bluuebunny/crossref_metadata_2025_split huggingface dataset:
Profiling in resolving inflammatory exudates identifies novel anti‐inflammatory and pro‐resolving mediators and signals for termination
Authors: Norling L. V. , Serhan C. N. 
Published: April 2010

Abstract.  Norling LV, Serhan CN (Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA). Profiling in resolving inflammatory exudates identifies novel anti‐inflammatory and pro‐resolving mediators and signals for termination (Review). J Intern Med 2010; 268:15–24.A highly orchestrated inflammatory response and its completion, termed resolution, are essential for ongoing health. Thus, complete understanding of the cellular and molecular events that govern natural resolution is vital. Using an unbiased systems approach to profile self‐limited inflammatory exudates, we identified a novel genus of specialized pro‐resolving lipid mediators (SPMs) comprised of three new families coined the resolvins, protectins and most recently the maresins biosynthesized from ω‐3 fatty acids. These join the lipoxin‐ and aspirin‐triggered lipoxins as anti‐inflammatory and pro‐resolving lipid mediators formed from arachidonic acid with the genus. SPMs have proven stereoselective, and control both the duration and magnitude of inflammation. Mapping these endogenous resolution circuits provides new avenues to probe the molecular basis of many widely occurring diseases where uncontrolled inflammation is characteristic. The focus of this JIM review is to depict recent advances from studies by the authors and colleagues on the biosynthesis and actions of these novel anti‐inflammatory, pro‐resolving and protective lipid mediators. Together these findings indicate that defective mechanisms and pathways in resolution may underlie our current appreciation of the inflammatory phenotype(s) that characterize some prevalent human diseases.
Neutrophil granules in health and disease
Authors: Häger M. , Cowland J. B. , Borregaard N. 
Published: April 2010

Abstract.  Häger M, Cowland JB, Borregaard N (University of Copenhagen, Copenhagen, Denmark). Neutrophil granules in health and disease (Review). J Intern Med 2010; 268:25–34.Neutrophil granules store proteins that are critically important for the neutrophil to move from the vascular bed to tissues and to kill microorganisms. This is illustrated in nature when individual proteins are deleted due to inherited mutations of their cognate genes, and such deficiencies result in the conditions leucocyte adhesion deficiency and chronic granulomatous disease. The granules of the neutrophil have traditionally been divided into two or three major types but are instead a continuum where several subtypes can be identified with differences in protein content and propensity for mobilization. This is explained by the ‘targeting by timing hypothesis’ which states that granules are filled with granule proteins that are synthesized at the time the granule is formed. The heterogeneity of granules arises because the synthesis of granule proteins is individually controlled and major differences exist in the timings of biosynthesis during granulocytopoiesis. This is largely controlled by gene transcription.
Microsomal prostaglandin E synthase‐1 and 5‐lipoxygenase: potential drug targets in cancer
Authors: Rådmark O. , Samuelsson B. 
Published: April 2010

Abstract.  Rådmark O, Samuelsson B (Karolinska Institutet, Stockholm, Sweden). Microsomal prostaglandin Esynthase‐1 and 5‐lipoxygenase: potential drug targets in cancer (Review). J Intern Med 2010; 268:5–14.There is strong evidence for a role of prostaglandin (PG)E2 in cancer cell proliferation and tumour development. In PGE2 biosynthesis, cyclooxygenases (COX‐1/2) convert arachidonic acid to PGH2, which can be isomerized to PGE2 by PGE synthases, including microsomal PGE synthase‐1 (MPGES‐1). Data describing genetic deletions of MPGES‐1 are reviewed. The results suggest that MPGES‐1 is an alternative therapeutic target for cancer cells and tumours that express this enzyme. Several compounds that target COX‐2 or MPGES‐1 also inhibit 5‐lipoxygenase. This may be advantageous for treatment of some forms of cancer.
Low temperature and anhydrous electron microscopy techniques to observe the infection process of the bacterial pathogen Xanthomonas fragariae on strawberry leaves
Authors: ALLAN‐WOJTAS P. , HILDEBRAND P.D. , BRAUN P.G. , SMITH‐KING H.L. , CARBYN S. , RENDEROS W.E. 
Published: April 2010

