bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel Cell-Associated Protection Assay Demonstrates the Ability of Certain Antibiotics To Protect Ocular Surface Cell Lines from Subsequent Clinical
Staphylococcus aureus
Challenge
Authors: Wingard J. B. , Romanowski E. G. , Kowalski R. P. , Mah F. S. , Ling Y. , Bilonick R. A. , Shanks R. M. Q. 
Published: June 2011

ABSTRACT

In vivo
effectiveness of topical antibiotics may depend on their ability to associate with epithelial cells to provide continued protection, but this contribution is not measured by standard antibiotic susceptibility tests. We report a new
in vitro
method that measures the ability of test antibiotics azithromycin (AZM), erythromycin (ERY), tetracycline (TET), and bacitracin (BAC) to associate with mammalian cells and to protect these cells from destruction by bacteria. Mammalian cell lines were grown to confluence using antibiotic-free medium and then incubated in medium containing a single antibiotic (0 to 512 μg/ml). After incubation, the cells were challenged with
Staphylococcus aureus
ocular isolates, without antibiotics added to the culture medium. Epithelial cell layer integrity was assessed by gentian violet staining, and the minimum cell layer protective concentration (MCPC) of an antibiotic sufficient to protect the mammalian cells from
S. aureus
was determined. Staining was also quantified and analyzed. Bacterial viability was determined by culture turbidity and growth on agar plates. Preincubation of Chang and human corneal limbal epithelial cells with AZM, ERY, and TET at ≥64 μg/ml provided protection against AZM-susceptible
S. aureus
strains, with increasing protection at higher concentrations. TET toxicity was demonstrated at >64 μg/ml, whereas AZM displayed toxicity to one cell line at 512 μg/ml. BAC failed to show consistent protection at any dose, despite bacterial susceptibility to BAC as determined by traditional antibiotic susceptibility testing. A range of antibiotic effectiveness was displayed in this cell association assay, providing data that may be considered in addition to traditional testing when determining therapeutic dosing regimens.
Genetic Context and Structural Diversity of Class 1 Integrons from Human Commensal Bacteria in a Hospital Intensive Care Unit
Authors: Betteridge Thu , Partridge Sally R. , Iredell Jonathan R. , Stokes H. W. 
Published: June 2011

ABSTRACT

Most surveys for class 1 integrons are at least partly predicated on PCR screening that targets integron conserved regions. However, class 1 integrons are structurally diverse, so dependence on conserved regions may lead to missing clinically relevant examples of class 1 integrons. Here, we surveyed a commensal population of bacteria from patients in an intensive care unit to identify class 1 integrons irrespective of their structure or genetic context. We identified several examples of class 1 integrons linked to complete Tn
402
-like or Tn
402
hybrid transposition modules and diverse insertion points with respect to the inverted repeat IRi boundary. The diversity and abundance of class 1 integrons identified are such that many novel elements seen here would not have been identified by commonly used methods, and they revealed an additional level of complexity.
PrsW Is Required for Colonization, Resistance to Antimicrobial Peptides, and Expression of Extracytoplasmic Function σ Factors in Clostridium difficile
Authors: Ho Theresa D. , Ellermeier Craig D. 
Published: June 2011

ABSTRACT

Clostridium difficile
is an anaerobic, Gram-positive, spore-forming, opportunistic pathogen that is the most common cause of hospital-acquired infectious diarrhea. In numerous pathogens, stress response mechanisms are required for survival within the host. Extracytoplasmic function (ECF) σ factors are a major family of signal transduction systems, which sense and respond to extracellular stresses. We have identified three
C. difficile
ECF σ factors. These ECF σ factors, CsfT, CsfU, and CsfV, induce their own expressions and are negatively regulated by their cognate anti-σ factors, RsiT, RsiU, and RsiV, respectively. The levels of expression of these ECF σ factors increase following exposure to the antimicrobial peptides bacitracin and/or lysozyme. The expressions of many ECF σ factors are controlled by site 1 and site 2 proteases, which cleave anti-σ factors. Using a retargeted group II intron, we generated a
C. difficile
mutation in
prsW
, a putative site 1 protease. The
C. difficile prsW
mutant exhibited decreased levels of expression of CsfT and CsfU but not of CsfV. When expressed in a heterologous host,
C. difficile
PrsW was able to induce the degradation of RsiT but not of RsiU. When the
prsW
mutant was tested in competition assays against its isogenic parent in the hamster model of
C. difficile
infection, we found that the
prsW
mutant was 30-fold less virulent than the wild type. The
prsW
mutant was also significantly more sensitive to bacitracin and lysozyme than the wild type in
in vitro
competition assays. Taken together, these data suggest that PrsW likely regulates the activation of the ECF σ factor CsfT in
C. difficile
and controls the resistance of
C. difficile
to antimicrobial peptides that are important for survival in the host.
CD1d-Independent Activation of Invariant Natural Killer T Cells by Staphylococcal Enterotoxin B through Major Histocompatibility Complex Class II/T Cell Receptor Interaction Results in Acute Lung Injury
Authors: Rieder Sadiye Amcaoglu , Nagarkatti Prakash , Nagarkatti Mitzi 
Published: June 2011

