bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Staphylococcal Cassette Chromosome
mec
Type, Tentatively Designated Type VIII, Harboring Class A
mec
and Type 4
ccr
Gene Complexes in a Canadian Epidemic Strain of Methicillin-Resistant
Staphylococcus aureus
Authors: Zhang Kunyan , McClure Jo-Ann , Elsayed Sameer , Conly John M. 
Published: December 2008

ABSTRACT

Staphylococcal cassette chromosome
mec
(SCC
mec
) is a mobile genetic element characterized by flanking terminal direct and, in most cases, inverted repeat sequences, the
mec
and
ccr
gene complexes, and their surrounding DNA regions. Unique combinations of the
mec
and
ccr
gene complexes generate various SCC
mec
types. Six SCC
mec
types have been reported to date. We describe here a novel SCC
mec
type identified in a Canadian methicillin-resistant
Staphylococcus aureus
(MRSA) epidemic strain. MRSA clinical isolates were screened for known SCC
mec
types by multiplex and conventional PCR methods. Three phenotypically and genotypically identical MRSA clinical isolates with a pulsotype identical to CMRSA9 were identified locally and found to be nontypeable by available SCC
mec
typing schemes. Complete sequencing of the SCC
mec
element revealed a nucleotide fragment of 32,168 bp integrated at an identical chromosomal integration site (
att
B
scc
) at the 3′ end of the
orfX
gene. The nucleotide sequences at the chromosome-SCC
mec
junction regions were typical of other SCC
mec
types, but the element harbored a unique combination of class A
mec
and type 4
ccr
gene complexes. Sequence recombination analysis suggested that this unique SCC
mec
type may be derived from homologous recombination between the previously described SCC
RP62A
of
S. epidermidis
strain RP62A and SCC composite island of
S. epidermidis
ATCC 12228, respectively, or via recombination of other staphylococcal strains that carry the same or similar mobile cassettes. We identified a previously undescribed type of SCC
mec
from isolate C10682, tentatively designated type VIII, and we provide compelling evidence supporting the ability of SCC elements to transfer horizontally or undergo recombination to generate new SCC
mec
types.
TheYersinia pestisAil Protein Mediates Binding and Yop Delivery to Host Cells Required for Plague Virulence
Authors: Felek Suleyman , Krukonis Eric S. 
Published: December 2008

ABSTRACTAlthough adhesion to host cells is a critical step in the delivery of cytotoxic Yop proteins byYersinia pestis, the mechanism has not been defined. To identify adhesins critical for Yop delivery, we initiated two transposon mutagenesis screens using themarinertransposon. To avoid redundant cell binding activities, we initiated the screen with a strain deleted for two known adhesins, pH 6 antigen and the autotransporter, YapC, as well as the Caf1 capsule, which is known to obscure some adhesins. The mutants that emerged contained insertions within theail(attachment and invasion locus) gene ofY. pestis. A reconstructed mutant with a single deletion in theaillocus (y1324) was severely defective for delivery of Yops to HEp-2 human epithelial cells and significantly defective for delivery of Yops to THP-1 human monocytes. Specifically, the Yop delivery defect was apparent when cell rounding and translocation of an ELK-tagged YopE derivative into host cells were monitored. Although theailmutant showed only a modest decrease in cell binding capacity in vitro, the KIM5 Δailmutant exhibited a >3,000-fold-increased 50% lethal dose in mice. Mice infected with the Δailmutant also had 1,000-fold fewer bacteria in their spleens, livers, and lungs 3 days after infection than did those infected with the parental strain, KIM5. Thus, the Ail protein is critical for bothY. pestistype III secretion in vitro and infection in mice.
Active and Passive Immunizations withBordetellaColonization Factor A Protect Mice against Respiratory Challenge withBordetella bronchiseptica
Authors: Sukumar Neelima , Love Cheraton F. , Conover Matt S. , Kock Nancy D. , Dubey Purnima , Deora Rajendar 
Published: December 2008

