bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nonclassical Pathway ofPseudomonas aeruginosaDNA-Induced Interleukin-8 Secretion in Cystic Fibrosis Airway Epithelial Cells
Authors: Delgado Mónica A. , Poschet Jens F. , Deretic Vojo 
Published: April 2006

ABSTRACTPseudomonas aeruginosais a critical colonizer of the respiratory tract in cystic fibrosis. The chronic infections with this microorganism contribute to excessive inflammation and progressive lung damage in cystic fibrosis patients. The full repertoire ofPseudomonasproducts that promote inflammation in the cystic fibrosis lung is not known. Here we show thatP. aeruginosaDNA released from the bacterium, but not human DNA from epithelial cells orEscherichia coliDNA, displays proinflammatory properties and induces human respiratory epithelial cells to secrete interleukin-8 (IL-8), a key chemokine causing excessive neutrophil infiltration in the cystic fibrosis lung. IL-8 secretion was not due to an increase in NF-κB- or activator protein-1-dependent IL-8 promoter transcription, but instead depended on p38 and Erk mitogen-activated protein kinases. No secretion of IL-8 was observed using conventional Toll-like receptor 9 ligands (CpG oligonucleotides), although it could be demonstrated that parts of the Toll-like receptor 9-signaling pathway were functional, since class B and C CpG oligonucleotide ligands stimulated production of RANTES chemokine. The IL-8 secretion in response toP. aeruginosaDNA was decreased by treatments that inhibit acidification of intracellular organelles, using chloroquine, a pH-neutralizing compound, or bafilomycin A1, an inhibitor of vacuolar H+-ATPase. These data indicate that DNA released fromP. aeruginosaduring chronic infections may significantly contribute to the proinflammatory processes in cystic fibrosis. Our findings also show that treatments with drugs diminishing organellar acidification may reduce the inflammatory response in cystic fibrosis.
Mutational Analysis of the
Escherichia coli melR
Gene Suggests a Two-State Concerted Model To Explain Transcriptional Activation and Repression in the Melibiose Operon
Authors: Kahramanoglou Christina , Webster Christine L. , el-Robh Mohamed Samir , Belyaeva Tamara A. , Busby Stephen J. W. 
Published: April 2006

ABSTRACT

Transcription of the
Escherichia coli melAB
operon is regulated by the MelR protein, an AraC family member whose activity is modulated by the binding of melibiose. In the absence of melibiose, MelR is unable to activate the
melAB
promoter but autoregulates its own expression by repressing the
melR
promoter. Melibiose triggers MelR-dependent activation of the
melAB
promoter and relieves MelR-dependent repression of the
melR
promoter. Twenty-nine single amino acid substitutions in MelR that result in partial melibiose-independent activation of the
melAB
promoter have been identified. Combinations of different substitutions result in almost complete melibiose-independent activation of the
melAB
promoter. MelR carrying each of the single substitutions is less able to repress the
melR
promoter, while MelR carrying some combinations of substitutions is completely unable to repress the
melR
promoter. These results argue that different conformational states of MelR are responsible for activation of the
melAB
promoter and repression of the
melR
promoter. Supporting evidence for this is provided by the isolation of substitutions in MelR that block melibiose-dependent activation of the
melAB
promoter while not changing melibiose-independent repression of the
melR
promoter. Additional experiments with a bacterial two-hybrid system suggest that interactions between MelR subunits differ according to the two conformational states.
Characterization of the Transcriptional Activators SalA and SyrF, Which Are Required for Syringomycin and Syringopeptin Production byPseudomonas syringaepv. syringae
Authors: Wang Nian , Lu Shi-En , Records Angela R. , Gross Dennis C. 
Published: April 2006