ABSTRACTThere are two important mechanisms of activation of invariant natural killer T cells (iNKT cells) by microbes: direct activation of the invariant T-cell receptor (TCR) by microbial glycolipids presented by CD1d and indirect activation, mediated by the responses of antigen-presenting cells to microbes. In this study, we provide evidence for a novel CD1d-independent direct activation of iNKT cells involving a microbial protein superantigen presented in the context of major histocompatibility complex class II (MHC-II), which plays a critical role in pathogenesis, thereby redefining the role of iNKT cells. Intranasal exposure to staphylococcal enterotoxin B (SEB) in C57BL/6 wild-type mice caused acute lung injury (ALI) characterized by vascular leak, cytokine storm, and infiltration of mononuclear cells in the lungs. In contrast, the vascular leak and inflammation were decreased by ∼50% in NKT cell-deficient Jα18−/−and CD1d−/−mice following SEB exposure, which was reversed following adoptive transfer of iNKT cells into CD1d−/−mice.In vitro, SEB could directly stimulate iNKT cells in a CD1d-independent manner via MHC-II/TCR interaction, specifically involving Vβ8. These studies not only demonstrate that iNKT cells can be activated directly by a bacterial protein superantigen independent of CD1d but also indicate that in addition to the conventional T cells, iNKT cells play a critical role in SEB-mediated ALI.
Migratory Activation of Primary Cortical Microglia upon Infection with Toxoplasma gondii
Authors: Dellacasa-Lindberg Isabel , Fuks Jonas M. , Arrighi Romanico B. G. , Lambert Henrik , Wallin Robert P. A. , Chambers Benedict J. , Barragan Antonio 
Published: June 2011

ABSTRACT

Disseminated toxoplasmosis in the central nervous system (CNS) is often accompanied by a lethal outcome. Studies with murine models of infection have focused on the role of systemic immunity in control of toxoplasmic encephalitis, while knowledge remains limited on the contributions of resident cells with immune functions in the CNS. In this study, the role of glial cells was addressed in the setting of recrudescent
Toxoplasma
infection in mice. Activated astrocytes and microglia were observed in the close vicinity of foci with replicating parasites
in situ
in the brain parenchyma.
Toxoplasma gondii
tachyzoites were allowed to infect primary microglia and astrocytes
in vitro
. Microglia were permissive to parasite replication, and infected microglia readily transmigrated across transwell membranes and cell monolayers. Thus, infected microglia, but not astrocytes, exhibited a hypermotility phenotype reminiscent of that recently described for infected dendritic cells. In contrast to gamma interferon-activated microglia,
Toxoplasma
-infected microglia did not upregulate major histocompatibility complex (MHC) class II molecules and the costimulatory molecule CD86. Yet
Toxoplasma
-infected microglia and astrocytes exhibited increased sensitivity to T cell-mediated killing, leading to rapid parasite transfer to effector T cells
in vitro
. We hypothesize that glial cells and T cells, besides their role in triggering antiparasite immunity, may also act as “Trojan horses,” paradoxically facilitating dissemination of
Toxoplasma
within the CNS. To our knowledge, this constitutes the first report of migratory activation of a resident CNS cell by an intracellular parasite.
Oral Exposure to Trypanosoma cruzi Elicits a Systemic CD8+T Cell Response and Protection against Heterotopic Challenge
Authors: Collins Matthew H. , Craft Julie M. , Bustamante Juan M. , Tarleton Rick L. 
Published: June 2011

