bluuebunny/crossref_metadata_2025_split huggingface dataset:
Invasion-Inhibitory Antibodies Elicited by Immunization with Plasmodium vivax Apical Membrane Antigen-1 Expressed in Pichia pastoris Yeast
Authors: Vicentin Elaine C. , Françoso Kátia S. , Rocha Mariana V. , Iourtov Dmitri , dos Santos Fernanda L. , Kubrusly Flávia S. , Sakauchi Maria A. , Raw Isaias , Nosten Francois , Rénia Laurent , Rodrigues Mauricio M. , Russell Bruce , Soares Irene S. 
Published: December 2013

ABSTRACT

In a recent vaccine trial performed with African children, immunization with a recombinant protein based on
Plasmodium falciparum
apical membrane antigen 1 (AMA-1) conferred a significant degree of strain-specific resistance against malaria. To contribute to the efforts of generating a vaccine against
Plasmodium vivax
malaria, we expressed the ectodomain of
P. vivax
AMA-1 (PvAMA-1) as a secreted soluble protein in the methylotrophic yeast
Pichia pastoris
. Recognized by a high percentage of sera from individuals infected by
P. vivax
, this recombinant protein was found to have maintained its antigenicity. The immunogenicity of this protein was evaluated in mice using immunization protocols that included homologous and heterologous prime-boost strategies with plasmid DNA and recombinant protein. We used the following formulations containing different adjuvants: aluminum salts (Alum),
Bordetella pertussis
monophosphoryl lipid A (MPLA), flagellin FliC from
Salmonella enterica
serovar Typhimurium, saponin Quil A, or incomplete Freund's adjuvant (IFA). The formulations containing the adjuvants Quil A or IFA elicited the highest IgG antibody titers. Significant antibody titers were also obtained using a formulation developed for human use containing MPLA or Alum plus MPLA. Recombinant PvAMA-1 produced under “conditions of good laboratory practice” provided a good yield, high purity, low endotoxin levels, and no microbial contaminants and reproduced the experimental immunizations. Most relevant for vaccine development was the fact that immunization with PvAMA-1 elicited invasion-inhibitory antibodies against different Asian isolates of
P. vivax
. Our results show that AMA-1 expressed in
P. pastoris
is a promising antigen for use in future preclinical and clinical studies.
Eosinophil Deficiency Compromises Lung Defense against Aspergillus fumigatus
Authors: Lilly Lauren M. , Scopel Michaella , Nelson Michael P. , Burg Ashley R. , Dunaway Chad W. , Steele Chad 
Published: December 2013

ABSTRACTExposure to the moldAspergillus fumigatusmay result in allergic bronchopulmonary aspergillosis, chronic necrotizing pulmonary aspergillosis, or invasive aspergillosis (IA), depending on the host's immune status. Neutrophil deficiency is the predominant risk factor for the development of IA, the most life-threatening condition associated withA. fumigatusexposure. Here we demonstrate that in addition to neutrophils, eosinophils are an important contributor to the clearance ofA. fumigatusfrom the lung. AcuteA. fumigatuschallenge in normal mice induced the recruitment of CD11b+Siglec F+Ly-6GloLy-6CnegCCR3+eosinophils to the lungs, which was accompanied by an increase in lungEpx(eosinophil peroxidase) mRNA levels. Mice deficient in the transcription factor dblGATA1, which exhibit a selective deficiency in eosinophils, demonstrated impairedA. fumigatusclearance and evidence of germinating organisms in the lung. Higher burden correlated with lower mRNA expression ofEpx(eosinophil peroxidase) andPrg2(major basic protein) as well as lower interleukin 1β (IL-1β), IL-6, IL-17A, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and CXCL1 levels. However, examination of lung inflammatory cell populations failed to demonstrate defects in monocyte/macrophage, dendritic cell, or neutrophil recruitment in dblGATA1-deficient mice, suggesting that the absence of eosinophils in dlbGATA1-deficient mice was the sole cause of impaired lung clearance. We show that eosinophils generated from bone marrow have potent killing activity againstA. fumigtausin vitro, which does not require cell contact and can be recapitulated by eosinophil whole-cell lysates. Collectively, our data support a role for eosinophils in the lung response afterA. fumigatusexposure.
The Phosphoenolpyruvate Phosphotransferase System in Group A Streptococcus Acts To Reduce Streptolysin S Activity and Lesion Severity during Soft Tissue Infection
Authors: Gera Kanika , Le Tuquynh , Jamin Rebecca , Eichenbaum Zehava , McIver Kevin S. 
Published: December 2013

