bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Three Novel Superantigen-Encoding Genes inStreptococcus equisubsp.zooepidemicus,szeF,szeN, andszeP
Authors: Paillot Romain , Darby Alistair C. , Robinson Carl , Wright Nicola L. , Steward Karen F. , Anderson Emma , Webb Katy , Holden Matthew T. G. , Efstratiou Androulla , Broughton Karen , Jolley Keith A. , Priestnall Simon L. , Marotti Campi Maria C. , Hughes Margaret A. , Radford Alan , Erles Kerstin , Waller Andrew S. 
Published: August 2010

ABSTRACTThe acquisition of superantigen-encoding genes byStreptococcus pyogeneshas been associated with increased morbidity and mortality in humans, and the gain of four superantigens byStreptococcus equiis linked to the evolution of this host-restricted pathogen from an ancestral strain of the opportunistic pathogenStreptococcus equisubsp.zooepidemicus. A recent study determined that the culture supernatants of severalS. equisubsp.zooepidemicusstrains possessed mitogenic activity but lacked known superantigen-encoding genes. Here, we report the identification and activities of three novel superantigen-encoding genes. The products ofszeF,szeN, andszePshare 59%, 49%, and 34% amino acid sequence identity with SPEH, SPEM, and SPEL, respectively. Recombinant SzeF, SzeN, and SzeP stimulated the proliferation of equine peripheral blood mononuclear cells, and tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ) production,in vitro. Although none of these superantigen genes were encoded within functional prophage elements,szeNandszePwere located next to a prophage remnant, suggesting that they were acquired by horizontal transfer. Eighty-one of 165 diverseS. equisubsp.zooepidemicusstrains screened, including 7 out of 15 isolates from cases of disease in humans, contained at least one of these new superantigen-encoding genes. The presence ofszeNorszeP, but notszeF, was significantly associated with mitogenic activity in theS. equisubsp.zooepidemicuspopulation (P< 0.000001,P< 0.000001, andP= 0.104, respectively). We conclude that horizontal transfer of these novel superantigens from and within the diverseS. equisubsp.zooepidemicuspopulation is likely to have implications for veterinary and human disease.
Escherichia coli
Subtilase Cytotoxin Induces Apoptosis Regulated by Host Bcl-2 Family Proteins Bax/Bak
Authors: May Kerrie L. , Paton James C. , Paton Adrienne W. 
Published: August 2010

ABSTRACT

Subtilase cytotoxin (SubAB) was first isolated from a Shiga toxigenic
Escherichia coli
(STEC) strain that was responsible for an outbreak of hemolytic-uremic syndrome and is the prototype of a new family of AB
5
cytotoxins. SubAB is a subtilase-like serine protease, and upon uptake by host cells, it is trafficked to the endoplasmic reticulum (ER), where it cleaves the essential ER chaperone BiP (GRP78) with high specificity. Previous work has shown that BiP cleavage by SubAB initiates ER stress-signaling pathways in host cells that eventuate in cell death associated with DNA fragmentation, a hallmark of apoptosis. The present study has investigated the role of the Bcl-2 protein family, which has been shown to regulate ER stress-induced apoptosis in other model systems. Examination of the cytotoxicity of SubAB for wild-type and
bax
−/−
/
bak
−/−
mouse embryonic fibroblasts and comparison of apoptotic markers in these cells revealed that SubAB cytotoxicity can be predominantly attributed to the activation of apoptotic pathways activated by Bax/Bak. The results of the present study further our understanding of the molecular mechanism whereby SubAB kills eukaryotic cells and contributes to STEC pathogenesis, in addition to consolidating the roles of Bcl-2 family members in the regulation of ER stress-induced apoptosis.
Parental attitudes towards and perceptions of their children's participation in clinical research: a developing-country perspective
Authors: Nabulsi Mona , Khalil Yvette , Makhoul Jihad 
Published: August 2010

