bluuebunny/crossref_metadata_2025_split huggingface dataset:
ThefbpABCOperon Is Required for Ton-Independent Utilization of Xenosiderophores byNeisseria gonorrhoeaeStrain FA19
Authors: Strange Heather R. , Zola Tracey A. , Cornelissen Cynthia Nau 
Published: November 2010

ABSTRACTNeisseria gonorrhoeaeproduces no known siderophores but can employ host-derived, iron-binding proteins, including transferrin and lactoferrin, as iron sources. Given the propensity of this pathogen to hijack rather than synthesize iron-sequestering molecules, we hypothesized that the ability to use siderophores produced by other bacteria, or xenosiderophores, may also play a role in the survival of the gonococcus. Among a panel of diverse siderophores, only the catecholate xenosiderophores enterobactin and salmochelin promoted growth of gonococcal strain FA19. Surprisingly, the internalization pathway was independent of TonB or any of the TonB-dependent transporters. Xenosiderophore-mediated growth was similarly independent of the pilin-extruding secretin formed by PilQ and of the hydrophobic-agent efflux system composed of MtrCDE. ThefbpABCoperon encodes a periplasmic-binding-protein-dependent ABC transport system that enables the gonococcus to transport iron into the cell subsequent to outer membrane translocation. We hypothesized that the FbpABC proteins, required for ferric iron transport from transferrin and lactoferrin, might also contribute to the utilization of xenosiderophores as iron sources. We created mutants that conditionally expressed FbpABC from an IPTG-inducible promoter. We determined that expression of FbpABC was required for growth of gonococcal strain FA19 in the presence of enterobactin and salmochelin. The monomeric component of enterobactin, dihydroxybenzoylserine (DHBS), and the S2 form of salmochelin specifically promoted FbpABC-dependent growth of FA19. This study demonstrated that the gonococcal FbpABC transport system is required for utilization of some xenosiderophores as iron sources and that growth promotion by these ferric siderophores can occur in the absence of TonB or individual TonB-dependent transporters.
Persistence of
Plasmodium falciparum
Parasites in Infected Pregnant Mozambican Women after Delivery
Authors: Serra-Casas Elisa , Menéndez Clara , Dobaño Carlota , Bardají Azucena , Quintó Llorençc , Ordi Jaume , Sigauque Betuel , Cisteró Pau , Mandomando Inacio , Alonso Pedro L. , Mayor Alfredo 
Published: November 2010

ABSTRACT

Pregnant women are susceptible to
Plasmodium falciparum
parasites that sequester in the placenta. The massive accumulation of infected erythrocytes in the placenta has been suggested to trigger the deleterious effects of malaria in pregnant women and their offspring. The risk of malaria is also high during the postpartum period, although mechanisms underlying this susceptibility are not known. Here, we aimed to identify host factors contributing to the risk of postpartum infections and to determine the origin of postpartum parasites by comparing their genotypes with those present at the time of delivery. To address this, blood samples were collected at delivery (
n
= 402) and postpartum (
n
= 354) from Mozambican women enrolled in a trial of intermittent preventive treatment in pregnancy (IPTp).
P. falciparum
was detected by real-time quantitative PCR (qPCR), and the parasite merozoite surface protein 1 (
msp-1
) and
msp-2
genes were genotyped. Fifty-seven out of 354 (16%) women were infected postpartum as assessed by qPCR, whereas prevalence by optical microscopy was only 4%. Risk of postpartum infection was lower in older women (odds ratio [OR] = 0.34, 95% confidence interval [CI] = 0.15 to 0.81) and higher in women with a placental infection at delivery (OR = 4.20, 95% CI = 2.19 to 8.08). Among 24 women with matched infections, 12 (50%) were infected postpartum with at least one parasite strain that was also present in their placentas. These results suggest that parasites infecting pregnant women persist after delivery and increase the risk of malaria during the postpartum period. Interventions that reduce malaria during pregnancy may translate into a lower risk of postpartum infection.
Quantitative PCR-Based Competitive Index for High-Throughput Screening of
Salmonella
Virulence Factors
Authors: Yoon Hyunjin , Gros Phillipe , Heffron Fred 
Published: November 2010

