bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of OprF as a Complement Component C3 Binding Acceptor Molecule on the Surface of Pseudomonas aeruginosa
Authors: Mishra Meenu , Ressler Adam , Schlesinger Larry S. , Wozniak Daniel J. 
Published: May 2015

ABSTRACT

Pseudomonas aeruginosa
is a versatile opportunistic pathogen that can cause devastating persistent infections. Complement is a highly conserved pathway of the innate immune system, and its role in the first line of defense against pathogens is widely appreciated. One of the earliest events in the complement cascade is the conversion of C3 to C3a and C3b, the latter typically binds to one or more acceptor molecules on the pathogen surface. We previously demonstrated that complement C3b binding acceptors exist on the
P. aeruginosa
surface. In the current study, we utilized either C3 polyclonal or C3b monoclonal antibodies in a far-Western technique followed by mass spectroscopy to identify the C3b acceptor molecule(s) on the
P. aeruginosa
surface. Our data provide evidence that OprF (an outer membrane porin, highly conserved in the
Pseudomonadaceae
) binds C3b. An
oprF
-deficient
P. aeruginosa
strain exhibits reduced C3 deposition compared to the wild type. We observed reduced internalization of
oprF
-deficient bacteria by neutrophils after opsonization compared with wild-type
P. aeruginosa
. Heterologous expression of OprF significantly enhanced C3b binding and increased serum-mediated bactericidal effects in complement-susceptible
Escherichia coli
. Furthermore, the predicted secondary structure of the C-terminal, surface-exposed region of OprF has high structural identity to the OmpA domain of several other Gram-negative bacteria, one of which is known to bind C3b. Therefore, these findings provide new insights into the biology of complement interactions with
P. aeruginosa
and other Gram-negative bacteria.
Allergic Lung Inflammation Reduces Tissue Invasion and Enhances Survival from Pulmonary Pneumococcal Infection in Mice, Which Correlates with Increased Expression of Transforming Growth Factor β1 and SiglecF
low
Alveolar Macrophages
Authors: Sanfilippo Alan M. , Furuya Yoichi , Roberts Sean , Salmon Sharon L. , Metzger Dennis W. 
Published: May 2015

ABSTRACT

Asthma is generally thought to confer an increased risk for invasive pneumococcal disease (IPD) in humans. However, recent reports suggest that mortality rates from IPD are unaffected in patients with asthma and that chronic obstructive pulmonary disease (COPD), a condition similar to asthma, protects against the development of complicated pneumonia. To clarify the effects of asthma on the subsequent susceptibility to pneumococcal infection, ovalbumin (OVA)-induced allergic lung inflammation (ALI) was induced in mice followed by intranasal infection with A66.1 serotype 3
Streptococcus pneumoniae
. Surprisingly, mice with ALI were significantly more resistant to lethal infection than non-ALI mice. The heightened resistance observed following ALI correlated with enhanced early clearance of pneumococci from the lung, decreased bacterial invasion from the airway into the lung tissue, a blunted inflammatory cytokine and neutrophil response to infection, and enhanced expression of transforming growth factor β1 (TGF-β1). Neutrophil depletion prior to infection had no effect on enhanced early bacterial clearance or resistance to IPD in mice with ALI. Although eosinophils recruited into the lung during ALI appeared to be capable of phagocytizing bacteria, neutralization of interleukin-5 (IL-5) to inhibit eosinophil recruitment likewise had no effect on early clearance or survival following infection. However, enhanced resistance was associated with an increase in levels of clodronate-sensitive, phagocytic SiglecF
low
alveolar macrophages within the airways following ALI. These findings suggest that, while the risk of developing IPD may actually be decreased in patients with acute asthma, additional clinical data are needed to better understand the risk of IPD in patients with different asthma phenotypes.
Vitamin A-Deficient Hosts Become Nonsymptomatic Reservoirs of Escherichia coli-Like Enteric Infections
Authors: McDaniel Kaitlin L. , Restori Katherine H. , Dodds Jeffery W. , Kennett Mary J. , Ross A. Catharine , Cantorna Margherita T. 
Published: May 2015

