bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthetic fibril peptide promotes clearance of scrapie prion protein by lysosomal degradation
Authors: Okemoto‐Nakamura Yuko , Yamakawa Yoshio , Hanada Kentaro , Tanaka Keiko , Miura Masami , Tanida Isei , Nishijima Masahiro , Hagiwara Ken'ichi 
Published: July 2008

ABSTRACTTransmissible spongiform encephalopathies are infectious and neurodegenerative disorders that cause neural deposition of aggregates of the disease‐associated form of PrPSc. PrPSc reproduces by recruiting and converting the cellular PrPC, and ScN2a cells support PrPSc propagation. We found that incubation of ScN2a cells with a fibril peptide named P9, which comprises an intrinsic sequence of residues 167–184 of mouse PrPC, significantly reduced the amount of PrPSc in 24 hr. P9 did not affect the rates of synthesis and degradation of PrPC. Interestingly, immunofluorescence analysis showed that the incubation of ScN2a cells with P9 induced colocalization of the accumulation of PrP with cathepsin D‐positive compartments, whereas the accumulation of PrP in the cells without P9 colocalized mainly with lysosomal associated membrane proteins (LAMP)‐1‐positive compartments but rarely with cathepsin D‐positive compartments in perinuclear regions. Lysosomal enzyme inhibitors attenuated the anti‐PrPSc activity; however, a proteasome inhibitor did not impair P9 activity. In addition, P9 neither promoted the ubiquitination of cellular proteins nor caused the accumulation of LC3‐II, a biochemical marker of autophagy. These results indicate that P9 promotes PrPSc redistribution from late endosomes to lysosomes, thereby attaining PrPSc degradation.
Toxoplasma gondii‐derived heat shock protein 70 induces lethal anaphylactic reaction through activation of cytosolic phospholipase A2 and platelet‐activating factor via Toll‐like receptor 4/myeloid differentiation factor 88
Authors: Fang Hao , Mun Hye‐Seong , Kikumura Akitoshi , Sayama Yusuke , Norose Kazumi , Yano Akihiko , Aosai Fumie 
Published: July 2008

ABSTRACT Toxoplasma gondii‐derived heat shock protein 70 (T.g.HSP70) was proven to induce IFN‐γ‐dependent lethal anaphylactic reaction in T. gondii‐infected mice through an alternative PAF‐mediated pathway, but not the classical immunoglobulin (Ig)E‐dependent pathway. Although marked IFN‐γ production was observed by CD11b+, CD11c+, CD4+ and CD8+ splenocytes, CD11b+ and CD11c+ cells were shown to be the key effecter cells which generated pro‐inflammatory lipid such as PAF and caused T.g.HSP70‐induced anaphylactic reaction. In the present study, we found that the T.g.HSP70‐induced anaphylactic reaction was not observed in TLR 4‐deficient (−/−) mice, whereas it was observed in WT and TLR2−/− mice. The mRNA expression of PAF‐AH, the main enzyme for PAF degradation, increased in T. gondii‐infected WT and TLR2−/− but not in TLR4−/− mice after T.g.HSP70 injection. Furthermore, phosphorylation of cPLA2, which is the key enzyme for pro‐inflammatory lipid generation, was detected in CD11b+ splenocytes of WT and TLR2−/− mice but not in TLR4−/− mice. Subsequently, cPLA2 activation was suppressed by inhibiting the TLR4‐directed p38 and p44/42 MAPK pathways. However, T.g.HSP70‐induced anaphylactic reaction was observed in TRIF−/− mice, but not in MyD88−/− mice. These findings indicate the cPLA2 activated‐PAF production via TLR4/MyD88‐dependent, but not TRIF‐dependent, signaling pathway in T.g.HSP70‐induced anaphylactic reaction in T. gondii‐infected mice.
Polymerase chain reaction detection of bacterial 16S rRNA gene in human blood
Authors: Moriyama Kosei , Ando Chie , Tashiro Kosuke , Kuhara Satoru , Okamura Seiichi , Nakano Shuji , Takagi Yasumitsu , Miki Takeyoshi , Nakashima Yoshiyuki , Hirakawa Hideki 
Published: July 2008

