bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptional regulator early growth response gene 2 (Egr2) is required for T cell anergy in vitro and in vivo
Authors: Zheng Yan , Zha Yuanyuan , Driessens Gregory , Locke Frederick , Gajewski Thomas F.
Published: November 2012

T cell receptor engagement in the absence of costimulation results in a hyporesponsive state termed anergy. Understanding the transcriptional regulation of other T cell differentiation states has provided critical information regarding the biology of T cell regulation in vivo. However, the transcriptional regulation of T cell anergy has been poorly understood. Using the key anergy target gene diacylglycerol kinase (DGK) α as a focal point, we identified early growth response gene 2 (Egr2) as a central transcription factor that regulates the anergic state. Conditional Egr2 deletion in peripheral T cells abolishes induced expression of DGK-α and other anergy genes and restores Ras/MAPK signaling, IL-2 production, and proliferation upon attempted anergy induction. Using superantigen- and tumor-induced anergy models, we found that Egr2 is necessary for anergy induction in vivo. Collectively, our results implicate Egr2 as an essential transcriptional regulator of the T cell anergy program.
Regulation of PTEN activity by p38δ-PKD1 signaling in neutrophils confers inflammatory responses in the lung
Authors: Ittner Arne , Block Helena , Reichel Christoph A. , Varjosalo Markku , Gehart Helmuth , Sumara Grzegorz , Gstaiger Matthias , Krombach Fritz , Zarbock Alexander , Ricci Romeo
Published: November 2012

Despite their role in resolving inflammatory insults, neutrophils trigger inflammation-induced acute lung injury (ALI), culminating in acute respiratory distress syndrome (ARDS), a frequent complication with high mortality in humans. Molecular mechanisms underlying recruitment of neutrophils to sites of inflammation remain poorly understood. Here, we show that p38 MAP kinase p38δ is required for recruitment of neutrophils into inflammatory sites. Global and myeloid-restricted deletion of p38δ in mice results in decreased alveolar neutrophil accumulation and attenuation of ALI. p38δ counteracts the activity of its downstream target protein kinase D1 (PKD1) in neutrophils and myeloid-restricted inactivation of PKD1 leads to exacerbated lung inflammation. Importantly, p38δ and PKD1 conversely regulate PTEN activity in neutrophils, thereby controlling their extravasation and chemotaxis. PKD1 phosphorylates p85α to enhance its interaction with PTEN, leading to polarized PTEN activity, thereby regulating neutrophil migration. Thus, aberrant p38δ–PKD1 signaling in neutrophils may underlie development of ALI and life-threatening ARDS in humans.
Congenital B cell lymphocytosis explained by novel germline CARD11 mutations
Authors: Snow Andrew L. , Xiao Wenming , Stinson Jeffrey R. , Lu Wei , Chaigne-Delalande Benjamin , Zheng Lixin , Pittaluga Stefania , Matthews Helen F. , Schmitz Roland , Jhavar Sameer , Kuchen Stefan , Kardava Lela , Wang Wei , Lamborn Ian T. , Jing Huie , Raffeld Mark , Moir Susan , Fleisher Thomas A. , Staudt Louis M. , Su Helen C. , Lenardo Michael J.
Published: November 2012

Nuclear factor-κB (NF-κB) controls genes involved in normal lymphocyte functions, but constitutive NF-κB activation is often associated with B cell malignancy. Using high-throughput whole transcriptome sequencing, we investigated a unique family with hereditary polyclonal B cell lymphocytosis. We found a novel germline heterozygous missense mutation (E127G) in affected patients in the gene encoding CARD11, a scaffolding protein required for antigen receptor (AgR)–induced NF-κB activation in both B and T lymphocytes. We subsequently identified a second germline mutation (G116S) in an unrelated, phenotypically similar patient, confirming mutations in CARD11 drive disease. Like somatic, gain-of-function CARD11 mutations described in B cell lymphoma, these germline CARD11 mutants spontaneously aggregate and drive constitutive NF-κB activation. However, these CARD11 mutants rendered patient T cells less responsive to AgR-induced activation. By reexamining this rare genetic disorder first reported four decades ago, our findings provide new insight into why activating CARD11 mutations may induce B cell expansion and preferentially predispose to B cell malignancy without dramatically perturbing T cell homeostasis.
Mn-doped TiO2 thin films with significantly improved optical and electrical properties
Authors: Lu Liu , Xia Xiaohong , Luo J K , Shao G
Published: November 2012

TiO2 thin films with various Mn doping contents were fabricated by reactive magnetron sputtering deposition at 550 °C and their structural, optical and electrical properties were characterized. All films were made of densely packed columnar grains with a fibrous texture along the normal direction of the substrate. The as-deposited structure in the pure TiO2 film consisted of anatase grains with the [1 0 1] texture. Mn incorporation stabilized the rutile phase and induced lattice contraction in the [1 0 0] direction. The texture in the Mn-doped films changed from [1 1 0] to [2 0 0] with increasing Mn content. The incorporation of Mn in the TiO2 lattice introduced intermediate bands into its narrowed forbidden gap, leading to remarkable red-shifts in the optical absorption edges, together with significantly improved electrical conductivity of the thin films. Hall measurement showed that the incorporation of Mn-induced p-type conductivity, with hole mobility in heavily doped TiO2 (∼40% Mn) being about an order higher than electron mobility in single-crystal rutile TiO2. Oxygen vacancies, on the other hand, interacted with substitutional Mn atoms to reduce its effect on optical and electrical properties.
Obtaining precise electron swarm parameters from a pulsed Townsend setup
Authors: Dahl Dominik A , Teich Timm H , Franck Christian M
Published: November 2012

