bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enterohemorrhagic Escherichia coli O157:H7 Shiga Toxins Inhibit Gamma Interferon-Mediated Cellular Activation
Authors: Ho Nathan K. , Ossa Juan C. , Silphaduang Uma , Johnson Roger , Johnson-Henry Kathene C. , Sherman Philip M. 
Published: April 2012

ABSTRACT

Enterohemorrhagic
Escherichia coli
(EHEC) serotype O157:H7 is a food-borne pathogen that causes significant morbidity and mortality in developing and industrialized nations. EHEC infection of host epithelial cells is capable of inhibiting the gamma interferon (IFN-γ) proinflammatory pathway through the inhibition of Stat-1 phosphorylation, which is important for host defense against microbial pathogens. The aim of this study was to determine the bacterial factors involved in the inhibition of Stat-1 tyrosine phosphorylation. Human HEp-2 and Caco-2 epithelial cells were challenged directly with either EHEC or bacterial culture supernatants and stimulated with IFN-γ, and then the protein extracts were analyzed by immunoblotting. The data showed that IFN-γ-mediated Stat-1 tyrosine phosphorylation was inhibited by EHEC secreted proteins. Using two-dimensional difference gel electrophoresis, EHEC Shiga toxins were identified as candidate inhibitory factors. EHEC Shiga toxin mutants were then generated and complemented in
trans
, and mutant culture supernatant was supplemented with purified Stx to confirm their ability to subvert IFN-γ-mediated cell activation. We conclude that while other factors are likely involved in the suppression of IFN-γ-mediated Stat-1 tyrosine phosphorylation,
E. coli
-derived Shiga toxins represent a novel mechanism by which EHEC evades the host immune system.
Phenotypic, Morphological, and Functional Heterogeneity of Splenic Immature Myeloid Cells in the Host Response to Tularemia
Authors: Rasmussen John W. , Tam Jason W. , Okan Nihal A. , Mena Patricio , Furie Martha B. , Thanassi David G. , Benach Jorge L. , van der Velden Adrianus W. M. 
Published: April 2012

ABSTRACTRecent studies have linked accumulation of the Gr-1+CD11b+cell phenotype with functional immunosuppression in diverse pathological conditions, including bacterial and parasitic infections and cancer. Gr-1+CD11b+cells were the largest population of cells present in the spleens of mice infected with sublethal doses of theFrancisella tularensislive vaccine strain (LVS). In contrast, the number of T cells present in the spleens of these mice did not increase during early infection. There was a significant delay in the kinetics of accumulation of Gr-1+CD11b+cells in the spleens of B-cell-deficient mice, indicating that B cells play a role in recruitment and maintenance of this population in the spleens of mice infected withF. tularensis. The splenic Gr-1+CD11b+cells in tularemia were a heterogeneous population that could be further subdivided into monocytic (mononuclear) and granulocytic (polymorphonuclear) cells using the Ly6C and Ly6G markers and differentiated into antigen-presenting cells followingex vivoculture. Monocytic, CD11b+Ly6ChiLy6G−cells but not granulocytic, CD11b+Ly6CintLy6G+cells purified from the spleens of mice infected withF. tularensissuppressed polyclonal T-cell proliferation via a nitric oxide-dependent pathway. Although the monocytic, CD11b+Ly6ChiLy6G−cells were able to suppress the proliferation of T cells, the large presence of Gr-1+CD11b+cells in mice that survivedF. tularensisinfection also suggests a potential role for these cells in the protective host response to tularemia.
CodY Deletion Enhances
In Vivo
Virulence of Community-Associated Methicillin-Resistant Staphylococcus aureus Clone USA300
Authors: Montgomery Christopher P. , Boyle-Vavra Susan , Roux Agnès , Ebine Kazumi , Sonenshein Abraham L. , Daum Robert S. 
Published: April 2012

