bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determination of Posaconazole Levels in Toenails of Adults with Onychomycosis following Oral Treatment with Four Regimens of Posaconazole for 12 or 24 Weeks
Authors: Krishna Gopal , Ma Lei , Martinho Monika , Prasad Pratapa , Wahl Janice , Tavakkol Amir 
Published: July 2011

ABSTRACT

Pharmacokinetic data from a randomized, parallel-group, multicenter study are presented. Adults with toenail onychomycosis (
n
= 146) received posaconazole (100 mg, 200 mg, or 400 mg) once daily (QD) for 24 weeks or 400 mg QD for 12 weeks. The posaconazole concentration in the great toenail exhibited a dose-related increase starting at week 2 for 24 weeks and a mean toenail-to-plasma concentration ratio of approximately 3:1 at the end of treatment for the 400-mg 24-week dose.
Emergence of Ertapenem Resistance in an Escherichia coli Clinical Isolate Producing Extended-Spectrum β-Lactamase AmpC
Authors: Guillon Hélène , Tande Didier , Mammeri Hedi 
Published: July 2011

ABSTRACT

Escherichia coli
isolate MEV, responsible for a bloodstream infection, was resistant to penicillins, cephalosporins, and ertapenem. Molecular and biochemical characterization revealed the production of a novel, chromosome-borne, extended-spectrum AmpC (ESAC) β-lactamase with a Ser-282 duplication and increased carbapenemase activity. This study demonstrates for the first time that chromosome-borne ESAC β-lactamases can contribute to the emergence of ertapenem resistance in
E. coli
clinical isolates.
Attaching and Effacing Bacterial Effector NleC Suppresses Epithelial Inflammatory Responses by Inhibiting NF-κB and p38 Mitogen-Activated Protein Kinase Activation
Authors: Sham Ho Pan , Shames Stephanie R. , Croxen Matthew A. , Ma Caixia , Chan Justin M. , Khan Mohammed A. , Wickham Mark E. , Deng Wanyin , Finlay B. Brett , Vallance Bruce A. 
Published: July 2011

ABSTRACT

Enteropathogenic
Escherichia coli
(EPEC) and enterohemorrhagic
E. coli
are noninvasive attaching and effacing (A/E) bacterial pathogens that cause intestinal inflammation and severe diarrheal disease. These pathogens utilize a type III secretion system to deliver effector proteins into host epithelial cells, modulating diverse cellular functions, including the release of the chemokine interleukin-8 (IL-8). While studies have implicated the effectors NleE (non-locus of enterocyte effacement [LEE]-encoded effector E) and NleH1 in suppressing IL-8 release, by preventing NF-κB nuclear translocation, the impact of these effectors only partially replicates the immunosuppressive actions of wild-type EPEC, suggesting another effector or effectors are involved. Testing an array of EPEC mutants, we identified the non-LEE-encoded effector C (NleC) as also suppressing IL-8 release. Infection by Δ
nleC
EPEC led to exaggerated IL-8 release from infected Caco-2 and HT-29 epithelial cells. NleC localized to EPEC-induced pedestals, with signaling studies revealing NleC inhibits both NF-κB and p38 mitogen-activated protein kinase (MAPK) activation. Using
Citrobacter rodentium
, a mouse-adapted A/E bacterium, we found that Δ
nleC
and wild-type
C. rodentium
-infected mice carried similar pathogen burdens, yet Δ
nleC
strain infection led to worsened colitis. Similarly, infection with Δ
nleC
C. rodentium
in a cecal loop model induced significantly greater chemokine responses than infection with wild-type bacteria. These studies thus advance our understanding of how A/E pathogens subvert host inflammatory responses.
Increased Survival and Reduced Neutrophil Infiltration of the Liver in Rab27a- but Not Munc13-4-Deficient Mice in Lipopolysaccharide-Induced Systemic Inflammation
Authors: Johnson Jennifer L. , Hong Hong , Monfregola Jlenia , Catz Sergio D. 
Published: July 2011

