bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of silicon oxide nanowires and nanotubes with cobalt-palladium or palladium catalysts
Authors: Esterina Ria , Liu X. M. , Ross C. A. , Adeyeye A. O. , Choi W. K.
Published: July 2012

The dewetting behaviors of cobalt (Co), cobalt palladium (CoPd), and palladium (Pd) thin films on oxidized silicon substrates were examined. We observed the formation of craters in the oxide layer and pits in the Si substrate for larger CoPd or Pd catalyst particles and thinner oxide. Nanowires and nanotubes were observed near the Si pits. The nanowires and nanotubes grow via a vapor-solid-solid or vapor-liquid-solid mechanism with the silicon vapor source provided from the substrate. The original Si atoms that form the nanowires or nanotubes were oxidized in situ by the residual oxygen atoms present in the chamber. Some of the nanotubes had a series of embedded sub-catalysts that formed branches from the primary nanotube.
Zonal flow triggers the L-H transition in the Experimental Advanced Superconducting Tokamak
Authors: Manz P. , Xu G. S. , Wan B. N. , Wang H. Q. , Guo H. Y. , Cziegler I. , Fedorczak N. , Holland C. , Müller S. H. , Thakur S. C. , Xu M. , Miki K. , Diamond P. H. , Tynan G. R.
Published: July 2012

The kinetic energy transfer between shear flows and the ambient turbulence is investigated in the Experimental Advanced Superconducting Tokamak during the L-H transition. As the rate of energy transfer from the turbulence into the shear flow becomes comparable to the energy input rate into the turbulence, the transition into the H-mode occurs. As the observed behavior exhibits several predicted features of zonal flows, the results show the key role that zonal flows play in mediating the transition into H-mode.
Threshold voltage modeling under size quantization for ultra-thin silicon double-gate metal-oxide-semiconductor field-effect transistor
Authors: Medury Aditya Sankar , Bhat K. N. , Bhat Navakanta
Published: July 2012

We report on the threshold voltage modeling of ultra-thin (1 nm–5 nm) silicon body double-gate (DG) MOSFETs using self-consistent Poisson-Schrodinger solver (SCHRED). We define the threshold voltage (Vth) of symmetric DG MOSFETs as the gate voltage at which the center potential (Φc) saturates to Φc(sat), and analyze the effects of oxide thickness (tox) and substrate doping (NA) variations on Vth. The validity of this definition is demonstrated by comparing the results with the charge transition (from weak to strong inversion) based model using SCHRED simulations. In addition, it is also shown that the proposed Vth definition, electrically corresponds to a condition where the inversion layer capacitance (Cinv) is equal to the oxide capacitance (Cox) across a wide-range of substrate doping densities. A capacitance based analytical model based on the criteria Cinv=Cox is proposed to compute Φc(sat), while accounting for band-gap widening. This is validated through comparisons with the Poisson-Schrodinger solution. Further, we show that at the threshold voltage condition, the electron distribution (n(x)) along the depth (“x”) of the silicon film makes a transition from a strong single peak at the center of the silicon film to the onset of a symmetric double-peak away from the center of the silicon film.
Measurements of photoconductive transients in vapor grown CdTe:Cl over wide temperature and dopant concentration ranges
Authors: Popovych V. D. , Bester M.
Published: July 2012

Carrier dynamics in CdTe:Cl single crystals grown by the modified physical vapor transport method were studied by means of photocurrent transient measurements. The effective electron lifetime was determined by fitting of the decay parts of the experimental photoconductivity curves with exponential functions. Temperature dependence of the lifetime in the range from about 10 to 325 K and also its dependence on dopant content in the range of NCl = 1017–5 × 1019 cm−3 in the initial charge is discussed. High values of room temperature electron lifetime (τ = 2.5–4.5 μs) and resistivity (ρ = 2 × 108–5 × 109 Ω·cm) for crystals with NCl = 1018–1019 cm−3 were obtained, thus verifying their suitability as material for uncooled detectors of ionizing radiation.
Effect of a splitter plate on the dynamics of a vortex pair
Authors: Rabinovitch Jason , Brion Vincent , Blanquart Guillaume
Published: July 2012

An experimental and numerical study was performed to investigate and compare the behavior of a counter-rotating vortex pair and a single vortex in the vicinity of a wall. This analysis is motivated by the theoretical equivalence, in the inviscid limit, between these two configurations. A wind tunnel with two NACA0012 profiles mounted vertically with an optional splitter plate in the center and a stereoscopic particle image velocimetry system was used to experimentally study these interactions. Many significant differences were found between the two configurations, including the growth of the Crow instability in the two vortex configuration, but not in the one vortex/wall configuration. The numerical results re-enforced the experimental results, and emphasized the fundamental physical differences between the two configurations. While modeling a vortex wall system with an image vortex may give correct integral results for loads experienced by blades, this model does not accurately describe the downstream dynamics of the vortex system.
Experimental investigation effects of blend hazelnut oil on compression ignition engine performance characteristics and emission
Authors: Can Ibrahim
Published: July 2012