ABSTRACTProduction of the phytotoxins syringomycin and syringopeptin byPseudomonas syringaepv. syringae is controlled by the regulatory genessalAandsyrF. Analysis with 70-mer oligonucleotide microarrays established that thesyr-sypgenes responsible for synthesis and secretion of syringomycin and syringopeptin belong to the SyrF regulon. Vector pMEKm12 was successfully used to express both SalA and SyrF proteins fused to a maltose-binding protein (MBP) inEscherichia coliandP. syringaepv. syringae. Both the MBP-SalA and MBP-SyrF fusion proteins were purified by maltose affinity chromatography. Gel shift analysis revealed that the purified MBP-SyrF, but not the MBP-SalA fusion protein, bound to a 262-bp fragment of thesyrB1promoter region containing thesyr-sypbox. Purified MBP-SalA caused a shift of a 324-bp band containing the putativesyrFpromoter. Gel filtration analysis and cross-linking experiments indicated that both SalA and SyrF form homodimers in vitro. Overexpression of the N-terminal regions of SalA and SyrF resulted in decreased syringomycin production by strain B301D and reduced levels of β-glucuronidase activities of thesypA::uidAandsyrB1::uidAreporters by 59% to 74%. The effect of SalA on the expression of thesyr-sypgenes is mediated by SyrF, which activates thesyr-sypgenes by directly binding to the promoter regions. Both SalA and SyrF resemble other LuxR family proteins in dimerization and interaction with promoter regions of target genes.
Posttranscriptional Control of the
Salmonella enterica
Flagellar Hook Protein FlgE
Authors: Lee Hee Jung , Hughes Kelly T. 
Published: April 2006

ABSTRACT

Previous work suggested that the FlgE (flagellar hook subunit) protein in
Salmonella enterica
serovar Typhimurium was posttranscriptionally regulated in response to the stage of flagellar assembly. Specifically, the FlgE protein could be detected in flagellar mutants defective at the stages of assembly before or after rod assembly but not in rod assembly mutants, yet
flgE
mRNA levels were unaffected. To elucidate posttranscriptional mechanisms involved in the coupling of
flgE
gene expression to hook assembly, the RNA sequences at the 5′ and 3′ ends of the
flgE
-containing mRNA processed from the large
flgBCDEFGHIJKL
operon were determined by rapid amplification of cDNA ends, and secretion of the FlgE protein in different flagellar assembly mutant strains was analyzed. The sequences 5′ and 3′ of the
flgE
gene where RNA processing occurred was within 15 bases upstream of the
flgD
stop codon and at bases 145 to 147 downstream of the
flgF
start codon, respectively. The ribosome binding site of the
flgD
gene was found to be inhibitory to
flgE
translation in strains deleted for the upstream
flgD
gene, unless the region 15 bases upstream of the
flgD
stop codon was present. Secretion of FlgE into the periplasm was monitored using β-lactamase (Bla) fusions as a periplasm-specific reporter, which conferred resistance to ampicillin when FlgE-Bla was secreted into the periplasm. Using this assay, we found that the effect of rod assembly mutants on FlgE levels was due to FlgE turnover in the periplasm and that the FliE rod component protein was required for efficient FlgE-Bla secretion.
Sll0254 (CrtL
diox
) Is a Bifunctional Lycopene Cyclase/Dioxygenase in Cyanobacteria Producing Myxoxanthophyll
Authors: Mohamed Hatem E. , Vermaas Wim F. J. 
Published: April 2006

ABSTRACT

Upon depletion of Sll0254 in
Synechocystis
sp. strain PCC 6803, cyclized carotenoids were replaced by linear, relatively hydrophilic carotenoids, and the amount of the two photosystems decreased greatly. Full segregants of the sll0254 deletion in
Synechocystis
were not obtained, implying that this gene is essential for survival, most likely to allow normal cell division. The N-terminal half of Sll0254 has limited similarity to the family of lycopene cyclases, has an additional dehydrogenase motif near the N terminus, and is followed by a Rieske 2Fe-2S center sequence signature. To test whether Sll0254 serves as a lycopene cyclase in
Synechocystis
, the corresponding gene was expressed in
Escherichia coli
strains that can produce lycopene or neurosporene. In the presence of Sll0254 these linear carotenoids were converted into cyclized, relatively hydrophilic pigments, with masses consistent with the introduction of two hydroxyl groups and with spectra indicative of only small changes in the number of conjugated double bonds. This suggests that Sll0254 catalyzes formation of oxygenated, cyclized carotenoids. We interpret the appearance of the hydroxyl groups in the carotenoids to be due to dioxygenase activity involving the Rieske 2Fe-2S center and the additional dehydrogenase domain. This dioxygenase activity is required in the myxoxanthophyll biosynthesis pathway, after or concomitant with cyclization on the other end of the molecule. We interpret Sll0254 to be a dual-function enzyme with both lycopene cyclase and dioxygenase activity and have named it CrtL
diox
.
Risk of affective and stress related disorders among employees in human service professions
Authors: Wieclaw J , Agerbo E , Mortensen P B , Bonde J P 
Published: April 2006

