bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Subtilase Cytotoxin (SubAB) Receptors Whose Signaling, in Association with SubAB-Induced BiP Cleavage, Is Responsible for Apoptosis in HeLa Cells
Authors: Yahiro Kinnosuke , Satoh Mamoru , Morinaga Naoko , Tsutsuki Hiroyasu , Ogura Kohei , Nagasawa Sayaka , Nomura Fumio , Moss Joel , Noda Masatoshi 
Published: November 2010

ABSTRACT

Subtilase cytotoxin (SubAB), which is produced by certain strains of Shiga-toxigenic
Escherichia coli
(STEC), causes the 78-kDa glucose-regulated protein (GRP78/BiP) cleavage, followed by induction of endoplasmic reticulum (ER) stress, leading to caspase-dependent apoptosis via mitochondrial membrane damage by Bax/Bak activation. The purpose of the present study was to identify SubAB receptors responsible for HeLa cell death. Four proteins, NG2, α2β1 integrin (ITG), L1 cell adhesion molecule (L1CAM), and hepatocyte growth factor receptor (Met), were identified to be SubAB-binding proteins by immunoprecipitation and purification, followed by liquid chromatography-tandem mass spectrometry analysis. SubAB-induced Bax conformational change, Bax/Bak complex formation, caspase activation, and cell death were decreased in β1 ITG, NG2, and L1CAM small interfering RNA-transfected cells, but unexpectedly, BiP cleavage was still observed. Pretreatment of cells with a function-blocking β1 ITG antibody (monoclonal antibody [MAb] P5D2) enhanced SubAB-induced caspase activation; MAb P5D2 alone had no effect on caspase activation. Furthermore, we found that SubAB induced focal adhesion kinase fragmentation, which was mediated by a proteasome-dependent pathway, and caspase activation was suppressed in the presence of proteasome inhibitor. Thus, β1 ITG serves as a SubAB-binding protein and may interact with SubAB-signaling pathways, leading to cell death. Our results raise the possibility that although BiP cleavage is necessary for SubAB-induced apoptotic cell death, signaling pathways associated with functional SubAB receptors may be required for activation of SubAB-dependent apoptotic pathways.
Distinct Time-Resolved Roles for Two Catabolite-Sensing Pathways during
Streptococcus pyogenes
Infection
Authors: Kietzman Colin C. , Caparon Michael G. 
Published: November 2010

ABSTRACT

Many Gram-positive pathogens link the expression of virulence genes to the presence of carbon source substrates using overlapping pathways for global control of carbon catabolite regulation. However, how these pathways are integrated to control the behavior of the transcriptome in time- and compartment-specific patterns is typically not well understood. In the present study, global transcriptome profiling was used to determine the extent to which glucose alters gene expression in
Streptococcus pyogenes
(group A streptococcus) and the contributions of the CcpA and LacD.1 catabolite control pathways to the regulation of this response
in vitro
. This analysis revealed that the expression of as many as 15% of the genes examined was regulated and that CcpA and LacD.1 together contribute to the regulation of 60% of this subset. However, numerous patterns were observed, including both CcpA- and LacD.1-specific and independent regulation, coregulation, and regulation of genes by these pathways independently of glucose. In addition, CcpA and LacD.1 had antagonistic effects on most coregulated genes. To resolve the roles of these regulators during infection, the expression of selected transcripts representative of different regulatory patterns was examined in a murine model of soft tissue infection. This revealed distinct patterns of misregulation with respect to time in CcpA
−
versus LacD.1
−
mutants. Taken together, these data support an important role for carbohydrate in the regulation of the transcriptome in tissue and suggest that the CcpA and LacD.1 pathways are organized to function at different times during the course of an infection.
Identification of Gene Products Involved in the Oxidative Stress Response of
Moraxella catarrhalis
Authors: Hoopman Todd C. , Liu Wei , Joslin Stephanie N. , Pybus Christine , Brautigam Chad A. , Hansen Eric J. 
Published: November 2010

