bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vitamin D Rescues Impaired Mycobacterium tuberculosis-Mediated Tumor Necrosis Factor Release in Macrophages of HIV-Seropositive Individuals through an Enhanced Toll-Like Receptor Signaling PathwayIn Vitro
Authors: Anandaiah Asha , Sinha Sanjeev , Bole Medhavi , Sharma Surendra K. , Kumar Narendra , Luthra Kalpana , Li Xin , Zhou Xiuqin , Nelson Benjamin , Han Xinbing , Tachado Souvenir D. , Patel Naimish R. , Koziel Henry 
Published: October 2012

ABSTRACTMycobacterium tuberculosisdisease represents an enormous global health problem, with exceptionally high morbidity and mortality in HIV-seropositive (HIV+) persons. Alveolar macrophages from HIV+persons demonstrate specific and targeted impairment of critical host cell responses, including impairedM. tuberculosis-mediated tumor necrosis factor (TNF) release and macrophage apoptosis. Vitamin D may promote anti-M. tuberculosisresponses through upregulation of macrophage NO, NADPH oxidase, cathelicidin, and autophagy mechanisms, but whether vitamin D promotes anti-M. tuberculosismechanisms in HIV+macrophages is not known. In the current study, human macrophages exposed toM. tuberculosisdemonstrated robust release of TNF, IκB degradation, and NF-κB nuclear translocation, and these responses were independent of vitamin D pretreatment. In marked contrast, HIV+U1 human macrophages exposed toM. tuberculosisdemonstrated very low TNF release and no significant IκB degradation or NF-κB nuclear translocation, whereas vitamin D pretreatment restored these critical responses. The vitamin D-mediated restored responses were dependent in part on macrophage CD14 expression. Importantly, similar response patterns were observed with clinically relevant human alveolar macrophages from healthy individuals and asymptomatic HIV+persons at high clinical risk ofM. tuberculosisinfection. Taken together with the observation that local bronchoalveolar lavage fluid (BALF) levels of vitamin D are severely deficient in HIV+persons, the data from this study demonstrate that exogenous vitamin D can selectively rescue impaired critical innate immune responsesin vitroin alveolar macrophages from HIV+persons at risk forM. tuberculosisdisease, supporting a potential role for exogenous vitamin D as a therapeutic adjuvant inM. tuberculosisinfection in HIV+persons.
Effects of Treatment on IgE Responses against Parasite Allergen-Like Proteins and Immunity to Reinfection in Childhood Schistosome and Hookworm Coinfections
Authors: Pinot de Moira Angela , Jones Frances M. , Wilson Shona , Tukahebwa Edridah , Fitzsimmons Colin M. , Mwatha Joseph K. , Bethony Jeffrey M. , Kabatereine Narcis B. , Dunne David W. 
Published: October 2012

ABSTRACTNaturally occurring human immunity to both schistosomiasis and hookworm infection has been associated with IgE responses against parasite allergen-like proteins. Since the two helminths frequently coinfect the same individuals, there is growing advocacy for their concurrent treatment. However, both helminths are known to exert strong immunomodulatory effects; therefore, coinfected individuals could have immune responses different from those characteristically seen in monoinfected individuals. In this study, we measured changes in IgE, IgG1, and IgG4 responses to schistosome and hookworm antigens, including the allergen-like proteinsSchistosoma mansonitegumental-allergen-like 1 protein (SmTAL1), SmTAL2, andNecator americanus Ancylostoma-secreted protein-2 (Na-ASP-2), following concurrent treatment of schoolchildren coinfected withSchistosoma mansoniand hookworm. Antibody responses to schistosome egg (soluble egg antigen and SmTAL2) or somatic adult hookworm (AHW) antigens either decreased after treatment or were unchanged, whereas those to schistosome worm antigens (soluble worm antigen and SmTAL1) increased. The observed different effects of treatment likely reflect the different modes of drug action and sites of infection for these two helminths. Importantly, there was no evidence that the simultaneous treatment of coinfected children with praziquantel and albendazole affected schistosome- and hookworm-specific humoral responses differently from those characteristic of populations in which only one organism is endemic; schistosome- and hookworm-specific responses were not associated, and there was no evidence for cross-regulation. Posttreatment increases in the levels of IgE to schistosome worm antigens were associated with lowerSchistosoma mansonireinfection intensity, while no associations between humoral responses to AHW antigen and protection from hookworm reinfection were observed in this sample of school-aged children.
Phosphoethanolamine Residues on the Lipid A Moiety of Neisseria gonorrhoeae Lipooligosaccharide Modulate Binding of Complement Inhibitors and Resistance to Complement Killing
Authors: Lewis Lisa A. , Shafer William M. , Dutta Ray Tathagat , Ram Sanjay , Rice Peter A. 
Published: October 2012

