bluuebunny/crossref_metadata_2025_split huggingface dataset:
Borrelia burgdorferi
Lacking DbpBA Exhibits an Early Survival Defect during Experimental Infection
Authors: Weening Eric H. , Parveen Nikhat , Trzeciakowski Jerome P. , Leong John M. , Höök Magnus , Skare Jonathan T. 
Published: September 2008

ABSTRACT

Several
Borrelia burgdorferi
genes induced under mammalian host conditions have been purported to be important in Lyme disease pathogenesis based on their binding to host structures. These genes include the
dbpBA
locus, whose products bind host decorin and glycosoaminoglycans. Recently, the
dbpBA
genes were reported to be involved in borrelial infectivity. Here we extended the previous observations by using culture and quantitative PCR to evaluate low- and high-dose murine infection by a Δ
dbpBA
::Gent
r
derivative of
B. burgdorferi
strain B31. The results indicate that the Δ
dbpBA
::Gent
r
mutant is attenuated in the ability to initially colonize and then persist in multiple tissues. The mutant exhibited a colonization defect as early as 3 days postinfection, before the development of an adaptive immune response, and after low-dose infection of SCID mice, which are deficient in adaptive immunity. These findings suggest that the inability to adhere to host decorin may promote clearance of
B. burgdorferi
, presumably via innate immune mechanisms. In a high-dose infection, the mutant disseminated to several tissues, particularly joint tissue, but it was generally cleared from these tissues by 3 weeks postinfection. Finally, following high-dose infection of SCID mice, the
dbpBA
mutant exhibited only a mild colonization defect, suggesting that the adaptive response is involved in the clearance of the mutant in immunocompetent mice. Taken together, these results suggest that the DbpBA proteins facilitate the colonization of multiple tissues by
B. burgdorferi
and are required for optimal resistance to both innate and adaptive immune mechanisms following needle inoculation.
Characterization of Two
Campylobacter jejuni
Strains for Use in Volunteer Experimental-Infection Studies
Authors: Poly Frédéric , Read Timothy D. , Chen Yu-Han , Monteiro Mario A. , Serichantalergs Oralak , Pootong Piyarat , Bodhidatta Ladaporn , Mason Carl J. , Rockabrand David , Baqar Shahida , Porter Chad K. , Tribble David , Darsley Michael , Guerry Patricia 
Published: September 2008

ABSTRACT

The development of vaccines against
Campylobacter jejuni
would be facilitated by the ability to perform phase II challenge studies. However, molecular mimicry of the lipooligosaccharide (LOS) of most
C. jejuni
strains with human gangliosides presents safety concerns about the development of Guillain-Barré syndrome. Clinical isolates of
C. jejuni
that appeared to lack genes for the synthesis of ganglioside mimics were identified by DNA probe analyses. Two clinical isolates from Southeast Asia (strains BH-01-0142 and CG8421) were determined to express the LOS type containing
N
-acetyl quinovosamine. No ganglioside structures were observed to be present in the LOSs of these strains, and pyrosequence analyses of the genomes of both strains confirmed the absence of genes involved in ganglioside mimicry. The capsule polysaccharide (CPS) of BH-01-0142 was determined to be composed of galactose (Gal), 6-deoxy-
ido
-heptose, and, in smaller amounts,
d
-
glycero
-
d
-
ido
-heptose, and the CPS of CG8421 was observed to contain Gal, 6-deoxy-
altro
-heptose,
N
-acetyl-glucosamine, and minor amounts of 6-deoxy-3-
O
-Me-
altro
-heptose. Both CPSs were shown to carry
O
-methyl-phosphoramidate. The two genomes contained strain-specific zones, some of which could be traced to a plasmid origin, and both contained a large chromosomal insertion related to the CJEI3 element of
C. jejuni
RM1221. The genomes of both strains shared a high degree of similarity to each other and, with the exception of the capsule locus of CG8421, to the type strain of the HS3 serotype, TGH9011.
Evidence that Membrane Rafts Are Not Required for the Action of
Clostridium perfringens
Enterotoxin
Authors: Caserta Justin A. , Hale Martha L. , Popoff Michel R. , Stiles Bradley G. , McClane Bruce A. 
Published: September 2008