ABSTRACTBacterial 16S ribosomal RNA genes (rDNA) were detected in blood samples from two healthy individuals by PCR under conditions involving 30 cycles that did not produce any visible products from negative control saline. Even from control samples, PCR involving 35–40 cycles yielded visible bands. Major clones detected in the blood samples, but not in control, were the Aquabacterium subgroup, Stenotrophomonas subgroup, Budvicia subgroup, Serratia subgroup, Bacillus subgroup and Flavobacteria subgroup. No clone was located within the bacteroides‐clostridium‐lactobacillus cluster, which is indigenous to gastrointestinal flora.
Effect of potato suberin on Streptomyces scabies proteome
Authors: LAUZIER ANNIE , SIMAO‐BEAUNOIR ANNE‐MARIE , BOURASSA SYLVIE , POIRIER GUY G. , TALBOT BRIAN , BEAULIEU CAROLE 
Published: July 2008

SUMMARYTwo‐dimensional (2D) PAGE was used to detect proteins induced in Streptomyces scabies by potato suberin, a lipidic plant polymer. Nineteen up‐regulated proteins were excised from 2D gels and analysed by N‐terminal sequencing or tandem mass spectrometry (MS/MS). Four of the up‐regulated proteins could be linked to the bacterial response to stress (AldH, GroES, TerD and LexA). Specific metabolic pathways seemed to be activated in the presence of suberin, as shown by the increased expression of specific transporters and of enzymes related not only to glycolysis, but also to nucleotide and amino acid metabolism. Suberin also appeared to influence secondary metabolism as it also caused the overproduction of the BldK proteins that are known to be involved in differentiation and secondary metabolism.
A requirement for calcium in the caspase‐independent killing of Burkitt lymphoma cell lines by Rituximab
Authors: Daniels Ian , Turzanski Julie , Haynes Andrew P. 
Published: July 2008

SummaryThe therapeutic monoclonal antibody rituximab has previously been shown to kill B cells in a caspase‐independent manner. The signalling pathways underpinning this novel death pathway are unknown. The present study showed that rituximab treatment of Burkitt lymphoma cell lines induced a slow rise in intracellular calcium ([Ca2+]i). This rise was only witnessed in cell lines that were killed by antibody, suggesting a critical role for Ca2+in mediating rituximab‐driven caspase‐independent cell death. Inhibition of the two main intracellular store‐located Ca2+channels, i.e. the ryanodine and inositol‐1,4,5‐triphosphate receptor channels by dantrolene and xestospongen‐c respectively did not prevent the rise in Ca2+seen with rituximab or protect cells from subsequent death. In sharp contrast, inhibition of Ca2+entry via plasma membrane channels with (2‐aminoethoxy) diphenylborate or SKF‐96365 or complete chelation of extracellular Ca2+with ethyleneglycol bis (aminoethylether) tetra‐acetate inhibited the rise in [Ca2+]iand increased cell viability. Together, these data suggest that ligation of the CD20 receptor with rituximab allows a slow sustained influx of Ca2+from the external environment that under certain conditions can lead to cell death.
Reduced level of the spindle checkpoint protein BUB1B is associated with aneuploidy in colorectal cancers
Authors: Burum‐Auensen E. , DeAngelis P. M. , Schjølberg A. R. , Røislien J. , Mjåland O. , Clausen O. P. F. 
Published: July 2008

Abstract.  Objectives: The majority of solid human malignancies demonstrate DNA aneuploidy as a consequence of chromosomal instability. We wanted to investigate whether Aurora A, Aurora B, BUB1B and Mad2 were associated with the development of aneuploidy in colorectal adenocarcinomas as suggested by several in vitro studies, and if their protein levels were related to alterations at the corresponding chromosomal loci. Materials and methods: Expression levels of these spindle proteins were investigated by immunohistochemistry using tissue micro‐arrays in a series of DNA aneuploid and diploid colorectal adenocarcinomas previously examined for genomic aberrations by comparative genomic hybridization. Results: All proteins were overexpressed in malignant tissues compared to controls (P < 0.001 for all). BUB1B level was significantly reduced in aneuploid compared to diploid cancers (P = 0.001), whereas expression of the other proteins was not associated with DNA ploidy status. High levels of Aurora A (P = 0.049) and low levels of Aurora B (P = 0.031) were associated with poor prognosis, but no associations were revealed between protein expression and genomic aberration. Conclusions: A significant reduction of BUB1B level was detected in aneuploid compared to diploid colorectal cancers, consistent with earlier studies showing that loss of spindle checkpoint function may be involved in development of DNA aneuploidy. Our data also show that spindle proteins are overexpressed in colorectal cancers, and that expression of the Aurora kinases is associated with prognosis in colorectal cancer.
Exogenous bone marrow cells do not rescue non‐irradiated mice from acute renal tubular damage caused by HgCl2, despite establishment of chimaerism and cell proliferation in bone marrow and spleen
Authors: Fang T.‐C. , Otto W. R. , Jeffery R. , Hunt T. , Alison M. R. , Cook H. T. , Wright N. A. , Poulsom R. 
Published: July 2008

