bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the Role of the Pathogenicity Island andvapGin the Virulence of the Intracellular Actinomycete PathogenRhodococcus equi
Authors: Coulson Garry B. , Agarwal Shruti , Hondalus Mary K. 
Published: May 2010

ABSTRACTRhodococcus equi, a facultative intracellular pathogen of macrophages, causes severe, life-threatening pneumonia in young foals and in people with underlying immune deficiencies.R. equivirulence is dependent on the presence of a large virulence plasmid that houses a pathogenicity island (PAI) encoding a novel family of surface-localized and secreted proteins of largely unknown function termed thevirulence-associatedproteins (VapACDEFGHI). To date,vapAand its positive regulatorsvirRandorf8are the only experimentally established virulence genes residing on the virulence plasmid. In this study, a PAI deletion mutant was constructed and, as anticipated, was attenuated for growth both in macrophages and in mice due to the absence ofvapAexpression. Expression ofvapAin the PAI mutant from a constitutive promoter, thereby eliminating the requirement for the PAI-encodedvapAregulators, resulted in delayed bacterial clearancein vivo, yet full virulence was not restored, indicating that additional virulence genes are indeed located within the deleted pathogenicity island region. Based on previous reports demonstrating that the PAI-carried genevapGis highly upregulated in macrophages and in the lungs ofR. equi-infected foals, we hypothesized thatvapGcould be an important virulence factor. However, analysis of a markedvapGdeletion mutant determined the gene to be dispensable for growth in macrophages andin vivoin mice.
Shiga Toxin 2 and Flagellin from Shiga-ToxigenicEscherichia coliSuperinduce Interleukin-8 through Synergistic Effects on Host Stress-Activated Protein Kinase Activation
Authors: Jandhyala Dakshina M. , Rogers Trisha J. , Kane Anne , Paton Adrienne W. , Paton James C. , Thorpe Cheleste M. 
Published: May 2010

ABSTRACTShiga toxins expressed in the intestinal lumen during infection with Shiga-toxigenicEscherichia colimust translocate across the epithelium and enter the systemic circulation to cause systemic (pathological) effects, including hemolytic uremic syndrome. The transepithelial migration of polymorphonuclear leukocytes in response to chemokine expression by intestinal epithelial cells is thought to promote uptake of Stx from the intestinal lumen by compromising the epithelial barrier. In the present study, we investigated the hypothesis that flagellin acts in conjunction with Shiga toxin to augment this chemokine expression. We investigated the relative contributions of nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling to transcription and translation of interleukin-8. Using reporter gene constructs, we showed that flagellin-mediated interleukin-8 gene transcription is heavily dependent on both NF-κB and extracellular signal-regulated kinase 1 and 2 (ERK-1/2) activation. In contrast, inhibition of p38 has no detectable effect on interleukin-8 gene transcription, even though flagellin-mediated activation of host p38 is critical for maximal interleukin-8 protein expression. Inhibition of MAPK-interacting kinase 1 suggests that p38 signaling affects the posttranscriptional regulation of interleukin-8 protein expression induced by flagellin. Cotreatment with Stx2 and flagellin results in a synergistic upregulation of c-Jun N-terminal protein kinases (JNKs), p38 activation, and a superinduction of interleukin-8 mRNA. This synergism was also evident at the protein level, with increased interleukin-8 protein detectable following cotreatment with flagellin and Stx2. We propose that flagellin, in conjunction with Shiga toxin, synergistically upregulates stress-activated protein kinases, resulting in superinduction of interleukin-8 and, ultimately, absorption of Stx into the systemic circulation.
Complement Receptor 1 Expression on Mouse Erythrocytes Mediates Clearance ofStreptococcus pneumoniaeby Immune Adherence
Authors: Li Jie , Wang Jennifer P. , Ghiran Ionita , Cerny Anna , Szalai Alexander J. , Briles David E. , Finberg Robert W. 
Published: May 2010

