bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sphingolipids involvement in plant endomembrane differentiation: the BY2 case
Authors: Aubert Anne , Marion Jessica , Boulogne Claire , Bourge Mickael , Abreu Susana , Bellec Yannick , Faure Jean‐Denis , Satiat‐Jeunemaitre Béatrice 
Published: January 2011

SummarySphingolipids play an essential role in the functioning of the secretory pathway in eukaryotic organisms. Their importance in the functional organization of plant cells has not been studied in any detail before. The sphingolipid synthesis inhibitor fumonisin B1 (FB1), a mycotoxin acting as a specific inhibitor of ceramide synthase, was tested for its effects on cell growth, cell polarity, cell shape, cell cycle and on the ultrastructure of BY2 cells. We used cell lines expressing different GFP‐tagged markers for plant cell compartments, as well as a Golgi marker fused to the photoconvertible protein Kaede. Light and electron microscopy, combined with flow cytometry, were applied to analyse the morphodynamics and architecture of compartments of the secretory pathway. The results indicate that FB1 treatment had severe effects on cell growth and cell shape, and induced a delay in cell division processes. The cell changes were accompanied by the formation of the endoplasmic reticulum (ER)‐derived tubular aggregates (FB1‐induced compartments), together with an inhibition of cargo transport from the ER to the Golgi apparatus. A change in polar localization of the auxin transporter PIN1 was also observed, but endocytic processes were little affected. Electron microscopy studies confirmed that molecular FB1 targets were distinct from brefeldin A (BFA) targets. We propose that the reported effects of inhibition of ceramide biosynthesis reflect the importance of sphingolipids during cell growth and establishment of cell polarity in higher plant cells, notably through their contribution to the functional organization of the ER or its differentiation into distinct compartments.
Cytokinin promotes flowering of Arabidopsis via transcriptional activation of the FT paralogue TSF
Authors: D’Aloia Maria , Bonhomme Delphine , Bouché Frédéric , Tamseddak Karim , Ormenese Sandra , Torti Stefano , Coupland George , Périlleux Claire 
Published: January 2011

SummaryCytokinins are involved in many aspects of plant growth and development, and physiological evidence also indicates that they have a role in floral transition. In order to integrate these phytohormones into the current knowledge of genetically defined molecular pathways to flowering, we performed exogenous treatments of adult wild type and mutant Arabidopsis plants, and analysed the expression of candidate genes. We used a hydroponic system that enables synchronous growth and flowering of Arabidopsis, and allows the precise application of chemicals to the roots for defined periods of time. We show that the application of N6‐benzylaminopurine (BAP) promotes flowering of plants grown in non‐inductive short days. The response to cytokinin treatment does not require FLOWERING LOCUS T (FT), but activates its paralogue TWIN SISTER OF FT (TSF), as well as FD, which encodes a partner protein of TSF, and the downstream gene SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1). Treatment of selected mutants confirmed that TSF and SOC1 are necessary for the flowering response to BAP, whereas the activation cascade might partially act independently of FD. These experiments provide a mechanistic basis for the role of cytokinins in flowering, and demonstrate that the redundant genes FT and TSF are differently regulated by distinct floral‐inducing signals.
Isolation and functional characterization of an influx silicon transporter in two pumpkin cultivars contrasting in silicon accumulation
Authors: Mitani Namiki , Yamaji Naoki , Ago Yukiko , Iwasaki Kozo , Ma Jian Feng 
Published: January 2011

SummaryA high accumulation of silicon (Si) is required for overcoming abiotic and biotic stresses, but the molecular mechanisms of Si uptake, especially in dicotyledonous species, is poorly understood. Herein, we report the identification of an influx transporter of Si in two Cucurbita moschata (pumpkin) cultivars greatly differing in Si accumulation, which are used for the rootstocks of bloom and bloomless Cucumis sativus (cucumber), respectively. Heterogeneous expression in both Xenopus oocytes and rice mutant defective in Si uptake showed that the influx transporter from the bloom pumpkin rootstock can transport Si, whereas that from the bloomless rootstock cannot. Analysis with site‐directed mutagenesis showed that, among the two amino acid residues differing between the two types of rootstocks, only changing a proline to a leucine at position 242 results in the loss of Si transport activity. Furthermore, all pumpkin cultivars for bloomless rootstocks tested have this mutation. The transporter is localized in all cells of the roots, and investigation of the subcellular localization with different approaches consistently showed that the influx Si transporter from the bloom pumpkin rootstock was localized at the plasma membrane, whereas the one from the bloomless rootstock was localized at the endoplasmic reticulum. Taken together, our results indicate that the difference in Si uptake between two pumpkin cultivars is probably the result of allelic variation in one amino acid residue of the Si influx transporter, which affects the subcellular localization and subsequent transport of Si from the external solution to the root cells.
The shade avoidance syndrome in Arabidopsis: a fundamental role for atypical basic helix–loop–helix proteins as transcriptional cofactors
Authors: Galstyan Anahit , Cifuentes‐Esquivel Nicolás , Bou‐Torrent Jordi , Martinez‐Garcia Jaime F. 
Published: January 2011