ABSTRACTGenetic defects in theRab27aorMunc13-4gene lead to immunodeficiencies in humans, characterized by frequent viral and bacterial infections. However, the role of Rab27a and Munc13-4 in the regulation of systemic inflammation initiated by Gram-negative bacterium-derived pathogenic molecules is currently unknown. Using a model of lipopolysaccharide-induced systemic inflammation, we show that Rab27a-deficient (Rab27aash/ash) mice are resistant to lipopolysaccharide (LPS)-induced death, while Munc13-4-deficient (Munc13-4jinx/jinx) mice show only moderate protection. Rab27aash/ashbut not Munc13-4jinx/jinxmice showed significantly decreased tumor necrosis factor alpha (TNF-α) plasma levels after LPS administration. Neutrophil sequestration in lungs from Rab27aash/ashand Munc13-4jinx/jinxLPS-treated mice was similar to that observed for wild-type mice. In contrast, Rab27a- but not Munc13-4-deficient mice showed decreased neutrophil infiltration in liver and failed to undergo LPS-induced neutropenia. Decreased liver infiltration in Rab27aash/ashmice was accompanied by lower CD44 but normal CD11a and CD11b expression in neutrophils. Both Rab27a- and Munc13-4-deficient mice showed decreased azurophilic granule secretionin vivo, suggesting that impaired liver infiltration and improved survival in Rab27aash/ashmice is not fully explained by deficient exocytosis of this granule subset. Altogether, our data indicate that Rab27a but not Munc13-4 plays an important role in neutrophil recruitment to liver and LPS-induced death during endotoxemia, thus highlighting a previously unrecognized role for Rab27a in LPS-mediated systemic inflammation.
Contribution of a Streptococcus mutans Antigen Expressed by a Salmonella Vector Vaccine in Dendritic Cell Activation
Authors: Xu Qingan , Katz Jenny , Zhang Ping , Ashtekar Amit R. , Gaddis Dalia E. , Fan Mingwen , Michalek Suzanne M. 
Published: July 2011

ABSTRACTASalmonellavector vaccine expressing the saliva-binding region (SBR) of the adhesin AgI/II ofStreptococcus mutanshas been shown to induce a mixed Th1/Th2 anti-SBR immune response in mice and to require Toll-like receptor 2 (TLR2), TLR4, and MyD88 signaling for the induction of mucosal anti-SBR antibody responses. Since dendritic cells (DC) are critical in innate and adaptive immunity, the present study assessed the role of SBR expression by the vector vaccine in DC activation. Bone marrow-derived DC from wild-type and TLR2, TLR4, and MyD88 knockout mice were stimulated withSalmonellavector BRD509, the SBR-expressingSalmonellavector vaccine BRD509(pSBRT7), or SBR protein, and the DC responses to different stimuli were compared by assessing costimulatory molecule expression, cytokine production, and signaling pathways. The DC response to both BRD509(pSBRT7) and BRD509 was dependent mainly on TLR4. BRD509(pSBRT7) and BRD509 induced upregulation of CD80, CD86, CD40, and major histocompatibility complex class II (MHC II) expression. Lower levels of interleukin-10 (IL-10) and IL-12p40 were produced by BRD509(pSBRT7)-stimulated DC than by BRD509-stimulated DC. Furthermore, BRD509(pSBRT7)-stimulated DC showed decreased p38 phosphorylation compared to that induced by DC stimulated with BRD509. However, BRD509(pSBRT7)-treated DC produced a higher level of IL-6 than BRD509-stimulated cells. The low IL-12p40 and high IL-6 cytokine profile expressed by BRD509(pSBRT7)-stimulated DC may represent a shift toward a Th2 response, as suggested by the increased expression in Jagged-1. These results provide novel evidence that a heterologous protein expressed by aSalmonellavector vaccine can differentially affect DC activation.
Looking for the Mojave-Sonora megashear in northeastern Mexico
Authors: Gray Gary G. , Lawton Timothy F. , Murphy Justin J. 
Published: July 2011

