bluuebunny/crossref_metadata_2025_split huggingface dataset:
Francisella tularensisSchu S4 O-Antigen and Capsule Biosynthesis Gene Mutants Induce Early Cell Death in Human Macrophages
Authors: Lindemann Stephen R. , Peng Kaitian , Long Matthew E. , Hunt Jason R. , Apicella Michael A. , Monack Denise M. , Allen Lee-Ann H. , Jones Bradley D. 
Published: November 2010

ABSTRACTFrancisella tularensisis capable of rampant intracellular growth and causes a potentially fatal disease in humans. Whereas many mutational studies have been performed with avirulent strains ofFrancisella, relatively little has been done with strains that cause human disease. We generated a near-saturating transposon library in the virulent strain Schu S4, which was subjected to high-throughput screening by transposon site hybridization through primary human macrophages, negatively selecting 202 genes. Of special note were genes in a locus of theFrancisellachromosome,FTT1236,FTT1237, andFTT1238. Mutants with mutations in these genes demonstrated significant sensitivity to complement-mediated lysis compared with wild-type Schu S4 and exhibited marked defects in O-antigen and capsular polysaccharide biosynthesis. In the absence of complement, these mutants were phagocytosed more efficiently by macrophages than wild-type Schu S4 and were capable of phagosomal escape but exhibited reduced intracellular growth. Microscopic and quantitative analyses of macrophages infected with mutant bacteria revealed that these macrophages exhibited signs of cell death much earlier than those infected with Schu S4. These data suggest thatFTT1236,FTT1237, andFTT1238are important for polysaccharide biosynthesis and that theFrancisellaO antigen, capsule, or both are important for avoiding the early induction of macrophage death and the destruction of the replicative niche.
CsrA Modulates Levels of Lipoproteins and Key Regulators of Gene Expression Critical for Pathogenic Mechanisms of
Borrelia burgdorferi
Authors: Karna S. L. Rajasekhar , Sanjuan Eva , Esteve-Gassent Maria D. , Miller Christine L. , Maruskova Mahulena , Seshu J. 
Published: November 2010

ABSTRACT

Carbon storage regulator A (CsrA) is an RNA binding protein that has been characterized in many bacterial species to play a central regulatory role by modulating several metabolic processes. We recently showed that a homolog of CsrA in
Borrelia burgdorferi
(CsrA
Bb
, BB0184) was upregulated in response to propagation of
B. burgdorferi
under mammalian host-specific conditions. In order to further delineate the role of CsrA
Bb
, we generated a deletion mutant designated ES10 in a linear plasmid 25-negative isolate of
B. burgdorferi
strain B31 (ML23). The deletion mutant was screened by PCR and Southern blot hybridization, and a lack of synthesis of CsrA
Bb
in ES10 was confirmed by immunoblot analysis. Analysis of ES10 propagated at pH 6.8/37°C revealed a significant reduction in the levels of OspC, DbpA, BBK32, and BBA64 compared to those for the parental wild-type strain propagated under these conditions, while there were no significant changes in the levels of either OspA or P66. Moreover, the levels of two regulatory proteins, RpoS and BosR, were also found to be lower in ES10 than in the control strain. Quantitative real-time reverse transcription-PCR analysis of total RNA extracted from the parental strain and

csrA
Bb

mutant revealed significant differences in gene expression consistent with the changes at the protein level. Neither the

csrA
Bb

mutant nor the
trans
-complemented strain was capable of infection following intradermal needle inoculation in C3H/HeN mice at either 10
3
or 10
5
spirochetes per mouse. The further characterization of molecular basis of regulation mediated by CsrA
Bb
will provide significant insights into the pathophysiology of
B. burgdorferi.
EMPTY INTERIOR RECURRENCE FOR CONTINUOUS FLOWS ON SURFACES
Authors: LÓPEZ VÍCTOR JIMÉNEZ , LÓPEZ GABRIEL SOLER 
Published: November 2010

In this paper we characterize topologically the empty interior subsets of a compact surface S which can be ω-limit sets of recurrent orbits (but not of nonrecurrent ones) of continuous flows on S. This culminates the classification of ω-limit sets for surface flows initiated in [Jiménez & Soler, 2001; Soler, 2003; Jiménez & Soler, 2004a, 2004b].We also show that this type of ω-limit sets can always be realized (up to topological equivalence) by smooth flows but cannot be realized by analytic flows.
Oxygen-isotope dating the Yilgarn regolith
Authors: Chivas Allan. R. , Atlhopheng Julius. R. 
Published: November 2010

