bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of the Lipopolysaccharide-CD14 Complex for the Activity of Hemolysin from Uropathogenic
Escherichia coli
Authors: Månsson Lisa E. , Kjäll Peter , Pellett Shahaireen , Nagy Gábor , Welch Rodney A. , Bäckhed Fredrik , Frisan Teresa , Richter-Dahlfors Agneta 
Published: November 2006

ABSTRACT

Bacterial pathogens produce a variety of exotoxins, which often become associated with the bacterial outer membrane component lipopolysaccharide (LPS) during their secretion. LPS is a potent proinflammatory mediator; however, it is not known whether LPS contributes to cell signaling induced by those microbial components to which it is attached. This is partly due to the common view that LPS present in bacterial component preparations is an experimental artifact. The
Escherichia coli
exotoxin hemolysin (Hly) is a known inducer of proinflammatory signaling in epithelial cells, and the signal transduction pathway involves fluctuation of the intracellular-Ca
2+
concentration. Since LPS is known to interact with Hly, we investigated whether it is required as a cofactor for the activity of Hly. We found that the LPS/Hly complex exploits the CD14/LPS-binding protein recognition system to bring Hly to the cell membrane, where intracellular-Ca
2+
signaling is initiated via specific activation of the small GTPase RhoA. Hly-induced Ca
2+
signaling was found to occur independently of the LPS receptor TLR4, suggesting that the role of LPS/CD14 is to deliver Hly to the cell membrane. In contrast, the cytolytic effect triggered by exposure of cells to high Hly concentrations occurs independently of LPS/CD14. Collectively, our data reveal a novel molecular mechanism for toxin delivery in bacterial pathogenesis, where LPS-associated microbial compounds are targeted to the host cell membrane as a consequence of their association with LPS.
Different Roles of the Two High-Oxygen-Affinity Terminal Oxidases of
Brucella suis
: Cytochrome
c
Oxidase, but Not Ubiquinol Oxidase, Is Required for Persistence in Mice
Authors: Jiménez de Bagüés Maria Pilar , Loisel-Meyer Séverine , Liautard Jean-Pierre , Jubier-Maurin Véronique 
Published: November 2006

ABSTRACT

The survival of
Brucella suis
mutant strains in mice demonstrated different roles of the two high-oxygen-affinity terminal oxidases. The
cbb3
-type cytochrome
c
oxidase was essential for chronic infection in oxygen-deficient organs. Lack of the cytochrome
bd
ubiquinol oxidase led to hypervirulence of bacteria, which could rely on nitrite accumulation inhibiting the inducible nitric oxide synthase of the host.
Comparative Analysis of the Abilities of Shiga Toxins 1 and 2 To Bind to and Influence Neutrophil Apoptosis
Authors: Flagler Michael J. , Strasser Jane E. , Chalk Claudia L. , Weiss Alison A. 
Published: November 2006

ABSTRACT

Hemolytic-uremic syndrome (HUS), the life-threatening complication following infection by the intestinal pathogen
Escherichia coli
O157:H7, is due to the ability of the pathogen to produce toxins in the Shiga toxin (Stx) family. Activated neutrophils are observed in HUS patients, yet it is unclear whether Stx exerts a direct effect on neutrophils or whether the toxin acts indirectly. The effect of Stx1 and Stx2 on human neutrophils was examined. Neither Stx1 nor Stx2 altered the rate of neutrophil apoptosis. Minimal binding of either toxin to neutrophils was observed, and the toxin was easily eluted from the cells. Stx1 and Stx2 were found to circulate in the plasma of mice following intravenous injection, and both toxins were cleared rapidly from the blood. Together these results suggest that neither Stx1 nor Stx2 interacts directly with neutrophils.
Identification of the Functional Initiation Codons of a Phase-Variable Gene of
Haemophilus influenzae
,
lic2A
, with the Potential for Differential Expression
Authors: Dixon Kevin , Bayliss Christopher D. , Makepeace Katherine , Moxon E. Richard , Hood Derek W. 
Published: November 2006