ABSTRACT

The
Staphylococcus aureus
global regulator CodY responds to nutrient availability by controlling the expression of target genes.
In vitro
, CodY represses the transcription of virulence genes, but it is not known if CodY also represses virulence
in vivo
. The dominant community-associated methicillin-resistant
S. aureus
(CA-MRSA) clone, USA300, is hypervirulent and has increased transcription of global regulators and virulence genes; these features are reminiscent of a strain defective in CodY. Sequence analysis revealed, however, that the
codY
genes of USA300 and other sequenced
S. aureus
isolates are not significantly different from the
codY
genes in strains known to have active CodY.
codY
was expressed in USA300, as well as in other pulsotypes assessed. Deletion of
codY
from a USA300 clinical isolate resulted in modestly increased expression of the global regulators
agr
and
saeRS
, as well as the gene encoding the toxin alpha-hemolysin (
hla
). A substantial increase (>30-fold) in expression of the
lukF-PV
gene, encoding part of the Panton-Valentine leukocidin (PVL), was observed in the
codY
mutant. All of these expression differences were reversed by complementation with a functional
codY
gene. Moreover, purified CodY protein bound upstream of the
lukSF-PV
operon, indicating that CodY directly represses expression of
lukSF-PV
. Deletion of
codY
increased the virulence of USA300 in necrotizing pneumonia and skin infection. Interestingly, deletion of
lukSF-PV
from the
codY
mutant did not attenuate virulence, indicating that the hypervirulence of the
codY
mutant was not explained by overexpression of PVL. These results demonstrate that CodY is active in USA300 and that CodY-mediated repression restrains the virulence of USA300.
Microbicidal Activity of Vascular Peroxidase 1 in Human Plasma via Generation of Hypochlorous Acid
Authors: Li Hong , Cao Zehong , Moore D. Ray , Jackson Patricia L. , Barnes Stephen , Lambeth J. David , Thannickal Victor J. , Cheng Guangjie 
Published: April 2012

ABSTRACT

Members of the heme peroxidase family play an important role in host defense. Myeloperoxidase (MPO) is expressed in phagocytes and is the only animal heme peroxidase previously reported to be capable of using chloride ion as a substrate to form the highly microbicidal species hypochlorous acid (HOCl) at neutral pH. Despite the potent bacterial killing activity of HOCl, individuals who fail to express MPO typically show only a modest increase in some fungal infections. This may point to the existence of redundant host defense mechanisms. Vascular peroxidase 1 (VPO1) is newly discovered member of the heme peroxidase family. VPO1 is expressed in cells of the cardiovascular system and is secreted into the bloodstream. In the present study, we investigate whether VPO1 is capable of generating HOCl and its role in host defense. Like MPO, VPO1 in the presence of H
2
O
2
and chloride generates HOCl. VPO1-dependent HOCl generation was demonstrated by chlorination of taurine and tyrosine using mass spectrometry. In addition, the VPO1/H
2
O
2
/Cl
−
system can cause the chlorination of monochlorodimedone and the oxidation of 5-thio-2-nitrobenzoic acid. Purified VPO1 and VPO1 in plasma mediate bacterial killing that is dependent on chloride and H
2
O
2
; killing is inhibited by peroxidase inhibitors and by the H
2
O
2
scavenger catalase. In the presence of erythrocytes, bacterial killing by VPO1 is slightly reduced. Thus, VPO1, in addition to MPO, is the second member of the heme peroxidase family capable of generating HOCl under physiological conditions. VPO1 is likely to participate in host defense, with bactericidal activity mediated through the generation of HOCl.
Complete Genome Sequences of Newcastle Disease Virus Strains Circulating in Chicken Populations of Indonesia
Authors: Xiao Sa , Paldurai Anandan , Nayak Baibaswata , Samuel Arthur , Bharoto Eny E. , Prajitno Teguh Y. , Collins Peter L. , Samal Siba K. 
Published: April 2012

ABSTRACT
Eight highly virulent Newcastle disease virus (NDV) strains were isolated from vaccinated commercial chickens in Indonesia during outbreaks in 2009 and 2010. The complete genome sequences of two NDV strains and the sequences of the surface protein genes (F and HN) of six other strains were determined. Phylogenetic analysis classified them into two new subgroups of genotype VII in the class II cluster that were genetically distinct from vaccine strains. This is the first report of complete genome sequences of NDV strains isolated from chickens in Indonesia.
Reciprocal gender effects of a keystone alpine plant species on other plants, pollinators, and arthropods
Authors: Lortie Christopher J. , Reid Anya M. 
Published: April 2012