Abstract

The broad-scale distribution of δ
18
O values of kaolinite developed in weathering profiles in the Yilgarn Craton is interpreted as reflecting their age. As Australia progressively moved from a near-polar latitude in the Permian to lower latitude, with most translation during the past 60 Ma, the imprint of varying oxygen-isotope composition of meteoric water (rainwater and groundwater) has been preserved in weathering minerals such as clays and iron oxides. This correlation, namely δ
18
O values of kaolinite v. palaeo-latitude (and therefore, age), is well understood for eastern Australia. We have applied the same approach to samples widely spaced across the entire Yilgarn Craton and find that kaolinite from the majority of partially dissected weathering profiles displays Neogene δ
18
O ages. There are older profiles, some seemingly of pre-late Mesozoic age, and these are predominantly in the north and east of the craton. There is no evidence within the δ
18
O-derived age pattern for a northern older plateau and a younger southern plateau, at least in terms of their primary age of deep weathering as equated to planation. Instead, the difference between northern and southern areas is that the southern area is more dissected and displays more deeply stripped weathering profiles.
A theory (involving tropical cyclones) on the formation of coarse-grained sand beach ridges in NE Australia
Authors: Nott Jonathan 
Published: November 2010

Abstract
A theory is presented that coarse-grained sand beach ridge plains in northeastern Australia have developed their final form (i.e. the height of the ridges above sea level) as a result of marine inundations generated by intense tropical cyclones. Although winds generated during such tempests are of more than sufficient velocity to transport coarse-grained sands the beach is typically inundated by the storm surge and waves during these events and hence there is no viable source for aeolian sand transport. Numerical storm surge and shallow water wave models are run for two sites (Cairns and Cowley Beach) and the results indicate that only wave run-ups generated by category 3 or more intense tropical cyclones can deposit the final units of sediment onto the sand beach ridges at these locations. It is suggested that as a sand beach ridge increases in height, via successive deposition of units of sand, progressively higher marine inundations are required to reach the ridge crest. The final height of the sand beach ridge is dependent upon the interplay of sediment supply rates to the coastal system and the intensity and frequency of tropical cyclones. If tropical cyclones are responsible for the final form of the sand beach ridges then these sequences can be used to assess the long-term climatology of intense tropical cyclones over this broad geographical region.
Sheltered sandy beaches of southwestern Australia
Authors: Travers A. , Eliot M. J. , Eliot I. G. , Jendrzejczak M. 
Published: November 2010

AbstractFour beach types were identified from field surveys of beach profiles on low-energy sandy beaches in Cockburn Sound, a micro-tidal, semi-enclosed basin in southwestern Australia. These were delineated by an exposure factor (Ef), which provided a surrogate for the relationship between incident wave energy and attenuation as a result of structures, banks and shoals. The four beach profiles identified were exponential, segmented, concave-curvilinear and convex-curvilinear in form. Whether the different profile shapes occurred in environments subject to different degrees of sheltering and protection under the same tidal regime was open to question. Beach profiles were examined for Como Beach and Princess Royal Harbour in Western Australia and compared with observations from Cockburn Sound to test this proposition. Cockburn Sound and Princess Royal Harbour are subject to minimal penetration of swell waves whereas Como Beach, in the Swan River Estuary, is wholly fetch limited. Profile forms identified in each environment were consistent with those described from Cockburn Sound. Similar profile types had similar exposure values for all sites such that Ef<1 was characteristic of exponential profiles, 1–1.5 of segmented, 1.5–2 of concave-curvilinear, and Ef>2 of convex-curvilinear. Although this approach requires further testing in low-energy environments subject to different tidal ranges and fluctuations in sea level, use of the exposure factor for delineation of low-energy sheltered beach types appears to be a robust procedure.
The Australian desert dunefields: formation and evolution in an old, flat, dry continent
Authors: Hesse Paul P. 
Published: November 2010

