bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cigarette Smoke Inhibits Airway Epithelial Cell Innate Immune Responses to Bacteria
Authors: Kulkarni Ritwij , Rampersaud Ryan , Aguilar Jorge L. , Randis Tara M. , Kreindler James L. , Ratner Adam J. 
Published: March 2010

ABSTRACTThe human upper respiratory tract, including the nasopharynx, is colonized by a diverse array of microorganisms. While the host generally exists in harmony with the commensal microflora, under certain conditions, these organisms may cause local or systemic disease. Respiratory epithelial cells act as local sentinels of the innate immune system, responding to conserved microbial patterns through activation of signal transduction pathways and cytokine production. In addition to colonizing microbes, these cells may also be influenced by environmental agents, including cigarette smoke (CS). Because of the strong relationship among secondhand smoke exposure, bacterial infection, and sinusitis, we hypothesized that components in CS might alter epithelial cell innate immune responses to pathogenic bacteria. We examined the effect of CS condensate (CSC) or extract (CSE) on signal transduction and cytokine production in primary and immortalized epithelial cells of human or murine origin in response to nontypeableHaemophilus influenzaeandStaphylococcus aureus. We observed that epithelial production of interleukin-8 (IL-8) and IL-6 in response to bacterial stimulation was significantly inhibited in the presence of CS (P< 0.001 for inhibition by either CSC or CSE). In contrast, epithelial production of beta interferon (IFN-β) was not inhibited. CSC decreased NF-κB activation (P< 0.05) and altered the kinetics of mitogen-activated protein kinase phosphorylation in cells exposed to bacteria. Treatment of CSC with antioxidants abrogated CSC-mediated reduction of epithelial IL-8 responses to bacteria (P> 0.05 compared to cells without CSC treatment). These results identify a novel oxidant-mediated immunosuppressive role for CS in epithelial cells.
TheBrucella abortusPhosphoglycerate Kinase Mutant Is Highly Attenuated and Induces Protection Superior to That of Vaccine Strain 19 in Immunocompromised and Immunocompetent Mice
Authors: Trant Cyntia G. M. C. , Lacerda Thais L. S. , Carvalho Natalia B. , Azevedo Vasco , Rosinha Gracia M. S. , Salcedo Suzana P. , Gorvel Jean-Pierre , Oliveira Sergio C. 
Published: March 2010

ABSTRACTBrucella abortusis a facultative intracellular bacterial pathogen that causes abortion in domestic animals and undulant fever in humans. The mechanism of virulence ofBrucellaspp. is not yet fully understood. Therefore, it is crucial to identify new molecules that can function as virulence factors to better understand the host-pathogen interplay. Herein, we identified the gene encoding the phosphoglycerate kinase (PGK) ofB. abortusstrain 2308. To test the role of PGK inBrucellapathogenesis, apgkdeletion mutant was constructed. Replacement of the wild-typepgkby recombination was demonstrated by Southern and Western blot analyses. TheB. abortusΔpgkmutant strain exhibited extreme attenuation in bone marrow-derived macrophages andin vivoin BALB/c, C57BL/6, 129/Sv, and interferon regulatory factor-1 knockout (IRF-1 KO) mice. Additionally, at 24 h postinfection the Δpgkmutant was not found within the same endoplasmic reticulum-derived compartment as the wild-type bacteria, but, instead, over 60% ofBrucella-containing vacuoles (BCVs) retained the late endosomal/lysosomal marker LAMP1. Furthermore, theB. abortusΔpgkdeletion mutant was used as a live vaccine. Challenge experiments revealed that the Δpgkmutant strain induced protective immunity in 129/Sv or IRF-1 KO mice that was superior to the protection conferred by commercial strain 19 or RB51. Finally, the results shown here demonstrated thatBrucellaPGK is critical for full bacterial virulence and that a Δpgkmutant may serve as a potential vaccine candidate in future studies.
Indispensable Role for the Eukaryotic-Like Ankyrin Domains of the Ankyrin B Effector ofLegionella pneumophilawithin Macrophages and Amoebae
Authors: Price Christopher T. D. , Al-Khodor Souhaila , Al-Quadan Tasneem , Abu Kwaik Yousef 
Published: March 2010