BackgroundPaediatric clinical research faces unique challenges that compromise optimal recruitment of children into clinical trials. A main barrier to enrolment of children is parental misconceptions about the research process. In developing countries, there is a knowledge gap regarding parental perceptions of and attitudes towards their children's participation in clinical trials.ObjectiveTo explore such perceptions and attitudes in Lebanese parents.Study design33 in-depth interviews were conducted with parents with and without previous research experience. Interviews were tape-recorded, transcribed in colloquial Arabic, and later subjected to thematic analysis.ResultsBenefit/risk ratio assessment was a major determinant of parental consent. Fear of adverse events or painful procedures in research was a recurring theme in most interviews. Whereas perception of direct benefit to the child, trust in the physician or institution, financial gains or having a positive previous experience in research facilitated consent, a complex informed consent form and misunderstanding of the term ‘randomisation’ hindered parental approval of participation.ConclusionLebanese parents have perceptions of and attitudes towards children's participation in clinical trials that are similar to those reported from the industrialised world. Improving communication with parents and building trust between researchers and parents is important for successful recruitment. Investigators planning to conduct paediatric trials in developing countries need to simplify consent forms and devise new ways to explain randomisation.
An architectural approach to the growth forms of Nothofagus pumilio (Nothofagaceae) along an altitudinal gradient
Authors: Stecconi Marina , Puntieri Javier G. , Barthélémy Daniel 
Published: August 2010

Variations in the architecture and axis structure of different growth forms of Nothofagus pumilio (Poepp. et Endl.) Krasser (Nothofagaceae) were studied along an altitudinal gradient. We evaluated the primary growth and branching pattern of annual shoots belonging to the main axis categories (trunk, main branches, and secondary (short) branches) of four growth forms developed at different altitudes (1200–1600 m a.s.l.) in northern Patagonia: (i) low shrubs at the high-altitude timberline, (ii) high shrubs at high altitude, (iii) low trees at mid-altitude slopes, and (iv) high trees at low-altitude single-species forests. Shoot structure and branch distribution along shoots were similar for all axis categories and growth forms. Significant differences between axis categories were found regarding the sizes of shoots, which decreased from trunk to secondary/short branches. For each axis category, shoots of similar size differed between growth forms in stem slenderness and internode length. The extent of differentiation between axis categories is key in the structural distinction between growth forms of N. pumilio.
Genetic diversity of mocó cotton (Gossypium hirsutumracemarie-galante) from the northeast of Brazil: implications for conservation
Authors: Pinto de Menezes Ivandilson Pessoa , Barroso Paulo Augusto Vianna , Hoffmann Lúcia Vieira , Lucena Valeska Silva , Giband Marc 
Published: August 2010

Mocó cotton ( Gossypium hirsutum L. race marie-galante (Watt) Hutch.) is a potential source of valuable alleles for breeding programs, mainly because of its great adaptability to semi-arid conditions. With the aim of quantifying mocó cotton genetic variability, 187 plants collected in the northeast of Brazil were evaluated using 12 microsatellite markers. A total of 62 alleles were amplified, ranging from three to eight polymorphic alleles per locus. Total genetic diversity was high (0.52), and when measured on a per state basis, was of 0.37 on average. The population showed a low level of heterozygozity (HO= 0.16), reflecting a high level of endogamy (FIS= 0.67). Phylogenetic analysis using the neighbor-joining method revealed that plants sampled in different states tended to cluster according to their geographic origin, except for those collected in the states of Paraíba and Rio Grande do Norte, which grouped together. Plants from the state of Piauí formed two groups, one with an apparent allelic contribution from G. barbadense, while the second group of plants was closer to those from the states of Paraíba and Rio Grande do Norte. Despite the high genetic diversity that was observed in the remaining populations, urgent conservation efforts should be undertaken, owing to the high level of endogamy and accelerated extinction process that characterizes these populations. Such efforts should focus on the collection and ex situ maintenance of representative genetic diversity.
Leaflet initiation is temporally and spatially separated in simple and complex tomato (Solanum lycopersicum) leaf mutants: a developmental analysis
Authors: Kang Julie , Sinha Neelima R. 
Published: August 2010

Formation of a compound leaf requires the involvement of multiple factors, including KNOX1 gene expression. To further characterize simple and complex tomato leaf mutants, we analyzed their morphology and development by assessing: leaf phenotypes, primary leaf morphogenesis, expression of the class I KNOX gene LeT6, and meristematic activity of the marginal blastozone. Mutants with alterations in lobing and (or) pinnation (decrease/increase) were analyzed. Primary leaflet initiation is delayed in mutants with decreased lobing. In contrast, leaflet initiation is advanced or similar to the wild type in mutants with deep lobes. Leaves with increased pinnation along the rachis require a protracted developmental program to form their final leaf morphology. Using a morphometric analysis, we show that leaf complexity can be quantified. The expression pattern of LeT6 correlates with histological analysis of meristematic activity of the marginal blastozone, suggesting that LeT6 may play a role, through some unknown mechanism, to regulate meristematic competence, not only in the marginal blastozone to regulate leaflet lobing, but along the entire length of the leaf to regulate pinnation in compound leaves.
Nutrient loading by anadromous alewife (Alosa pseudoharengus): contemporary patterns and predictions for restoration efforts
Authors: West Derek C. , Walters Annika W. , Gephard Stephen , Post David M. 
Published: August 2010