ABSTRACTTrypanosoma cruziinfects millions of people in Latin America and often leads to the development of Chagas disease.T. cruziinfection can be acquired at or near the bite site of the triatomine vector, butper osinfection is also a well-documented mode of transmission, as evidenced by recent microepidemics of acute Chagas disease attributed to the consumption of parasite-contaminated foods and liquids. It would also be convenient to deliver vaccines forT. cruziby the oral route, particularly live parasite vaccines intended for the immunization of reservoir hosts. For these reasons, we were interested in better understanding immunity toT. cruzifollowing oral infection or oral vaccination, knowing that the route of infection and site of antigen encounter can have substantial effects on the ensuing immune response. Here, we show that the route of infection does not alter the ability ofT. cruzito establish infection in muscle tissue nor does it impair the generation of a robust CD8+T cell response. Importantly, oral vaccination with attenuated parasites provides protection against wild-type (WT)T. cruzichallenge. These results strongly support the development of whole-organism-based vaccines targeting reservoir species as a means to alleviate the burden of Chagas disease in affected regions.
Oligopeptide Permease A5 Modulates Vertebrate Host-Specific Adaptation of Borrelia burgdorferi
Authors: Raju B. V. Subba , Esteve-Gassent Maria D. , Karna S. L. Rajasekhar , Miller Christine L. , Van Laar Tricia A. , Seshu J. 
Published: June 2011

ABSTRACT

Borrelia burgdorferi
, the agent of Lyme disease, undergoes rapid adaptive gene expression in response to signals unique to its arthropod vector or vertebrate hosts. Among the upregulated genes under vertebrate host conditions is one of the five annotated homologs of oligopeptide permease A (OppA5, BBA34). A mutant lacking
oppA5
was constructed in an lp25-deficient isolate of
B. burgdorferi
strain B31, and the minimal regions of infectivity were restored via a shuttle vector pBBE22 with or without an intact copy of
bba34
. Immunoblot analysis of the
bba34
mutant revealed a reduction in the levels of RpoS, BosR, and CsrA
Bb
with a concomitant reduction in the levels of OspC, DbpA, BBK32, and BBA64. There were no changes in the levels of OspA, NapA, P66, and three other OppA orthologs. Quantitative transcriptional analysis correlated with the changes in the protein levels. However, the
bba34
mutant displayed comparable infectivities in the C3H/HeN mice and the wild-type strain, despite the reduction in several pathogenesis-related proteins. Supplementation of the growth medium with increased levels of select components, notably sodium acetate and sodium bicarbonate, restored the levels of several proteins in the
bba34
mutant to wild-type levels. We speculate that the transport of acetate appears to contribute to the accumulation of key metabolites, like acetyl phosphate, that facilitate the adaptation of
B. burgdorferi
to the vertebrate host by the activation of the Rrp2-RpoN-RpoS pathway. These studies underscore the importance of solute transport to host-specific adaptation of
B. burgdorferi
.
Lack of Association between theTlr4(Lpsd/Lpsd) Genotype and Increased Susceptibility to Escherichia coli Bladder Infections in Female C3H/HeJ Mice
Authors: Suhs Kaleigh A. , Marthaler Brodie R. , Welch Rodney A. , Hopkins Walter J. 
Published: June 2011

