bluuebunny/crossref_metadata_2025_split huggingface dataset:
Involvement of T6 Pili in Biofilm Formation by Serotype M6 Streptococcus pyogenes
Authors: Kimura Keiji Richard , Nakata Masanobu , Sumitomo Tomoko , Kreikemeyer Bernd , Podbielski Andreas , Terao Yutaka , Kawabata Shigetada 
Published: December 2011

ABSTRACT

The group A streptococcus (GAS)
Streptococcus pyogenes
is known to cause self-limiting purulent infections in humans. The role of GAS pili in host cell adhesion and biofilm formation is likely fundamental in early colonization. Pilus genes are found in the FCT (
f
ibronectin-binding protein,
c
ollagen-binding protein, and
t
rypsin-resistant antigen) genomic region, which has been classified into nine subtypes based on the diversity of gene content and nucleotide sequence. Several epidemiological studies have indicated that FCT type 1 strains, including serotype M6, produce large amounts of monospecies biofilm
in vitro
. We examined the direct involvement of pili in biofilm formation by serotype M6 clinical isolates. In the majority of tested strains, deletion of the
tee6
gene encoding pilus shaft protein T6 compromised the ability to form biofilm on an abiotic surface. Deletion of the
fctX
and
srtB
genes, which encode pilus ancillary protein and class C pilus-associated sortase, respectively, also decreased biofilm formation by a representative strain. Unexpectedly, these mutant strains showed increased bacterial aggregation compared with that of the wild-type strain. When the entire FCT type 1 pilus region was ectopically expressed in serotype M1 strain SF370, biofilm formation was promoted and autoaggregation was inhibited. These findings indicate that assembled FCT type 1 pili contribute to biofilm formation and also function as attenuators of bacterial aggregation. Taken together, our results show the potential role of FCT type 1 pili in the pathogenesis of GAS infections.
Mutation of the Sensor Kinase
chvG
in Rhizobium leguminosarum Negatively Impacts Cellular Metabolism, Outer Membrane Stability, and Symbiosis
Authors: Vanderlinde Elizabeth M. , Yost Christopher K. 
Published: December 2011

ABSTRACT

Two-component signal transduction systems (TCS) are a main strategy used by bacteria to sense and adapt to changes in their environment. In the legume symbiont
Rhizobium leguminosarum
biovar viciae VF39, mutation of
chvG
, a histidine kinase, caused a number of pleiotropic phenotypes. ChvG mutants are unable to grow on proline, glutamate, histidine, or arginine as the sole carbon source. The
chvG
mutant secreted smaller amounts of acidic and neutral surface polysaccharides and accumulated abnormally large amounts of poly-ß-hydroxybutyrate. Mutation of
chvG
caused symbiotic defects on peas, lentils, and vetch; nodules formed by the
chvG
mutant were small and white and contained only a few cells that had failed to differentiate into bacteroids. Mutation of
chvG
also destabilized the outer membrane of
R. leguminosarum
, resulting in increased sensitivity to membrane stressors. Constitutive expression of
ropB
, the outer membrane protein-encoding gene, restored membrane stability and rescued the sensitivity phenotypes described above. Similar phenotypes have been described for mutations in other ChvG-regulated genes encoding a conserved operon of unknown function and in the
fabXL
genes required for synthesis of the lipid A very-long-chain fatty acid, suggesting that ChvG is a key component of the envelope stress response in
Rhizobium leguminosarum
. Collectively, the results of this study demonstrate the important and unique role the ChvG/ChvI TCS plays in the physiology, metabolism, and symbiotic competency of
R. leguminosarum
.
EspD Is Critical for the Virulence-Mediating ESX-1 Secretion System in Mycobacterium tuberculosis
Authors: Chen Jeffrey M. , Boy-Röttger Stefanie , Dhar Neeraj , Sweeney Nathan , Buxton Roger S. , Pojer Florence , Rosenkrands Ida , Cole Stewart T. 
Published: December 2011

