bluuebunny/crossref_metadata_2025_split huggingface dataset:
P Bodies Inhibit Retrotransposition of Endogenous Intracisternal A Particles
Authors: Lu Chunye , Contreras Xavier , Peterlin B. Matija 
Published: April 2011

ABSTRACT
mRNA-processing bodies (P bodies) are cytoplasmic foci that contain translationally repressed mRNA. Since they are important for the retrotransposition of Ty elements and brome mosaic virus in yeast cells, we assessed the role of P bodies in the movement of endogenous intracisternal A particles (IAPs) in mammalian cells. In contrast to the case for these other systems, their disruption via knockdown of RCK or eukaryotic initiation factor E transporter (eIF4E-T) increased IAP retrotransposition as well as levels of IAP transcripts, Gag proteins, and reverse transcription products. This increase was not mediated by impairing the microRNA pathway. Rather, the removal of P bodies shifted IAP mRNA from nonpolysomal to polysomal fractions. Although IAP mRNA localized to P bodies, Gag was targeted to the endoplasmic reticulum (ER), from which IAP buds. Thus, by sequestering IAP mRNA away from Gag, P bodies inhibit rather than promote IAP retrotransposition.
Human Herpesvirus 6 Suppresses T Cell Proliferation through Induction of Cell Cycle Arrest in Infected Cells in the G
2
/M Phase
Authors: Li Lingyun , Gu Bin , Zhou Feng , Chi Jing , Wang Fang , Peng Guangyong , Xie Fangyi , Qing Jian , Feng Dongju , Lu Shiqiang , Yao Kun 
Published: April 2011

ABSTRACT

Human herpesvirus 6 (HHV-6) is an important immunosuppressive and immunomodulatory virus that primarily infects immune cells and strongly suppresses the proliferation of infected cells. However, the mechanisms responsible for the regulation and suppression mediated by HHV-6 are still unknown. In this study, we examined the ability of HHV-6A to manipulate cell cycle progression in infected cells and explored the potential molecular mechanisms. We demonstrated that infection with HHV-6A imposed a growth-inhibitory effect on HSB-2 cells by inducing cell cycle arrest at the G
2
/M phase. We then showed that the activity of the Cdc2–cyclin B1 complex was significantly decreased in HHV-6A-infected HSB-2 cells. Furthermore, we found that inactivation of Cdc2–cyclin B1 in HHV-6A-infected cells occurred through the inhibitory Tyr15 phosphorylation resulting from elevated Wee1 expression and inactivated Cdc25C. The reduction of Cdc2–cyclin B1 activity in HHV-6-infected cells was also partly due to the increased expression of the cell cycle-regulatory molecule p21 in a p53-dependent manner. In addition, HHV-6A infection activated the DNA damage checkpoint kinases Chk2 and Chk1. Our data suggest that HHV-6A infection induces G
2
/M arrest in infected T cells via various molecular regulatory mechanisms. These results further demonstrate the potential mechanisms involved in immune suppression and modulation mediated by HHV-6 infection, and they provide new insights relevant to the development of novel vaccines and immunotherapeutic approaches.
The Conserved YAGL Motif in Human Metapneumovirus Is Required for Higher-Order Cellular Assemblies of the Matrix Protein and for Virion Production
Authors: Sabo Yosef , Ehrlich Marcelo , Bacharach Eran 
Published: April 2011

ABSTRACTYXXL motifs in cellular and viral proteins have a variety of functions. The matrix (M) protein of the respiratory pathogen human metapneumovirus (hMPV) contains two such conserved motifs—YSKL and YAGL. We mutated these sequences to analyze their contributions to hMPV infectivity. The mutant clones were capable of intracellular replication; however, the YAGL but not YSKL mutants were defective at spreading in infected cultures. We improved the reverse genetics system for hMPV and generated cell lines that stably expressed selectable, replicating full-length genomes for both the wild type and the mutant clones, allowing microscopic and biochemical analyses of these viruses. YAGL mutants produced normal cellular levels of M protein but failed to release virions, while ectopic coexpression of wild-type M generated particles that were restricted to a single cycle of infection. The YAGL motif did not act as a late (L) domain, however, since hMPV budding was independent of the cellular endosomal sorting complex required for transport (ESCRT) machinery and because replacement of the YAGL motif with classical L domains generated defective viruses. Instead, the YAGL mutants had defective M assemblies lacking a normal filamentous appearance and showed poor extractability from the cell compared to the wild-type protein. The mutant proteins were not grossly misfolded, however, as they interacted with cellular membranes and coassembled with wild-type M proteins. Thus, the YAGL motif is an important determinant of hMPV assembly. Furthermore, the selectable hMPV genomes described here should extend the use of reverse genetics systems in the analysis of spreading-defective viruses.
PERIODIC ORBITS OF A DYNAMICAL SYSTEM RELATED TO A KNOT
Authors: LYUBICH LILYA 
Published: April 2011