A swarm parameter experiment is introduced, which implements the pulsed Townsend (PT) electrical method with a high degree of automatization. The experimental setup and measurement procedures are described in detail, and a comprehensive definition of the swarm model is given and used for signal analysis. The intrinsic parameters of electron drift currents in the PT method are identified, and novel regression methods are presented for obtaining electron swarm parameters from PT measurements. The setup and methods are verified with measurements in Ar, N2 and CO2, which are focused on the (E/N)-range between dominating electron attachment and weakly dominating ionization. The present data are compared with experimental reference data, and to electron transport coefficients calculated by a Boltzmann solver and simulated by a Monte Carlo method. Excellent agreement was found between the present data and the Monte Carlo results, but there are significant discrepancies to widely used recommended swarm parameters of N2 and CO2. Finally, it is proposed to revise some hitherto recommended values of electron transport coefficients.
Fluid simulation of the phase-shift effect in Ar/CF4 capacitively coupled plasmas
Authors: Zhang Yu-Ru , Bogaerts Annemie , Wang You-Nian
Published: November 2012

A two-dimensional self-consistent fluid model combined with the full set of Maxwell equations is employed to investigate an Ar/CF4 capacitively coupled plasma, focusing on the phase-shift effect on the plasma characteristics at various frequencies and gas mixture ratios. When the discharge is sustained by a single frequency at 13.56 MHz in an Ar/CF4 mixture with a ratio of 0.9/0.1, no obvious difference is detected between the electron densities obtained in the so-called electrostatic model (with only the static electric fields taken into account) and the electromagnetic model (which includes the electromagnetic effects). However, as the frequency increases to 60 and 100 MHz, the difference becomes distinct, due to the significant influence of the electromagnetic effects.

The phase-shift effect on the plasma radial uniformity has also been investigated in a dual frequency discharge, i.e. when the top driven source is switched on with a phase difference φ ranging from 0 to π, in the frequency range 13.56–100 MHz. At low concentration of CF4 (10%), Ar+ ions are the major positive ions in the entire range of frequencies. When the frequency is low, i.e. 13.56 MHz, the Ar+ density exhibits an off-axis peak at φ = 0 due to the edge effect, and a better uniformity caused by the phase-shift modulation is obtained at φ = π. At 60 MHz, the Ar+ density varies from edge-peaked at φ = 0 to uniform (i.e. at φ = 0.53π), and finally at φ = π, a broad maximum is observed at the centre due to the standing-wave effect. As the frequency increases to 100 MHz, the best radial uniformity is reached at 0.25π, and the maximum moves again towards the radial wall in the reverse-phase case (φ = π) due to the dominant skin effect.

When the frequency is fixed at 100 MHz, the phase-shift control shows a different behaviour at a high concentration of CF4. For instance, the

density profiles shift from edge-high over uniform to centre-high, as the CF4 content increases from 10% to 90%, which indicates that the skin effect is suppressed by the high electronegativity of the Ar/CF4 = 0.1/0.9 mixture. Moreover, the ratio of the total negative ion density to electron density decreases with increasing frequency, and it increases with CF4 content. In addition,

ions become the major positive ions in the discharge with 90% CF4.
Formation process and electron-beam incident energy dependence of one-dimensional uneven peanut-shaped C60 polymer studied using in situ high-resolution infrared spectroscopy and density-functional calculations
Authors: Takashima Akito , Nishii Toshiaki , Onoe Jun
Published: November 2012

A 3 kV electron-beam irradiation of a C60 film gives rise to formation of one-dimensional (1D) uneven peanut-shaped C60 polymer with a cross-linked structure close to that of the P08 C120 stable isomer obtained from the general Stone–Wales rearrangement. In this study, we examined the evolution of infrared (IR) spectra of C60 films with respect to electron beam (EB) irradiation time, using in situ high-resolution IR spectroscopy and first-principles density-functional calculations, and found semi-quantitatively that the 1D uneven peanut-shaped C60 polymer is formed via intermediate polymers with a cross-linkage close to that of P04 and P06 C120 isomers obtained from GWS rearrangement. In addition, we examined the dependence of EB-induced C60 polymerization on an incident energy of EB in the range 3–7 kV. IR spectra obtained for 5 and 7 kV EB irradiation of C60films showed the same product as for 3 kV EB irradiation. However, when 5 and 7 kV EBs continued to irradiate C60 films for a long time after the polymer formation, the 1D peanut-shaped polymer did not proceed to become 1D polymers with a more coalesced linkage than that of the P08 one but was destroyed to become amorphous carbons.
Experimental imaging of separatrix splitting on DIII-D
Authors: Shafer M.W. , Unterberg E.A. , Orlov D.M. , Evans T.E. , Harris J.H. , Hillis D.L. , Maingi R. , Moyer R.A. , Nazikian R. , Wingen A.
Published: November 2012

