bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gastric mucin phenotype defines tumour progression and prognosis of intrahepatic cholangiocarcinoma: gastric foveolar type is associated with aggressive tumour behaviour
Authors: Aishima S , Kuroda Y , Nishihara Y , Taguchi K , Taketomi A , Maehara Y , Tsuneyoshi M 
Published: June 2006

Aims : To identify the role of mucus core protein (MUC) in intrahepatic cholangiocarcinoma (ICC).Methods and results : We examined the expression profile of MUC2, MUC5AC and MUC6 by immunohistochemical staining in 100 ICCs and compared the clinicopathological factors and the immunohistochemical results. The expression frequency was: MUC2, 9%; MUC5AC, 40%; and MUC6, 21%. According to the gastric mucin expression profile, ICCs were classified into the following groups: null type (n = 43), gastric foveolar type (n = 36), pyloric gland type (n = 11) and gastric combined type (n = 10). Half of the gastric foveolar type and the gastric combined type were located in the hilar region, but the other types were predominant at the periphery (P = 0.0004). Well‐differentiated components were more often detected in the gastric combined type and the pyloric gland type (P = 0.0281). The gastric foveolar type was associated with a higher incidence of lymph node metastasis (P < 0.0001). The pyloric gland type was associated with better survival and the gastric foveolar type was associated with worse survival. The gastric mucin phenotype was an independent prognostic factor by multivariate survival analysis.Conclusion : The gastric foveolar type of ICC was more often associated with aggressive tumour development, whereas the pyloric gland type exhibited less aggressive behaviour.
The relation of pepsinogen group II (PGII) expression to intestinal metaplasia and gastric cancer
Authors: Stemmermann G N , Nomura A M Y 
Published: June 2006

Aims : A substantial minority of intestinal metaplasia (IM)‐associated stomach cancers express a gastric product—pepsinogen group II (PGII). The aim of this study was to examine PGII expression as it relates to IM and to tumour heterogeneity.Methods and results : The extent of IM was divided into four levels: none, minimal, moderate, extensive. Stomach specimens (N = 165) were stained for PGII and two tumour markers, epidermal growth factor receptor (EGFr) and p53. PGII was more likely to be expressed with moderate or extensive IM than with minimal or no IM (P = 0.05). Cancers that expressed PGII were more likely to be of high stage than those that did not (P = 0.035). Of 25 cases that expressed all three markers (PGII, EGFr, p53), 20 (80%) had stage 3 or 4 disease, compared with 11 (37%) advanced cancers expressing none of the markers (P = 0.001). Cancers expressing one or two markers were between these extremes.Conclusions : PGII+ cancers in IM‐associated gastric cancers may derive from residual gastric glands, or may arise from postinduction reversion to a gastric phenotype from intestinalized cells. This is supported by the more frequent association of PGII expression with the most extensive degrees of IM and its association with high‐stage cancers that display heterogeneity in tumour marker expression.
Specific morphological features predictive for the basal phenotype in grade 3 invasive ductal carcinoma of breast
Authors: Fulford L G , Easton D F , Reis‐Filho J S , Sofronis A , Gillett C E , Lakhani S R , Hanby A 
Published: June 2006

Aims : Cytokeratin (CK) 14, a myoepithelial marker, is also expressed in a proportion of breast carcinomas. There is evidence that these tumours show a differing metastatic pattern and clinical outcome from other invasive ductal carcinomas (IDCs) and may need different management. Currently, they are not identified in routine practice and no morphological guidelines exist to aid their identification. The aim of this study was to analyse the histological features of CK14+ IDC.Methods and results : A detailed histological review of 453 grade 3 IDCs revealed 88 (19.4%) that expressed CK14. Assessment was made independently by two pathologists using a standardized ‘tick‐box’ proforma covering grade, architectural and cytological features. The results were analysed using logistic regression to identify features that predicted for basal phenotype. Concordance between the two pathologists was fair to good for most parameters (κ 0.4–0.6). On multiple logistic regression, the basal phenotype was highly significantly associated with the presence of a central scar (P = 0.005), tumour necrosis (P < 0.0001), presence of spindle cells (P = 0.006) or squamous metaplasia (P < 0.0001), high total mitotic count (> 40 per 10 high‐power field) (P = 0.0002) and high nuclear–cytoplasmic ratio (P = 0.0002).Conclusions : Specific morphological features are strongly associated with basal‐like breast carcinoma. These could be used in routine diagnostic practice to identify this important subset of tumours.
Extracellular superoxide dismutase has a highly specific localization in idiopathic pulmonary fibrosis/usual interstitial pneumonia
Authors: Kinnula V L , Hodgson U A , Lakari E K , Tan R J , Sormunen R T , Soini Y M , Kakko S J , Laitinen T H , Oury T D , Pääkkö P K 
Published: June 2006