ABSTRACT

The action of bacterial pore-forming toxins typically involves membrane rafts for binding, oligomerization, and/or cytotoxicity.
Clostridium perfringens
enterotoxin (CPE) is a pore-forming toxin with a unique, multistep mechanism of action that involves the formation of complexes containing tight junction proteins that include claudins and, sometimes, occludin. Using sucrose density gradient centrifugation, this study evaluated whether the CPE complexes reside in membrane rafts and what role raft microdomains play in complex formation and CPE-induced cytotoxicity. Western blot analysis revealed that the small CPE complex and the CPE hexamer 1 (CH-1) complex, which is sufficient for CPE-induced cytotoxicity, both localize outside of rafts. The CH-2 complex was also found mainly in nonraft fractions, although a small pool of raft-associated CH-2 complex that was sensitive to cholesterol depletion with methyl-β-cyclodextrin (MβCD) was detected. Pretreatment of Caco-2 cells with MβCD had no appreciable effect on CPE-induced cytotoxicity. Claudin-4 was localized to Triton X-100-soluble gradient fractions of control or CPE-treated Caco-2 cells, indicating a raft-independent association for this CPE receptor. In contrast, occludin was present in raft fractions of control Caco-2 cells. Treatment with either MβCD or CPE caused most occludin molecules to shift out of lipid rafts, possibly due (at least in part) to the association of occludin with the CH-2 complex. Collectively, these results suggest that CPE is a unique pore-forming toxin for which membrane rafts are not required for binding, oligomerization/pore formation, or cytotoxicity.
Antibodies to Capsular Polysaccharide and Clumping Factor A Prevent Mastitis and the Emergence of Unencapsulated and Small-Colony Variants ofStaphylococcus aureusin Mice
Authors: Tuchscherr Lorena P. N. , Buzzola Fernanda R. , Alvarez Lucía P. , Lee Jean C. , Sordelli Daniel O. 
Published: September 2008

ABSTRACTThe pathogenesis ofStaphylococcus aureusinfections is influenced by multiple virulence factors that are expressed under variable conditions, and this has complicated the design of an effective vaccine. Clinical trials that targeted the capsule or clumping factor A (ClfA) failed to protect the recipients against staphylococcal infections. We passively immunized lactating mice with rabbit antibodies toS. aureuscapsular polysaccharide (CP) serotype 5 (CP5) or CP8 or with monoclonal antibodies to ClfA. Mice immunized with antibodies to CP5 or CP8 or with ClfA had significantly reduced tissue bacterial burdens 4 days after intramammary challenge with encapsulatedS. aureusstrains. After several passages in mice passively immunized with CP-specific antiserum, increasing numbers of stable unencapsulated variants ofS. aureuswere cultured from the infected mammary glands. Greater numbers of these unencapsulatedS. aureusvariants than of the corresponding encapsulated parental strains were internalized in vitro in MAC-T bovine cells. Furthermore, small-colony variants (SCVs) were recovered from the infected mammary glands after several passages in mice passively immunized with CP-specific antiserum. A combination of antibodies effectively sterilized mammary glands in a significant number of passively immunized mice. More importantly, passive immunization with antibodies to both CP and ClfA fully inhibited the emergence of unencapsulated “escape mutants” and significantly reduced the appearance of SCVs. A vaccine formulation comprising CP conjugates plus a surface-associated protein adhesin may be more effective than either antigen alone for prevention ofS. aureusinfections.
Immunogenicity of Recombinant Attenuated
Salmonella enterica
Serovar Typhimurium Vaccine Strains Carrying a Gene That Encodes
Eimeria tenella
Antigen SO7
Authors: Konjufca Vjollca , Jenkins Mark , Wang Shifeng , Juarez-Rodriguez Maria Dolores , Curtiss Roy 
Published: September 2008