Abstract
A new map, the first based on interpretation of satellite imagery, reveals both the complexity of Australia's dunefields and their relationships with topography, climate and substrate. Of the five main sand seas, the Mallee, Strzelecki and Simpson in eastern Australia cover Quaternary sedimentary basins whereas the Great Victoria and Great Sandy dunefields in the west are formed by reworking of valley and piedmont sediments in a non-basinal landscape of low-relief ridge and valley topography. These dunefields cover large areas of the arid zone and semi-arid zone and small areas of dunes in sub-humid areas around the margins of the continent reflecting past expansion of arid climates during glacial stages of the last several glacial cycles. Several areas of low relief stand out as being largely dune-free: the limestone Nullarbor Plain, clay plains of the Georgina Basin and floodplains of rivers in the Carpentaria, Lake Eyre and Murray–Darling drainage basins where sand is rare or not transported by diminished Late Quaternary rivers. The Yilgarn Block of southwestern Australia is also surprisingly free of dunes, possibly as a result of long, deep weathering. Everywhere the history of climate change is evident in dune morphology and distribution, including large areas where the sand dune orientations are markedly divergent from modern sand moving wind directions.
Intracoronary Versus Intravenous Administration of Abciximab in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention With Thrombus Aspiration
Authors: Gu Youlan L. , Kampinga Marthe A. , Wieringa Wouter G. , Fokkema Marieke L. , Nijsten Maarten W. , Hillege Hans L. , van den Heuvel Ad F.M. , Tan Eng-Shiong , Pundziute Gabija , van der Werf Rik , Hoseyni Guyomi Siyrous , van der Horst Iwan C.C. , Zijlstra Felix , de Smet Bart J.G.L. 
Published: November 2010

Background—
Administration of the glycoprotein IIb/IIIa inhibitor abciximab is an effective adjunctive treatment strategy during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Although small-scale studies have suggested beneficial effects of intracoronary over intravenous administration of abciximab, this has not been investigated in a medium-scale randomized clinical trial.

Methods and Results—

A total of 534 ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention with thrombus aspiration within 12 hours of symptom onset were randomized to either an intracoronary or an intravenous bolus of abciximab (0.25 mg/kg). Patients were pretreated with aspirin, heparin, and clopidogrel. The primary end point was the incidence of restored myocardial reperfusion, defined as complete ST-segment resolution. Secondary end points included myocardial reperfusion as assessed by myocardial blush grade, enzymatic infarct size, and major adverse cardiac events at 30 days. The incidence of complete ST-segment resolution was similar in the intracoronary and intravenous groups (64% versus 62%;
P
=0.562). However, the incidence of myocardial blush grade 2/3 was higher in the intracoronary group than in the intravenous group (76% versus 67%;
P
=0.022). Furthermore, enzymatic infarct size was smaller in the intracoronary than in the intravenous group (
P
=0.008). The incidence of major adverse cardiac events was similar in both groups (5.5% versus 6.1%;
P
=0.786).

Conclusions—
In ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention with thrombus aspiration, intracoronary administration of abciximab compared with intravenous administration does not improve myocardial reperfusion as assessed by ST-segment resolution. However, intracoronary administration is associated with improved myocardial reperfusion as assessed by myocardial blush grade and a smaller enzymatic infarct size.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00927615.
Novel Chemical Suppressors of Long QT Syndrome Identified by an In Vivo Functional Screen
Authors: Peal David S. , Mills Robert W. , Lynch Stacey N. , Mosley Janet M. , Lim Evi , Ellinor Patrick T. , January Craig T. , Peterson Randall T. , Milan David J. 
Published: November 2010

Background—

Genetic long QT (LQT) syndrome is a life-threatening disorder caused by mutations that result in prolongation of cardiac repolarization. Recent work has demonstrated that a zebrafish model of LQT syndrome faithfully recapitulates several features of human disease, including prolongation of ventricular action potential duration, spontaneous early afterdepolarizations, and 2:1 atrioventricular block in early stages of development. Because of their transparency, small size, and absorption of small molecules from their environment, zebrafish are amenable to high-throughput chemical screens. We describe a small-molecule screen using the zebrafish
KCNH2
mutant
breakdance
to identify compounds that can rescue the LQT type 2 phenotype.

