bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploiting maximal dependence decomposition to identify conserved motifs from a group of aligned signal sequences
Authors: Lee Tzong-Yi , Lin Zong-Qing , Hsieh Sheng-Jen , Bretaña Neil Arvin , Lu Cheng-Tsung 
Published: May 2011

Abstract
Summary: Bioinformatics research often requires conservative analyses of a group of sequences associated with a specific biological function (e.g. transcription factor binding sites, micro RNA target sites or protein post-translational modification sites). Due to the difficulty in exploring conserved motifs on a large-scale sequence data involved with various signals, a new method, MDDLogo, is developed. MDDLogo applies maximal dependence decomposition (MDD) to cluster a group of aligned signal sequences into subgroups containing statistically significant motifs. In order to extract motifs that contain a conserved biochemical property of amino acids in protein sequences, the set of 20 amino acids is further categorized according to their physicochemical properties, e.g. hydrophobicity, charge or molecular size. MDDLogo has been demonstrated to accurately identify the kinase-specific substrate motifs in 1221 human phosphorylation sites associated with seven well-known kinase families from Phospho.ELM. Moreover, in a set of plant phosphorylation data-lacking kinase information, MDDLogo has been applied to help in the investigation of substrate motifs of potential kinases and in the improvement of the identification of plant phosphorylation sites with various substrate specificities. In this study, MDDLogo is comparable with another well-known motif discover tool, Motif-X.
Contact: francis@saturn.yzu.edu.tw
Supplementary information: Supplementary data are available at Bioinformatics online.
An Evaluation of Using Population Pharmacokinetic Models to Estimate Pharmacodynamic Parameters for Propofol and Bispectral Index in Children
Authors: Coppens Marc J. , Eleveld Douglas J. , Proost Johannes H. , Marks Luc A. M. , Van Bocxlaer Jan F. P. , Vereecke Hugo , Absalom Anthony R. , Struys Michel M. R. F. 
Published: May 2011

Background
To study propofol pharmacodynamics in a clinical setting a pharmacokinetic model must be used to predict drug plasma concentrations. Some investigators use a population pharmacokinetic model from existing literature and minimize the pharmacodynamic objective function. The purpose of the study was to determine whether this method selects the best-performing pharmacokinetic model in a set and provides accurate estimates of pharmacodynamic parameters in models for bispectral index in children after propofol administration.

Methods
Twenty-eight children classified as American Society of Anesthesiologists physical status 1 who were given general anesthesia for dental treatment were studied. Anesthesia was given using target-controlled infusion of propofol based on the Kataria model. Propofol target plasma concentration was 7 μg/ml for 15 min, followed by 1 μg/ml for 15 min or until signs of awakening, followed by 5 μg/ml for 15 min. Venous blood samples were taken 1, 2, 5, 10, and 15 min after each change in target. A classic pharmacokinetic-pharmacodynamic model was estimated, and the methodology of other studies was duplicated using pharmacokinetic models from the literature and (re-)estimating the pharmacodynamic models.

Results
There is no clear relationship between pharmacokinetic precision and the pharmacodynamic objective function. Low pharmacodynamic objective function values are not associated with accurate estimation of the pharmacodynamic parameters when the pharmacokinetic model is taken from other sources.

Conclusion
Minimization of the pharmacodynamic objective function does not select the most accurate pharmacokinetic model. Using population pharmacokinetic models from the literature instead of the 'true' pharmacokinetic model can lead to better predictions of bispectral index while incorrectly estimating the pharmacodynamic parameters.
Spinal Anesthesia in Infant Rats
Authors: Yahalom Barak , Athiraman Umeshkumar , Soriano Sulpicio G. , Zurakowski David , Carpino Elizabeth A. , Corfas Gabriel , Berde Charles B. 
Published: May 2011

Background
Previous studies in infant rats and case-control studies of human infants undergoing surgery have raised concerns about potential neurodevelopmental toxicities of general anesthesia. Spinal anesthesia is an alternative to general anesthesia for some infant surgeries. To test for potential toxicity, a spinal anesthesia model in infant rats was developed.

Methods
Rats of postnatal ages 7, 14, and 21 days were assigned to no treatment, 1% isoflurane for either 1 h or 6 h, or lumbar spinal injection of saline or bupivacaine at doses of 3.75 mg/kg (low dose) or 7.5 mg/kg (high dose). Subgroups of animals underwent neurobehavioral testing and blood gas analysis. Brain and lumbar spinal cord sections were examined for apoptosis using cleaved caspase-3 immunostaining. The lumbar spinal cord was examined histologically.Rats exposed to spinal or general anesthesia as infants underwent Rotarod testing of motor performance as adults. Data were analyzed using ANOVA with general linear models, Friedman tests, and Mann-Whitney U tests, as appropriate.