ABSTRACTThe Dot/Icm-translocated ankyrin B (AnkB) effector ofLegionella pneumophilaexhibits molecular mimicry of eukaryotic F-box proteins and is essential for intracellular replication in macrophages and protozoa. In addition to two eukaryotic-like ankyrin (ANK) domains, AnkB harbors a conserved eukaryotic F-box domain, which is involved in polyubiquitination of proteins throughout the eukaryotic kingdom. We have recently shown that the F-box domain of the AnkB effector is essential for decoration of theLegionella-containing vacuole (LCV) with polyubiquitinated proteins within macrophages and protozoan hosts. To decipher the role of the two ANK domains in the function of AnkB, we have constructed in-frame deletion of either or both of the ANK domain-encoding regions (ankBΔA1,ankBΔA2, andankBΔA1A2) totrans-complement theankBnull mutant. Deletion of the ANK domains results in defects in intracellular proliferation and decoration of the LCV with polyubiquitinated proteins. Export of the truncated variants of AnkB was reduced, and this may account for the observed defects. However, while full-length AnkB ectopically expressed in mammalian cellstrans-rescues theankBnull mutant for intracellular proliferation, ectopic expression of AnkBΔA1, AnkBΔA2, and AnkBΔA1A2 fails totrans-rescue theankBnull mutant. Importantly, ectopically expressed full-length AnkB is targeted to the host cell plasma membrane, where it recruits polyubiquitinated proteins. In contrast, AnkBΔA1, AnkBΔA2, and AnkBΔA1A2 are diffusely distributed throughout the cytosol and fail to recruit polyubiquitinated proteins. We conclude that the two eukaryotic-like ANK domains of AnkB are essential for intracellular proliferation, for targeting AnkB to the host membranes, and for decoration of the LCV with polyubiquitinated proteins.
Space Microbiology
Authors: Horneck Gerda , Klaus David M. , Mancinelli Rocco L. 
Published: March 2010

SUMMARY

The responses of microorganisms (viruses, bacterial cells, bacterial and fungal spores, and lichens) to selected factors of space (microgravity, galactic cosmic radiation, solar UV radiation, and space vacuum) were determined in space and laboratory simulation experiments. In general, microorganisms tend to thrive in the space flight environment in terms of enhanced growth parameters and a demonstrated ability to proliferate in the presence of normally inhibitory levels of antibiotics. The mechanisms responsible for the observed biological responses, however, are not yet fully understood. A hypothesized interaction of microgravity with radiation-induced DNA repair processes was experimentally refuted. The survival of microorganisms in outer space was investigated to tackle questions on the upper boundary of the biosphere and on the likelihood of interplanetary transport of microorganisms. It was found that extraterrestrial solar UV radiation was the most deleterious factor of space. Among all organisms tested, only lichens (
Rhizocarpon geographicum
and
Xanthoria elegans
) maintained full viability after 2 weeks in outer space, whereas all other test systems were inactivated by orders of magnitude. Using optical filters and spores of
Bacillus subtilis
as a biological UV dosimeter, it was found that the current ozone layer reduces the biological effectiveness of solar UV by 3 orders of magnitude. If shielded against solar UV, spores of
B. subtilis
were capable of surviving in space for up to 6 years, especially if embedded in clay or meteorite powder (artificial meteorites). The data support the likelihood of interplanetary transfer of microorganisms within meteorites, the so-called lithopanspermia hypothesis.
Trade-Offs between Competition and Defense Specialists among Unicellular Planktonic Organisms: the “Killing the Winner” Hypothesis Revisited
Authors: Winter Christian , Bouvier Thierry , Weinbauer Markus G. , Thingstad T. Frede 
Published: March 2010