ABSTRACT

Simple sequence repeats located within reading frames mediate phase-variable ON/OFF switches in gene expression by generating frameshifts. Multiple translation initiation codons in different reading frames are found upstream of most
Haemophilus influenzae
tetranucleotide repeat tracts, raising the possibility of multiple active reading frames and more than two levels of gene expression for these loci. Phase variation between three levels of gene expression (strong, weak, and none) was observed when
lic2A
was fused to a
lacZ
reporter gene. The
lic2A
5′ CAAT repeat tract is preceded by four 5′ ATG codons (x, y, z1, and z2) in two reading frames. Each of these initiation codons was inactivated by site-directed mutagenesis. Strong expression from frame 1 was associated with x but not y. Weak expression from frame 2 was mainly dependent on the z2 codon, and there was no expression from frame 3. Using monoclonal antibodies specific for a digalactoside epitope of lipopolysaccharide whose synthesis requires Lic2A, two levels (strong and undetectable) of antibody reactivity were detected, suggesting that weak expression of
lic2A
is not discernible at the phenotypic level. Inactivation of the x initiation codon resulted in loss of strong expression of the digalactoside epitope and elevated killing by human serum. The failure to detect more than two phenotypes for
lic2A
, despite clear evidence of weak expression from the z1/z2 initiation codons, leaves open the question of whether or not multiple initiation codons are associated with more complex patterns of phenotypic variation rather than classical phase-variable switching between two phenotypes.
Global Analysis of theMycobacterium tuberculosisZur (FurB) Regulon
Authors: Maciąg Anna , Dainese Elisa , Rodriguez G. Marcela , Milano Anna , Provvedi Roberta , Pasca Maria R. , Smith Issar , Palù Giorgio , Riccardi Giovanna , Manganelli Riccardo 
Published: November 2006

ABSTRACTThe proteins belonging to the Fur family are global regulators of gene expression involved in the response to several environmental stresses and to the maintenance of divalent cation homeostasis. TheMycobacterium tuberculosisgenome encodes two Fur-like proteins, FurA and a protein formerly annotated FurB. Since in this paper we show that it represents a zinc uptake regulator, we refer to it as Zur. The gene encoding Zur is found in an operon together with the gene encoding a second transcriptional regulator (Rv2358). In a previous work we demonstrated that Rv2358 is responsible for the zinc-dependent repression of the Rv2358-zuroperon, favoring the hypothesis that these genes represent key regulators of zinc homeostasis. In this study we generated azurmutant inM. tuberculosis, examined its phenotype, and characterized the Zur regulon by DNA microarray analysis. Thirty-two genes, presumably organized in 16 operons, were found to be upregulated in thezurmutant. Twenty-four of them belonged to eight putative transcriptional units preceded by a conserved 26-bp palindrome. Electrophoretic mobility shift experiments demonstrated that Zur binds to this palindrome in a zinc-dependent manner, suggesting its direct regulation of these genes. The proteins encoded by Zur-regulated genes include a group of ribosomal proteins, three putative metal transporters, the proteins belonging to early secretory antigen target 6 (ESAT-6) cluster 3, and three additional proteins belonging to the ESAT-6/culture filtrate protein 10 (CFP-10) family known to contain immunodominant epitopes in the T-cell response toM. tuberculosisinfection.
Aggregation during Fruiting Body Formation in
Myxococcus xanthus
Is Driven by Reducing Cell Movement
Authors: Sliusarenko Oleksii , Zusman David R. , Oster George 
Published: November 2006

ABSTRACT

When starved,
Myxococcus xanthus
cells assemble themselves into aggregates of about 10
5
cells that grow into complex structures called fruiting bodies, where they later sporulate. Here we present new observations on the velocities of the cells, their orientations, and reversal rates during the early stages of fruiting body formation. Most strikingly, we find that during aggregation, cell velocities slow dramatically and cells orient themselves in parallel inside the aggregates, while later cell orientations are circumferential to the periphery. The slowing of cell velocity, rather than changes in reversal frequency, can account for the accumulation of cells into aggregates. These observations are mimicked by a continuous agent-based computational model that reproduces the early stages of fruiting body formation. We also show, both experimentally and computationally, how changes in reversal frequency controlled by the Frz system mutants affect the shape of these early fruiting bodies.
Identification and Characterization of an RTX Toxin in the Emerging Pathogen
Kingella kingae
Authors: Kehl-Fie Thomas E. , St. Geme Joseph W. 
Published: November 2006