Objectives:To examine the risk of affective and stress related disorders among men and women employed in human service professions.Methods:Population based case-control study using data from national registers. Cases (n = 28 971) were identified in the Danish Psychiatric Central Research Register among all hospitalised patients and outpatients aged 18–65 who received a first time ever diagnosis of affective (ICD-10, F30–39) or stress related (ICD-10, F40–48) disorder from 1 January 1995 to 31 December 1998. Each case was assigned five never admitted referents (n = 144 855) of the same gender and age, randomly drawn from a 5% sample of the Danish population obtained from Statistics Denmark’s Integrated Database for Labour Market Research. Occupation held the year before matching was classified according to the Danish version of the International Classification of Occupation. Health care, education, social work, and customer services were defined as human service professions and constituted 21% of all employed in the study. Adjusted risks (hazard ratios) relative to all other occupations were calculated for 24 human service occupations.Results:The relative risk of depression in human service professions was 1.35 (95% CI 1.24 to 1.47) for women and 1.49 (95% CI 1.29 to 1.73) for men. The risk of stress was 1.18 (95% CI 1.11 to 1.26) for women and 1.49 (95% CI 1.32 to 1.67) for men. Specific professions contributed differentially to the magnitude of risk, with education and social services displaying the highest risks. No increase in risks was found in customer service occupations. Gender was a significant modifying factor with the highest risk levels in men.Conclusions:There was a consistent association between employment in human service occupations and the risk of affective and stress related disorders. Risks were highest for men working in these typically female professions. More work is needed to distinguish work hazards from effects attributable to selection mechanisms and personality characteristics.
Dermoscopy Improves Accuracy of Primary Care Physicians to Triage Lesions Suggestive of Skin Cancer
Authors: Argenziano Giuseppe , Puig Susana , Zalaudek Iris , Sera Francesco , Corona Rosamaria , Alsina Mercè , Barbato Filomena , Carrera Cristina , Ferrara Gerardo , Guilabert Antonio , Massi Daniela , Moreno-Romero Juan A. , Muñoz-Santos Carlos , Petrillo Gianluca , Segura Sonia , Soyer H. Peter , Zanchini Renato , Malvehy Josep 
Published: April 2006

Purpose Primary care physicians (PCPs) constitute an appropriate target for new interventions and educational campaigns designed to increase skin cancer screening and prevention. The aim of this randomized study was to determine whether the adjunct of dermoscopy to the standard clinical examination improves the accuracy of PCPs to triage lesions suggestive of skin cancer. Patients and Methods PCPs in Barcelona, Spain, and Naples, Italy, were given a 1-day training course in skin cancer detection and dermoscopic evaluation, and were randomly assigned to the dermoscopy evaluation arm or naked-eye evaluation arm. During a 16-month period, 73 physicians evaluated 2,522 patients with skin lesions who attended their clinics and scored individual lesions as benign or suggestive of skin cancer. All patients were re-evaluated by expert dermatologists at clinics for pigmented lesions. Referral accuracy of both PCP groups was calculated by their scores, which were compared to those tabulated for dermatologists. Results Referral sensitivity, specificity, and positive and negative predictive values were 54.1%, 71.3%, 11.3%, and 95.8%, respectively, in the naked-eye arm, and 79.2%, 71.8%, 16.1%, and 98.1%, respectively, in the dermoscopy arm. Significant differences were found in terms of sensitivity and negative predictive value (P = .002 and P = .004, respectively). Histopathologic examination of equivocal lesions revealed 23 malignant skin tumors missed by PCPs performing naked-eye observation and only six by PCPs using dermoscopy (P = .002). Conclusion The use of dermoscopy improves the ability of PCPs to triage lesions suggestive of skin cancer without increasing the number of unnecessary expert consultations.
Phase II Study of Capecitabine, Oxaliplatin, and Erlotinib in Previously Treated Patients With Metastastic Colorectal Cancer
Authors: Meyerhardt Jeffrey A. , Zhu Andrew X. , Enzinger Peter C. , Ryan David P. , Clark Jeffrey W. , Kulke Matthew H. , Earle Craig C. , Vincitore Michele , Michelini Ann , Sheehan Susan , Fuchs Charles S. 
Published: April 2006