Aims : Recent studies suggest the importance of oxidant stress in the progression of pulmonary fibrosis. The aim of this study was to investigate extracellular superoxide dismutase (ECSOD), the major antioxidant enzyme of the extracellular matrix of human lung, in biopsy‐proven idiopathic pulmonary fibrosis (IPF) related to usual interstitial pneumonia (UIP).Methods and results : Fibrotic areas and fibroblastic foci in UIP lungs were notable for absence of ECSOD by immunohistochemistry. Western blotting showed significantly lowered immunoreactivity of ECSOD in fibrotic compared with non‐fibrotic areas of the diseased lung. The only cell type that showed intense ECSOD positivity in UIP was the interstitial mast cell. In order to investigate the mechanism for ECSOD depletion in fibrotic areas, alveolar epithelial cells were exposed to tumour necrosis factor‐α and transforming growth factor (TGF)‐β1; TGF‐β suggested a trend towards decreased synthesis. Patients with UIP were also assessed to determine whether this disease is associated with a naturally occurring mutation in ECSOD (Arg213Gly) which leads to a loss of tissue binding of ECSOD. No significant differences could be found in the allele or genotype frequencies of this polymorphism between 63 UIP patients and 61 control subjects.Conclusion : Overall, consistent with several other antioxidant enzymes, ECSOD is very low in fibrotic areas of UIP, which may further increase the oxidant burden in this disease.
Insular shifts in body size of rice frogs in the Zhoushan Archipelago, China
Authors: WU ZHENGJUN , LI YIMING , MURRAY BRAD R. 
Published: June 2006

Summary

Differences in body size between mainland and island populations have been reported for reptiles, birds and mammals. Despite widespread recognition of insular shifts in body size in these taxa, there have been no reports of such body size shifts in amphibians.
We provide the first evidence of an insular shift in body size for an amphibian species, the rice frog Rana limnocharis. We found significant increases in body size of rice frogs on most sampled islands in the Zhoushan archipelago when compared with neighbouring mainland China.
Large body size in rice frogs on islands was significantly related to increased population density, in both breeding and non‐breeding seasons. Increases in rice frog density were significantly related to higher resource availability on islands. Increased resource availability on islands has led to higher carrying capacities, which has subsequently facilitated higher densities and individual growth rates, resulting in larger body size in rice frogs. We also suggest that large body size has evolved on islands, as larger individuals are competitively superior under conditions of harsh intraspecific competition at high densities.
Increases in body size in rice frogs were not related to several factors that have been implicated previously in insular shifts in body size in other taxa. We found no significant relationships between body size of rice frogs and prey size, number of larger or smaller frog species, island area or distance of islands from the mainland.
Our findings contribute to the formation of a broad, repeatable ecological generality for insular shifts in body size across a range of terrestrial vertebrate taxa, and provide support for recent theoretical work concerning the importance of resource availability for insular shifts in body size.
Maternal antibodies in a wild altricial bird: effects on offspring immunity, growth and survival
Authors: PIHLAJA MARJO , SIITARI HELI , ALATALO RAUNO V. 
Published: June 2006