Methods and Results—

Zebrafish
breakdance
embryos were exposed to test compounds at 48 hours of development and scored for rescue of 2:1 atrioventricular block at 72 hours in a 96-well format. Only compounds that suppressed the LQT phenotype in 3 of 3 fish were considered hits. Screen compounds were obtained from commercially available small-molecule libraries (Prestwick and Chembridge). Initial hits were confirmed with dose-response testing and time-course studies. Optical mapping with the voltage-sensitive dye di-4 ANEPPS was performed to measure compound effects on cardiac action potential durations. Screening of 1200 small molecules resulted in the identification of flurandrenolide and 2-methoxy-N-(4-methylphenyl) benzamide (2-MMB) as compounds that reproducibly suppressed the LQT phenotype. Optical mapping confirmed that treatment with each compound caused shortening of ventricular action potential durations. Structure activity studies and steroid receptor knockdown suggest that flurandrenolide functions via the glucocorticoid signaling pathway.

Conclusions—
Using a zebrafish model of LQT type 2 syndrome in a high-throughput chemical screen, we have identified 2 compounds, flurandrenolide and the novel compound 2-MMB, as small molecules that rescue the zebrafish LQT type 2 syndrome by shortening the ventricular action potential duration. We provide evidence that flurandrenolide functions via the glucocorticoid receptor–mediated pathway. These 2 molecules and future discoveries from this screen should yield novel tools for the study of cardiac electrophysiology and may lead to novel therapeutics for human LQT patients.
Cryoablation Versus Radiofrequency Energy for the Ablation of Atrioventricular Nodal Reentrant Tachycardia (the CYRANO Study)
Authors: Deisenhofer Isabel , Zrenner Bernhard , Yin Yue-hui , Pitschner Heinz-Friedrich , Kuniss Malte , Großmann Georg , Stiller Sascha , Luik Armin , Veltmann Christian , Frank Julia , Linner Julia , Estner Heidi L. , Pflaumer Andreas , Wu Jinjin , von Bary Christian , Ücer Ekrem , Reents Tilko , Tzeis Stylianos , Fichtner Stephanie , Kathan Susanne , Karch Martin R. , Jilek Clemens , Ammar Sonia , Kolb Christof , Liu Zeng-Chang , Haller Bernhard , Schmitt Claus , Hessling Gabriele 
Published: November 2010

Background—
Cryoablation has emerged as an alternative to radiofrequency catheter ablation (RFCA) for the treatment of atrioventricular (AV) nodal reentrant tachycardia (AVNRT). The purpose of this prospective randomized study was to test whether cryoablation is as effective as RFCA during both short-term and long-term follow-up with a lower risk of permanent AV block.

Methods and Results—

A total of 509 patients underwent slow pathway cryoablation (n=251) or RFCA (n=258). The primary end point was immediate ablation failure, permanent AV block, and AVNRT recurrence during a 6-month follow-up. Secondary end points included procedural parameters, device functionality, and pain perception. Significantly more patients in the cryoablation group than the RFCA group reached the primary end point (12.6% versus 6.3%;
P
=0.018). Whereas immediate ablation success (96.8% versus 98.4%) and occurrence of permanent AV block (0% versus 0.4%) did not differ, AVNRT recurrence was significantly more frequent in the cryoablation group (9.4% versus 4.4%;
P
=0.029). In the cryoablation group, procedure duration was longer (138±54 versus 123±48 minutes;
P
=0.0012) and more device problems occurred (13 versus 2 patients;
P
=0.033). Pain perception was lower in the cryoablation group (
P
<0.001).

Conclusions—
Cryoablation for AVNRT is as effective as RFCA over the short term but is associated with a higher recurrence rate at the 6-month follow-up. The risk of permanent AV block does not differ significantly between cryoablation and RFCA. The potential benefits of cryoenergy relative to ablation safety and pain perception are counterbalanced by longer procedure times, more device problems, and a high recurrence rate.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00196222.
Evaluation of the Second Generation of a Bioresorbable Everolimus Drug-Eluting Vascular Scaffold for Treatment of De Novo Coronary Artery Stenosis
Authors: Serruys Patrick W. , Onuma Yoshinobu , Ormiston John A. , de Bruyne Bernard , Regar Evelyn , Dudek Dariusz , Thuesen Leif , Smits Pieter C. , Chevalier Bernard , McClean Dougal , Koolen Jacques , Windecker Stephan , Whitbourn Robert , Meredith Ian , Dorange Cécile , Veldhof Susan , Miquel-Hebert Karine , Rapoza Richard , García-García Hector M. 
Published: November 2010

Background—
The first generation of the bioresorbable everolimus drug-eluting vascular scaffold showed signs of shrinkage at 6 months, which largely contributed to late luminal loss. Nevertheless, late luminal loss was less than that observed with bare metal stents. To maintain the mechanical integrity of the device up to 6 months, the scaffold design and manufacturing process of its polymer were modified.