Abstract
Basement outcrops are rare in northeastern Mexico, but the effect of older basement structures on the current structural plan is clear. Two large structures, the San Marcos fault and the northern edge of the Sierra Madre Oriental, are oriented roughly east-west, and have been postulated as sites of the Mojave-Sonora megashear. Both structures were probably active in the late Jurassic. The San Marcos fault continued to be active into the Cretaceous, while the northern edge of the Sierra Madre Oriental became inactive. Both structures were strongly reactivated during the Laramide orogeny. Potential fields data integrated with regional geologic mapping suggests a series of horsts and grabens were created during Middle-Late Jurassic rifting of the basement, but that relative displacements are far less than those proposed for the Mojave-Sonora megashear system. The northern edge of the Sierra Madre Oriental, with its large left-step along the Monterrey salient, is kinematically more compatible with the postulated left-lateral offset along the Mojave-Sonora megashear, while the San Marcos fault has numerous right-stepping offsets, which is kinematically incom-patible with the Mojave-Sonora megashear hypothesis. In general, however, these data do not support the concept of a large-offset left-lateral megashear in northeastern Mexico.
Tropical cyclone development, structure, and impact on the Louisiana-Texas coast
Authors: Ashmore Richard A. 
Published: July 2011

Abstract
Each year from June through November, tropical cyclones are a common potential problem for those living in coastal communities along the southwest Louisiana and southeast Texas coasts. Developing from small tropical disturbances, tropical cyclone strength is determined by many factors: ocean temperature, upper and lower wind circulation, latitudinal position, etc. Ecological, geological, and economic effects of strong-to-devastating tropical cyclones on coastal areas are typically extreme. Since the 1860s, seven strong or greater tropical cyclones have struck the Louisiana-Texas coast. Their impact has made an indelible impression on the coastline as well as on the communities in the area
Chenier Plain road log
Authors: Ashmore Richard A. , Owen Donald E. 
Published: July 2011

Abstract
Each year from June through November, tropical cyclones are a common potential problem for those living in coastal communities along the southwest Louisiana and southeast Texas coasts. Developing from small tropical disturbances, tropical cyclone strength is determined by many factors: ocean temperature, upper and lower wind circulation, latitudinal position, etc. Ecological, geological, and economic effects of strong-to-devastating tropical cyclones on coastal areas are typically extreme. Since the 1860s, seven strong or greater tropical cyclones have struck the Louisiana-Texas coast. Their impact has made an indelible impression on the coastline as well as on the communities in the area
New investigations of Pleistocene glacial and pluvial records in northeastern Nevada
Authors: Munroe Jeffrey S. , Laabs Benjamin J.C. 
Published: July 2011

Abstract
The Great Basin of the western United States offers tremendous potential for exploring the response of mountain glaciers and lowland lakes to climate changes during the Last Glacial Maximum (LGM, MIS-2, ca. 22–18 ka B.P.) and subsequent glacial-interglacial transition. The combination of well-distributed alpine moraine records and pluvial lake deposits offers an unparalleled opportunity to develop a more precise understanding of temperature and precipitation changes during the latest Pleistocene and into the Holocene. This field trip provides an overview of recent and ongoing work illuminating aspects of the glacial and pluvial history of northeastern Nevada from the LGM to the present. The route of this trip involves three full days of stops separated by two nights in Elko, Nevada. The first day focuses on glacial deposits at the type locality for the LGM Angel Lake Glaciation on the eastern side of the East Humboldt Range. The second day explores the geomorphic record of pluvial Lakes Franklin and Clover on the east side of the Ruby–East Humboldt Mountains and describes recent efforts to develop a chronology for the late Pleistocene regression of these lakes. The final day again focuses on glacial geology, starting with the type locality of the pre-LGM Lamoille Glaciation on the west side of the Ruby Mountains, and ending with several stops along the scenic drive up Lamoille Canyon.
Tectonomagmatic evolution of distinct arc terranes in the Blue Mountains Province, Oregon and Idaho
Authors: Northrup C.J. , Schmitz M. , Kurz G. , Tumpane K. 
Published: July 2011