ABSTRACT

Salmonella enterica
serovar Typhimurium is an intracellular pathogen and a main cause of food-borne illness. In this study, a quantitative PCR (qPCR)-based competitive index (CI) method was developed to simultaneously compare the growth of multiple
Salmonella
strains. This method was applied to a mixture of 17
Salmonella
mutants lacking regulator genes, and their survival ratios were compared based on expression of natural resistance-associated macrophage protein 1 (Nramp1). Nramp1, as a major host innate immune component, controls the intracellular replication of pathogens. Deletion strains containing unique DNA barcodes in place of regulator genes were mixed with the parental control, and the bacteria were inoculated into congenic mice differing only at Nramp1. Most of the deletion strains were outcompeted by wild-type bacteria in either mouse strain, and the lack of Nramp1 didn't increase the tested strain/parent control replication ratios. When the same collection of mutants was tested in congenic mouse-derived primary macrophages, a major Nramp1-expressing cell type, six strains (Δ
himD
, Δ
phoP
/
phoQ
, Δ
rpoE
, Δ
rpoS
, Δ
ompR
/
envZ
, and Δ
hfq
strains) grew better in Nramp1
−/−
than in Nramp1
+/+
macrophages, suggesting that these six regulators may play roles in overcoming Nramp1-mediated bactericidal activity in primary macrophages. The discrepancy in survival of macrophages and that of mice suggests either that there are differences in macrophage populations or that other cell types expressing Nramp1 control
Salmonella
proliferation in the host. The method described allows competitive infection analysis to be carried out on complex mixtures of bacteria and provides high reproducibility from independent biological replicates.
Role of Purine Biosynthesis inBacillus anthracisPathogenesis and Virulence
Authors: Jenkins Amy , Cote Christopher , Twenhafel Nancy , Merkel Tod , Bozue Joel , Welkos Susan 
Published: November 2010

ABSTRACTBacillus anthracis, the etiological agent of anthrax, is a spore-forming, Gram-positive bacterium and a category A biothreat agent. Screening of a library of transposon-mutagenizedB. anthracisspores identified a mutant displaying an altered phenotype that harbored a mutated gene encoding the purine biosynthetic enzyme PurH. PurH is a bifunctional protein that catalyzes the final steps in the biosynthesis of the purine IMP. We constructed and characterized definedpurHmutants of the virulentB. anthracisAmes strain. The virulence of thepurHmutants was assessed in guinea pigs, mice, and rabbits. The spores of thepurHmutants were as virulent as wild-type spores in mouse intranasal and rabbit subcutaneous infection models but were partially attenuated in a mouse intraperitoneal model. In contrast, thepurHmutant spores were highly attenuated in guinea pigs regardless of the administration route. The reduced virulence in guinea pigs was not due solely to a germination defect, since both bacilli and toxins were detectedin vivo, suggesting that the significant attenuation was associated with a growth defectin vivo. We hypothesize that an intact purine biosynthetic pathway is required for the virulence ofB. anthracisin guinea pigs.
Upper respiratory tract infection is reduced in physically fit and active adults
Authors: Nieman David C , Henson Dru A , Austin Melanie D , Sha Wei 
Published: November 2010

ObjectiveLimited data imply an inverse relationship between physical activity or fitness level and the rates of upper respiratory tract infection (URTI). The purpose of this study was to monitor URTI symptoms and severity in a heterogeneous group of community adults and contrast across tertiles of physical activity and fitness levels while adjusting for potential confounders.DesignA group of 1002 adults (ages 18–85 years, 60% female, 40% male) were followed for 12 weeks during the winter and fall seasons while monitoring URTI symptoms and severity using the Wisconsin Upper Respiratory Symptom Survey. Subjects reported frequency of aerobic activity, and rated their physical fitness level using a 10-point Likert scale. A general linear model, with adjustment for seven confounders, was used to examine the effect of exercise frequency and fitness level on the number of days with URTI and severity of symptoms.ResultsThe number of days with URTI during the 12-week period was significantly reduced, 43% in subjects reporting ≥5 days/week aerobic exercise compared to those who were largely sedentary (≤1 day/week) and 46% when comparing subjects in the high versus low fitness tertile. URTI severity and symptomatology were also reduced 32% to 41% between high and low aerobic activity and physical fitness tertiles.ConclusionsPerceived physical fitness and frequency of aerobic exercise are important correlates of reduced days with URTI and severity of symptoms during the winter and fall common cold seasons.
MINIMIZING THE GROSS-PITAEVSKII ENERGY FUNCTIONAL WITH THE SOBOLEV GRADIENT — ANALYTICAL AND NUMERICAL RESULTS
Authors: KAZEMI PARIMAH , ECKART MICHAEL 
Published: November 2010