ABSTRACT

ESAT-6 system 1 (ESX-1)-mediated secretion in
Mycobacterium tuberculosis
is dependent on proteins encoded by the cotranscribed
espA-espC-espD
gene cluster. While the roles of EspA and EspC with respect to the ESX-1 secretion system have been actively investigated, the function of EspD remains unknown. We show that EspD is secreted by
M. tuberculosis
, but unlike EspA and EsxA, its export does not exclusively require the ESX-1 system. Evidence for stabilization of cellular levels of EspA and EspC by EspD is presented, and depletion of EspD results in loss of EsxA secretion. Site-directed mutagenesis of EspD reveals that its role in the maintenance of cellular levels of EspA in
M. tuberculosis
is distinct from its facilitation of EsxA secretion. The same mutagenesis experiments have also shown that secretion of EspD is not required for the secretion of EsxA. Our findings highlight a critical and complex role for EspD in modulating the ESX-1 secretion system in
M. tuberculosis
.
Isolation and Characterization of the Prochlorococcus Carboxysome Reveal the Presence of the Novel Shell Protein CsoS1D
Authors: Roberts Evan W. , Cai Fei , Kerfeld Cheryl A. , Cannon Gordon C. , Heinhorst Sabine 
Published: December 2011

ABSTRACT

Cyanobacteria, including members of the genus
Prochlorococcus
, contain icosahedral protein microcompartments known as carboxysomes that encapsulate multiple copies of the CO
2
-fixing enzyme ribulose 1,5-bisphosphate carboxylase/oxygenase (RubisCO) in a thin protein shell that enhances the catalytic performance of the enzyme in part through the action of a shell-associated carbonic anhydrase. However, the exact mechanism by which compartmentation provides a catalytic advantage to the enzyme is not known. Complicating the study of cyanobacterial carboxysomes has been the inability to obtain homogeneous carboxysome preparations. This study describes the first successful purification and characterization of carboxysomes from the marine cyanobacterium
Prochlorococcus marinus
MED4. Because the isolated
P. marinus
MED4 carboxysomes were free from contaminating membrane proteins, their protein complement could be assessed. In addition to the expected shell proteins, the CsoS1D protein that is not encoded by the canonical
cso
gene clusters of α-cyanobacteria was found to be a low-abundance shell component. This finding and supporting comparative genomic evidence have important implications for carboxysome composition, structure, and function. Our study indicates that carboxysome composition is probably more complex than was previously assumed based on the gene complements of the classical
cso
gene clusters.
Conventional testing methods produce submaximal values of maximum oxygen consumption
Authors: Beltrami Fernando G , Froyd Christian , Mauger Alexis R , Metcalfe Alan J , Marino Frank , Noakes Timothy D 
Published: December 2011

BackgroundThis study used a novel protocol to test the hypothesis that a plateau in oxygen consumption (VO2max) during incremental exercise testing to exhaustion represents the maximal capacity of the cardiovascular system to transport oxygen.MethodsTwenty-six subjects were randomly divided into two groups matched by their initial VO2max. On separate days, the reverse group performed (i) an incremental uphill running test on a treadmill (INC1) plus verification test (VER) at a constant workload 1 km h−1higher than the last completed stage in INC1; (ii) a decremental test (DEC) in which speed started as same as the VER but was reduced progressively and (iii) a final incremental test (INCF). The control group performed only INC on the same days that the reverse group was tested.ResultsVO2maxremained within 0.6 ml kg−1min−1across the three trials for the control group (p=0.93) but was 4.4% higher during DEC compared with INC1(63.9±3.8 vs 61.2±4.8 ml kg−1min−1, respectively, p=0.004) in the reverse group, even though speed at VO2maxwas lower (14.3±1.1 vs 16.2±0.7 km h−1for DEC and INC1, respectively, p=0.0001). VO2maxremained significantly higher during INCF(63.6±3.68 ml kg−1min−1, p=0.01), despite an unchanged exercise time between INC1and INCF.ConclusionThese findings go against the concept that a plateau in oxygen consumption measured during the classically described INC and VER represents a systemic limitation to oxygen use. The reasons for a higher VO2during INCFfollowing the DEC test are unclear.
Comparing ingress and egress detection to secure interdomain routing
Authors: Goebel Christoph , Neumann Dirk , Krishnan Ramayya 
Published: December 2011