ABSTRACT

Kingella kingae
is an emerging bacterial pathogen that is increasingly recognized as the causative agent of a variety of pediatric diseases, including septic arthritis and osteomyelitis. The pathogenesis of
K. kingae
disease is believed to begin with colonization of the upper respiratory tract. In the present study, we examined interactions between
K. kingae
and cultured respiratory epithelial cells and observed potent cytotoxicity, detected by both microscopy and lactic acid dehydrogenase (LDH) release assays. Experiments with synovial and macrophage cell lines revealed cytotoxicity for these cell types as well. Using mariner mutagenesis and a screen for loss of cytotoxicity, a genetic locus encoding an RTX toxin system was identified. Disruption of the
K. kingae
RTX locus resulted in a loss of cytotoxicity for respiratory epithelial, synovial, and macrophage cell lines. DNA sequence analysis demonstrated that the RTX locus is flanked by insertion elements and has a reduced G+C content compared to that of the whole genome. Two relatively less invasive
Kingella
species,
K. oralis
and
K. denitrificans
, were found to be noncytotoxic and to lack the RTX region, as determined by LDH release assays and Southern blotting. We concluded that
K. kingae
expresses an RTX toxin that has wide cellular specificity and was likely acquired horizontally. The possible roles for this toxin in the pathogenesis of
K. kingae
disease include breaching of the epithelial barrier and destruction of target tissues, such as synovium (joint lining).
The
lspA
Gene, Encoding the Type II Signal Peptidase of
Rickettsia typhi
: Transcriptional and Functional Analysis
Authors: Rahman M. Sayeedur , Ceraul Shane M. , Dreher-Lesnick Sheila M. , Beier Magda S. , Azad Abdu F. 
Published: November 2006

ABSTRACT

Lipoprotein processing by the type II signal peptidase (SPase II) is known to be critical for intracellular growth and virulence for many bacteria, but its role in rickettsiae is unknown. Here, we describe the analysis of
lspA
, encoding a putative SPase II, an essential component of lipoprotein processing in gram-negative bacteria, from
Rickettsia typhi
. Alignment of deduced amino acid sequences shows the presence of highly conserved residues and domains that are essential for SPase II activity in lipoprotein processing. The transcription of
lspA
,
lgt
(encoding prolipoprotein transferase), and
lepB
(encoding type I signal peptidase), monitored by real-time quantitative reverse transcription-PCR, reveals a differential expression pattern during various stages of rickettsial intracellular growth. The higher transcriptional level of all three genes at the preinfection time point indicates that only live and metabolically active rickettsiae are capable of infection and inducing host cell phagocytosis.
lspA
and
lgt
, which are involved in lipoprotein processing, show similar levels of expression. However,
lepB
, which is involved in nonlipoprotein secretion, shows a higher level of expression, suggesting that LepB is the major signal peptidase for protein secretion and supporting our in silico prediction that out of 89 secretory proteins, only 14 are lipoproteins. Overexpression of
R. typhi lspA
in
Escherichia coli
confers increased globomycin resistance, indicating its function as SPase II. In genetic complementation, recombinant
lspA
from
R. typhi
significantly restores the growth of temperature-sensitive
E. coli
Y815 at the nonpermissive temperature, supporting its biological activity as SPase II in prolipoprotein processing.
Anthrax: a disease in waiting?
Authors: Dognany L , Welsby P D 
Published: November 2006

Abstract
Anthrax was a relatively unknown disease in the Western world until 2001, when spores were maliciously mailed in the US, causing five deaths. The mortality of the disease, the stability of its spores and the subsequent lack of person-to-person spread make anthrax an attractive biological weapon for terrorists with a desire for targeted mass destruction.
The role of research training during higher medical education in the promotion of academic medicine in the UK
Authors: Myint P K , MacLullich A M J , Witham M D 
Published: November 2006

Abstract

Objectives
To examine the research activities and perceived barriers to research among higher specialist trainees in geriatric medicine and to show how trainees active in research might have a role in assisting their peers in getting started in research.

Design
Cross-sectional questionnaire survey on research activities, attitudes to doing research and perceived difficulties in doing research.

Setting and participants
Trainee members of the British Geriatrics Society (BGS) in the UK.