ABSTRACTVitamin A deficiency (A−) remains a public health concern in developing countries and is associated with increased susceptibility to infection.Citrobacter rodentiumwas used to model humanEscherichia coliinfections. A−mice developed a severe and lethal (40%) infection. Vitamin A-sufficient (A+) mice survived and cleared the infection by day 25. Retinoic acid treatment of A−mice at the peak of the infection eliminatedC. rodentiumwithin 16 days. Inflammation levels were not different between A+and A−mouse colons, although the A−mice were still infected at day 37. Increased mortality of A−mice was not due to systemic cytokine production, an inability to clear systemicC. rodentium, or increased pathogenicity. Instead, A−mice developed a severe gut infection with most of the A−mice surviving and resolving inflammation but not eliminating the infection. Improvements in vitamin A status might decrease susceptibility to enteric pathogens and prevent potential carriers from spreading infection to susceptible populations.
The Human Antimicrobial Protein Calgranulin C Participates in Control of Helicobacter pylori Growth and Regulation of Virulence
Authors: Haley Kathryn P. , Delgado Alberto G. , Piazuelo M. Blanca , Mortensen Brittany L. , Correa Pelayo , Damo Steven M. , Chazin Walter J. , Skaar Eric P. , Gaddy Jennifer A. 
Published: May 2015

ABSTRACT

During infectious processes, antimicrobial proteins are produced by both epithelial cells and innate immune cells. Some of these antimicrobial molecules function by targeting transition metals and sequestering these metals in a process referred to as “nutritional immunity.” This chelation strategy ultimately starves invading pathogens, limiting their growth within the vertebrate host. Recent evidence suggests that these metal-binding antimicrobial molecules have the capacity to affect bacterial virulence, including toxin secretion systems. Our previous work showed that the S100A8/S100A9 heterodimer (calprotectin, or calgranulin A/B) binds zinc and represses the elaboration of the
H. pylori
cag
type IV secretion system (T4SS). However, there are several other S100 proteins that are produced in response to infection. We hypothesized that the zinc-binding protein S100A12 (calgranulin C) is induced in response to
H. pylori
infection and also plays a role in controlling
H. pylori
growth and virulence. To test this, we analyzed gastric biopsy specimens from
H. pylori
-positive and -negative patients for S100A12 expression. These assays showed that S100A12 is induced in response to
H. pylori
infection and inhibits bacterial growth and viability
in vitro
by binding nutrient zinc. Furthermore, the data establish that the zinc-binding activity of the S100A12 protein represses the activity of the
cag
T4SS, as evidenced by the gastric cell “hummingbird” phenotype, interleukin 8 (IL-8) secretion, and CagA translocation assays. In addition, high-resolution field emission gun scanning electron microscopy (FEG-SEM) was used to demonstrate that S100A12 represses biogenesis of the
cag
T4SS. Together with our previous work, these data reveal that multiple S100 proteins can repress the elaboration of an oncogenic bacterial surface organelle.
Immunogold Localization of Key Metabolic Enzymes in the Anammoxosome and on the Tubule-Like Structures of Kuenenia stuttgartiensis
Authors: de Almeida Naomi M. , Neumann Sarah , Mesman Rob J. , Ferousi Christina , Keltjens Jan T. , Jetten Mike S. M. , Kartal Boran , van Niftrik Laura 
Published: May 2015

