bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular mechanisms underlying the interaction of protein phosphatase-1c with ASPP proteins
Authors: Skene-Arnold Tamara D. , Luu Hue Anh , Uhrig R. Glen , De Wever Veerle , Nimick Mhairi , Maynes Jason , Fong Andrea , James Michael N. G. , Trinkle-Mulcahy Laura , Moorhead Greg B. , Holmes Charles F. B. 
Published: October 2012

The serine/threonine PP-1c (protein phosphatase-1 catalytic subunit) is regulated by association with multiple regulatory subunits. Human ASPPs (apoptosis-stimulating proteins of p53) comprise three family members: ASPP1, ASPP2 and iASPP (inhibitory ASPP), which is uniquely overexpressed in many cancers. While ASPP2 and iASPP are known to bind PP-1c, we now identify novel and distinct molecular interactions that allow all three ASPPs to bind differentially to PP-1c isoforms and p53. iASPP lacks a PP-1c-binding RVXF motif; however, we show it interacts with PP-1c via a RARL sequence with a Kd value of 26 nM. Molecular modelling and mutagenesis of PP-1c–ASPP protein complexes identified two additional modes of interaction. First, two positively charged residues, Lys260 and Arg261 on PP-1c, interact with all ASPP family members. Secondly, the C-terminus of the PP-1c α, β and γ isoforms contain a type-2 SH3 (Src homology 3) poly-proline motif (PxxPxR), which binds directly to the SH3 domains of ASPP1, ASPP2 and iASPP. In PP-1cγ this comprises residues 309–314 (PVTPPR). When the Px(T)PxR motif is deleted or mutated via insertion of a phosphorylation site mimic (T311D), PP-1c fails to bind to all three ASPP proteins. Overall, we provide the first direct evidence for PP-1c binding via its C-terminus to an SH3 protein domain.
Exploring the dominant role of Cav1 channels in signalling to the nucleus
Authors: Ma Huan , Cohen Samuel , Li Boxing , Tsien Richard W. 
Published: October 2012

Calcium is important in controlling nuclear gene expression through the activation of multiple signal-transduction pathways in neurons. Compared with other voltage-gated calcium channels, CaV1 channels demonstrate a considerable advantage in signalling to the nucleus. In this review, we summarize the recent progress in elucidating the mechanisms involved. CaV1 channels, already advantaged in their responsiveness to depolarization, trigger communication with the nucleus by attracting colocalized clusters of activated CaMKII (Ca2+/calmodulin-dependent protein kinase II). CaV2 channels lack this ability, but must work at a distance of &gt;1 μm from the CaV1-CaMKII co-clusters, which hampers their relative efficiency for a given rise in bulk [Ca2+]i (intracellular [Ca2+]). Moreover, Ca2+ influx from CaV2 channels is preferentially buffered by the ER (endoplasmic reticulum) and mitochondria, further attenuating their effectiveness in signalling to the nucleus.
Reading Vocabulary in Children With and Without Hearing Loss: The Roles of Task and Word Type
Authors: Coppens Karien M. , Tellings Agnes , Verhoeven Ludo , Schreuder Robert 
Published: October 2012

Purpose
To address the problem of low reading comprehension scores among children with hearing impairment, it is necessary to have a better understanding of their reading vocabulary. In this study, the authors investigated whether task and word type differentiate the reading vocabulary knowledge of children with and without severe hearing loss.

Method
Seventy-two children with hearing loss and 72 children with normal hearing performed a lexical and a use decision task. Both tasks contained the same 180 words divided over 7 clusters, each cluster containing words with a similar pattern of scores on 8 word properties (word class, frequency, morphological family size, length, age of acquisition, mode of acquisition, imageability, and familiarity).

Results
Whereas the children with normal hearing scored better on the 2 tasks than the children with hearing loss, the size of the difference varied depending on the type of task and word.