SummaryIn many animals immunity is not fully developed until adulthood but the young still need protection against various sets of pathogens. Thus, bird nestlings are highly dependent on antibodies received from their mother (in the eggs) during their rapid early growth period. The relationship between maternal immunity and the development of neonates’ own immunity has been poorly studied.It has been suggested that immune function plays an important part in mediating resource competition between different life‐history traits, e.g. growth and reproduction. Maternal investment of antibodies has potentially permanent effects on offspring phenotype. Thus, the trade‐offs between the immune function and other important life‐history traits in the offspring will also affect the fitness of the mother.Our supplemental feeding experiment in the magpiePica picaindicates that the immunoglobulin levels of offspring at hatching are dependent on a mother's nutritional condition. In addition, the amount of maternal immunoglobulins transferred to offspring increases along the laying order within a nest.We also found that at the age of 8–10 days the immunoglobulin production of the offspring has already begun. Furthermore, the maternal immunoglobulin levels of the offspring at hatching were positively related to their immunoglobulin levels on day 10.Maternal immunoglobulins did not significantly affect offspring growth, but there was a negative relationship between self‐produced immunoglobulins and growth over the first 10 days, indicating a trade‐off between these traits. Nestlings’ weight, however, had a positive relationship with immunoglobulin production suggesting that the observed trade‐off between growth and immunoglobulin production is due to catch‐up growth of nestlings with a low hatching weight. We found that within nests nestlings with higher maternal antibody levels had higher survival rate until day 20, but between nests there was an opposite relationship.Evidently, there is a trade‐off, in magpies, between maternal resources, immune function and growth, shaping the evolution of maternal investment in offspring immunity.
The impact of role discrepancy on nurses’ intention to quit their jobs
Authors: Takase Miyuki , Maude Phillip , Manias Elizabeth 
Published: June 2006

Aims and objective.  The purpose of this study was to investigate the impact of role discrepancy on nurses’ intention to quit their jobs.Background.  Nurses experience role discrepancy, which refers to incompatibility between the roles nurses desire and expect to take, and the roles they actually engage in at work. However, there is a paucity of information as to how this role discrepancy affects nurses’ intention to quit their jobs.Design.  A correlational design was used to investigate the impact of role discrepancy on nurses’ intention to quit their jobs.Methods.  A total of 346 Australian nurses participated in this study by completing questionnaires. The results were analysed by t‐test, polynomial regression and response surface analysis.Results.  Nurses tended to experience role discrepancy, in particular, in decision making with hospital policies and provision of patient education. The overall results show that this role discrepancy contributes to nurses’ intention to quit their jobs. Nurses’ intention to quit their jobs also increased when they had a low desire to engage in nursing roles and when they only performed a few roles. When specific dimensions of nursing roles were examined, a role discrepancy in the use of nursing skills, such as participation in decision making and providing patient education and emotional support, had little impact on their turnover intention. On the contrary, a role discrepancy in task delegation practice showed a significant association with nurses’ intention to leave their jobs.Conclusions.  Role discrepancy has been experienced by many nurses, and this discrepancy partially contributes to nurses’ intention to quit their jobs.Relevance to clinical practice.  To reduce nursing turnover, it is important to create a work environment where nurses are inspired to engage in various nursing roles and their work desires are reinforced by existing work opportunities.
Pdr1 regulates multidrug resistance in Candida glabrata: gene disruption and genome‐wide expression studies
Authors: Vermitsky John‐Paul , Earhart Kelly D. , Smith W. Lamar , Homayouni Ramin , Edlind Thomas D. , Rogers P. David 
Published: June 2006