Results
Bupivacaine 3.75 mg/kg was effective for spinal anesthesia in all age groups. Impairments in sensory and motor function recovered in 40-60 min. Blood gases were similar among groups. Brain and spinal cord apoptosis increased in rats receiving 6 h of 1% isoflurane, but not among the other treatments. All groups showed intact motor performance at adulthood.

Conclusions
Spinal anesthesia is technically feasible in infant rats and appears benign in terms of neuroapoptotic and neuromotor sequelae.
Infectious Complications in Pediatric Acute Liver Failure
Authors: Godbole Gauri , Shanmugam Naresh , Dhawan Anil , Verma Anita 
Published: May 2011

ABSTRACTObjectives:Acute liver failure (ALF) is rare in children but carries high mortality. Infectious complications (IC) in adults are an important cause of mortality; however, there are few data in the pediatric population. The aim of the study was to determine the incidence of IC and their effects on the outcome in children with ALF.Materials and Methods:The present study is a retrospective review of the case records of children presenting with ALF to our center. All patients with ALF received antibiotics and antifungal as prophylaxis from day 1 and high‐dose acyclovir was given to neonates only (stopped when herpes simplex was ruled out). Biochemical parameters, duration of ventilation and intensive care, overall hospital stay, and patient outcome were compared between patients with IC and non‐IC.Results:A total of 145 children (78 boys), median (range) age 4.22 (1 day–16 years) years, were studied. Thirty‐seven of 145 (25%) patients had proven IC. The predominant infections included 14 episodes of bacteremia in 13 patients and lower respiratory tract infection and urinary tract infection in 10 and 8 patients, respectively. IC occurred in patients after a median (range) duration of 16 (0–54) days of admission. Median (range) duration of hospital stay in patients with IC was 38 (1–201) days and was significantly higher than in those without IC (10 [1–74] days), P < 0.0001. Overall mortality was 21% (31), of which 7% (11) was from the IC group and 14% (20) from the non‐IC group; the difference was not statistically significant.Conclusions:Infections were more frequent after 2 weeks of admission. Patients with sepsis had longer hospital stays and prolonged ventilation. Invasive fungal infections were rare in pediatric ALF with adequate doses of antifungal prophylaxis.
Clathrin Mediates Endocytosis and Polar Distribution of PIN Auxin Transporters inArabidopsis
Authors: Kitakura Saeko , Vanneste Steffen , Robert Stéphanie , Löfke Christian , Teichmann Thomas , Tanaka Hirokazu , Friml Jiří 
Published: May 2011

AbstractEndocytosis is a crucial mechanism by which eukaryotic cells internalize extracellular and plasma membrane material, and it is required for a multitude of cellular and developmental processes in unicellular and multicellular organisms. In animals and yeast, the best characterized pathway for endocytosis depends on the function of the vesicle coat protein clathrin. Clathrin-mediated endocytosis has recently been demonstrated also in plant cells, but its physiological and developmental roles remain unclear. Here, we assessed the roles of the clathrin-mediated mechanism of endocytosis in plants by genetic means. We interfered with clathrin heavy chain (CHC) function through mutants and dominant-negative approaches in Arabidopsis thaliana and established tools to manipulate clathrin function in a cell type–specific manner. The chc2 single mutants and dominant-negative CHC1 (HUB) transgenic lines were defective in bulk endocytosis as well as in internalization of prominent plasma membrane proteins. Interference with clathrin-mediated endocytosis led to defects in constitutive endocytic recycling of PIN auxin transporters and their polar distribution in embryos and roots. Consistent with this, these lines had altered auxin distribution patterns and associated auxin transport-related phenotypes, such as aberrant embryo patterning, imperfect cotyledon specification, agravitropic growth, and impaired lateral root organogenesis. Together, these data demonstrate a fundamental role for clathrin function in cell polarity, growth, patterning, and organogenesis in plants.
The Jasmonate-ZIM-Domain Proteins Interact with the WD-Repeat/bHLH/MYB Complexes to Regulate Jasmonate-Mediated Anthocyanin Accumulation and Trichome Initiation inArabidopsis thaliana
Authors: Qi Tiancong , Song Susheng , Ren Qingcuo , Wu Dewei , Huang Huang , Chen Yan , Fan Meng , Peng Wen , Ren Chunmei , Xie Daoxin 
Published: May 2011

