bluuebunny/crossref_metadata_2025_split huggingface dataset:
Roles of proinflammatory cytokines and the Fas/Fas ligand interaction in the pathogenesis of inflammatory myopathies
Authors: Kondo Masahiro , Murakawa Yohko , Harashima Nanae , Kobayashi Shotai , Yamaguchi Shuhei , Harada Mamoru 
Published: December 2008

SummaryWithin the lesions of inflammatory myopathies, muscle fibres and invading mononuclear cells express Fas and Fas ligand (FasL), respectively. However, the roles of the Fas/FasL interaction in the pathogenesis of inflammatory myopathies are not fully understood. In the present study, we investigated the roles of proinflammatory cytokines and the Fas/FasL system in the pathogenesis of inflammatory myopathies. In vitro culturing of muscle cells with the proinflammatory cytokines interferon‐γ, tumour necrosis factor‐α, and interleukin (IL)‐1β synergistically increased Fas expression, susceptibility to Fas‐mediated apoptosis, and the expression of cytoplasmic caspases 8 and 3. In addition, culturing of muscle cells with activated CD4+ T cells induced muscle cell apoptosis, which was partially inhibited by anti‐FasL antibody. We also tested the possibility that T helper (Th) 17, which is an IL‐17‐producing helper T‐cell subset that plays crucial roles in autoimmune and inflammatory responses, participates in the pathogenesis of inflammatory myopathies. Interestingly, in vitro culturing of dendritic cells with anti‐Fas immunoglobulin M (IgM) or activated CD4+ T cells induced the expression of mRNA for IL‐23p19, but not for IL‐12p35, in addition to proinflammatory cytokines. Furthermore, IL‐23p19 and IL‐17 mRNAs were detected in the majority of biopsy samples from patients with inflammatory myopathies. Taken together, these results suggest that proinflammatory cytokines enhance Fas‐mediated apoptosis of muscle cells, and that the Fas/FasL interaction between invading dendritic cells and CD4+ T cells induces local production of IL‐23 and proinflammatory cytokines, which can promote the proliferation of Th17 cells and enhance Fas‐mediated apoptosis of muscle cells, respectively.
Common themes emerge in the transcriptional control of T helper and developmental cell fate decisions regulated by the T‐box, GATA and ROR families
Authors: Miller Sara A. , Weinmann Amy S. 
Published: December 2008

SummaryCellular differentiation requires the precise action of lineage‐determining transcription factors. In the immune system, CD4+ T helper cells differentiate into at least three distinct effector lineages, T helper type 1 (Th1), Th2 and Th17, with the fate of the cell at least in part determined by the transcription factors T‐box expressed in T cells (T‐bet), GATA‐3 and retinoid‐related orphan receptor γt (RORγt), respectively. Importantly, these transcription factors are members of larger families that are required for numerous developmental transitions from early embryogenesis into adulthood. Mutations in members of these transcription factor families are associated with a number of human genetic diseases due to a failure in completing lineage‐specification events when the factor is dysregulated. Mechanistically, there are both common and distinct functional activities that are utilized by T‐box, GATA and ROR family members to globally alter the cellular gene expression profiles at specific cell fate decision checkpoints. Therefore, understanding the molecular events that contribute to the ability of T‐bet, GATA‐3 and RORγt to define T helper cell lineages can provide valuable information relevant to the establishment of other developmental systems and, conversely, information from diverse developmental systems may provide unexpected insights into the molecular mechanisms utilized in T helper cell differentiation.
Toll‐like receptor agonists induce inflammation and cell death in a model of head and neck squamous cell carcinomas
Authors: Rydberg Camilla , Månsson Anne , Uddman Rolf , Riesbeck Kristian , Cardell Lars‐Olaf 
Published: December 2008

