bluuebunny/crossref_metadata_2025_split huggingface dataset:
Burkholderia mallei
Cluster 1 Type VI Secretion Mutants Exhibit Growth and Actin Polymerization Defects in RAW 264.7 Murine Macrophages
Authors: Burtnick Mary N. , DeShazer David , Nair Vinod , Gherardini Frank C. , Brett Paul J. 
Published: November 2009

ABSTRACT

Burkholderia mallei
is a facultative intracellular pathogen that causes severe disease in animals and humans. Recent studies have shown that the cluster 1 type VI secretion system (T6SS-1) expressed by this organism is essential for survival in a hamster model of glanders. To better understand the role of T6SS-1 in the pathogenesis of disease, studies were initiated to examine the interactions of
B. mallei tssE
mutants with RAW 264.7 murine macrophages. Results obtained by utilizing modified gentamicin protection assays indicated that although the
tssE
mutants were able to survive within RAW 264.7 cells, significant growth defects were observed in comparison to controls. In addition, analysis of infected monolayers by differential interference contrast and fluorescence microscopy demonstrated that the
tssE
mutants lacked the ability to induce multinucleated giant cell formation. Via the use of fluorescence microscopy,
tssE
mutants were shown to undergo escape from lysosome-associated membrane protein 1-positive vacuoles. Curiously, however, following entry into the cytosol, the mutants exhibited actin polymerization defects resulting in inefficient intra- and intercellular spread characteristics. Importantly, all mutant phenotypes observed in this study could be restored by complementation. Based upon these findings, it appears that T6SS-1 plays a critical role in growth and actin-based motility following uptake of
B. mallei
by RAW 264.7 cells.
DesT Coordinates the Expression of Anaerobic and Aerobic Pathways for Unsaturated Fatty Acid Biosynthesis in
Pseudomonas aeruginosa
Authors: Subramanian Chitra , Rock Charles O. , Zhang Yong-Mei 
Published: October 2009

ABSTRACT

The
fabA
and
fabB
genes are responsible for anaerobic unsaturated fatty acid formation in
Pseudomonas aeruginosa
. Expression of the
fabAB
operon was repressed by exogenous unsaturated fatty acids, and DNA sequences upstream of the translational start site were used to affinity purify DesT. The single protein interaction with the
fabAB
promoter detected in wild-type cell extracts was absent in the
desT
deletion strain, as was the repression of
fabAB
expression by unsaturated fatty acids. Thus, DesT senses the overall composition of the acyl-coenzyme A pool to coordinate the expression of the operons for the anaerobic (
fabAB
) and aerobic (
desCB
) pathways for unsaturated fatty acid synthesis.
Inefficient Tat-Dependent Export of Periplasmic Amidases in an
Escherichia coli
Strain with Mutations in Two DedA Family Genes
Authors: Sikdar Rakesh , Doerrler William T. 
Published: October 2009

ABSTRACT

The DedA family genes are found in most bacterial genomes. Two of these proteins are
Escherichia coli
YqjA and YghB, predicted inner membrane proteins of unknown function sharing 61% amino acid identity. The
E. coli
single deletion mutants are largely without phenotype, but the double mutant (BC202; Δ
yqjA
::Tet
r
Δ
yghB
::Kan
r
) is characterized by incomplete cell division, temperature sensitivity, and altered phospholipid levels (K. Thompkins et al., J. Bacteriol. 190:4489-4500, 2008). In this report, we have better characterized the cell division chaining defect of BC202. Fluorescence recovery after photobleaching indicates that 58% of the cells in chains are compartmentalized by at least a cytoplasmic membrane. Green fluorescent protein fusions to the cell division proteins FtsZ, ZipA, FtsI, FtsL, and FtsQ are correctly localized to new septation sites in BC202. Periplasmic amidases AmiC and AmiA, secreted by the twin arginine transport (Tat) pathway, are localized to the cytoplasm in BC202. Overexpression of AmiA, AmiC, or AmiB, a periplasmic amidase secreted via the general secretory pathway, restores normal cell division but does not suppress the temperature sensitivity of BC202, indicating that YghB and YqjA may play additional roles in cellular physiology. Strikingly, overexpression of the Tat export machinery (TatABC) results in normal cell division and growth at elevated temperatures. These data collectively suggest that the twin arginine pathway functions inefficiently in BC202, likely due to the altered levels of membrane phospholipids in this mutant. These results underscore the importance of membrane composition in the proper function of the Tat protein export pathway.
Intra-arterial or intravenous thrombolysis for acute ischemic stroke? The SYNTHESIS pilot trial
Authors: Ciccone A , Valvassori L , Ponzio M , Ballabio E , Gasparotti R , Sessa M , Scomazzoni F , Tiraboschi P , Sterzi R ,   the SYNTHESIS Investigators
Published: October 2009