Perturbations in the plasma boundary due to the application of non-axisymmetric n = 3 fields (δ
B/B ∼ 10−4−10−3) were measured in the X-point region in DIII-D by tangential imaging of extreme ultra-violet and soft x-ray emission. Vacuum-field calculations show that these perturbations take the form of lobes extending outwards from the unperturbed separatrix. These structures can be resolved in experiment by performing a differential measurement of the image for different toroidal phases of the applied perturbation. Forward modelling of the line-integrated image with a synthetic diagnostic is used to directly compare the measurement with vacuum-field calculations. Results indicate the existence of these lobes match well with the measured data. These lobes are observed to shift poloidally on the high-field side of the magnetic axis as the edge magnetic safety factor is varied, consistent with vacuum-field calculations.
Radiative type-III ELMy H-mode in all-tungsten ASDEX Upgrade
Authors: Rapp J. , Kallenbach A. , Neu R. , Eich T. , Fischer R. , Herrmann A. , Potzel S. , van Rooij G.J. , Zielinski J.J.
Published: November 2012

The type-III ELMy H-mode might be the solution for an integrated ITER operation scenario fulfilling the fusion power amplification factor (output fusion power to input heating power) of Q = 10 with simultaneous acceptable steady-state and transient power loads to the plasma-facing components. This highly radiative type-III ELMy H-mode is achieved by nitrogen seeding. Experiments on the tokamak ASDEX Upgrade, in which all plasma-facing components are coated with tungsten, showed favourable confinement conditions (H
98(y,2) = 1) at high plasma pressure (β
N = 2.4). The power load to the plasma-facing components is as low as ≈3 MW m−2 during the peak heat loads due to edge localized modes (ELMs) at high radiative power fractions of f
rad ≈ 0.75. In those high-density discharges the central impurity concentration is very low as a result of hollow nitrogen density profiles and minimal erosion of tungsten. The tungsten erosion is not only suppressed in between ELMs, when the divertor is detached, but also during the type-III ELM activity. Such low impurity concentrations in the plasma core might lead to even higher fusion amplification factors in ITER than 10. This is a demonstration of the compatibility of the radiating type-III ELMy H-mode with a tungsten divertor and main chamber wall, with sufficient confinement and favourable power exhaust characteristics. Together with previous results in all-carbon devices this demonstration strengthens the case for a potential application of a Q = 10 scenario on ITER.
Formularization of the confinement enhancement factor as a function of the heating profile for FFHR-d1 core plasma design
Authors: Miyazawa J. , Goto T. , Sakamoto R. , Motojima G. , Suzuki C. , Funaba H. , Morisaki T. , Masuzaki S. , Yamada I. , Murakami S. , Suzuki Y. , Yokoyama M. , Peterson B.J. , Yamada H. , Sagara A.
Published: November 2012

A quantitative estimation of the confinement enhancement due to the heating profile effect is introduced to the helical fusion DEMO reactor design of FFHR-d1, based on the experimental results of the Large Helical Device. By applying this to the direct profile extrapolation (DPE) method, radial profiles in the reactor are extrapolated from experimental results. In reactor plasmas, the heat deposition profile of alpha heating is expected to be peaked in the core region as in the case of tangential neutral beam (NB) injection on low-density plasmas. The height of the pressure profile normalized by the gyro-Bohm-type parameter dependence increases with the power (∼0.6) of the peaking factor of the heat deposition profile, as long as the core confinement degradation observed in low-density plasmas is ignored. According to this observation, the confinement enhancement factor expected under the self-ignition condition ranges from ∼1.1 to ∼1.7, for example, depending on the used data. Degradation of the global energy confinement observed in high-density NB-heated plasmas is mitigated and the gyro-Bohm-type parameter dependence reappears after introducing the confinement enhancement due to the heating profile effect. Finally, typical example profiles in FFHR-d1 are provided by the DPE method for future analyses.
Active feedback stabilization of the flute instability in a mirror machine using field-aligned coils
Authors: Lifshitz A. , Be'ery I. , Fisher A. , Ron A. , Fruchtman A.
Published: November 2012

A plasma confined in linear mirror machines is unstable even at low β, mainly because of the flute instability. One possible way to stabilize the plasma is to use active feedback to correct the plasma shape in real time. The theoretically investigated apparatus consists of feedback coils aligned with the magnetic field, immersed in a cold plasma around the hot core. When the current through the feedback coils changes, the plasma moves to conserve the magnetic flux via compressional Alfvén waves. An analytical model is used to find a robust feedback algorithm with zero residual currents. It is shown that due to the plasma's rotation, maximal stability is obtained with a large phase angle between the perturbations' modes and the feedback integral-like term. Finally, a two-dimensional MHD simulation implementing the above algorithm in fact shows stabilization of the plasma with zero residual currents.
Two-dimensional characterization of ELM precursors in NSTX
Authors: Sechrest Y. , Munsat T. , Battaglia D.J. , Zweben S.J.
Published: November 2012