ABSTRACTLoss of phosphoethanolamine (PEA) from the lipid A of gonococcal strain FA19 results in increased sensitivity to killing by the classical pathway of complement. Here we demonstrate that loss of PEA from lipid A diminishes binding of the complement regulatory protein C4b binding protein (C4BP) to the FA19 porin B (PorB), providing a molecular basis to explain the susceptibility of anlptAnull strain of FA19 to killing by normal human serum (NHS). Loss of PEA from lipid A in three additional gonococcal strains that expressed diverse PorB molecules also resulted in decreased C4BP binding, increased deposition of C4b, and increased susceptibility to killing by NHS. Complementation oflptAnull strains withlptArestored C4BP binding, decreased C4b deposition, and increased resistance to killing by NHS. These effects of lipid A PEA on C4BP binding to gonococcal PorB and serum resistance were simulated when gonococcal PorB was expressed in a meningococcal background. Loss of PEA from lipid A also affected binding of the alternative pathway regulator factor H (fH) to PorB of some strains. For instance, PorB molecules oflptAnull mutants of strains 252 and 1291 bound less fH than those of their parent strains when lipooligosaccharide (LOS) was sialylated, whereas PorB molecules oflptAnull mutants of strains FA1090 and 273 retained the ability to bind fH when LOS was sialylated. These data indicate that replacement of lipid A with PEA alters binding of C4BP and fH to PorB and contributes to the ability of gonococci to resist complement-mediated killing.
Anaplasma phagocytophilum Asp14 Is an Invasin That Interacts with Mammalian Host Cells via Its C Terminus To Facilitate Infection
Authors: Kahlon Amandeep , Ojogun Nore , Ragland Stephanie A. , Seidman David , Troese Matthew J. , Ottens Andrew K. , Mastronunzio Juliana E. , Truchan Hilary K. , Walker Naomi J. , Borjesson Dori L. , Fikrig Erol , Carlyon Jason A. 
Published: October 2012

ABSTRACT

Anaplasma phagocytophilum
, a member of the family
Anaplasmataceae
, is the tick-transmitted obligate intracellular bacterium that causes human granulocytic anaplasmosis. The life cycle of
A. phagocytophilum
is biphasic, transitioning between the noninfectious reticulate cell (RC) and infectious dense-cored (DC) forms. We analyzed the bacterium's DC surface proteome by selective biotinylation of surface proteins, NeutrAvidin affinity purification, and mass spectrometry. Transcriptional profiling of selected outer membrane protein candidates over the course of infection revealed that
aph_0248
(designated
asp14
[14-kDa
A. phagocytophilum
surface protein]) expression was upregulated the most during
A. phagocytophilum
cellular invasion.
asp14
transcription was induced during transmission feeding of
A. phagocytophilum
-infected ticks on mice and was upregulated when the bacterium engaged its receptor, P-selectin glycoprotein ligand 1. Asp14 localized to the
A. phagocytophilum
surface and was expressed during
in vivo
infection. Treating DC organisms with Asp14 antiserum or preincubating mammalian host cells with glutathione
S
-transferase (GST)–Asp14 significantly inhibited infection of host cells. Moreover, preincubating host cells with GST-tagged forms of both Asp14 and outer membrane protein A, another
A. phagocytophilum
invasin, pronouncedly reduced infection relative to treatment with either protein alone. The Asp14 domain that is sufficient for cellular adherence and invasion lies within the C-terminal 12 to 24 amino acids and is conserved among other
Anaplasma
and
Ehrlichia
species. These results identify Asp14 as an
A. phagocytophilum
surface protein that is critical for infection, delineate its invasion domain, and demonstrate the potential of targeting Asp14 in concert with OmpA for protecting against infection by
A. phagocytophilum
and other
Anaplasmataceae
pathogens.
Extremely Drug-Resistant Salmonella enterica Serovar Senftenberg Infections in Patients in Zambia
Authors: Hendriksen Rene S. , Joensen Katrine Grimstrup , Lukwesa-Musyani Chileshe , Kalondaa Annie , Leekitcharoenphon Pimlapas , Nakazwe Ruth , Aarestrup Frank M. , Hasman Henrik , Mwansa James C. L. 
Published: October 2012