SummaryPreserving the structural arrangement of the components of a bacterial infection process within a plant for microscopy study is a technical challenge because of the different requirements of each component for optimal preservation and visualization. We used low temperature scanning electron microscopy (cryo‐SEM), anhydrous fixation at ambient temperature and freeze‐substitution for transmission electron microscopy to examine fractured and sectioned strawberry leaves infected with Xanthomonas fragariae. Cryo‐SEM images of fractured samples showed the bacterial colonization of mesophyll air spaces in the leaf, limited by the vascular bundles and the orientation and packing of bacteria in extracellular polysaccharide. Transmission electron microscopy of samples fixed using osmium tetroxide dissolved in FC‐72 solvent at ambient temperature showed that the entire plant/bacteria/extracellular polysaccharide system was preserved in situ, and showed plasmolysis of mesophyll cells and disruption of organelles. In freeze‐substitution samples, osmium tetroxide in FC‐72 solvent gave superior preservation of the extracellular polysaccharide as compared to a conventional cocktail. In addition, strands believed to be xanthan were preferentially contrasted to show their density and orientation around the bacterial cells. We conclude that anhydrous fixation using osmium tetroxide in FC‐72 at ambient temperature gave the best preservation of the entire system, and freeze‐substitution using this same fixative enhanced the visualization of strands in the biofilm.
Automated focusing in bright‐field microscopy for tuberculosis detection
Authors: OSIBOTE O.A. , DENDERE R. , KRISHNAN S. , DOUGLAS T.S. 
Published: April 2010

SummaryAutomated microscopy to detectMycobacterium tuberculosisin sputum smear slides would enable laboratories in countries with a high tuberculosis burden to cope efficiently with large numbers of smears. Focusing is a core component of automated microscopy, and successful autofocusing depends on selection of an appropriate focus algorithm for a specific task. We examined autofocusing algorithms for bright‐field microscopy of Ziehl–Neelsen stained sputum smears. Six focus measures, defined in the spatial domain, were examined with respect to accuracy, execution time, range, full width at half maximum of the peak and the presence of local maxima. Curve fitting around an estimate of the focal plane was found to produce good results and is therefore an acceptable strategy to reduce the number of images captured for focusing and the processing time. Vollath's F4measure performed best for full z‐stacks, with a mean difference of 0.27 μm between manually and automatically determined focal positions, whereas it is jointly ranked best with the Brenner gradient for curve fitting.
The LysR‐type regulator QseA regulates both characterized and putative virulence genes in enterohaemorrhagic Escherichia coli O157:H7
Authors: Kendall Melissa M. , Rasko David A. , Sperandio Vanessa 
Published: April 2010

SummaryEnterohaemorrhagic Escherichia coli (EHEC) colonizes the large intestine, causing attaching and effacing (AE) lesions. Most of the genes involved in AE lesion formation are encoded within a chromosomal pathogenicity island termed the locus of enterocyte effacement (LEE). The LysR‐type transcriptional factor QseA regulates the LEE by binding to the regulatory region of ler. We performed transcriptome analyses comparing wild‐type (WT) EHEC and the qseA mutant to elucidate QseA's role in gene regulation. During both growth phases, several genes carried in O‐islands were activated by QseA, whereas genes involved in cell metabolism were repressed. During late‐logarithmic growth, QseA activated expression of the LEE genes as well as non‐LEE‐encoded effector proteins. We also performed electrophoretic mobility shift assays, competition experiments and DNase I footprints. The results demonstrated that QseA directly binds both the ler proximal and distal promoters, its own promoter, as well as promoters of genes encoded in EHEC‐specific O‐islands. Additionally, we mapped the transcriptional start site of qseA, leading to the identification of two promoter sequences. Taken together, these results indicate that QseA acts as a global regulator in EHEC, co‐ordinating expression of virulence genes.
PavB is a surface‐exposed adhesin of Streptococcus pneumoniae contributing to nasopharyngeal colonization and airways infections
Authors: Jensch Inga , Gámez Gustavo , Rothe Michael , Ebert Sandra , Fulde Marcus , Somplatzki Daniela , Bergmann Simone , Petruschka Lothar , Rohde Manfred , Nau Roland , Hammerschmidt Sven 
Published: April 2010

SummaryThe genomic analysis of Streptococcus pneumoniae strains identified the Pneumococcal adherence and virulence factor B (PavB), whose repetitive sequences, designated Streptococcal Surface REpeats (SSURE), interact with human fibronectin. Here, we showed the gene in all tested pneumococci and identified that the observed differences in the molecular mass of PavB rely on the number of repeats, ranging from five to nine SSURE. PavB interacted with fibronectin and plasminogen in a dose‐dependent manner as shown by using various SSURE peptides. In addition, we identified PavB as colonization factor. Mice infected intranasally with ΔpavB pneumococci showed significantly increased survival times compared with wild‐type bacteria. Importantly, the pavB‐mutant showed a delay in transmigration to the lungs as observed in real‐time using bioluminescent pneumococci and decreased colonization rates in a nasopharyngeal carriage model. In co‐infection experiments the wild‐type out‐competed the pavB‐mutant and infections of epithelial cells demonstrated that PavB contributes to adherence to host cell. Blocking experiments suggested a function of PavB as adhesin, which was confirmed by direct binding of SSURE peptides to host cells. Finally, PavB may represent a new vaccine candidate as SSURE peptides reacted with human sera. Taken together, PavB is a surface‐exposed adhesin, which contributes to pneumococcal colonization and infections of the respiratory airways.
Pneumococcal microbial surface components recognizing adhesive matrix molecules targeting of the extracellular matrix
Authors: Paterson Gavin K. , Orihuela Carlos J. 
Published: April 2010

