bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective pharmacokinetic study of intravenous busulfan in hematopoietic stem cell transplantation in 25 children
Authors: Okamoto Yasuhiro , Nagatoshi Yoshihisa , Kosaka Yoshiyuki , Kikuchi Akira , Kato Shunichi , Kigasawa Hisato , Horikoshi Yasuo , Oda Megumi , Kaneda Makoto , Mori Tetsuya , Mugishima Hideo , Tsuchida Masahiro , Taniguchi Shuichi , Kawano Yoshifumi 
Published: February 2014

AbstractThe aim of this study was to prospectively evaluate the PK and safety of ivBU in 25 Japanese children (median age six yr; range, five months–17 yr) as one of a combination of drugs in a pretransplant regimen. The patients had acute leukemia (n = 14), CML (2), JMML (5), solid tumors (2), chronic granulomatous disease (1), or metachromatic leukodystrophy (1). Five different dose schedules were used according to the patient's ABW: <9 kg (1.0 mg/kg), 9 to <16 (1.2 mg/kg), 16–23 (1.1 mg/kg), >23–34 (0.95 mg/kg), and >34 kg of BW (0.8 mg/kg). Each dose was given over two h, and sample blood was drawn at nine or 11 separate points for analysis by gas chromatography–mass spectrometry. The AUC varied from 796 to 1905 μmol min/L, and 19 of the 25 patients (76%) remained within the target range without dose adjustment. Two were diagnosed with engraftment failure. Hepatic VOD developed in four, and only one of these showed high AUC (>1500 μmol min/L). Toxicities did not correlate with the BU level. Our data showed very similar PK to those in previous studies, and these dose schedules are applicable to Japanese children.
Reviewing GAA‐BAP shrimp farm data to determine whether certification lessens environmental impacts
Authors: Tlusty Michael F. , Tausig Heather 
Published: February 2014

AbstractThe sustainable seafood movement is over a decade old. It has done much to raise awareness regarding improper production and harvest of seafood and to derive a course to lessen the deleterious environmental impacts of this industry. Certification has been a key tool, yet few programmes have demonstrated comprehensive improvements. Here, the degree of aquaculture improvement through the implementation of certification was assessed using data from the Global Aquaculture Alliance (GAA) Best Aquaculture Practice (BAP) shrimp standard. An examination of 323 audits from 192 farms spanning 2005–2012 showed that overall, 35% of the farms were conditionally certified, indicating they had to improve prior to being certified. This version of the BAP shrimp farm audit had both compliance and scored components. Out of the 28 critical points, only six were in full compliance by all farms during all audits and hence provided no value to determine farm performance. Farms that passed the audit without compliance issues had a greater aggregate scored value than those that farms with noncompliances. However, performance‐based metrics exhibited few differences between the compliant and noncompliant farms. Overall, issues pertaining to water quality were a leading cause of farms being scored as noncompliant, although they were distributed among the seven different water quality parameters. Certification systems have not been designed specifically to demonstrate adherence to continual improvement. Because of this, and the multitude of factors with which a fully compliant farm needs to acquiesce, the specific means by which certification improves aquaculture and the overall value of improvement will remain challenging to demonstrate.
A Bayesian Hierarchical Downscaling Model for South-West Western Australia Rainfall
Authors: Song Yong , Li Yun , Bates Bryson , Wikle Christopher K. 
Published: February 2014

SummaryDownscaled rainfall projections from climate models are essential for many meteorological and hydrological applications. The technique presented utilizes an approach that efficiently parameterizes spatiotemporal dynamic models in terms of the close association between mean sea level pressure patterns and rainfall during winter over south-west Western Australia by means of Bayesian hierarchical modelling. This approach allows us to understand characteristics of the spatiotemporal variability of the mean sea level pressure patterns and the associated rainfall patterns. An application is presented to show the effectiveness of the technique to reconstruct present day rainfall and to predict future rainfall.
Spatial Two-Tissue Compartment Model for Dynamic Contrast-Enhanced Magnetic Resonance Imaging
Authors: Sommer Julia C. , Schmid Volker J. 
Published: February 2014