AbstractJasmonates (JAs) mediate plant responses to insect attack, wounding, pathogen infection, stress, and UV damage and regulate plant fertility, anthocyanin accumulation, trichome formation, and many other plant developmental processes. Arabidopsis thaliana Jasmonate ZIM-domain (JAZ) proteins, substrates of the CORONATINE INSENSITIVE1 (COI1)–based SCFCOI1 complex, negatively regulate these plant responses. Little is known about the molecular mechanism for JA regulation of anthocyanin accumulation and trichome initiation. In this study, we revealed that JAZ proteins interact with bHLH (Transparent Testa8, Glabra3 [GL3], and Enhancer of Glabra3 [EGL3]) and R2R3 MYB transcription factors (MYB75 and Glabra1), essential components of WD-repeat/bHLH/MYB transcriptional complexes, to repress JA-regulated anthocyanin accumulation and trichome initiation. Genetic and physiological evidence showed that JA regulates WD-repeat/bHLH/MYB complex-mediated anthocyanin accumulation and trichome initiation in a COI1-dependent manner. Overexpression of the MYB transcription factor MYB75 and bHLH factors (GL3 and EGL3) restored anthocyanin accumulation and trichome initiation in the coi1 mutant, respectively. We speculate that the JA-induced degradation of JAZ proteins abolishes the interactions of JAZ proteins with bHLH and MYB factors, allowing the transcriptional function of WD-repeat/bHLH/MYB complexes, which subsequently activate respective downstream signal cascades to modulate anthocyanin accumulation and trichome initiation.
Microtubule-Associated Proteins MAP65-1 and MAP65-2 Positively Regulate Axial Cell Growth in EtiolatedArabidopsisHypocotyls
Authors: Lucas Jessica R. , Courtney Stephanie , Hassfurder Mathew , Dhingra Sonia , Bryant Adam , Shaw Sidney L. 
Published: May 2011

AbstractThe Arabidopsis thaliana MAP65-1 and MAP65-2 genes are members of the larger eukaryotic MAP65/ASE1/PRC gene family of microtubule-associated proteins. We created fluorescent protein fusions driven by native promoters that colocalized MAP65-1 and MAP65-2 to a subset of interphase microtubule bundles in all epidermal hypocotyl cells. MAP65-1 and MAP65-2 labeling was highly dynamic within microtubule bundles, showing episodes of linear extension and retraction coincident with microtubule growth and shortening. Dynamic colocalization of MAP65-1/2 with polymerizing microtubules provides in vivo evidence that plant cortical microtubules bundle through a microtubule-microtubule templating mechanism. Analysis of etiolated hypocotyl length in map65-1 and map65-2 mutants revealed a critical role for MAP65-2 in modulating axial cell growth. Double map65-1 map65-2 mutants showed significant growth retardation with no obvious cell swelling, twisting, or morphological defects. Surprisingly, interphase microtubules formed coaligned arrays transverse to the plant growth axis in dark-grown and GA4-treated light-grown map65-1 map65-2 mutant plants. We conclude that MAP65-1 and MAP65-2 play a critical role in the microtubule-dependent mechanism for specifying axial cell growth in the expanding hypocotyl, independent of any mechanical role in microtubule array organization.
The biosynthesis of Caryophyllaceae‐like cyclic peptides in Saponaria vaccaria L. from DNA‐encoded precursors
Authors: Condie Janet A. , Nowak Goska , Reed Darwin W. , Balsevich J. John , Reaney Martin J. T. , Arnison Paul G. , Covello Patrick S. 
Published: May 2011