SummaryThe attachment of bacteria to host cells and tissues, and their subsequent invasion and dissemination are key processes during pathogenesis. In this issue of Molecular Microbiology, Jensch and co‐workers provide further molecular insight into these events during infection with the Gram positive bacterium Streptococcus pneumoniae. Their characterization of pneumococcal adherence and virulence factor B (PavB), a bacterial surface protein with orthologues in other streptococci, show that it binds to the extracellar matrix components fibronection and plasminogen by virtue of repetitive sequences‐designated streptococcal surface repeats. In mice, a pavB mutant showed reduced nasopharyngeal colonization and was attenuated in a lung infection model. As discussed here in the context of the pneumococcus, the study of PavB highlights the central role during microbal pathogenesis of targetting the extracellular matrix by so‐called microbial surface components recognizing adhesive matrix molecules (MSCRAMMs).
Hyperosmosis enhances radiation and hydroxyurea resistance of Schizosaccharomyces pombe checkpoint mutants through the spindle checkpoint and delayed cytokinesis
Authors: Alao John P. , Huis in 't Veld Pim J. , Buhse Frederike , Sunnerhagen Per 
Published: April 2010

SummaryThe DNA damage and stress response pathways interact to regulate cellular responses to genotoxins and environmental stresses. How these pathways interact in Schizosaccharomyces pombe is not well understood. We demonstrate that osmotic stress suppresses the DNA damage sensitivity of checkpoint mutants, and that this occurs through three distinct cell cycle delays. A delay in G2/M is dependent on Srk1. Progression through mitosis is halted by the Mad2‐dependent spindle checkpoint. Finally, cytokinesis is impaired by modulating Cdc25 expression. These three delays, imposed by osmotic stress, together compensate for the loss of checkpoint signalling.
Changes in diurnal patterns within the Populus transcriptome and metabolome in response to photoperiod variation
Authors: HOFFMAN DANIEL E. , JONSSON PÄR , BYLESJÖ MAX , TRYGG JOHAN , ANTTI HENRIK , ERIKSSON MARIA E. , MORITZ THOMAS 
Published: April 2010

ABSTRACTChanges in seasonal photoperiod provides an important environmental signal that affects the timing of winter dormancy in perennial, deciduous, temperate tree species, such as hybrid aspen (Populus tremula × Populus tremuloides). In this species, growth cessation, cold acclimation and dormancy are induced in the autumn by the detection of day‐length shortening that occurs at a given critical day length. Important components in the detection of such day‐length changes are photoreceptors and the circadian clock, and many plant responses at both the gene regulation and metabolite levels are expected to be diurnal. To directly examine this expectation and study components in these events, here we report transcriptomic and metabolomic responses to a change in photoperiod from long to short days in hybrid aspen. We found about 16% of genes represented on the arrays to be diurnally regulated, as assessed by our pre‐defined criteria. Furthermore, several of these genes were involved in circadian‐associated processes, including photosynthesis and primary and secondary metabolism. Metabolites affected by the change in photoperiod were mostly involved in carbon metabolism. Taken together, we have thus established a molecular catalog of events that precede a response to winter.
Nucleotide binding and dimerization at the chloroplast pre‐protein import receptor, atToc33, are not essential in vivo but do increase import efficiency
Authors: Aronsson Henrik , Combe Jonathan , Patel Ramesh , Agne Birgit , Martin Meryll , Kessler Felix , Jarvis Paul 
Published: April 2010