ObjectiveTo assess the feasibility, safety and preliminary efficacy of intra-arterial thrombolysis (IAT) compared with standard intravenous thrombolysis (IVT) for acute ischemic stroke.MethodsEligible patients with ischemic stroke, who were devoid of contraindications, started IVT within 3 h or IAT as soon as possible within 6 h. Patients were randomized within 3 h of onset to receive either intravenous alteplase, in accordance with the current European labeling, or up to 0.9 mg/kg intra-arterial alteplase (maximum 90 mg), over 60 min into the thrombus, if necessary with mechanical clot disruption and/or retrieval. The purpose of the study was to determine the proportion of favorable outcome at 90 days. Safety endpoints included symptomatic intracranial hemorrhage (SICH), death and other serious adverse events.Results54 patients (25 IAT) were enrolled. Median time from stroke onset to start to treatment was 3 h 15 min for IAT and 2 h 35 min for IVT (p<0.001). Almost twice as many patients on IAT as those on IVT survived without residual disability (12/25 vs 8/29; OR 3.2; 95% CI 0.9 to 11.4; p=0.067). SICH occurred in 2/25 patients on IAT and in 4/29 on IVT (OR 0.5; CI 0.1 to 3.3; p=0.675). Mortality at day 7 was 5/25 (IAT) compared with 4/29 (IVT) (OR 1.6; CI 0.4 to 6.7; p=0.718). There was no significant difference in the rate of other serious adverse events.ConclusionsRapid initiation of IAT is a safe and feasible alternative to IVT in acute ischemic stroke.Trial registration number NCT00540527.
THE TRAPPED-ION QUBIT: COHERENT CONTROL IN INFINITE-DIMENSIONAL QUANTUM SYSTEMS
Authors: RANGAN C. 
Published: November 2009

Theories of quantum control have, until recently, made the assumption that the Hilbert space of a quantum system can be truncated to finite dimensions. Such truncations, which can be achieved for most quantum systems via bandwidth restrictions, have enabled the development of a rich variety of quantum control and optimal control schemes. Recent studies in quantum information processing have addressed the control of infinite-dimensional quantum systems such as the quantum states of a trapped-ion. Controllability in an infinite-dimensional quantum system is hard to prove with conventional methods, and infinite-dimensional systems provide unique challenges in designing control fields. In this paper, we will discuss the control of a popular system for quantum computing the trapped-ion qubit. This system, modeled by a spin-half particle coupled to a quantized harmonic oscillator, is an example for a surprisingly rich variety of control problems. We will show how this infinite-dimensional quantum system can be examined via the lens of the Finite Controllability Theorem, two-color STIRAP, the generalized Heisenberg system, etc. These results are important from the viewpoint of developing more efficient quantum control protocols, particularly in quantum computing systems. This work shows how one can expand the scope of quantum control research to beyond that of finite-dimensional quantum systems.
Using Latent Class Models to Explore Cross-national Typologies of Public Engagement with Science and Technology in Europe
Authors: Stares Sally 
Published: November 2009