ABSTRACT

Moraxella catarrhalis
is subjected to oxidative stress from both internal and environmental sources. A previous study (C. D. Pericone, K. Overweg, P. W. Hermans, and J. N. Weiser, Infect. Immun.
68
:3990-3997, 2000) indicated that a wild-type strain of
M. catarrhalis
was very resistant to killing by exogenous hydrogen peroxide (H
2
O
2
). The gene encoding OxyR, a LysR family transcriptional regulator, was identified and inactivated in
M. catarrhalis
strain O35E, resulting in an increase in sensitivity to killing by H
2
O
2
in disk diffusion assays and a concomitant aerobic serial dilution effect. Genes encoding a predicted catalase (KatA) and an alkyl hydroperoxidase (AhpCF) showed dose-dependent upregulation in wild-type cells exposed to H
2
O
2
. DNA microarray and real-time reverse transcription-PCR (RT-PCR) analyses identified
M. catarrhalis
genes whose expression was affected by oxidative stress in an OxyR-dependent manner. Testing of
M. catarrhalis
O35E
katA
and
ahpC
mutants for their abilities to scavenge exogenous H
2
O
2
showed that the KatA catalase was responsible for most of this activity in the wild-type parent strain. The introduction of the same mutations into
M. catarrhalis
strain ETSU-4 showed that the growth of a ETSU-4
katA
mutant was markedly inhibited by the addition of 50 mM H
2
O
2
but that this mutant could still form a biofilm equivalent to that produced by its wild-type parent strain.
Neurobehavioral effects of long-term exposure to pesticides: results from the 4-year follow-up of the PHYTONER Study
Authors: Baldi Isabelle , Gruber Anne , Rondeau Virginie , Lebailly Pierre , Brochard Patrick , Fabrigoule Colette 
Published: November 2010

ObjectiveThe aim of the PHYTONER study is to investigate the role of pesticides on neurobehavioral performances in French vineyard workers.Methods929 workers affiliated to the health insurance system for farmers in the Bordeaux area of south-western France were enrolled in the study in 1997–1998. They were contacted for a first follow-up in 2001–2003. Participants completed a questionnaire and nine neurobehavioral tests. They were classified according to their life-long pesticide exposure, as directly exposed, indirectly exposed or non-exposed. Educational level, age, sex, alcohol consumption, smoking, psychotropic drug use and depressive symptoms were taken into account in the analysis.Results614 subjects were available for investigation at follow-up. Follow-up analysis confirmed that the risk of obtaining a low performance on the tests was higher in exposed subjects, with ORs ranging from 1.35 to 5.60. Evolution of performances over the follow-up period demonstrated that exposed subjects had the worst decreases in performance. The risk of having a two-point lower score on the Mini-Mental State Examination was 2.15 (95% CI 1.18 to 3.94) in exposed subjects.ConclusionThese results suggest long-term cognitive effects of chronic exposure to pesticides and raise the issue of the risk of evolution towards dementia. The PHYTONER study is the first to provide prospective data on the natural history of neurological disorders associated with pesticide exposure.
Long-term effects on humoral immunity among workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
Authors: Saberi Hosnijeh Fatemeh , Boers Daisy , Portengen Lützen , Bueno-de-Mesquita H Bas , Heederik Dick , Vermeulen Roel 
Published: November 2010

