bluuebunny/crossref_metadata_2025_split huggingface dataset:
The contribution of pseudouridine to stabilities and structure of RNAs
Authors: Kierzek Elzbieta , Malgowska Magdalena , Lisowiec Jolanta , Turner Douglas H. , Gdaniec Zofia , Kierzek Ryszard 
Published: December 2013

Abstract
Thermodynamic data are reported revealing that pseudouridine (Ψ) can stabilize RNA duplexes when replacing U and forming Ψ-A, Ψ-G, Ψ-U and Ψ-C pairs. Stabilization is dependent on type of base pair, position of Ψ within the RNA duplex, and type and orientation of adjacent Watson–Crick pairs. NMR spectra demonstrate that for internal Ψ-A, Ψ-G and Ψ-U pairs, the N3 imino proton is hydrogen bonded to the opposite strand nucleotide and the N1 imino proton may also be hydrogen bonded. CD spectra show that general A-helix structure is preserved, but there is some shifting of peaks and changing of intensities. Ψ has two hydrogen donors (N1 and N3 imino protons) and two hydrogen bond acceptors because the glycosidic bond is C-C rather than C-N as in uridine. This greater structural potential may allow Ψ to behave as a kind of structurally driven universal base because it can enhance stability relative to U when paired with A, G, U or C inside a double helix. These structural and thermodynamic properties may contribute to the biological functions of Ψ.
Computational analysis reveals a correlation of exon-skipping events with splicing, transcription and epigenetic factors
Authors: Ye Zhenqing , Chen Zhong , Lan Xun , Hara Stephen , Sunkel Benjamin , Huang Tim H.-M. , Elnitski Laura , Wang Qianben , Jin Victor X. 
Published: December 2013

Abstract
Alternative splicing (AS), in higher eukaryotes, is one of the mechanisms of post-transcriptional regulation that generate multiple transcripts from the same gene. One particular mode of AS is the skipping event where an exon may be alternatively excluded or constitutively included in the resulting mature mRNA. Both transcript isoforms from this skipping event site, i.e. in which the exon is either included (inclusion isoform) or excluded (skipping isoform), are typically present in one cell, and maintain a subtle balance that is vital to cellular function and dynamics. However, how the prevailing conditions dictate which isoform is expressed and what biological factors might influence the regulation of this process remain areas requiring further exploration. In this study, we have developed a novel computational method, graph-based exon-skipping scanner (GESS), for de novo detection of skipping event sites from raw RNA-seq reads without prior knowledge of gene annotations, as well as for determining the dominant isoform generated from such sites. We have applied our method to publicly available RNA-seq data in GM12878 and K562 cells from the ENCODE consortium and experimentally validated several skipping site predictions by RT-PCR. Furthermore, we integrated other sequencing-based genomic data to investigate the impact of splicing activities, transcription factors (TFs) and epigenetic histone modifications on splicing outcomes. Our computational analysis found that splice sites within the skipping-isoform-dominated group (SIDG) tended to exhibit weaker MaxEntScan-calculated splice site strength around middle, ‘skipping’, exons compared to those in the inclusion-isoform-dominated group (IIDG). We further showed the positional preference pattern of splicing factors, characterized by enrichment in the intronic splice sites immediately bordering middle exons. Finally, our analysis suggested that different epigenetic factors may introduce a variable obstacle in the process of exon–intron boundary establishment leading to skipping events.
A new epoch of quantum manipulation
Authors: Han Yongjian , Wang Zhen , Guo Guang-Can 
Published: December 2013

Abstract
The behavior of individual microscopic particles, such as an atom (or a photon), predicted using quantum mechanics, is dramatically different from the behavior of classical particles, such as a planet, determined using classical mechanics. How can the counter-intuitive behavior of the microscopic particle be verified and manipulated experimentally? David Wineland and Serge Haroche, who were awarded the Nobel Prize in physics in 2012, developed a set of methods to isolate the ions and photons from their environment to create a genuine quantum system. Furthermore, they also developed methods to measure and manipulate these quantum systems, which open a path not only to explore the fundamental principles of quantum mechanics, but also to develop a much faster computer: a quantum computer.
Morphometrics of a wild Asian elephant exhibiting disproportionate dwarfism
Authors: de Silva Shermin , Weerathunga U. S. , Kumara T. V. 
Published: December 2013

