bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Operators and Promoters That Control SXT Conjugative Transfer
Authors: Beaber John W. , Waldor Matthew K. 
Published: August 2004

ABSTRACT

Transfer of SXT, a
Vibrio cholerae
-derived integrating conjugative element that encodes multiple antibiotic resistance genes, is repressed by SetR, a λ
434
c
I-related repressor. Here we identify divergent promoters between
s086
and
setR
that drive expression of the regulators of SXT transfer. One transcript encodes the activators of transfer,
setC
and
setD
. The second transcript codes for SetR and, like the
c
I transcript of lambda, is leaderless. SetR binds to four operators located between
setR
and
s086
; the locations and relative affinities of these sites suggest a model for regulation of SXT transfer.
Analysis of Chimeric Chemoreceptors inBacillus subtilisReveals a Role for CheD in the Function of the McpC HAMP Domain
Authors: Kristich Christopher J. , Ordal George W. 
Published: August 2004

ABSTRACTMotile prokaryotes use a sensory circuit for control of the motility apparatus in which ligand-responsive chemoreceptors regulate phosphoryl flux through a modified two-component signal transduction system. The chemoreceptors exhibit a modular architecture, comprising an N-terminal sensory module, a C-terminal output module, and a HAMP domain that connects the N- and C-terminal modules and transmits sensory information between them via an unknown mechanism. The sensory circuits mediated by two chemoreceptors ofBacillus subtilishave been studied in detail. McpB is known to regulate chemotaxis towards the attractant asparagine in a CheD-independent manner, whereas McpC requires CheD to regulate chemotaxis towards the attractant proline. Although CheD is a phylogenetically widespread chemotaxis protein, there exists only a limited understanding of its function. We have constructed chimeras between McpB and McpC to probe the role of CheD in facilitating sensory transduction by McpC. We found that McpC can be converted to a CheD-independent receptor by the replacement of one-half of its HAMP domain with the corresponding sequence from McpB, suggesting that McpC HAMP domain function is complex and may require intermolecular interactions with the CheD protein. When considered in combination with the previous observation that CheD catalyzes covalent modification of the C-terminal modules ofB. subtilisreceptors, these results suggest that CheD may interact with chemoreceptors at multiple, functionally distinct sites.
Mutational Analysis of the
fruA
Promoter Region Demonstrates that C-Box and 5-Base-Pair Elements Are Important for Expression of an Essential Developmental Gene of
Myxococcus xanthus
Authors: Srinivasan D. , Kroos Lee 
Published: August 2004

ABSTRACT

Myxococcus xanthu
s uses extracellular signals during development to regulate gene expression. C-signaling regulates the expression of many genes induced after 6 h into development. FruA is a protein that is necessary for cells to respond to C-signaling, but expression of the
fruA
gene does not depend on C-signaling. Yet the
fruA
promoter region has a C box and a 5-bp element, similar to the promoter regions of several C-signal-dependent genes, where these sequences are crucial. Here, we show that the C box and 5-bp elements are important for expression of
fruA
, demonstrating for the first time that these sequences play a role in the expression of a gene that does not depend on C-signaling and is required for
M. xanthus
development.
Examining the associations between physical work demands and work injury rates between men and women in Ontario, 1990–2000
Authors: Smith P M , Mustard C A 
Published: August 2004

Aims:To describe the decline in injury rates between 1990 and 2000 within occupations stratified across three levels of physical demands and gender, adjusting for industry, in Canada’s largest province.Methods:Records of injury compensation claims were obtained from the Ontario Workplace Safety & Insurance Board. The population likely to be insured by the Ontario Workplace Safety & Insurance Board was estimated from Statistics Canada’s Labour Force Survey. Injury rates were calculated by three broad levels of physical demands, separately for men and women.Results:Injury rates decreased across each grouping of lower physical demands at work for both men and women, with the largest absolute differences in manual occupational groups (high physical demands). Occupations classified as manual (high physical demands) and mixed (moderate physical demands) showed larger differences in injury rates between genders than did non-manual (low physical demands), although the directions of these differences were not always consistent across different natures of injury classification.Conclusions:The absolute reduction in injury rates in Ontario between 1990 and 2000 was dominated by the reduction in injury rates for men and women in manual and mixed occupations. However, not all types of injury have declined to the same extent. A large proportion of differences in injury rates between men and women can be attributed to the differential labour force participation across occupations and industries, as well as the differential tasks within occupational groups.
Primary osteoarthritis and occupation in the Quebec national health and social survey
Authors: Rossignol M 
Published: August 2004