ABSTRACTComplement-containing immune complexes can be presented to phagocytes by human erythrocytes bearing complement receptor 1 (CR1). Although this has long been assumed to be a mechanism by which humans are able to protect themselves from “extracellular” bacteria such as pneumococci, there is little direct evidence. In these studies we have investigated this question by comparing results for erythrocytes from transgenic mice expressing human CR1 on their erythrocytes to the results for wild-type mouse erythrocytes that do not express CR1. We demonstrate that human CR1 expression on murine erythrocytes allows immune adherence to beads opsonized with either mouse or human serum as a source of complement. The role of CR1 in immune adherence was supported by studies showing that it was blocked by the addition of antibody to human CR1. Furthermore, human CR1 expression enhances the immune adherence of opsonized pneumococci to erythrocytesin vitro, and the pneumococci attached to erythrocytes via CR1 can be transferredin vitroto live macrophages. Even more importantly, we observed that if complement-opsonized pneumococci are injected intravenously with CR1+mouse erythrocytes into wild-type mice (after a shortin vitroincubation), they are cleared faster than opsonized pneumococci similarly injected with wild-type mouse erythrocytes. Finally, we have shown that the intravenous (i.v.) injection of pneumococci into CR1+mice also results in more rapid blood clearance than in wild-type mice. These data support that immune adherence via CR1 on erythrocytes likely plays an important role in the clearance of opsonized bacteria from human blood.
Polyamines Can Increase Resistance ofNeisseria gonorrhoeaeto Mediators of the Innate Human Host Defense
Authors: Goytia Maira , Shafer William M. 
Published: May 2010

ABSTRACTPolyamines are biogenic polycationic molecules involved in key cellular functions. Extracellular polyamines found in bodily fluids or laboratory media can be imported by bacteria or bind to negatively charged bacterial surface structures, where they can impair binding of antimicrobials. We hypothesized that the presence of polyamines in fluids that bathe urogenital mucosal surfaces could alter the susceptibility of the sexually transmitted strict human pathogenNeisseria gonorrhoeaeto mediators of the innate host defense. Herein we report that polyamines can significantly increase gonococcal resistance to two structurally diverse cationic antimicrobial peptides (polymyxin B and LL-37) but not to antibiotics that exert activity in the cytosol or periplasm (e.g., ciprofloxacin, spectinomycin, or penicillin). The capacity of polyamines to increase gonococcal resistance to cationic antimicrobial peptides was dose dependent, correlated with the degree of cationicity, independent of a polyamine transport system involving the polyamine permeases PotH and PotI, and was reversible. In addition, we found that polyamines increase gonococcal resistance to complement-mediated killing by normal human serum. We propose that polyamines in genital mucosal fluids may enhance gonococcal survival during infection by reducing bacterial susceptibility to host-derived antimicrobials that function in innate host defense.
The Structure ofNeisseria meningitidisLipid A Determines Outcome in Experimental Meningococcal Disease
Authors: Fransen Floris , Hamstra Hendrik Jan , Boog Claire J. , van Putten Jos P. , van den Dobbelsteen Germie P. J. M. , van der Ley Peter 
Published: May 2010

ABSTRACTLipopolysaccharide (LPS), a major component of the meningococcal outer membrane, is sensed by the host through activation of Toll-like receptor 4 (TLR4). Recently, we demonstrated that a surprisingly large fraction ofNeisseria meningitidisdisease isolates are lipid A mutants, due to inactivating mutations in thelpxL1gene. ThelpxL1mutants activate human TLR4 much less efficiently than wild-type bacteria, which may be advantageous by allowing them to escape from the innate immune system. Here we investigated the influence of lipid A structure on virulence in a mouse model of meningococcal sepsis. One limitation, however, is that murine TLR4 recognizeslpxL1mutant bacteria much better than human TLR4. We show that anlpxL2mutant, another lipid A mutant lacking an acyl chain at a different position, activates murine TLR4 less efficiently than thelpxL1mutant. Therefore, thelpxL2mutant in mice might be a better model for infections withlpxL1mutants in humans. Interestingly, we found that thelpxL2mutant is more virulent in mice than the wild-type strain, whereas thelpxL1mutant is actually much less virulent than the wild-type strain. These results demonstrate the crucial role ofN. meningitidislipid A structure in virulence.
Differential immunophenotypic analysis of dendritic cell tumours
Authors: Orii Tomohiko , Takeda Hiroaki , Kawata Sumio , Maeda Kunihiko , Yamakawa Mitsunori 
Published: May 2010