The global economy and society increasingly depends on computer networks linked together by the Internet. The importance of computer networks reaches far beyond the telecommunications sector since they have become a critical factor for many other crucial infrastructures and markets. With threats mounting and security incidents becoming more frequent, concerns about network security grow.
It is an acknowledged fact that some of the most fundamental network protocols that make the Internet work are exposed to serious threats. One of them is the Border Gateway Protocol (BGP) which determines how Internet traffic is routed through the topology of administratively independent networks that the Internet is comprised of. Despite the existence of a steadily growing number of BGP security proposals, to date none of them has been adopted.
Using a precise definition of BGP robustness we experimentally show that the degree of robustness is distributed unequally across the administrative domains of the Internet, the so-called Autonomous Systems (ASes). The experiments confirm the intuition that the contribution ASes are able to make towards securing the correct working of the inter-domain routing infrastructure by deploying countermeasures against routing attacks differ depending on their position in the AS topology. We also show that the degree of this asymmetry can be controlled by the choice of the security strategy. We compare the strengths and weaknesses of two fundamentally different approaches in increasing BGP's robustness which we termed ingress and egress detection of false route advertisements and indicate their implications. Our quantitative results have important implications for Internet security policy, in particular with respect to the crucial question where to start the deployment of which type of security scheme in order to maximize the Internet's robustness to routing attacks.
Immunotherapy with PI3K Inhibitor and Toll-Like Receptor Agonist Induces IFN-γ+IL-17+ Polyfunctional T Cells That Mediate Rejection of Murine Tumors
Authors: Marshall Neil A. , Galvin Karen C. , Corcoran Anna-Maria B. , Boon Louis , Higgs Rowan , Mills Kingston H.G. 
Published: December 2011

Abstract
The immunosuppressive microenvironment in tumors hampers the induction of antitumor immunity by vaccines or immunotherapies. Toll-like receptor (TLR) ligands have the potential to treat tumors, but they can exert a mixture of positive and negative effects on inflammation in the tumor microenvironment. In this study, we show that specific small molecule inhibitors of phosphoinositide 3-kinase (PI3K) relieve immunosuppression to heighten the proinflammatory effects of TLR ligands that support antitumor immunity. Multiple strategies to inhibit PI3K in dendritic cells (DC) each led to suppression of interleukin (IL)-10 and TGF-β but did affect IL-12 or IL-1β induction by the TLR5 ligand flagellin. In three different mouse models of cancer, combining flagellin with a class I PI3K inhibitor, either with or without a DC vaccine, delayed tumor growth and increased survival, with some animals exhibiting complete rejection and resistance to secondary challenge. Tumor growth suppression was associated with increased accumulation of polyfunctional T cells that secreted multiple effector cytokines, including IFN-γ, IL-17, and IL-2. Therapeutic protection was abolished in mice deficient in IL-17 or deprived of IFN-γ. Together, our results indicate that PI3K inhibition heighten the antitumor properties of TLR ligands, eliciting tumor regression directly but also indirectly by relieving suppressive signals that restrict potent antitumor T-cell responses. These findings suggest important uses for PI3K inhibitors in heightening responses to cancer immunotherapy and immunochemotherapy. Cancer Res; 72(3); 581–91. ©2011 AACR.
Targeting Protein Synthesis in a Myc/mTOR-Driven Model of Anorexia-Cachexia Syndrome Delays Its Onset and Prolongs Survival
Authors: Robert Francis , Mills John R. , Agenor Aouod , Wang Dantong , DiMarco Sergio , Cencic Regina , Tremblay Michel L. , Gallouzi Imed Eddine , Hekimi Siegfried , Wing Simon S. , Pelletier Jerry 
Published: December 2011

AbstractAnorexia-cachexia syndrome (ACS) is a major determinant of cancer-related death that causes progressive body weight loss due to depletion of skeletal muscle mass and body fat. Here, we report the development of a novel preclinical murine model of ACS in which lymphomas harbor elevated Myc and activated mTOR signaling. The ACS phenotype in this model correlated with deregulated expression of a number of cytokines, including elevated levels of interleukin-10 which was under the direct translational control of mTOR. Notably, pharmacologic intervention to impair protein synthesis restored cytokine production to near-normal levels, delayed ACS progression, and extended host survival. Together, our findings suggest a new paradigm to treat ACS by strategies which target protein synthesis to block the production of procachexic factors. Cancer Res; 72(3); 747–56. ©2011 AACR.
Epithelial–Mesenchymal Transition Predicts Sensitivity to the Dual IGF-1R/IR Inhibitor OSI-906 in Hepatocellular Carcinoma Cell Lines
Authors: Zhao Hui , Desai Vidhi , Wang Jian , Epstein David M. , Miglarese Mark , Buck Elizabeth 
Published: December 2011