ABSTRACTObtaining essential nutrients, such as carbohydrates, is an important process for bacterial pathogens to successfully colonize host tissues. The phosphoenolpyruvate phosphotransferase system (PTS) is the primary mechanism by which bacteria transport sugars and sense the carbon state of the cell. The group A streptococcus (GAS) is a fastidious microorganism that has adapted to a variety of niches in the human body to elicit a wide array of diseases. A ΔptsImutant (enzyme I [EI] deficient) generated in three different strains of M1T1 GAS was unable to grow on multiple carbon sources (PTS and non-PTS). Complementation withptsIexpressed under its native promoter in single copy was able to rescue the growth defect of the mutant. In a mouse model of GAS soft tissue infection, all ΔptsImutants exhibited a significantly larger and more severe ulcerative lesion than mice infected with the wild type. Increased transcript levels ofsagAand streptolysin S (SLS) activity during exponential-phase growth was observed. We hypothesized that early onset of SLS activity would correlate with the severity of the lesions induced by the ΔptsImutant. In fact, infection of mice with a ΔptsI sagBdouble mutant resulted in a lesion comparable to that of either the wild type or asagBmutant alone. Therefore, a functional PTS is not required for subcutaneous skin infection in mice; however, it does play a role in coordinating virulence factor expression and disease progression.
The Adaptor CARD9 Is Required for Adaptive but Not Innate Immunity to Oral Mucosal Candida albicans Infections
Authors: Bishu Shrinivas , Hernández-Santos Nydiaris , Simpson-Abelson Michelle R. , Huppler Anna R. , Conti Heather R. , Ghilardi Nico , Mamo Anna J. , Gaffen Sarah L. 
Published: December 2013

ABSTRACT

Oropharyngeal candidiasis (OPC [thrush]) is an opportunistic infection caused by the commensal fungus
Candida albicans
. OPC is common in individuals with HIV/AIDS, infants, patients on chemotherapy, and individuals with congenital immune defects. Immunity to OPC is strongly dependent on the interleukin-23 (IL-23)/IL-17R axis, as mice and humans with defects in IL-17R signaling (
IL17F
,
ACT1
,
IL-17RA
) or in genes that direct Th17 differentiation (
STAT3
,
STAT1
,
CARD9
) are prone to mucocutaneous candidiasis. Conventional Th17 cells are induced in response to
C. albicans
infection via signals from C-type lectin receptors, which signal through the adaptor CARD9, leading to production of Th17-inducing cytokines such as IL-6, IL-1β, and IL-23. Recent data indicate that IL-17 can also be made by numerous innate cell subsets. These innate “type 17” cells resemble conventional Th17 cells, but they can be activated without need for prior antigen exposure. Because
C. albicans
is not a commensal organism in rodents and mice are thus naive to this fungus, we had the opportunity to assess the role of CARD9 in innate versus adaptive responses using an OPC infection model. As expected, CARD9
−/−
mice failed to mount an adaptive Th17 response following oral
Candida
infection. Surprisingly, however, CARD9
−/−
mice had preserved innate IL-17-dependent responses to
Candida
and were almost fully resistant to OPC. Thus, CARD9 is important primarily for adaptive immunity to
C. albicans
, whereas alternate recognition systems appear to be needed for effective innate responses.
Role of Epidermal Growth Factor Receptor Signaling in the Interaction of Neisseria meningitidis with Endothelial Cells
Authors: Slanina Heiko , Mündlein Sabrina , Hebling Sabrina , Schubert-Unkmeir Alexandra 
Published: December 2013

ABSTRACTNeisseria meningitidis, the causative agent of meningitis and septicemia, attaches to and invades various cell types. Both steps induce and/or require tyrosine phosphorylation of host cell proteins. Here, we used a phospho array platform to identify active receptor tyrosine kinases (RTKs) and key signaling nodes inN. meningitidis-infected brain endothelial cells to decipher RTK-dependent signaling pathways necessary for bacterial uptake. We detected several activated RTKs, including the ErbB family receptors epidermal growth factor receptor (EGFR), ErbB2, and ErbB4. We found that pharmacological inhibition and genetic ablation of ErbB receptor tyrosine phosphorylation and expression resulted in decreased bacterial uptake and heterologous expression of EGFR, ErbB2, or ErbB4 in Chinese ovary hamster (CHO-K1) cells, which do not express of EGFR and ErbB4; the decrease caused a significant increase in meningococcal invasion. Activation of EGFR and ErbB4 was mediated by transactivation via the common ligand HB-EGF (heparin-binding EGF-like ligand), which was significantly elevated in infected cell culture supernatants. We furthermore determined thatN. meningitidisinduced phosphorylation of EGFR at Tyr845 independent of ligand binding, which required c-Src activation and was involved in mediating uptake ofN. meningitidisinto eukaryotic cells. Increased uptake was repressed by expression of EGFR Y845F, which harbored a point mutation in the kinase domain. In addition, activation of ErbB4 at its autophosphorylation site, Tyr1284, and phosphorylation of ErbB2 Thr686 were observed. Altogether, our results provide evidence that EGFR, ErbB2, and ErbB4 are activated in response toN. meningitidisinfection and shed new light on the role of ErbB signaling in meningococcal infection biology.
Neither Dectin-2 nor the Mannose Receptor Is Required for Resistance to Coccidioides immitis in Mice
Authors: Viriyakosol Suganya , Jimenez Maria del Pilar , Saijo Sinobu , Fierer Joshua 
Published: December 2013