Public engagement with science and technology is a central theme in the field of Public Understanding of Science (PUS), particularly in Europe. Alongside public consultation exercises and similar activities aimed at generating engagement, there is a need for good survey indicators of the general climate for engagement with science and technology among the public. With internationally focused PUS studies increasing in prominence, such survey indicators should ideally characterise engagement in approximately the same way across a range of countries, to facilitate sensible cross-national analyses involving this construct. This article presents cross-national analyses of two sets of questions posed in the Eurobarometer survey on public perceptions of biotechnology, conducted in 2002 in fifteen European countries. The items analysed capture a range of elements of the concept of engagement, both with science and technology, in general, and with biotechnology, in particular. Latent class models are used to explore typologies of types of engagement: substantively, to understand their content, and methodologically, to identify items which do not work well in these classifications. The analyses are also used to assess the statistical cross-national comparability of such typologies, and consequently to describe variations in levels of engagement across countries.
Gene expression classifiers for relapse-free survival and minimal residual disease improve risk classification and outcome prediction in pediatric B-precursor acute lymphoblastic leukemia
Authors: Kang Huining , Chen I.-Ming , Wilson Carla S. , Bedrick Edward J. , Harvey Richard C. , Atlas Susan R. , Devidas Meenakshi , Mullighan Charles G. , Wang Xuefei , Murphy Maurice , Ar Kerem , Wharton Walker , Borowitz Michael J. , Bowman W. Paul , Bhojwani Deepa , Carroll William L. , Camitta Bruce M. , Reaman Gregory H. , Smith Malcolm A. , Downing James R. , Hunger Stephen P. , Willman Cheryl L. 
Published: October 2009

Abstract
To determine whether gene expression profiling could improve outcome prediction in children with acute lymphoblastic leukemia (ALL) at high risk for relapse, we profiled pretreatment leukemic cells in 207 uniformly treated children with high-risk B-precursor ALL. A 38-gene expression classifier predictive of relapse-free survival (RFS) could distinguish 2 groups with differing relapse risks: low (4-year RFS, 81%, n = 109) versus high (4-year RFS, 50%, n = 98; P < .001). In multivariate analysis, the gene expression classifier (P = .001) and flow cytometric measures of minimal residual disease (MRD; P = .001) each provided independent prognostic information. Together, they could be used to classify children with high-risk ALL into low- (87% RFS), intermediate- (62% RFS), or high- (29% RFS) risk groups (P < .001). A 21-gene expression classifier predictive of end-induction MRD effectively substituted for flow MRD, yielding a combined classifier that could distinguish these 3 risk groups at diagnosis (P < .001). These classifiers were further validated on an independent high-risk ALL cohort (P = .006) and retainedindependent prognostic significance (P < .001) in the presence of other recently described poor prognostic factors (IKAROS/IKZF1 deletions, JAK mutations, and kinase expression signatures). Thus, gene expression classifiers improve ALL risk classification and allow prospective identification of children who respond or fail current treatment regimens. These trials were registered at http://clinicaltrials.gov under NCT00005603.
Ubiquitination and degradation of the thrombopoietin receptor c-Mpl
Authors: Saur Sebastian J. , Sangkhae Veena , Geddis Amy E. , Kaushansky Kenneth , Hitchcock Ian S. 
Published: October 2009

AbstractRegulation of growth factor and cytokine signaling is essential for maintaining physiologic numbers of circulating hematopoietic cells. Thrombopoietin (Tpo), acting through its receptor c-Mpl, is required for hematopoietic stem cell maintenance and megakaryopoiesis. Therefore, the negative regulation of Tpo signaling is critical in many aspects of hematopoiesis. In this study, we determine the mechanisms of c-Mpl degradation in the negative regulation of Tpo signaling. We found that, after Tpo stimulation, c-Mpl is degraded by both the lysosomal and proteasomal pathways and c-Mpl is rapidly ubiquitinated. Using site-directed mutagenesis, we were able to determine that c-Mpl is ubiquitinated on both of its intracellular lysine (K) residues (K553 and K573). By mutating these residues to arginine, ubiquitination and degradation were significantly reduced and caused hyperproliferation in cell lines expressing these mutated receptors. Using short interfering RNA and dominant negative overexpression, we also found that c-Cbl, which is activated by Tpo, acts as an E3 ubiquitin ligase in the ubiquitination of c-Mpl. Our findings identify a previously unknown negative regulatory pathway for Tpo signaling that may significantly impact our understanding of the mechanisms affecting the growth and differentiation of hematopoietic stem cells and megakaryocytes.
A prototype nonpeptidyl, hydrazone class, thrombopoietin receptor agonist, SB-559457, is toxic to primary human myeloid leukemia cells
Authors: Kalota Anna , Gewirtz Alan M. 
Published: October 2009