ObjectivesEpidemiological studies have shown inconsistent effects on immunological parameters in subjects exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In this study we investigated changes in humoral immunity and prevalence of atopic diseases among workers from a Dutch historical cohort occupationally exposed to chlorophenoxy herbicides and contaminants including TCDD.Methods45 workers who had been exposed to high levels of TCDD in the past and 108 non-exposed workers (39 from the same factory as the exposed subjects (internal control group) and 69 from a comparable factory but without TCDD exposure (external control group)) were included in the study. Blood immunoglobulin (Ig) and complement factor (C) concentrations and specific IgE antibodies to a panel of common allergens were measured using quantitative nephelometry or ELISA. TCDD plasma levels were measured and back-extrapolated to the time of last exposure (TCDDmax) using a one-compartment first order kinetic model.ResultsA borderline significant negative association between both current and predicted TCDD levels and C4 was found in multivariate analyses (β=−0.020; 95% CI=−0.040–0.010 and β=−0.020; 95% CI=−0.030–0.00, respectively). History of eczema was significantly associated with current TCDD levels in both crude (OR=1.5; 95% CI=1.03−2.2) and adjusted models (OR=1.7; 95% CI=1.08−2.7).ConclusionsOur results do not support an association between TCDD exposure and markers of humoral immunity except possibly C4. Interestingly, decreased levels of C4 have been linked to lymphoma risk, which provides some support to the putative link between TCDD and non-Hodgkin lymphoma.
The task-dependent effect of tags and ratings on social media access
Authors: Clements Maarten , De Vries Arjen P. , Reinders Marcel J. T. 
Published: November 2010

Recently, online social networks have emerged that allow people to share their multimedia files, retrieve interesting content, and discover like-minded people. These systems often provide the possibility to annotate the content with tags and ratings.
Using a random walk through the social annotation graph, we have combined these annotations into a retrieval model that effectively balances the personal preferences and opinions of like-minded users into a single relevance ranking for either content, tags, or people. We use this model to identify the influence of different annotation methods and system design aspects on common ranking tasks in social content systems.
Our results show that a combination of rating and tagging information can improve tasks like search and recommendation. The optimal influence of both sources on the ranking is highly dependent on the retrieval task and system design. Results on content search and tag suggestion indicate that the profile created by a user's annotations can be used effectively to adapt the ranking to personal preferences. The random walk reduces sparsity problems by smoothly integrating indirectly related concepts in the relevance ranking, which is especially valuable for cold-start users or individual tagging systems like YouTube and Flickr.
Understanding overlay characteristics of a large-scale peer-to-peer IPTV system
Authors: Vu Long , Gupta Indranil , Nahrstedt Klara , Liang Jin 
Published: November 2010

This article presents results from our measurement and modeling efforts on the large-scale peer-to-peer (p2p) overlay graphs spanned by the PPLive system, the most popular and largest p2p IPTV (Internet Protocol Television) system today. Unlike other previous studies on PPLive, which focused on either network-centric or user-centric measurements of the system, our study is unique in (a) focusing on PPLive overlay-specific characteristics, and (b) being the first to derive mathematical models for its distributions of node degree, session length, and peer participation in simultaneous overlays.
Our studies reveal characteristics of multimedia streaming p2p overlays that are markedly different from existing file-sharing p2p overlays. Specifically, we find that: (1) PPLive overlays are similar to random graphs in structure and thus more robust and resilient to the massive failure of nodes, (2) Average degree of a peer in the overlay is independent of the channel population size and the node degree distribution can be fitted by a piecewise function, (3) The availability correlation between PPLive peer pairs is bimodal, that is, some pairs have highly correlated availability, while others have no correlation, (4) Unlike p2p file-sharing peers, PPLive peers are impatient and session lengths (discretized, per channel) are typically geometrically distributed, (5) Channel population size is time-sensitive, self-repeated, event-dependent, and varies more than in p2p file-sharing networks, (6) Peering relationships are slightly locality-aware, and (7) Peer participation in simultaneous overlays follows a Zipf distribution. We believe that our findings can be used to understand current large-scale p2p streaming systems for future planning of resource usage, and to provide useful and practical hints for future design of large-scale p2p streaming systems.
Evidence-based trust
Authors: Wang Yonghong , Singh Munindar P. 
Published: November 2010

