bluuebunny/crossref_metadata_2025_split huggingface dataset:
Members of the CIP4 family of proteins participate in the regulation of platelet‐derived growth factor receptor‐β‐dependent actin reorganization and migration
Authors: Toguchi Marcia , Richnau Ninna , Ruusala Aino , Aspenström Pontus 
Published: November 2009

Background information. The F‐BAR {Fes/CIP4 [Cdc42 (cell division cycle 42)‐interacting protein 4] homology and BAR (Bin/amphiphysin/Rvs)} proteins have emerged as important co‐ordinators of signalling pathways that regulate actin assembly and membrane dynamics. The presence of the F‐BAR domain is the hallmark of this family of proteins and the CIP4 (Cdc42‐interacting protein 4) was one of the first identified vertebrate F‐BAR proteins. There are three human CIP4 paralogues, namely CIP4, FBP17 (formin‐binding protein 17) and Toca‐1 (transducer of Cdc42‐dependent actin assembly 1). The CIP4‐like proteins have been implicated in Cdc42‐dependent actin reorganization and in regulation of membrane deformation events visible as tubulation of lipid bilayers.Results. We performed side‐by‐side analyses of the three CIP4 paralogues. We found that the three CIP4‐like proteins vary in their effectiveness to catalyse membrane tubulation and actin reorganization. Moreover, we show that the CIP4‐dependent membrane tubulation is enhanced in the presence of activated Cdc42. Some F‐BAR members have been shown to have a role in the endocytosis of the EGF (epidermal growth factor) receptor and this prompted us to study the involvement of the CIP4‐like proteins in signalling of the PDGFRβ [PDGF (platelet‐derived growth factor) β‐receptor]. We found that knock‐down of CIP4‐like proteins resulted in a prolonged formation of PDGF‐induced dorsal ruffles, as well as an increased PDGF‐dependent cell migration. This was most likely a consequence of a sustained PDGFRβ activation caused by delayed internalization of the receptor in the cells treated with siRNA (small interfering RNA) specific for the CIP4‐like proteins.Conclusions. Our findings show that CIP4‐like proteins induced membrane tubulation downstream of Cdc42 and that they have important roles in PDGF‐dependent actin reorganization and cell migration by regulating internalization and activity of the PDGFRβ. Moreover, the results suggest an important role for the CIP4‐like proteins in the regulation of the activity of the PDGFRβ.
Validating a 3-Point Prediction Rule for Surgical Site Infection after Coronary Artery Bypass Surgery
Authors: Chen Luke F. , Anderson Deverick J. , Kaye Keith S. , Sexton Daniel J. 
Published: November 2009

Background.Surgical site infection (SSI) after coronary artery bypass graft (CABG) surgery is an increasing healthcare problem. Investigators from Australia proposed a new, 3-point scale that assesses SSI risk on the basis of diagnosis of diabetes mellitus and body mass index.Objective.To validate the Australian Clinical Risk Index among patients undergoing CABG surgery in the United States.Design and Setting.Nested case-control study involving patients undergoing CABG surgery at 9 hospitals during 1991-2002.Patients.Case patients were those who developed SSIs after CABG surgery. Control subjects were matched to case patients on the basis of hospital, age, and procedure date.Methods.Odds ratios (ORs) for SSIs were calculated for the comparison of case patients with control subjects for all risk categories determined using the Australian Clinical Risk Index and National Nosocomial Infections Surveillance System (NNIS) risk index. An adjusted area under the curve was used to compare predictive values among risk indices.Results.Four hundred sixty patients were studied, including 269 patients with SSI and 191 control subjects. NNIS risk group 2 was associated with increased rate of SSI (OR, 1.79; 95% confidence interval [CI], 1.19-2.67). No patient had an NNIS risk index of 3. The remaining NNIS categories were not predictive of infection. In contrast, an increase in Australian Clinical Risk Index was associated with an increase in risk of SSI (category 2: OR, 2.39 [95% CI, 1.33-4.29]; category 3: OR, 4.46 [95% CI, 1.83-10.85]).Conclusions.The NNIS risk index predicts the risk of SSI associated with many procedures, but it has limited use in predicting the risk of SSI after CABG surgery. The new Australian Clinical Risk Index stratified patients into discrete groups associated with increased risk of SSI. Data from our study support the use of this new risk index in the US population.
Target prediction and a statistical sampling algorithm for RNA–RNA interaction
Authors: Huang Fenix W. D. , Qin Jing , Reidys Christian M. , Stadler Peter F. 
Published: November 2009