SummaryToll‐like receptors (TLRs) are increasingly implicated in the pathogenesis of cancer. The present study describes TLR expression and function in healthy and malignant airway epithelial cells. The squamous cell carcinoma cell line Detroit‐562 was compared with the healthy bronchial epithelial cell line NL‐20 and primary human nasal epithelial cells (HNECs). TLR2, TLR3 and TLR5 were present in primary head and neck squamous cell carcinomas (HNSCCs). Consistent with this, Detroit‐562 expressed TLR2, TLR3 and TLR5, whereas NL‐20 expressed mainly TLR3 and HNECs expressed TLR2‐5. In Detroit‐562, Pam3CSK4, poly(I:C) and flagellin, ligands for TLR2, TLR3 and TLR5, respectively, induced an up‐regulation of intercellular adhesion molecule 1 (ICAM‐1), an increase in interleukin (IL)‐6 and IL‐8 secretion and a decrease in cell viability. Additionally, poly(I:C) affected IL‐1β production and the migratory behaviour of Detroit‐562. NL‐20 responded with a slight increase in IL‐8 secretion upon poly(I:C) stimulation. Poly(I:C) induced a small increase in IL‐1β, IL‐6 and IL‐8 production in HNECs, while Pam3CSK4increased viability. The TLR signalling was transcription‐dependent, but the pathways involved differed among TLRs as well as cells. In Detroit‐562, TLR2 and TLR5 activation was mediated via c‐jun N‐terminal kinase (JNK)‐, p38‐, phosphatidylinositol 3‐kinase (PI3K)‐ and nuclear factor (NF)‐κB‐related pathways, while TLR3 was dependent on NF‐κB. In NL‐20, TLR3 signalled via p38, and in HNECs, NF‐κB, JNK and extracellular signal‐regulated kinase (ERK) appeared to be involved. We found that TLR agonists induced a robust response in HNSCCs, characterized by generation of inflammation and cell death. A similar response was not seen in normal epithelial cells. Thus, the TLR system should be considered an important target in future antitumour immunotherapy.
Rhizobia utilize pathogen‐like effector proteins during symbiosis
Authors: Kambara Kumiko , Ardissone Silvia , Kobayashi Hajime , Saad Maged M. , Schumpp Olivier , Broughton William J. , Deakin William J. 
Published: December 2008

SummaryA type III protein secretion system (T3SS) is an important host range determinant for the infection of legumes by Rhizobium sp. NGR234. Although a functional T3SS can have either beneficial or detrimental effects on nodule formation, only the rhizobial‐specific positively acting effector proteins, NopL and NopP, have been characterized. NGR234 possesses three open reading frames potentially encoding homologues of effector proteins from pathogenic bacteria. NopJ, NopM and NopT are secreted by the T3SS of NGR234. All three can have negative effects on the interaction with legumes, but NopM and NopT also stimulate nodulation on certain plants. NopT belongs to a family of pathogenic effector proteases, typified by the avirulence protein, AvrPphB. The protease domain of NopT is required for its recognition and a subsequent strong inhibition in infection of Crotalaria juncea. In contrast, the negative effects of NopJ are relatively minor when compared with those induced by its Avr homologues. Thus NGR234 uses a mixture of rhizobial‐specific and pathogen‐derived effector proteins. Whereas some legumes recognize an effector as potentially pathogen‐derived, leading to a block in the infection process, others perceive both the negative‐ and positive‐acting effectors concomitantly. It is this equilibrium of effector action that leads to modulation of symbiotic development.
Haem acquisition is facilitated by a novel receptor Hma and required by uropathogenic Escherichia coli for kidney infection
Authors: Hagan Erin C. , Mobley Harry L. T. 
Published: December 2008

SummaryIron acquisition, mediated by specific outer membrane receptors, is critical for colonization of the urinary tract by uropathogenic Escherichia coli (UPEC). The role of specific iron sources in vivo, however, remains largely unknown. In this study, we identified a 79 kDa haem receptor, haemacquisition protein Hma, and established that it functions independently of ChuA to mediate haemin uptake by UPEC strain CFT073. We demonstrated that expression of hma promotes TonB‐dependent haemin utilization and the Hma protein binds haemin with high affinity (Kd = 8 μM). Hma, however, lacks conserved His residues shown to mediate haem uptake by other bacterial receptors. In contrast, we identified Tyr‐126 as a residue necessary for Hma‐mediated haemin utilization. In a murine co‐infection model of UTI, an isogenic hma mutant was out‐competed by wild‐type CFT073 in the kidneys (P < 0.001) and spleens (P <  0.0001) of infected mice, indicating its expression provided a competitive advantage in these organs. Furthermore, a hma chuA double mutant, which is unable to utilize haemin, was unable to colonize the kidneys to wild‐type levels during independent infection (P = 0.02). Thus, we demonstrate that UPEC requires haem for kidney colonization and that uptake of this iron source is mediated, in part, by the novel receptor, Hma.
Novel Escherichia coli RF1 mutants with decreased translation termination activity and increased sensitivity to the cytotoxic effect of the bacterial toxins Kid and RelE
Authors: Diago‐Navarro Elizabeth , Mora Liliana , Buckingham Richard H. , Díaz‐Orejas Ramón , Lemonnier Marc 
Published: December 2008