ABSTRACT

Anaerobic ammonium-oxidizing (anammox) bacteria oxidize ammonium with nitrite as the terminal electron acceptor to form dinitrogen gas in the absence of oxygen. Anammox bacteria have a compartmentalized cell plan with a central membrane-bound “prokaryotic organelle” called the anammoxosome. The anammoxosome occupies most of the cell volume, has a curved membrane, and contains conspicuous tubule-like structures of unknown identity and function. It was suggested previously that the catalytic reactions of the anammox pathway occur in the anammoxosome, and that proton motive force was established across its membrane. Here, we used antibodies raised against five key enzymes of the anammox catabolism to determine their cellular location. The antibodies were raised against purified native hydroxylamine oxidoreductase-like protein kustc0458 with its redox partner kustc0457, hydrazine dehydrogenase (HDH; kustc0694), hydroxylamine oxidase (HOX; kustc1061), nitrite oxidoreductase (NXR; kustd1700/03/04), and hydrazine synthase (HZS; kuste2859-61) of the anammox bacterium
Kuenenia stuttgartiensis
. We determined that all five protein complexes were exclusively located inside the anammoxosome matrix. Four of the protein complexes did not appear to form higher-order protein organizations. However, the present data indicated for the first time that NXR is part of the tubule-like structures, which may stretch the whole length of the anammoxosome. These findings support the anammoxosome as the locus of catabolic reactions of the anammox pathway.

IMPORTANCE
Anammox bacteria are environmentally relevant microorganisms that contribute significantly to the release of fixed nitrogen in nature. Furthermore, the anammox process is applied for nitrogen removal from wastewater as an environment-friendly and cost-effective technology. These microorganisms feature a unique cellular organelle, the anammoxosome, which was proposed to contain the energy metabolism of the cell and tubule-like structures with hitherto unknown function. Here, we purified five native enzymes catalyzing key reactions in the anammox metabolism and raised antibodies against these in order to localize them within the cell. We showed that all enzymes were located within the anammoxosome, and nitrite oxidoreductase was located exclusively at the tubule-like structures, providing the first insights into the function of these subcellular structures.
In Salmonella enterica, Ethanolamine Utilization Is Repressed by 1,2-Propanediol To Prevent Detrimental Mixing of Components of Two Different Bacterial Microcompartments
Authors: Sturms Ryan , Streauslin Nicholas A. , Cheng Shouqiang , Bobik Thomas A. 
Published: May 2015

ABSTRACT

Bacterial microcompartments (MCPs) are a diverse family of protein-based organelles composed of metabolic enzymes encapsulated within a protein shell. The function of bacterial MCPs is to optimize metabolic pathways by confining toxic and/or volatile metabolic intermediates. About 20% of bacteria produce MCPs, and there are at least seven different types. Different MCPs vary in their encapsulated enzymes, but all have outer shells composed of highly conserved proteins containing bacterial microcompartment domains. Many organisms have genes encoding more than one type of MCP, but given the high homology among shell proteins, it is uncertain whether multiple MCPs can be functionally expressed in the same cell at the same time. In these studies, we examine the regulation of the 1,2-propanediol (1,2-PD) utilization (Pdu) and ethanolamine utilization (Eut) MCPs in
Salmonella
. Studies showed that 1,2-PD (shown to induce the Pdu MCP) represses transcription of the Eut MCP and that the PocR regulatory protein is required. The results indicate that repression of the Eut MCP by 1,2-PD is needed to prevent detrimental mixing of shell proteins from the Eut and Pdu MCPs. Coexpression of both MCPs impaired the function of the Pdu MCP and resulted in the formation of hybrid MCPs composed of Eut and Pdu MCP components. We also show that plasmid-based expression of individual shell proteins from the Eut MCP or the β-carboxysome impaired the function of Pdu MCP. Thus, the high conservation among bacterial microcompartment (BMC) domain shell proteins is problematic for coexpression of the Eut and Pdu MCPs and perhaps other MCPs as well.