ABSTRACTBordetella colonizationfactorA(BcfA) is an outer membrane immunogenic protein, which is critical for efficient colonization of the murine respiratory tract. These properties of BcfA prompted us to examine its utility in inducing a protective immune response againstBordetella bronchisepticain a mouse model of intranasal infection. Mice vaccinated with BcfA demonstrated reduced pathology in the lungs and harbored lower bacterial burdens in the respiratory tract. Immunization with BcfA led to the generation of BcfA-specific antibodies in both the sera and lungs, and passive immunization led to the reduction ofB. bronchisepticain the tracheas and lungs. These results suggest that protection after immunization with BcfA is mediated in part by antibodies against BcfA. To further investigate the mechanism of BcfA-induced immune clearance, we examined the role of neutrophils and macrophages. Our results demonstrate that neutrophils are critical for anti-BcfA antibody-mediated clearance and that opsonization with anti-BcfA serum enhances phagocytosis ofB. bronchisepticaby murine macrophages. We show that immunization with BcfA results in the production of gamma interferon and subclasses of immunoglobulin G antibodies that are consistent with the induction of a Th1-type immune response. In combination, our findings suggest that the mechanism of BcfA-mediated immunity involves humoral and cellular responses. Expression of BcfA is conserved among multiple clinical isolates ofB. bronchiseptica. Our results demonstrate the striking protective efficacy of BcfA-mediated immunization, thereby highlighting its utility as a potential vaccine candidate. These results also provide a model for the development of cell-free vaccines againstB. bronchiseptica.
Mushroom crops in relation to weather in the southwestern Yukon
Authors: Krebs C. J. , Carrier Patrick , Boutin S. , Boonstra R. , Hofer Elizabeth 
Published: December 2008

Epigeous mushroom production in the boreal forest ecosystem varies dramatically from year to year. We tested the hypothesis that the aboveground production of epigeous mushrooms in the Kluane region, Yukon, could be predicted by summer rainfall. There is a single crop in this part of the boreal zone with maximum production during the first 2 weeks of August. We measured standing crops from 1993 to 2007 at 13 areas along 210 km of the Alaska Highway and Haines Road in the southwestern Yukon. Aboveground mushroom crops averaged 24 kg/ha wet weight but varied from 0.0 to 117 kg/ha over the 15 years of study, with a coefficient of variation among years of 143%. Epigeous mushroom production could be predicted from June rainfall of the current year and May rainfall of the year previous with R2 = 0.85. Part of the lack of a perfect fit to rainfall was due to the constraint that years of high mushroom crops could not be followed by another high year, no matter what the rainfall pattern. We were not able to identify the species of mushrooms in this study but we confirm from natural history observations that mushrooms are a critical food for several of the small mammal species in the Yukon boreal forest.
Developmental morphology of the flower of Anaphyllopsis americana and its relevance to our understanding of basal Araceae
Authors: Barabé Denis , Lacroix Christian 
Published: December 2008

The inflorescence of Anaphyllopsis americana (Engler) A. Hay consists of more than 100 flowers arranged in recognizable spirals. Each flower has four broad tepals enclosing four stamens that are not visible prior to anthesis. The unilocular ovary contains one ovule and bears a discoid stigma. The floral primordia are first initiated on the upper portion of the inflorescence. At an early stage during their development, the floral primordia have a circular shape. Two lateral tepals are initiated nearly simultaneously followed by two median tepals. After their initiation, each stamen is associated with a tepal of the same radius; the two lateral stamens are initiated first, directly opposite to the lateral tepals. The unilocular nature of the ovary is clearly visible during the early stages of development of the gynoecium. At dehiscence, anther wall raphides are present in anther locules and are mixed with pollen. The mode of floral development observed in Anaphyllopsis is similar to that reported for Anthurium jenmanii Engl. However, this similarity in mode of development may be linked to structural constraints rather than phylogenetic relationships. The presence of a few pentamerous flowers in the inflorescence of Anaphyllopsis suggests a possible relationship with Dracontium . This would be in accordance with recent molecular studies showing that Anaphyllopsis and Dracontium are closely related.
TV news and the echo of Murrow
Authors: Barnett Steven 
Published: December 2008

Television journalism in the UK honours the vision of America’s greatest newsman. But for how long can standards be maintained? Fifty years after Edward R Murrow, the man credited with inventing television journalism in America, made a famous speech to the annual convention of the Radio and Television National Directors Association, media professor Barnett examines the state of TV in the UK and the U.S. and writes: “American television journalism has failed; British television journalism – for the time being – has succeeded. Why? And for how long?”
BH3-only protein Bim more critical than Puma in tyrosine kinase inhibitor–induced apoptosis of human leukemic cells and transduced hematopoietic progenitors carrying oncogenic FLT3
Authors: Nordigården Amanda , Kraft Maria , Eliasson Pernilla , Labi Verena , Lam Eric W.-F. , Villunger Andreas , Jönsson Jan-Ingvar 
Published: December 2008