SummaryNovel mutations in prfA, the gene for the polypeptide release factor RF1 of Escherichia coli, were isolated using a positive genetic screen based on the parD (kis, kid) toxin–antitoxin system. This original approach allowed the direct selection of mutants with altered translational termination efficiency at UAG codons. The isolated prfA mutants displayed a ∼10‐fold decrease in UAG termination efficiency with no significant changes in RF1 stability in vivo. All three mutations, G121S, G301S and R303H, were situated close to the nonsense codon recognition site in RF1:ribosome complexes. The prfA mutants displayed increased sensitivity to the RelE toxin encoded by the relBE system of E. coli, thus providing in vivo support for the functional interaction between RF1 and RelE. The prfA mutants also showed increased sensitivity to the Kid toxin. Since this toxin can cleave RNA in a ribosome‐independent manner, this result was not anticipated and provided first evidence for the involvement of RF1 in the pathway of Kid toxicity. The sensitivity of the prfA mutants to RelE and Kid was restored to normal levels upon overproduction of the wild‐type RF1 protein. We discuss these results and their utility for the design of novel antibacterial strategies in the light of the recently reported structure of ribosome‐bound RF1.
Vβ Usage and T Regulatory Cells in Children Following Partial or Total Thymectomy after Open Heart Surgery in Infancy
Authors: Eysteinsdottir J. H. , Freysdottir J. , Skaftadottir I. , Helgason H. , Haraldsson A. , Ogmundsdottir H. M. 
Published: December 2008

AbstractDuring open heart surgery in infants the thymus was usually removed, partly or completely. Our previous studies on 16 such children indicated reduced T‐cell output later in life with signs of extrathymic maturation of the T cells, but no reduction in T regulatory cells (CD4+CD25+). The diversity of the T‐cell repertoire in these children was examined to test if the extrathymic microenvironment could alter Vβ usage. The expression of Foxp3 and CD127 in CD4+CD25high T cells was measured in order to determine whether the T regulatory cells had the phenotype of natural T regulatory cells. There was a wide distribution of Vβ usage in both study and control groups. Significant variability was found in Vβ usage for CD4+ and CD8+ T cells when the distribution of the percentage of T cells expressing each Vβ family was analysed between individuals within each group (P < 0.001; Kruskal–Wallis). Significant difference was also found in average usage of Vβ2, Vβ5.1 and Vβ14 chains within CD4+ T cells and Vβ2, Vβ8 and Vβ21.3 chains within CD8+ cells between the groups (P < 0.05; Student’s t‐test). There was no difference between the two groups with regard to the proportion of CD4+CD25high T cells and no difference in the average expression of Foxp3 or CD127 within the CD4+CD25high population. Our data provide evidence that cardiothoracic surgery in infants and total or partial thymectomy alters Vβ usage, suggesting more limited selection in such children than in the control group. The frequency of natural T regulatory cells seems to be unimpaired.
Crosstalk between biotic and abiotic stress responses in tomato is mediated by the AIM1 transcription factor
Authors: AbuQamar Synan , Luo Hongli , Laluk Kristin , Mickelbart Michael V. , Mengiste Tesfaye 
Published: December 2008