Summary Candida glabrata emerged in the last decade as a common cause of mucosal and invasive fungal infection, in large part due to its intrinsic or acquired resistance to azole antifungals such as fluconazole. In C. glabrata clinical isolates, the predominant mechanism behind azole resistance is upregulated expression of multidrug transporter genes CDR1 and PDH1. We previously reported that azole‐resistant mutants (MIC ≥ 64 μg ml−1) of strain 66032 (MIC = 16 μg ml−1) similarly show coordinate CDR1‐PDH1 upregulation, and in one of these (F15) a putative gain‐of‐function mutation was identified in the single homologue of Saccharomyces cerevisiae transcription factors Pdr1–Pdr3. Here we show that disruption of C. glabrata PDR1 conferred equivalent fluconazole hypersensitivity (MIC = 2 μg ml−1) to both F15 and 66032 and eliminated both constitutive and fluconazole‐induced CDR1‐PDH1 expression. Reintroduction of wild‐type or F15 PDR1 fully reversed these effects; together these results demonstrate a role for this gene in both acquired and intrinsic azole resistance. CDR1 disruption had a partial effect, reducing fluconazole trailing in both strains while restoring wild‐type susceptibility (MIC = 16 μg ml−1) to F15. In an azole‐resistant clinical isolate, PDR1 disruption reduced azole MICs eight‐ to 64‐fold with no effect on sensitivity to other antifungals. To extend this analysis, C. glabrata microarrays were generated and used to analyse genome‐wide expression in F15 relative to its parent. Homologues of 10 S. cerevisiae genes previously shown to be Pdr1–Pdr3 targets were upregulated (YOR1, RTA1, RSB1, RPN4, YLR346c and YMR102c along with CDR1, PDH1 and PDR1 itself) or downregulated (PDR12); roles for these genes include small molecule transport and transcriptional regulation. However, expression of 99 additional genes was specifically altered in C. glabrata F15; their roles include transport (e.g. QDR2, YBT1), lipid metabolism (ATF2, ARE1), cell stress (HSP12, CTA1), DNA repair (YIM1, MEC3) and cell wall function (MKC7, MNT3). These azole resistance‐associated changes could affect C. glabrata tissue‐specific virulence; in support of this, we detected differences in F15 oxidant, alcohol and weak acid sensitivities. C. glabrata provides a promising model for studying the genetic basis of multidrug resistance and its impact on virulence.
Neisseria meningitidis NhhA is a multifunctional trimeric autotransporter adhesin
Authors: Scarselli Maria , Serruto Davide , Montanari Paolo , Capecchi Barbara , Adu‐Bobie Jeannette , Veggi Daniele , Rappuoli Rino , Pizza Mariagrazia , Aricò Beatrice 
Published: June 2006

SummaryNhhA, Neisseriahia/hsf homologue, or GNA0992, is an oligomeric outer membrane protein of Neisseria meningitidis, recently included in the family of trimeric autotransporter adhesins. In this study we present the structural and functional characterization of this protein. By expressing in Escherichia coli the full‐length gene, deletion mutants and chimeric proteins of NhhA, we demonstrated that the last 72 C‐terminal residues are able to allow trimerization and localization of the N‐terminal protein domain to the bacterial surface. In addition, we investigated on the possible role of NhhA in bacterial–host interaction events. We assessed in vitro the ability of recombinant purified NhhA to bind human epithelial cells as well as laminin and heparan sulphate. Furthermore, we shown that E. coli strain expressing NhhA was able to adhere to epithelial cells, and observed a reduced adherence in a meningococcal isogenic MC58ΔNhhA mutant. We concluded that this protein is a multifunctional adhesin, able to promote the bacterial adhesion to host cells and extracellular matrix components. Collectively, our results underline a putative role of NhhA in meningococcal pathogenesis and ascertain its structural and functional belonging to the emerging group of bacterial autotransporter adhesins with trimeric architecture.
PtxR modulates the expression of QS‐controlled virulence factors in the Pseudomonas aeruginosa strain PAO1
Authors: Carty Nancy L. , Layland Nancy , Colmer‐Hamood Jane A. , Calfee M. Worth , Pesci Everett C. , Hamood Abdul N. 
Published: June 2006

SummaryThe production of several virulence factors by Pseudomonas aeruginosa is regulated through the hierarchical cell‐density dependent quorum sensing (QS) systems las and rhl. A third component of the QS hierarchy, the Pseudomonas quinolone signal PQS, also controls the expression of several genes. We previously described P. aeruginosa PtxR as a transcriptional activator of the exotoxin A gene toxA. Here, we provide evidence that PtxR regulates the production of other virulence factors. Mutation of ptxR in PAO1 increased pyocyanin production. This increase was reduced in the presence of a ptxR plasmid. Throughout the growth cycle, PtxR reduced the expression of the pyocyanin operon phzA1‐G1 but not phzA2‐G2. As pyocyanin production is stringently controlled by QS, we examined the effect of PtxR on QS‐related genes in PAO1. PtxR also reduced the expression of the PQS synthesis operon pqsABCDE. ptxR mutation increased the expression of the rhamnolipid synthesis gene rhlA but decreased lasB expression. The expression of the RhlI synthase gene rhlI and the production of the C4‐HSL autoinducer were increased in the ptxR mutant, while the expression of the LasI synthase gene lasI and the production of 3OC12‐HSL were reduced. These results suggest that PtxR negatively regulates the expression of the rhamnolipid and pyocyanin genes through rhlI and the pqsABCDE operon while it positively regulates the expression of lasB through lasI.
Shutdown decay of mRNA
Authors: Condon Ciarán 
Published: June 2006