SummaryIn the quantitative analysis of dynamic contrast-enhanced magnetic resonance imaging compartment models allow the uptake of contrast medium to be described with biologically meaningful kinetic parameters. As simple models often fail to describe adequately the observed uptake behaviour, more complex compartment models have been proposed. However, the non-linear regression problem arising from more complex compartment models often suffers from parameter redundancy. We incorporate spatial smoothness on the kinetic parameters of a two-tissue compartment model by imposing Gaussian Markov random-field priors on them. We analyse to what extent this spatial regularization helps to avoid parameter redundancy and to obtain stable parameter point estimates per voxel. Choosing a full Bayesian approach, we obtain posteriors and point estimates by running Markov chain Monte Carlo simulations. The approach proposed is evaluated for simulated concentration time curves as well as for in vivo data from a breast cancer study.
Quantification of capillary blood cell flow using reflectance confocal microscopy
Authors: Cinotti E. , Gergelé L. , Perrot J. L. , Dominé A. , Labeille B. , Borelli P. , Cambazard F. 
Published: February 2014

Background/purposeIn vivo reflectance confocal microscopy (IVCM) is a new tool for skin microcirculation. However, the measure of quantitative blood cell flow (QBCF) has not been standardized. We studied the inter‐investigator and the intra‐capillary reproducibility of the manual measure of QBCF on IVCM videos and investigated if a software program might help measure QBCF and be sensitive to vascular occlusion tests.MethodsThe inter‐investigator reproducibility of the manual QBCF was evaluated on 107 videos. The intra‐capillary reproducibility of QBCF measured manually and by 2 semi‐automatic procedures based on Image J software analysis was evaluated on 19 capillaries. One of the semi‐automatic methods (peaks of luminous intensity) was also used to measure the QBCF during vascular occlusion tests.ResultsThe manual measure did not show a good inter‐investigator reproducibility (Pearson's coefficient <0.5). The ‘peaks of luminous intensity’ method was found to have a good intra‐capillary reproducibility and to be sensitive to vascular occlusion.ConclusionDifferently from the manual count, the count of peaks of luminous intensity by Image J software seems to be promising to measure QBCF. The future is to create software allowing for real‐time measure of the QBCF based on the peaks of luminous intensity inside the capillaries recorded by IVCM.
Repeated folding stress‐induced morphological changes in the dermal equivalent
Authors: Arai Koji Y. , Sugimoto Mami , Ito Kanako , Ogura Yuki , Akutsu Nobuko , Amano Satoshi , Adachi Eijiro , Nishiyama Toshio 
Published: February 2014

Background/purposeRepeated mechanical stresses applied to the same region of the skin are thought to induce morphological changes known as wrinkle. However, the underlying mechanisms are not fully understood. To study the mechanisms, we examined effects of repeated mechanical stress on the dermal equivalent.MethodsWe developed a novel device to apply repeated folding stress to the dermal equivalent. After applying the mechanical stress, morphological changes of the dermal equivalent and expression of several genes related to extracellular matrix turn over and cell contraction were examined.ResultsThe repeated folding stress induced a noticeable decrease in the width of the dermal equivalent. The mechanical stress altered orientations of collagen fibrils. Hydroxyproline contents, dry weights and cell viability of the dermal equivalents were not affected by the mechanical stress. On the other hand, Rho‐associated coiled‐coil‐containing kinase (ROCK) specific inhibitor Y27632 completely suppressed the decrease in the width of the dermal equivalent.ConclusionThe present results revealed that either degradation of collagen or changes in the number of cells were not responsible for the decrease in the width of the dermal equivalent and indicate that the repeated mechanical stress induces unidirectional contraction in the dermal equivalent through the RhoA‐ROCK signaling pathway.
Compositional changes of human hair melanin resulting from bleach treatment investigated by nanoscale secondary ion mass spectrometry
Authors: Kojima Toru , Yamada Hiromi , Isobe Mitsuru , Yamamoto Toshihiko , Takeuchi Miyuki , Aoki Dan , Matsushita Yasuyuki , Fukushima Kazuhiko 
Published: February 2014

Background/purposeIt is important to understand the influence of bleach treatment on human hair because it is one of the most important chemical treatments in hair cosmetic processes. A comparison of the elemental composition of melanin between virgin hair and bleached hair would provide important information about the structural changes of melanin. To investigate the elemental composition of melanin granules in virgin black hair and bleached hair, these hair cross‐sections are analyzed by using a nanoscale secondary ion mass spectrometry (NanoSIMS).MethodsThe virgin black hair and bleached hair samples were embedded in resin and smooth hair cross‐sections were obtained using an ultramicrotome. NanoSIMS measurements were performed using a Cs+ primary ion beam to detect negative secondary ions.ResultsMore intensive 16O− ions were detected from the melanin granules of bleached hair than from those of virgin black hair in NanoSIMS 16O− ion image. In addition, it was indicated that 16O− ion intensity and 16O‐/12C14N− ion intensity ratio of melanin granules in bleached hair were higher than those in virgin black hair.ConclusionNanoscale secondary ion mass spectrometry analysis of the cross‐sections of virgin black hair and bleached hair indicated that the oxygen content in melanin granules was increased by bleach treatment.
SHUGOSHINs and PATRONUS protect meiotic centromere cohesion in Arabidopsis thaliana
Authors: Zamariola Linda , De Storme Nico , Vannerum Katrijn , Vandepoele Klaas , Armstrong Susan J. , Franklin F. Christopher H. , Geelen Danny 
Published: February 2014