Background:The scientific evidence available is consistent in linking osteoarthritis (OA) and occupation but is lacking information regarding preventable risks in the workplace.Aims:To explore the effect of different dimensions of physical demand in the relation between self reported OA and occupation.Methods:Nationwide population survey of employed and self employed adults aged 25–64.Results:Of the 11 144 workers surveyed, 3.1% (two females for one male) reported a problem with OA (any site). They reported some degree of limitations in their daily activities in a proportion that was six times higher (26.8%) than the rest of the population of the same age without OA and twice as high for absence from work in the previous year (23.8%). Of the different dimensions of risks used in the survey and controlling for age, body mass index, and smoking, “use of force with tools or machines” showed a statistically significant association with OA in males and females. In occupations significant risks of OA were identified in male unskilled labourers and skilled labourers, and in female technicians, and workers in the services sector.Conclusions:Results of the present survey indicated that occupational stresses associated with OA may differ substantially between male and female workers and that specific risks may affect the younger workforce (25–44 years old) in some occupations, including housekeeping and other ill defined skilled and unskilled labour.
Occupational and environmental exposures and lung cancer in an industrialised area in Italy
Authors: Fano V , Michelozzi P , Ancona C , Capon A , Forastiere F , Perucci C A 
Published: August 2004

Aims:To investigate the effects of occupational exposures and residence near to industrial sites on lung cancer mortality in an area in Italy.Methods:234 cases of lung cancer and 729 controls matched by sex, age, and date of death were enrolled. Environmental exposure was evaluated using historical residence data. A geographical information system was used to compute distances from residence to pollution source (cement factory, power plants, harbour) and an average distance was computed for each subject. Odds ratios (OR) and 95% confidence intervals (CI) in a logistic regression model were used to estimate the relative risk of lung cancer associated with the risk factors (smoking habits and occupational exposure) collected by questionnaire; ORs for distances from pollution sources and from city centre were computed, adjusting for smoking habits, education, and occupation.Results:Smoking habits (⩽10 cigarettes/day, OR = 2.28; 11–20, OR = 4.64; >20, OR = 6.61) and occupational exposure to asbestos (OR = 3.50) were significantly associated with lung cancer risk. Reported traffic level of area of residence and residence near the four sources were not associated with increased risk of lung cancer. There was a significantly increased risk for those residing outside the city centre, in the southern outskirts (OR = 1.51).Conclusions:The increased lung cancer risk observed in the area can partly be explained by occupational exposures. The increased risk in the outskirts of the city is consistent with the results of dispersion models that indicate high levels of pollutant deposition in the same area.
Agricultural pesticide use and adenocarcinomas of the stomach and oesophagus
Authors: Lee W J , Lijinsky W , Heineman E F , Markin R S , Weisenburger D D , Ward M H 
Published: August 2004

Aims:To evaluate the risk of the stomach and oesophageal adenocarcinomas associated with farming and agricultural pesticide use.Methods:Population based case-control study in eastern Nebraska. Telephone interviews were conducted with men and women diagnosed with adenocarcinoma of the stomach (n = 170) or oesophagus (n = 137) between 1988 and 1993, and controls (n = 502) randomly selected from the same geographical area. Unconditional logistic regression was used to calculate adjusted odds ratios (ORs) for farming and for use of individual and chemical classes of insecticides and herbicides, including pesticides classified as nitrosatable (able to form N-nitroso compounds on reaction with nitrite). Non-farmers were used as the reference category for all analyses.Results:Ever living or working on a farm, duration of farming, and size of the farm were not associated with stomach or oesophageal adenocarcinomas. There was no association for either cancer with ever-use of insecticides (stomach OR 0.9, 95% CI 0.6 to 1.4; oesophagus OR 0.7, 95% CI 0.4 to 1.1) or herbicides (stomach OR 0.9, 95% CI 0.5 to 1.4; oesophagus OR 0.7, 95% CI 0.4 to 1.2). Likewise, individual pesticides, including individual nitrosatable pesticides, were not significantly associated with risk.Conclusions:No significant associations were found between specific agricultural pesticide exposures and the risk of stomach or oesophageal adenocarcinomas among Nebraska farmers.
A cohort study of mortality among Ontario pipe trades workers
Authors: Finkelstein M M , Verma D K 
Published: August 2004