The term facilitation generally describes positive interactions between plants, and a common approach in these studies is to identify a dominant plant to structure sampling. Unfortunately, whilst this field has rapidly expanded community ecology, it rarely includes other trophic levels such as insects and pollinators. Here, we combine facilitation, pollination, and reciprocity measures to explore the general hypothesis that sexual dimorphism in a benefactor plant species mediates its impact. The following three predictions were tested and supported using the gynodioecious alpine cushion plant Silene acaulis (L.) Jacq.: (i) that the trait set of a gynodioecious benefactor plant varies between genders; (ii) that dimorphism changes the facilitation of other plants, arthropods, and pollinators; and (iii) that insect selectivity, particularly pollinators, reciprocally impacts the reproductive output of the two genders. Female S. acaulis cushion plants produced significantly more flowers but they were smaller than those of hermaphrodites. Hermaphrodite cushions facilitated other plant species and pollinators more effectively than females, whilst females strongly facilitated more arthropods. Finally, female plants have significantly higher reproductive output as estimated by fruit and seed production, and this was directly related to visitation rate by pollinators. Hence, this study clearly establishes the value of combining some of the common themes of pollination biology such as sexual dimorphism, floral morphology, and measuring reproduction with the study of positive plant–plant interactions.
Stochastic decomposition in production inventory with service time (abstract only)
Authors: Krishnamoorthy A. , Narayanan Viswanath C. 
Published: April 2012

We study an (s, S) inventory system with positive service time (for an overview of the work reported so far in inventory with positive service time one may refer to Krishnamoorthy, Lakshmi and Manikandan: A survey on inventory models with positive service time, OPSEARCH, DOI 10.1007/s12597-010-0032-z). This leads to a queue of demands being formed. The process of demand arrival constitutes a Poisson process. The duration of each service is exponentially distributed. Our model is a supply chain where items are added to the inventory through a production process. This starts each time the inventory level goes down to s and continues to be on until inventory level reaches S with the time required to add one unit of the item into the inventory when the production is on, are independent, identically distributed exponential random variables. Further all distributions involved in this paper are assumed to be mutually independent. We assume that no customer joins the queue when the inventory level is 0. This assumption leads us to an explicit product form solution for the steady state probability vector, using a simple approach. This is despite the fact that there is a strong correlation between lead time (the time required to add an item into the inventory) and the number of customers joining the queue during the lead time (except when the inventory level is zero during which time no customer joins the queue). The technique is to combine the steady state probability vector of the classical M/M/1 queue and that of the production inventory system where each service requires negligible time and no backlogs are allowed. Using a similar technique, the expected length of a production cycle is also obtained explicitly. The optimality of the highest inventory level S and the production switching on level s has been studied using a cost function constructed using the steady state system performance measures. Since we have obtained explicit expressions for these measures, analytic expressions have been derived for the optimal values of S and s.
To show that our method can be applied to other similar problems, we analyze in detail a variant of the above problem (discussed in Schwarz M, Sauer. C, Daduna, H., Kulik, R and Szekli, R: M/M/1 Queueing systems with inventory, Queueing Systems, 54,55-78, 2006). For that model, we assume that in a production run, production occurs only once in a cycle and the amount produced is sufficient to take the inventory level back to S. A brief discussion on the application of our method to inventory system with lead time for replenishment has also been provided.
The multi-armed bandit, with constraints
Authors: Denardo Eric V. , Feinberg Eugene A. , Rothblum Uriel G. 
Published: April 2012