Methods and Results—

Quantitative coronary angiography, intravascular ultrasound with analysis of radiofrequency backscattering, and as an optional assessment, optical coherence tomography (OCT) were performed at baseline and at a 6-month follow-up. Forty-five patients successfully received a single bioresorbable everolimus drug-eluting vascular scaffold. One patient had postprocedural release of myocardial enzyme without Q-wave occurrence; 1 patient with OCT-diagnosed disruption of the scaffold caused by excessive postdilatation was treated 1 month later with a metallic drug-eluting stent. At follow-up, 3 patients declined recatheterization, 42 patients had quantitative coronary angiography, 37 had quantitative intravascular ultrasound, and 25 had OCT. Quantitative coronary angiography disclosed 1 edge restenosis (1 of 42; in-segment binary restenosis, 2.4%). At variance with the ultrasonic changes seen with the first generation of bioresorbable everolimus drug-eluting vascular scaffold at 6 months, the backscattering of the polymeric struts did not decrease over time, the scaffold area was reduced by only 2.0% with intravascular ultrasound, and no change was noted with OCT. On an intention-to-treat basis, the late lumen loss amounted to 0.19±0.18 mm with a limited relative decrease in minimal luminal area of 5.4% on intravascular ultrasound. OCT showed at follow-up that 96.8% of the struts were covered and that malapposition of at least 1 strut, initially observed in 12 scaffolds, was detected at follow-up in only 3 scaffolds. Mean neointimal growth measured by OCT between and on top of the polymeric struts equaled 1.25 mm
2
, or 16.6% of the scaffold area.

Conclusion—
Modified manufacturing process of the polymer and geometric changes in the polymeric platform have substantially improved the medium-term performance of this new generation of drug-eluting scaffold to become comparable to those of current drug eluting stents.

Clinical Trial Registration—

URL:
http://clinicaltrials.gov
. Unique identifier: NCT00856856.
Inhibition of Hyaluronan Synthesis Accelerates Murine Atherosclerosis
Authors: Nagy Nadine , Freudenberger Till , Melchior-Becker Ariane , Röck Katharina , ter Braak Michael , Jastrow Holger , Kinzig Martina , Lucke Susann , Suvorava Tatsiana , Kojda Georg , Weber Artur A. , Sörgel Fritz , Levkau Bodo , Ergün Süleyman , Fischer Jens W. 
Published: November 2010

Background—
Hyaluronan is thought to mediate neointimal hyperplasia but also vasoprotection as an integral component of the endothelial glycocalyx. The present study addressed for the first time the effects of long-term pharmacological inhibition of hyaluronan synthesis on vascular function and atherosclerosis.

Methods and Results—
Four-week-old apolipoprotein E–deficient mice on a Western diet received orally an inhibitor of hyaluronan synthesis, 4-methylumbelliferone (4-MU; 10 mg/g body wt), resulting in 600 nmol/L 4-MU in plasma. As a result, aortic plaque burden was markedly increased at 25 weeks. Furthermore, acetylcholine-dependent relaxation of aortic rings was decreased and mean arterial blood pressure was increased in response to 4-MU. However, hydralazine blunted the hypertensive effect of 4-MU without inhibiting the proatherosclerotic effect. A photothrombosis model revealed a prothrombotic state that was not due to increased platelet activation or increased thrombin activation as monitored by CD62P expression and the endogenous thrombin potential. Importantly, increased recruitment of macrophages to vascular lesions was detected after 2 and 21 weeks of 4-MU treatment by immunohistochemistry, by intravital microscopy, and in a peritonitis model. As a potential underlying mechanism, severe damage of the endothelial glycocalyx after 2 and 21 weeks of treatment with 4-MU was detected by electron microscopy of the innominate artery and myocardial capillaries. Furthermore, 600 nmol/L 4-MU inhibited hyaluronan synthesis in cultured endothelial cells.

Conclusions—
The data suggest that systemic inhibition of hyaluronan synthesis by 4-MU interferes with the protective function of the endothelial glycocalyx, thereby facilitating leukocyte adhesion, subsequent inflammation, and progression of atherosclerosis.