SummaryIn meiosis, chromosome cohesion is maintained by the cohesin complex, which is released in a two‐step manner. At meiosis I, the meiosis‐specific cohesin subunit Rec8 is cleaved by the protease Separase along chromosome arms, allowing homologous chromosome segregation. Next, in meiosis II, cleavage of the remaining centromere cohesin results in separation of the sister chromatids. In eukaryotes, protection of centromeric cohesion in meiosis I is mediated by SHUGOSHINs (SGOs). The Arabidopsis genome contains two SGO homologs. Here we demonstrate that Atsgo1 mutants show a premature loss of cohesion of sister chromatid centromeres at anaphase I and that AtSGO2 partially rescues this loss of cohesion. In addition to SGOs, we characterize PATRONUS which is specifically required for the maintenance of cohesion of sister chromatid centromeres in meiosis II. In contrast to the Atsgo1 Atsgo2 double mutant, patronus T‐DNA insertion mutants only display loss of sister chromatid cohesion after meiosis I, and additionally show disorganized spindles, resulting in defects in chromosome segregation in meiosis. This leads to reduced fertility and aneuploid offspring. Furthermore, we detect aneuploidy in sporophytic tissue, indicating a role for PATRONUS in chromosome segregation in somatic cells. Thus, ploidy stability is preserved in Arabidopsis by PATRONUS during both meiosis and mitosis.
Functional analysis of chimeric lysin motif domain receptors mediating Nod factor‐induced defense signaling in Arabidopsis thaliana and chitin‐induced nodulation signaling in Lotus japonicus
Authors: Wang Wei , Xie Zhi‐Ping , Staehelin Christian 
Published: February 2014

SummaryThe expression of chimeric receptors in plants is a way to activate specific signaling pathways by corresponding signal molecules. Defense signaling induced by chitin from pathogens and nodulation signaling of legumes induced by rhizobial Nod factors (NFs) depend on receptors with extracellular lysin motif (LysM) domains. Here, we constructed chimeras by replacing the ectodomain of chitin elicitor receptor kinase 1 (AtCERK1) of Arabidopsis thaliana with ectodomains of NF receptors of Lotus japonicus (LjNFR1 and LjNFR5). The hybrid constructs, named LjNFR1–AtCERK1 and LjNFR5–AtCERK1, were expressed in cerk1‐2, an A. thaliana CERK1 mutant lacking chitin‐induced defense signaling. When treated with NFs from Rhizobium sp. NGR234, cerk1‐2 expressing both chimeras accumulated reactive oxygen species, expressed chitin‐responsive defense genes and showed increased resistance to Fusarium oxysporum. In contrast, expression of a single chimera showed no effects. Likewise, the ectodomains of LjNFR1 and LjNFR5 were replaced by those of OsCERK1 (Oryza sativa chitin elicitor receptor kinase 1) and OsCEBiP (O. sativa chitin elicitor‐binding protein), respectively. The chimeras, named OsCERK1–LjNFR1 and OsCEBiP–LjNFR5, were expressed in L. japonicus NF receptor mutants (nfr1‐1; nfr5‐2) carrying a GUS (β‐glucuronidase) gene under the control of the NIN (nodule inception) promoter. Upon chitin treatment, GUS activation reflecting nodulation signaling was observed in the roots of NF receptor mutants expressing both chimeras, whereas a single construct was not sufficient for activation. Hence, replacement of ectodomains in LysM domain receptors provides a way to specifically trigger NF‐induced defense signaling in non‐legumes and chitin‐induced nodulation signaling in legumes.
The tomato mutation nxd1 reveals a gene necessary for neoxanthin biosynthesis and demonstrates that violaxanthin is a sufficient precursor for abscisic acid biosynthesis
Authors: Neuman Hadar , Galpaz Navot , Cunningham Francis X. , Zamir Dani , Hirschberg Joseph 
Published: February 2014