Anadromous alewives ( Alosa pseudoharengus ) have the potential to alter the nutrient budgets of coastal lakes as they migrate into freshwater as adults and to sea as juveniles. Alewife runs are generally a source of nutrients to the freshwater lakes in which they spawn, but juveniles may export more nutrients than adults import in newly restored populations. A healthy run of alewives in Connecticut imports substantial quantities of phosphorus; mortality of alewives contributes 0.68 g P·fish–1, while surviving fish add 0.18 g P, 67% of which is excretion. Currently, alewives contribute 23% of the annual phosphorus load to Bride Lake, but this input was much greater historically, with larger runs of bigger fish contributing 2.5 times more phosphorus in the 1960s. A mesocosm experiment in a nearby lake showed that juvenile alewife growth is strongly density dependent, but early survival may be too low for juvenile outmigration to balance adult inputs. In eutrophic systems where nutrients are a concern, managers can limit nutrient loading by capping adult returns at a level where juvenile populations would not be suppressed.
Trends in the abundance of marine fishes
Authors: Hutchings Jeffrey A. , Minto Cóilín , Ricard Daniel , Baum Julia K. , Jensen Olaf P. 
Published: August 2010

The Convention on Biological Diversity (CBD) established a target in 2002 to reduce the rate of biodiversity loss by 2010. Using a newly constructed global database for 207 populations (108 species), we examine whether the 2010 target has been met for marine fishes, while accounting for population biomass relative to maximum sustainable yield, BMSY. Although rate of decline has eased for 59% of populations declining before 1992 (a pattern consistent with a literal interpretation of the target), the percentage of populations below BMSY has remained unchanged and the rate of decline has increased among several top predators, many of which are below 0.5BMSY. Combining population trends, a global multispecies index indicates that marine fishes declined 38% between 1970 and 2007. The index has been below BMSY since the mid-1980s and stable since the early 1990s. With the exception of High Seas pelagic fishes and demersal species in the Northeast Pacific and Australia – New Zealand, the multispecies indices are currently below BMSY in many regions. We conclude that the 2010 CBD target represents a weak standard for recovering marine fish biodiversity and that meaningful progress will require population-specific recovery targets and associated time lines for achieving those targets.
Investigations of lithium-chloro-borate glass-ceramic and its elastic properties
Authors: Shivaprakash Y. , Anavekar R. V. 
Published: August 2010

Elastic properties and microstructural studies of 0.3Li2O-0.2LiCl-0.5B2O3 glass-ceramics have been carried out for a precursor glass prepared using the rapid melt quenching technique. Quenched glasses were heat treated (by three step process) at 150 °C for 2, 4, 6, and 8 h. Scanning electron microscopy and X-ray diffraction studies clearly indicate gradual growth of different phases in the glass matrix with increasing time of heat-treatment. IR studies reveal the structural modification in the network as the precursor glass transformed into glass-ceramic. Elastic properties have been measured by performing ultrasonic wave velocity measurements at a frequency of 10 MHz. Longitudinal and shear moduli of the samples tend to increase with heat-treatment time. However, the bulk modulus is almost insensitive to heat treatment. The Debye temperature was found to increase, and the Poisson ratio lies in the range 0.2–0.3 (typical for covalently bonded networks) with an increase in heat-treatment time.
FZD4 as a Mediator of ERG Oncogene–Induced WNT Signaling and Epithelial-to-Mesenchymal Transition in Human Prostate Cancer Cells
Authors: Gupta Santosh , Iljin Kristiina , Sara Henri , Mpindi John Patrick , Mirtti Tuomas , Vainio Paula , Rantala Juha , Alanen Kalle , Nees Matthias , Kallioniemi Olli 
Published: August 2010