ABSTRACT

Recombinant attenuated
Salmonella
vaccines against avian coccidiosis were developed to deliver
Eimeria
species antigens to the lymphoid tissues of chickens via the type 3 secretion system (T3SS) and the type 2 secretion system (T2SS) of
Salmonella
. For antigen delivery via the T3SS, the
Eimeria tenella
gene encoding sporozoite antigen SO7 was cloned downstream of the translocation domain of the
Salmonella enterica
serovar Typhimurium
sopE
gene in the parental pYA3868 and pYA3870 vectors to generate pYA4156 and pYA4157. Newly constructed T3SS vectors were introduced into host strain χ8879 (Δ
phoP233
Δ
sptP1033
::
xylE
Δ
asdA16
), an attenuated derivative of the highly virulent UK-1 strain. The SopE-SO7 fusion protein was secreted by the T3SS of
Salmonella
. The vector pYA4184 was constructed for delivery of the SO7 antigen via the T2SS. The SO7 protein was toxic to
Salmonella
when larger amounts were synthesized; thus, the synthesis of this protein was placed under the control of the
lacI
repressor gene, whose expression in turn was dependent on the amount of available arabinose in the medium. The pYA4184 vector was introduced into host strain χ9242 (Δ
phoP233
Δ
asdA16
Δ
araBAD23
Δ
relA198
::
araC
P
BAD
lacI
TT [TT is the T4
ipIII
transcription terminator]). In addition to SO7, for immunization and challenge studies we used the EAMZ250 antigen of
Eimeria acervulina
, which was previously shown to confer partial protection against
E. acervulina
challenge when it was delivered via the T3SS. Immunization of chickens with a combination of the SO7 and EAMZ250 antigens delivered via the T3SS induced superior protection against challenge by
E. acervulina
. In contrast, chickens immunized with SO7 that was delivered via the T2SS of
Salmonella
were better protected from challenge by
E. tenella
.
An In Vivo and In Vitro Model of
Plasmodium falciparum
Rosetting and Autoagglutination Mediated by
varO
, a Group A
var
Gene Encoding a Frequent Serotype
Authors: Vigan-Womas Inès , Guillotte Micheline , Le Scanf Cécile , Igonet Sébastien , Petres Stéphane , Juillerat Alexandre , Badaut Cyril , Nato Farida , Schneider Achim , Lavergne Anne , Contamin Hugues , Tall Adama , Baril Laurence , Bentley Graham A. , Mercereau-Puijalon Odile 
Published: September 2008

ABSTRACT

In the
Saimiri sciureus
monkey, erythrocytes infected with the varO antigenic variant of the
Plasmodium falciparum
Palo Alto 89F5 clone bind uninfected red blood cells (rosetting), form autoagglutinates, and have a high multiplication rate, three phenotypic characteristics that are associated with severe malaria in human patients. We report here that varO parasites express a
var
gene having the characteristics of group A
var
genes, and we show that the varO Duffy binding-like 1α
1
(DBL1α
1
) domain is implicated in the rosetting of both
S. sciureus
and human erythrocytes. The soluble varO N-terminal sequence (NTS)-DBL1α
1
recombinant domain, produced in a baculovirus-insect cell system, induced high titers of antibodies that reacted with varO-infected red blood cells and disrupted varO rosettes. varO parasites were culture adapted in vitro using human erythrocytes. They formed rosettes and autoagglutinates, and they had the same surface serotype and expressed the same
varO
gene as the monkey-propagated parasites. To develop an in vitro model with highly homogeneous varO parasites, rosette purification was combined with positive selection by panning with a varO NTS-DBL1α
1
-specific mouse monoclonal antibody. The single-variant, clonal parasites were used to analyze seroprevalence for varO at the village level in a setting where malaria is holoendemic (Dielmo, Senegal). We found 93.6% (95% confidence interval, 89.7 to 96.4%) seroprevalence for varO surface-reacting antibodies and 86.7% (95% confidence interval, 82.8 to 91.6%) seroprevalence for the recombinant NTS-DBL1α
1
domain, and virtually all permanent residents had seroconverted by the age of 5 years. These data imply that the varO model is a relevant in vivo and in vitro model for rosetting and autoagglutination that can be used for rational development of vaccine candidates and therapeutic strategies aimed at preventing malaria pathology.
Targeted Mutagenesis in PathogenicLeptospiraSpecies: Disruption of the LigB Gene Does Not Affect Virulence in Animal Models of Leptospirosis
Authors: Croda Julio , Figueira Claudio Pereira , Wunder Elsio A. , Santos Cleiton S. , Reis Mitermayer G. , Ko Albert I. , Picardeau Mathieu 
Published: September 2008