SummaryCarotenoid pigments are indispensable for plant life. They are synthesized within plastids where they provide essential functions in photosynthesis. Carotenoids serve as precursors for the synthesis of the strigolactone phytohormones, which are made from β‐carotene, and of abscisic acid (ABA), which is produced from certain xanthophylls. Despite the significant progress that has been made in our understanding of the carotenoid biosynthesis pathway, the synthesis of the xanthophyll neoxanthin has remained unknown. We report here on the isolation of a tomato (Solanum lycopersicum) mutant, neoxanthin‐deficient 1 (nxd1), which lacks neoxanthin, and on the cloning of a gene that is necessary for neoxanthin synthesis in both tomato and Arabidopsis. The locus nxd1 encodes a gene of unknown function that is conserved in all higher plants. The activity of NXD1 is essential but cannot solely support neoxanthin synthesis. Lack of neoxanthin does not significantly reduce the fitness of tomato plants in cultivated field conditions and does not impair the synthesis of ABA, suggesting that in tomato violaxanthin is a sufficient precursor for ABA production in vivo.
Pollen tube NAD(P)H oxidases act as a speed control to dampen growth rate oscillations during polarized cell growth
Authors: Lassig Roman , Gutermuth Timo , Bey Till D. , Konrad Kai R. , Romeis Tina 
Published: February 2014

SummaryReactive oxygen species (ROS) produced by NAD(P)H oxidases play a central role in plant stress responses and development. To better understand the function of NAD(P)H oxidases in plant development, we characterized the Arabidopsis thaliana NAD(P)H oxidases RBOHH and RBOHJ. Both proteins were specifically expressed in pollen and dynamically targeted to distinct and overlapping plasma membrane domains at the pollen tube tip. Functional loss of RBOHH and RBOHJ in homozygous double mutants resulted in reduced fertility. Analyses of pollen tube growth revealed remarkable differences in growth dynamics between Col–0 and rbohh–1 rbohj–2 pollen tubes. Growth rate oscillations of rbohh–1 rbohj–2 pollen tubes showed strong fluctuations in amplitude and frequency, ultimately leading to pollen tube collapse. Prior to disintegration, rbohh–1 rbohj–2 pollen tubes exhibit high‐frequency growth oscillations, with significantly elevated growth rates, suggesting that an increase in the rate of cell‐wall exocytosis precedes pollen tube collapse. Time‐lapse imaging of exocytic dynamics revealed that NAD(P)H oxidases slow down pollen tube growth to coordinate the rate of cell expansion with the rate of exocytosis, thereby dampening the amplitude of intrinsic growth oscillations. Using the Ca2+ reporter Yellow Cameleon 3.6, we demonstrate that high‐amplitude growth rate oscillations in rbohh–1 rbohj–2 pollen tubes are correlated with growth‐dependent Ca2+ bursts. Electrophysiological experiments involving double mutant pollen tubes and pharmacological treatments also showed that ROS influence K+ homeostasis. Our results indicate that, by limiting pollen tube growth, ROS produced by NAD(P)H oxidases modulate the amplitude and frequency of pollen tube growth rate oscillations.
TaADF7, an actin‐depolymerizing factor, contributes to wheat resistance against Puccinia striiformis f. sp. tritici
Authors: Fu Yanping , Duan Xiaoyuan , Tang Chunlei , Li Xiaorui , Voegele Ralf T. , Wang Xiaojie , Wei Guorong , Kang Zhensheng 
Published: February 2014

SummaryThe actin cytoskeleton is involved in plant defense responses; however, the role of the actin‐depolymerizing factor (ADF) family, which regulates actin cytoskeletal dynamics, in plant disease resistance, is largely unknown. Here, we characterized a wheat (Triticum aestivum) ADF gene, TaADF7, with three copies located on chromosomes 1A, 1B, and 1D, respectively. All three copies encoded the same protein, although there were variations in 19 nucleotide positions in the open reading frame. Transcriptional expression of the three TaADF7 copies were all sharply elevated in response to avirulent Puccinia striiformis f. sp. tritici (Pst) infection, with similar expression patterns. TaADF7 regulated the actin cytoskeletal dynamics by targeting the actin cytoskeleton to execute actin binding/severing activities. When the TaADF7 copies were all silenced by virus‐induced gene silencing, the growth of Pst hypha increased and sporadic urediniospores were observed, as compared with control plants, upon inoculation with avirulent Pst. In addition, the accumulation of reactive oxygen species (ROS) and the hypersensitive response (HR) were greatly weakened, whereas cytochalasin B partially rescued the HR in TaADF7 knock‐down plants. Together, these findings suggest that TaADF7 is likely to contribute to wheat resistance against Pst infection by modulating the actin cytoskeletal dynamics to influence ROS accumulation and the HR.
Cytokinin signaling stabilizes the response activator ARR1
Authors: Kurepa Jasmina , Li Yan , Smalle Jan A. 
Published: February 2014