Abstract
TMPRSS2-ERG and other gene fusions involving ETS factors and genes with strong promoter elements are common in prostate cancer. Although ERG activation has been linked to invasive properties of prostate cancers, the precise mechanisms and pathways of ERG-mediated oncogenesis remain poorly understood. Here, we show that ERG knockdown in VCaP prostate cancer cells causes an activation of cell adhesion, resulting in strongly induced active β1-integrin and E-cadherin expression as well as changes in WNT signaling. These observations were corroborated by data from ERG-overexpressing nontransformed prostate epithelial cells as well as gene expression data from clinical prostate cancer samples, which both indicated a link between ERG and epithelial-to-mesenchymal transition (EMT). Upregulation of several WNT pathway members was seen in ERG-positive prostate cancers, with frizzled-4 (FZD4) showing the strongest overexpression as verified by both reverse transcription-PCR and immunostaining. Both ERG knockin and knockdown modulated the levels of FZD4 expression. FZD4 silencing could mimic the ERG knockdown phenotype by inducing active β1-integrin and E-cadherin expression, whereas FZD4 overexpression reversed the phenotypic effects seen with ERG knockdown. Taken together, our results provide mechanistic insights to ERG oncogenesis in prostate cancer, involving activation of WNT signaling through FZD4, leading to cancer-promoting phenotypic effects, including EMT and loss of cell adhesion. Cancer Res; 70(17); 6735–45. ©2010 AACR.
ZIC1 Overexpression Is Oncogenic in Liposarcoma
Authors: Brill Elliott , Gobble Ryan , Angeles Christina , Lagos-Quintana Mariana , Crago Aimee , Laxa Bernadette , DeCarolis Penelope , Zhang Lei , Antonescu Cristina , Socci Nicholas D. , Taylor Barry S. , Sander Chris , Koff Andrew , Singer Samuel 
Published: August 2010

Abstract
Liposarcomas are aggressive mesenchymal cancers with poor outcomes that exhibit remarkable histologic diversity (there are five recognized subtypes). Currently, the mainstay of therapy for liposarcoma is surgical excision because liposarcomas are often resistant to traditional chemotherapy. In light of the high mortality associated with liposarcoma and the lack of effective systemic therapy, we sought novel genomic alterations driving liposarcomagenesis that might serve as therapeutic targets. ZIC1, a critical transcription factor for neuronal development, is overexpressed in all five subtypes of liposarcoma compared with normal fat, and in liposarcoma cell lines compared with adipose-derived stem cells. Here, we show that ZIC1 contributes to the pathogenesis of liposarcoma. ZIC1 knockdown inhibits proliferation, reduces invasion, and induces apoptosis in dedifferentiated and myxoid/round cell liposarcoma cell lines, but not in either adipose-derived stem cells or in a lung cancer cell line with low ZIC1 expression. ZIC1 knockdown is associated with increased nuclear expression of p27 proteins and the downregulation of prosurvival target genes BCL2L13, JunD, Fam57A, and EIF3M. Our results show that ZIC1 expression is essential for liposarcomagenesis and that targeting ZIC1 or its downstream targets might lead to novel therapy for liposarcoma. Cancer Res; 70(17); 6891–901. ©2010 AACR.
Tipping the Balance: Cdk2 Enables Myc to Suppress Senescence
Authors: Hydbring Per , Larsson Lars-Gunnar 
Published: August 2010

Abstract
Intrinsic tumor-suppressor pathways protect healthy cells from transformation by activated oncogenes like MYC or RAS through induction of apoptosis or cellular senescence, respectively. However, when expressed together, MYC and RAS evade these barriers and initiate tumorigenesis. Although Ras suppresses Myc-induced apoptosis, the role of Myc in this cooperation has remained undefined. In a recent report, we showed that Myc represses Ras-induced senescence, thereby overcoming the second major barrier of tumorigenesis. Inhibition of Ras-induced senescence required specific phosphorylation of Myc by cyclin-dependent kinase 2 (Cdk2) and was abrogated by pharmacologic Cdk2 inhibitors, urging a reevaluation of this kinase as a therapeutic target in Myc- or Ras-driven tumors. Cancer Res; 70(17); 6687–91. ©2010 AACR.
New Strategies in Hepatocellular Carcinoma: Genomic Prognostic Markers
Authors: Villanueva Augusto , Hoshida Yujin , Toffanin Sara , Lachenmayer Anja , Alsinet Clara , Savic Radoslav , Cornella Helena , Llovet Josep M. 
Published: August 2010