AimsThe phenotypic and biological characteristics of dendritic cell (DC) tumours have not been fully elucidated. The aim of this study was to compare the immunophenotypic characteristics of DC-related markers and cell-cycle-associated markers among DC tumours and finally to utilise them for differential diagnosis of DC tumours.MethodsTissue sections from 28 patients with DC tumours were immunohistochemically examined using DC-related and cell-cycle-associated markers.ResultsThe Langerhans cell histiocytosis (LCH) and Langerhans cell sarcoma (LCS) samples were positive for S-100 protein, CD1a, Langerin, fascin, DEC-205 and DC-SIGN. Interdigitating dendritic cell sarcoma (IDCS) was positive for S-100 protein and fascin and negative for Langerin. In addition, two IDCS samples were positive for CD1a, DEC-205 and DC-SIGN. The labelling indices of Ki-67, cyclin A, cyclin B1 and acetylated histone H3 on the LCS and IDCS specimens were significantly higher than those on the LCH specimens. The expression of p53 was also significantly higher in the LCS specimens than in the LCH specimens. The numbers of infiltrating CD123+and FOXP3+cells were also significantly higher in the LCS samples than in the LCH and IDCS samples. Follicular dendritic cell sarcoma was distinguished from other DC tumours by the lack of DC-SIGN, Langerin and DCE-205.ConclusionsThese results suggest that Langerin can be used to distinguish LCS from IDCS, and DC-SIGN and DEC-205 can be used to identify DC tumour cells. The frequency of cell-cycle-associated markers can be used for the differential diagnosis of malignant and benign DC tumours.
Recruitment of minority ethnic groups into clinical cancer research trials to assess adherence to the principles of the Department of Health Research Governance Framework: national sources of data and general issues arising from a study in one hospital trust in England
Authors: Godden Sylvia , Ambler Gareth , Pollock Allyson M 
Published: May 2010

BackgroundThis article describes the issues encountered when designing a study to evaluate recruitment of minority ethnic groups into clinical cancer research in order to monitor adherence to the principles for good practice set out in the Department of Health, Research Governance Framework, England.Methods(i) A review of routine data sources to determine whether their usefulness as a source of data on prevalence of cancer in the population by ethnic category. (ii) A local case study at one hospital trust to ascertain whether the ethnicity of cancer trial participants was representative of admitted cancer patients.Results(i) The lack of a comparator population makes it problematic to assess recruitment levels by ethnic group in clinical research. (ii) The odds of being in a trial were 30% lower for a member of a minority ethnic group compared to a white cancer patient after adjusting for disease, age and gender, OR 0.70 (0.53 to 0.94). These results differed for each ethnic group; Asian patients did not appear under-represented while Black and Chinese did so. However, there are important caveats to the findings based on the limited recording of ethnicity.ConclusionsThe lack of available data on the ethnicity of participants in clinical research and the prevalence of cancer in the population according to ethnicity makes it difficult to design a study to monitor representation of minority ethnic groups. This information is necessary to assess adherence to the Research Governance Framework principle that research evidence reflects the diversity of the population.
Ethical and existential challenges associated with a cancer diagnosis
Authors: Pascal Jan , Endacott Ruth 
Published: May 2010

BackgroundAt the point of cancer diagnosis, practitioners may wrestle with ethical dilemmas associated with medico-legal implications of diagnosis, treatment options and disclosure to family members. The patient's perspective can take a different route, focusing on ethical and existential questions about the value and purpose of life, culminating in the question: how do I lead my life after diagnosis?ObjectiveTo explore the ethical and existential challenges associated with a cancer diagnosis from the perspective of cancer survivors.DesignQualitative design using specifically phenomenological methods to enable focus on subjective experience. Two in-depth interviews were conducted over a 6-month period.SettingBendigo, Victoria, Australia.Participants15 participants (n=11 women and n=4 men) volunteered to be interviewed. Age ranged from 32 to 85 years of age; length of survival 0.5–25 years; with a range of cancer diagnoses.ResultsFindings demonstrated that participants experienced existential and ethical challenges associated with a cancer diagnosis and subsequent survivorhood. These challenges were present regardless of cancer stage or diagnostic type and pervaded throughout length of survival. The existential challenges included the experience of anxiety and uncertainty about recurrence and metastatic disease. In particular, participants reported iatrogenic uncertainty induced by tests and treatment with follow-up regimes underscoring the fragility of survivor status. Uncertainty served as a ‘wake-up call’ and precipitated ethical challenges. Such challenges involved making meaning of survivorhood and questioning of morals, values and relationships. At times these questions were painful and difficult, creating unease about leading a ‘good’ and purposeful life. Entering ethically rocky terrain was also considered identity enhancing, with reports that a cancer diagnosis could have benefits as well as challenges.ConclusionThis study identified a number of challenges associated with a cancer diagnosis; these have implications for the preparation of medical, nursing and social work practitioners and should be considered during the design of follow-up support for cancer patients and those in recovery.
Do long periods off work in peak expiratory flow monitoring improve the sensitivity of occupational asthma diagnosis?
Authors: Moore Vicky C , Jaakkola Maritta S , Burge Cedd B S G , Pantin Charles F A , Robertson Alastair S , Burge P Sherwood 
Published: May 2010