SummaryThe atToc33 protein is one of several pre‐protein import receptors in the outer envelope of Arabidopsis chloroplasts. It is a GTPase with motifs characteristic of such proteins, and its loss in the plastid protein import 1 (ppi1) mutant interferes with the import of photosynthesis‐related pre‐proteins, causing a chlorotic phenotype in mutant plants. To assess the significance of GTPase cycling by atToc33, we generated several atToc33 point mutants with predicted effects on GTP binding (K49R, S50N and S50N/S51N), GTP hydrolysis (G45R, G45V, Q68A and N101A), both binding and hydrolysis (G45R/K49N/S50R), and dimerization or the functional interaction between dimeric partners (R125A, R130A and R130K). First, a selection of these mutants was assessed in vitro, or in yeast, to confirm that the mutations have the desired effects: in relation to nucleotide binding and dimerization, the mutants behaved as expected. Then, activities of selected mutants were tested in vivo, by assessing for complementation of ppi1 in transgenic plants. Remarkably, all tested mutants mediated high levels of complementation: complemented plants were similar to the wild type in growth rate, chlorophyll accumulation, photosynthetic performance, and chloroplast ultrastructure. Protein import into mutant chloroplasts was also complemented to >50% of the wild‐type level. Overall, the data indicate that neither nucleotide binding nor dimerization at atToc33 is essential for chloroplast import (in plants that continue to express the other TOC receptors in native form), although both processes do increase import efficiency. Absence of atToc33 GTPase activity might somehow be compensated for by that of the Toc159 receptors. However, overexpression of atToc33 (or its close relative, atToc34) in Toc159‐deficient plants did not mediate complementation, indicating that the receptors do not share functional redundancy in the conventional sense.
Staphylococcus aureus invades the epithelium in nasal polyposis and induces IL‐6 in nasal epithelial cells in vitro
Authors: Sachse F. , Becker K. , Von Eiff C. , Metze D. , Rudack C. 
Published: April 2010

To cite this article: Sachse F, Becker K, von Eiff C, Metze D, Rudack C. Staphylococcus aureus invades the epithelium in nasal polyposis and induces IL‐6 in nasal epithelial cells in vitro. Allergy 2010; 65: 1430–1437.AbstractBackground:  Staphylococcus aureus has been associated with chronic rhinosinusitis with nasal polyps (CRSwNP) pathogenesis but its role is still controversially discussed. Here, we demonstrate S. aureus detection in the mucosa of CRSwNP. In addition, intracellular residency of S. aureus in nasal polyp epithelial cells (NPECs) and its capability to induce TH‐2 cytokines were analyzed in vitro.Methods:  Staphylococcus aureus detection in CRSwNP (n = 25), CRS without polyps (CRSsNP, n = 5), and turbinate mucosa (TM, n = 10) was performed by peptide nucleic acid‐fluorescence in situ hybridization (PNA‐FISH) and microbial cultivation from tissue biopsies. Intracellular residency was examined by intracellular persistence assay and electron microscopy. IL‐6 and IL‐13 responses to S. aureus infection and supernatants were quantified by ELISA.Results:  Peptide nucleic acid‐fluorescence in situ hybridization positive bacterial cells were significantly increased in the epithelium of CRSwNP (17/25) compared to CRSsNP (0/5) and TM (1/10). Good concordance of PNA‐FISH results and S. aureus cultivation was found applying Cohen’s κ for CRSwNP (κ = 0.841) and TM (κ = 1.0). Intracellular persistence assay with S. aureus strain Newman and its corresponding small‐colony variant mutant strain III33 demonstrated intracellular survival and replication of S. aureus within NPECs. Both S. aureus strains significantly induced IL‐6 but not IL‐13 in infected NPECs and in NPECs challenged with corresponding staphylococcal supernatants.Conclusion:  Invasion of the epithelium by S. aureus was a phenomenon seen predominantly in CRSwNP. Regardless of an intra‐ or extracellular localization in the epithelium, S. aureus is capable to induce IL‐6 synthesis in vitro and thus may contribute to the TH‐2 cytokine pattern in CRSwNP.
Prebiotic oligosaccharides: In vitro evidence for gastrointestinal epithelial transfer and immunomodulatory properties
Authors: Eiwegger Thomas , Stahl Bernd , Haidl Paul , Schmitt Joachim , Boehm Günther , Dehlink Eleonora , Urbanek Radvan , Szépfalusi Zsolt 
Published: April 2010