SummaryCyclic peptides (CPs) are produced in a very wide range of taxa. Their biosynthesis generally involves either non‐ribosomal peptide synthases or ribosome‐dependent production of precursor peptides. Plants within the Caryophyllaceae and certain other families produce CPs which generally consist of 5–9 proteinogenic amino acids. The biological roles for these CPs in the plant are not very clear, but many of them have activity in mammalian systems. There is currently very little known about the biosynthesis of CPs in the Caryophyllaceae. A collection of expressed sequence tags from developing seeds of Saponaria vaccaria was investigated for information about CP biosynthesis. This revealed genes that appeared to encode CP precursors which are subsequently cyclized to mature CPs. This was tested and confirmed by the expression of a cDNA encoding a putative precursor of the CP segetalin A in transformed S. vaccaria roots. Similarly, extracts of developing S. vaccaria seeds were shown to catalyze the production of segetalin A from the same putative (synthetic) precursor. Moreover, the presence in S. vaccaria seeds of two segetalins, J [cyclo(FGTHGLPAP)] and K [cyclo(GRVKA)], which was predicted by sequence analysis, was confirmed by liquid chromatography/mass spectrometry. Sequence analysis also predicts the presence of similar CP precursor genes in Dianthus caryophyllus and Citrus spp. The data support the ribosome‐dependent biosynthesis of Caryophyllaceae‐like CPs in the Caryophyllaceae and Rutaceae.
Role of tomato BRANCHED1‐like genes in the control of shoot branching
Authors: Martín‐Trillo Mar , Grandío Eduardo González , Serra François , Marcel Fabien , Rodríguez‐Buey María Luisa , Schmitz Gregor , Theres Klaus , Bendahmane Abdelhafid , Dopazo Hernán , Cubas Pilar 
Published: May 2011

SummaryIn angiosperms, shoot branching greatly determines overall plant architecture and affects fundamental aspects of plant life. Branching patterns are determined by genetic pathways conserved widely across angiosperms. In Arabidopsis thaliana (Brassicaceae, Rosidae) BRANCHED1 (BRC1) plays a central role in this process, acting locally to arrest axillary bud growth. In tomato (Solanum lycopersicum, Solanaceae, Asteridae) we have identified two BRC1‐like paralogues, SlBRC1a and SlBRC1b. These genes are expressed in arrested axillary buds and both are down‐regulated upon bud activation, although SlBRC1a is transcribed at much lower levels than SlBRC1b. Alternative splicing of SlBRC1a renders two transcripts that encode two BRC1‐like proteins with different C‐t domains due to a 3′‐terminal frameshift. The phenotype of loss‐of‐function lines suggests that SlBRC1b has retained the ancestral role of BRC1 in shoot branch suppression. We have isolated the BRC1a and BRC1b genes of other Solanum species and have studied their evolution rates across the lineages. These studies indicate that, after duplication of an ancestral BRC1‐like gene, BRC1b genes continued to evolve under a strong purifying selection that was consistent with the conserved function of SlBRC1b in shoot branching control. In contrast, the coding sequences of Solanum BRC1a genes have evolved at a higher evolution rate. Branch‐site tests indicate that this difference does not reflect relaxation but rather positive selective pressure for adaptation.
Wheat flowering repressor VRN2 and promoter CO2 compete for interactions with NUCLEAR FACTOR‐Y complexes
Authors: Li Chengxia , Distelfeld Assaf , Comis Alfio , Dubcovsky Jorge 
Published: May 2011

SummaryThe transition from vegetative to reproductive development in the temperate cereals is mainly regulated by seasonal cues including vernalization (determined mainly by VRN1 and VRN2 genes) and photoperiod (determined mainly by PPD1 and CO2 genes). The wheat VRN3 gene, which is similar to Arabidopsis FT, plays a central role in the integration of the competing signals from these two pathways. Under long days, VRN3 transcription is down‐regulated by VRN2, a unique flowering repressor in cereals, and up‐regulated by CO2. Overexpression of VRN3 overcomes VRN2 repression and promotes VRN1 transcription and flowering initiation. Using yeast two‐ and three‐hybrid assays we show here that the CCT domains present in VRN2 and CO2 proteins interact with the same subset of eight NF‐Y proteins, and that these CCT proteins compete with NF‐YA for interactions with NF‐YB proteins. We have confirmed all these interactions in vitro, and the interactions between VRN2 and two of the three NF‐YB proteins were further confirmed in planta. In addition, we show that mutations in the CCT domain of VRN2 that eliminate the vernalization requirement in winter wheat also reduce the strength of the interactions between VRN2 and NF‐Y proteins, and the ability of VRN2 to compete with CO2. Taken together, our results suggest that the interactions between CCT and NF‐Y proteins play an important role in the integration of the vernalization and photoperiod seasonal signals, and provide a flexible combinatorial system to integrate multiple developmental and environmental signals in the regulation of flowering initiation in the temperate cereals.
Pseudomonas syringae colonizes distant tissues in Nicotiana benthamiana through xylem vessels
Authors: Misas‐Villamil Johana C. , Kolodziejek Izabella , van der Hoorn Renier A. L. 
Published: May 2011