ABSTRACTThe pathogenic mechanisms ofLeptospira interrogans, the causal agent of leptospirosis, remain largely unknown. This is mainly due to the lack of tools for genetically manipulating pathogenicLeptospiraspecies. Thus, homologous recombination between introduced DNA and the corresponding chromosomal locus has never been demonstrated for this pathogen. Leptospiral immunoglobulin-like repeat (Lig) proteins were previously identified as putativeLeptospiravirulence factors. In this study, aligBmutant was constructed by allelic exchange inL. interrogans; in this mutant a spectinomycin resistance (Spcr) gene replaced a portion of theligBcoding sequence. Gene disruption was confirmed by PCR, immunoblot analysis, and immunofluorescence studies. TheligBmutant did not show decrease virulence compared to the wild-type strain in the hamster model of leptospirosis. In addition, inoculation of rats with theligBmutant induced persistent colonization of the kidneys. Finally, LigB was not required to mediate bacterial adherence to cultured cells. Taken together, our data provide the first evidence of site-directed homologous recombination in pathogenicLeptospiraspecies. Furthermore, our data suggest that LigB does not play a major role in dissemination of the pathogen in the host and in the development of acute disease manifestations or persistent renal colonization.
The
Toxoplasma gondii
Dense Granule Protein GRA7 Is Phosphorylated upon Invasion and Forms an Unexpected Association with the Rhoptry Proteins ROP2 and ROP4
Authors: Dunn Joe Dan , Ravindran Sandeep , Kim Seon-Kyeong , Boothroyd John C. 
Published: September 2008

ABSTRACT

The obligate intracellular parasite
Toxoplasma gondii
infects warm-blooded animals throughout the world and is an opportunistic pathogen of humans. As it invades a host cell,
Toxoplasma
forms a novel organelle, the parasitophorous vacuole, in which it resides during its intracellular development. The parasite modifies the parasitophorous vacuole and its host cell with numerous proteins delivered from rhoptries and dense granules, which are secretory organelles unique to the phylum
Apicomplexa
. For the majority of these proteins, little is known other than their localization. Here we show that the dense granule protein GRA7 is phosphorylated but only in the presence of host cells. Within 10 min of invasion, GRA7 is present in strand-like structures in the host cytosol that contain rhoptry proteins. GRA7 strands also contain GRA1 and GRA3. Independently of its phosphorylation state, GRA7 associates with the rhoptry proteins ROP2 and ROP4 in infected host cells. This is the first report of interactions between proteins secreted from rhoptries and dense granules.
Higher fasting plasma glucose levels within the normoglycaemic range and rotator cuff tears
Authors: Longo U G , Franceschi F , Ruzzini L , Spiezia F , Maffulli N , Denaro V 
Published: September 2008

Objective:To determine the plasma glucose levels in non-diabetic patients with rotator cuff tear.Design:Frequency-matched case–control study.Setting:University Teaching Hospital.Participants:The study included 194 subjects who were operated on at our institution. Group 1 included 97 consecutive patients (36 men and 61 women; mean age: 62.9 years, range 37 to 82) who underwent arthroscopic repair of a rotator cuff tear in 2007 and 2008. Group 2 (control group) included 97 patients (36 men and 61 women; mean age: 61.6 years, range 36 to 80) who underwent arthroscopic meniscectomy for a meniscal tear in the same period, and had no evidence of shoulder pathology. These patients were frequency-matched by age (within 3 years) and gender with patients of Group 1.Main outcome measure:Measurement of fasting plasma glucose levels.Results:Patients with rotator cuff tears (Group 1) showed statistically significantly higher fasting plasma glucose levels within the normoglycaemic range (p = 0.007) than patients with meniscal tear (Group 2).Conclusions:The present study suggests that normal, but in the high range of normal, increasing plasma glucose levels may be a risk factor for rotator cuff tear. An enhanced understanding of these factors holds the promise of new approaches to the prevention and management of rotator cuff tears.
Transactional events for ML
Authors: Effinger-Dean Laura , Kehrt Matthew , Grossman Dan 
Published: September 2008