ABSTRACT

Two cases of extremely drug-resistant
Salmonella enterica
serovar Senftenberg isolated from patients in Zambia were investigated by utilizing MIC determinations and whole-genome sequencing. The isolates were resistant to, and harbored genes toward, nine drug classes, including fluoroquinolones and extended-spectrum cephalosporins, contained two plasmid replicons, and differed by 93 single-nucleotide polymorphisms.
A Case of Q Fever Prosthetic Joint Infection and Description of an Assay for Detection of Coxiella burnetii
Authors: Tande Aaron J. , Cunningham Scott A. , Raoult Didier , Sim Franklin H. , Berbari Elie F. , Patel Robin 
Published: October 2012

ABSTRACT

We present the first published case of
Coxiella burnetii
prosthetic joint infection. Diagnosis was established with PCR and culture of periprosthetic tissue and synovial fluid (and serology). A novel PCR assay is described herein. Q fever should be considered in patients with prosthetic joint infection without an identified pathogen.
Cleavage of the Junin Virus Nucleoprotein Serves a Decoy Function To Inhibit the Induction of Apoptosis during Infection
Authors: Wolff Svenja , Becker Stephan , Groseth Allison 
Published: October 2012

ABSTRACT

The regulation of apoptosis during infection is an important factor for host survival and, in some cases, also for the virus life cycle. At the same time, mechanisms to prevent the induction of apoptosis have been observed in numerous viral pathogens, but until now the role of apoptosis during arenavirus infection has not been investigated. Junin virus (JUNV) belongs to the New World arenavirus serogroup of the
Arenaviridae
and is the causative agent of Argentine hemorrhagic fever. We have demonstrated that infection with JUNV in cell culture does not induce apoptosis but leads to cleavage of the nucleoprotein (NP) into discrete products resembling caspase cleavage events. Similar specific NP degradation patterns were also observed in NP-transfected cell lines, and a closer examination of the sequence of NP showed several putative caspase cleavage motifs. Point mutations that abolished these cleavage motifs were consistent with the loss of certain cleavage products. Consistent with these data, further studies showed that treatment with a caspase inhibitor also reduced NP cleavage, indicating that the observed cleavage events were occurring as a result of caspase activity with NP as a substrate. Finally, we showed that expression of NP suppresses the cleavage of caspase 3 in cells treated with an apoptosis activator. Based on these findings, we propose that NP functions as a decoy substrate for caspase cleavage in order to inhibit the induction of apoptosis in JUNV-infected cells.
The Tale of the Long Tail: the Cytoplasmic Domain of HIV-1 gp41
Authors: Postler Thomas S. , Desrosiers Ronald C. 
Published: October 2012