IntroductionSerial peak expiratory flow (PEF) monitoring is a useful confirmatory test for occupational asthma diagnosis. As weekends off work may not be long enough for PEF records to recover, this study investigated whether including longer periods off work in PEF monitoring improves the sensitivity of occupational asthma diagnosis.MethodsSerial PEF measurements from workers with occupational asthma and from workers not at work during their PEF record, containing minimum data amounts and at least one rest period with ≥7 consecutive days off work, were analysed. Diagnostic sensitivity and specificity of the area between the curves (ABC) score from waking time and Oasys score for occupational asthma were calculated for each record by including only consecutive rest days 1–3 in any rest period, including only consecutive rest days from day 4 onwards in any rest period or including all available data.ResultsAnalysing all available off work data (including periods away from work of ≥7 days) increased the mean ABC score by 17% from 35.1 to 41.0 l/min/h (meaning a larger difference between rest and work day PEF values) (p=0.331) and the Oasys score from 3.2 to 3.3 (p=0.588). It improved the sensitivity of the ABC score for an occupational asthma diagnosis from 73% to 80% while maintaining specificity at 96%. The effect on the Oasys score using discriminant analysis was small (sensitivity changed from 85% to 88%).ConclusionsSensitivity of PEF monitoring using the ABC score for the diagnosis of occupational asthma can be improved by having a longer period off work.
Influence of precommercial thinning on understory vegetation of young-growth Sitka spruce forests in southeastern Alaska
Authors: Cole Elizabeth C. , Hanley Thomas A. , Newton Michael 
Published: May 2010

The effects of precommercial thinning on the understory vegetative cover of 16- to 18-year-old spruce–hemlock ( Picea sitchensis (Bong.) Carrière – Tsuga heterophylla (Raf.) Sarg.) stands were studied in seven replicate areas over seven growing seasons postthinning. Vegetative cover was analyzed at the class level, but species-specific effects were examined in relation to their value as food for Sitka black-tailed deer ( Odocoileus hemionus sitkensis Cowan). When compared with unthinned controls, thinned stands (3.6–6.3 m spacing) had significantly greater understory cover. However, all thinned spacings led to similar understory cover. Conifer cover recovered to about two-thirds of its prethinning level within seven growing seasons posttreatment. Understory nonconiferous cover increased during the first 2–4 years postthinning but began to decline with increasing conifer cover during the next 3 years, nearly reaching pretreatment levels by year 7. In unthinned understories, vegetative cover had declined and was significantly lower than that beneath thinned stands. Summer food resource values for deer were increased by thinning. Winter food resource values were increased by thinning for snow-free conditions but were unaffected for conditions when herb-layer forbs were buried by snow.
Thinning and site quality influence aboveground tree carbon stocks in yellow-poplar forests of the southern Appalachians
Authors: Keyser Tara L. 
Published: May 2010