Gas puff imaging has been used to capture the two-dimensional evolution of edge-localized mode (ELM) precursors. Precursor events were observed preceding ELMs and ELM-induced H–L back-transitions in radio-frequency heated H-mode plasmas, and the growth of the precursor mode through the ELM filamentation was imaged in the plane perpendicular to the local B-field. Strong edge intensity modulations appeared to propagate in the electron diamagnetic direction while steadily drifting radially outwards. Intensity fluctuations were observed at frequencies around 20 kHz and wavenumbers of 0.05–0.2 cm−1. Upon growing to a trigger point, precursor fluctuations were seen to form filamentary structures and move into the scrape-off layer (SOL) explosively with radial velocities peaking at 8 km s−1. Once in the SOL, filaments reverse their propagation direction and travel in the ion diamagnetic direction. Edge intensity fluctuations are strongly correlated with magnetic signals from Mirnov coils, and toroidally distributed coils estimated toroidal mode numbers of n = 5–10. Quantitatively similar precursors have been observed in ohmic H-mode plasmas as well, though significantly fewer events are seen in the ohmic cases and none were observed in the near-threshold NBI H-modes studied.
MetaGeneTack: ab initio detection of frameshifts in metagenomic sequences
Authors: Tang Shiyuyun , Antonov Ivan , Borodovsky Mark
Published: November 2012

Summary: Frameshift (FS) prediction is important for analysis and biological interpretation of metagenomic sequences. Since a genomic context of a short metagenomic sequence is rarely known, there is not enough data available to estimate parameters of species-specific statistical models of protein-coding and non-coding regions. The challenge of ab initio FS detection is, therefore, two fold: (i) to find a way to infer necessary model parameters and (ii) to identify positions of frameshifts (if any). Here we describe a new tool, MetaGeneTack, which uses a heuristic method to estimate parameters of sequence models used in the FS detection algorithm. It is shown on multiple test sets that the MetaGeneTack FS detection performance is comparable or better than the one of earlier developed program FragGeneScan.

Availability and implementation: MetaGeneTack is available as a web server at http://exon.gatech.edu/GeneTack/cgi/metagenetack.cgi. Academic users can download a standalone version of the program from http://exon.gatech.edu/license_download.cgi.

Contact:  borodovsky@gatech.edu

Supplementary information: Supplementary data are available at Bioinformatics online.
Pathway hunting by random survival forests
Authors: Chen Xi , Ishwaran Hemant
Published: November 2012

Motivation: Pathway or gene set analysis has been widely applied to genomic data. Many current pathway testing methods use univariate test statistics calculated from individual genomic markers, which ignores the correlations and interactions between candidate markers. Random forests-based pathway analysis is a promising approach for incorporating complex correlation and interaction patterns, but one limitation of previous approaches is that pathways have been considered separately, thus pathway cross-talk information was not considered.

Results: In this article, we develop a new pathway hunting algorithm for survival outcomes using random survival forests, which prioritize important pathways by accounting for gene correlation and genomic interactions. We show that the proposed method performs favourably compared with five popular pathway testing methods using both synthetic and real data. We find that the proposed methodology provides an efficient and powerful pathway modelling framework for high-dimensional genomic data.

Availability: The R code for the analysis used in this article is available upon request.

Contact:  xi.steven.chen@gmail.com

Supplementary information:  Supplementary data are available at Bioinformatics online.
PBSIM: PacBio reads simulator—toward accurate genome assembly
Authors: Ono Yukiteru , Asai Kiyoshi , Hamada Michiaki
Published: November 2012

Motivation: PacBio sequencers produce two types of characteristic reads (continuous long reads: long and high error rate and circular consensus sequencing: short and low error rate), both of which could be useful for de novo assembly of genomes. Currently, there is no available simulator that targets the specific generation of PacBio libraries.

Results: Our analysis of 13 PacBio datasets showed characteristic features of PacBio reads (e.g. the read length of PacBio reads follows a log-normal distribution). We have developed a read simulator, PBSIM, that captures these features using either a model-based or sampling-based method. Using PBSIM, we conducted several hybrid error correction and assembly tests for PacBio reads, suggesting that a continuous long reads coverage depth of at least 15 in combination with a circular consensus sequencing coverage depth of at least 30 achieved extensive assembly results.

Availability: PBSIM is freely available from the web under the GNU GPL v2 license (http://code.google.com/p/pbsim/).

Contact:  mhamada@k.u-tokyo.ac.jp

Supplementary information:  Supplementary data are available at Bioinformatics online.
HD-CNV: hotspot detector for copy number variants
Authors: Butler Jenna L. , Osborne Locke Marjorie Elizabeth , Hill Kathleen A. , Daley Mark
Published: November 2012

Summary: Copy number variants (CNVs) are a major source of genetic variation. Comparing CNVs between samples is important in elucidating their potential effects in a wide variety of biological contexts. HD-CNV (hotspot detector for copy number variants) is a tool for downstream analysis of previously identified CNV regions from multiple samples, and it detects recurrent regions by finding cliques in an interval graph generated from the input. It creates a unique graphical representation of the data, as well as summary spreadsheets and UCSC (University of California, Santa Cruz) Genome Browser track files. The interval graph, when viewed with other software or by automated graph analysis, is useful in identifying genomic regions of interest for further study.

Availability and implementation: HD-CNV is an open source Java code and is freely available, with tutorials and sample data from http://daleylab.org.

Contact:  jcamer7@uwo.ca
Binary Interval Search: a scalable algorithm for counting interval intersections
Authors: Layer Ryan M. , Skadron Kevin , Robins Gabriel , Hall Ira M. , Quinlan Aaron R.
Published: November 2012

Motivation: The comparison of diverse genomic datasets is fundamental to understand genome biology. Researchers must explore many large datasets of genome intervals (e.g. genes, sequence alignments) to place their experimental results in a broader context and to make new discoveries. Relationships between genomic datasets are typically measured by identifying intervals that intersect, that is, they overlap and thus share a common genome interval. Given the continued advances in DNA sequencing technologies, efficient methods for measuring statistically significant relationships between many sets of genomic features are crucial for future discovery.