Abstract.  Objective: Various studies have shown that bone marrow stem cells can rescue mice from acute renal tubular damage under a conditioning advantage (irradiation or cisplatin treatment) favouring donor cell engraftment and regeneration; however, it is not known whether bone marrow cells (BMCs) can contribute to repair of acute tubular damage in the absence of a selection pressure for the donor cells. The aim of this study was to examine this possibility. Materials and methods: Ten‐week‐old female mice were assigned into control non‐irradiated animals having only vehicle treatment, HgCl2‐treated non‐irradiated mice, HgCl2‐treated non‐irradiated mice infused with male BMCs 1 day after HgCl2, and vehicle‐treated mice with male BMCs. Tritiated thymidine was given 1 h before animal killing. Results: Donor BMCs could not alleviate non‐irradiated mice from acute tubular damage caused by HgCl2, deduced by no reduction in serum urea nitrogen combined with negligible cell engraftment. However, donor BMCs could home to the bone marrow and spleen and display proliferative activity. This is the first report to show that despite no preparative myeloablation of recipients, engrafted donor BMCs can synthesize DNA in the bone marrow and spleen. Conclusions: Exogenous BMCs do not rescue non‐irradiated mice from acute renal tubular damage caused by HgCl2, despite establishment of chimerism and cell proliferation in bone marrow and spleen.
Living on an island: consequences of childhood abuse, attachment disruption and adversity in later life
Authors: Frederick John , Goddard Chris 
Published: July 2008

ABSTRACTThis paper reports on a study which sought to obtain greater knowledge and understanding of the life circumstances of a group of people who had experienced adversity and abuse in childhood. A qualitative research strategy involving in‐depth interviews with individuals was used to help achieve the study's aim. The study found that interviewees detailed multiple risks to their development during childhood and adolescence, including experiences of child abuse, being placed in care and major grief and loss experiences. Most had left home in their mid‐teenage years and had little or no contact with their families of origin. Interviewees had very limited social networks and described difficulties in making and keeping friends. Many reported unstable and often violent personal relationships. As suggested by attachment theory, this study supports the notion of developmental continuities from adverse childhood experiences into later life, particularly in relation to personal and social relationships. Recommendations for a number of suitable methods of intervention and support are outlined.
Social Work Practices: silences and elisions in the plan to ‘transform’ the lives of children ‘looked after’ in England
Authors: Garrett Paul Michael 
Published: July 2008

ABSTRACTThis paper critically examines the government's proposals for the reform of services for children in public care, or ‘looked after’, in England and, more specifically, the proposal to set up Social Work Practices (SWPs, see Note 1). These are envisaged as groups of social workers, commissioned by but independent of local authorities. The changes have been mapped out by a Green Paper Care Matters: Transforming the Lives of Children and Young People in Care published in October 2006, a subsequent working group report, and Care Matters: Time for Change, a White Paper published in June 2007. This was followed, in November, by the publication of the Children and Young Persons’ Bill. It is argued that there are, at least, two issues which could be focused on by those seeking to counter moves to introduce SWPs. First, the enhanced role being given to private sector providers because, it is maintained, public services provided by local authorities are unambiguously ‘failing’ children. Second, the fact that the views of parents and ‘looked after’ children are mostly excluded from the dominant and ‘official’ discourse on SWPs.
Dyadic Developmental Psychotherapy: an evidence‐based treatment for children with complex trauma and disorders of attachment
Authors: Becker‐Weidman Arthur , Hughes Daniel 
Published: July 2008

ABSTRACTDyadic Developmental Psychotherapy (DDP) is a family therapy treatment based on Attachment Theory. It is an integration of several approaches, methods and techniques that have a strong evidence base. The approach was originally developed to treat children with disorders of attachment and has been shown to be effective. It has since been more broadly used to help families with a variety of difficulties, including complex trauma. This paper outlines the primary principles and components of DDP and the evidence to support the effectiveness of the components and, therefore, of DDP.
Immunoglobulin E recognition patterns to purified Kiwifruit (Actinidinia deliciosa) allergens in patients sensitized to Kiwi with different clinical symptoms
Authors: Palacin A. , Rodriguez J. , Blanco C. , Lopez‐Torrejon G. , Sánchez‐Monge R. , Varela J. , Jiménez M. A. , Cumplido J. , Carrillo T. , Crespo J. F. , Salcedo G. 
Published: July 2008