The colorfully-named and much-studied multi-armed bandit is the following Markov decision problem: At epochs 1, 2, ... , a decision maker observes the current state of each of several Markov chains with rewards (bandits) and plays one of them. The Markov chains that are not played remain in their current states. The Markov chain that is played evolves for one transition according to its transition probabilities, earning an immediate reward (possibly negative) that can depend upon its current state and on the state to which transition occurs. Henceforth, to distinguish the states of the individual Markov chains from those of the Markov decision problem, the latter are called multi-states. Each multi-state prescribes a state for each of the Markov chains.
This version of the multi-armed bandit problem was originally solved by John Gittins. It has a large range of operations research applications including applications to resource allocation, scheduling, project management, and search.
A key result for the multi-armed bandit is that attention can be restricted to a simple class of decision procedures. A label is assigned to each state of each bandit such that no two states have the same label, even if they are in different bandits. A priority rule is a policy that, given each multistate, plays the Markov chain whose current state has the lowest label. The literature includes several different proofs of the optimality of a priority rule. Nearly all of these proofs rest on a family of optimal stopping times, one for each state of each bandit.
A different approach is taken here. Pair-wise comparison, rather than optimal stopping, is used to demonstrate the optimality of a priority rule. This is accomplished for models having linear and exponential utility functions. Elementary row operations are used to identify an optimal priority rule and to compute its expected utility for a given starting state.
Our analysis covers the cases of linear and exponential utilities. In the case of a linear utility function, the model is generalized to include constraints that link the bandits. With C constraints, an optimal policy is shown to take the form of an initial randomization over C + 1 priority rules, and column generation is proposed as a solution method.
The proposed computational methods are based on several matrix algorithms. First, an algorithm, called the Triangularizer, transforms the one-step rewards and transition probability matrixes for individual bandits by applying elementary row operations. The transformed matrixes, called finalized, are triangle: all their elements on diagonals and below diagonals are equal to zero. For a given index policy, running the transformed bandits is equivalent to running the original bandits. Second, the transition probabilities and one-step rewards of the transformed bandits are used to compute the performance characteristics of index policies in polynomial times. These computations are used by the column generation algorithm for multi-armed bandits with constraints.
Mice Expressing Activated PI3K Rapidly Develop Advanced Colon Cancer
Authors: Leystra Alyssa A. , Deming Dustin A. , Zahm Christopher D. , Farhoud Mohammed , Olson Terrah J. Paul , Hadac Jamie N. , Nettekoven Laura A. , Albrecht Dawn M. , Clipson Linda , Sullivan Ruth , Washington Mary Kay , Torrealba Jose R. , Weichert Jamey P. , Halberg Richard B. 
Published: April 2012

Abstract
Aberrations in the phosphoinositide 3-kinase (PI3K) signaling pathway play a key role in the pathogenesis of numerous cancers by altering cellular growth, metabolism, proliferation, and apoptosis. Mutations in the catalytic domain of PI3K that generate a dominantly active kinase are commonly found in human colorectal cancers and have been thought to drive tumor progression but not initiation. However, the effects of constitutively activated PI3K upon the intestinal mucosa have not been previously studied in animal models. Here, we show that the expression of a dominantly active form of the PI3K protein in the mouse intestine results in hyperplasia and advanced neoplasia. Mice expressing constitutively active PI3K in the epithelial cells of the distal small bowel and colon rapidly developed invasive adenocarcinomas in the colon that spread into the mesentery and adjacent organs. The histologic characteristics of these tumors were strikingly similar to invasive mucinous colon cancers in humans. Interestingly, these tumors formed without a benign polypoid intermediary, consistent with the lack of aberrant WNT signaling observed. Together, our findings indicate a noncanonical mechanism of colon tumor initiation that is mediated through activation of PI3K. This unique model has the potential to further our understanding of human disease and facilitate the development of therapeutics through pharmacologic screening and biomarker identification. Cancer Res; 72(12); 2931–6. ©2012 AACR.
Can a National Lung Cancer Screening Program in Combination with Smoking Cessation Policies Cause an Early Decrease in Tobacco Deaths in Italy?
Authors: Carreras Giulia , Gorini Giuseppe , Paci Eugenio 
Published: April 2012