Abstract
Motivation: It has been proven that the accessibility of the target sites has a critical influence on RNA–RNA binding, in general and the specificity and efficiency of miRNAs and siRNAs, in particular. Recently, O(N6) time and O(N4) space dynamic programming (DP) algorithms have become available that compute the partition function of RNA–RNA interaction complexes, thereby providing detailed insights into their thermodynamic properties.
Results: Modifications to the grammars underlying earlier approaches enables the calculation of interaction probabilities for any given interval on the target RNA. The computation of the ‘hybrid probabilities’ is complemented by a stochastic sampling algorithm that produces a Boltzmann weighted ensemble of RNA–RNA interaction structures. The sampling of k structures requires only negligible additional memory resources and runs in O(k·N3).
Availability: The algorithms described here are implemented in C as part of the rip package. The source code of rip2 can be downloaded from http://www.combinatorics.cn/cbpc/rip.html and http://www.bioinf.uni-leipzig.de/Software/rip.html.
Contact: duck@santafe.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
Tracking the geographical spread of avian influenza (H5N1) with multiple phylogenetic trees
Authors: Hovmöller Rasmus , Alexandrov Boyan , Hardman Jori , Janies Daniel 
Published: November 2009

AbstractAvian influenza (H5N1) has been of great social and economic importance since it first infected humans in Hong Kong in 1997. A highly pathogenic strain has spread from China and has killed humans in east Asia, west Africa, south Asia, and the Middle East. Recently, several molecular phylogenetic studies have focused on the relationships of various clades of H5N1 and their spread over time, space, and various hosts. These studies examining the geographical spread of H5N1 have based their conclusions on a single tree. This tree often results from the analysis of the genomic segment coding for the haemagglutinin (HA) or neuraminidase (NA) proteins and a limited sample of viral isolates. Here we present the first study using multiple candidate trees to estimate geographical transmission routes of H5N1. In addition, we use all high‐quality HA and NA sequences available to the public as of June 2008. We estimated geographical transmission routes of H5N1 by optimizing multistate characters with states representing different geographical regions over a pool of presumed minimum‐length trees. We also developed means to visualize our results in Keyhole Markup Language (KML) for virtual globes. We provide these methods as a web application entitled “Routemap” (http://routemap.osu.edu). The resulting visualizations are akin to airline route maps but they depict the routes of spread of viral lineages. We compare our results with the results of previous studies. We focus on the sensitivity of results to sampling of tree space, character coding schemes, optimization methods, and taxon sampling. In conclusion, we find that using one tree and a single character optimization method will ignore many of the transmission routes indicated by genetic sequence and geographical data.© The Willi Hennig Society 2009.
Glutathione S‐transferase M1 inhibits dexamethasone‐induced apoptosis in association with the suppression of Bim through dual mechanisms in a lymphoblastic leukemia cell line
Authors: Hosono Naoko , Kishi Shinji , Iho Sumiko , Urasaki Yoshimasa , Yoshida Akira , Kurooka Hisanori , Yokota Yoshifumi , Ueda Takanori 
Published: November 2009

(Cancer Sci2010; 101: 767–773)Glutathione S‐transferase μ (GSTM1) is mainly known as a detoxification enzyme but it has also been shown to be a negative regulator of apoptosis‐related signaling cascades. Recently GSTM1 has been reported to be a significant risk factor for hematological relapse in childhood acute lymphoblastic leukemia, although the underlying mechanism remains largely unknown. Glucocorticoids play a crucial role in the treatment of childhood acute lymphoblastic leukemia, therefore we hypothesized that GSTM1 plays important roles in glucocorticoid‐induced apoptotic pathways. To clarify the relationship betweenGSTM1and drug resistance,GSTM1was transfected into a T‐acute lymphoblastic leukemia cell line, CCRF‐CEM (CEM), and we established the GSTM1‐expressing cell lines CEM/M1‐4 and CEM/M1‐9. Transduction ofGSTM1into CEM selectively decreased cellular sensitivity to dexamethasone in a manner that was independent of glutathione conjugation, but was due to apoptosis inhibition. Dexamethasone‐induced p38‐MAPK and Bim activation were concomitantly suppressed. Interestingly, nuclear factor kappa b (NF‐κB) p50 activity was upregulated in GSTM1‐expressing CEM. Inhibition of NF‐κB by the pharmacological agent BAY11‐7082 greatly enhanced the sensitivity of the GSTM1‐expressing CEM to dexamethasone and was accompanied by an increase in Bim expression. Thus, we propose that GSTM1, a novel regulator of dexamethasone‐induced apoptosis, causes dexamethasone resistance by suppression of Bim through dual mechanisms of both downregulation of p38‐MAPK and upregulation of NF‐κB p50.
The potential role of epigenetic therapy in multiple myeloma
Authors: Smith Emma M. , Boyd Kevin , Davies Faith E. 
Published: November 2009