Abstract
Constitutively activating internal tandem duplications (ITD) of FLT3 (FMS-like tyrosine kinase 3) are the most common mutations in acute myeloid leukemia (AML) and correlate with poor prognosis. Receptor tyrosine kinase inhibitors targeting FLT3 have developed as attractive treatment options. Because relapses occur after initial responses, identification of FLT3-ITD–mediated signaling events are important to facilitate novel therapeutic interventions. Here, we have determined the growth-inhibitory and proapototic mechanisms of 2 small molecule inhibitors of FLT3, AG1295 or PKC412, in hematopoietic progenitor cells, human leukemic cell lines, and primary AML cells expressing FLT3-ITD. Inactivation of the PI3-kinase pathway, but not of Ras–mitogen-activated protein (MAP) kinase signaling, was essential to elicit cytotoxic responses. Both compounds induced up-regulation of proapoptotic BH3-only proteins Bim and Puma, and subsequent cell death. However, only silencing of Bim, or its direct transcriptional activator FOXO3a, abrogated apoptosis efficiently. Similar findings were made in bone marrow cells from gene-targeted mice lacking Bim and/or Puma infected with FLT3-ITD and treated with inhibitor, where loss of Puma only provided transient protection from apoptosis, but loss of Bim preserved clonal survival upon FLT3-ITD inhibition.
A predictive model for respiratory syncytial virus (RSV) hospitalisation of premature infants born at 33–35 weeks of gestational age, based on data from the Spanish FLIP study
Authors: Simões Eric AF , Carbonell-Estrany Xavier , Fullarton John R , Liese Johannes G , Figueras-Aloy Jose , Doering Gunther , Guzman Juana ,   European RSV Risk Factor Study Group
Published: December 2008

Abstract

Background
The aim of this study, conducted in Europe, was to develop a validated risk factor based model to predict RSV-related hospitalisation in premature infants born 33–35 weeks' gestational age (GA).

Methods
The predictive model was developed using risk factors captured in the Spanish FLIP dataset, a case-control study of 183 premature infants born between 33–35 weeks' GA who were hospitalised with RSV, and 371 age-matched controls. The model was validated internally by 100-fold bootstrapping. Discriminant function analysis was used to analyse combinations of risk factors to predict RSV hospitalisation. Successive models were chosen that had the highest probability for discriminating between hospitalised and non-hospitalised infants. Receiver operating characteristic (ROC) curves were plotted.

Results
An initial 15 variable model was produced with a discriminant function of 72% and an area under the ROC curve of 0.795. A step-wise reduction exercise, alongside recalculations of some variables, produced a final model consisting of 7 variables: birth ± 10 weeks of start of season, birth weight, breast feeding for ≤ 2 months, siblings ≥ 2 years, family members with atopy, family members with wheeze, and gender. The discrimination of this model was 71% and the area under the ROC curve was 0.791. At the 0.75 sensitivity intercept, the false positive fraction was 0.33. The 100-fold bootstrapping resulted in a mean discriminant function of 72% (standard deviation: 2.18) and a median area under the ROC curve of 0.785 (range: 0.768–0.790), indicating a good internal validation. The calculated NNT for intervention to treat all at risk patients with a 75% level of protection was 11.7 (95% confidence interval: 9.5–13.6).

Conclusion
A robust model based on seven risk factors was developed, which is able to predict which premature infants born between 33–35 weeks' GA are at highest risk of hospitalisation from RSV. The model could be used to optimise prophylaxis with palivizumab across Europe.
Phosphorylated ERα, HIF-1α, and MAPK Signaling As Predictors of Primary Endocrine Treatment Response and Resistance in Patients With Breast Cancer
Authors: Generali Daniele , Buffa Francesca M. , Berruti Alfredo , Brizzi Maria P. , Campo Leticia , Bonardi Simone , Bersiga Alessandra , Allevi Giovanni , Milani Manuela , Aguggini Sergio , Papotti Mauro , Dogliotti Luigi , Bottini Alberto , Harris Adrian L. , Fox Stephen B. 
Published: December 2008