ABSTRACTToll-like receptor 4 is thought to have a primary role in host defense againstEscherichia colibladder colonization, based on mouse models of urinary tract infection using C3H/HeJ female mice. This strain carries a point mutation in theTlr4gene, which renders the mice unresponsive to lipopolysaccharide (LPS) and thus limits the bladder inflammatory response and infection resolution. The importance ofTlr4as the sole genetic determinant of resistance or susceptibility can be questioned, however, by the observation that C3H/HeOuJ female mice with a functional Tlr4 do not effectively resolveE. colibladder infections. The present study further examined this inconsistency by investigating the association ofTlr4 LpsdandLpsnalleles with bladder infection susceptibility by using genetic crosses of C3H/HeJ mice withTlr4(Lpsn/Lpsn) or (Lpsn/Lpsd) mice. Heterozygous offspring of C3H/HeJ (Lpsd/Lpsd) × BALB/cAnN (Lpsn/Lpsn) mice successfully resolved bladder infections induced by a uropathogenicE. colistrain, while heterozygous mice from a C3H/HeJ (Lpsd/Lpsd) × C3H/HeOuJ (Lpsn/Lpsn) cross had severe infections. A backcross of C3H/HeJ (Lpsd/Lpsd) with (BALB/cAnN × C3H/HeJ)F1(Lpsn/Lpsd) produced mice that were either resistant or susceptible toE. colibladder infections and hadLpsd/LpsdorLpsn/LpsdTlr4genotypes. TheLpsd/LpsdorLpsn/Lpsdgenotypes were present in individual mice with unresolved bladder infections, and theLpsd/Lpsdgenotype was found in infection-resistant mice. These results indicate that at least one gene other thanTlr4strongly influences susceptibility toE. colibladder infections in C3H/HeJ mice.IMPORTANCEWe have previously demonstrated that mouse strains with either a functional or nonfunctional Tlr4 were not able to resolve inducedEscherichia colibladder infections and that a chromosomal site distinct fromTlr4was associated with an inability to resolve bladder infections in C3H/HeJ mice. The present study has further investigated the relevance of Tlr4 in bladder infection resolution by defining theTlr4alleles present in offspring of genetic crosses of C3H/HeJ mice with infection-resistant and -susceptible inbred strains. The results of these experiments showed that mice with a normal Tlr4 on different genetic backgrounds were not able to clearE. colibladder infections and that animals with a defective Tlr4 could successfully resolve infections. These results strongly imply the presence of a gene other than inTlr4as an important genetic determinant of infection resistance/susceptibility in C3H/HeJ and other inbred mouse strains used in mouse models of infectious diseases.
The role of physical activity on cardiometabolic risk in adult greek women
Authors: Papadopoulou EE , Kontopoulou K , Kouidi E , Psirropoulos D , Deligiannis A 
Published: June 2011

IntroductionCardiovascular disease (CVD) is the leading cause of death in Western populations. In clinical practice, the goal is to identify high-risk individuals, since global CVD risk information may contribute to CVD prevention. Therefore, it is important to take into account the metabolic syndrome-related CVD risk, as well as the risk posed by traditional CVD risk factors. Several studies have shown that physical inactivity is an independent risk factor for CVD, although it is not included in the traditional cardiometabolic risk factors. Limited information exists about the prevalence of cardiometabolic risk factors, the role of physical activity on them and the burden of CVD in the adult female Greek population.PurposeThe purpose of this study was to examine the effects of physical activity on the cardiometabolic risk factors in Greek healthy adult women.MethodsEighty eight women, aged 45.4±6.9 years, without any chronic disease, volunteered to participate in this study. All women were submitted to medical and anthropometric evaluation (measurement of waist circumference, weight, BMI and blood pressure) and laboratory testing for: total choles-terol, LDL, HDL, triglycerides, glucose, CRP, apoA1 and apoB (automatic biochemical analyzer, Roche). Finally, all women filled-in a questionnaire of physical activity (International Physical Activity Questionnaire-IPAQ).ResultsOf the total sample, 60.2% had a positive family his-tory of CVD, 46.6% were smokers and 9.1% alcohol drink-ers. Physical activity, based on the IPAQ, was found to have a mixed impact on the traditional cardiometabolic risk factors, by affecting mainly the levels of total cholesterol and HDL cholesterol. There was no correlation found among physical activity, blood pressure and the rest of the studied biochemical parameters in women.ConclusionsIncreased physical activity can reduce the car-diometabolic risk and improve the lipid profile in Greek adult women. Our results indicated that regular physical activity of any kind is essential for fitness and health. All health care professionals are encouraged to inform, consult and motivate individuals to be active.
The effect of ankle and knee bracing on joint stability and performance during different tasks
Authors: Richards Jim 
Published: June 2011