Results: We introduce the Binary Interval Search (BITS) algorithm, a novel and scalable approach to interval set intersection. We demonstrate that BITS outperforms existing methods at counting interval intersections. Moreover, we show that BITS is intrinsically suited to parallel computing architectures, such as graphics processing units by illustrating its utility for efficient Monte Carlo simulations measuring the significance of relationships between sets of genomic intervals.

Availability:  https://github.com/arq5x/bits.

Contact:  arq5x@virginia.edu

Supplementary information: Supplementary data are available at Bioinformatics online.
Demethylesterification of Cell Wall Pectins in Arabidopsis Plays a Role in Seed Germination
Authors: Müller Kerstin , Levesque-Tremblay Gabriel , Bartels Sebastian , Weitbrecht Karin , Wormit Alexandra , Usadel Bjoern , Haughn George , Kermode Allison R.
Published: November 2012

The methylesterification status of cell wall homogalacturonans, mediated through the action of pectin methylesterases (PMEs), influences the biophysical properties of plant cell walls such as elasticity and porosity, important parameters for cell elongation and water uptake. The completion of seed germination requires cell wall extensibility changes in both the radicle itself and in the micropylar tissues surrounding the radicle. In wild-type seeds of Arabidopsis (Arabidopsis thaliana), PME activities peaked around the time of testa rupture but declined just before the completion of germination (endosperm weakening and rupture). We overexpressed an Arabidopsis PME inhibitor to investigate PME involvement in seed germination. Seeds of the resultant lines showed a denser methylesterification status of their cell wall homogalacturonans, but there were no changes in the neutral sugar and uronic acid composition of the cell walls. As compared with wild-type seeds, the PME activities of the overexpressing lines were greatly reduced throughout germination, and the low steady-state levels neither increased nor decreased. The most striking phenotype was a significantly faster rate of germination, which was not connected to altered testa rupture morphology but to alterations of the micropylar endosperm cells, evident by environmental scanning electron microscopy. The transgenic seeds also exhibited an apparent reduced sensitivity to abscisic acid with respect to its inhibitory effects on germination. We speculate that PME activity contributes to the temporal regulation of radicle emergence in endospermic seeds by altering the mechanical properties of the cell walls and thereby the balance between the two opposing forces of radicle elongation and mechanical resistance of the endosperm.
iRootHair: A Comprehensive Root Hair Genomics Database
Authors: Kwasniewski Miroslaw , Nowakowska Urszula , Szumera Jakub , Chwialkowska Karolina , Szarejko Iwona
Published: November 2012

The specialized root epidermis cells of higher plants produce long, tubular outgrowths called root hairs. Root hairs play an important role in nutrient and water uptake, and they serve as a valuable model in studies of plant cell morphogenesis. More than 1,300 articles that describe the biological processes of these unique cells have been published to date. As new fields of root hair research are emerging, the number of new papers published each year and the volumes of new relevant data are continuously increasing. Therefore, there is a general need to facilitate studies on root hair biology by collecting, presenting, and sharing the available information in a systematic, curated manner. Consequently, in this paper, we present a comprehensive database of root hair genomics, iRootHair, which is accessible as a Web-based service. The current version of the database includes information about 153 root hair-related genes that have been identified to date in dicots and monocots along with their putative orthologs in higher plants with sequenced genomes. In order to facilitate the use of the iRootHair database, it is subdivided into interrelated, searchable sections that describe genes, processes of root hair formation, root hair mutants, and available references. The database integrates bioinformatics tools with a focus on sequence identification and annotation. iRootHair is a unique resource for root hair research that integrates the large volume of data related to root hair genomics in a single, curated, and expandable database that is freely available at www.iroothair.org.
Rapid Reversion from Monomer to Dimer Regenerates the Ultraviolet-B Photoreceptor UV RESISTANCE LOCUS8 in Intact Arabidopsis Plants
Authors: Heilmann Monika , Jenkins Gareth I.
Published: November 2012

Arabidopsis (Arabidopsis thaliana) UV RESISTANCE LOCUS8 (UVR8) is a photoreceptor that specifically mediates photomorphogenic responses to ultraviolet (UV)-B in plants. UV-B photoreception induces the conversion of the UVR8 dimer into a monomer that interacts with the CONSTITUTIVELY PHOTOMORPHOGENIC1 (COP1) protein to regulate gene expression. However, it is not known how the dimeric photoreceptor is regenerated in plants. Here, we show, by using inhibitors of protein synthesis and degradation via the proteasome, that the UVR8 dimer is not regenerated by rapid de novo synthesis following destruction of the monomer. Rather, regeneration occurs by reversion from the monomer to the dimer. However, regeneration of dimeric UVR8 in darkness following UV-B exposure occurs much more rapidly in vivo than in vitro with illuminated plant extracts or purified UVR8, indicating that rapid regeneration requires intact cells. Rapid dimer regeneration in vivo requires protein synthesis, the presence of a carboxyl-terminal 27-amino acid region of UVR8, and the presence of COP1, which is known to interact with the carboxyl-terminal region. However, none of these factors can account fully for the difference in regeneration kinetics in vivo and in vitro, indicating that additional proteins or processes are involved in UVR8 dimer regeneration in vivo.
The effect of ovine and bovine milk on the textural properties of Lighvan cheese during ripening
Authors: Aminifar Mehrnaz , Hamedi Manouchehr , Emam‐Djomeh Zahra , Mehdinia Ali
Published: November 2012