SummaryPlants deploy diverse molecular and cellular mechanisms to survive in stressful environments. The tomato (Solanum lycopersicum) abscisic acid‐induced myb1 (SlAIM1) gene encoding an R2R3MYB transcription factor is induced by pathogens, plant hormones, salinity and oxidative stress, suggesting a function in pathogen and abiotic stress responses. Tomato SlAIM1 RNA interference (RNAi) plants with reduced SlAIM1 gene expression show an increased susceptibility to the necrotrophic fungus Botrytis cinerea, and increased sensitivity to salt and oxidative stress. Ectopic expression of SlAIM1 is sufficient for tolerance to high salinity and oxidative stress. These responses correlate with reduced sensitivity to abscisic acid (ABA) in the SlAIM1 RNAi, but increased sensitivity in the overexpression plants, suggesting SlAIM1‐mediated ABA responses are required to integrate tomato responses to biotic and abiotic stresses. Interestingly, when exposed to high root‐zone salinity levels, SlAIM1 RNAi plants accumulate more Na+, whereas the overexpression lines accumulate less Na+ relative to wild‐type plants, suggesting that SlAIM1 regulates ion fluxes. Transmembrane ion flux is a hallmark of early responses to abiotic stress and pathogen infection preceding hypersensitive cell death and necrosis. Misregulation of ion fluxes can result in impaired plant tolerance to necrotrophic infection or abiotic stress. Our data reveal a previously uncharacterized connection between ABA, Na+ homeostasis, oxidative stress and pathogen response, and shed light on the genetic control of crosstalk between plant responses to pathogens and abiotic stress. Together, our data suggest SlAIM1 integrates plant responses to pathogens and abiotic stresses by modulating responses to ABA.
Late‐onset Papillon–Lefevre syndrome with pyogenic liver abscesses: report of one case
Authors: Yazdanfar Ameneh , Farahnaki Sasan 
Published: December 2008

A 25‐year‐old woman living in Hamedan, Iran, presented originally at 7 years of age with erythematous, hyperkeratotic lesions on the palms and soles with extension to the dorsal side of the hands and feet. Involvement of the elbows and knees was also seen. From 12 years of age, she started to lose her teeth. At the same age, she experienced fever, chills, malaise, myalgia, and right upper quadrant abdominal pain. With a diagnosis of pyogenic liver abscesses, the patient underwent successful surgical treatment. Examination revealed erythematous, hyperkeratotic, scaling plaques on the palms and soles, dorsal side of the hands and feet (Fig. 1), elbows and knees. All the teeth were missing from the mouth (Fig. 2), and she used a dental prosthesis. A surgical scar was observed on the right upper quadrant of the abdomen (Fig. 3). Skull X‐ray and computed tomography scan were normal. Skin biopsy of the dorsal right hand demonstrated hyperkeratosis, focal parakeratosis, hypergranulosis, and acanthosis with a mild inflammatory infiltrate around the vessels (Fig. 4).Hyperkeratotic plaques on the hands and feetimageLoss of permanent teethimageSurgical scar on the right upper quadrant of the abdomen and hyperkeratotic plaques on the handimageHyperkeratosis, focal parakeratosis, hypergranulosis, and acanthosis (hematoxylin and eosin, ×40)image
Trends in air quality in the UK
Authors: AYRES J. G. 
Published: December 2008

Ayres JG. Trends in air quality in the UK.Many problems are encountered when assessing trends in air quality, including changes in methods of measuring pollutants over time, different sampling timeframes, and the number and distribution of monitoring sites. Nevertheless, reasonable projections have been established for trends in sulphur dioxide (SO2), particulate matter, nitrogen dioxide (NO2), and ozone levels in the UK, which allow some estimate of future levels. The major source of SO1 is coal‐fired power stations. Since the Clean Air Act of 1956, SO2 levels have decreased substantially. Nevertheless, a small but progressive increase in SO2 emissions is predicted over the next 15 years, but this is unlikely to exceed current UK air quality standards on a frequent basis. Particulate pollution (as black smoke) has also decreased dramatically since the 1960s, when the main source was fossil fuel burning. In the 1990s, the main source of particle emissions is from heavy goods vehicles. If measures currently under consideration in the UK are implemented, annual emissions may decrease to below 60 kT over the next decade, but a progressive increase is predicted thereafter. No significant changes have occurred with respect to oxides of nitrogen (NOx) and ozone levels over the last 20 years. It is predicted that NOx emissions will decline in the future due in part to the introduction of catalytic converters, while trends in ozone levels will depend on substrate supply (NOx and hydrocarbons) and weather conditions. Despite short‐term trends downwards in air pollutant levels, trends may reverse in the next millennium, and continued efforts must be made to develop new ways of reducing ambient air pollutant levels.
Epidemiology of pollution‐induced airwav disease in Japan
Authors: MIYAMOTO T. 
Published: December 2008