AbstractDwarfism is a condition characterized by shorter stature, at times accompanied by differential skeletal growth pro-portions relative to the species-typical physical conformation. Causes vary and well-documented in humans as well as certain mammalian species in captive or laboratory conditions, but rarely observed in the wild. Here we report on a single case of apparent dwarfism in a free-ranging adult male Asian elephant (Elephas maximus) in Sri Lanka, comparing physical dimensions to those of other males in the same population, males in other populations, and records in previous literature. The subject was found to have a shoulder height of approximately 195cm, is shorter than the average height of typical mature males, with a body length of 218cm. This ratio of body length to height deviates from what is typically observed, which is approximately 1:1. In absolute height the subject was similar to the attributes of a captive elephant documented in 1955 in Sri Lanka, also said to be a dwarf, however the two specimens differed in the relative proportions of height vs. body length. The subject also exhibits a slight elongation of the skull. We discuss how this phenotype compares to cases of dwarfism in other non-human animals.
CELLULOSE SYNTHASE INTERACTIVE3 Regulates Cellulose Biosynthesis in Both a Microtubule-Dependent and Microtubule-Independent Manner inArabidopsi s
Authors: Lei Lei , Li Shundai , Du Juan , Bashline Logan , Gu Ying 
Published: December 2013

AbstractAnisotropic plant cell growth depends on the coordination between the orientation of cortical microtubules and the orientation of nascent cellulose microfibrils. CELLULOSE SYNTHASE INTERACTIVE1 (CSI1) is a key scaffold protein that guides primary cellulose synthase complexes (CSCs) along cortical microtubules during cellulose biosynthesis. Here, we investigated the function of the CSI1-like protein, CSI3, in Arabidopsis thaliana. Similar to CSI1, CSI3 associates with primary CSCs in vitro, colocalizes with CSCs in vivo, and exhibits the same plasma membrane localization and bidirectional motility as CSI1. However, ProCSI1:GFP-CSI3 cannot complement the anisotropic cell growth defect in csi1 mutants, suggesting that CSI3 is not functionally equivalent to CSI1. Also, the colocalization ratio between CSI1 and CSI3 is low, which may suggest heterogeneity within the CSC population. csi1 csi3 double mutants showed an enhanced cell expansion defect as well as an additive reduction of CSC velocities, and CSI3 dynamics are dependent on CSI1 function. We propose that CSI3 is an important regulator of plant cellulose biosynthesis and plant anisotropic cell growth that modulates the velocity of CSCs in both a microtubule-dependent and microtubule-independent manner.
Calcium/Calmodulin-Dependent Protein Kinase Is Negatively and Positively Regulated by Calcium, Providing a Mechanism for Decoding Calcium Responses during Symbiosis Signaling
Authors: Miller J. Benjamin , Pratap Amitesh , Miyahara Akira , Zhou Liang , Bornemann Stephen , Morris Richard J. , Oldroyd Giles E.D. 
Published: December 2013

AbstractThe establishment of symbiotic associations in plants requires calcium oscillations that must be decoded to invoke downstream developmental programs. In animal systems, comparable calcium oscillations are decoded by calmodulin (CaM)–dependent protein kinases, but symbiotic signaling involves a calcium/CaM–dependent protein kinase (CCaMK) that is unique to plants. CCaMK differs from the animal CaM kinases by its dual ability to bind free calcium, via calcium binding EF-hand domains on the protein, or to bind calcium complexed with CaM, via a CaM binding domain. In this study, we dissect this dual regulation of CCaMK by calcium. We find that calcium binding to the EF-hand domains promotes autophosphorylation, which negatively regulates CCaMK by stabilizing the inactive state of the protein. By contrast, calcium-dependent CaM binding overrides the effects of autophosphorylation and activates the protein. The differential calcium binding affinities of the EF-hand domains compared with those of CaM suggest that CCaMK is maintained in the inactive state at basal calcium concentrations and is activated via CaM binding during calcium oscillations. This work provides a model for decoding calcium oscillations that uses differential calcium binding affinities to create a robust molecular switch that is responsive to calcium concentrations associated with both the basal state and with oscillations.
TheTrans-Acting Short Interfering RNA3 Pathway and NO APICAL MERISTEM Antagonistically Regulate Leaf Margin Development and Lateral Organ Separation, as Revealed by Analysis of anargonaute7/lobed leaflet1Mutant inMedicago truncatula
Authors: Zhou Chuanen , Han Lu , Fu Chunxiang , Wen Jiangqi , Cheng Xiaofei , Nakashima Jin , Ma Junying , Tang Yuhong , Tan Yang , Tadege Million , Mysore Kirankumar S. , Xia Guangmin , Wang Zeng-Yu 
Published: December 2013