An evidence-based account of trust is essential for an appropriate treatment of application-level interactions among autonomous and adaptive parties. Key examples include social networks and service-oriented computing. Existing approaches either ignore evidence or only partially address the twin challenges of mapping evidence to trustworthiness and combining trust reports from imperfectly trusted sources. This article develops a mathematically well-formulated approach that naturally supports discounting and combining evidence-based trust reports.
This article understands an agent Alice's trust in an agent Bob in terms of Alice's certainty in her belief that Bob is trustworthy. Unlike previous approaches, this article formulates certainty in terms of evidence based on a statistical measure defined over a probability distribution of the probability of positive outcomes. This definition supports important mathematical properties ensuring correct results despite conflicting evidence: (1) for a fixed amount of evidence, certainty increases as conflict in the evidence decreases and (2) for a fixed level of conflict, certainty increases as the amount of evidence increases. Moreover, despite a subtle definition of certainty, this work (3) establishes a bijection between evidence and trust spaces, enabling robust combination of trust reports and (4) provides an efficient algorithm for computing this bijection.
The MACODO organization model for context-driven dynamic agent organizations
Authors: Weyns Danny , Haesevoets Robrecht , Helleboogh Alexander 
Published: November 2010

Today's distributed applications such as sensor networks, mobile multimedia applications, and intelligent transportation systems pose huge engineering challenges. Such systems often comprise different components that interact with each other as peers, as such forming a decentralized system. The system components and collaborations change over time, often in unanticipated ways. Multiagent systems belong to a class of decentralized systems that are known for realizing qualities such as adaptability, robustness, and scalability in such environments. A typical way to structure and manage interactions among agents is by means of organizations. Existing approaches usually endow agents with a dual responsibility: on the one hand agents have to play roles providing the associated functionality in the organization, on the other hand agents are responsible for setting up organizations and managing organization dynamics. Engineering realistic multiagent systems in which agents encapsulate this dual responsibility is a complex task.
In this article, we present an organization model for context-driven dynamic agent organizations. The model defines abstractions that support application developers to describe dynamic organizations. The organization model is part of an integrated approach, called MACODO: Middleware Architecture for COntext-driven Dynamic agent Organizations. The complementary part of the MACODO approach is a middleware platform that supports the distributed execution of dynamic organizations specified using the abstractions, as described in Weyns et al. [2009].
In the model, the life-cycle management of dynamic organizations is separated from the agents: organizations are first-class citizens, and their dynamics are governed by laws. The laws specify how changes in the system (e.g., an agent joins an organization) and changes in the context (e.g., information observed in the environment) lead to dynamic reorganizations. As such, the model makes it easier to understand and specify dynamic organizations in multiagent systems, and promotes reusing the life-cycle management of dynamic organizations. The organization model is formally described to specify the semantics of the abstractions, and ensure its type safety. We apply the organization model to specify dynamic organizations for a traffic monitoring application.
Microfluidic-Based Multiplex qRT-PCR Identifies Diagnostic and Prognostic microRNA Signatures in the Sera of Prostate Cancer Patients
Authors: Moltzahn Felix , Olshen Adam B. , Baehner Lauren , Peek Andrew , Fong Lawrence , Stöppler Hubert , Simko Jeffry , Hilton Joan F. , Carroll Peter , Blelloch Robert 
Published: November 2010

AbstractRecent prostate-specific antigen–based screening trials indicate an urgent need for novel and noninvasive biomarker identification strategies to improve the prediction of prostate cancer behavior. Noncoding microRNAs (miRNA) in the serum and plasma have been shown to have potential as noninvasive markers for physiologic and pathologic conditions. To identify serum miRNAs that diagnose and correlate with the prognosis of prostate cancer, we developed a multiplex quantitative reverse transcription PCR method involving the purification of multiplex PCR products followed by uniplex analysis on a microfluidics chip to evaluate 384 human miRNAs. Using Dgcr8 and Dicer knockout (small RNA-deficient) mouse ES cells as the benchmark, we confirmed the validity of our technique and uncovered a considerable lack of accuracy in previously published methods. Profiling 48 sera from healthy men and untreated prostate cancer patients with differing CAPRA scores, we identified miRNA signatures that allow us to diagnose cancer patients and correlate with a prognosis. These serum signatures include oncogenic and tumor-suppressive miRNAs, suggesting functional roles in prostate cancer progression. Cancer Res; 71(2); 550–60. ©2010 AACR.
Interleukin 6, but Not T Helper 2 Cytokines, Promotes Lung Carcinogenesis
Authors: Ochoa Cesar E. , Mirabolfathinejad Seyedeh Golsar , Ruiz Venado Ana , Evans Scott E. , Gagea Mihai , Evans Christopher M. , Dickey Burton F. , Moghaddam Seyed Javad 
Published: November 2010