SummaryThis review describes the role that epigenetic changes play in the pathogenesis of cancer, concentrating on the plasma cell malignancy multiple myeloma, and highlights recent findings regarding the efficacy of epigenetic therapeutic agents in laboratory studies and clinical trials. DNA methylation is altered in a wide range of cancers with hypermethylation of CpG islands associated with silencing of tumour suppressor genes. Genes found to be silenced by methylation in myeloma samples include VHL, TP53, CDKN2A, and TGFBR2. Myeloma is linked to the overexpression of a histone methylatransferase (MMSET) and inactivating mutations of a histone demethylase (UTX), suggesting that the regulation of histone methylation is a potential therapeutic target. Abnormal expression of histone deacetylases (HDACs) has been widely described in solid tumours and haematological malignancies. In myeloma, histone deacetylase inhibitors show promising results both in laboratory‐based cell culture studies and in clinical trials, where they demonstrate particularly good therapeutic outcome when administered in combination with other standard chemotherapeutic agents. The study of epigenetics shows great promise for understanding the alterations in gene expression that underlie malignancies and provides exciting novel drugable targets.
A multi‐centre study of candidate genes for wheeze and allergy: the International Study of Asthma and Allergies in Childhood Phase 2
Authors: Genuneit J. , Cantelmo J. L. , Weinmayr G. , Wong G. W. K. , Cooper P. J. , Riikjärv M.‐A. , Gotua M. , Kabesch M. , Von Mutius E. , Forastiere F. , Crane J. , Nystad W. , El‐Sharif N. , Batlles‐Garrido J. , García‐Marcos L. , García‐Hernández G. , Morales‐Suarez‐Varela M. , Nilsson L. , Bråbäck L. , Saraçlar Y. , Weiland S. K. , Cookson W. O. C. , Strachan D. , Moffatt M. F. ,   the ISAAC Phase 2 Study Group
Published: November 2009

SummaryBackground
Common polymorphisms have been identified in genes suspected to play a role in asthma. We investigated their associations with wheeze and allergy in a case–control sample from Phase 2 of the International Study of Asthma and Allergies in Childhood.Methods
We compared 1105 wheezing and 3137 non‐wheezing children aged 8–12 years from 17 study centres in 13 countries. Genotyping of 55 candidate single nucleotide polymorphisms (SNPs) in 14 genes was performed using the Sequenom System. Logistic regression models were fitted separately for each centre and each SNP. A combined per allele odds ratio and measures of heterogeneity between centres were derived by random effects meta‐analysis.Results
Significant associations with wheeze in the past year were detected in only four genes (IL4R, TLR4, MS4A2, TLR9, P<0.05), with per allele odds ratios generally <1.3. Variants in IL4R and TLR4 were also related to allergen‐specific IgE, while polymorphisms in FCER1B (MS4A2) and TLR9 were not. There were also highly significant associations (P<0.001) between SPINK5 variants and visible eczema (but not IgE levels) and between IL13 variants and total IgE. Heterogeneity of effects across centres was rare, despite differences in allele frequencies.Conclusions
Despite the biological plausibility of IgE‐related mechanisms in asthma, very few of the tested candidates showed evidence of association with both wheeze and increased IgE levels. We were unable to confirm associations of the positional candidates DPP10 and PHF11 with wheeze, although our study had ample power to detect the expected associations of IL13 variants with IgE and SPINK5 variants with eczema.
Immunotherapy with a modified birch pollen extract in allergic rhinoconjunctivitis: clinical and immunological effects
Authors: Ceuppens J. L. , Bullens D. , Kleinjans H. , Van Der Werf J. ,   the PURETHAL Birch Efficacy Study Group
Published: November 2009