AbstractLeaf shape elaboration and organ separation are critical for plant morphogenesis. We characterized the developmental roles of LOBED LEAFLET1 by analyzing a recessive mutant in the model legume Medicago truncatula. An ortholog of Arabidopsis thaliana ARGONAUTE7 (AGO7), Mt-AGO7/LOBED LEAFLET1, is required for the biogenesis of a trans-acting short interfering RNA (ta-siRNA) to negatively regulate the expression of AUXIN RESPONSE FACTORs in M. truncatula. Loss of function in AGO7 results in pleiotropic phenotypes in different organs. The prominent phenotype of the ago7 mutant is lobed leaf margins and more widely spaced lateral organs, suggesting that the trans-acting siRNA3 (TAS3) pathway negatively regulates the formation of boundaries and the separation of lateral organs in M. truncatula. Genetic interaction analysis with the smooth leaf margin1 (slm1) mutant revealed that leaf margin formation is cooperatively regulated by the auxin/SLM1 (ortholog of Arabidopsis PIN-FORMED1) module, which influences the initiation of leaf margin teeth, and the TAS3 ta-siRNA pathway, which determines the degree of margin indentation. Further investigations showed that the TAS3 ta-siRNA pathway and NO APICAL MERISTEM (ortholog of Arabidopsis CUP-SHAPED COTYLEDON) antagonistically regulate both leaf margin development and lateral organ separation, and the regulation is partially dependent on the auxin/SLM1 module.
ArabidopsisPhosphoglycerate Dehydrogenase1 of the Phosphoserine Pathway Is Essential for Development and Required for Ammonium Assimilation and Tryptophan Biosynthesis
Authors: Benstein Ruben Maximilian , Ludewig Katja , Wulfert Sabine , Wittek Sebastian , Gigolashvili Tamara , Frerigmann Henning , Gierth Markus , Flügge Ulf-Ingo , Krueger Stephan 
Published: December 2013

AbstractIn plants, two independent serine biosynthetic pathways, the photorespiratory and glycolytic phosphoserine (PS) pathways, have been postulated. Although the photorespiratory pathway is well characterized, little information is available on the function of the PS pathway in plants. Here, we present a detailed characterization of phosphoglycerate dehydrogenases (PGDHs) as components of the PS pathway in Arabidopsis thaliana. All PGDHs localize to plastids and possess similar kinetic properties, but they differ with respect to their sensitivity to serine feedback inhibition. Furthermore, analysis of pgdh1 and phosphoserine phosphatase mutants revealed an embryo-lethal phenotype and PGDH1-silenced lines were inhibited in growth. Metabolic analyses of PGDH1-silenced lines grown under ambient and high CO2 conditions indicate a direct link between PS biosynthesis and ammonium assimilation. In addition, we obtained several lines of evidence for an interconnection between PS and tryptophan biosynthesis, because the expression of PGDH1 and PHOSPHOSERINE AMINOTRANSFERASE1 is regulated by MYB51 and MYB34, two activators of tryptophan biosynthesis. Moreover, the concentration of tryptophan-derived glucosinolates and auxin were reduced in PGDH1-silenced plants. In essence, our results provide evidence for a vital function of PS biosynthesis for plant development and metabolism.
Genome-Wide Analysis of Branched-Chain Amino Acid Levels inArabidopsisSeeds
Authors: Angelovici Ruthie , Lipka Alexander E. , Deason Nicholas , Gonzalez-Jorge Sabrina , Lin Haining , Cepela Jason , Buell Robin , Gore Michael A. , DellaPenna Dean 
Published: December 2013

AbstractBranched-chain amino acids (BCAAs) are three of the nine essential amino acids in human and animal diets and are important for numerous processes in development and growth. However, seed BCAA levels in major crops are insufficient to meet dietary requirements, making genetic improvement for increased and balanced seed BCAAs an important nutritional target. Addressing this issue requires a better understanding of the genetics underlying seed BCAA content and composition. Here, a genome-wide association study and haplotype analysis for seed BCAA traits in Arabidopsis thaliana revealed a strong association with a chromosomal interval containing two BRANCHED-CHAIN AMINO ACID TRANSFERASES, BCAT1 and BCAT2. Linkage analysis, reverse genetic approaches, and molecular complementation analysis demonstrated that allelic variation at BCAT2 is responsible for the natural variation of seed BCAAs in this interval. Complementation analysis of a bcat2 null mutant with two significantly different alleles from accessions Bayreuth-0 and Shahdara is consistent with BCAT2 contributing to natural variation in BCAA levels, glutamate recycling, and free amino acid homeostasis in seeds in an allele-dependent manner. The seed-specific phenotype of bcat2 null alleles, its strong transcription induction during late seed development, and its subcellular localization to the mitochondria are consistent with a unique, catabolic role for BCAT2 in BCAA metabolism in seeds.
CAROTENOID CLEAVAGE DIOXYGENASE4Is a Negative Regulator of β-Carotene Content inArabidopsisSeeds
Authors: Gonzalez-Jorge Sabrina , Ha Sun-Hwa , Magallanes-Lundback Maria , Gilliland Laura Ullrich , Zhou Ailing , Lipka Alexander E. , Nguyen Yen-Nhu , Angelovici Ruthie , Lin Haining , Cepela Jason , Little Holly , Buell C. Robin , Gore Michael A. , DellaPenna Dean 
Published: December 2013