ABSTRACTEnvelope glycoproteins (Env) of lentiviruses typically possess unusually long cytoplasmic domains, often 150 amino acids or longer. It is becoming increasingly clear that these sequences contribute a diverse array of functional activities to the life cycle of their viruses. The cytoplasmic domain of gp41 (gp41CD) is required for replication of human immunodeficiency virus type 1 (HIV-1) in most but not all cell types, whereas it is largely dispensable for replication of simian immunodeficiency virus (SIV). Functionally, gp41CD has been shown to regulate rapid clathrin-mediated endocytosis of Env. The resultant low levels of Env expression at the cell surface likely serve as an immune avoidance mechanism to limit accessibility to the humoral immune response. Intracellular trafficking of Env is also regulated by gp41CD through interactions with a variety of cellular proteins. Furthermore, gp41CD has been implicated in the incorporation of Env into virions through an interaction with the virally encoded matrix protein. Most recently, the gp41CDs of HIV-1 and SIV were shown to activate the key cellular-transcription factor NF-κB via the serine/threonine kinase TAK1. Less well understood are the cytotoxicity- and apoptosis-inducing activities of gp41CD as well as potential roles in modulating the actin cytoskeleton and overcoming host cell restrictions. In this review, we summarize what is currently known about the cytoplasmic domains of HIV-1 and SIV and attempt to integrate the wealth of information in terms of defined functional activities.
Induction of Stress Granule-Like Structures in Vesicular Stomatitis Virus-Infected Cells
Authors: Dinh Phat X. , Beura Lalit K. , Das Phani B. , Panda Debasis , Das Anshuman , Pattnaik Asit K. 
Published: October 2012

ABSTRACT

Previous studies from our laboratory revealed that cellular poly(C) binding protein 2 (PCBP2) downregulates vesicular stomatitis virus (VSV) gene expression. We show here that VSV infection induces the formation of granular structures in the cytoplasm containing cellular RNA-binding proteins, including PCBP2, T-cell-restricted intracellular antigen 1 (TIA1), and TIA1-related protein (TIAR). Depletion of TIA1 via small interfering RNAs (siRNAs), but not depletion of TIAR, results in enhanced VSV growth and gene expression. The VSV-induced granules appear to be similar to the stress granules (SGs) generated in cells triggered by heat shock or oxidative stress but do not contain some of the
bona fide
SG markers, such as eukaryotic initiation factor 3 (eIF3) or eIF4A, or the processing body (PB) markers, such as mRNA-decapping enzyme 1A (DCP1a), and thus may not represent canonical SGs or PBs. Our results revealed that the VSV-induced granules, called SG-like structures here, contain the viral replicative proteins and RNAs. The formation and maintenance of the SG-like structures required viral replication and ongoing protein synthesis, but an intact cytoskeletal network was not necessary. These results suggest that cells respond to VSV infection by aggregating the antiviral proteins, such as PCBP2 and TIA1, to form SG-like structures. The functional significance of these SG-like structures in VSV-infected cells is currently under investigation.
Shame! Self-stigmatisation as an obstacle to sick doctors returning to work: a qualitative study
Authors: Henderson Max , Brooks Samantha K , del Busso Lilliana , Chalder Trudie , Harvey Samuel B , Hotopf Matthew , Madan Ira , Hatch Stephani 
Published: October 2012

ObjectiveTo explore the views of sick doctors on the obstacles preventing them returning to work.DesignQualitative study.SettingSingle participating centre recruiting doctors from all over the UK.ParticipantsDoctors who had been away from work for at least 6 months with physical or mental health problems, drug or alcohol problems, General Medical Council involvement or any combination of these, were eligible. Eligible doctors were recruited in conjunction with the Royal Medical Benevolent Fund, the General Medical Council and the Practitioner Health Programme. These organisations approached 77 doctors; 19 participated. Each doctor completed an in-depth semistructured interview. We used a constant comparison method to identify and agree on the coding of the data and the identification of a number of central themes.ResultsThe doctors described that being away from work left them isolated and sad. Many experienced negative reactions from their family and some deliberately concealed their problems. Doctors described a lack of support from colleagues and feared a negative response when returning to work. Self-stigmatisation was central to the participants’ accounts; several described themselves as failures and appeared to have internalised the negative views of others.ConclusionsSelf-stigmatising views, which possibly emerge from the belief that ‘doctors are invincible’, represent a major obstacle to doctors returning to work. From medical school onwards cultural change is necessary to allow doctors to recognise their vulnerabilities so they can more easily generate strategies to manage if they become unwell.
SEARCHING POLYHEDRA BY ROTATING HALF-PLANES
Authors: VIGLIETTA GIOVANNI 
Published: October 2012