SummaryBackground
Modification of allergens by glutaraldehyde in extracts used for immunotherapy reduces the risk for side‐effects, but the therapeutic efficacy of such extracts still requires further evaluation. The aim of this study was to show the efficacy and safety of immunotherapy with a single‐strength glutaraldehyde‐modified aluminium hydroxide‐adsorbed extract of birch pollen.Methods
In a multi‐centre, randomized, placebo‐controlled double‐blind setting, starting in 2001 between 1 August and 15 December, birch pollen‐allergic subjects (n=62) were injected subcutaneously with increasing doses of the allergen extract or placebo at weekly intervals over a 6‐week period (or longer if adverse reactions occurred). Maintenance dose was given monthly for at least 18 months till June 2003. Efficacy was evaluated on the basis of the clinical index score (CIS), a combined symptom and medication score.Results
Fifty‐eight patients could be evaluated for clinical efficacy. Treatment with the birch pollen extract resulted in a lower CIS for the eye and nose during the peak birch pollen season of 2003, compared with placebo (reductions of 42% and 31%, respectively) (P=0.017 and 0.039). Active treatment induced IgG and IgG4 antibodies reacting with Bet v 1 (P<0.001). Sera from treated patients had a blocking effect on Bet v 1‐induced basophil activation (P<0.04). No major adverse reactions occurred, and local reactions, if occurring, were mild.Conclusion
Immunotherapy with a modified slow‐release birch pollen extract, administered in a single‐strength preparation with a rapid dose increase, is safe and efficacious. IgG and IgG4 antibodies against native Bet v 1 are induced, which block basophil activation.
Phosphorus and nitrogen in a monomictic freshwater lake: employing cyanobacterial bioreporters to gain new insights into nutrient bioavailability
Authors: GILLOR OSNAT , HADAS ORA , POST ANTON F. , BELKIN SHIMSHON 
Published: November 2009

Summary1. It is an uncontested paradigm that an adequate supply of the macronutrients nitrogen (N) and phosphorus (P) is critical for maintaining phytoplankton primary production in aquatic ecosystems; it has also been suggested that there is an optimal total N : total P ratio for this globally significant process.2. This ratio, normally assessed by chemical determination of the major dissolved N and P species, poses a dilemma: do chemical measurements actually reflect the bioavailable fraction of these nutrient pools? Accurate determination of the various N and P species and their fluxes into phytoplankton cells is notoriously difficult.3. To provide a possible solution to this difficulty, we engineered strains of the cyanobacterium Synechococcus sp. strain PCC 7942 that ‘report’ on N and P bioavailability via a bioluminescent signal. These strains were used to quantify, for the first time, bioavailable concentrations of these essential macronutrients in a freshwater lake.4. Only a small fraction (0.01–1%) of the chemically determined P may actually be bioavailable to this unicellular cyanobacterium and, by inference, to the phytoplankton community in general. In contrast, bioavailable N comprises most of the dissolved N pool. Consequently, bioavailable N : P ratios based on these assays are higher then those based on chemical determinations, indicating that P limitation in Lake Kinneret is more extensive then previously thought.
Characterizing dispersal patterns in a threatened seabird with limited genetic structure
Authors: HALL LAURIE A. , PALSBØLL PER J. , BEISSINGER STEVEN R. , HARVEY JAMES T. , BÉRUBÉ MARTINE , RAPHAEL MARTIN G. , NELSON S. KIM , GOLIGHTLY RICHARD T. , MCFARLANE‐TRANQUILLA LAURA , NEWMAN SCOTT H. , PEERY M. ZACHARIAH 
Published: November 2009

AbstractGenetic assignment methods provide an appealing approach for characterizing dispersal patterns on ecological time scales, but require sufficient genetic differentiation to accurately identify migrants and a large enough sample size of migrants to, for example, compare dispersal between sexes or age classes. We demonstrate that assignment methods can be rigorously used to characterize dispersal patterns in a marbled murrelet (Brachyramphus marmoratus) population from central California that numbers approximately 600 individuals and is only moderately differentiated (FST∼ 0.03) from larger populations to the north. We used coalescent simulations to select a significance level that resulted in a low and approximately equal expected number of type I and II errors and then used this significance level to identify a population of origin for 589 individuals genotyped at 13 microsatellite loci. The proportion of migrants in central California was greatest during winter when 83% of individuals were classified as migrants compared to lower proportions during the breeding (6%) and post‐breeding (8%) seasons. Dispersal was also biased toward young and female individuals, as is typical in birds. Migrants were rarely members of parent‐offspring pairs, suggesting that they contributed few young to the central California population. A greater number of migrants than expected under equilibrium conditions, a lack of individuals with mixed ancestry, and a small number of potential source populations (two), likely allowed us to use assignment methods to rigorously characterize dispersal patterns for a population that was larger and less differentiated than typically thought required for the identification of migrants.
Co‐evolution of multipartite interactions between an extended tmRNA tag and a robust Lon protease in Mycoplasma
Authors: Ge Zhiyun , Karzai A. Wali 
Published: November 2009