SummaryThe shade avoidance syndrome (SAS) refers to a set of plant responses aimed at anticipating eventual shading by potential competitors. The SAS is initiated after perception of nearby vegetation as a reduction in the red to far‐red ratio (R:FR) of the incoming light. Low R:FR light is perceived by the phytochromes, triggering dramatic changes in gene expression that, in seedlings, eventually result in an increased hypocotyl elongation to overgrow competitors. This response is inhibited by genes such as PHYTOCHROME RAPIDLY REGULATED 1 (PAR1), PAR2 and LONG HYPOCOTYL IN FR 1 (HFR1), which are transcriptionally induced by low R:FR. Although PAR1/PAR2 and HFR1 proteins belong to different groups of basic helix–loop–helix (bHLH) transcriptional regulators, they all lack a typical basic domain required for binding to E‐box and G‐box motifs in the promoter of target genes. By overexpressing derivatives of PAR1 and HFR1 we show that these proteins are actually transcriptional cofactors that do not need to bind DNA to directly regulate transcription. We conclude that protein–protein interactions involving the HLH domain of PAR1 and HFR1 are a fundamental aspect of the mechanism by which these proteins regulate gene expression, most likely through interaction with true transcription factors that do bind to the target genes and eventually unleash the observed SAS responses.
Arabidopsis SNARE protein SEC22 is essential for gametophyte development and maintenance of Golgi‐stack integrity
Authors: El‐Kasmi Farid , Pacher Tobias , Strompen Georg , Stierhof York‐Dieter , Müller Lena M. , Koncz Csaba , Mayer Ulrike , Jürgens Gerd 
Published: January 2011

SummaryMembrane traffic contributes to plant growth and development. However, the functional significance of SNARE proteins involved in membrane fusion of the early secretory pathway has not been explored with respect to plant development. Here we analyze the Arabidopsis v‐SNARE SEC22. Loss of SEC22 function impairs gametophyte development, as indicated by reciprocal crosses between wild‐type plants and plants heterozygous for T‐DNA insertions in the SEC22 gene. sec22 mutant pollen becomes abnormal during the bicellular stage, eventually giving rise to degenerated pollen grains. Most mutant embryo sacs fail to support embryogenesis and display unfused polar nuclei in their central cell. Immunolocalization by both light and electron microscopy revealed an association of mutant‐complementing Myc‐tagged SEC22 with the central and peripheral endoplasmic reticulum (ER). Ultrastructural analysis of developing sec22 mutant pollen demonstrated Golgi fragmentation and consumption. As a consequence, the plasma membrane‐targeted syntaxin SYP124 was retained in the ER. Our results suggest that SEC22 plays an essential role in early secretory traffic between the ER and the Golgi.
The Challenge of New Daily Persistent Headache
Authors: Evans Randolph W. , Seifert Tad D. 
Published: January 2011

(Headache 2011;51:145‐154)New daily persistent headache is a rare chronic daily headache of long duration characterized by the abrupt onset of persistent headache that generally develops over less than 3 days and does not remit. While it was initially thought to be a benign, self‐limiting disorder, further research has shown that a significant percentage of patients continue to suffer for many years, often experiencing pain that is refractory to treatment. This article reviews the symptoms, pathophysiology, diagnostic criteria, diagnostic testing, treatment, and prognosis.
Health‐related quality of life and postoperative recovery in fast‐track hysterectomy
Authors: WODLIN NINNIE BORENDAL , NILSSON LENA , KJØLHEDE PREBEN 
Published: January 2011