Miyamoto T. Epidemiology of pollution‐induced airway disease in Japan.Air pollution has been implicated as one of the factors responsible for the increased incidence of allergic diseases seen over recent years. Epidemiological studies in Japan demonstrate that atopic subjects living in urban areas are more likely to suffer from the effects of air pollution, with increased coughing, sputum production, wheezing and throat irritation. Furthermore, animal studies show that high concentrations of pollutant gases can promote airway sensitization. The incidence of allergic rhinitis and asthma have been shown to be greater in areas where there is heavy traffic and hence high levels of automobile exhaust emissions. Intranasal administration of diesel exhaust particles in mice produces a stimulatory effect on immunoglobulin E production, and a similar finding has also been shown with suspended particulate matter in air. Air pollutants, such as ozone and nitrogen dioxide (NO2), have been shown to stimulate the production of granulocyte‐macrophage colony stimulating factor, which may play a vital role in airway hyperreactivity and asthma. In comparative studies of asthma in urban and rural areas, history of airway infection and a younger age of onset were found to be sifificantly greater in urban areas. When the asthmatic patients were divided into two groups according to environmental NO2 levels (group I: NO2 >30 ppb; group II: NO2 <30 ppb), no signficant difference regarding the various parameters was noted between the two groups, except for a greater severity of asthma in adults in group I, and a greater severity in children in group 11. These studies imply that air pollution may be one reason for the increase in allergic diseases in Japan, but a definitive conclusion cannot be drawn, and further investigation is warranted.
Quantification of house‐dust‐mite populations
Authors: Hill M. R. 
Published: December 2008

Since the proposal that allergen from the mite Dermatophagoides pteronyssinusis identical to the house‐dust allergen supposed to cause asthma and allergy, interestin the abundance, species diversity, and frequency of mites in the home has expanded.Surveys and ecologic studies have confirmed the ubiquity of mites in house dust, especially mites of the family Pyroglyphidae, but most do not give an accurate estimate of population size or mite exposure. These are still important issues today in attempts to quantify theexposure to house‐dust mite that constitutes a risk, to assess mite‐eradication trials, and to determine fluctuations in mite population. The problems encountered with common methods of house‐dust sampling, mite extraction, and measuring house‐dust allergen arediscussed.
Cornulin, a marker of late epidermal differentiation, is down‐regulated in eczema
Authors: Liedén A. , Ekelund E. , Kuo I ‐C. , Kockum I. , Huang C ‐H. , Mallbris L. , Lee S. P. , Seng L. K. , Chin G. Y. , Wahlgren C ‐F. , Palmer C. N. A. , Björkstén B. , Ståhle M. , Nordensköld M. , Bradley M. , Chua K. Y. , D’Amato M. 
Published: December 2008

Background:  Eczema is a common chronic inflammatory skin disorder which shows strong genetic predisposition. To identify new potential molecular determinants of the disease pathogenesis, we performed a gene expression study in an eczema mouse model. This analysis identified a marked down regulation of the cornulin gene (CRNN), a member of the epidermal differentiation complex, in the eczema‐like skin. We then investigated CRNN as an eczema candidate gene and studied its polymorphism and the expression in the skin of eczema patients.Methods:  An eczema‐like phenotype was induced in mice by allergen (Der p2) patching. Gene expression analysis was performed with the subtractive suppression hybridization method and validated by real time PCR and the transmission disequilibrium test was used to test for genetic associations in 406 multiplex eczema families.Results:  Der p 2 patched mice developed a localized eczema and a Th 2 skewed systemic response. Real time PCR analysis confirmed a down regulation of CRNN mRNA in eczema‐like skin in the mouse model and in human eczema. The CRNN polymorphism rs941934 was significantly associated with atopic eczema in the genetic analysis (P = 0.006), though only as part of an extended haplotype including a known associated variant (2282del4) in the filaggrin gene.Conclusions:  CRNN mRNA expression is decreased in eczematous skin. Further studies are needed to verify whether the associated cornulin polymorphism contribute to the genetic susceptibility in eczema.