SummaryAlthough plasmid‐borne and chromosomal toxin–antitoxin (TA) operons have been known for some time, the recent identification of mRNA as the target of at least two different classes of toxins has led to a dramatic renewal of interest in these systems as mediators of stress responses. Members of the MazF/PemK family, the so‐called mRNA interferases, are ribonucleases that inhibit translation by destroying cellular mRNAs under stress conditions, while the founder member of the RelE family promotes cleavage of mRNAs through the ribosome. Detailed structures of these enzymes, often in complex with their inhibitors, have provided vital clues to their mechanisms of action. The primary role and regulation of these systems has been the subject of some controversy. One model suggests they play a beneficial role by wiping the slate clean and preventing wasteful energy consumption by the translational apparatus during adaptation to stress conditions, while another favours the idea that their main function is programmed cell death. The two models might not be mutually exclusive if a side‐effect of prolonged exposure to toxic RNase activity without de novo synthesis of the inhibitor were a state of dormancy for which we do not yet understand the key to recovery. In this review, I discuss the recent developments in the rapidly expanding field of what I refer to as bacterial shutdown decay.
In vivo, fliC expression by Salmonella enterica serovar Typhimurium is heterogeneous, regulated by ClpX, and anatomically restricted
Authors: Cummings Lisa A. , Wilkerson W. David , Bergsbaken Tessa , Cookson Brad T. 
Published: June 2006

SummaryFliC is a natural antigen recognized by the innate and adaptive immune systems during Salmonella infection in mice and humans; however, the regulatory mechanisms governing its expression in vivo are incompletely understood. Here, we use flow cytometry to quantify fliC gene expression in single bacteria. In vitro, fliC transcription was not uniformly positive; a viable fliC‐negative subpopulation was also identified. Intracellular Salmonella repressed transcription of fliC and its positive regulator fliA, but constitutively transcribed the master regulator flhD; fliC repression required ClpXP protease, known to degrade FlhD. In orally infected mice, fliC transcription was anatomically restricted: Salmonella transcribed fliC in the Peyer's Patches (PP) but not in the mesenteric lymph nodes and spleen. The intracellularly transcribed pagC promoter was upregulated by Salmonella in all tissues, defining the infected PP as a unique environment that initiates expression of intracellularly induced genes and yet permits transcription of fliC. Because a single bacterium can escape the GI tract to colonize deeper tissues, heterogeneous gene expression may have important implications for Salmonella pathogenesis: FliC‐positive bacteria in the PP could stimulate inflammation and facilitate the priming of FliC‐specific immune responses, while FliC‐negative bacteria escape host detection in the gut and spread to systemic sites of replication.
Identification of the lipopolysaccharide modifications controlled by the Salmonella PmrA/PmrB system mediating resistance to Fe(III) and Al(III)
Authors: Nishino Kunihiko , Hsu Fong‐Fu , Turk John , Cromie Michael J. , Wösten Marc M. S. M. , Groisman Eduardo A. 
Published: June 2006

SummaryIron is an essential metal but can be toxic in excess. While several homeostatic mechanisms prevent oxygen‐dependent killing promoted by Fe(II), little is known about how cells cope with Fe(III), which kills by oxygen‐independent means. Several Gram‐negative bacterial species harbour a regulatory system – termed PmrA/PmrB – that is activated by and required for resistance to Fe(III). We now report the identification of the PmrA‐regulated determinants mediating resistance to Fe(III) and Al(III) in Salmonella enterica serovar Typhimurium. We establish that these determinants remodel two regions of the lipopolysaccharide, decreasing the negative charge of this major constituent of the outer membrane. Remodelling entails the covalent modification of the two phosphates in the lipid A region with phosphoethanolamine and 4‐aminoarabinose, which has been previously implicated in resistance to polymyxin B, as well as dephosphorylation of the Hep(II) phosphate in the core region by the PmrG protein. A mutant lacking the PmrA‐regulated Fe(III) resistance genes bound more Fe(III) than the wild‐type strain and was defective for survival in soil, suggesting that these PmrA‐regulated lipopolysaccharide modifications aid Salmonella's survival and spread in non‐host environments.