Following [6] we consider a knot group G, its commutator subgroup K = [G, G], a finite group Σ and the space Hom (K, Σ) of all representations ρ : K → Σ, endowed with the weak topology. We choose a meridian x ∈ G of the knot and consider the homeomorphism σx of Hom (K, Σ) onto itself: σxρ(a) = ρ(xax-1) ∀ a ∈ K, ρ ∈ Hom (K, Σ). As proven in [5], the dynamical system ( Hom (K, Σ), σx) is a shift of finite type. In the case when Σ is abelian, Hom (K, Σ) is finite. In this paper we calculate the periods of orbits of ( Hom (K, ℤ/p), σx), where p is prime, in terms of the roots of the Alexander polynomial of the knot. In the case of two-bridge knots we give a complete description of the set of periods.
Bortezomib Primes Glioblastoma, Including Glioblastoma Stem Cells, for TRAIL by Increasing tBid Stability and Mitochondrial Apoptosis
Authors: Unterkircher Thomas , Cristofanon Silvia , Vellanki Sri Hari Krishna , Nonnenmacher Lisa , Karpel-Massler Georg , Wirtz Christian Rainer , Debatin Klaus-Michael , Fulda Simone 
Published: April 2011

Abstract
Purpose: Searching for novel approaches to sensitize glioblastoma for cell death, we investigated the proteasome inhibitor bortezomib.
Experimental Design: The effect of bortezomib on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)–induced apoptosis signaling pathways was analyzed in glioblastoma cell lines, primary glioblastoma cultures, and in an in vivo model.
Results: Bortezomib and TRAIL synergistically trigger cell death and reduce colony formation of glioblastoma cells (combination index &lt; 0.1). Investigations into the underlying molecular mechanisms reveal that bortezomib and TRAIL act in concert to cause accumulation of tBid, the active cleavage product of Bid. Also, the stability of TRAIL-derived tBid markedly increases on proteasome inhibition. Notably, knockdown of Bid significantly decreases bortezomib- and TRAIL-mediated cell death. By comparison, silencing of Noxa, which is also upregulated by bortezomib, does not confer protection. Coinciding with tBid accumulation, the activation of Bax/Bak and loss of mitochondrial membrane potential are strongly increased in cotreated cells. Overexpression of Bcl-2 significantly reduces mitochondrial perturbations and cell death, underscoring the functional relevance of the mitochondrial pathway. In addition, bortezomib cooperates with TRAIL to reduce colony formation of glioblastoma cells, showing an effect on long-term survival. Of note, bortezomib profoundly enhances TRAIL-triggered cell death in primary cultured glioblastoma cells and in patient-derived glioblastoma stem cells, underlining the clinical relevance. Importantly, bortezomib cooperates with TRAIL to suppress tumor growth in an in vivo glioblastoma model.
Conclusion: These findings provide compelling evidence that the combination of bortezomib and TRAIL presents a promising novel strategy to trigger cell death in glioblastoma, including glioblastoma stem cells, which warrants further investigation. Clin Cancer Res; 17(12); 4019–30. ©2011 AACR.
The Role of Planetary Waves in the Downward Influence of Stratospheric Final Warming Events
Authors: Sun Lantao , Robinson Walter A. , Chen Gang 
Published: April 2011

Abstract
Stratospheric final warming events are simulated in an idealized atmospheric model by imposing a winter-to-summer transition in radiative equilibrium temperature only in the stratosphere. Large ensembles of events are simulated with different strengths of topographic forcing. It is found that the dates of final warmings become earlier and their downward influence on the troposphere becomes stronger for greater topographic amplitudes. This result is similar to observed differences between the downward influence of the final warming in the Northern and Southern Hemispheres. The mechanisms through which the final warming exerts its influence on the tropospheric circulation are investigated using a zonally symmetric model. It is found that lower-stratospheric wave driving induces a residual circulation that affects the tropospheric circulation. The stratosphere also affects the propagation of planetary waves in the upper troposphere, resulting in a burst of wave activity and a rapid deceleration of tropospheric zonal winds at the time of the final warming. These results highlight the important roles of planetary waves in the downward influence of the stratospheric final warming events.
Long-term beta blockers for stable angina: systematic review and meta-analysis
Authors: Shu De Fen , Dong Bi Rong , Lin Xiu Fang , Wu Tai Xiang , Liu Guan Jian 
Published: April 2011