ABSTRACT

We investigated the roles of the mannose receptor (MR) and Dectin-2 in resistance to pulmonary coccidioidomycosis in C57BL/6 (B6) mice and in the interaction of myeloid cells with spherules, using B6 mice with targeted mutations in
Mrc1
and
Clec4n
. Spherules are the tissue form of
Coccidioides
, and we determined that the MR on bone marrow-derived dendritic cells (BMDC) was important for recognition of spherules (formalin-killed spherules [FKS]) and for secretion of interleukin 10 (IL-10) and proinflammatory cytokines in response to FKS by both elicited macrophages and BMDC. Infected MR knockout (KO) mice produced more IL-10 in their lungs than did B6 mice, and MR KO mice also made more protective Th-17 cytokines. In contrast to the MR, Dectin-2 was not required for recognition of FKS by BMDC or for the production of cytokines by BMDC in response to FKS. However, Dectin-2 KO was required for stimulation of elicited peritoneal macrophages. Despite that, lung cytokine levels were not significantly different in Dectin-2 KO mice and B6 mice 14 days after infection, except for IL-1β, which was higher in Dectin-2 KO lungs. Although both Dectin-2
−/−
and MR
−/−
myeloid cells had reduced proinflammatory cytokine responses to FKS
in vitro
, neither MR nor Dectin-2 deficiency reduced the resistance of B6 mice to pulmonary coccidioidomycosis.
Filifactor alocis Infection and Inflammatory Responses in the Mouse Subcutaneous Chamber Model
Authors: Wang Qian , Jotwani Ravi , Le Junyi , Krauss Jennifer L. , Potempa Jan , Coventry Susan C. , Uriarte Silvia M. , Lamont Richard J. 
Published: December 2013

ABSTRACT

Recent microbiome studies have implicated a role for
Filifactor alocis
in periodontal disease. In this study, we investigated the colonization and survival properties of
F. alocis
in a mouse subcutaneous chamber model of infection and characterized host innate immune responses. An infection of 10
9
F. alocis
successfully colonized all chambers; however, the infection was cleared after 72 h.
F. alocis
elicited a local inflammatory response with neutrophils recruited into the chambers at 2 h postinfection along with an increase in levels of the proinflammatory cytokines interleukin 1β (IL-1β), IL-6, and tumor necrosis factor (TNF).
F. alocis
also induced apoptosis in chamber epithelial cells and neutrophils. Consistent with resolution of infection, neutrophil numbers and cytokine levels returned to baseline by 72 h. Fluorescent
in situ
hybridization (FISH) and quantitative PCR demonstrated that
F. alocis
exited the chambers and spread to the spleen, liver, lung, and kidney. Massive neutrophil infiltration was observed in the spleen and lungs, and the recruited neutrophils were in close proximity to the infecting bacteria. Significant epithelial injury was observed in the kidneys. Infection of all tissues was resolved after 7 days. This first
in vivo
study of the pathogenicity of
F. alocis
shows that in the chamber model the organism can establish a proinflammatory, proapoptotic local infection which is rapidly resolved by the host concordant with neutrophil influx. Moreover,
F. alocis
can spread to, and transiently infect, remote tissues where neutrophils can also be recruited.
Identification of a Crucial Residue Required for Staphylococcus aureus LukAB Cytotoxicity and Receptor Recognition
Authors: DuMont Ashley L. , Yoong Pauline , Liu Xiang , Day Christopher J. , Chumbler Nicole M. , James David B. A. , Alonzo Francis , Bode Nadine J. , Lacy D. Borden , Jennings Michael P. , Torres Victor J. 
Published: December 2013