Results
A total of 122 responses (30% response rate) were received after a single mailing and a follow-up questionnaire to trainees attending the BGS national conference. Although 64% (67/104) of respondents would like to undertake a period of research, many perceived barriers preventing them from planning, funding and executing a research project. Among those who had not undertaken research, the majority (70%, 42/60) indicated that they have no clear idea of a topic to research, 64% (39/61) did not know how to develop an idea and 62% (38/61) indicated that they did not know how to get funding. Trainees motivated to do research were faced with particular difficulties with regards to funding and selection of a project topic.

Conclusions
One useful method would be systematically to provide basic information to trainees on how to enter into the early stages of research. This would help to overcome some of the unnecessary uncertainty that many trainees keen to do research seem to have.
Acute mountain sickness: medical problems associated with acute and subacute exposure to hypobaric hypoxia
Authors: Clarke C 
Published: November 2006

Abstract
This article summarises the medical problems of travel to altitudes above 3000 m. These are caused by chronic hypoxia. Acute mountain sickness (AMS), a self limiting common illness is almost part of normal acclimatisation—a transient condition lasting for several days. However, in &lt;2% of people staying above 4000 m, serious illnesses related to hypoxia develop – high altitude pulmonary oedema and cerebral oedema. These are potentially fatal but can be largely avoided by gradual ascent. Short vacations, pressure from travel companies and peer groups often encourage ascent to 4000 m more rapidly than is prudent. Sensible guidelines for ascent are outlined, clinical features, management and treatment of these conditions.
Study to outline the efficacy and illustrate techniques for steroid injection for trigger finger and thumb
Authors: Akhtar S , Burke F D 
Published: November 2006

Abstract

Aim
To outline the efficacy of a steroid injection in treating trigger finger. Our study defines the anatomy of the A1 pulley, and suggests methods for simple and safe flexor sheath injection for trigger finger and thumb.

Method
Systematic review of published literature on trigger finger and thumb and its treatment, particularly steroid injection. The use of the knowledge of the superficial landmarks of the A1 pulley with the techniques described were combined to provide a comprehensive guide to injecting steroids in patients with trigger finger and thumb.

Results
Several studies are outlined, which provided evidence to suggest that a steroid injection into the flexor sheath of the affected digit is successful in treating most of the patients. Methods of identifying the superficial landmarks of the A1 pulley and of approaching the pulley without injury to surrounding structures are also outlined in the literature. Two different techniques used to infiltrate the flexor sheath were described.

Conclusion
Steroid injection in the flexor sheath at the level of the A1 pulley is an effective method of treating patients with trigger finger and should be considered as the preferred treatment. Specific anatomical landmarks and methods allow the procedure to be carried out without fear of inadvertent damage to surrounding structures.
Predicting outcome of acute non-variceal upper gastrointestinal haemorrhage without endoscopy using the clinical Rockall Score
Authors: Tham T C K , James C , Kelly M 
Published: November 2006

Abstract

Background
The Rockall risk scoring system uses clinical criteria and endoscopy to identify patients at risk of adverse outcomes after acute upper gastrointestinal haemorrhage. A clinical Rockall score obtained using only the clinical criteria may be able to predict outcome without endoscopy.

Aim
To validate the clinical Rockall Score in predicting outcome after acute non-variceal upper gastrointestinal haemorrhage.

Methods
A retrospective observational study of consecutive patients who were admitted with non-variceal acute upper gastrointestinal haemorrhage was undertaken. Medical records were abstracted using a standardised form.

Results
102 cases were identified (51 men and 51 women; mean age 59 years). 38 (37%) patients considered to be at low risk of adverse outcomes (clinical Rockall Score 0) had no adverse outcomes and did not require transfusion. Patients with a clinical Rockall Score of 1–3 had no adverse outcomes, although 13 of 45 (29%) patients required blood transfusions. Clinical Rockall Scores &gt;3 (n = 19) were associated with adverse outcomes (rebleeding in 4 (21%), surgery in 1 (5%) and death in 2 (10%)).