The effect of milk origin on the physicochemical characteristics, microstructure and texture of Lighvan cheese was investigated over a 90‐day ripening period. Besides fat, other physicochemical properties of Lighvan cheese were affected by milk type. The moisture content of Lighvan cheese decreased when half or all the ovine milk was substituted with bovine milk. The Lighvan cheese's microstructural properties and porosity were affected by type of milk and ripening time. Compaction of cheeses manufactured from ovine and mixed ovine and bovine milk is similar, and more than that of bovine Lighvan cheese. Ovine Lighvan cheese is harder and less brittle than bovine and mixed bovine and ovine.
Sick leave during pregnancy: a longitudinal study of rates and risk factors in a Norwegian population
Authors: Dørheim SK , Bjorvatn B , Eberhard‐Gran M
Published: November 2012

Objective

To describe the prevalence of, reasons given for, and factors associated with sick leave during pregnancy.

Design

Longitudinal, population‐based descriptive study.

Setting

Akershus University Hospital, Norway.

Population

All women scheduled to give birth at the hospital (November 2008 to April 2010).

Methods

Consenting women were handed a questionnaire at the routine ultrasound check at 17 weeks of gestation. Women returning this questionnaire received a second questionnaire at 32 weeks of gestation. Multiple logistic regression analyses were performed to examine associations with somatic, psychiatric and social factors.

Main outcome measures

Rates and duration of sick leave.

Results

By 32 weeks of gestation, 63.2% of the 2918 women included were on sick leave, and 75.3% had been on sick leave at some point during their pregnancy. Pelvic girdle pain and fatigue/sleep problems were the main reasons given for sick leave. Being on sick leave in all trimesters was strongly associated with hyperemesis, exercising less than weekly, chronic pain before or during pregnancy, infertility treatment (all P < 0.001); younger maternal age, conflicts in the workplace (both P < 0.01); multiparity, previous depression, insomnia and lower education (all P < 0.05). Sick leave was associated with elective caesarean section and higher infant birthweight (P < 0.01). Adjustment of the work situation was associated with 1 week shorter duration of sick leave.

Conclusions

Most women receive sick leave during pregnancy, but sick leave might not be caused by pregnancy alone. Previous medical and psychiatric history, work conditions and socio‐economic factors need to be addressed to understand sick leave during pregnancy.
Timing of administration of prophylactic antibiotics for caesarean section: a systematic review and meta‐analysis
Authors: Baaqeel H , Baaqeel R
Published: November 2012

Background

Prophylactic antibiotics reduce infectious morbidity from caesarean section. The timing of their administration, however, is a matter of controversy.

Objectives

To examine maternal and neonatal infectious morbidity in women receiving preoperative prophylaxis compared with those receiving intraoperative administration.

Search strategy

Medline, Embase, Current Controlled Trials and Cochrane Central were searched from their inception dates to December 2011.

Selection criteria

Randomised controlled trials of a single dose of any antibiotic comparing preoperative with intraoperative administration were selected.

Data collection and analysis

Trial characteristics, outcomes and quality measures, based on the Cochrane tool for risk of bias, were independently extracted. The random effect model of DerSimonian and Laird to estimate relative risks (RRs) for maternal and neonatal outcomes was used.

Main results

Six trials met the inclusion criteria, reporting on 2313 women and 2345 newborns. Preoperative administration was associated with a significant 41% reduction in the rate of endometritis compared with intraoperative administration (RR 0.59; 95% confidence interval [95% CI] 0.37–0.94; I2 0%). In the preoperative group, there were nonsignificant reductions in the rates of wound infection (RR 0.71; 95% CI 0.44–1.14; I2 0%), maternal febrile morbidity (RR 0.94; 95% CI 0.46–1.95; I2 0%), neonatal sepsis (RR 0.81; 95% CI 0.47–1.41; I2 0%), neonatal septic work‐up (RR 0.93; 95% CI 0.71–1.21; I2 0%) and neonatal intensive‐care unit admission (RR 0.92; 95% CI 0.65–1.28; I2 0%). There were nonsignificant increases in the rates of maternal pyelonephritis (RR 1.09; 95% CI 0.49–2.43; I2 0%) and neonatal pneumonia (RR 3.36; 95% CI 0.55–20.47; I2 0%).