ABSTRACT

The bicomponent leukotoxins produced by
Staphylococcus aureus
kill host immune cells through osmotic lysis by forming β-barrel pores in the host plasma membrane. The current model for bicomponent pore formation proposes that octameric pores, comprised of two separate secreted polypeptides (S and F subunits), are assembled from water-soluble monomers in the extracellular milieu and multimerize on target cell membranes. However, it has yet to be determined if all staphylococcal bicomponent leukotoxin family members exhibit these properties. In this study, we report that leukocidin A/B (LukAB), the most divergent member of the leukotoxin family, exists as a heterodimer in solution rather than two separate monomeric subunits. Notably, this property was found to be associated with enhanced toxin activity. LukAB also differs from the other bicomponent leukotoxins in that the S subunit (LukA) contains 33- and 10-amino-acid extensions at the N and C termini, respectively. Truncation mutagenesis revealed that deletion of the N terminus resulted in a modest increase in LukAB cytotoxicity, whereas the deletion of the C terminus rendered the toxin inactive. Within the C terminus of LukA, we identified a glutamic acid at position 323 that is critical for LukAB cytotoxicity. Furthermore, we discovered that this residue is conserved and required for the interaction between LukAB and its cellular target CD11b. Altogether, these findings provide an in-depth analysis of how LukAB targets neutrophils and identify novel targets suitable for the rational design of anti-LukAB inhibitors.
Requirement of the Pseudomonas aeruginosa CbrA Sensor Kinase for Full Virulence in a Murine Acute Lung Infection Model
Authors: Yeung Amy T. Y. , Janot Laure , Pena Olga M. , Neidig Anke , Kukavica-Ibrulj Irena , Hilchie Ashley , Levesque Roger C. , Overhage Joerg , Hancock Robert E. W. 
Published: December 2013

ABSTRACT

Pseudomonas aeruginosa
is an opportunistic pathogen that is a major cause of respiratory tract and other nosocomial infections. The sensor kinase CbrA is a central regulator of carbon and nitrogen metabolism and
in vitro
also regulates virulence-related processes in
P. aeruginosa
. Here, we investigated the role of CbrA in two murine models of infection. In both peritoneal infections in leukopenic mice and lung infection models, the
cbrA
mutant was less virulent since substantially larger numbers of
cbrA
mutant bacteria were required to cause the same level of infection as wild-type or complemented bacteria. In contrast, in the chronic rat lung model the
cbrA
mutant grew and persisted as well as the wild type, indicating that the decrease of
in vivo
virulence of the
cbrA
mutant did not result from growth deficiencies on particular carbon substrates observed
in vitro
. In addition, a mutant in the cognate response regulator CbrB showed no defect in virulence in the peritoneal infection model, ruling out the involvement of certain alterations of virulence properties in the
cbrA
mutant including defective swarming motility, increased biofilm formation, and cytotoxicity, since these alterations are controlled through CbrB. Further investigations indicated that the mutant was more susceptible to uptake by phagocytes
in vitro
, resulting in greater overall bacterial killing. Consistent with the virulence defect, it took a smaller number of
Dictyostelium discoideum
amoebae to kill the
cbrA
mutant than to kill the wild type. Transcriptional analysis of the
cbrA
mutant during
D. discoideum
infection led to the conclusion that CbrA played an important role in the iron metabolism, protection of
P. aeruginosa
against oxidative stress, and the regulation of certain virulence factors.
Children with Invasive Staphylococcus aureus Disease Exhibit a Potently Neutralizing Antibody Response to the Cytotoxin LukAB
Authors: Thomsen Isaac P. , DuMont Ashley L. , James David B. A , Yoong Pauline , Saville Benjamin R. , Soper Nicole , Torres Victor J. , Creech C. Buddy 
Published: December 2013

ABSTRACT

Despite the importance of
Staphylococcus aureus
as a common invasive bacterial pathogen, the humoral response to infection remains inadequately defined, particularly in children. The purpose of this study was to assess the humoral response to extracellular staphylococcal virulence factors, including the bicomponent leukotoxins, which are critical for the cytotoxicity of
S. aureus
toward human neutrophils. Children with culture-proven
S. aureus
infection were prospectively enrolled and stratified by disease type. Fifty-three children were enrolled in the study, of which 90% had invasive disease. Serum samples were obtained during the acute (within 48 h) and convalescent (4 to 6 weeks postinfection) phases, at which point both IgG titers against
S. aureus
exotoxins were determined, and the functionality of the generated antibodies was evaluated. Molecular characterization of clinical isolates was also performed. We observed a marked rise in antibody titer from acute-phase to convalescent-phase sera for LukAB, the most recently described
S. aureus
bicomponent leukotoxin. LukAB production by the isolates was strongly correlated with cytotoxicity
in vitro
, and sera containing anti-LukAB antibodies potently neutralized cytotoxicity. Antibodies to
S. aureus
antigens were detectable in healthy pediatric controls but at much lower titers than in sera from infected subjects. The discovery of a high-titer, neutralizing antibody response to LukAB during invasive infections suggests that this toxin is produced
in vivo
and that it elicits a functional humoral response.
Scope of Nursing Care in Polish Intensive Care Units
Authors: Wysokiński Mariusz , Ksykiewicz-Dorota Anna , Fidecki Wiesław 
Published: December 2013