In this contribution, we prove the global existence and uniqueness of a trajectory that globally converges to the minimizer of the Gross-Pitaevskii energy functional for a large class of external potentials. Using the method of Sobolev gradients, we can provide an explicit construction of this minimizing sequence. Based upon this theoretical framework we numerically apply these results to a specific realization of the external potential and illustrate the main benefits of the method of Sobolev gradients, which are high numerical stability and rapid convergence toward the minimizer.
Proof of Concept: Network and Systems Biology Approaches Aid in the Discovery of Potent Anticancer Drug Combinations
Authors: Azmi Asfar S. , Wang Zhiwei , Philip Philip A. , Mohammad Ramzi M. , Sarkar Fazlul H. 
Published: November 2010

Abstract
Cancer therapies that target key molecules have not fulfilled expected promises for most common malignancies. Major challenges include the incomplete understanding and validation of these targets in patients, the multiplicity and complexity of genetic and epigenetic changes in the majority of cancers, and the redundancies and cross-talk found in key signaling pathways. Collectively, the uses of single-pathway targeted approaches are not effective therapies for human malignances. To overcome these barriers, it is important to understand the molecular cross-talk among key signaling pathways and how they may be altered by targeted agents. Innovative approaches are needed, such as understanding the global physiologic environment of target proteins and the effects of modifying them without losing key molecular details. Such strategies will aid the design of novel therapeutics and their combinations against multifaceted diseases, in which efficacious combination therapies will focus on altering multiple pathways rather than single proteins. Integrated network modeling and systems biology have emerged as powerful tools benefiting our understanding of drug mechanisms of action in real time. This review highlights the significance of the network and systems biology–based strategy and presents a proof of concept recently validated in our laboratory using the example of a combination treatment of oxaliplatin and the MDM2 inhibitor MI-219 in genetically complex and incurable pancreatic adenocarcinoma. Mol Cancer Ther; 9(12); 3137–44. ©2010 AACR.
Titin is a Target of Matrix Metalloproteinase-2
Authors: Ali Mohammad A.M. , Cho Woo Jung , Hudson Bryan , Kassiri Zamaneh , Granzier Henk , Schulz Richard 
Published: November 2010

Background—
Titin is the largest mammalian (≈3000 to 4000 kDa) and myofilament protein that acts as a molecular spring in the cardiac sarcomere and determines systolic and diastolic function. Loss of titin in ischemic hearts has been reported, but the mechanism of titin degradation is not well understood. Matrix metalloproteinase-2 (MMP-2) is localized to the cardiac sarcomere and, on activation in ischemia/reperfusion injury, proteolyzes specific myofilament proteins. Here we determine whether titin is an intracellular substrate for MMP-2 and if its degradation during ischemia/reperfusion contributes to cardiac contractile dysfunction.

Methods and Results—
Immunohistochemistry and confocal microscopy in rat and human hearts showed discrete colocalization between MMP-2 and titin in the Z-disk region of titin and that MMP-2 is localized mainly to titin near the Z disk of the cardiac sarcomere. Both purified titin and titin in skinned cardiomyocytes were proteolyzed when incubated with MMP-2 in a concentration-dependent manner, and this was prevented by MMP inhibitors. Isolated rat hearts subjected to ischemia/reperfusion injury showed cleavage of titin in ventricular extracts by gel electrophoresis, which was confirmed by reduced titin immunostaining in tissue sections. Inhibition of MMP activity with ONO-4817 prevented ischemia/reperfusion-induced titin degradation and improved the recovery of myocardial contractile function. Titin degradation was also reduced in hearts from MMP-2 knockout mice subjected to ischemia/reperfusion in vivo compared with wild-type controls.

