate the association between urinary TCPs and parent-reported ADHD among 2546 children aged 6–15 years.ResultsChildren with low levels (<3.58 μg/g) and high levels (≥3.58 μg/g) of urinary 2,4,6-TCP had a higher risk of parent-reported ADHD compared to children with levels below the limit of detection (OR 1.54, 95% CI 0.97 to 2.43 and OR 1.77, 95% CI 1.18 to 2.66, respectively; p for trend=0.006) after adjusting for covariates. No association was found between urinary 2,4,5-TCP and parent-reported ADHD.ConclusionExposure to TCP may increase the risk of behavioural impairment in children. The potential neurotoxicity of these chemicals should be considered in public health efforts to reduce environmental exposures/contamination, especially in countries where organochlorine pesticides are still commonly used.
HIGH-ORDER OUT-OF-PLANE EXPANSION FOR 3D FIELDS
Authors: MAKINO K. , BERZ M. , JOHNSTONE C. 
Published: May 2011

The precise determination of the dynamics in accelerators with complicated field arrangements such as Fixed Field Alternating Gradient accelerators (FFAG) depends critically on the ability to describe the appearing magnetic fields in full 3D. However, frequently measurements or models of FFAG fields postulate their behavior in the midplane only, and rely on the fact that this midplane field and its derivatives determine the field in all of space. The detailed knowledge of the resulting out-of-plane fields is critical for a careful assessment of the vertical dynamics. We describe a method based on the differential algebraic (DA) approach to obtain the resulting out-of-plane expansions to any order in an order-independent, straightforward fashion. In particular, the resulting fields satisfy Maxwell's equations to the order of the expansion up to machine precision errors, and without any inaccuracies that can arise from conventional divided difference or finite element schemes for the computation of out-of-plane fields. The method relies on re-writing the underlying PDE as a fixed point problem involving DA operations, and in particular the differential algebraic integration operator. We illustrate the performance of the method for a variety of practical examples, and obtain estimates for the orders necessary to describe the fields to a prescribed accuracy.
Aspects of crinoid palaeontology, Much Wenlock Limestone Formation, Wenlock Edge, Shropshire (Silurian)
Authors: Donovan S. K. , Lewis D. N. 
Published: May 2011

SUMMARY
Fossil crinoids are common in the Much Wenlock Limestone Formation of the type area in Shropshire, yet remain poorly known because of their fragmentary preservation. Calceocrinid disparids are recognized from Wenlock Edge for the first time on the basis of distinctive brachial ossicles. More proximal brachials have a broad, U-shaped adoral groove and an axial canal; distal ossicles have a narrower, V-shaped adoral groove and no axial canal. What remains surprising is that the most distinctive element of the calceocrinid endoskeleton, the fused basal circlet, remains unknown from Wenlock Edge.
A crinoid pluricolumnal displaying an irregular line of three pits that show a progressive increase in size was infested while the crinoid was alive; this is indicated by the swollen column and deformities of columnals. Such infestations are rare in the British Silurian. The pits may have been made by a single infesting organism which migrated up or down the column in response to the influence of gravity.
Crinoid roots from the Upper Devonian of north Devon: morphology, function and systematics
Authors: Donovan S. K. , Ewin T. A. M. 
Published: May 2011

SUMMARY

A small collection of well-preserved crinoid attachment structures from the Upper Devonian Pilton Formation of north Devon indicates the presence of two distinct species.
Sostronocrinus mundus
(Whidborne) lived attached to an unlithified sedimentary substrate by the vertical insertion of a robust, terminal rhizoidal holdfast abetted by robust, unbranched radices oriented laterally or curved distally. There was a strong differentiation of morphology between the radicular attachment and the more proximal column, which lacked radices.
Eumorphocrinus porteri
(Whidborne) attached to a similar substrate by an irregularly heteromorphic, tapering radicular runner bearing branched radices that promoted permanent attachment close to the sediment surface. These radices were probably developed on at least part of the more proximal column. The highest columnals of the dististele do not bear radices and, therefore, are not nodals. The dististele was previously unknown in both of these species.
Using X-ray images to analyse graptolite distribution and alignment in Welsh mudrocks
Authors: Snelling Andrea M. , Zalasiewicz Jan A. , Reeds Ian 
Published: May 2011