IMPORTANCE
Bacterial MCPs are encoded by nearly 20% of bacterial genomes, and almost 40% of those genomes contain multiple MCP gene clusters. In this study, we examine how the regulation of two different MCP systems (Eut and Pdu) is integrated in
Salmonella
. Our findings indicate that 1,2-PD (shown to induce the Pdu MCP) represses the Eut MCP to prevent detrimental mixing of Eut and Pdu shell proteins. These findings suggest that numerous organisms which produce more than one type of MCP likely need some mechanism to prevent aberrant shell protein interactions.
Early arrival at the emergency department is associated with better collaterals, smaller established infarcts and better clinical outcomes with endovascular stroke therapy: SWIFT study
Authors: Liebeskind David S , Jahan Reza , Nogueira Raul G , Jovin Tudor G , Lutsep Helmi L , Saver Jeffrey L 
Published: May 2015

Background and purposeIncreasing time from symptom onset to emergency department arrival may incur greater ischemic injury and decreased likelihood of good outcomes after acute stroke therapy. The impact of time may be assessed bythe extent of acute CT changes, status of collateral vessels, and clinical outcomes.MethodsThe SOLITAIRE FR With the Intention For Thrombectomy (SWIFT) trial comparing two neurothrombectomy treatments was analyzed by time, Alberta Stroke Program Early CT Scores (ASPECTS), angiographic collaterals, and 90-day modified Rankin Scale outcomes. We determined the interaction of time with ASPECTS, collateral grade, reperfusion, and clinical outcomes, with established determinants of angiographic and clinical outcomes as covariates.Results137 patients (52% female) of mean age 67±12 years and median pretreatment NIH Stroke Scale score 18 (range 8–28) were enrolled. Median onset to door (OTD) time was 180 min (IQR 95–250). Presentation within 3 h of last known well was associated with absence of any prestroke disability and presence of atrial fibrillation but was unrelated to age, sex, other vascular risk factors, deficit severity, glucose level, or blood pressure. Worse collaterals were noted with longer OTD intervals: collateral grade 0–1 (n=32): mean 232±84 min; grade 2 (n=48): 164±99 min; grade 3 (n=35): 155±104 min; grade 4 (n=4): 54±16 min (p<0.001). Later presentation was associated with more extensive early infarct imaging changes (median ASPECTS 8 (IQR 7–9) >3 h vs 9 (IQR 8–10) <3 h, p=0.015). Multivariable analyses identified time >3 h as the only predictor of extensive infarct on imaging (ASPECTS ≤7), p=0.003. Earlier presentation was strongly associated with better 90-day modified Rankin Scale outcomes (p<0.001).ConclusionsTime was a critical factor in successful clinical outcomes for neurothrombectomy in the SWIFT trial. Shorter times to presentation were associated with better collaterals, smaller established infarcts, and better clinical outcome after revascularization.
Smoothed Complexity Theory
Authors: Bläser Markus , Manthey Bodo 
Published: May 2015

Smoothed analysis is a new way of analyzing algorithms introduced by Spielman and Teng. Classical methods like worst-case or average-case analysis have accompanying complexity classes, such as P and Avg-P, respectively. Whereas worst-case or average-case analysis give us a means to talk about the running time of a particular algorithm, complexity classes allow us to talk about the inherent difficulty of problems.
Smoothed analysis is a hybrid of worst-case and average-case analysis and compensates some of their drawbacks. Despite its success for the analysis of single algorithms and problems, there is no embedding of smoothed analysis into computational complexity theory, which is necessary to classify problems according to their intrinsic difficulty.
We propose a framework for smoothed complexity theory, define the relevant classes, and prove some first hardness results (of bounded halting and tiling) and tractability results (binary optimization problems, graph coloring, satisfiability) within this framework.
Demo proposal
Authors: Levy Amit A. , Terei David , Stefan Deian , Maziéres David 
Published: May 2015

Simple is a web framework for Haskell. Simple came out of our work on Hails, a platform for secure web applications. For Hails, we needed a flexible web framework that uses no unsafe language features and can be used to build apps outside the IO monad. Unlike many mainstream web frameworks, Simple does not enforce a particular structure or paradigm. Instead, it simply provides a set of composable building blocks to help developers structure and organize their web applications.
We've used Simple to build both traditional web applications as well as applications with explicit, strong safety and security guarantees. In the demonstration, we'll focus on the former -- introducing the framework and motivating it's utility for traditional web apps -- and show how we can leverage the LIO information flow control library to add mandatory security policies to apps.
A Meta Lambda Calculus with Cross-Level Computation
Authors: Tobisawa Kazunori 
Published: May 2015