AbstractBiologic characterization of SB-559457 (SB), a nonpeptidyl hydrazone class of thrombopoietin receptor (Mpl) agonist, revealed toxicity toward human leukemia cells. Antiproliferative effects followed by significant, nonapoptotic, cell death within 72 hours occurred in 24 of 26 acute myeloid leukemia, 0 of 6 acute lymphoblastic leukemia, and 3 of 6 chronic myeloid leukemia patient samples exposed to SB, but not recombinant human thrombopoietin (rhTpo), in liquid suspension culture. Further investigation revealed increased phosphorylation of p70S6/S6 kinases in SB-, but not in rhTpo-, treated cells. Expression profiling of cells exposed to SB versus rhTpo revealed statistically significant, more than 2-fold changes in GAPDH and REDD1 gene expression, confirmed by quantitative reverse-transcribed polymerase chain reaction. These genes, induced in energy or hypoxia stressed cells, have been implicated in cell death pathways, and may provide important clues to the mechanism of SB-induced, leukemic cell death. These results suggest that nonpeptidyl, hydrazone class Mpl agonists may be clinically useful antileukemic agents by virtue of their combined thrombopoietic and antileukemic effects.
Bortezomib and high-dose melphalan as conditioning regimen before autologous stem cell transplantation in patients with de novo multiple myeloma: a phase 2 study of the Intergroupe Francophone du Myélome (IFM)
Authors: Roussel Murielle , Moreau Philippe , Huynh Anne , Mary Jean-Yves , Danho Clotaire , Caillot Denis , Hulin Cyrille , Fruchart Christophe , Marit Gérald , Pégourié Brigitte , Lenain Pascal , Araujo Carla , Kolb Brigitte , Randriamalala Edouard , Royer Bruno , Stoppa Anne-Marie , Dib Mammoun , Dorvaux Véronique , Garderet Laurent , Mathiot Claire , Avet-Loiseau Hervé , Harousseau Jean-Luc , Attal Michel ,   for the Intergroupe Francophone du Myélome (IFM)
Published: November 2009

Abstract
Autologous stem cell transplantation (ASCT) is recommended for younger patients with newly diagnosed multiple myeloma. Achieving complete response (CR) or at least very good partial response (VGPR) is a major prognostic factor for survival with 20% to 30% of patients achieving CR after ASCT. Bortezomib has shown synergistic effects with melphalan and no prolonged hematologic toxicity. In this Intergroupe Francophone du Myélome (IFM) phase 2 study, 54 untreated patients were enrolled between July and December 2007 to receive bortezomib (1 mg/m2 × 4) and melphalan (200 mg/m2) as conditioning regimen (Bor-HDM). Overall, 70% of patients achieved at least VGPR, including 17 patients with CR (32%) after ASCT. No toxic deaths were observed. Bortezomib did not increase hematologic toxicity. Only 1 grade 3 to 4 peripheral neuropathy was reported. A matched control analysis was conducted comparing our cohort with patients from the IFM 2005-01 trial (HDM alone). Patients were matched for response to induction therapy and type of induction: CR was higher in the Bor-HDM group (35% vs 11%; P = .001), regardless of induction therapy. These results suggest that Bor-HDM is a safe and promising conditioning regimen. Randomized studies are needed to assess whether this conditioning regimen is superior to HDM alone. This trial was registered at www.clinicaltrials.gov as NCT00642395.
Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet
Authors: Döhner Hartmut , Estey Elihu H. , Amadori Sergio , Appelbaum Frederick R. , Büchner Thomas , Burnett Alan K. , Dombret Hervé , Fenaux Pierre , Grimwade David , Larson Richard A. , Lo-Coco Francesco , Naoe Tomoki , Niederwieser Dietger , Ossenkoppele Gert J. , Sanz Miguel A. , Sierra Jorge , Tallman Martin S. , Löwenberg Bob , Bloomfield Clara D. 
Published: October 2009