Conclusions
Performance differences between the 2 groups increased as words and tasks became more complex. Despite delays, children with hearing loss showed a similar pattern of vocabulary acquisition as their peers with normal hearing. For the most precise assessment of reading vocabulary possible, a range of tasks and word types should be used.
Effects of Noise Suppression on Intelligibility: Experts' Opinions and Naïve Normal-Hearing Listeners' Performance
Authors: Hilkhuysen Gaston L. M. , Gaubitch Nikolay , Huckvale Mark 
Published: October 2012

Purpose
In this study, the authors investigated how well experts can adjust the settings of a commercial noise-reduction system to optimize the intelligibility for naive normal-hearing listeners.

Method
In Experiment 1, 5 experts adjusted parameters for a noise-reduction system while aiming to optimize intelligibility. The stimuli consisted of speech presented in car-cabin noise or babble at 5 different signal-to-noise ratios (SNRs). In Experiment 2, the effects of processing with these settings were measured with 10 listeners undertaking an intelligibility test. In Experiment 3, the intelligibility of a broad range of settings was investigated with another 10 listeners to determine whether the experts' chosen settings could have been improved.

Results
Low Cronbach's alphas indicated that parameter settings varied considerably within and across experts. For very low SNRs, mean proposed settings differed from those for higher SNRs. The different settings had no significant effects on intelligibility for naive normal-hearing listeners. At high SNRs, the settings proposed by experts were found to deteriorate intelligibility. Superior intelligibility for naive normal-hearing listeners was achievable from settings other than the ones proposed by the experts.

Conclusion
While attempting to enhance noisy speech, experts may propose settings that deteriorate intelligibility for naive normal-hearing listeners.
Discovering chimeric transcripts in paired-end RNA-seq data by using EricScript
Authors: Benelli Matteo , Pescucci Chiara , Marseglia Giuseppina , Severgnini Marco , Torricelli Francesca , Magi Alberto 
Published: October 2012

Abstract
Motivation: The discovery of novel gene fusions can lead to a better comprehension of cancer progression and development. The emergence of deep sequencing of trancriptome, known as RNA-seq, has opened many opportunities for the identification of this class of genomic alterations, leading to the discovery of novel chimeric transcripts in melanomas, breast cancers and lymphomas. Nowadays, few computational approaches have been developed for the detection of chimeric transcripts. Although all of these computational methods show good sensitivity, much work remains to reduce the huge number of false-positive calls that arises from this analysis.
Results: We proposed a novel computational framework, named chimEric tranScript detection algorithm (EricScript), for the identification of gene fusion products in paired-end RNA-seq data. Our simulation study on synthetic data demonstrates that EricScript enables to achieve higher sensitivity and specificity than existing methods with noticeably lower running times. We also applied our method to publicly available RNA-seq tumour datasets, and we showed its capability in rediscovering known gene fusions.
Availability: The EricScript package is freely available under GPL v3 license at http://ericscript.sourceforge.net.
Contact: matteo.benelli@gmail.com
Supplementary information: Supplementary data are available at Bioinformatics online.
Genotype calling and phasing using next-generation sequencing reads and a haplotype scaffold
Authors: Menelaou Androniki , Marchini Jonathan 
Published: October 2012

Abstract
Motivation: Given the current costs of next-generation sequencing, large studies carry out low-coverage sequencing followed by application of methods that leverage linkage disequilibrium to infer genotypes. We propose a novel method that assumes study samples are sequenced at low coverage and genotyped on a genome-wide microarray, as in the 1000 Genomes Project (1KGP). We assume polymorphic sites have been detected from the sequencing data and that genotype likelihoods are available at these sites. We also assume that the microarray genotypes have been phased to construct a haplotype scaffold. We then phase each polymorphic site using an MCMC algorithm that iteratively updates the unobserved alleles based on the genotype likelihoods at that site and local haplotype information. We use a multivariate normal model to capture both allele frequency and linkage disequilibrium information around each site. When sequencing data are available from trios, Mendelian transmission constraints are easily accommodated into the updates. The method is highly parallelizable, as it analyses one position at a time.
Results: We illustrate the performance of the method compared with other methods using data from Phase 1 of the 1KGP in terms of genotype accuracy, phasing accuracy and downstream imputation performance. We show that the haplotype panel we infer in African samples, which was based on a trio-phased scaffold, increases downstream imputation accuracy for rare variants (R2 increases by &gt;0.05 for minor allele frequency &lt;1%), and this will translate into a boost in power to detect associations. These results highlight the value of incorporating microarray genotypes when calling variants from next-generation sequence data.
Availability: The method (called MVNcall) is implemented in a C++ program and is available from http://www.stats.ox.ac.uk/∼marchini/#software.
Contact: marchini@stats.ox.ac.uk
Supplementary information: Supplementary data are available at Bioinformatics online.
The Pepper Extracellular Xyloglucan-Specific Endo-β-1,4-Glucanase Inhibitor Protein Gene,CaXEGIP1, Is Required for Plant Cell Death and Defense Responses
Authors: Choi Hyong Woo , Kim Nak Hyun , Lee Yeon Kyeong , Hwang Byung Kook 
Published: October 2012