SummaryThe ability to move from the primary infection site and colonize distant tissue in the leaf is an important property of bacterial plant pathogens, yet this aspect has hardly been investigated for model pathogens. Here we show that GFP‐expressing Pseudomonas syringae pv. syringae DC3000 that lacks the HopQ1‐1 effector (PtoDC3000ΔhQ) has a strong capacity to colonize distant leaf tissue from wound‐inoculated sites in N. benthamiana. Distant colonization occurs within 1 week after toothpick inoculation and is characterized by distant colonies in the apoplast along the vasculature. Distant colonization is blocked by the non‐host resistance response triggered by HopQ1‐1 in an SGT1‐dependent manner and is associated with an explosive growth of the bacterial population, and displays robust growth differences between compatible and incompatible interactions. Scanning electron microscopy revealed that PtoDC3000ΔhQ bacteria are present in xylem vessels, indicating that they use the xylem to move through the leaf blade. Distant colonization does not require flagellin‐mediated motility, and is common for P. syringae pathovars that represent different phylogroups.
3D position of pericentromeric heterochromatin within the nucleus of a patient with ICF syndrome
Authors: Dupont C , Guimiot F , Perrin L , Marey I , Smiljkovski D , Le Tessier D , Lebugle C , Baumann C , Bourdoncle P , Tabet A‐C , Aboura A , Benzacken B , Dupont J‐M 
Published: May 2011

Dupont C, Guimiot F, Perrin L, Marey I, Smiljkovski D, Le Tessier D, Lebugle C, Baumann C, Bourdoncle P, Tabet A‐C, Aboura A, Benzacken B, Dupont J‐M. 3D position of pericentromeric heterochromatin within the nucleus of a patient with ICF syndrome.ICF (immunodeficiency, centromeric region instability, facial anomalies) syndrome is a rare autosomal recessive disorder characterised by severe immunodeficiency, craniofacial anomalies and chromosome instability. Chromosome analyses from blood samples show a high frequency of decondensation of pericentromeric heterochromatin (PH) and rearrangements involving chromosomes 1 and 16. It is the first and, as far as we know, the only disease associated with a mutation in a DNA methyltransferase gene, DNMT3B, with significant hypomethylation of the classical satellite DNA, the major component of the juxtacentromeric heterochromatin. To better understand the complex links between the hypomethylation of the satellite DNA, the cytogenetic anomalies and the clinical features of ICF syndrome, we performed three‐dimensional (3D) FISH on preserved cells from a patient with a suspected ICF phenotype. Analysis of DNMT3B did not reveal any mutation in our patient, making this case an ICF type 2. The results of 3D‐FISH showed a statistically significant change in the intranuclear position of PH of chromosome 1 in cells of the patient as compared to normal cells. It is difficult to understand how a defect in the methylation pathway can be responsible for the various symptoms of this condition. From our observations we suggest a mechanistic link between the reorganisation of the nuclear architecture and the altered gene expression.
CHD7 mutations causing CHARGE syndrome are predominantly of paternal origin
Authors: Pauli S , von Velsen N , Burfeind P , Steckel M , Mänz J , Buchholz A , Borozdin W , Kohlhase J 
Published: May 2011

Pauli S, von Velsen N, Burfeind P, Steckel M, Mänz J, Buchholz A, Borozdin W, Kohlhase J. CHD7 mutations causing CHARGE syndrome are predominantly of paternal origin.CHARGE (coloboma, heart defects, atresia of the choanae, retarded growth and development, genital hypoplasia, ear anomalies and deafness) syndrome is a congenital malformation syndrome caused by mutations in the CHD7 gene in approximately 2/3 of cases. In the vast majority of cases, CHARGE syndrome is sporadic. There are only a few reports of parent‐to‐child transmission and somatic or gonadal mosaicism. To determine the parental origin of CHD7 mutations in sporadic CHARGE syndrome, we screened 30 families for informative exonic or intronic polymorphisms located near the detected CHD7 mutation. An informative polymorphism could be identified in 13 out of 30 families. Linkage analysis was performed between the CHD7 mutation and the polymorphism in the child. In 12 out of 13 families, the mutation affected the paternal allele (92.3%). In our cohort, the mean paternal age at birth was 32.92 years. Comparing the age of fathers of an affected CHARGE patient with the paternal age of the German population in general, we could not observe any paternal age effect. Taken together, we show in this study that de novo CHD7 mutations occur predominantly in the male germ line.