Conclusion—
MMP-2 localizes to titin at the Z-disk region of the cardiac sarcomere and contributes to titin degradation in myocardial ischemia/reperfusion injury.
Bundle-Branch Block Morphology and Other Predictors of Outcome After Cardiac Resynchronization Therapy in Medicare Patients
Authors: Bilchick Kenneth C. , Kamath Sandeep , DiMarco John P. , Stukenborg George J. 
Published: November 2010

Background—
Clinical trials of cardiac resynchronization therapy (CRT) have enrolled a select group of patients, with few patients in subgroups such as right bundle-branch block (RBBB). Analysis of population-based outcomes provides a method to identify real-world predictors of CRT outcomes.

Methods and Results—

Medicare Implantable Cardioverter-Defibrillator Registry (2005 to 2006) data were merged with patient outcomes data. Cox proportional-hazards models assessed death and death/heart failure hospitalization outcomes in patients with CRT and an implantable cardioverter-defibrillator (CRT-D). The 14 946 registry patients with CRT-D (median follow-up, 40 months) had 1-year, 3-year, and overall mortality rates of 12%, 32%, and 37%, respectively. New York Heart Association class IV heart failure status (1-year hazard ratio [HR], 2.23; 3-year HR, 1.98;
P
<0.001) and age ≥80 years (1-year HR, 1.74; 3-year HR, 1.75;
P
<0.001) were associated with increased mortality both early and late after CRT-D. RBBB (1-year HR, 1.44; 3-year HR, 1.37;
P
<0.001) and ischemic cardiomyopathy (1-year HR, 1.39; 3-year HR, 1.44;
P
<0.001) were the next strongest adjusted predictors of both early and late mortality. RBBB and ischemic cardiomyopathy together had twice the adjusted hazard for death (HR, 1.99;
P
<0.001) as left BBB and nonischemic cardiomyopathy. QRS duration of at least 150 ms predicted more favorable outcomes in left BBB but had no impact in RBBB. A secondary analysis showed lower hazards for CRT-D compared with standard implantable cardioverter-defibrillators in left BBB compared with RBBB.

Conclusions—
In Medicare patients, RBBB, ischemic cardiomyopathy, New York Heart Association class IV status, and advanced age were powerful adjusted predictors of poor outcome after CRT-D. Real-world mortality rates 3 to 4 years after CRT-D appear higher than previously recognized.
Bone Marrow–Derived Cells Contribute to Vascular Inflammation but Do Not Differentiate Into Smooth Muscle Cell Lineages
Authors: Iwata Hiroshi , Manabe Ichiro , Fujiu Katsuhito , Yamamoto Tetsufumi , Takeda Norifumi , Eguchi Kosei , Furuya Akiko , Kuro-o Makoto , Sata Masataka , Nagai Ryozo 
Published: November 2010

Background—
It has been proposed that bone marrow–derived cells infiltrate the neointima, where they differentiate into smooth muscle (SM) cells; however, technical limitations have hindered clear identification of the lineages of bone marrow–derived “SM cell–like” cells.

Methods and Results—

Using a specific antibody against the definitive SM cell lineage marker SM myosin heavy chain (SM-MHC) and mouse lines in which reporter genes were driven by regulatory programs for either
SM-MHC
or
SM
α
-actin
, we demonstrated that although some bone marrow–derived cells express SM α-actin in the wire injury–induced neointima, those cells did not express SM-MHC, even 30 weeks after injury. Likewise, no SM-MHC
+
bone marrow–derived cells were found in vascular lesions in
apolipoprotein E
−/−
mice or in a heart transplantation vasculopathy model. Instead, the majority of bone marrow–derived SM α-actin
+
cells were also CD115
+
CD11b
+
F4/80
+
Ly-6C
+
, which is the surface phenotype of inflammatory monocytes. Moreover, adoptively transferred CD11b
+
Ly-6C
+
bone marrow cells expressed SM α-actin in the injured artery. Expression of inflammation-related genes was significantly higher in neointimal subregions rich in bone marrow–derived SM α-actin
+
cells than in other regions.