SummaryBackground
Green kiwifruit allergy is on the rise. However, no surveys testing purified major kiwi allergens have been carried out in a large population, including both kiwi‐sensitized [skin prick test (SPT)‐positive] and truly kiwi‐allergic patients.Objective
To isolate major kiwifruit allergens, and to explore their relevance by in vitro and in vivo methods in a large kiwi‐sensitized and ‐allergic population.Methods
A large group (n=92) of kiwi‐sensitized patients with different clinical symptoms were selected, and double‐blind, placebo‐controlled, food challenges to kiwi were performed in 52 of them. The three major IgE‐binding proteins from kiwifruit extracts were isolated and characterized by N‐terminal amino acid sequencing and molecular size and glycosylation analysis. The allergenic potency of the three kiwi allergens, and of avocado Pers a 1 as a model allergen associated with the latex‐fruit syndrome, was tested by specific IgE quantitation, immunodetection assays and SPTs.Results
The isolated kiwifruit allergens were identified as actinidin Act d 1, glycosylated thaumatin‐like Act d 2 and a novel 40 kDa glycoprotein designated as Act d 3.02. Specific IgE to each of the three allergens was found in over 60% of sera from kiwi‐sensitized patients, and Act d 1 and Act d 2 induced positive SPT responses in over 50% of the tested patients. A significant link between IgE levels to Act d 1 and Act d 3 and anaphylaxis was uncovered. Avocado Pers a 1 showed an in vitro sensitization prevalence of around 45%, but a low in vivo reactivity.Conclusion
Act d 1, Act d 2 and Act d 3 are major allergens in the population studied. Severe symptoms after kiwi ingestion are associated with high IgE levels to Act d 1 and Act d 3.
Induction of T‐helper type 2 cytokine release and up‐regulated expression of protease‐activated receptors on mast cells by recombinant American cockroach allergen Per a 7
Authors: Zhang Z. , Zhang H. , Yang H. , Zhang L. , Chen X. , Zheng X. , He S. 
Published: July 2008

SummaryBackground
The cockroach is a major source of indoor allergens, which cause perennial rhinitis and asthma. Per a 7 is one of the major allergens from the American cockroach, eliciting IgE reaction in over 50% of sera from allergic individuals. However, the actions of Per a 7 in the pathogenesis of allergic diseases remain poorly understood.Objective
The aim of the study was to investigate the effects of Per a 7 on the expression of protease‐activated receptors (PARs) on murine mast cells and the release of T‐helper type 2 (Th2) cytokines from these cells.Methods
Per a 7 gene was cloned and expressed in Escherichia coli. The purified recombinant Per a 7 (rPer a 7) was used to challenge murine mast cells P815 and the expression of PARs was determined by using real‐time quantitative RT‐PCR and flow cytometry. The release of IL‐4 and IL‐13 was detected with ELISA.Results
rPer a 7 was solubly expressed in E. coli and the purified rPer a 7 reacted with 75% (six out of eight) of the sera from cockroach‐allergic patients. Following stimulation of rPer a 7, the expression of PAR‐1, PAR‐2, PAR‐3 and PAR‐4 mRNAs on P815 cells increased by 8.7‐, 6.8‐, 14.4‐ and 8.8‐fold, respectively, following 2‐ and 6‐h incubation periods, and the expression of PAR‐1, PAR‐2 and PAR‐4 proteins was enhanced following 16‐h incubation. rPer a 7 provoked approximately up to a 4.8‐ and 2.3‐fold increase in IL‐4 and IL‐13 release from P815 cells following 6‐ and 16‐h incubation periods.Conclusion
rPer a 7 induced up‐regulation of PAR expression on P815 cells and provoked Th2 cytokines IL‐4 and IL‐13 secretion from these murine mast cells, which implicated that this major cockroach allergen is likely to contribute to the development of cockroach‐related allergic disease.
Toll‐like receptor 4 agonists adsorbed to aluminium hydroxide adjuvant attenuate ovalbumin‐specific allergic airway disease: role of MyD88 adaptor molecule and interleukin‐12/interferon‐γ axis
Authors: Bortolatto J. , Borducchi É. , Rodriguez D. , Keller A. C. , Faquim‐Mauro E. , Bortoluci K. R. , Mucida D. , Gomes E. , Christ A. , Schnyder‐Candrian S. , Schnyder B. , Ryffel B. , Russo M. 
Published: July 2008