Little information exists regarding the effects of intermediate stand management activities (e.g., thinning) on C storage. This lack of information has created uncertainty regarding trade-offs between the benefits observed following thinning and C storage. Using long-term growth data, this study examines the effect of thinning on C storage while controlling for the effects of site quality in yellow-poplar ( Liriodendron tulipifera L.) forests throughout the southern Appalachian Mountains. In 1960, one hundred and eighteen 0.1 ha plots were established in yellow-poplar forests throughout the southern Appalachians and subsequently thinned to a randomly assigned residual basal area (RBA) (square metres per hectare). Carbon storage increased through time across all levels of RBA. RBA had a long-term effect on C storage with greater C storage occurring at greater RBA. On average-quality sites, thinning to 30 m2·ha–1stored 84% more C than thinning to 10 m2·ha–1. At no time did plots with progressively lower RBA store more C than plots with progressively higher RBA. The results from this study provide information about the effects of intermediate silvicultural disturbance on C dynamics of the aboveground live tree pool in a complex landscape and may be used to inform decisions regarding trade-offs between active management and C storage.
Caractérisation de la structure spatiale des individus ligneux dans une « brousse tachetée » au sud-ouest du Niger
Authors: Diouf Abdoulaye , Barbier Nicolas , Mahamane Ali , Lejoly Jean , Saadou Mahamane , Bogaert Jan 
Published: May 2010

La structure spatiale des végétations périodiques en zones arides est liée, selon des modèles d’auto-organisation, à des processus locaux (facilitation ou compétition). La présente étude visait à vérifier l’importance de ces processus et le rôle du Combretum micranthum G. Don à travers une description de la distribution spatiale des ligneux d’une brousse tachetée au sud-ouest du Niger à l’aide de la fonction K de Ripley. L’organisation spatiale des ligneux révèle une structure à deux échelles : (i) agrégative (rayon moyen, 9–15 m) et (ii) répulsive (vers 35 m), correspondant au patron périodique d’ensemble. Seul le C. micranthum présente une distribution similaire, suggérant un rôle d’espèce « clé de voûte », déterminant la structure d’ensemble. Une agrégation locale d’espèces secondaires autour du C. micranthum suggère fortement une facilitation de portée (1–3 m) proportionnelle au rayon moyen du houppier des arbustes matures, conformément aux prédictions des modèles et aux études empiriques de la dynamique hydrique du sol. L’absence de relation spatiale entre le C. micranthum et les autres espèces de la famille des Combretaceae formant entre elles des agrégats suggère l’existence d’une structure à trois composantes. Ces éléments permettront d’aiguiller les démarches empiriques et d’améliorer les modèles, lesquels s’avèrent indispensables pour la gestion des végétations sahéliennes face aux contraintes d’aridité et d’exploitation.
Simulating independence
Authors: Barak B. , Kindler G. , Shaltiel R. , Sudakov B. , Wigderson A. 
Published: May 2010

We present new explicit constructions of
deterministic
randomness extractors, dispersers and related objects. We say that a distribution
X
on binary strings of length
n
is a δ-source if
X
assigns probability at most 2

−δ
n

to any string of length
n
. For every δ>0, we construct the following poly(
n
)-time computable functions:

2-source disperser:
D:({0, 1}

n

)
2
→ {0, 1} such that for any two independent δ-sources
X
1
,
X
2
we have that the support of
D
(
X
1
,
X
2
) is {0, 1}.

Bipartite Ramsey graph:
Let
N
=2

n

. A corollary is that the function
D
is a 2-coloring of the edges of
K

N,N

(the complete bipartite graph over two sets of
N
vertices) such that any induced subgraph of size
N
δ
by
N
δ
is not monochromatic.

3-source extractor:
E
:({0, 1}
n
)
3
→ {0, 1} such that for any three independent δ-sources
X
1
,
X
2
,
X
3
we have that
E
(
X
1
,
X
2
,
X
3
) is
o
(1)-close to being an unbiased random bit.

No previous explicit construction was known for either of these for any δ<1/2, and these results constitute significant progress to long-standing open problems.

A component in these results is a new construction of condensers that may be of independent interest: This is a function
C
:{0, 1}
n
→ ({0, 1}
n/c
)
d
(where
c
and
d
are constants that depend only on δ) such that for every δ-source
X
one of the output blocks of
C(X)
is (exponentially close to) a 0.9-source. (This result was obtained independently by Ran Raz.)

The constructions are quite involved and use as building blocks other new and known objects. A recurring theme in these constructions is that objects that were designed to work with independent inputs, sometimes perform well enough with correlated, high entropy inputs.
The construction of the disperser is based on a new technique which we call “the challenge-response mechanism” that (in some sense) allows “identifying high entropy regions” in a given pair of sources using only one sample from the two sources.