Objectives: To assess the effects of long-term beta blockers in patients with stable angina. Methods: We reviewed the literature up to June 2010 from CENTRAL, MEDLINE, EMBASE, CBM, and CNKI for randomized controlled trials. The appropriate data were meta-analysed using Revman 5.0. Results: Twenty-six trials including 6108 patients were identified. The treatment with beta blockers has significantly decreased all-cause mortality when compared with no control (OR 0.40, 95% CI 0.20 to 0.79), but has had no statistically differences when compared with placebo (OR 0.92, 95% CI 0.62 to 1.38) and with calcium-channel blocker (CCB) (OR 0.84, 95% CI 0.49 to 1.44). This was similar in patients with fatal and non-fatal acute myocardial infarction when compared with placebo (OR 0.82, 95% CI 0.57 to 1.17) or CCB (OR 1.08, 95% CI 0.71 to 1.66); on revascularization and quality of life. The beta blockers reduced the incident of unstable angina compared to no treatment (OR 0.14, 95% CI 0.07 to 0.29), but increased unstable angina compared to placebo (OR 3.32, 95% CI 1.50 to 7.36). There was a significant reduction of nitrate consumption when beta blockers were compared with CCBs (OR −1.18, 95% CI −1.54 to −0.82), but not with placebo and trimetazidine. There was no significant difference in angina attack between each group. Side effects in beta blocker were similar with ones in controls. Conclusions: Beta blockers may decrease the death and unstable angina when compared with no treatment, but no more effective than other anti-anginal agents on prophylaxis of myocardial ischaemia in stable angina patients.
Hospitalization for pain in patients with sickle cell disease treated with sildenafil for elevated TRV and low exercise capacity
Authors: Machado Roberto F. , Barst Robyn J. , Yovetich Nancy A. , Hassell Kathryn L. , Kato Gregory J. , Gordeuk Victor R. , Gibbs J. Simon R. , Little Jane A. , Schraufnagel Dean E. , Krishnamurti Lakshmanan , Girgis Reda E. , Morris Claudia R. , Rosenzweig Erika B. , Badesch David B. , Lanzkron Sophie , Onyekwere Onyinye , Castro Oswaldo L. , Sachdev Vandana , Waclawiw Myron A. , Woolson Rob , Goldsmith Jonathan C. , Gladwin Mark T. ,   on behalf of the walk-PHaSST Investigators and Patients
Published: April 2011

Abstract
In adults with sickle cell disease (SCD), an increased tricuspid regurgitation velocity (TRV) by Doppler echocardiography is associated with increased morbidity and mortality. Although sildenafil has been shown to improve exercise capacity in patients with pulmonary arterial hypertension, it has not been evaluated in SCD. We therefore sought to determine whether sildenafil could improve exercise capacity in SCD patients with increased TRV and a low exercise capacity. A TRV ≥ 2.7 m/s and a 6-minute walk distance (6MWD) between 150 and 500 m were required for enrollment in this 16-week, double-blind, placebo-controlled sildenafil trial. After 74 of the screened subjects were randomized, the study was stopped early due to a higher percentage of subjects experiencing serious adverse events in the sildenafil arm (45% of sildenafil, 22% of placebo, P = .022). Subject hospitalization for pain was the predominant cause for this difference: 35% with sildenafil compared with 14% with placebo (P = .029). There was no evidence of a treatment effect on 6MWD (placebo-corrected effect −9 m; 95% confidence interval [95% CI] −56-38; P = .703), TRV (P = .503), or N-terminal pro-brain natriuretic peptide (P = .410). Sildenafil appeared to increase hospitalization rates for pain in patients with SCD. This study is registered at www.clinicaltrials.gov as NCT00492531.
SNP array–based karyotyping: differences and similarities between aplastic anemia and hypocellular myelodysplastic syndromes
Authors: Afable Manuel G. , Wlodarski Marcin , Makishima Hideki , Shaik Mohammed , Sekeres Mikkael A. , Tiu Ramon V. , Kalaycio Matt , O'Keefe Christine L. , Maciejewski Jaroslaw P. 
Published: April 2011