Braces are commonly used for prevention and treatment of ankle and knee injuries by individuals who take part in sporting activities which involve challenges to the stability of joints. However, the use of ankle and knee bracing is less common in the conservative management of joint pain and pathology which is not sporting related. In all cases, the braces are attempting to provide improved stability of the joints in the coronal and transverse plane, but there has been much debate on whether bracing offers a functional or proprioceptive effect.Much of the biomechanical testing to date has been conducted using very simple biomechanical models, which allow do not allow accurate measures of the movement and moments about the foot, ankle and knee joints in the coronal and transverse planes. From this it is safe to say that the effect of ankle and knee bracing on the coronal and transverse plane mechanics of the lower limb have not received any adequate attention in the research literature, although clinically these are the very things that such devices often claim to support and control. The importance of coronal and torsional movement and moments of the foot, ankle and knee joints has previously been identified. However, little or no work has been published to see how the torsional and coronal mechanics of the ankle and knee joints are changed during functional tasks using devices designed to control and give stability to these joints.This workshop will consider the action of several methods of orthotic management of the ankle and knee joints on a variety of conditions by considering the research evidence. In each case, advanced methods of analysis have been used to determine the biomechanical changes and how these can be related to the clinical benefits. This will highlight not just the effects about the foot and ankle but also the effects of treating the foot and ankle on the knee, hip and pelvis. The data on a variety of methods of bracing for patellofemoral pain and ankle stability will be considered, with particular attention on the nature of the functional and proprioceptive effects of each method.
Cost-benefit analysis in occupational health: a comparison of intervention scenarios for occupational asthma and rhinitis among bakery workers
Authors: Meijster Tim , van Duuren-Stuurman Birgit , Heederik Dick , Houba Remko , Koningsveld Ernst , Warren Nicholas , Tielemans Erik 
Published: June 2011

ObjectivesUse of cost-benefit analysis in occupational health increases insight into the intervention strategy that maximises the cost-benefit ratio. This study presents a methodological framework identifying the most important elements of a cost-benefit analysis for occupational health settings. One of the main aims of the methodology is to evaluate cost-benefit ratios for different stakeholders (employers, employees and society). The developed methodology was applied to two intervention strategies focused on reducing respiratory diseases.MethodsA cost-benefit framework was developed and used to set up a calculation spreadsheet containing the inputs and algorithms required to calculate the costs and benefits for all cost elements. Inputs from a large variety of sources were used to calculate total costs, total benefits, net costs and the benefit-to-costs ratio for both intervention scenarios.ResultsImplementation of a covenant intervention program resulted in a net benefit of €16 848 546 over 20 years for a population of 10 000 workers. Implementation was cost-effective for all stakeholders. For a health surveillance scenario, total benefits resulting from a decreased disease burden were estimated to be €44 659 352. The costs of the interventions could not be calculated.ConclusionThis study provides important insights for developing effective intervention strategies in the field of occupational medicine. Use of a model based approach enables investigation of those parameters most likely to impact on the effectiveness and costs of interventions for work related diseases. Our case study highlights the importance of considering different perspectives (of employers, society and employees) in assessing and sharing the costs and benefits of interventions.
Heterogeneity Maintenance in Glioblastoma: A Social Network
Authors: Bonavia Rudy , Inda Maria-del-Mar , Cavenee Webster K. , Furnari Frank B. 
Published: June 2011

Abstract
Glioblastoma multiforme (GBM), the most common intracranial tumor in adults, is characterized by extensive heterogeneity at the cellular and molecular levels. This insidious feature arises inevitably in almost all cancers and has great significance for the general outcome of the malignancy, because it confounds our understanding of the disease and also intrinsically contributes to the tumor's aggressiveness and poses an obstacle to the design of effective therapies. The classic view that heterogeneity arises as the result of a tumor's “genetic chaos” and the more contemporary cancer stem cell (CSC) hypothesis tend to identify a single cell population as the therapeutic target: the prevailing clone over time in the first case and the CSC in the latter. However, there is growing evidence that the different tumor cell populations may not be simple bystanders. Rather, they can establish a complex network of interactions between each other and with the tumor microenvironment that eventually strengthens tumor growth and increases chances to escape therapy. These differing but complementary ideas about the origin and maintenance of tumor heterogeneity and its importance in GBM are reviewed here. Cancer Res; 71(12); 4055–60. ©2011 AACR.