Conclusions

Compared with intraoperative administration, preoperative antibiotics significantly reduce the rate of endometritis. The lack of neonatal adverse effects should be cautiously interpreted given the limited power of the trials to detect such effects.
Enhanced AMPA receptor activity increases operant alcohol self‐administration and cue‐induced reinstatement
Authors: Cannady Reginald , Fisher Kristen R. , Durant Brandon , Besheer Joyce , Hodge Clyde W.
Published: November 2012

Long‐term alcohol exposure produces neuroadaptations that contribute to the progression of alcohol abuse disorders. Chronic alcohol consumption results in strengthened excitatory neurotransmission and increased α‐amino‐3‐hydroxyl‐5‐methyl‐4‐isoxazole‐propionate receptors (AMPA) receptor signaling in animal models. However, the mechanistic role of enhanced AMPA receptor activity in alcohol‐reinforcement and alcohol‐seeking behavior remains unclear. This study examined the role of enhanced AMPA receptor function using the selective positive allosteric modulator, aniracetam, in modulating operant alcohol self‐administration and cue‐induced reinstatement. Male alcohol‐preferring (P‐) rats, trained to self‐administer alcohol (15%, v/v) versus water were pre‐treated with aniracetam to assess effects on maintenance of alcohol self‐administration. To determine reinforcer specificity, P‐rats were trained to self‐administer sucrose (0.8%, w/v) versus water, and effects of aniracetam were tested. The role of aniracetam in modulating relapse of alcohol‐seeking was assessed using a response contingent cue‐induced reinstatement procedure in P‐rats trained to self‐administer 15% alcohol. Aniracetam pre‐treatment significantly increased alcohol‐reinforced responses relative to vehicle treatment. This increase was not attributed to aniracetam‐induced hyperactivity as aniracetam pre‐treatment did not alter locomotor activity. AMPA receptor involvement was confirmed because 6,7‐dinitroquinoxaline‐2,3‐dione (AMPA receptor antagonist) blocked the aniracetam‐induced increase in alcohol self‐administration. Aniracetam did not alter sucrose‐reinforced responses in sucrose‐trained P‐rats, suggesting that enhanced AMPA receptor activity is selective in modulating the reinforcing function of alcohol. Finally, aniracetam pre‐treatment potentiated cue‐induced reinstatement of alcohol‐seeking behavior versus vehicle‐treated P‐rats. These data suggest that enhanced glutamate activity at AMPA receptors may be key in facilitating alcohol consumption and seeking behavior, which could ultimately contribute to the development of alcohol abuse disorders.
Renal pericytes: regulators of medullary blood flow
Authors: Kennedy‐Lydon T. M. , Crawford C. , Wildman S. S. P. , Peppiatt‐Wildman C. M.
Published: November 2012

Regulation of medullary blood flow (MBF) is essential in maintaining normal kidney function. Blood flow to the medulla is supplied by the descending vasa recta (DVR), which arise from the efferent arterioles of juxtamedullary glomeruli. DVR are composed of a continuous endothelium, intercalated with smooth muscle‐like cells called pericytes. Pericytes have been shown to alter the diameter of isolated and in situ DVR in response to vasoactive stimuli that are transmitted via a network of autocrine and paracrine signalling pathways. Vasoactive stimuli can be released by neighbouring tubular epithelial, endothelial, red blood cells and neuronal cells in response to changes in NaCl transport and oxygen tension. The experimentally described sensitivity of pericytes to these stimuli strongly suggests their leading role in the phenomenon of MBF autoregulation. Because the debate on autoregulation of MBF fervently continues, we discuss the evidence favouring a physiological role for pericytes in the regulation of MBF and describe their potential role in tubulo‐vascular cross‐talk in this region of the kidney. Our review also considers current methods used to explore pericyte activity and function in the renal medulla.
Recent advances in laparoscopic surgery
Authors: Lee Wei‐Jei , Chan Chien‐Pin , Wang Bing‐Yen
Published: November 2012

Laparoscopic surgery has been widely adopted and new technical innovation, procedures and evidence based knowledge are persistently emerging. This review documents recent major advancements in laparoscopic surgery. A PubMed search was made in order to identify recent advances in this field. We reviewed the recent data on randomized trials in this field as well as papers of systematic review. Laparoscopic cholecystectomy is the most frequently performed procedure, followed by laparoscopic bariatric surgery. Although bile duct injuries are relatively uncommon (0.15%–0.6%), intraoperative cholangiography still plays a role in reducing the cost of litigation. Laparoscopic bariatric surgery is the most commonly performed laparoscopic gastrointestinal surgery in the USA, and laparoscopic Nissen fundoplication is the treatment of choice for intractable gastroesophageal reflux disease. Recent randomized trials have demonstrated that laparoscopic gastric and colorectal cancer resection are safe and oncologically correct procedures. Laparoscopic surgery has also been widely developed in hepatic, pancreatic, gynecological and urological surgery. Recently, SILS and robotic surgery have penetrated all specialties of abdominal surgery. However, evidence‐based medicine has failed to show major advantages in SILS, and the disadvantage of robotic surgery is the high costs related to purchase and maintenance of technology. Laparoscopic surgery has become well developed in recent decades and is the choice of treatment in abdominal surgery. Recently developed SILS techniques and robotic surgery are promising but their benefits remain to be determined.
Antifungal agents and therapy for infants and children with invasive fungal infections: a pharmacological perspective
Authors: Lestner Jodi M. , Smith P. Brian , Cohen‐Wolkowiez Michael , Benjamin Daniel K. , Hope William W.
Published: November 2012

Invasive fungal infections, although relatively rare, are life‐threatening diseases in premature infants and immunocompromised children. While many advances have been made in antifungal therapeutics in the last two decades, knowledge of the pharmacokinetics and pharmacodynamics of antifungal agents for infants and children remains incomplete. This review summarizes the pharmacology and clinical utility of currently available antifungal agents and discusses the opportunities and challenges for future research.
Searching the Internet for help with pain: Adolescent search, coping, and medication behaviour
Authors: Henderson Ellen M. , Keogh Edmund , Rosser Benjamin A. , Eccleston Christopher
Published: November 2012

Objectives

To explore a community sample of adolescents for engagement with online pain resources. To assess if the use of the Internet to search for health information correlated with measures of coping, risk taking, catastrophizing about pain, and engaging in the self‐management of pain.