Abstract
Recent mapping, U-Pb zircon geochronology, trace-element geochemistry, and tracer isotope geochemistry of plutonic and volcanic rocks in the Wallowa and Olds Ferry terranes of the Blue Mountains Province yield new insights into their tectonic evolution and pre-accretion history. Igneous rocks of the Wallowa arc terrane formed in two magmatic episodes of contrasting duration and geochemical characteristics. Magmatism in the first episode lasted for at least 20 Ma (ca. 268–248 Ma), spanning the Middle Permian to the Early Triassic and was of generally calc-alkaline affinity. Rock units associated with this episode include the Hunsaker Creek and Windy Ridge formations of the Wallowa terrane, as well as potentially equivalent tonalite and diorite plutonic rocks in the Cougar Creek Complex and related basement exposures, which show midcrustal levels of the terrane. The second episode of magmatism in the Wallowa arc was remarkably brief (U-Pb zircon dates range from 229.43 ± 0.08 Ma to 229.13 ± 0.45 Ma) and dominated by mafic to intermediate compositions of tholeiitic affinity. Rock units associated with the second episode may include the Wild Sheep Creek and Doyle Creek formations, as well as ubiquitous dikes and plutons in the Cougar Creek Complex and similar basement exposures. After 229 Ma, the Wallowa arc apparently became dormant.
The record of igneous activity in the Olds Ferry arc contrasts with that of the Wallowa in its age range and the continuity of calc-alkaline magmatism. Radiometric ages and stratigraphic field relationships allow the magmatic history of the Olds Ferry terrane to be divided into at least three cycles separated by brief hiatuses and collectively spanning the late Middle Triassic through the Early Jurassic (ca. 237– 187 Ma). Rock units related to these episodes are divided by unconformities, and they include the Brownlee pluton, lower Huntington Formation, and upper Huntington Formation. Magmatic activity in the Olds Ferry arc may have persisted until at least 174 Ma, based on the presence of volcanic ash horizons in the lower portion of the overlying Weatherby Formation of the Izee basin. All cycles of Olds Ferry magmatism display generally calc-alkaline affinity.
The contrasting magmatic histories of the Wallowa and Olds Ferry arc terranes provide the basis for at least two conclusions. First, these arcs formed as separate tectonic entities, rather than as a single composite arc. Second, progressive closure of the ocean basin between the arcs in the Late Triassic and Early Jurassic was related to continued subduction beneath the Olds Ferry arc, but the Wallowa arc was apparently dormant during much of that interval.
Paleontology and stratigraphy of middle Eocene rock units in the Bridger and Uinta Basins, Wyoming and Utah
Authors: Murphey Paul C. , Townsend K.E. Beth , Friscia Anthony R. , Evanoff Emmett 
Published: July 2011

Abstract
The Bridger Formation is located in the Green River basin in southwest Wyoming, and the Uinta and Duchesne River formations are located in the Uinta basin in Utah. These three rock units and their diverse fossil assemblages have great scientific importance and are also of historic interest to vertebrate paleontologists. Notably, they are also the stratotypes for the three middle Eocene North American Land Mammal “Ages,” the Bridgerian, Uintan, and Duchesnean, from oldest to youngest. The fossils and sediments of these formations provide a critically important record of biotic, environmental, and climatic history spanning ~10 million years (49–39 Ma). This article features a detailed field excursion through portions of the Green River and Uinta basins that focuses on locations of geologic, paleontologic, and historical interest. In support of the field excursion, we also provide a review of current knowledge of these formations with emphasis on lithostratigraphy, biochronology, depositional and paleoenvironmental history, and the history of scientific exploration.
Blocking Hedgehog Survival Signaling at the Level of the GLI Genes Induces DNA Damage and Extensive Cell Death in Human Colon Carcinoma Cells
Authors: Mazumdar Tapati , DeVecchio Jennifer , Agyeman Akwasi , Shi Ting , Houghton Janet A. 
Published: July 2011