Aims:To study mortality in a cohort of members of the United Association of Journeymen and Apprentices of the Plumbing and Pipe Fitting Industry of the United States and Canada and to compare results with two previous proportional mortality studies.Methods:A cohort of 25 285 workers who entered the trade after 1949 was assembled from records of the international head office. Mortality was ascertained by linkage to the Canadian Mortality Registry at Statistics Canada. Standardised mortality ratios were computed using Ontario general population mortality rates as the reference.Results:There were significant increases in lung cancer mortality rates (SMR 1.27; 95% CI 1.13 to 1.42). Increased lung cancer risk was observed among plumbers, pipefitters, and sprinkler fitters. Increased risk was observed among workers joining the Union as late as the 1970s. A random effects meta-analysis of this study and the two PMR studies found significant increases in oesophageal (RR 1.24; 95% CI 1.00 to 1.53), lung (RR 1.31; 95% CI 1.19 to 1.44), and haematological/lymphatic (RR 1.21; 95% CI 1.08 to 1.35) malignancies.Conclusions:The mortality pattern is consistent with the effects of occupational exposure to asbestos. Increased risk due to other respiratory carcinogens such as welding fume cannot be excluded. There are substantial amounts of asbestos in place in industrial and commercial environments. The education and training of workers to protect themselves against inhalation hazards will be necessary well into the future.
Identification of talin head domain as an immunodominant epitope of the antiplatelet antibody response in patients with HIV-1-associated thrombocytopenia
Authors: Koefoed Klaus , Ditzel Henrik J. 
Published: August 2004

AbstractHIV-1-associated thrombocytopenia (HIV-1-ITP) is a common complication of HIV-1 infection, frequently caused by increased peripheral platelet destruction mediated by antiplatelet antibodies (Abs) and/or platelet-bound immune complexes. Little is known about the specificity of the antiplatelet Abs at a molecular level. Here, we used immunoglobulin G (IgG) phage-display libraries generated from 3 HIV-1-ITP patients to isolate a large panel of human monoclonal antiplatelet Abs by selection on unfixed platelets. The platelet antigen recognized by all the cloned Abs was identified to be the talin head domain (talin-H), a cleavage product of talin that can be generated by platelet activation or HIV-1 protease. Talin-H was found in HIV-1-ITP-circulating immune complexes, and antitalin Abs were detected in HIV-1-ITP sera but not in controls. The cloned anti-talin-H IgGs were highly somatically mutated, indicative of an antigen-driven, affinity-matured response. These findings suggest that talin-H Ab may be a marker of HIV-1-ITP elicited due to exposure of immunodominant epitopes on talin-H as a result of a disease-related process. Abs to talin-H and related immune complexes (ICs) may contribute to HIV-1-ITP. (Blood. 2004;104:4054-4062)
Impaired CD40L signaling is a cause of defective IL-12 and TNF-α production in Sézary syndrome: circumvention by hexameric soluble CD40L
Authors: French Lars E. , Huard Bertrand , Wysocka Maria , Shane Ryan , Contassot Emmanuel , Arrighi Jean-François , Piguet Vincent , Calderara Silvio , Rook Alain H. 
Published: August 2004