Abstract Objective. To determine whether health‐related quality of life (HRQoL) and postoperative recovery of women who undergo abdominal hysterectomy in a fast‐track program under general anesthesia (GA) differ from women who receive spinal anesthesia with intrathecal morphine (SA). Design. Secondary analysis from an open randomized controlled multicenter study. Setting. Five hospitals in south‐east Sweden. Population. One hundred and eighty women admitted for abdominal hysterectomy for benign disease were randomized; 162 completed the study, 80 with GA and 82 with SA. Methods. The HRQoL was measured preoperatively using the EuroQoL EQ‐5D and the Short‐Form‐36 health survey (SF‐36) questionnaires. The EQ‐5D was used daily for 1 week; thereafter, once weekly for 4 weeks and again 6 months after operation. The SF‐36 was completed at 5 weeks and 6 months. Dates of commencing and ending sick leave were registered. Main Outcome Measures. Changes in HRQoL; duration of sick leave. Results. The HRQoL improved significantly faster in women after SA than after GA. Sick leave was significantly shorter after SA than after GA (median 22.5 vs. 28 days). Recovery of HRQoL and duration of sick leave were negatively influenced by postoperative complications. In particular, the mental component of HRQoL was negatively affected by minor complications, even 6 months after the operation. Conclusions. Spinal anesthesia with intrathecal morphine provided substantial advantages in fast‐track abdominal hysterectomy for benign gynecological disorders by providing faster recovery and shorter sick leave compared with general anesthesia.
Mode of anesthesia and postoperative symptoms following abdominal hysterectomy in a fast‐track setting
Authors: WODLIN NINNIE BORENDAL , NILSSON LENA , ÅRESTEDT KRISTOFER , KJØLHEDE PREBEN ,   for the ‘GASPI’ Study Group
Published: January 2011

Abstract Objective. To determine whether postoperative symptoms differ between women who undergo abdominal benign hysterectomy in a fast‐track model under general anesthesia or spinal anesthesia with intrathecal morphine. Design. Secondary analysis from a randomized, open, multicenter study. Setting. Five hospitals in south‐east Sweden. Population. One‐hundred and eighty women scheduled for benign hysterectomy were randomized; 162 completed the study; 82 were allocated to spinal and 80 to general anesthesia. Methods. The Swedish Postoperative Symptoms Questionnaire, completed daily for 1 week and thereafter once a week until 5 weeks postoperatively. Main Outcome Measures. Occurrence, intensity and duration of postoperative symptoms. Results. Women who had hysterectomy under spinal anesthesia with intrathecal morphine experienced significantly less discomfort postoperatively compared with those who had the operation under general anesthesia. Spinal anesthesia reduced the need for opioids postoperatively. The most common symptoms were pain, nausea and vomiting, itching, drowsiness and fatigue. Abdominal pain, drowsiness and fatigue occurred significantly less often and with lower intensity among the spinal anesthesia group. Although postoperative nausea and vomiting was reported equally in the two groups, vomiting episodes were reported significantly more often during the first day after surgery in the spinal anesthesia group. Spinal anesthesia was associated with a higher prevalence of postoperative itching. Conclusions. Spinal anesthesia with intrathecal morphine carries advantages regarding postoperative symptoms and recovery following fast‐track abdominal hysterectomy.
Expression of Concern: Intrauterine insemination versus timed intercourse with clomiphene citrate in polycystic ovary syndrome: a randomized controlled trial
Authors: ABU HASHIM HATEM , OMBAR OSAMA , ABD ELAAL IBRAHIM 
Published: January 2011

Abstract Objective. To compare the efficacy of intrauterine insemination vs. timed intercourse with clomiphene citrate as a first‐line treatment for anovulatory infertility associated with polycystic ovary syndrome. Design. A randomized controlled trial following the CONSORT criteria. Setting. A university hospital and a private practice setting. Patients. 188 women (525 cycles) with polycystic ovary syndrome. Main outcome measures. Women received three consecutive cycles of ovulation induction with clomiphene citrate and intrauterine insemination (n=93, 259 cycles) or three consecutive cycles of clomiphene citrate with timed intercourse (n=95, 266 cycles). Outcome measures. Clinical pregnancy rate per cycle, number of growing and mature follicles, serum estradiol, endometrial thickness at the hCG day, serum progesterone, ovulation, miscarriage and live birth rates. Results. There were no differences between the two groups regarding the clinical pregnancy rate per cycle or per woman (8.49 vs. 7.89% and 23.6 vs. 22.1%; p=0.26 and p=0.33, respectively). Two twin pregnancies occurred in each group. Miscarriage and live birth rates were comparable (18.1 vs. 19% and 19.35 vs. 17.89%; p=0.31 and p=0.33, respectively). No ectopic, higher‐order pregnancies or cases of ovarian hyperstimulation syndrome occurred. No differences were found regarding the number of follicles, serum progesterone, ovulation rates, estradiol levels or endometrial thickness at the hCG day (7.7±0.4 vs. 7.5±0.6mm; p=0.54). Conclusions. Ovulation induction with clomiphene citrate and timed intercourse is as effective as that with intrauterine insemination for achieving pregnancy in polycystic ovary syndrome and could represent the initial treatment option, being less invasive and less expensive than intrauterine insemination.
Existence of Solution and Positive Solution for a Nonlinear Third-Order "Equation missing" -Point BVP
Authors: Sun Jian-Ping , Jin Fan-Xia 
Published: January 2011