Abstract
Canonical Hedgehog (HH) signaling is characterized by Smoothened (Smo)-dependent activation of the transcription factors Gli1 and Gli2, which regulate HH target genes. In human colon carcinoma cells, treatment with the Gli small-molecule inhibitor GANT61 induces extensive cell death in contrast to the Smo inhibitor cyclopamine. Here we elucidate cellular events upstream of cell death elicited by GANT61, which reveal the basis for its unique cytotoxic activity in colon carcinoma cells. Unlike cyclopamine, GANT61 induced transient cellular accumulation at G1–S (24 hours) and in early S-phase (32 hours), with elevated p21Cip1, cyclin E, and cyclin A in HT29 cells. GANT61 induced DNA damage within 24 hours, with the appearance of p-ATM and p-Chk2. Pharmacologic inhibition of Gli1 and Gli2 by GANT61 or genetic inhibition by transient transfection of the Gli3 repressor (Gli3R) downregulated Gli1 and Gli2 expression and induced γH2AX, PARP cleavage, caspase-3 activation, and cell death. GANT61 induced γH2AX nuclear foci, while transient transfection of Gli3R showed expression of Gli3R and γH2AX foci within the same nuclei in HT29, SW480, and HCT116. GANT61 specifically targeted Gli1 and Gli2 substantiated by specific inhibition of (i) direct binding of Gli1 and Gli2 to the promoters of target genes HIP1 and BCL-2, (ii) Gli-luciferase activity, and (iii) transcriptional activation of BCL-2. Taken together, these findings establish that inhibition of HH signaling at the level of the GLI genes downstream of Smo is critical in the induction of DNA damage in early S-phase, leading to cell death in human colon carcinoma cells. Cancer Res; 71(17); 5904–14. ©2011 AACR.
Iron Overload Decreases Ca
V
1.3-Dependent L-Type Ca
2+
Currents Leading to Bradycardia, Altered Electrical Conduction, and Atrial Fibrillation
Authors: Rose Robert A. , Sellan Michael , Simpson Jeremy A. , Izaddoustdar Farzad , Cifelli Carlo , Panama Brian K. , Davis Mark , Zhao Dongling , Markhani Moniba , Murphy Geoffrey G. , Striessnig Joerg , Liu Peter P. , Heximer Scott P. , Backx Peter H. 
Published: July 2011

Background—
Chronic iron overload (CIO) is associated with blood disorders such as thalassemias and hemochromatosis. A major prognostic indicator of survival in patients with CIO is iron-mediated cardiomyopathy characterized by contractile dysfunction and electrical disturbances, including slow heart rate (bradycardia) and heart block.

Methods and Results—

We used a mouse model of CIO to investigate the effects of iron on sinoatrial node (SAN) function. As in humans, CIO reduced heart rate (≈20%) in conscious mice as well as in anesthetized mice with autonomic nervous system blockade and in isolated Langendorff-perfused mouse hearts, suggesting that bradycardia originates from altered intrinsic SAN pacemaker function. Indeed, spontaneous action potential frequencies in SAN myocytes with CIO were reduced in association with decreased L-type Ca
2+
current (I
Ca,L
) densities and positive (rightward) voltage shifts in I
Ca,L
activation. Pacemaker current (I
f
) was not affected by CIO. Because I
Ca,L
in SAN myocytes (as well as in atrial and conducting system myocytes) activates at relatively negative potentials due to the presence of Ca
V
1.3 channels (in addition to Ca
V
1.2 channels), our data suggest that elevated iron preferentially suppresses Ca
V
1.3 channel function. Consistent with this suggestion, CIO reduced Ca
V
1.3 mRNA levels by ≈40% in atrial tissue (containing SAN) and did not lower heart rate in Ca
V
1.3 knockout mice. CIO also induced PR-interval prolongation, heart block, and atrial fibrillation, conditions also seen in Ca
V
1.3 knockout mice.