Conclusions—

It appears that bone marrow–derived SM α-actin
+
cells are of monocyte/macrophage lineage and are involved in vascular remodeling. It is very unlikely that these cells acquire the definitive SM cell lineage.
A Synthetic Aperture Radar–Based Climatology of Open-Cell Convection over the Northeast Pacific Ocean
Authors: Sikora Todd D. , Young George S. , Fisher Caren M. , Stepp Matthew D. 
Published: November 2010

Abstract
This paper presents an 8-yr (1999–2006) climatology of the frequency of open-cell convection over the northeastern Pacific Ocean and the thermodynamic and kinematic environment associated with its development. The climatology is based on synthetic aperture radar–derived wind speed images and reanalysis data. The climatology shows that open-cell convection was a cold-season phenomenon, having occurred in environments in which the difference in temperature between the near-surface air and the sea surface is negative and in environments with positive surface sensible and latent heat fluxes. Within the region between the surface and 500 hPa, the 700–850-hPa layer median static stability was near moist adiabatic while that for the remainder was conditionally unstable. The median magnitude of the vertical wind shear was largest in the 925-hPa–near-surface and 500–700-hPa layers while that at midlevels was relatively weak. Similarities are highlighted between the organization of open-cell convection over the northeastern Pacific Ocean and tropical deep moist maritime convection in terms of cold-pool dynamics. Avenues for future work are discussed.
A Robust Mechanism for Strengthening of the Brewer–Dobson Circulation in Response to Climate Change: Critical-Layer Control of Subtropical Wave Breaking
Authors: Shepherd Theodore G. , McLandress Charles 
Published: November 2010

Abstract
Climate models consistently predict a strengthened Brewer–Dobson circulation in response to greenhouse gas (GHG)-induced climate change. Although the predicted circulation changes are clearly the result of changes in stratospheric wave drag, the mechanism behind the wave-drag changes remains unclear. Here, simulations from a chemistry–climate model are analyzed to show that the changes in resolved wave drag are largely explainable in terms of a simple and robust dynamical mechanism, namely changes in the location of critical layers within the subtropical lower stratosphere, which are known from observations to control the spatial distribution of Rossby wave breaking. In particular, the strengthening of the upper flanks of the subtropical jets that is robustly expected from GHG-induced tropospheric warming pushes the critical layers (and the associated regions of wave drag) upward, allowing more wave activity to penetrate into the subtropical lower stratosphere. Because the subtropics represent the critical region for wave driving of the Brewer–Dobson circulation, the circulation is thereby strengthened. Transient planetary-scale waves and synoptic-scale waves generated by baroclinic instability are both found to play a crucial role in this process. Changes in stationary planetary wave drag are not so important because they largely occur away from subtropical latitudes.
The Spatial and Temporal Variability of Convective Storms over the Northeast United States during the Warm Season
Authors: Murray John C. , Colle Brian A. 
Published: November 2010

Abstract
A spatial and temporal climatology of convective storms over the Northeast United States during the warm season (April–September) is presented using composite National Operational Weather radar (NOWrad) data at 2-km grid spacing from 1996 to 2007 as well as cloud-to-ground lightning from the National Lightning Data Network (NLDN) on a 10-km grid from 2001 to 2007. There are preferred regions for convective storms within New York’s Hudson River Valley, western and southeastern Pennsylvania, central New Jersey, and across the Delmarva Peninsula. A favored initiation area during the early afternoon is the immediate lee of the Appalachians, with a tendency for these convective systems to move eastward to the coast by late evening. There is a sharp gradient in convective frequency within 20 km of the coast on average as a result of the relatively stable marine boundary layer, but as the sea surface warms by midsummer this convective activity increases near the coast, with a nocturnal (0600–1200 UTC) convective maximum over the coastal waters. Convective frequency can vary by more than 40% interannually across subregions of the Northeast. There was 40%–50% more convection across southern New England and Long Island during 1998–2001 than in 2002–05, which was partially the result of more frequent and amplified trough activity in 1998–2001, which helped to trigger convective storms.
Spatial composites using the North American Regional Reanalysis (NARR) highlight some of the synoptic flow patterns associated with the enhanced convective frequencies. Convective storms tend to weaken rapidly from west to east across southern New England when there is low-level southerly flow from the relatively cool ocean. Severe convection is favored over the populated New York City and Long Island coastal regions when there is warm, moist, and unstable air extending northward along the mid-Atlantic coastal plain, with west-southwesterly flow at low levels and an approaching shortwave trough at midlevels.