Abstract
A growing body of data indicates that inhibiting the type 1 insulin-like growth factor receptor (IGF-1R) might be an effective treatment strategy for hepatocellular carcinoma (HCC). OSI-906 is a dual IGF-1R/IR kinase inhibitor currently in phase II clinical development for HCC. However, biomarkers are lacking to help identify patients with HCC who are more likely to benefit from OSI-906 treatment. We sought to determine the effect of OSI-906 on proliferation against a panel of 21 HCC cell lines and to investigate molecular determinants of responsiveness to OSI-906. We identified a subset of HCC cell lines that was sensitive to OSI-906, and sensitivity is associated with elevated phosphorylation levels of IGF-1R and IR and greater inhibition of AKT signaling. Dual targeting of both receptors seems to be important for maximal inhibition as treatment with a selective IGF-1R–neutralizing antibody was associated with increased IR signaling, whereas OSI-906 fully inhibited both phosphorylated IR and IGF-1R and resulted in greater inhibition of the IRS/AKT pathway. Epithelial–mesenchymal transition (EMT) seems to predict HCC cell sensitivity to OSI-906, as the epithelial phenotype is strongly associated with expression of IGF-2 and IR, activation of IGF-1R and IR, and sensitivity to OSI-906, alone or in combination with erlotinib. Induction of EMT upon treatment with TGFβ reduced sensitivity to OSI-906. Collectively, these data support the concept for dual IGF-1R/IR targeting in HCC, where EMT status and expressions of IGF-2 and IR may be used to identify those patients who are most likely to benefit from treatment with an IGF-1R/IR dual inhibitor. Mol Cancer Ther; 11(2); 503–13. ©2011 AACR.
Cervical Cancer Prevention in Low- and Middle-Income Countries: Feasible, Affordable, Essential
Authors: Sahasrabuddhe Vikrant V. , Parham Groesbeck P. , Mwanahamuntu Mulindi H. , Vermund Sten H. 
Published: December 2011

Abstract
The annual worldwide burden of the preventable disease cervical cancer is more than 530,000 new cases and 275,000 deaths, with the majority occurring in low- and middle-income countries (LMIC), where cervical cancer screening and early treatment are uncommon. Widely used in high-income countries, Pap smear (cytology based) screening is expensive and challenging for implementation in LMICs, where lower-cost, effective alternatives such as visual inspection with acetic acid (VIA) and rapid human papillomavirus (HPV)-based screening tests offer promise for scaling up prevention services. Integrating HPV screening with VIA in “screen-and-treat-or-refer” programs offers the dual benefits of HPV screening to maximize detection and using VIA to triage for advanced lesions/cancer, as well as a pelvic exam to address other gynecologic issues. A major issue in LMICs is coinfection with human immunodeficiency virus (HIV) and HPV, which further increases the risk for cervical cancer and marks a population with perhaps the greatest need of cervical cancer prevention. Public–private partnerships to enhance the availability of cervical cancer prevention services within HIV/AIDS care delivery platforms through initiatives such as Pink Ribbon Red Ribbon present an historic opportunity to expand cervical cancer screening in LMICs. Cancer Prev Res; 5(1); 11–17. ©2011 AACR.
Bisoprolol Delays Progression Towards Right Heart Failure in Experimental Pulmonary Hypertension
Authors: de Man Frances S. , Handoko M. Louis , van Ballegoij Joris J.M. , Schalij Ingrid , Bogaards Sylvia J.P. , Postmus Pieter E. , van der Velden Jolanda , Westerhof Nico , Paulus Walter J. , Vonk-Noordegraaf Anton 
Published: December 2011

Background—
In pulmonary arterial hypertension (PH), sympathetic adrenergic activity is highly elevated. Sympathetic overactivity is a compensatory mechanism at first, but might be detrimental for cardiac function in the long run. We therefore investigated whether chronic low-dose treatment with bisoprolol (a cardioselective β-blocker) has beneficial effects on cardiac function in experimental PH.