PurposeWe aimed to identify signaling pathways involved in the response and resistance to aromatase inhibitor therapy in patients with breast cancer.Patients and MethodsOne hundred fourteen women with T2-4 N0-1, estrogen receptor (ER) α–positive tumors were randomly assigned to neoadjuvant letrozole or letrozole plus metronomic cyclophosphamide. Twenty-four tumor proteins involved in apoptosis, cell survival, hypoxia, angiogenesis, growth factor, and hormone signaling were assessed by immunohistochemistry in pretreatment samples (eg, caspase 3, phospho- mammalian target of rapamycin, hypoxia-inducible factor 1α [HIF-1α], vascular endothelial growth factor, mitogen-activated protein kinase [MAPK], phosphorylated epidermal growth factor receptor, phosphorylated ERα [pERα]). A multivariate generalized linear regression approach was applied using a penalized least-square minimization to perform variable selection and regularization. Ten-fold cross-validation and iterative leave-one-out were employed to validate and test the model, respectively. Tumor size, nodal status, age, tumor grade, histological type, and treatment were included in the analysis.ResultsNinety-one patients (81%) attained a disease response, 48 achieved a complete clinical response (43%) whereas 22 did not respond (19%). Increased pERα and decreased p44/42 MAPK were significant factors for complete response to treatment in all leave-one-out iterations. Increased p44/42 MAPK and HIF-1α were significant factors for treatment resistance in all leave-one-out iterations. There was no significant interaction between these variables and treatment.ConclusionActivated ERα form was an independent factor for sensitivity to chemoendocrine treatment, whereas HIF-1α and p44/42 MAPK were independent factors for resistance. Although further confirmatory analyses are needed, these findings have clear potential implications for future strategies in the management of clinical trials with aromatase inhibitors in the breast cancer.
Increased Incidence of Transformation and Myelodysplasia/Acute Leukemia in Patients With Waldenström Macroglobulinemia Treated With Nucleoside Analogs
Authors: Leleu Xavier , Soumerai Jacob , Roccaro Aldo , Hatjiharissi Evdoxia , Hunter Zachary R. , Manning Robert , Ciccarelli Bryan T. , Sacco Antonio , Ioakimidis Leukothea , Adamia Sophia , Moreau Anne-Sophie , Patterson Christopher J. , Ghobrial Irene M. , Treon Steven P. 
Published: December 2008

Purpose Nucleoside analogs (NAs) are considered as appropriate agents in the treatment of Waldenström macroglobulinemia (WM), a lymphoplasmacytic lymphoma. Sporadic reports on increased incidence of transformation to high-grade non-Hodgkin's lymphoma and development of therapy-related myelodysplasia/acute leukemia (t-MDS/AML) among patients with WM treated with NAs prompted us to examine the incidence of such events in a large population of patients with WM. Patients and Methods We examined the incidence of these events in 439 patients with WM, 193 and 136 of whom were previously treated with and without an NA, respectively, and 110 of whom had similar long-term follow-up without treatment. The median follow-up for all patients was 5 years. Results Overall, 12 patients (6.2%) either developed transformation (n = 9; 4.7%) or developed t-MDS/AML (n = 3; 1.6%) among NA-treated patients, compared with one patient (0.4%) who developed transformation in the non-NA treated group (P < .001); no such events occurred among untreated patients. Transformation and t-MDS/AML occurred at a median of 5 years from onset of NA therapy. The median survival of NA-treated patients who developed transformation did not differ from other NA-treated patients as a result of effective salvage treatment used for transformed disease. However, all NA-treated patients who developed t-MDS/AML died at a median of 5 months. Conclusion These data demonstrate an increased incidence of disease transformation to high-grade NHL and the development of t-MDS/AML among patients with WM treated with NAs.
Favorable Long-Term Survival After Reduced-Intensity Allogeneic Transplantation for Multiple-Relapse Aggressive Non-Hodgkin's Lymphoma
Authors: Thomson Kirsty J. , Morris Emma C. , Bloor Adrian , Cook Gordon , Milligan Don , Parker Anne , Clark Fiona , Yung Lynny , Linch David C. , Chakraverty Ronjon , Peggs Karl S. , Mackinnon Stephen 
Published: December 2008