Introduction. The TISS-28 scale, which may be used for nursing staff scheduling in ICU, does not reflect the complete scope of nursing resulting from varied cultural and organizational conditions of individual systems of health care.Aim. The objective of the study was an attempt to provide an answer to the question what scope of nursing care provided by Polish nurses in ICU does the TISS-28 scale reflect?Material and Methods. The methods of working time measurement were used in the study. For the needs of the study, 252 hours of continuous observation (day-long observation) and 3.697 time-schedule measurements were carried out.Results. The total nursing time was 4125.79 min. (68.76 hours), that is, 60.15% of the total working time of Polish nurses during the period analyzed. Based on the median test, the difference was observed on the level ofχ2=16945.8, P<0.001between the nurses’ workload resulting from performance of activities qualified into the TISS-28 scale and load resulting from performance of interventions within the scopes of care not considered in this scale in Polish ICUs.Conclusions. The original version of the TISS-28 scale does not fully reflect the workload among Polish nurses employed in ICUs.
Prostate Cancer Genetic-susceptibility Locus on Chromosome 20q13 is Amplified and Coupled to Androgen Receptor-regulation in Metastatic Tumors
Authors: Labbé David P. , Nowak Dawid G. , Deblois Geneviève , Lessard Laurent , Giguère Vincent , Trotman Lloyd C. , Tremblay Michel L. 
Published: December 2013

Abstract
The 20q13 chromosomal region has been previously identified as the hereditary prostate cancer genetic-susceptibility locus on chromosome 20 (HPC20). In this study, the 20q13 region was shown to be frequently co-amplified with the androgen receptor (AR) in metastatic prostate cancer. Furthermore, the AR signaling axis, which plays an essential role in the pathogenesis of prostate cancer, was demonstrated to be central to the regulation of the 20q13 common amplified region (CAR). High-resolution mapping analyses revealed hot spots of AR recruitment to response elements in the vicinity of most genes located on the 20q13 CAR. Moreover, amplification of AR significantly co-occurred with CAR amplification on 20q13 and it was confirmed that the majority of AR-bound genes on the 20q13 CAR were indeed regulated by androgens. These data reveal that amplification of the AR is tightly linked to amplification of the AR-regulated CAR region on 20q13. These results suggest that the cross-talk between gene amplification and gene transcription is an important step in the development of castration-resistant metastatic disease.
Implications: These novel results are a noteworthy example of the cross-talk between gene amplification and gene transcription in the development of advanced prostate cancer.
Visual Overview: http://mcr.aacrjournals.org/content/early/2014/02/07/1541-7786.MCR-13-0477/F1.large.jpg. Mol Cancer Res; 12(2); 184–9. ©2013 AACR.
Pitiríase liquenóide
Authors: Foss Norma T. , Rocha Luiz S. D’Oliveira , Roselino Ana Maria F. , Donadi Eduardo A. 
Published: December 2013

Modelo de estudo:Estudo de prevalência. Objetivos: Embora a pitiríase liquenóide seja uma dermatose incomum, 12 casos foram por nós observados nos últimos três anos. Assim, neste estudo, avaliamos os perfis clínicos e histopatológicos dos pacientes com pitiríase liquenóide, atendidos na Divisão de Dermatologia. Além disso, tipificamos os antígenos HLA de classes I e II nesses pacientes.Metodologia: Foram estudados 21 pacientes com diagnóstico clínico e histopatológico de pitiríase liquenóide. As tipificações dos antígenos de histocompatibilidade de classes I e II foram realizadas, utilizando-se métodos sorológicos. Resultados: A maioria dos casos ocorreu entre crianças e ou adultos jovens, no outono e inverno. As lesões típicas de forma disseminada foram as mais freqüentes. Os achados histopatológicos mostraram lesões dos tipos agudo e crônico. O antígeno HLA-B17 estava significantemente aumentado nos pacientes em relação aos controles (P<0,005).Conclusões: Embora a etiologia da pitiríase liquenóide não seja conhecida, os achados aqui relatados mostram que o marcador HLA-B17 é prevalente entre os doentes.