AbstractSézary syndrome (SzS) is an advanced form of cutaneous T-cell lymphoma characterized by peripheral blood involvement, impaired cell-mediated immunity, and T-helper 1 (TH1) cytokine production. To understand the mechanism of these defects, we studied the expression and function of CD40L in peripheral blood mononuclear cells (PBMCs) of patients with SzS. We found that PBMCs of patients with SzS have a defect in interleukin-12 (IL-12) and tumor necrosis factor-α (TNF-α) production upon anti-CD3 stimulation and that tumor CD4+ T lymphocytes have a specific defect in CD40L induction after anti-CD3 ligation in vitro. This defect may explain the poor IL-12 production, because IL-12 production by anti-CD3-stimulated PBMCs was dependent on CD40L in healthy donors. The observed defect in tumor cell CD40L expression appears to be due to inappropriate T-cell signaling upon CD3 ligation, because expression of other T-cell activation antigens such as CD25, and to a lesser extent CD69, are also impaired on tumor cells. Importantly however, the inability of SzS PBMCs to appropriately produce IL-12 and TNF-α could be restored by recombinant hexameric CD40L. Taken together, our results demonstrate that impaired IL-12 and TNF-α production in SzS is associated with defective CD4+ T lymphocyte CD40L induction and indicate that CD40L may have therapeutic potential in SzS. (Blood. 2005;105:219-225)
Evidence that genetic deletion of the TNF receptor p60 or p80 in macrophages modulates RANKL-induced signaling
Authors: Takada Yasunari , Aggarwal Bharat B. 
Published: August 2004

AbstractIn the current report, we investigated the possibility of a cross-talk between receptor activator of NF-κB ligand (RANKL) and tumor necrosis factor α (TNF-α) using macrophage cell lines derived from wild-type mice and from mice with genetic deletion of the type 1 TNF receptor (p60-/-), the type 2 TNF receptor (p80-/-), or both receptors (p60-/-p80-/-). Deletion of TNF receptors sensitized the cells to RANKL-induced NF-κB activation, in order from least to most sensitive of p60-/- less than p80-/- less than p60-/-p80-/-. The effect on nuclear factor-κB (NF-κB) activation correlated with RANKL-induced IκBα kinase activation. Deletion of both TNF receptors also potentiated RANKL-induced c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1 and 2 (ERK1/2), and p38 mitogen-activated protein kinase (MAPK) activations in a dose- and time-dependent manner. Nitric oxide (NO) production and expression of inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2) induced by RANKL was also maximally induced in double knock-out cells. RANKL had no effect on the proliferation of wild-type cells, but deletion of TNF receptors induced growth modulatory effects. We also found that tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6), which mediates RANKL signaling, was constitutively bound to RANK in TNF receptor-deleted cells but not in wild-type cells, and this binding was enhanced by RANKL. Overall our results show that RANKL signaling is modulated by the TNF receptors and thus provide evidence of cross-talk between the receptors of 2 cytokines. (Blood. 2004;104: 4113-4121)
Regulation of stem cell factor receptor signaling by Cbl family proteins (Cbl-b/c-Cbl)
Authors: Zeng Shan , Xu Zhiheng , Lipkowitz Stan , Longley Jack B. 
Published: August 2004

AbstractActivation of the KIT receptor tyrosine kinase contributes to the pathogenesis of several human diseases, but the mechanisms regulating KIT signaling have not been fully characterized. Here, we show that stem cell factor (SCF), the ligand for KIT, induces the interaction between KIT and Cbl proteins and their mutual degradation. Upon SCF stimulation, KIT binds to and induces the phosphorylation of Cbl proteins, which in turn act as E3 ligases, mediating the ubiquitination and degradation of KIT and themselves. Tyrosine kinase binding and RING finger domains of Cbl are essential for Cbl-mediated ubiquitination and degradation of KIT. We propose a negative feedback loop controlling the SCF-KIT signaling pathway, in which SCF activates KIT. The activated KIT in turn induces phosphorylation and activation of Cbl proteins. The Cbl proteins then bind and direct the degradation of activated KIT, leading to down-regulation of KIT signaling. (Blood. 2005;105:226-232)
p38 MAPK activation controls the TLR3-mediated up-regulation of cytotoxicity and cytokine production in human NK cells
Authors: Pisegna Simona , Pirozzi Gianluca , Piccoli Mario , Frati Luigi , Santoni Angela , Palmieri Gabriella 
Published: August 2004