Transactional events (TE) are an approach to concurrent programming that enriches the first-class synchronous message-passing of Concurrent ML (CML) with a combinator that allows multiple messages to be passed as part of one all-or-nothing synchronization. Donnelly and Fluet (2006) designed and implemented TE as a Haskell library and demonstrated that it enables elegant solutions to programming patterns that are awkward or impossible in CML. However, both the definition and the implementation of TE relied fundamentally on the code in a synchronization not using mutable memory, an unreasonable assumption for mostly functional languages like ML where functional interfaces may have impure implementations.
We present a definition and implementation of TE that supports ML-style references and nested synchronizations, both of which were previously unnecessary due to Haskell's more restrictive type system. As in prior work, we have a high-level semantics that makes nondeterministic choices such that synchronizations succeed whenever possible and a low-level semantics that uses search to implement the high-level semantics soundly and completely. The key design trade-off in the semantics is to allow updates to mutable memory without requiring the implementation to consider all possible thread interleavings. Our solution uses first-class heaps and allows interleavings only when a message is sent or received. We have used Coq to prove the high- and low-level semantics equivalent.
We have implemented our approach by modifying the Objective Caml run-time system. By modifying the run-time system, rather than relying solely on a library, we can eliminate the potential for nonterminating computations within unsuccessful synchronizations to run forever.
Functional translation of a calculus of capabilities
Authors: Charguéraud Arthur , Pottier François 
Published: September 2008

Reasoning about imperative programs requires the ability to track aliasing and ownership properties. We present a type system that provides this ability, by using regions, capabilities, and singleton types. It is designed for a high-level calculus with higher-order functions, algebraic data structures, and references (mutable memory cells). The type system has polymorphism, yet does not require a value restriction, because capabilities act as explicit store typings.
We exhibit a type-directed, type-preserving, and meaning-preserving translation of this imperative calculus into a pure calculus. Like the monadic translation, this is a store-passing translation. Here, however, the store is partitioned into multiple fragments, which are threaded through a computation only if they are relevant to it. Furthermore, the decomposition of the store into fragments can evolve dynamically to reflect ownership transfers.
The translation offers deep insight about the inner workings and soundness of the type system. If coupled with a semantic model of its target calculus, it leads to a semantic model of its imperative source calculus. Furthermore, it provides a foundation for our long-term objective of designing a system for specifying and certifying imperative programs with dynamic memory allocation.
Paradise
Authors: Augustsson Lennart , Mansell Howard , Sittampalam Ganesh 
Published: September 2008

We have implemented a two-stage language, Paradise, for building reusable components which are used to price financial products. Paradise is embedded in Haskell and makes heavy use of type-class based overloading, allowing the second stage to be compiled into a variety of backend platforms.
Paradise has enabled us to begin moving away from implementation directly in monolithic Excel spreadsheets and towards a more modular and retargetable approach.
A scheduling framework for general-purpose parallel languages
Authors: Fluet Matthew , Rainey Mike , Reppy John 
Published: September 2008

The trend in microprocessor design toward multicore and manycore processors means that future performance gains in software will largely come from harnessing parallelism. To realize such gains, we need languages and implementations that can enable parallelism at many different levels. For example, an application might use both explicit threads to implement course-grain parallelism for independent tasks and implicit threads for fine-grain data-parallel computation over a large array. An important aspect of this requirement is supporting a wide range of different scheduling mechanisms for parallel computation.
In this paper, we describe the scheduling framework that we have designed and implemented for Manticore, a strict parallel functional language. We take a micro-kernel approach in our design: the compiler and runtime support a small collection of scheduling primitives upon which complex scheduling policies can be implemented. This framework is extremely flexible and can support a wide range of different scheduling policies. It also supports the nesting of schedulers, which is key to both supporting multiple scheduling policies in the same application and to hierarchies of speculative parallel computations.
In addition to describing our framework, we also illustrate its expressiveness with several popular scheduling techniques. We present a (mostly) modular approach to extending our schedulers to support cancellation. This mechanism is essential for implementing eager and speculative parallelism. We finally evaluate our framework with a series of benchmarks and an analysis.
Mixin' up the ML module system
Authors: Dreyer Derek , Rossberg Andreas 
Published: September 2008

ML modules provide hierarchical namespace management, as well as fine-grained control over the propagation of type information, but they do not allow modules to be broken up into mutually recursive, separately compilable components. Mixin modules facilitate recursive linking of separately compiled components, but they are not hierarchically composable and typically do not support type abstraction. We synthesize the complementary advantages of these two mechanisms in a novel module system design we call MixML.
A MixML module is like an ML structure in which some of the components are specified but not defined. In other words, it unifies the ML structure and signature languages into one. MixML seamlessly integrates hierarchical composition, translucent MLstyle data abstraction, and mixin-style recursive linking. Moreover, the design of MixML is clean and minimalist; it emphasizes how all the salient, semantically interesting features of the ML module system (as well as several proposed extensions to it) can be understood simply as stylized uses of a small set of orthogonal underlying constructs, with mixin composition playing a central role.