SUMMARYA trade-off between strategies maximizing growth and minimizing losses appears to be a fundamental property of evolving biological entities existing in environments with limited resources. In the special case of unicellular planktonic organisms, the theoretical framework describing the trade-offs between competition and defense specialists is known as the “killing the winner” hypothesis (KtW). KtW describes how the availability of resources and the actions of predators (e.g., heterotrophic flagellates) and parasites (e.g., viruses) determine the composition and biogeochemical impact of such organisms. We extend KtW conceptually by introducing size- or shape-selective grazing of protozoans on prokaryotes into an idealized food web composed of prokaryotes, lytic viruses infecting prokaryotes, and protozoans. This results in a hierarchy analogous to a Russian doll, where KtW principles are at work on a lower level due to selective viral infection and on an upper level due to size- or shape-selective grazing by protozoans. Additionally, we critically discuss predictions and limitations of KtW in light of the recent literature, with particular focus on typically neglected aspects of KtW. Many aspects of KtW have been corroborated byin situand experimental studies of isolates and natural communities. However, a thorough test of KtW is still hampered by current methodological limitations. In particular, the quantification of nutrient uptake rates of the competing prokaryotic populations and virus population-specific adsorption and decay rates appears to be the most daunting challenge for the years to come.
Getting in the Loop: Regulation of Development inCaulobacter crescentus
Authors: Curtis Patrick D. , Brun Yves V. 
Published: March 2010

SUMMARYCaulobacter crescentusis an aquatic Gram-negative alphaproteobacterium that undergoes multiple changes in cell shape, organelle production, subcellular distribution of proteins, and intracellular signaling throughout its life cycle. Over 40 years of research has been dedicated to this organism and its developmental life cycles. Here we review a portion of many developmental processes, with particular emphasis on how multiple processes are integrated and coordinated both spatially and temporally. While much has been discovered aboutCaulobacter crescentusdevelopment, areas of potential future research are also highlighted.
Agent-oriented embedded electronic measuring systems
Authors: Chan Hing Kai 
Published: March 2010

Introduction

Agent technology has attracted the attention of academia in many domains in the past decade. It is probably due to the fact that computer systems have been becoming complicated with distribution and openness characteristics. Agent-based systems, or multi-agent systems in general, are contemporary paradigm for software development. Ashri et al. claimed that "the underlying concept of decentralized, autonomous control expressed through agents that are able to communicate and cooperate to achieve goals is especially appealing for applications in heterogeneous and dynamic computing environments."
Jennings refers agent-oriented software development approach to as "decomposing the problem into multiple, autonomous components that can act and interact in flexible ways to achieve their set objectives." Jennings also advocates that agent-oriented software development approach offers the following advantages:
• Decompose a complex problem effectively so that the problem space can be divided into smaller sub-problem space;
• A natural way of modelling such systems because they are, most often, decentralized in nature; and
• Interaction among agents is appropriate for modelling the dependencies that exist in complex systems.
In the instrumentation and measurement domain, application of agent technology is still in its infancy. Dobrowiecki et al. discussed how measuring instruments are related to artificial intelligence, in particular agent technology. They presented a general idea of agent-based system which is "to order a service from an agent and to delegate any responsibility of direct control, rather than to monitor closely the progress of the problem solving". Amigoni et al. claimed that agent techniques have evolved and improved over the years such that "impacts on measurement systems whose nature and conceptual interpretation have radically changed." Real-life applications of agent technology in this domain are not well documented. It is not easy to find a successful application of agent-based instrumentation and measuring system, although PC-based distributed instrumentation and measuring systems are not uncommon. In fact, they are usually configured as client-server systems.
In this article, two real-life agent-oriented applications which are embedded measuring systems will be reviewed. In fact, the two cases are commercial products and have already been mass produced. The reasons why such distributed approach is used will be revealed. In fact, one of them is limited by the outlook design so that two individual functional units (which are agents) have to be built for each final product. On the other hand, the other one is decomposed into different independent units to simplify the software development and product design, which is a collaborative work by three independent companies. Main issues, including difficulties, that came across during the course of development of the two cases with respect to agent-oriented design will be addressed in this article.
Fast and accurate processor models for efficient MPSoC design
Authors: Schirner Gunar , Gerstlauer Andreas , Dömer Rainer 
Published: March 2010