AbstractExperimental approaches targeting carotenoid biosynthetic enzymes have successfully increased the seed β-carotene content of crops. However, linkage analysis of seed carotenoids in Arabidopsis thaliana recombinant inbred populations showed that only 21% of quantitative trait loci, including those for β-carotene, encode carotenoid biosynthetic enzymes in their intervals. Thus, numerous loci remain uncharacterized and underutilized in biofortification approaches. Linkage mapping and genome-wide association studies of Arabidopsis seed carotenoids identified CAROTENOID CLEAVAGE DIOXYGENASE4 (CCD4) as a major negative regulator of seed carotenoid content, especially β-carotene. Loss of CCD4 function did not affect carotenoid homeostasis during seed development but greatly reduced carotenoid degradation during seed desiccation, increasing β-carotene content 8.4-fold relative to the wild type. Allelic complementation of a ccd4 null mutant demonstrated that single-nucleotide polymorphisms and insertions and deletions at the locus affect dry seed carotenoid content, due at least partly to differences in CCD4 expression. CCD4 also plays a major role in carotenoid turnover during dark-induced leaf senescence, with β-carotene accumulation again most strongly affected in the ccd4 mutant. These results demonstrate that CCD4 plays a major role in β-carotene degradation in drying seeds and senescing leaves and suggest that CCD4 orthologs would be promising targets for stabilizing and increasing the level of provitamin A carotenoids in seeds of major food crops.
Abscisic Acid–Responsive Guard Cell Metabolomes of Arabidopsis Wild-Type and gpa1 G-Protein Mutants
Authors: Jin Xiaofen , Wang Rui-Sheng , Zhu Mengmeng , Jeon Byeong Wook , Albert Reka , Chen Sixue , Assmann Sarah M. 
Published: December 2013

Abstract
Individual metabolites have been implicated in abscisic acid (ABA) signaling in guard cells, but a metabolite profile of this specialized cell type is lacking. We used liquid chromatography–multiple reaction monitoring mass spectrometry for targeted analysis of 85 signaling-related metabolites in Arabidopsis thaliana guard cell protoplasts over a time course of ABA treatment. The analysis utilized ∼350 million guard cell protoplasts from ∼30,000 plants of the Arabidopsis Columbia accession (Col) wild type and the heterotrimeric G-protein α subunit mutant, gpa1, which has ABA-hyposensitive stomata. These metabolomes revealed coordinated regulation of signaling metabolites in unrelated biochemical pathways. Metabolites clustered into different temporal modules in Col versus gpa1, with fewer metabolites showing ABA-altered profiles in gpa1. Ca2+-mobilizing agents sphingosine-1-phosphate and cyclic adenosine diphosphate ribose exhibited weaker ABA-stimulated increases in gpa1. Hormone metabolites were responsive to ABA, with generally greater responsiveness in Col than in gpa1. Most hormones also showed different ABA responses in guard cell versus mesophyll cell metabolomes. These findings suggest that ABA functions upstream to regulate other hormones, and are also consistent with G proteins modulating multiple hormonal signaling pathways. In particular, indole-3-acetic acid levels declined after ABA treatment in Col but not gpa1 guard cells. Consistent with this observation, the auxin antagonist α-(phenyl ethyl-2-one)-indole-3-acetic acid enhanced ABA-regulated stomatal movement and restored partial ABA sensitivity to gpa1.
Structural basis for adaptation of lactobacilli to gastrointestinal mucus
Authors: Etzold Sabrina , Kober Olivia I. , MacKenzie Donald A. , Tailford Louise E. , Gunning A. Patrick , Walshaw John , Hemmings Andrew M. , Juge Nathalie 
Published: December 2013