Conclusions—

Our results demonstrate that CIO selectively reduces Ca
V
1.3-mediated I
Ca,L
, leading to bradycardia, slowing of electrical conduction, and atrial fibrillation as seen in patients with iron overload.
Success of Ablation for Atrial Fibrillation in Isolated Left Ventricular Diastolic Dysfunction
Authors: Cha Yong-Mei , Wokhlu Anita , Asirvatham Samuel J. , Shen Win-Kuang , Friedman Paul A. , Munger Thomas M. , Oh Jae K. , Monahan Kristi H. , Haroldson Janis M. , Hodge David O. , Herges Regina M. , Hammill Stephen C. , Packer Douglas L. 
Published: July 2011

Background—
The efficacy of radiofrequency ablation for atrial fibrillation (AF) in patients with left ventricular (LV) systolic dysfunction and isolated diastolic dysfunction is uncertain.

Methods and Results—

A prospective cohort of patients with normal and abnormal LV function underwent ablation for antiarrhythmic drug (AAD)-refractory AF. Three groups were compared: 111 patients with systolic dysfunction, defined as LV ejection fraction (LVEF) ≤40%; 157 patients with isolated diastolic dysfunction but preserved LVEF ≥50%; and 100 patients with normal LV function. The primary end point was AAD-free AF elimination at 1 year after ablation. This end point was achieved in 62% of patients with systolic dysfunction, 75% of those with diastolic dysfunction, and 84% of controls (
P
=0.007). AF control on or off AADs was achieved in 76% of patients with systolic dysfunction, 85% of those with diastolic dysfunction, and 89% of controls (
P
=0.08). In the systolic dysfunction group, 49% experienced an increase in LVEF by ≥5% after ablation, of which 64% achieved normal LVEF. In the diastolic dysfunction group, 30% of patients demonstrated at least 1 grade improvement in diastolic dysfunction. Multivariable analysis demonstrated an increased relative risk of arrhythmia recurrence of 1.8 (95% CI, 1.1 to 3.1;
P
=0.02) in systolic dysfunction and 1.7 (1.0 to 2.7;
P
=0.04) in isolated diastolic dysfunction compared with normal function.

Conclusions—
Although an ablative approach for AF in patients with systolic or diastolic dysfunction is associated with an increased long-term recurrence risk, there is potential for substantial quality-of-life improvement and LV functional benefit.
Physical Fidelity Versus Cognitive Fidelity Training in Procedural Skills Acquisition
Authors: Hochmitz Ilanit , Yuviler-Gavish Nirit 
Published: July 2011

Objective: The current study examined whether training simulators for the acquisition of procedural skills should emphasize physical fidelity or cognitive fidelity of the task. Background: Simulation-based training for acquiring and practicing procedural skills is becoming widely established. Generally speaking, these simulators offer technological sophistication but disregard theory-based design, leaving unanswered the question of what task features should be represented in the simulators. The authors compared real-world training and two alternative virtual trainers, one emphasizing physical fidelity and the other cognitive fidelity of the task. Method: Participants were randomly assigned to one of four training groups in a LEGO® assembly task: virtual-physical fidelity, cognitive fidelity, real world, and control. A posttraining test to assess the development of procedural skills was conducted. Results: Both the virtual-physical fidelity and cognitive fidelity training methods produced better performance time than no training at all, as did the real-world training. The cognitive fidelity training was inferior in terms of test time compared to the real-world training, whereas the virtual-physical fidelity training was not. In contrast, only the real-world and the cognitive fidelity groups, and not the virtual-physical fidelity group, required significantly less time than the control group for error correction. Conclusion: The two training methods have complementary advantages. Application: Combining physical fidelity and cognitive training methods can enhance procedural skills acquisition when real-world training is not practicable.