Purpose The role of allogeneic transplantation with reduced-intensity conditioning in diffuse large B-cell lymphoma (DLBCL) is currently unclear, with relatively little published data. We report the outcome of reduced-intensity transplantation (RIT) in a cohort of 48 consecutive patients with relapsed/refractory DLBCL (30 patients with de novo disease and 18 patients with transformed follicular lymphoma) who underwent transplantation with an alemtuzumab-containing regimen, with a median follow-up of 52 months. Patients and Methods Patients had experienced treatment failure with a median of five lines of prior therapy, including autologous transplantation in 69%, and 17% of patients were chemotherapy refractory at transplantation. Median age was 46 years, and 38% of patients had matched/mismatched unrelated donors. Conditioning was with alemtuzumab, fludarabine, and melphalan, and additional graft-versus-host disease (GVHD) prophylaxis was with cyclosporine. Results All patients were successfully engrafted. Only 17% of patients developed grade 2 to 4 acute GVHD, with 13% experiencing extensive chronic GVHD. Four-year estimated nonrelapse mortality was 32%, and relapse risk was 33%. Twelve patients received donor lymphocyte infusions ± chemoimmunotherapy for relapse, and five patients obtained durable remissions, giving current progression-free survival (PFS) and overall survival (OS) rates at 4 years of 48% and 47%, respectively. Patients who had chemotherapy-sensitive disease before RIT had current PFS and OS rates at 4 years of 55% and 54%, respectively. Chemotherapy-refractory patients had a poor outcome. Conclusion The encouraging survival rates with extended follow-up suggest a role for RIT in chemotherapy-sensitive relapsed DLBCL, even in patients who have previously experienced treatment failure with autologous transplantation. Future studies will be required to determine whether any subset of patients with relapsed DLBCL should be considered for RIT versus autologous transplantation.
Insulin, the Insulin-Like Growth Factor Axis, and Mortality in Patients With Nonmetastatic Colorectal Cancer
Authors: Wolpin Brian M. , Meyerhardt Jeffrey A. , Chan Andrew T. , Ng Kimmie , Chan Jennifer A. , Wu Kana , Pollak Michael N. , Giovannucci Edward L. , Fuchs Charles S. 
Published: December 2008

PurposeObesity, sedentary lifestyle, and Western dietary pattern have been linked to increased risk of cancer recurrence and mortality among patients with surgically resected colorectal cancer. Excess energy balance leads to increased circulating insulin and depressed levels of circulating insulin-like growth factor binding protein (IGFBP) -1, which promote cancer cell growth in preclinical models.Patients and MethodsAmong 373 patients diagnosed with nonmetastatic colorectal cancer between 1991 and 2004, we performed a prospective observational study nested within two large US cohorts to evaluate the association between mortality and prediagnosis circulating C-peptide (a marker of insulin secretion), IGFBP-1, insulin-like growth factor-I (IGF-I), and IGFBP-3.ResultsCompared with patients in the bottom quartile, patients in the top quartile of plasma C-peptide had an age-adjusted hazard ratio (HR) for death of 1.87 (95% CI, 1.04 to 3.36; P = .03 for trend), whereas those in the top quartile of circulating IGFBP-1 had a significant reduction in mortality (HR = 0.48; 95% CI, 0.28 to 0.84; P = .02 for trend). Little change in these estimates was noted after adjusting for other covariates known or suspected to influence survival. No associations were noted between mortality and IGF-I or IGFBP-3, which are two components of the IGF axis not closely correlated with lifestyle factors.ConclusionAmong patients with surgically resected colorectal cancer, higher levels of prediagnosis plasma C-peptide and lower levels of prediagnosis plasma IGFBP-1 were associated with increased mortality. Circulating insulin and IGFBP-1 are potential mediators of the association between lifestyle factors and mortality after colorectal cancer resection.
Challenges to metallomics and analytical chemistry solutions
Authors: Mounicou Sandra , Lobinski Ryszard 
Published: December 2008

Abstract
Metal ions play a fundamental role in the chemistry of life. The understanding of the molecular bases of the living process requires the knowledge of the correlations existing between metal ions and the genome and the derived -omes: transcriptome, proteome, and metabolome. An indispensable step on this way is the characterization of the coordination environment of metal ions present and the identification and quantification of metal-containing chemical species. The ensemble of research activities related to metal ions in biological systems has been recently referred to as "metallomics" [1]. The progress in this field is largely dependent on the high-throughput acquisition of multielement and -species analytical data in biological samples. The paper gives a brief overview of the state of the art of analytical techniques and methods for the multielement quantitative analysis of biological microsamples, and for the detection, identification, and quantitation of metal-containing proteins and low-molecular-weight metabolites. The potential contribution of molecular biology techniques in terms of linking information on metals and metal-species to the genome of an organism is highlighted.