SummaryThe mucus layer covering the gastrointestinal (GI) epithelium is critical in selecting and maintaining homeostatic interactions with our gut bacteria. However, the underpinning mechanisms of these interactions are not understood. Here, we provide structural and functional insights into the canonical mucus‐binding protein (MUB), a multi‐repeat cell‐surface adhesin found in Lactobacillus inhabitants of the GI tract. X‐ray crystallography together with small‐angle X‐ray scattering demonstrated a ‘beads on a string’ arrangement of repeats, generating 174 nm long protein fibrils, as shown by atomic force microscopy. Each repeat consists of tandemly arranged Ig‐ and mucin‐binding protein (MucBP) modules. The binding of full‐length MUB was confined to mucus via multiple interactions involving terminal sialylated mucin glycans. While individual MUB domains showed structural similarity to fimbrial proteins from Gram‐positive pathogens, the particular organization of MUB provides a structural explanation for the mechanisms in which lactobacilli have adapted to their host niche by maximizing interactions with the mucus receptors, potentiating the retention of bacteria within the mucus layer. Together, this study reveals functional and structural features which may affect tropism of microbes across mucus and along the GI tract, providing unique insights into the mechanisms adopted by commensals and probiotics to adapt to the mucosal environment.
Risk of maternal and neonatal complications in subsequent pregnancy after planned caesarean section in a first birth, compared with emergency caesarean section: a nationwide comparative cohort study
Authors: Kok N , Ruiter L , Hof M , Ravelli A , Mol BW , Pajkrt E , Kazemier B 
Published: December 2013

ObjectiveTo compare the difference in risks of neonatal and maternal complications, including uterine rupture, in a second birth following a planned caesarean section versus emergency caesarean section in the first birth.DesignProspective cohort study.SettingPopulation‐based cohort in the Netherlands.PopulationLinked data set of outcomes for term caesarean section in a first birth followed by a consecutive delivery.MethodsWe conducted a prospective cohort analysis using data from the Dutch Perinatal Registry. We included primiparous women who gave birth to term singleton infants through planned or emergency caesarean from January 2000 through December 2007, and who had a second singleton delivery during the same period (n = 41 109). Odds ratios and adjusted odds ratios were calculated.Main outcome measuresMaternal and neonatal complications, specifically uterine rupture, in second births associated with planned and emergency caesareans in the first birth.ResultsWomen with a history of a planned caesarean section in the first birth (n = 11 445) had a 0.24% risk for uterine rupture, compared with a 0.16% risk for women with a history of emergency caesarean section (n = 29 664; aOR 1.4, 95% CI 0.8–2.4). In multivariate logistic regression, women with planned caesareans in a first birth had a significantly increased risk of stillbirth (aOR 1.5, 95% CI 1.0–2.2) and postpartum haemorrhage (aOR 1.1, 95% CI 1.0–1.2) in second births, compared with women with emergency caesareans in the first birth.ConclusionsWe found a moderately increased risk of postpartum haemorrhage and a small to moderately increased risk of uterine rupture and stillbirth as a long‐term effect of prior planned caesarean delivery on second births.
Sustained improvement in health‐related quality of life measures in patients with inflammatory bowel disease receiving prolonged anti‐tumor necrosis factor therapy
Authors: Sherman Michael , Tsynman Donald N , Kim Albert , Arora Jyoti , Pietras Timothy , Messing Susan , St Hilaire Lydia , Yoon Sonia , Decross Arthur , Shah Ashok , Saubermann Lawrence 
Published: December 2013

ObjectiveThe aim of this study was to determine whether the effects of prolonged therapy (≥1 year) with anti‐tumor necrosis factor (TNF) agents were sustained on the health‐related quality of life (HRQoL) in patients with inflammatory bowel disease (IBD).MethodsA cross‐sectional survey of patients with IBD who were treated with anti‐TNF agents was performed. Results of the validated HRQoL measures (inflammatory bowel disease questionnaire [IBDQ], EuroQoL‐5 dimensions [EQ‐5D], health status visual analogue scale [VAS] and the Zung self‐rating depression scale) were recorded and compared between patients treated with anti‐TNF agents for <1 year and ≥1 year.ResultsA total of 41 patients were finally enrolled in the study. Among them, 11 (26.8%) had received anti‐TNF therapy for less than one year with a median duration of 7 months (range 3–11 months), while the other 30 (73.2%) had been treated for ≥1 year with a median duration of 42 months (range 12–104 months). Crohn's disease was the most common type in both groups. None of the mean IBDQ, EQ‐5D and EQ‐5D plus VAS, or Zung self‐rating depression scale scores differed significantly between the two groups of patients.ConclusionsImprovements in HRQoL for IBD patients on anti‐TNF therapy were sustained for longer than one year. HRQoL measures for IBD patients treated with anti‐TNF therapy for <1 year do not differ significantly from those treated for ≥1 year, but a trend towards improved HRQoL measures with prolonged therapy can be obtained.