AbstractIn 2003, an international working group last reported on recommendations for diagnosis, response assessment, and treatment outcomes in acute myeloid leukemia (AML). Since that time, considerable progress has been made in elucidating the molecular pathogenesis of the disease that has resulted in the identification of new diagnostic and prognostic markers. Furthermore, therapies are now being developed that target disease-associated molecular defects. Recent developments prompted an international expert panel to provide updated evidence- and expert opinion–based recommendations for the diagnosis and management of AML, that contain both minimal requirements for general practice as well as standards for clinical trials. A new standardized reporting system for correlation of cytogenetic and molecular genetic data with clinical data is proposed.
HER/ErbB receptor interactions and signaling patterns in human mammary epithelial cells
Authors: Zhang Yi , Opresko Lee , Shankaran Harish , Chrisler William B , Wiley H Steven , Resat Haluk 
Published: October 2009

AbstractBackgroundKnowledge about signaling pathways is typically compiled based on data gathered using different cell lines. This approach implicitly assumes that the cell line dependence is not important. However, different cell lines do not always respond to a particular stimulus in the same way, and lack of coherent data collected from closely related cellular systems can be detrimental to the efforts to understand the regulation of biological processes. To address this issue, we created a clone library of human mammary epithelial (HME) cells that expresses different levels of HER2 and HER3 receptors in combination with endogenous EGFR/HER1. Using our clone library, we have quantified the receptor activation patterns and systematically tested the validity of the existing hypotheses about the interaction patterns between HER1-3 receptors.ResultsOur study identified HER2 as the dominant dimerization partner for both EGFR and HER3. Contrary to earlier suggestions, we find that lateral interactions with HER2 do not lead to strong transactivation between EGFR and HER3, i.e., EGFR activation and HER3 activation are only weakly linked in HME cells. We also find that observed weak transactivation is uni-directional where stimulation of EGFR leads to HER3 activation whereas HER3 stimulation does not activate the EGFR. Repeating our experiments at lower cell confluency established that cell confluency is not a major factor in the observed interaction patterns. We have also quantified the dependence of the kinetics of Erk and Akt activation on different HER receptors. We found that HER3 signaling makes the strongest contribution to Akt activation and that, stimulation of either EGFR or HER3 leads to significant Erk activation.ConclusionOur study shows that clone cell libraries can be a powerful resource in systems biology research by making it possible to differentiate between various hypotheses in a consistent cellular background. Using our constructed clone library we profiled the cell signaling patterns to establish the role of HER2 in the crosstalk between EGFR and HER3 receptors in HME cells. Our results for HME cells show that the weak linkage between EGFR and HER3 pathways can lead to distinct downstream cellular signaling patterns in response to the ligands of these two receptors.
Topological analysis of a haloacid permease of a Burkholderi a sp. bacterium with a PhoA-LacZ reporter
Authors: Tse Yuk Man , Yu Manda , Tsang Jimmy SH 
Published: October 2009

Abstract

Background
2-Haloacids can be found in the natural environment as degradative products of natural and synthetic halogenated compounds. They can also be generated by disinfection of water and have been shown to be mutagenic and to inhibit glyceraldehyde-3-phosphate dehydrogenase activity. We have recently identified a novel haloacid permease Deh4p from a bromoacetate-degrading bacterium Burkholderia sp. MBA4. Comparative analyses suggested that Deh4p is a member of the Major Facilitator Superfamily (MFS), which includes thousands of membrane transporter proteins. Members of the MFS usually possess twelve putative transmembrane segments (TMS). Deh4p was predicted to have twelve TMS. In this study we characterized the topology of Deh4p with a PhoA-LacZ dual reporters system.

Results
Thirty-six Deh4p-reporter recombinants were constructed and expressed in E. coli. Both PhoA and LacZ activities were determined in these cells. Strength indices were calculated to determine the locations of the reporters. The results mainly agree with the predicted model. However, two of the TMS were not verified. This lack of confirmation of the TMS, using a reporter, has been reported previously. Further comparative analysis of Deh4p has assigned it to the Metabolite:H+ Symporter (MHS) 2.A.1.6 family with twelve TMS. Deh4p exhibits many common features of the MHS family proteins. Deh4p is apparently a member of the MFS but with some atypical features.

Conclusion
The PhoA-LacZ reporter system is convenient for analysis of the topology of membrane proteins. However, due to the limitation of the biological system, verification of some of the TMS of the protein was not successful. The present study also makes use of bioinformatic analysis to verify that the haloacid permease Deh4p of Burkholderia sp. MBA4 is a MFS protein but with atypical features.