Conclusions
The clinical Rockall Score without endoscopy may be a useful prognostic indicator in this cohort of patients with acute non-variceal upper gastrointestinal haemorrhage. This score may reduce the need for urgent endoscopy in low-risk patients, which can instead be carried out on a more elective outpatient basis.
Falsely raised TSH levels due to human anti-mouse antibody interfering with thyrotropin assay
Authors: Krishnan S G S , Pathalapati R , Kaplan L , Cobbs R K 
Published: November 2006

Abstract
The case of a 39-year-old woman who was referred for weight gain and amenorrhoea is reported. Laboratory evaluation showed high levels of thyroid-stimulating hormone (TSH). The patient was started on increasing doses of levothyroxine for subclinical hypothyroidism. TSH remained persistently raised and the patient became thyrotoxic. Evaluation at another laboratory showed normal levels of TSH, raising the possibility of interfering substances. TSH levels were normalised with the addition of mouse serum to the patient's sample, confirming the presence of human anti-mouse antibodies as the interfering substance in the TSH assay.
Land Surface Microwave Emissivities over the Globe for a Decade
Authors: Prigent Catherine , Aires Filipe , Rossow William B. 
Published: November 2006

Microwave land surface emissivities have been calculated over the globe for ~10 yr between 19 and 85 GHz at 53° incidence angle for both orthogonal polarizations, using satellite observations from the Special Sensor Microwave Imager (SSM/I). Ancillary data (IR satellite observations and meteorological reanalysis) help remove the contribution from the atmosphere, clouds, and rain from the measured satellite signal and separate surface temperature from emissivity variations. The method to calculate the emissivity is general and can be applied to other sensors. The monthly mean emissivities are available for the community, with a 0.25° × 0.25° spatial resolution.
The emissivities are sensitive to variations of the vegetation density, the soil moisture, the presence of standing water at the surface, or the snow behavior, and can help characterize the land surface properties.
These emissivities (not illustrated in this paper) also allow for improved atmospheric retrieval over land and can help evaluate land surface emissivity models at global scales.
Insulin Treatment and the Problem of Weight Gain in Type 2 Diabetes
Authors: Carver Catherine 
Published: November 2006

Purpose Insulin therapy has been shown to benefit the prognosis in patients with type 2 diabetes, but its initiation and intensification is often delayed through concerns about hypoglycemia and weight gain. In addition, weight gain is linked to the pathophysiology of type 2 diabetes and contributes to the overall risk for adverse cardiovascular outcomes. This article attempts to summarize this issue and examine the options available for weight management. Methods A broad range of literature has been reviewed to distil important, consistent facts about insulin and weight gain and the options available for limiting the problem. Results Unfortunately, the great benefits of insulin therapy may be potentially undermined by weight gain. Weight gain is physiologically and psychologically undesirable, especially in patients with diabetes who are already overweight. The fear of weight gain with some medications contributes to psychological insulin resistance, which may discourage patients from commencing or following insulin regimens. However, new diabetes treatments and lifestyle interventions can be used to mitigate these problems. Conclusions The exact choice of insulin and oral medications and weight loss interventions are important considerations in the overall management of patients with type 2 diabetes. Changes in a patient’s lifestyle, such as modifications to diet and implementing an exercise program, are first-line treatments for type 2 diabetes and can also counteract insulin-induced weight gain.
Symptom Interpretation in Women With Diabetes and Myocardial Infarction
Authors: Mayer Dorothy “Dale” , Rosenfeld Anne 
Published: November 2006

Purpose The purpose of this study was to describe the role of diabetes in acute myocardial infarction (MI) symptom interpretation. Methods This is a secondary data analysis of a study of treatment-seeking delay in women with acute MI (N = 52). This study included a subsample of those with diabetes (n = 16). Women were interviewed while hospitalized with MI about their actions, thoughts, and feelings from symptom onset to entry into the health care system. Qualitative description was the method of analysis. Results Three major themes were identified in the qualitative data: diabetes and decision making, presenting symptoms, and symptom attribution. Not all women included information about diabetes in their story, but those who checked blood sugars generally found it to be elevated. Diabetes was a factor in decision making for more than half of the sample. Presenting symptoms were variable but raised hypotheses about shortness of breath as a common presenting symptom for women with diabetes and MI. The third theme, symptom attribution, revealed confusion as to the cause of symptoms. Conclusions These results provide insight into symptom interpretation in women with diabetes and MI. Women with diabetes should consider atypical symptoms such as shortness of breath, gastrointestinal symptoms, and fluctuating blood sugars as reasons to seek care. Education for women with diabetes should include action plans for how to recognize and respond to symptoms. More research on the influence of diabetes on MI symptom attribution and decision making is needed.