Abstract
In aplastic anemia (AA), contraction of the stem cell pool may result in oligoclonality, while in myelodysplastic syndromes (MDS) a single hematopoietic clone often characterized by chromosomal aberrations expands and outcompetes normal stem cells. We analyzed patients with AA (N = 93) and hypocellular MDS (hMDS, N = 24) using single nucleotide polymorphism arrays (SNP-A) complementing routine cytogenetics. We hypothesized that clinically important cryptic clonal aberrations may exist in some patients with BM failure. Combined metaphase and SNP-A karyotyping improved detection of chromosomal lesions: 19% and 54% of AA and hMDS cases harbored clonal abnormalities including copy-neutral loss of heterozygosity (UPD, 7%). Remarkably, lesions involving the HLA locus suggestive of clonal immune escape were found in 3 of 93 patients with AA. In hMDS, additional clonal lesions were detected in 5 (36%) of 14 patients with normal/noninformative routine cytogenetics. In a subset of AA patients studied at presentation, persistent chromosomal genomic lesions were found in 10 of 33, suggesting that the initial diagnosis may have been hMDS. Similarly, using SNP-A, earlier clonal evolution was found in 4 of 7 AA patients followed serially. In sum, our results indicate that SNP-A identify cryptic clonal genomic aberrations in AA and hMDS leading to improved distinction of these disease entities.
Genomic characterization implicates iAMP21 as a likely primary genetic event in childhood B-cell precursor acute lymphoblastic leukemia
Authors: Rand Vikki , Parker Helen , Russell Lisa J. , Schwab Claire , Ensor Hannah , Irving Julie , Jones Lisa , Masic Dino , Minto Lynne , Morrison Heather , Ryan Sarra , Robinson Hazel , Sinclair Paul , Moorman Anthony V. , Strefford Jonathan C. , Harrison Christine J. 
Published: April 2011

Abstract
Intrachromosomal amplification of chromosome 21 (iAMP21) defines a distinct subgroup of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) that has a dismal outcome when treated with standard therapy. For improved diagnosis and risk stratification, the initiating genetic events need to be elucidated. To investigate the genetic basis of BCP-ALL, genomes of 94 iAMP21 patients were interrogated by arrays, FISH, and multiplex ligation-dependent probe amplification. Most copy number alterations targeted chromosome 21, reinforcing the complexity of this chromosome. The common region of amplification on chromosome 21 was refined to a 5.1-mb region that included RUNX1, miR-802, and genes mapping to the Down syndrome critical region. Recurrent abnormalities affecting genes in key pathways were identified: IKZF1 (22%), CDKN2A/B (17%), PAX5 (8%), ETV6 (19%), and RB1 (37%). Investigation of clonal architecture provided evidence that these abnormalities, and P2RY8-CRLF2, were secondary to chromosome 21 rearrangements. Patient outcome was uniformly poor with standard therapy irrespective of the presence or absence of these changes. This study has provided evidence that chromosome 21 instability is the only anomaly among those so far investigated that is common to all iAMP21 patients, and therefore the initiating event is likely to be found among the complex structural rearrangements of this abnormal chromosome.
Alternative donor transplantation after reduced intensity conditioning: results of parallel phase 2 trials using partially HLA-mismatched related bone marrow or unrelated double umbilical cord blood grafts
Authors: Brunstein Claudio G. , Fuchs Ephraim J. , Carter Shelly L. , Karanes Chatchada , Costa Luciano J. , Wu Juan , Devine Steven M. , Wingard John R. , Aljitawi Omar S. , Cutler Corey S. , Jagasia Madan H. , Ballen Karen K. , Eapen Mary , O'Donnell Paul V. ,   on behalf of the Blood and Marrow Transplant Clinical Trials Network
Published: April 2011

Abstract
The Blood and Marrow Transplant Clinical Trials Network conducted 2 parallel multicenter phase 2 trials for individuals with leukemia or lymphoma and no suitable related donor. Reduced intensity conditioning (RIC) was used with either unrelated double umbilical cord blood (dUCB) or HLA-haploidentical related donor bone marrow (Haplo-marrow) transplantation. For both trials, the transplantation conditioning regimen incorporated cyclophosphamide, fludarabine, and 200 cGy of total body irradiation. The 1-year probabilities of overall and progression-free survival were 54% and 46%, respectively, after dUCB transplantation (n = 50) and 62% and 48%, respectively, after Haplo-marrow transplantation (n = 50). The day +56 cumulative incidence of neutrophil recovery was 94% after dUCB and 96% after Haplo-marrow transplantation. The 100-day cumulative incidence of grade II-IV acute GVHD was 40% after dUCB and 32% after Haplo-marrow transplantation. The 1-year cumulative incidences of nonrelapse mortality and relapse after dUCB transplantation were 24% and 31%, respectively, with corresponding results of 7% and 45%, respectively, after Haplo-marrow transplantation. These multicenter studies confirm the utility of dUCB and Haplo-marrow as alternative donor sources and set the stage for a multicenter randomized clinical trial to assess the relative efficacy of these 2 strategies. The trials are registered at www.clinicaltrials.gov under NCT00864227 (BMT CTN 0604) and NCT00849147 (BMT CTN 0603).
Transcriptomic analysis of milk somatic cells in mastitis resistant and susceptible sheep upon challenge with Staphylococcus epidermidis and Staphylococcus aureus
Authors: Bonnefont Cécile MD , Toufeer Mehdi , Caubet Cécile , Foulon Eliane , Tasca Christian , Aurel Marie-Rose , Bergonier Dominique , Boullier Séverine , Robert-Granié Christèle , Foucras Gilles , Rupp Rachel 
Published: April 2011