Purpose To investigate the combination of erlotinib, capecitabine, and oxaliplatin in patients who were previously treated for metastatic colorectal cancer. Patients and Methods Patients were eligible if they had metastatic colorectal cancer that progressed, were intolerant to first-line chemotherapy, or had disease recurrence within 1 year of adjuvant therapy for early-stage disease. Each 21-day cycle consisted of daily oral erlotinib at 150 mg, oral capecitabine at 1,000 mg/m2 (reduced to 750 mg/m2 after the first 13 patients) twice a day on days 1 to 14, and intravenous oxaliplatin at 130 mg/m2 on day 1. Results Thirty-two patients were enrolled onto this phase II study. By intention-to-treat analyses, eight patients (25%) experienced a partial response and 14 patients (44%) had stable disease for at least 12 weeks. The median progression-free survival was 5.4 months and the median overall survival was 14.7 months. These results were essentially unchanged when limited to the cohort of patients (78%) who received prior irinotecan for metastatic colorectal cancer. Most common grade 3 to 4 toxicities included diarrhea (38%), nausea/emesis (19%), fatigue (16%), dehydration (16%), and dermatitis (13%); grade 3 or 4 toxicities were reduced with a lower starting dose of capecitabine. Conclusion The combination of capecitabine, oxaliplatin, and erlotinib seems to have promising activity against metastatic colorectal cancer in patients who received prior chemotherapy, with a relatively higher response rate and progression-free survival compared with previous reports of either infusional FU, leucovorin, and oxaliplatin or capecitabine and oxaliplatin in similar patient populations.
Topological Shift Spaces
Authors: Betten Dieter 
Published: April 2006

Abstract
Two of the problems listed in [14, 74.17] ask to prove or disprove the following statements:

A)
For each differentiable planar map ƒ : IR2 → IR2 the set of all differentials defines a spread of IR4.

B)
If the differentials of a differentiable map ƒ : IR2 → IR2 define a spread of IR4 then the map ƒ is planar.

By restricting to vertical 3-dimensional subspaces, we get the notion of a 3-dimensional shift space, and for differentiable shift spaces we may formulate analogous problems A′ and B′. Under the additional assumption that there exists a 1-dimensional group of shears, we prove A′ and B′ for 3-dimensional shift spaces and—as a corollary—also A and B for 4-dimensional shift planes.
Affine parts of topological unitals
Authors: Stroppel Markus 
Published: April 2006

Abstract
We study different, non-compact groups acting on
unitals in compact projective planes in such a way that the geometry can be
reconstructed from the group action. These unitals have many ambient
automorphisms, but are not induced by polarities. In passing, we construct
polarities for a class of eight-dimensional translation planes, and study the
corresponding unitals.
Conceptual blending, somatic marking, and normativity: a case example from ancient Chinese
Authors: Slingerland Edward G. 
Published: April 2006

Abstract
One purpose of this article is to support
the universalist claims of conceptual blending theory by documenting its
application to an ancient Chinese philosophical text, and also to provide illustrations
of complex multiple-scope blends constructed over the course of conceptual
blending by suggesting that, in many cases, the primary purpose of achieving human
scale is not to help us apprehend a situation, but rather to help us to know how
too feel about it. This argument is essentially an attempt to connect the
insights of conceptual blending theorists with those of neuroscientists such Antonio
Damasio who argues for the importance of somatic states and emotional reactions
in human value-creation and decision-making.
Non-verbal humor and joke performance
Authors: Norrick Neal R. 
Published: April 2006

AbstractMany jokes fall outside the province of script theory, because they depend on performance in various ways. Interactional features of the joke performance, along with pantomime, gestures, voice shifts, and so on, require modes of description separate from the verbally oriented script theory. There are significant differences between the written joke text and the oral joke performance, and these differences cast doubt on the simple extendibility of script theory from written joke texts to the spoken joke performance.
Analyzing conversational data in GTVH terms: A new approach to the issue of identity construction via humor
Authors: Archakis Argiris , Tsakona Villy 
Published: April 2006