AbstractSeveral epidemiologic studies have found that smokers with chronic obstructive pulmonary disease (COPD), an inflammatory disease of the lung, have an increased risk of lung cancer compared with smokers without COPD. We have shown a causal role for COPD-like airway inflammation in lung cancer promotion in the CCSPCre/LSL-K-rasG12D mouse model (CC-LR). In contrast, existing epidemiologic data do not suggest any definite association between allergic airway inflammation and lung cancer. To test this, CC-LR mice were sensitized to ovalbumin (OVA) and then challenged with an OVA aerosol weekly for 8 weeks. This resulted in eosinophilic lung inflammation associated with increased levels of T helper 2 cytokines and mucous metaplasia of airway epithelium, similar to what is seen in asthmatic patients. However, this type of inflammation did not result in a significant difference in lung surface tumor number (49 ± 9 in OVA vs. 52 ± 5 in control) in contrast to a 3.2-fold increase with COPD-like inflammation. Gene expression analysis of nontypeable Haemophilus influenzae (NTHi)-treated lungs showed upregulation of a different profile of inflammatory genes, including interleukin 6 (IL-6), compared with OVA-treated lungs. Therefore, to determine the causal role of cytokines that mediate COPD-like inflammation in lung carcinogenesis, we genetically ablated IL-6 in CC-LR mice. This not only inhibited intrinsic lung cancer development (1.7-fold) but also inhibited the promoting effect of extrinsic COPD-like airway inflammation (2.6-fold). We conclude that there is a clear specificity for the nature of inflammation in lung cancer promotion, and IL-6 has an essential role in lung cancer promotion. Cancer Prev Res; 4(1); 51–64. ©2010 AACR.
Long-Term Outcome After ICD and CRT Implantation and Influence of Remote Device Follow-Up
Authors: Saxon Leslie A. , Hayes David L. , Gilliam F. Roosevelt , Heidenreich Paul A. , Day John , Seth Milan , Meyer Timothy E. , Jones Paul W. , Boehmer John P. 
Published: November 2010

Background—
Outcome data for patients receiving implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy–defibrillator (CRT-D) devices treated outside of clinical trials are lacking. No clinical trial has evaluated mortality after device implantation or after shock therapy in large numbers of patients with implanted devices that regularly transmit device data over a network.

Methods and Results—

Survival status in patients implanted with ICD and CRT devices across the United States from a single manufacturer was assessed. Outcomes were compared between patients followed in device clinic settings and those who regularly transmit remote data collected from the device an average of 4 times monthly. Shock delivery and electrogram analysis could be ascertained from patients followed on the network, enabling survival after ICD shock to be evaluated. One- and 5-year survival rates in 185 778 patients after ICD implantation were 92% and 68% and were 88% and 54% for CRT-D device recipients. In 8228 patients implanted with CRT-only devices, survival was 82% and 48% at 1 and 5 years, respectively. For the 69 556 ICD and CRT-D patients receiving remote follow-up on the network, 1- and 5-year survival rates were higher compared with those in the 116 222 patients who received device follow-up in device clinics only (50% reduction;
P
<0.0001). There were no differences between patients followed on or off the remote network for the characteristics of age, gender, implanted device year or type, and economic or educational status. Shock therapy was associated with subsequent mortality risk for both ICD and CRT-D recipients.

Conclusions—
Survival after ICD and CRT-D implantation in patients treated in naturalistic practice compares favorably with survival rates observed in clinical trials. Remote follow-up of device data is associated with excellent survival, but arrhythmias that result in device therapy in this population are associated with a higher mortality risk compared with patients who do not require shock therapy.