AbstractIn this paper, we are concerned with the following nonlinear third-order "Equation missing"-point boundary value problem: "Equation missing", "Equation missing", "Equation missing", "Equation missing", "Equation missing". Some existence criteria of solution and positive solution are established by using the Schauder fixed point theorem. An example is also included to illustrate the importance of the results obtained.
Measures of Noncircularity and Fixed Points of Contractive Multifunctions
Authors: Marrero Isabel 
Published: January 2011

AbstractIn analogy to the Eisenfeld-Lakshmikantham measure of nonconvexity and the Hausdorff measure of noncompactness, we introduce two mutually equivalent measures of noncircularity for Banach spaces satisfying a Cantor type property, and apply them to establish a fixed point theorem of Darbo type for multifunctions. Namely, we prove that every multifunction with closed values, defined on a closed set and contractive with respect to any one of these measures, has the origin as a fixed point.
Fetal Cell Microchimerism and Cancer: A Nexus of Reproduction, Immunology, and Tumor Biology
Authors: Kallenbach Lisa R. , Johnson Kirby L. , Bianchi Diana W. 
Published: January 2011

AbstractFetal cell microchimerism (FCM) is the persistence of fetal cells in the maternal circulation and organs following pregnancy. Proposed hypotheses about the function of fetal cells in the pathogenesis of maternal cancer include promotion of tumorigenesis, protection by providing immunosurveillance, and participation in tissue repair. To date, studies of FCM and cancer have been primarily descriptive and quantitative. More research is needed to understand the cellular phenotype of the microchimeric cells in maternal tumors and whether they have a functional role. This research will require further study using a multidisciplinary approach, incorporating knowledge of the fetomaternal relationship, tumor biology, immunology, and clinical oncology. Cancer Res; 71(1); 8–12. ©2011 AACR.
Carminomycin I Is an Apoptosis Inducer That Targets the Golgi Complex in Clear Cell Renal Carcinoma Cells
Authors: Woldemichael Girma M. , Turbyville Thomas J. , Linehan W. Marston , McMahon James B. 
Published: January 2011

AbstractClear cell renal cell carcinoma (CCRCC) evolves due to mutations in the Von Hippel–Lindau (VHL) tumor suppressor gene. Although the loss of VHL enables survival and proliferation of CCRCC cells, it is also expected to introduce vulnerabilities that may be exploited for therapeutics discovery. To this end, we developed a high-throughput screen to identify small molecules derived from plants, microorganisms, and marine organisms to which CCRCC cells are sensitive. Screening over 8,000 compounds using this approach, we report here the identification of the microbially derived compound carminomycin I (CA) as an effective inhibitor of VHL-defective (VHL−/−) CCRCC cell proliferation. CA also induced apoptosis in CCRCC cells by a mechanism independent of p53 or hypoxia-inducible factor 2. We found that P-glycoprotein (P-gp) sequestered CA within the Golgi complex. Interestingly, Golgi sequestration was critical for the antiproliferative effects of CA and P-gp inhibitors abrogated this activity. Furthermore, CA induced cleavage of the Golgi protein p115 and the translocation of its C-terminal fragment to the nucleus. Finally, examination of the activity of the VHL-interacting Golgi protein, endoplasmic reticulum-Golgi intermediate compartment, ERGIC-53 showed that VHL could mediate protection from CA in CCRCC cells. Our natural product–based screening approach has revealed the P-gp–mediated localization of anticancer compounds within the Golgi in CCRCC cells as a potential strategy of targeting VHL-deficient CCRCC cells. Cancer Res; 71(1); 134–42. ©2011 AACR.
Novel Synthetic Antagonists of Canonical Wnt Signaling Inhibit Colorectal Cancer Cell Growth
Authors: Waaler Jo , Machon Ondrej , von Kries Jens Peter , Wilson Steven Ray , Lundenes Elsa , Wedlich Doris , Gradl Dietmar , Paulsen Jan Erik , Machonova Olga , Dembinski Jennifer L. , Dinh Huyen , Krauss Stefan 
Published: January 2011