Abstract

Background
The existence of a genetic basis for host responses to bacterial intramammary infections has been widely documented, but the underlying mechanisms and the genes are still largely unknown. Previously, two divergent lines of sheep selected for high/low milk somatic cell scores have been shown to be respectively susceptible and resistant to intramammary infections by Staphylococcus spp. Transcriptional profiling with an 15K ovine-specific microarray of the milk somatic cells of susceptible and resistant sheep infected successively by S. epidermidis and S. aureus was performed in order to enhance our understanding of the molecular and cellular events associated with mastitis resistance.

Results
The bacteriological titre was lower in the resistant than in the susceptible animals in the 48 hours following inoculation, although milk somatic cell concentration was similar. Gene expression was analysed in milk somatic cells, mainly represented by neutrophils, collected 12 hours post-challenge. A high number of differentially expressed genes between the two challenges indicated that more T cells are recruited upon inoculation by S. aureus than S. epidermidis. A total of 52 genes were significantly differentially expressed between the resistant and susceptible animals. Further Gene Ontology analysis indicated that differentially expressed genes were associated with immune and inflammatory responses, leukocyte adhesion, cell migration, and signal transduction. Close biological relationships could be established between most genes using gene network analysis. Furthermore, gene expression suggests that the cell turn-over, as a consequence of apoptosis/granulopoiesis, may be enhanced in the resistant line when compared to the susceptible line.

Conclusions
Gene profiling in resistant and susceptible lines has provided good candidates for mapping the biological pathways and genes underlying genetically determined resistance and susceptibility towards Staphylococcus infections, and opens new fields for further investigation.
Identification and characterization of plant Haspin kinase as a histone H3 threonine kinase
Authors: Kurihara Daisuke , Matsunaga Sachihiro , Omura Tomohiro , Higashiyama Tetsuya , Fukui Kiichi 
Published: April 2011

Abstract

Background
Haspin kinases are mitotic kinases that are well-conserved from yeast to human. Human Haspin is a histone H3 Thr3 kinase that has important roles in chromosome cohesion during mitosis. Moreover, phosphorylation of histone H3 at Thr3 by Haspin in fission yeast, Xenopus, and human is required for accumulation of Aurora B on the centromere, and the subsequent activation of Aurora B kinase activity for accurate chromosome alignment and segregation. Although extensive analyses of Haspin have been carried out in yeast and animals, the function of Haspin in organogenesis remains unclear.

Results
Here, we identified a Haspin kinase, designated AtHaspin, in Arabidopsis thaliana. The purified AtHaspin phosphorylated histone H3 at both Thr3 and Thr11 in vitro. Live imaging of AtHaspin-tdTomato and GFP-α-tubulin in BY-2 cells showed that AtHaspin-tdTomato localized on chromosomes during prometaphase and metaphase, and around the cell plate during cytokinesis. This localization of AtHaspin overlapped with that of phosphorylated Thr3 and Thr11 of histone H3 in BY-2 cells. AtHaspin-GFP driven by the native promoter was expressed in root meristems, shoot meristems, floral meristems, and throughout the whole embryo at stages of high cell division. Overexpression of a kinase domain mutant of AtHaspin decreased the size of the root meristem, which delayed root growth.

Conclusions
Our results indicated that the Haspin kinase is a histone H3 threonine kinase in A. thaliana. AtHaspin phosphorylated histone H3 at both Thr3 and Thr11 in vitro. The expression and dominant-negative analysis showed that AtHaspin may have a role in mitotic cell division during plant growth. Further analysis of coordinated mechanisms involving Haspin and Aurora kinases will shed new light on the regulation of chromosome segregation in cell division during plant growth and development.