AbstractPlants produce various proteinaceous inhibitors to protect themselves against microbial pathogen attack. A xyloglucan-specific endo-β-1,4-glucanase inhibitor1 gene, CaXEGIP1, was isolated and functionally characterized in pepper (Capsicum annuum) plants. CaXEGIP1 was rapidly and strongly induced in pepper leaves infected with avirulent Xanthomonas campestris pv vesicatoria, and purified CaXEGIP1 protein significantly inhibited the hydrolytic activity of the glycoside hydrolase74 family xyloglucan-specific endo-β-1,4-glucanase from Clostridium thermocellum. Soluble-modified green fluorescent protein-tagged CaXEGIP1 proteins were mainly localized to the apoplast of onion (Allium cepa) epidermal cells. Agrobacterium tumefaciens-mediated overexpression of CaXEGIP1 triggered pathogen-independent, spontaneous cell death in pepper and Nicotiana benthamiana leaves. CaXEGIP1 silencing in pepper conferred enhanced susceptibility to virulent and avirulent X. campestris pv vesicatoria, accompanied by a compromised hypersensitive response and lowered expression of defense-related genes. Overexpression of dexamethasone:CaXEGIP1 in Arabidopsis (Arabidopsis thaliana) enhanced resistance to Hyaloperonospora arabidopsidis infection. Comparative histochemical and proteomic analyses revealed that CaXEGIP1 overexpression induced a spontaneous cell death response and also increased the expression of some defense-related proteins in transgenic Arabidopsis leaves. This response was also accompanied by cell wall thickening and darkening. Together, these results suggest that pathogen-inducible CaXEGIP1 positively regulates cell death-mediated defense responses in plants.
Knockdown of a Rice Stelar Nitrate Transporter Alters Long-Distance Translocation But Not Root Influx
Authors: Tang Zhong , Fan Xiaorong , Li Qing , Feng Huimin , Miller Anthony J. , Shen Qirong , Xu Guohua 
Published: October 2012

AbstractRoot nitrate uptake is well known to adjust to the plant’s nitrogen demand for growth. Long-distance transport and/or root storage pools are thought to provide negative feedback signals regulating root uptake. We have characterized a vascular specific nitrate transporter belonging to the high-affinity Nitrate Transporter2 (NRT2) family, OsNRT2.3a, in rice (Oryza sativa ssp. japonica ‘Nipponbare’). Localization analyses using protoplast expression, in planta promoter-β-glucuronidase assay, and in situ hybridization showed that OsNRT2.3a was located in the plasma membrane and mainly expressed in xylem parenchyma cells of the stele of nitrate-supplied roots. Knockdown expression of OsNRT2.3a by RNA interference (RNAi) had impaired xylem loading of nitrate and decreased plant growth at low (0.5 mm) nitrate supply. In comparison with the wild type, the RNAi lines contained both nitrate and total nitrogen significantly higher in the roots and lower in the shoots. The short-term [15N]NO3 − influx (5 min) in entire roots and NO3 − fluxes in root surfaces showed that the knockdown of OsNRT2.3a in comparison with the wild type did not affect nitrate uptake by roots. The RNAi plants showed no significant changes in the expression of some root nitrate transporters (OsNRT2.3b, OsNRT2.4, and OsNAR2.1), but transcripts for nia1 (nitrate reductase) had increased and OsNRT2.1 and OsNRT2.2 had decreased when the plants were supplied with nitrate. Taken together, the data demonstrate that OsNRT2.3a plays a key role in long-distance nitrate transport from root to shoot at low nitrate supply level in rice.
Action of Gibberellins on Growth and Metabolism of Arabidopsis Plants Associated with High Concentration of Carbon Dioxide
Authors: Ribeiro Dimas M. , Araújo Wagner L. , Fernie Alisdair R. , Schippers Jos H.M. , Mueller-Roeber Bernd 
Published: October 2012