Design

A cross‐sectional online study of community‐based adolescents (n = 105) recruited via schools to examine their use of the Internet to seek pain‐related information.

Methods

Adolescents completed questionnaires of pain coping, catastrophic thinking, risk‐taking behaviour, and medication use. Descriptive analyses were undertaken on event rates of pertinent behaviours, principally on information seeking and pain management behaviour. Correlational analyses were undertaken between coping and information seeking, and medication use.

Results

Few participants engaged in online pain information seeking. Those who did were more likely to be female and scored higher on medication use, catastrophizing, risk taking, and the total score on the Pain Coping Questionnaire.

Conclusions

Although adolescents are high users of the Internet, paradoxically they do not appear to use the Internet for information about pain and pain management. Further research should assess inhibitory and disinhibitory factors associated with information seeking about pain and chronic illness on the Internet.

Statement of Contribution

What is already known on this subject? Internet use in adolescents is common, mobile, and displays a level of technical awareness unparalleled by adults. The internet is postulated in previous research to present a platform for the delivery of health care, particularly information to aid health decision‐making for young people.

What does this study add? This study explores how adolescents use the internet to look for health information, particularly on pain and where this falls in a general profile of coping with illness. Interestingly and counterintuitively, adolescents did not use the internet to look for health or pain information. We hypothesize that there may be something about information on pain management that does not readily transfer to the digital world in a way that is useful to adolescent users.
Optogenetic reporters
Authors: Alford Spencer C. , Wu Jiahui , Zhao Yongxin , Campbell Robert E. , Knöpfel Thomas
Published: November 2012

The discovery of naturally evolved fluorescent proteins and their subsequent tuning by protein engineering provided the basis for a large family of genetically encoded biosensors that report a variety of physicochemical processes occurring in living tissue. These optogenetic reporters are powerful tools for live‐cell microscopy and quantitative analysis at the subcellular level. In this review, we present an overview of the transduction mechanisms that have been exploited for engineering these genetically encoded reporters. Finally, we discuss current and future efforts towards the combined use of various optogenetic actuators and reporters for simultaneously controlling and imaging the physiology of cells and tissues.
Up‐regulation of aldolase A and methylglyoxal production in adipocytes
Authors: Liu Jianghai , Desai Kaushik , Wang Rui , Wu Lingyun
Published: November 2012

Background and Purpose

We previously reported that up‐regulation of aldolase B, a key enzyme in fructose metabolism, was mainly responsible for vascular methylglyoxal (MG) overproduction under different pathological conditions. Here we investigated whether aldolase A, an enzyme of the glycolytic pathway, also caused MG overproduction in insulin‐sensitive adipocytes.

Experimental Approach

The relative contributions of different metabolic pathways or enzymes to MG generation were evaluated in cultured 3T3‐L1 adipocytes.

Key Results

Glucose (25 mM) had no effect on aldolase A gene expression, but insulin (100 nM) up‐regulated aldolase A mRNA and protein levels in the absence or presence of 25 mM glucose in adipocytes. Treatment with insulin increased levels of basal or glucose (25 mM)‐induced MG and glucose 6‐phosphate. However, insulin, glucose (25 mM) or their combination had no effect on cellular levels of sorbitol and fructose, but down‐regulated gene expression of aldolase B to a similar extent, when compared with the control group. Incubation of 3T3‐L1 adipocytes with fructose, acetone, acetol, threonine or glycine (25 mM), with or without insulin did not alter cellular MG levels. The elevated MG levels induced by insulin, glucose (25 mM) or their combination in adipocytes was completely reduced by siRNA knock down of aldolase A or application of 2‐deoxy‐D‐glucose (a non‐specific inhibitor of glucose uptake and glycolysis), but not by knock down of aldolase B.

Conclusion and Implications

Insulin enhanced MG overproduction in insulin‐sensitive adipocytes by up‐regulating aldolase A, a mechanism that could be involved in the development of insulin resistance and obesity.
An investigation of the needs of grandparents who are raising grandchildren
Authors: Harnett Paul H. , Dawe Sharon , Russell Melissa
Published: November 2012

Evidence suggests that children in out‐of‐home care function better when placed in kinship compared with foster care. Less is known about the functioning of children in the unique form of kinship care where grandparents are caring full‐time for their grandchildren in informal care arrangements. As grandparent carers are increasingly taking on this role, it is timely to investigate the functioning of the children in this form of care and the characteristics of the grandparents themselves. We compared the functioning of children in the two types of care. We also investigated carer characteristics, including the relationship between child functioning, social support and daily hassles on carer stress. One hundred fourteen cares and 180 children were assessed on a range of demographic and clinical measures. Children in grandparent care were displaying better behavioural and adaptive functioning than children living with foster carers. Grandparent carers reported higher levels of distress in the carer role. Predictors of carer stress included severity of child behaviour problems and daily hassles. Both group of carers and the children in their care would benefit from increased support from treatment services.