Eiwegger T, Stahl B, Haidl P, Schmitt J, Boehm G, Dehlink E, Urbanek R, Szépfalusi Z. Prebiotic oligosaccharides: In vitro evidence for gastrointestinal epithelial transfer and immunomodulatory properties. Pediatr Allergy Immunol 2010: 21: 1179–1188. © 2010 John Wiley & Sons A/SPrebiotic oligosaccharides are present in breast milk and evidence is pointing toward immunomodulatory properties of the acidic fraction. Recently, prebiotic supplements of infant formula [short‐chain galacto (scGOS)‐, long‐chain fructo (lcFOS)‐oligosaccharides] showed preventive effects on atopic disease development.We aimed to define the direct immunologic effects of these oligosaccharides and of human (aHMOS) and cows’ milk (aCMOS) acidic oligosaccharides and to investigate the systemic uptake of prebiotic supplements of infant formula and a specific pectin‐derived acidic oligosaccharide hydrolysate (pAOS) in vitro.After assurance of LPS‐free conditions (limulus assay, toll like receptor‐2, ‐4 transfected human embryonic kidney‐cells), in vitro‐transfer through a CaCo‐2 cell monolayer was measured using high‐pH anion exchange chromatography with pulsed amperometric detection. Direct effects on proliferation, cytokine‐induction of cord blood mononuclear cells and modulation of allergen‐specific CD4+ T‐cell cytokine profiles from allergic and non‐allergic individuals were investigated.Transfer of scGOS/lcFOS and pAOS in‐vitro was detected with a rate of transfer of 4–14%, depending on the molecular size and structure. AHMOS induced IFN‐γ and IL‐10 but not the Th‐2 cytokine IL‐13 at physiologic concentrations (10–100 μg/ml) in cord blood, whereas aCMOS did not induce any of these cytokines. AHMOS significantly suppressed Th‐2 type cytokine‐production by Ara h1‐specific CD4+ T cells (CFSElow CD3+CD4+cells) from peanut allergic patients.In conclusion, human milk‐derived acidic oligosaccharides may modulate postnatal allergen‐specific immune responses by the suppression of Th‐2‐type responses in atopy‐prone individuals. Moreover, there is in vitro evidence for epithelial transport of prebiotic oligosaccharides.
Psoriasis among Sarawakian natives in a tertiary skin centre in Sarawak
Authors: Yap Felix Boon‐Bin 
Published: April 2010

ABSTRACTA prospective cross‐sectional study was done between December 2007 and June 2009 in the skin clinic, Sarawak General Hospital, to determine the clinical characteristics of 138 Sarawakian natives with a clinical diagnosis of psoriasis. Women made up 50.7% and the mean age of the patients was 45.2 years. Of the group, 94.2% had chronic stable plaque psoriasis, 86.9% had a body surface area involvement of less than 10%, 60.9% had nail disease, 22.5% had joint disease and 55.1% had minimal effects to their quality of life because of their psoriasis.
Increased expression of ubiquitin‐specific protease 22 can promote cancer progression and predict therapy failure in human colorectal cancer
Authors: Liu Yan Long , Yang Yan Mei , Xu Hui , Dong Xin Shu 
Published: April 2010

AbstractBackground and Aims:  Increasing experimental evidence suggests that ubiquitin‐specific protease 22 (USP22) could exhibit a critical function in pathological processes, including oncogenesis and cell cycle progression. The aim of this study was to investigate the role of USP22 and the association with its potential targets in colorectal cancer (CRC).Methods:  We evaluated the implication of USP22 and the candidate targets, such as B‐cell‐specific murine leukemia virus integration site‐1 (BMI‐1), cellular homolog of avian myelocytomatosis virus oncogene (c‐Myc), cyclin D2, inhibiter of cyclin‐dependent kinase (CDK) 4 (p16INK4a), and an alternate reading frame product of the CDKN2A locus (p14ARF), in matched samples comprising carcinoma and adjacent non‐cancerous mucosa from 82 patients with CRC using quantitative reverse transcription–polymerase chain reaction and immunostaining analyses.Results:  The USP22 mRNA expression in the CRC tissues was significantly higher than those in the non‐cancerous mucosa tissues (P < 0.0001). Increased mRNA expression of USP22 was associated with advanced American Joint Committee on Cancer stage (P = 0.033) and high likelihood of therapy failure after radical resection (P < 0.0001). The Cox regression analysis revealed that the USP22 mRNA expression level was a significant factor for predicting prognosis (P < 0.0001). The statistical correlation analysis in mRNA levels showed that USP22 was strongly correlated with BMI‐1 (r = 0.790, P < 0.0001), c‐Myc (r = 0.528, P < 0.0001), and cyclin D2 (r = 0.657, P < 0.0001), but not p16INK4a (r = 0.103, P = 0.358) or p14ARF (r = −0.039, P = 0.731).Conclusion:  Our results indicate that activation of USP22 correlates with CRC progression and therapy failure. Additionally, the oncogenic role of USP22 in the progression of CRC can be mechanistically linked with BMI‐1, c‐Myc, and cyclin D2, but not with p16INK4a and p14ARF.