Abstract
Although the positive effect of elevated CO2 concentration [CO2] on plant growth is well known, it remains unclear whether global climate change will positively or negatively affect crop yields. In particular, relatively little is known about the role of hormone pathways in controlling the growth responses to elevated [CO2]. Here, we studied the impact of elevated [CO2] on plant biomass and metabolism in Arabidopsis (Arabidopsis thaliana) in relation to the availability of gibberellins (GAs). Inhibition of growth by the GA biosynthesis inhibitor paclobutrazol (PAC) at ambient [CO2] (350 µmol CO2 mol−1) was reverted by elevated [CO2] (750 µmol CO2 mol−1). Thus, we investigated the metabolic adjustment and modulation of gene expression in response to changes in growth of plants imposed by varying the GA regime in ambient and elevated [CO2]. In the presence of PAC (low-GA regime), the activities of enzymes involved in photosynthesis and inorganic nitrogen assimilation were markedly increased at elevated [CO2], whereas the activities of enzymes of organic acid metabolism were decreased. Under ambient [CO2], nitrate, amino acids, and protein accumulated upon PAC treatment; however, this was not the case when plants were grown at elevated [CO2]. These results suggest that only under ambient [CO2] is GA required for the integration of carbohydrate and nitrogen metabolism underlying optimal biomass determination. Our results have implications concerning the action of the Green Revolution genes in future environmental conditions.
Systems Dynamic Modeling of a Guard Cell Cl− Channel Mutant Uncovers an Emergent Homeostatic Network Regulating Stomatal Transpiration
Authors: Wang Yizhou , Papanatsiou Maria , Eisenach Cornelia , Karnik Rucha , Williams Mary , Hills Adrian , Lew Virgilio L. , Blatt Michael R. 
Published: October 2012

Abstract
Stomata account for much of the 70% of global water usage associated with agriculture and have a profound impact on the water and carbon cycles of the world. Stomata have long been modeled mathematically, but until now, no systems analysis of a plant cell has yielded detail sufficient to guide phenotypic and mutational analysis. Here, we demonstrate the predictive power of a systems dynamic model in Arabidopsis (Arabidopsis thaliana) to explain the paradoxical suppression of channels that facilitate K+ uptake, slowing stomatal opening, by mutation of the SLAC1 anion channel, which mediates solute loss for closure. The model showed how anion accumulation in the mutant suppressed the H+ load on the cytosol and promoted Ca2+ influx to elevate cytosolic pH (pHi) and free cytosolic Ca2+ concentration ([Ca2+]i), in turn regulating the K+ channels. We have confirmed these predictions, measuring pHi and [Ca2+]i in vivo, and report that experimental manipulation of pHi and [Ca2+]i is sufficient to recover K+ channel activities and accelerate stomatal opening in the slac1 mutant. Thus, we uncover a previously unrecognized signaling network that ameliorates the effects of the slac1 mutant on transpiration by regulating the K+ channels. Additionally, these findings underscore the importance of H+-coupled anion transport for pHi homeostasis.
Multiple repeat caesarean section in the UK: incidence and consequences to mother and child. A national, prospective, cohort study
Authors: Cook JR , Jarvis S , Knight M , Dhanjal MK 
Published: October 2012