SUMMARY
X-ray imaging of graptolites is here shown to enhance greatly the amount and type of fossil evidence available, both for biostratigraphical study and for palaeoceanographical and palaeoecological analysis. The technique requires there to be sufficient density contrast between the fossils and the enclosing rock, as with the pyritized graptolites within the Silurian (Llandovery, Aeronian) mudrocks of central Wales investigated herein. Graptolite species previously not encountered using traditional collecting techniques were recorded in significant numbers using X-ray imaging and include two species recorded for the first time in Britain. Stratigraphic variation has been found in the numbers of pyritized graptolites, and this is inversely related to the amount of free aggregated pyrite within the rock. Biserial graptolite specimens show systematic patterns of alignment by currents, and construction of stereo and anaglyph images enables 3-dimensional visualisation of spatial information, allowing the geometry and microstratigraphic relationship of one graptolite to another to be discerned. CT-scan techniques show better-resolved 3D morphology, but digital X-ray techniques, being more rapid, may remain optimal for many routine uses in palaeontology.
Metformin, Independent of AMPK, Induces mTOR Inhibition and Cell-Cycle Arrest through REDD1
Authors: Ben Sahra Isaam , Regazzetti Claire , Robert Guillaume , Laurent Kathiane , Le Marchand-Brustel Yannick , Auberger Patrick , Tanti Jean-François , Giorgetti-Peraldi Sophie , Bost Frédéric 
Published: May 2011

Abstract
Metformin is a widely prescribed antidiabetic drug associated with a reduced risk of cancer. Many studies show that metformin inhibits cancer cell viability through the inhibition of mTOR. We recently showed that antiproliferative action of metformin in prostate cancer cell lines is not mediated by AMP-activated protein kinase (AMPK). We identified REDD1 (also known as DDIT4 and RTP801), a negative regulator of mTOR, as a new molecular target of metformin. We show that metformin increases REDD1 expression in a p53-dependent manner. REDD1 invalidation, using siRNA or REDD1−/− cells, abrogates metformin inhibition of mTOR. Importantly, inhibition of REDD1 reverses metformin-induced cell-cycle arrest and significantly protects from the deleterious effects of metformin on cell transformation. Finally, we show the contribution of p53 in mediating metformin action in prostate cancer cells. These results highlight the p53/REDD1 axis as a new molecular target in anticancer therapy in response to metformin treatment. Cancer Res; 71(13);4366–72. ©2011 AACR.
Evidence That Serum Levels of the Soluble Receptor for Advanced Glycation End Products Are Inversely Associated with Pancreatic Cancer Risk: A Prospective Study
Authors: Jiao Li , Weinstein Stephanie J. , Albanes Demetrius , Taylor Philip R. , Graubard Barry I. , Virtamo Jarmo , Stolzenberg-Solomon Rachael Z. 
Published: May 2011

Abstract
Cigarette smoking, obesity, type 2 diabetes, and, to a lesser extent, meat cooked at high temperatures are associated with pancreatic cancer. Cigarette smoke and foods cooked at higher temperatures are major environmental sources of advanced glycation end products (AGE). AGEs accumulate during hyperglycemia and elicit oxidative stress and inflammation through interaction with the receptor for AGEs (RAGE). Soluble RAGE (sRAGE) acts as an anti-inflammatory factor to neutralize AGEs and block the effects mediated by RAGE. In this study, we investigated the associations of prediagnostic measures of Nϵ-(carboxymethyl)-lysine (CML)-AGE and sRAGE with pancreatic cancer in a case–cohort study within a cohort of 29,133 Finnish male smokers. Serum samples and exposure information were collected at baseline (1985–1988). We measured CML-AGE, sRAGE, glucose, and insulin concentrations in fasting serum from 255 incident pancreatic cancer cases that arose through April 2005 and from 485 randomly sampled subcohort participants. Weighted Cox proportional hazard regression models were used to calculate relative risks (RR) and 95% CI, adjusted for age, years of smoking, and body mass index. CML-AGE and sRAGE were mutually adjusted. CML-AGE levels were not associated with pancreatic cancer [fifth compared with first quintile, RR (95% CI): 0.68 (0.38–1.22), Ptrend = 0.27]. In contrast, sRAGE levels were inversely associated with pancreatic cancer [fifth compared with first quintile, RR (95% CI): 0.46 (0.23–0.73), Ptrend = 0.002]. Further adjustment for glucose or insulin levels did not change the observed associations. Our findings suggest that sRAGE is inversely associated with pancreatic cancer risk among Finnish male smokers. Cancer Res; 71(10); 3582–9. ©2011 AACR.
mTOR Kinase Inhibitor AZD8055 Enhances the Immunotherapeutic Activity of an Agonist CD40 Antibody in Cancer Treatment
Authors: Jiang Qun , Weiss Jonathan M. , Back Timothy , Chan Tim , Ortaldo John R. , Guichard Sylvie , Wiltrout Robert H. 
Published: May 2011