Abstract
Objective is to predict smoking attributable deaths (SAD) for lung cancer and all causes in Italy, 2015 to 2040, assuming a yet unimplemented tobacco control policies (TCP) and a national, low-dose, lung cancer, computed tomography (CT) annual screening program (CT screen).
A dynamic model describing the evolution of smoking habits was developed to estimate quit rates, 1986 to 2009, and to predict SAD under different scenarios: keeping the status quo; raising cigarette taxes by 20%; implementing cessation treatment policies (funding treatment, setting up an active quitline, promoting counseling among health professionals); introducing a three-round annual CT screen for current and former heavy smokers aged 55 to 74, 70% compliance, 20% lung cancer mortality reduction; combining all the above-mentioned measures.
The CT screen brought a 3.0% constant annual reduction in lung cancer SAD and decreased or postponed all-cause SAD by 1.7% annually (a half due to respiratory diseases), relative to the status quo scenario. The effect was noticeable after few years from its introduction. TCP showed a steadily strengthening effect starting from 5 to 10 years after implementation. The lung cancer and all-cause SAD under cessation treatment policies, for instance, were reduced by 8.4% and 12.0% in 2030, respectively, and by 16.1% and 20.0% in 2040. TCP gave a greater effect than CT screen in reducing all-cause SAD because cessation brought about a reduction in smoking-related SAD other than lung cancer and respiratory diseases.
Combining TCP and CT screen could bring about an early decrease in lung cancer and respiratory disease SAD due to CT screen, followed by a more substantial drop in all-cause SAD in subsequent decades due to TCP. Cancer Prev Res; 5(6); 874–82. ©2012 AACR.
Atrial Fibrillation Inducibility in the Absence of Structural Heart Disease or Clinical Atrial Fibrillation
Authors: Kumar Saurabh , Kalman Jonathan M. , Sutherland Fiona , Spence Steven J. , Finch Sue , Sparks Paul B. 
Published: April 2012

Background—
Inducibility of atrial fibrillation (AF) after pulmonary vein isolation has been used to guide additional left atrial ablation in paroxysmal AF. The sensitivity and specificity of AF induction in this setting remains uncertain. We examined the incidence and characteristics of inducible AF in patients without structural heart disease or clinical AF and the effect of different induction protocols on AF inducibility.

Methods and Results—

In 44 patients with supraventricular tachycardia with no history of AF or risk factors for AF, atrial refractoriness and conduction were measured, followed by AF induction attempts (10/patient). Each induction was performed after a waiting time that exceeded twice the duration of induced AF from the preceding induction. AF ≥1 minute was considered inducible, and ≥5 minutes as sustained. Burst pacing (at 200 ms for 10 seconds) was compared to decremental pacing (from 200 ms to shortest cycle length, resulting in 1:1 atrial capture for 10 seconds). After 10 inductions, AF was inducible in 49.5%, and sustained in 29.5% of patients. The incidence of both inducible and sustained AF increased with each induction. Apart from male gender, no clinical or electrophysiological features were associated with sustained AF. Decremental pacing was associated with a higher incidence of sustained AF (41.2% versus 14.8%,
P
=0.049), longer duration of AF (
P
=0.006), and shorter mean AF cycle length (
P
<0.001) compared with burst pacing.

Conclusions—
Inducible and sustained AF is common in patients in the absence of structural heart disease or clinical AF, and its incidence varies according to gender, method of induction, and number of inductions. There is a direct relationship between AF persistence and number of inductions, which has not reached a plateau after 10 inductions.
Gap Junctions and Connexin Hemichannels Underpin Hemostasis and Thrombosis
Authors: Vaiyapuri Sakthivel , Jones Chris I. , Sasikumar Parvathy , Moraes Leonardo A. , Munger Stephanie J. , Wright Joy R. , Ali Marfoua S. , Sage Tanya , Kaiser William J. , Tucker Katherine L. , Stain Christopher J. , Bye Alexander P. , Jones Sarah , Oviedo-Orta Ernesto , Simon Alexander M. , Mahaut-Smith Martyn P. , Gibbins Jonathan M. 
Published: April 2012

Background—
Connexins are a widespread family of membrane proteins that assemble into hexameric hemichannels, also known as connexons. Connexons regulate membrane permeability in individual cells or couple between adjacent cells to form gap junctions and thereby provide a pathway for regulated intercellular communication. We have examined the role of connexins in platelets, blood cells that circulate in isolation but on tissue injury adhere to each other and the vessel wall to prevent blood loss and to facilitate wound repair.

Methods and Results—

We report the presence of connexins in platelets, notably connexin37, and that the formation of gap junctions within platelet thrombi is required for the control of clot retraction. Inhibition of connexin function modulated a range of platelet functional responses before platelet-platelet contact and reduced laser-induced thrombosis in vivo in mice. Deletion of the
Cx37
gene (
Gja4
) in transgenic mice reduced platelet aggregation, fibrinogen binding, granule secretion, and clot retraction, indicating an important role for connexin37 hemichannels and gap junctions in platelet thrombus function.

Conclusions—
Together, these data demonstrate that platelet gap junctions and hemichannels underpin the control of hemostasis and thrombosis and represent potential therapeutic targets.