SummaryMessenger RNAs that lack in‐frame stop codons promote ribosome stalling and accumulation of aberrant and potentially harmful polypeptides. The SmpB‐tmRNA quality control system has evolved to solve problems associated with non‐stop mRNAs, by rescuing stalled ribosomes and directing the addition of a peptide tag to the C‐termini of the associated proteins, marking them for proteolysis. In Escherichia coli, the ClpXP system is the major contributor to disposal of tmRNA‐tagged proteins. We have shown that the AAA+ Lon protease can also degrade tmRNA‐tagged proteins, but with much lower efficiency. Here, we present a unique case of enhanced recognition and degradation of an extended Mycoplasma pneumoniae (MP) tmRNA tag by the MP‐Lon protease. We demonstrate that MP‐Lon can efficiently and selectively degrade MP‐tmRNA‐tagged proteins. Most significantly, our studies reveal that the larger (27 amino acids long) MP‐tmRNA tag contains multiple discrete signalling motifs for efficient recognition and rapid degradation by Lon. We propose that higher‐affinity multipartite interactions between MP‐Lon and the extended MP‐tmRNA tag have co‐evolved from pre‐existing weaker interactions, as exhibited by Lon in E. coli, to better fulfil the function of MP‐Lon as the sole soluble cytoplasmic protease responsible for the degradation of tmRNA‐tagged proteins.
Active crustal shortening in NE Syria revealed by deformed terraces of the River Euphrates
Authors: Abou Romieh Mohammad , Westaway Rob , Daoud Mohamad , Radwan Yousef , Yassminh Rayan , Khalil Ahlam , Al‐Ashkar Abeer , Loughlin Susan , Arrell Katherine , Bridgland David 
Published: November 2009

AbstractThe Africa–Arabia plate boundary comprises the Red Sea oceanic spreading centre and the left‐lateral Dead Sea Fault Zone (DSFZ); however, previous work has indicated kinematic inconsistency between its continental and oceanic parts. The Palmyra Fold Belt (PFB) splays ENE from the DSFZ in SW Syria and persists for ∼400 km to the River Euphrates, but its significance within the regional pattern of active crustal deformation has hitherto been unclear. We report deformation of Euphrates terraces consistent with Quaternary right‐lateral transpression within the PFB, indicating anticlockwise rotation (estimated as 0.3° Ma−1 about 36.0°N 39.8°E) of the block between the PFB and the northern DSFZ relative to the Arabian Plate interior. The northern DSFZ is shown to be kinematically consistent with the combination of Euler vectors for the PFB and the Red Sea spreading, resolving the inconsistency previously evident. The SW PFB causes a significant earthquake hazard, previously unrecognized, to the city of Damascus.
North Arch volcanic fields near Hawaii are evidence favouring the restite‐root hypothesis for the origin of hotspot swells
Authors: Yamamoto Michiko , Morgan Jason Phipps 
Published: November 2009

AbstractA pronounced regional bathymetric swell is a common feature of oceanic hotspot volcanism. Recently, the hypothesis of a buoyant sublithospheric swell‐root has been favoured, the root being either a ‘refracted plume’ of hot, buoyant and hence low‐viscosity plume material embedded within surrounding higher viscosity asthenosphere, or a ‘restite‐root’ composed of hot and more viscous residues to hotspot melt‐extraction from the hottest central portion of the upwelling plume. In this article, we present numerical experiments that show that these two scenarios predict different flow and melting patterns whenever the plume passes beneath an obliquely oriented fracture zone where the base of the overriding lithosphere changes in thickness. We find that the restite‐root hypothesis predicts an asymmetric spatial pattern of persistent ‘arch volcanism’ strikingly similar to that found in the Hawaiian chain surrounding the Molokai Fracture Zone. In contrast, the ‘refracted plume’ hypothesis predicts more chaotic patterns quite different from the off‐chain pattern of Hawaiian volcanism.