AbstractmTOR is a central mediator of cancer cell growth, but it also directs immune cell differentiation and function. On this basis, we had explored the hypothesis that mTOR inhibition can enhance cancer immunotherapy. Here, we report that a combination of αCD40 agonistic antibody and the ATP-competitive mTOR kinase inhibitory drug AZD8055 elicited synergistic antitumor responses in a model of metastatic renal cell carcinoma. In contrast to the well-established mTOR inhibitor rapamycin, AZD8055 increased the infiltration, activation, and proliferation of CD8+ T cells and natural killer cells in liver metastatic foci when combined with the CD40 agonist. AZD8055/αCD40-treated mice also display an increased incidence of matured macrophages and dendritic cells compared with that achieved in mice by αCD40 or AZD8055 treatment alone. We found that the combination treatment also increased macrophage production of TNFα, which played an indispensable role in activation of the observed antitumor immune response. Levels of Th1 cytokines, including interleukin 12, IFN-γ, TNFα, and the Th1-associated chemokines RANTES, MIG, and IP-10 were each elevated significantly in the livers of mice treated with the combinatorial therapy versus individual treatments. Notably, the AZD8055/αCD40-induced antitumor response was abolished in IFN-γ−/− and CD40−/− mice, establishing the reliance of the combination therapy on host IFN-γ and CD40 expression. Our findings offer a preclinical proof of concept that, unlike rapamycin, the ATP-competitive mTOR kinase inhibitor AZD8055 can contribute with αCD40 treatment to trigger a restructuring of the tumor immune microenvironment to trigger regressions of an established metastatic cancer. Cancer Res; 71(12); 4074–84. ©2011 AACR.
Mitochondrial Subversion in Cancer
Authors: Chatterjee Aditi , Dasgupta Santanu , Sidransky David 
Published: May 2011

AbstractMitochondria control essential cellular activities including generation of ATP via oxidative phosphorylation. Mitochondrial DNA (mtDNA) mutations in the regulatory D-loop region and somatic mtDNA mutations are common in primary human cancers. The biological impact of a given mutation may vary, depending on the nature of the mutation and the proportion of mutant mtDNAs carried by the cell. Identification of mtDNA mutations in precancerous lesions supports their early contribution to cell transformation and cancer progression. Introduction of mtDNA mutations in transformed cells has been associated with increased ROS production and tumor growth. Studies reveal that increased and altered mtDNA plays a role in the development of cancer but further work is required to establish the functional significance of specific mitochondrial mutations in cancer and disease progression. This review offers some insight into the extent of mtDNA mutations, their functional consequences in tumorigenesis, mitochondrial therapeutics, and future clinical application. Cancer Prev Res; 4(5); 638–54. ©2011 AACR.
A Randomized Placebo-Controlled Prevention Trial of Aspirin and/or Resistant Starch in Young People with Familial Adenomatous Polyposis
Authors: Burn John , Bishop D. Timothy , Chapman Pamela D. , Elliott Faye , Bertario Lucio , Dunlop Malcolm G. , Eccles Diana , Ellis Anthony , Evans D. Gareth , Fodde Riccardo , Maher Eamonn R. , Möslein Gabriela , Vasen Hans F. A. , Coaker Julie , Phillips Robin K. S. , Bülow Steffen , Mathers John C. 
Published: May 2011

Abstract
Evidence supporting aspirin and resistant starch (RS) for colorectal cancer prevention comes from epidemiologic and laboratory studies (aspirin and RS) and randomized controlled clinical trials (aspirin). Familial adenomatous polyposis (FAP) strikes young people and, untreated, confers virtually a 100% risk of colorectal cancer and early death. We conducted an international, multicenter, randomized, placebo-controlled trial of aspirin (600 mg/d) and/or RS (30 g/d) for from 1 to 12 years to prevent disease progression in FAP patients from 10 to 21 years of age. In a 2 × 2 factorial design, patients were randomly assigned to the following four study arms: aspirin plus RS placebo; RS plus aspirin placebo; aspirin plus RS; RS placebo plus aspirin placebo; they were followed with standard annual clinical examinations including endoscopy. The primary endpoint was polyp number in the rectum and sigmoid colon (at the end of intervention), and the major secondary endpoint was size of the largest polyp. A total of 206 randomized FAP patients commenced intervention, of whom 133 had at least one follow-up endoscopy and were therefore included in the primary analysis. Neither intervention significantly reduced polyp count in the rectum and sigmoid colon: aspirin relative risk = 0.77 (95% CI, 0.54–1.10; versus nonaspirin arms); RS relative risk = 1.05 (95% CI, 0.73–1.49; versus non-RS arms). There was a trend toward a smaller size of largest polyp in patients treated with aspirin versus nonaspirin—mean 3.8 mm versus 5.5 mm for patients treated 1 or more years (adjusted P = 0.09) and mean 3.0 mm versus 6.0 mm for patients treated more than 1 year (P = 0.02); there were similar weaker trends with RS versus non-RS. Exploratory translational endpoints included crypt length (which was significantly shorter in normal-appearing mucosa in the RS group over time) and laboratory measures of proliferation (including Ki67). This clinical trial is the largest ever conducted in the setting of FAP and found a trend of reduced polyp load (number and size) with 600 mg of aspirin daily. RS had no clinical effect on adenomas. Cancer Prev Res; 4(5); 655–65. ©2011 AACR.