Objective  To estimate the incidence of multiple repeat caesarean section (MRCS) (five or more) in the UK and to describe the outcomes for women and their babies relative to women having fewer repeat caesarean sections.Design  A national population‐based prospective cohort study using the UK Obstetric Surveillance System (UKOSS).Setting  All UK hospitals with consultant‐led maternity units.Population  Ninety‐four women having their fifth or greater MRCS between January 2009 and December 2009, and 175 comparison women having their second to fourth caesarean section.Methods  Prospective cohort and comparison identification through the UKOSS monthly mailing system.Main outcome measures  Incidence, maternal and neonatal complications. Relative risk, unadjusted (OR) and adjusted (aOR) odds ratio estimates.Results  The estimated UK incidence of MRCS was 1.20 per 10 000 maternities [95% confidence interval (CI), 0.97–1.47]. Women with MRCS had significantly more major obstetric haemorrhages (>1500 ml) (aOR, 18.6; 95% CI, 3.89–88.8), visceral damage (aOR, 17.6; 95% CI, 1.85–167.1) and critical care admissions (aOR, 15.5; 95% CI, 3.16–76.0), than women with lower order repeat caesarean sections. These risks were greatest in the 18% of women with MRCS who also had placenta praevia or accreta. Neonates of mothers having MRCS were significantly more likely to be born prior to 37 weeks of gestation (OR, 6.15; 95% CI, 2.56–15.78) and therefore had higher rates of complications and admissions.Conclusions  MRCS is associated with greater maternal and neonatal morbidity than fewer caesarean sections. The associated maternal morbidity is largely secondary to placenta praevia and accreta, whereas higher rates of preterm delivery are most likely a response to antepartum haemorrhage.
Comparison of 454 pyrosequencing methods for characterizing the major histocompatibility complex of nonmodel species and the advantages of ultra deep coverage
Authors: Oomen Rebekah A. , Gillett Roxanne M. , Kyle Christopher J. 
Published: October 2012

AbstractCharacterization and population genetic analysis of multilocus genes, such as those found in the major histocompatibility complex (MHC) is challenging in nonmodel vertebrates. The traditional method of extensive cloning and Sanger sequencing is costly and time‐intensive and indirect methods of assessment often underestimate total variation. Here, we explored the suitability of 454 pyrosequencing for characterizing multilocus genes for use in population genetic studies. We compared two sample tagging protocols and two bioinformatic procedures for 454 sequencing through characterization of a 185‐bp fragment of MHC DRB exon 2 in wolverines (Gulo gulo) and further compared the results with those from cloning and Sanger sequencing. We found 10 putative DRB alleles in the 88 individuals screened with between two and four alleles per individual, suggesting amplification of a duplicated DRB gene. In addition to the putative alleles, all individuals possessed an easily identifiable pseudogene. In our system, sequence variants with a frequency below 6% in an individual sample were usually artefacts. However, we found that sample preparation and data processing procedures can greatly affect variant frequencies in addition to the complexity of the multilocus system. Therefore, we recommend determining a per‐amplicon‐variant frequency threshold for each unique system. The extremely deep coverage obtained in our study (approximately 5000×) coupled with the semi‐quantitative nature of pyrosequencing enabled us to assign all putative alleles to the two DRB loci, which is generally not possible using traditional methods. Our method of obtaining locus‐specific MHC genotypes will enhance population genetic analyses and studies on disease susceptibility in nonmodel wildlife species.
Mouse models of laminopathies
Authors: Zhang Haoyue , Kieckhaefer Julia E. , Cao Kan 
Published: October 2012

AbstractThe A‐ and B‐type lamins are nuclear intermediate filament proteins in eukaryotic cells with a broad range of functions, including the organization of nuclear architecture and interaction with proteins in many cellular functions. Over 180 disease‐causing mutations, termed ‘laminopathies,’ have been mapped throughout LMNA, the gene for A‐type lamins in humans. Laminopathies can range from muscular dystrophies, cardiomyopathy, to Hutchinson–Gilford progeria syndrome. A number of mouse lines carrying some of the same mutations as those resulting in human diseases have been established. These LMNA‐related mouse models have provided valuable insights into the functions of lamin A biogenesis and the roles of individual A‐type lamins during tissue development. This review groups these LMNA‐related mouse models into three categories: null mutants, point mutants, and progeroid mutants. We compare their phenotypes and discuss their potential implications in laminopathies and aging.