Methods and Results—

PH was induced in rats by a single injection of monocrotaline (60 mg/kg). Pressure telemetry in PH rats revealed that 10 mg/kg bisoprolol was the lowest dose that blunted heart rate response during daily activity. Ten days after monocrotaline injection, echocardiography was performed and PH rats were randomized for bisoprolol treatment (oral gavage) or vehicle (n=7/group). At end of study (body mass loss >5%), echocardiography was repeated, with additional pressure-volume measurements and histomolecular analyses. Compared with control, right ventricular (RV) systolic pressure and arterial elastance (measure of vascular resistance) more than tripled in PH. Bisoprolol delayed time to right heart failure (
P
<0.05). RV afterload was unaffected, however, bisoprolol treatment increased RV contractility and filling (both
P
<0.01), and partially restored right ventriculo-arterial coupling and cardiac output (both
P
<0.05). Bisoprolol restored RV β-adrenergic receptor signaling. Histology revealed significantly less RV fibrosis and myocardial inflammation in bisoprolol treated PH rats.

Conclusions—
In experimental PH, treatment with bisoprolol delays progression toward right heart failure, and partially preserves RV systolic and diastolic function. These promising results suggest a therapeutic role for β-blockers in PH that warrants further clinical investigation.
An Unsuspected Property of Natriuretic Peptides
Authors: Chan Noel Yan-Ki , Seyedi Nahid , Takano Kenichi , Levi Roberto 
Published: December 2011

Background—
Although natriuretic peptides are considered cardioprotective, clinical heart failure trials with recombinant brain natriuretic peptide (nesiritide) failed to prove it. Unsuspected proadrenergic effects might oppose the anticipated benefits of natriuretic peptides.

Methods and Results—
We investigated whether natriuretic peptides induce catecholamine release in isolated hearts, sympathetic nerve endings (cardiac synaptosomes), and PC12 cells bearing a sympathetic neuron phenotype. Perfusion of isolated guinea pig hearts with brain natriuretic peptide elicited a 3-fold increase in norepinephrine release, which doubled in ischemia/reperfusion conditions. Brain natriuretic peptide and atrial natriuretic peptide also released norepinephrine from cardiac synaptosomes and dopamine from nerve growth factor–differentiated PC12 cells in a concentration-dependent manner. These catecholamine-releasing effects were associated with an increase in intracellular calcium and abolished by blockade of calcium channels and calcium transients, demonstrating a calcium-dependent exocytotic process. Activation of the guanylyl cyclase-cyclic GMP-protein-kinase-G system with nitroprusside or membrane-permeant cyclic GMP analogs mimicked the proexocytotic effect of natriuretic peptides, an action associated with an increase in intracellular cyclic AMP (cAMP) and protein-kinase-A activity. Cyclic AMP enhancement resulted from an inhibition of phosphodiesterase type 3–induced cAMP hydrolysis. Collectively, these findings indicate that, by inhibiting phosphodiesterase type 3, natriuretic peptides sequentially enhance intracellular cAMP levels, protein kinase A activity, intracellular calcium, and catecholamine exocytosis.

Conclusions—
Our results show that natriuretic peptides, at concentrations likely to be reached at cardiac sympathetic nerve endings in advanced congestive heart failure, promote norepinephrine release via a protein kinase G–induced inhibition of phosphodiesterase type 3–mediated cAMP hydrolysis. We propose that this proadrenergic action may counteract the beneficial cardiac and hemodynamic effects of natriuretic peptides and thus explain the ineffectiveness of nesiritide as a cardiac failure medication.
Radiation stability of nanosilica-based urea–formaldehyde composite materials
Authors: Samaržija-Jovanović Suzana , Jovanović Vojislav , Marković Gordana , Konstantinović Sandra , Marinović-Cincović Milena 
Published: December 2011

Three types of nanosilica-based urea–formaldehyde (UF) hybrid composite materials with a formaldehyde-to-urea (F/U) ratio of 0.8 were synthesized (UF with SiO2—Resin 1, UF + SiO2 + thiourea [TU]—Resin 2 and UF + SiO2 + thiosemicarbazide [TSC]—Resin 3). The thermal behavior of obtained materials was studied by nonisothermal thermogravimetric analysis (TGA), differential thermal gravimetry (DTG), differential thermal analysis (DTA) and differential scanning calorimetry (DSC) and supported by data from Fourier transform infrared spectroscopy (FTIR). Nanosilica-based UF hybrid composites have been irradiated (50 kGy) and after that their radiation stability was evaluated on the basis of thermal behavior. The percentage of free formaldehyde in all prepared samples was determined. DTG peaks of unmodified nanosilica-based UF resin (UF with SiO2) are shifted to a high temperature. The minimum percentage values of free formaldehyde (3%) for samples based on UF with SiO2 and UF + SiO2 + TSC after irradiation dose of 50 kGy are detected.