SummaryThe cytokinins play essential roles in the development and environmental responses of higher plants. Cytokinin signaling leads to the phosphorylation‐dependent activation of two classes of Arabidopsis response regulators (RRs): the type‐B RR (RRB) transcriptional activators that promote the expression of cytokinin response genes and the type‐A RRs (RRAs) that are encoded by primary cytokinin response genes and function as response inhibitors. We show that cytokinin signaling increases the abundance of ARR1, a ubiquitously expressed RRB, by preventing its degradation by the 26S proteasome. We also show that the RRAs act to suppress ARR1 accumulation, thus providing an explanation for their inhibitory action in cytokinin signaling. Collectively, our results reveal an additional regulatory mechanism in the cytokinin response pathway that involves the cytokinin‐dependent stability control of a major RRB response activator.
Consequences of state transitions on the structural and functional organization of Photosystem I in the green alga Chlamydomonas reinhardtii
Authors: Drop Bartlomiej , Yadav K.N. Sathish , Boekema Egbert J. , Croce Roberta 
Published: February 2014

SummaryState transitions represent a photoacclimation process that regulates the light‐driven photosynthetic reactions in response to changes in light quality/quantity. It balances the excitation between photosystem I (PSI) and II (PSII) by shuttling LHCII, the main light‐harvesting complex of green algae and plants, between them. This process is particularly important in Chlamydomonas reinhardtii in which it is suggested to induce a large reorganization in the thylakoid membrane. Phosphorylation has been shown to be necessary for state transitions and the LHCII kinase has been identified. However, the consequences of state transitions on the structural organization and the functionality of the photosystems have not yet been elucidated. This situation is mainly because the purification of the supercomplexes has proved to be particularly difficult, thus preventing structural and functional studies. Here, we have purified and analysed PSI and PSII supercomplexes of C. reinhardtii in states 1 and 2, and have studied them using biochemical, spectroscopic and structural methods. It is shown that PSI in state 2 is able to bind two LHCII trimers that contain all four LHCII types, and one monomer, most likely CP29, in addition to its nine Lhcas. This structure is the largest PSI complex ever observed, having an antenna size of 340 Chls/P700. Moreover, all PSI‐bound Lhcs are efficient in transferring energy to PSI. A projection map at 20 Å resolution reveals the structural organization of the complex. Surprisingly, only LHCII type I, II and IV are phosphorylated when associated with PSI, while LHCII type III and CP29 are not, but CP29 is phosphorylated when associated with PSII in state2.
Kinase activity and calmodulin binding are essential for growth signaling by the phytosulfokine receptor PSKR1
Authors: Hartmann Jens , Fischer Cornelia , Dietrich Petra , Sauter Margret 
Published: February 2014

SummaryThe cell growth‐promoting peptide phytosulfokine (PSK) is perceived by leucine‐rich repeat (LRR) receptor kinases. To elucidate PSK receptor function we analyzed PSKR1 kinase activity and binding to Ca2+ sensors and evaluated the contribution of these activities to growth control in planta. Ectopically expressed PSKR1 was capable of auto‐ and transphosphorylation. Replacement of a conserved lysine within the ATP‐binding region by a glutamate resulted in the inhibition of auto‐ and transphosphorylation kinase activities. Expression of the kinase‐inactive PSKR1(K762E) receptor in the pskr null background did not restore root or shoot growth. Instead, the mutant phenotype was enhanced suggesting that the inactive receptor protein exerts growth‐inhibitory activity. Bioinformatic analysis predicted a putative calmodulin (CaM)‐binding site within PSKR1 kinase subdomain VIa. Bimolecular fluorescence complementation analysis demonstrated that PSKR1 binds to all isoforms of CaM, more weakly to the CaM‐like protein CML8 but apparently not to CML9. Mutation of a conserved tryptophan (W831S) within the predicted CaM‐binding site strongly reduced CaM binding. Expression of PSKR1(W831S) in the pskr null background resulted in growth inhibition that was similar to that of the kinase‐inactive receptor. We conclude that PSK signaling requires Ca2+/CaM binding and kinase activity of PSKR1 in planta. We further propose that the inactivated kinase interferes with other growth‐promoting signaling pathway(s).