Abstract
Accurate prognosis prediction in oncology is critical. In patients with hepatocellular carcinoma (HCC), unlike most solid tumors, the coexistence of two life-threatening conditions, cancer and cirrhosis, makes prognostic assessments difficult. Despite the usefulness of clinical staging systems for HCC in routine clinical decision making (e.g., Barcelona-Clinic Liver Cancer algorithm), there is still a need to refine and complement outcome predictions. Recent data suggest the ability of gene signatures from the tumor (e.g., EpCAM signature) and adjacent tissue (e.g., poor-survival signature) to predict outcome in HCC (either recurrence or overall survival), although independent external validation is still required. In addition, novel information is being produced by alternative genomic sources such as microRNA (miRNA; e.g., miR-26a) or epigenomics, areas in which promising preliminary data are thoroughly explored. Prognostic models need to contemplate the impact of liver dysfunction and risk of subsequent de novo tumors in a patient’s life expectancy. The challenge for the future is to precisely depict genomic predictors (e.g., gene signatures, miRNA, or epigenetic biomarkers) at each stage of the disease and their specific influence to determine patient prognosis. Clin Cancer Res; 16(19); 4688–94. ©2010 AACR.
Multigene Expression–Based Predictors for Sensitivity to Vorinostat and Velcade in Non–Small Cell Lung Cancer
Authors: Nagji Alykhan S. , Cho Sang-Hoon , Liu Yuan , Lee Jae K. , Jones David R. 
Published: August 2010

Abstract
The ability to predict the efficacy of molecularly targeted therapies for non–small cell lung cancer (NSCLC) for an individual patient remains problematic. The purpose of this study was to identify, using a refined “coexpression extrapolation (COXEN)” algorithm with a continuous spectrum of drug activity, tumor biomarkers that predict drug sensitivity and therapeutic efficacy in NSCLC to Vorinostat, a histone deacetylase inhibitor, and Velcade, a proteasome inhibitor. Using our refined COXEN algorithm, biomarker prediction models were discovered and trained for Vorinostat and Velcade based on the in vitro drug activity profiles of nine NSCLC cell lines (NCI-9). Independently, a panel of 40 NSCLC cell lines (UVA-40) were treated with Vorinostat or Velcade to obtain 50% growth inhibition values. Genome-wide expression profiles for both the NCI-9 and UVA-40 cell lines were determined using the Affymetrix HG-U133A platform. Modeling generated multigene expression signatures for Vorinostat (45-gene; P = 0.002) and Velcade (15-gene; P = 0.0002), with one overlapping gene (CFLAR). Examination of Vorinostat gene ontogeny revealed a predilection for cellular replication and death, whereas that of Velcade suggested involvement in cellular development and carcinogenesis. Multivariate regression modeling of the refined COXEN scores significantly predicted the activity of combination therapy in NSCLC cells (P = 0.007). Through the refinement of the COXEN algorithm, we provide an in silico method to generate biomarkers that predict tumor sensitivity to molecularly targeted therapies. Use of this refined COXEN method has significant implications for the a priori examination of targeted therapies to more effectively streamline subsequent clinical trial design and cost. Mol Cancer Ther; 9(10); 2834–43. ©2010 AACR.
Induction of Nonapoptotic Cell Death by Activated Ras Requires Inverse Regulation of Rac1 and Arf6
Authors: Bhanot Haymanti , Young Ashley M. , Overmeyer Jean H. , Maltese William A. 
Published: August 2010

Abstract
Methuosis is a unique form of nonapoptotic cell death triggered by alterations in the trafficking of clathrin-independent endosomes, ultimately leading to extreme vacuolization and rupture of the cell. Methuosis can be induced in glioblastoma cells by expression of constitutively active Ras. This study identifies the small GTPases, Rac1 and Arf6, and the Arf6 GTPase-activating protein, GIT1, as key downstream components of the signaling pathway underlying Ras-induced methuosis. The extent to which graded expression of active H-Ras(G12V) triggers cytoplasmic vacuolization correlates with the amount of endogenous Rac1 in the active GTP state. Blocking Rac1 activation with the specific Rac inhibitor, EHT 1864, or coexpression of dominant-negative Rac1(T17N), prevents the accumulation of vacuoles induced by H-Ras(G12V). Coincident with Rac1 activation, H-Ras(G12V) causes a decrease in the amount of active Arf6, a GTPase that functions in the recycling of clathrin-independent endosomes. The effect of H-Ras(G12V) on Arf6 is blocked by EHT 1864, indicating that the decrease in Arf6-GTP is directly linked to the activation of Rac1. Constitutively active Rac1(G12V) interacts with GIT1 in immunoprecipitation assays. Ablation of GIT1 by short hairpin RNA prevents the decrease in active Arf6, inhibits vacuolization, and prevents loss of cell viability in cells expressing Rac1(G12V). Together, the results suggest that perturbations of endosome morphology associated with Ras-induced methuosis are due to downstream activation of Rac1 combined with reciprocal inactivation of Arf6. The latter seems to be mediated through Rac1 stimulation of GIT1. Further insights into this pathway could suggest opportunities for the induction of methuosis in cancers that are resistant to apoptotic cell death. Mol Cancer Res; 8(10); 1358–74. ©2010 AACR.