We propose meta lambda calculus Lambda-* as a basic model of textual substitution via metavariables. The most important feature of the calculus is that every beta-redex can be reduced regardless of whether the beta-redex contains meta-level variables or not. Such a meta lambda calculus has never been achieved before due to difficulty to manage binding structure consistently with alpha-renaming in the presence of meta-level variables. We overcome the difficulty by introducing a new mechanism to deal with substitution and binding structure in a systematic way without the notion of free variables and alpha-renaming.
Calculus Lambda-* enables us to investigate cross-level terms that include a certain type of level mismatch. Cross-level terms have been regarded as meaningless terms and left out of consideration thus far. We find that some cross-level terms behave as quotes and `eval' command in programming languages. With these terms, we show a procedural language as an application of the calculus, which sheds new light on the notions of stores and recursion via meta-level variables.
A Calculus for Relaxed Memory
Authors: Crary Karl , Sullivan Michael J. 
Published: May 2015

We propose a new approach to programming multi-core, relaxed-memory architectures in imperative, portable programming languages. Our memory model is based on explicit, programmer-specified requirements for order of execution and the visibility of writes. The compiler then realizes those requirements in the most efficient manner it can. This is in contrast to existing memory models, which---if they allow programmer control over synchronization at all---are based on inferring the execution and visibility consequences of synchronization operations or annotations in the code.
We formalize our memory model in a core calculus called RMC\@. Outside of the programmer's specified requirements, RMC is designed to be strictly more relaxed than existing architectures. It employs an aggressively nondeterministic semantics for expressions, in which actions can be executed in nearly any order, and a store semantics that generalizes Sarkar et al.'s and Alglave et al.'s models of the Power architecture. We establish several results for RMC, including sequential consistency for two programming disciplines, and an appropriate notion of type safety. All our results are formalized in Coq.
Decentralizing SDN Policies
Authors: Padon Oded , Immerman Neil , Karbyshev Aleksandr , Lahav Ori , Sagiv Mooly , Shoham Sharon 
Published: May 2015

Software-defined networking (SDN) is a new paradigm for operating and managing computer networks. SDN enables logically-centralized control over network devices through a "controller" --- software that operates independently of the network hardware. Network operators can run both in-house and third-party SDN programs on top of the controller, e.g., to specify routing and access control policies.
In practice, having the controller handle events limits the network scalability. Therefore, the feasibility of SDN depends on the ability to efficiently decentralize network event-handling by installing forwarding rules on the switches. However, installing a rule too early or too late may lead to incorrect behavior, e.g., (1) packets may be forwarded to the wrong destination or incorrectly dropped; (2) packets handled by the switch may hide vital information from the controller, leading to incorrect forwarding behavior. The second issue is subtle and sometimes missed even by experienced programmers.
The contributions of this paper are two fold. First, we formalize the correctness and optimality requirements for decentralizing network policies. Second, we identify a useful class of network policies which permits automatic synthesis of a controller which performs optimal forwarding rule installation.
Dependent Information Flow Types
Authors: Lourenço Luísa , Caires Luís 
Published: May 2015

In this paper, we develop a novel notion of dependent information flow types. Dependent information flow types fit within the standard framework of dependent type theory, but, unlike usual dependent types, crucially allow the security level of a type, rather than just the structural data type itself, to depend on runtime values.
Our dependent function and dependent sum information flow types provide a direct, natural and elegant way to express and enforce fine grained security policies on programs, including programs that manipulate structured data types in which the security level of a structure field may depend on values dynamically stored in other fields, still considered a challenge to security enforcement in software systems such as data-centric web-based applications.
We base our development on the very general setting of a minimal lambda-calculus with references and collections. We illustrate its expressiveness, showing how secure operations on relevant scenarios can be modelled and analysed using our dependent information flow type system, which is also shown to be amenable to algorithmic type checking. Our main results include type-safety and non-interference theorems ensuring that well-typed programs do not violate prescribed security policies.