With growing system complexity and ever-increasing software content, the development of embedded software for upcoming MPSoC architectures is a tremendous challenge. Traditional ISS-based validation becomes infeasible due to the large complexity.
Addressing the need for flexible and fast simulating models, we introduce in this article our approach of abstract processor modeling in the context of multiprocessor architectures. We combine modeling of computation on processors with an abstract RTOS and accurate interrupt handling into a versatile, multifaceted processor model with several levels of features.
Our processor models are utilized in a framework allowing designers to develop a system in a top-down manner using automatic model generation and compilation down to a given MPSoC architecture. During generation, instances of our processor models are integrated into a system model combining software, hardware, and bus communication. The generated system model serves for rapid design space exploration and a fast and accurate system validation.
Our experimental results show the benefits of our processor modeling using an actual multiprocessor mobile phone baseband platform. Our abstract models of this complex system reach a simulation speed of 300MCycles/s within a high accuracy of less than 3% error. In addition, our results quantify the speed/accuracy trade-off at varying abstraction levels of our models to guide future processor model designers.
Cerebrospinal fluid ATP metabolites in multiple sclerosis
Authors: Lazzarino G. , Amorini AM , Eikelenboom MJ , Killestein J. , Belli A. , Di Pietro V. , Tavazzi B. , Barkhof F. , Polman CH , Uitdehaag BMJ , Petzold A. 
Published: March 2010

Increased axonal energy demand and mitochondrial failure have been suggested as possible causes for axonal degeneration and disability in multiple sclerosis. Our objective was to test whether ATP depletion precedes clinical, imaging and biomarker evidence for axonal degeneration in multiple sclerosis. The method consisted of a longitudinal study which included 21 patients with multiple sclerosis. High performance liquid chromatography was used to quantify biomarkers of the ATP metabolism (oxypurines and purines) from the cerebrospinal fluid at baseline. The Expanded Disability Status Scale, MRI brain imaging measures for brain atrophy (ventricular and parenchymal fractions), and cerebrospinal fluid biomarkers for axonal damage (phosphorylated and hyperphosphorylated neurofilaments) were quantified at baseline and 3-year follow-up. Central ATP depletion (sum of ATP metabolites >19.7 µmol/litre) was followed by more severe progression of disability if compared to normal ATP metabolites (median 1.5 versus 0, p< 0.05). Baseline ATP metabolite levels correlated with change of Expanded Disability Status Scale in the pooled cohort ( r= 0.66, p= 0.001) and subgroups (relapsing—remitting patients: r= 0.79, p< 0.05 and secondary progressive/primary progressive patients: r= 0.69, p< 0.01). There was no relationship between central ATP metabolites and either biomarker or MRI evidence for axonal degeneration. The data suggests that an increased energy demand in multiple sclerosis may cause a quantifiable degree of central ATP depletion. We speculate that the observed clinical disability may be related to depolarisation associated conduction block.
Evaluation of enteropathy-associated T-cell lymphoma comparing standard therapies with a novel regimen including autologous stem cell transplantation
Authors: Sieniawski Michal , Angamuthu Nithia , Boyd Kathryn , Chasty Richard , Davies John , Forsyth Peter , Jack Fergus , Lyons Simon , Mounter Philip , Revell Paul , Proctor Stephen J. , Lennard Anne L. 
Published: March 2010

Abstract
Enteropathy associated T-cell lymphoma (EATL) is a rare type of peripheral T-cell lymphoma. At present, there are no standardized diagnostic or treatment protocols for EATL. We describe EATL in a population-based setting and evaluate a new treatment with aggressive chemotherapy and autologous stem cell transplantation (ASCT). From 1979 onward the Scotland and Newcastle Lymphoma Group prospectively collected data on all patients newly diagnosed with lymphoma in the Northern Region of England and Scotland. Between 1994 and 1998, records of all patients diagnosed with EATL were reviewed, and 54 patients had features of EATL. Overall incidence was 0.14/100 000 per year. Treatment was systemic chemotherapy (mostly anthracycline-based chemotherapy) with or without surgery in 35 patients and surgery alone in 19 patients. Median progression-free survival (PFS) was 3.4 months and overall survival (OS) was 7.1 months. The novel regimen IVE/MTX (ifosfamide, vincristine, etoposide/methotrexate)–ASCT was piloted from 1998 for patients eligible for intensive treatment, and 26 patients were included. Five-years PFS and OS were 52% and 60%, respectively, and were significantly improved compared with the historical group treated with anthracycline-based chemotherapy (P = .01 and P = .003, respectively). EATL is a rare lymphoma with an unfavorable prognosis when treated with conventional therapies. The IVE/MTX-ASCT regimen is feasible with acceptable toxicity and significantly improved outcome.
Improved survival of children and adolescents with sickle cell disease
Authors: Quinn Charles T. , Rogers Zora R. , McCavit Timothy L. , Buchanan George R. 
Published: March 2010