AbstractNatural killer (NK) cells are a component of the innate immunity against viral infections through their rapid cytotoxic activity and cytokine production. Although the synthetic double-stranded (ds) RNA polyinosinic-polycytidylic acid (poly I:C), a mimic of a common product of viral infections, is known to rapidly up-regulate their in vivo functions, NK cell ability to directly respond to dsRNA is still mostly unknown. Our results show that treatment with poly I:C significantly up-regulates both natural and CD16-mediated cytotoxicity of highly purified human NK cells. Poly I:C also induces the novel capability of producing CXCL10 chemokine in human NK cells and synergistically enhances interferon-γ (IFN-γ) production induced by either adaptive or innate cytokines. In accordance with the expression of Toll-like receptor-3 (TLR3) and of TRIF/TICAM-1 adaptor, poly I:C stimulation induces the activation of interferon regulatory factor-3 (IRF-3) transcription factor and of p38 mitogen-activated protein kinase (MAPK) in human NK cells. Finally, we demonstrate that p38 MAPK activity is required for the dsRNA-dependent enhancement of cytotoxicity and CXCL10 production. The occurrence of dsRNA-induced signaling and functional events closely correlates with the TLR3 mRNAprofile in different NK cell populations. Taken together, these data identify p38 as a central component of NK cell ability to directly respond to dsRNA pathogen-associated molecular pattern (PAMP).
Expression of Rgmc, the murine ortholog of hemojuvelin gene, is modulated by development and inflammation, but not by iron status or erythropoietin
Authors: Krijt Jan , Vokurka Martin , Chang Ko-Tung , Nečas Emanuel 
Published: August 2004

Abstract
Mutations of hepcidin (HAMP) and hemo-juvelin (HJV) genes have been recently demonstrated to result in juvenile hemochromatosis. Expression of HAMP is regulated by iron status or infection, whereas regulation of HJV is yet unknown. Using quantitative real-time polymerase chain reaction, we compared expression of Hamp and Rgmc (the murine ortholog of HJV) in livers of mice treated with iron, erythropoietin, or lipopolysaccharide (LPS), as well as during fetal and postnatal development. Iron overload increased Hamp expression without effect on Rgmc mRNA. Erythropoietin decreased Hamp mRNA, but Rgmc expression was unchanged. Hamp mRNA level decreased after birth by 4 orders of magnitude, without significant changes in Rgmc expression. Administration of LPS elevated Hamp mRNA levels, while markedly decreasing hepatic Rgmc mRNA levels (to ∼5% after 6 hours). The responses of Hamp and Rgmc were quite different and suggested that human HJV expression could be modulated by inflammation.
Site-specific mutagenesis of Drosophila proliferating cell nuclear antigen enhances its effects on calf thymus DNA polymerase δ
Authors: Mozzherin Dmitry Ju , McConnell Maeve , Miller Holly , Fisher Paul A 
Published: August 2004

Abstract
Background
We and others have shown four distinct and presumably related effects of mammalian proliferating cell nuclear antigen (PCNA) on DNA synthesis catalyzed by mammalian DNA polymerase δ(pol δ). In the presence of homologous PCNA, pol δ exhibits 1) increased absolute activity; 2) increased processivity of DNA synthesis; 3) stable binding of synthetic oligonucleotide template-primers (t1/2 of the pol δ•PCNA•template-primer complex ≥2.5 h); and 4) enhanced synthesis of DNA opposite and beyond template base lesions. This last effect is potentially mutagenic in vivo. Biochemical studies performed in parallel with in vivo genetic analyses, would represent an extremely powerful approach to investigate further, both DNA replication and repair in eukaryotes.

Results
Drosophila PCNA, although highly similar in structure to mammalian PCNA (e.g., it is >70% identical to human PCNA in amino acid sequence), can only substitute poorly for either calf thymus or human PCNA (~10% as well) in affecting calf thymus pol δ. However, by mutating one or only a few amino acids in the region of Drosophila PCNA thought to interact with pol δ, all four effects can be enhanced dramatically.

Conclusions
Our results therefore suggest that all four above effects depend at least in part on the PCNA-pol δ interaction. Moreover unlike mammals, Drosophila offers the potential for immediate in vivo genetic analyses. Although it has proven difficult to obtain sufficient amounts of homologous pol δ for parallel in vitro biochemical studies, by altering Drosophila PCNA using site-directed mutagenesis as suggested by our results, in vitro biochemical studies may now be performed using human and/or calf thymus pol δ preparations.