SummaryBackground
Epidemiological and experimental data suggest that bacterial lipopolysaccharides (LPS) can either protect from or exacerbate allergic asthma. Lipopolysaccharides trigger immune responses through toll‐like receptor 4 (TLR4) that in turn activates two major signalling pathways via either MyD88 or TRIF adaptor proteins. The LPS is a pro‐Type 1 T helper cells (Th1) adjuvant while aluminium hydroxide (alum) is a strong Type 2 T helper cells (Th2) adjuvant, but the effect of the mixing of both adjuvants on the development of lung allergy has not been investigated.Objective
We determined whether natural (LPS) or synthetic (ER‐803022) TLR4 agonists adsorbed onto alum adjuvant affect allergen sensitization and development of airway allergic disease. To dissect LPS‐induced molecular pathways, we used TLR4‐, MyD88‐, TRIF‐, or IL‐12/IFN‐γ‐deficient mice.Methods
Mice were sensitized with subcutaneous injections of ovalbumin (OVA) with or without TLR4 agonists co‐adsorbed onto alum and challenged with intranasally with OVA. The development of allergic lung disease was evaluated 24 h after last OVA challenge.Results
Sensitization with OVA plus LPS co‐adsorbed onto alum impaired in dose‐dependent manner OVA‐induced Th2‐mediated allergic responses such as airway eosinophilia, type‐2 cytokines secretion, airway hyper‐reactivity, mucus hyper production and serum levels of IgE or IgG1 anaphylactic antibodies. Although the levels of IgG2a, Th1‐affiliated isotype increased, investigation into the lung‐specific effects revealed that LPS did not induce a Th1 pattern of inflammation. Lipopolysaccharides impaired the development of Th2 immunity, signaling via TLR4 and MyD88 molecules and via the IL‐12/IFN‐γ axis, but not through TRIF pathway. Moreover, the synthetic TLR4 agonists that proved to have a less systemic inflammatory response than LPS also protected against allergic asthma development.Conclusion
Toll‐like receptor 4 agonists co‐adsorbed with allergen onto alum down‐modulate allergic lung disease and prevent the development of polarized T cell‐mediated airway inflammation.
Prior SO2 exposure promotes airway inflammation and subepithelial fibrosis following repeated ovalbumin challenge
Authors: Cai C. , Xu J. , Zhang M. , Chen X‐D. , Li L. , Wu J. , Lai H‐W. , Zhong N‐S. 
Published: July 2008

SummaryBackground
Exposure to allergens or air pollutants often leads to asthma exacerbations associated with aggravation of airway inflammation. Although, repeated allergen challenge often induces chronic allergic airway inflammation (CAAI) and airway remodelling, yet, the effects of brief exposure to air pollutants such as SO2 on development of CAAI and airway remodelling remain to be clarified.Objective
The aim of the experiment was to investigate the effects of acute neutrophilic airway inflammation induced by brief exposure to SO2 on development of CAAI and subepithelial fibrosis (SEF) in a murine model of asthma.Methods
Acute airway inflammation was induced by brief exposure to 50 p.p.m. SO2 (1 h/d, 3 days). CAAI and SEF in BALB/c mice were induced by repeated challenge with ovalbumin (OVA) for 5 or 9 weeks with or without prior exposure to SO2. Bronchoalveolar lavage fluid (BALF) eosinophilia as index of CAAI, BALF endothelin‐1 (ET‐1) and TGF‐β1 levels, morphometric evaluation of fibrotic area beneath subbasement membrane and lung hydroxyproline content (Hyp) as indexes of SEF were monitored.Results
Exposure to SO2 led to acute neutrophilic inflammation and epithelial sloughing with profound elevation of BALF ET‐1. Repeated OVA challenge resulted in CAAI and SEF along with elevation of Hyp, increase of fibrotic area beneath subbasement membrane and elevation of BALF TGF‐β1. Preceding SO2 exposure exaggerated BALF eosinophilia, facilitated and enhanced SEF with more significant elevation of BALF ET‐1 and TGF‐β1 levels compared with OVA‐challenged mice without prior exposure to SO2. The increase of Hyp was positively correlated with elevation of BALF TGF‐β1 during CAAI (r=0.842, P<0.01).Conclusion
This data demonstrated that SEF developed in parallel with severity and time course of CAAI following repeated OVA challenge. SO2‐induced acute epithelial injury and neutrophilic inflammation could enhance CAAI and promote SEF, probably through overexpression of ET‐1 and TGF‐β1.