AbstractThe survival of young children with sickle cell disease (SCD) has improved, but less is known about older children and adolescents. We studied the Dallas Newborn Cohort (DNC) to estimate contemporary 18-year survival for newborns with SCD and document changes in the causes and ages of death over time. We also explored whether improvements in the quality of medical care were temporally associated with survival. The DNC now includes 940 subjects with 8857 patient-years of follow-up. Most children with sickle cell anemia (93.9%) and nearly all children with milder forms of SCD (98.4%) now live to become adults. The incidence of death and the pattern of mortality changed over the duration of the cohort. Sepsis is no longer the leading cause of death. All the recent deaths in the cohort occurred in patients 18 years or older, most shortly after the transition to adult care. Quality of care in the DNC has improved over time, with significantly more timely initial visits and preventive interventions for young children. In summary, most children with SCD now survive the childhood years, but young adults who transition to adult medical care are at high risk for early death.
Promoter choice and translational repression determine cell type–specific cell surface density of the inhibitory receptor CD85j expressed on different hematopoietic lineages
Authors: Lamar David L. , Weyand Cornelia M. , Goronzy Jörg J. 
Published: March 2010

AbstractCD85j (ILT2/LILRB1/LIR-1) is an inhibitory receptor that recognizes major histocompatibility complex (MHC) class Ia and Ib alleles that are widely expressed on all cell types. On ligand recognition, CD85j diminishes kinase activity by recruiting phosphatases to motifs within its cytoplasmic domain. Within the hematopoietic system, CD85j is expressed with cell-specific patterns and cell surface densities that reflect the different roles of cell contact-mediated inhibition in these lineages. While monocytes ubiquitously have high cell surface expression, B lymphocytes start to express CD85j at intermediate levels during early B-cell maturation and natural killer (NK) cells and T cells exhibit a low level of expression on only a subset of cells. The cell-specific expression pattern is accomplished by 2 complementing but not independent mechanisms. Lymphocytes and monocytes use distinct promoters to drive CD85j expression. The lymphocyte promoter maps 13 kilobases (kb) upstream of the monocyte promoter; its use results in the inclusion of a distant exon into the 5′-untranslated region. A short sequence stretch within this exon has the unique function of repressing CD85j protein translation and is responsible for the subdued expression in lymphocytes. These cell-specific mechanisms allow tailoring of CD85j levels to the distinct roles it plays in different hematopoietic lineages.
The Apcmin mouse has altered hematopoietic stem cell function and provides a model for MPD/MDS
Authors: Lane Steven W. , Sykes Stephen M. , Al-Shahrour Fatima , Shterental Sebastian , Paktinat Mahnaz , Lo Celso Cristina , Jesneck Jonathan L. , Ebert Benjamin L. , Williams David A. , Gilliland D. Gary 
Published: March 2010

Abstract
Apc, a negative regulator of the canonical Wnt signaling pathway, is a bona-fide tumor suppressor whose loss of function results in intestinal polyposis. APC is located in a commonly deleted region on human chromosome 5q, associated with myelodysplastic syndrome (MDS), suggesting that haploinsufficiency of APC contributes to the MDS phenotype. Analysis of the hematopoietic system of mice with the Apcmin allele that results in a premature stop codon and loss of function showed no abnormality in steady state hematopoiesis. Bone marrow derived from Apcmin mice showed enhanced repopulation potential, indicating a cell intrinsic gain of function in the long-term hematopoietic stem cell (HSC) population. However, Apcmin bone marrow was unable to repopulate secondary recipients because of loss of the quiescent HSC population. Apcmin mice developed a MDS/myeloproliferative phenotype. Our data indicate that Wnt activation through haploinsufficiency of Apc causes insidious loss of HSC function that is only evident in serial transplantation strategies. These data provide a cautionary note for HSC-expansion strategies through Wnt pathway activation, provide evidence that cell extrinsic factors can contribute to the development of myeloid disease, and indicate that loss of function of APC may contribute to the phenotype observed in patients with MDS and del(5q).