AbstractThe central aim of this paper is to apply the General Theory of Verbal Humor (henceforth GTVH; Attardo 2001) to conversational narratives and to integrate it with sociopragmatic approaches. We consider script opposition as a necessary prerequisite for humor and its perlocutionary effect (i.e. eliciting laughter) as a secondary criterion for the characterization of a narrative as humorous. Despite the fact that one of the most common social functions of humor is the construction of solidarity and in-group identity, there is relatively little sociolinguistic research on this issue. Thus, a more particular aim of this paper is to illustrate how humor can be a flexible discourse strategy to construct particular aspects of social identities by focusing on a particular aspect of humor encoded in GTVH terms as the knowledge resource of “target”. It will be shown that, in our conversational data coming from a cohesive group of young Greek males, interlocutors select targets either outside or inside their group and that, while in the first case humor criticizes the “other” behavior, in the latter case it serves as a correction mechanism of in-group behavior in a rather covert manner. In both cases, the target of humor reinforces the already existing bonds among group members, while bringing the evaluative dimension of humor to the surface. It is therefore suggested that the target of humor is an important heuristic tool for describing its social function, revealing how it is exploited by conversationalists to project their shared beliefs and values, i.e. their social identity.
The Social Impact of Gender and Culture on Decision-Making in Genetic Testing
Authors: Stieber Roger Kerstin 
Published: April 2006

AbstractThis paper discusses how gender and culture / ethnicity or race shape interpretations of possible genetic tests for adult onset health conditions in families. The context for this discussion includes the process of psychotherapy. On the one hand, genetic counseling (especially in the context of recent advances in science research) can re-configure family relationships and thus may make new meaning of shifting definitions of family. On the other hand, ‘access’ to or understanding genetics is commonly achieved according to personal as well as social factors removed from the scientific aspect of these diagnoses. Psychotherapy is one such site. This distinction between genetics and people’s application of potential genetic diagnoses, as well as between genetics and social cultural values, is explored in this paper.
From Warnock to the Stem Cell Bank—Evaluating the UK's Regulatory Measures for Stem Cell Research
Authors: Twine Richard 
Published: April 2006

AbstractThe United Kingdom government regards its regulations for stem cell research as some of the most rigorous in the world. This paper chronologically outlines the important stages in the evolution of these regulatory measures over the past twenty years, including the Warnock Report, the Human Fertilisation and Embryology Act 1990, the subsequent series of reports and consultations, and the establishment of the UK stem cell bank. Attending both to the discursive framing of stem cell research and the ethical issues faced, an assessment is made in terms of the appropriateness, adequacy and effectiveness of the UK's regulatory measures. Although institutional learning is detected in areas such as improving public engagement, the UK regulatory process has been open to the accusation of a scientific community regulating itself. This paper recommends that in order to avoid any possible complacency further improvements in public inclusiveness and interdisciplinary representation on regulatory committees should be sought.
Portugues Ethical Debates on Euthanasia
Authors: Pinto Cristina Rosamond 
Published: April 2006

AbstractIntroductionMedical Sciences Faculties along with other Associations and the Department of Bioethics and Medical Law have conducted lately debates about Euthanasia.The need to bestow quality and dignity en every phase of life namely when one faces death has been particularly focused. Even on a terminal phase of life people may live with quality and discover the dimension of their own suffering meaning the understanding of positive factors underlying the concept of pain.In Portugal Ethical Committees are endorsed not only to medical scientists, lawyers, lay associations but to priests who happen to preside to some of these Ethical Committees.
Biotechnological Potential of Marine Sponges and their Associated Bacteria as Producers of New Pharmaceuticals (Part II)
Authors: Thoms Carsten , Schupp Peter 
Published: April 2006

AbstractThe supply problemThe examples of sponge-derived compounds in advanced stages of clinical trials presented in part I of this article emphasize the potential of sponges as auspicious source for drugs against various human diseases.However, compared to the vast number of over 4000 compounds isolated from sponges during the last three decades, the number of sponge-derived drugs that have already entered the market is surprisingly small. There are two major reasons for this phenomenon: One is the extremely long time frame involved in the process of drug development. For instance, to develop the famous anticancer drug Taxol® from its initial description in the yew tree to its approval as a commercial pharmaceutical took over 20 years. The presented examples of sponge-derived compounds in clinical trials, this long time frame is by far no exception. Thus, as many interesting compounds were initially reported already in the 1980s and early 1990s, there is hope that within the following years the number of commercially available ”marine drugs” will considerably increase.