THE SEARCHLIGHT SCHEDULING PROBLEM was first studied in 2-dimensional polygons, where the goal is for point guards in fixed positions to rotate searchlights to catch an evasive intruder. Here the problem is extended to 3-dimensional polyhedra, with the guards now boundary segments who rotate half-planes of illumination. After carefully detailing the 3-dimensional model, several results are established. The first is a nearly direct extension of the planar one-way sweep strategy using what filling guards, a generalization that succeeds despite there being no well-defined we call notion in 3-dimensional space of planar "clockwise rotation." Next follow two results: every polyhedron with r > 0 reflex edges can be searched by at most r2 suitably placed boundary guards, whereas just r edguards suffice if the polyhedron is orthogonal. (Mini-mizing the number of guards to search a given polyhedron is easily seen to be NP-hard.) Finally we show that deciding whether a given set of boundary guards has a successful search schedule is strongly NP-hard. A number of peripheral results are proved en route to these central theorems, and several open problems remain for future work.
Static bus schedule aware scratchpad allocation in multiprocessors
Authors: Chattopadhyay Sudipta , Roychoudhury Abhik 
Published: October 2012

Compiler controlled memories or scratchpad memories offer more predictable program execution times than cache memories. Scratchpad memories are often employed in multi-processor system-on-chip (MPSoC) platforms which seek to meet the performance needs of embedded applications while limiting power consumption and timing unpredictability. Scratchpad allocation schemes optimize performance while ensuring predictable execution times (as compared to caches).
In this work, we develop a compile-time scratchpad allocation framework for multi-processor platforms, where the processors (virtually) share on-chip scratchpad space and external memory is accessed through a shared bus. Our allocation method considers the waiting time for bus access while deciding which memory blocks to load into the shared scratchpad memory space. Incorporating the bus schedule into our scratchpad allocation method leads to a global optimization of an application, as compared to employing local scratchpad allocation schemes in individual processors which locally optimize the per-processor execution time. We evaluate the efficacy, sensitivity and efficiency of our memory allocation scheme on two real-world embedded applications - an application controlling an Unmanned Aerial Vehicle (UAV), and a (fragment of) an in-orbit spacecraft software.
Cache persistence analysis
Authors: Cullmann Christoph 
Published: October 2012

To compute a worst-case execution time (WCET) estimate for a program, the architectural effects of the underlying hardware must be modeled. For modern processors this results in the need for a cache and pipeline analysis. The timing-relevant result of the cache analysis is the categorization of the accesses to cached memory. Categorizations that are obtainable by the well-known must and may cache analysis are always-hit, always-miss and not-classified. The cache persistence analysis tries to provide additional information for the not-classified case to limit the number of misses.
There exists a cache persistence analysis by Ferdinand and Wilhelm based on abstract interpretation computing these classifications. In this paper, we present a correctness issue with this analysis and a novel analysis that fixes it. For fully timing compositional architectures the persistence information is straightforward to use. We will focus on the application of the persistence analysis for state-of-the-art architectures that show timing anomalies. Such architectures do not allow to quantify the costs of a single cache hit or miss in isolation. To make the usage of the persistence information feasible, we integrate the novel persistence analysis together with a novel path analysis approach into the industrially used WCET analyzer aiT.
Access permission contracts for scripting languages
Authors: Heidegger Phillip , Bieniusa Annette , Thiemann Peter 
Published: October 2012

The ideal software contract fully specifies the behavior of an operation. Often, in particular in the context of scripting languages, a full specification may be cumbersome to state and may not even be desired. In such cases, a partial specification, which describes selected aspects of the behavior, may be used to raise the confidence in an implementation of the operation to a reasonable level.

We propose a novel kind of contract for object-based languages that specifies the side effects of an operation with
access permissions
. An access permission contract uses sets of access paths to express read and write permissions for the properties of the objects accessible from the operation.

We specify a monitoring semantics for access permission contracts and implement this semantics in a contract system for JavaScript. We prove soundness and stability of violation under increasing aliasing for our semantics.
Applications of access permission contracts include enforcing modularity, test-driven development, program understanding, and regression testing. With respect to testing and understanding, we find that adding access permissions to contracts increases the effectiveness of error detection through contract monitoring by 6-13%.