Abstract
Canonical Wnt signaling is deregulated in several types of human cancer where it plays a central role in tumor cell growth and progression. Here we report the identification of 2 new small molecules that specifically inhibit canonical Wnt pathway at the level of the destruction complex. Specificity was verified in various cellular reporter systems, a Xenopus double-axis formation assay and a gene expression profile analysis. In human colorectal cancer (CRC) cells, the new compounds JW67 and JW74 rapidly reduced active β-catenin with a subsequent downregulation of Wnt target genes, including AXIN2, SP5, and NKD1. Notably, AXIN2 protein levels were strongly increased after compound exposure. Long-term treatment with JW74 inhibited the growth of tumor cells in both a mouse xenograft model of CRC and in ApcMin mice (multiple intestinal neoplasia, Min). Our findings rationalize further preclinical and clinical evaluation of these new compounds as novel modalities for cancer treatment. Cancer Res; 71(1); 197–205. ©2010 AACR.
Higher miRNA Tolerance in Immortal Li-Fraumeni Fibroblasts with Abrogated Interferon Signaling Pathway
Authors: Li Qunfang , Tainsky Michael A. 
Published: January 2011

Abstract
The IFN pathway is abrogated in fibroblasts from Li-Fraumeni syndrome (LFS) patients during spontaneous cellular immortalization, a necessary step in carcinogenesis. Microarray profiling of differentially expressed microRNAs (miRNA) revealed that most miRNAs were upregulated in IFN pathway–defective MDAH087-10 fibroblasts compared with MDAH087-N cells with relatively normal IFN signaling. Overexpression of Dicer, a critical enzyme in miRNA biogenesis, promoted cell growth and colony formation in MDAH087-10 cells. However, double-stranded miRNA produced by Dicer enhanced the expression of IFN-stimulated genes in MDAH087-N cells resulting in significant cell death and reduced cell growth. Furthermore, manipulation of the IFN pathway in immortal LFS fibroblasts through transcription factor IRF7 reversed their response to Dicer overexpression due to changed IFN pathway activity. Dicer overexpressing MDAH087-N cells contained lower levels of miRNA than vector control, and conversely much higher miRNA expression was detected in Dicer-transfected MDAH087-10 cells. Therefore, cells with a defective IFN pathway have a higher miRNA tolerance than cells with normal IFN pathway. This work indicates for the first time that the IFN pathway as mediated through the transcription factor IRF7 must be disrupted to permit miRNA upregulation to occur in early carcinogenesis. The IFN pathway appears to provide a checkpoint for miRNA level tolerance and its abrogation leads to cellular immortalization. Cancer Res; 71(1); 255–65. ©2010 AACR.
Activation and Involvement of Ral GTPases in Colorectal Cancer
Authors: Martin Timothy D. , Samuel Jonathan C. , Routh Elizabeth D. , Der Channing J. , Yeh Jen Jen 
Published: January 2011

Abstract
Current approaches to block KRAS oncogene function focus on inhibition of K-Ras downstream effector signaling. We evaluated the antitumor activity of selumetinib (AZD6244, ARRY-142886), a potent and selective MEK1/2 inhibitor, on a panel of colorectal carcinoma (CRC) cells and found no inhibition of KRAS mutant CRC cell anchorage-independent growth. Although AKT activity was elevated in KRAS mutant cells, and PI3K inhibition did impair the growth of MEK inhibitor-insensitive CRC cell lines, concurrent treatment with selumetinib did not provide additional antitumor activity. Therefore, we speculated that inhibition of the Ral guanine exchange factor (RalGEF) effector pathway may be a more effective approach for blocking CRC growth. RalGEFs are activators of the related RalA and RalB small GTPases and we found activation of both in CRC cell lines and patient tumors. Interfering RNA stable suppression of RalA expression reduced CRC tumor cell anchorage-independent growth, but surprisingly, stable suppression of RalB greatly enhanced soft agar colony size and formation frequency. Despite their opposing activities, both RalA and RalB regulation of anchorage-independent growth required interaction with RalBP1/RLIP76 and components of the exocyst complex. Interestingly, RalA interaction with the Exo84 but not Sec5 exocyst component was necessary for supporting anchorage-independent growth, whereas RalB interaction with Sec5 but not Exo84 was necessary for inhibition of anchorage-independent growth. We suggest that anti-RalA–selective therapies may provide an effective approach for KRAS mutant CRC. Cancer Res; 71(1); 206–15. ©2010 AACR.