Studies on alternative fuels are important due to the worldwide depletion and accelerated exploitation of oil reserves. In this study, experiments were conducted to study the performance, emission, and specific fuel consumption of a compression ignition (CI) engine using hazelnut oil-based fuels. The main problems posed when using vegetable oil in a compression ignition engine are poor atomization, carbon deposits, ring sticking, etc. This is because of the high viscosity and low volatility of vegetable oil. The blending of hazelnut oil with diesel fuel has been shown to be an effective method to reduce engine problems associated with the high viscosity of hazelnut oil. A number of tests are conducted in a CI engine using different fuel mix ratios. To validate the result, the trials are repeated three times. The engine works at a fixed full load, but at different speeds, i.e., 1000 rpm, 1500 rpm, 2000 rpm, 2500 rpm, 3000 rpm, and 3500 rpm. The performance, specific fuel consumption, and the emission characteristics of exhaust gases of the engine are analyzed and compared. Measurements have indicated a negligible loss of engine power, a slight increase in specific fuel consumption, and a reduction in engine nitrogen oxides, hydrocarbons, and soot emission using blends of hazelnut oil with diesel fuel as compared to diesel fuel. The reduction in engine soot emission has been observed to increase with the increase of hazelnut oil percentage in the fuel blend.
Sustainability aspects and optimization of linseed biodiesel blends for compression ignition engine
Authors: Jindal S. , Salvi B. L.
Published: July 2012

The present work is aimed at experimental optimization of the linseed biodiesel blends as sustainable fuel for compression ignition engine. The experiments were conducted to study the comparative combustion, performance, and emissions characteristics of linseed biodiesel-diesel fuelled single cylinder compression ignition engine. The comparison was done with base fuel as diesel and linseed oil biodiesel at 1500 ± 10 rpm. Experiments were performed at various blends of linseed biodiesel and engine loads. At full load and LB10, comparable mass fraction burnt, better rate of pressure rise and brake mean effective pressure, improved indicated thermal efficiency (10% to 12%) and lower specific fuel consumption (4% to 6%) were observed. The emission of CO and hydrocarbon and opacity were reduced. But there was slight increase in CO2 and NO emissions. The optimized blend for linseed biodiesel can be taken as LB10. The linseeds are plant produce, which is renewable in nature and the products (i.e., linseed biodiesel) are recycled in the environment. So practically zero CO2 addition to the environment as compared to mineral fuels, leading to the mitigation of CO2.
Evidence for phase separation of ethanol-water mixtures at the hydrogen terminated nanocrystalline diamond surface
Authors: Janssens Stoffel D. , Drijkoningen Sien , Saitner Marc , Boyen Hans-Gerd , Wagner Patrick , Larsson Karin , Haenen Ken
Published: July 2012

Interactions between ethanol-water mixtures and a hydrophobic hydrogen terminated nanocrystalline diamond surface, are investigated by sessile drop contact angle measurements. The surface free energy of the hydrophobic surface, obtained with pure liquids, differs strongly from values obtained by ethanol-water mixtures. Here, a model which explains this difference is presented. The model suggests that, due to a higher affinity of ethanol for the hydrophobic surface, when compared to water, a phase separation occurs when a mixture of both liquids is in contact with the H-terminated diamond surface. These results are supported by a computational study giving insight in the affinity and related interaction at the liquid-solid interface.
Bifurcation theory for the L-H transition in magnetically confined fusion plasmas
Authors: Weymiens W. , de Blank H. J. , Hogeweij G. M. D. , de Valença J. C.
Published: July 2012

The mathematical field of bifurcation theory is extended to be applicable to 1-dimensionally resolved systems of nonlinear partial differential equations, aimed at the determination of a certain specific bifurcation. This extension is needed to be able to properly analyze the bifurcations of the radial transport in magnetically confined fusion plasmas. This is of special interest when describing the transition from the low-energy-confinement state to the high-energy-confinement state of the radial transport in fusion plasmas (i.e., the L-H transition), because the nonlinear dynamical behavior during the transition corresponds to the dynamical behavior of a system containing such a specific bifurcation. This bifurcation determines how the three types (sharp, smooth, and oscillating) of observed L-H transitions are organized as function of all the parameters contained in the model.
Improved long-term electrical stability of pulsed high-power diodes using dense carbon fiber velvet cathodes
Authors: Yang Jie , Shu Ting , Wang Hui
Published: July 2012

The influence of fibrous velvet cathodes on the electrical stability of a planar high-power diode powered by a ∼230 kV, ∼110 ns pulse has been investigated. The current density was on the order of ∼123 A/cm2. A combination of time-resolved electrical and optical diagnostics has been employed to study the basic phenomenology of the temporal and spatial evolution of the diode plasmas. Additionally, an impedance model was used to extract information about this plasma from voltage and current profiles. The results from the two diagnostics were compared. By comparison with commercial polymer velvet cathode, the dense carbon fiber velvet cathode showed superior long-term electrical stability as judged by the change in cathode turn-on field, ignition delays, diode impedance, and surface plasma characteristics during the voltage flattop, a promising result for applications where reliable operation at high power is required. Finally, it was shown that the interaction of the electron beam with the stainless steel anode did not lead to the formation of anode plasma. These results may be of interest to the high power microwave systems with cold cathodes.
Synthesis of Poly(2-methyl-2-oxazoline) Star Polymers with a β-Cyclodextrin Core
Authors: Pereira Guillaume , Huin Cécile , Morariu Simona , Bennevault-Celton Véronique , Guégan Philippe
Published: July 2012

Synthesis of star polymers with a β-cyclodextrin (CD) core was undertaken using the arm-first, then the core-first strategy. Cationic ring opening polymerisation (CROP) of 2-methyl-2-oxazoline (MeOx) was first initiated by allyl bromide, and then quenched with heptakis(6-deoxy-6-amino)β-CD in order to get a 7-arm star polymer. Then heptakis(6-deoxy-6-iodo-2,3-di-O-acetyl)β-CD was synthesised in order to get an initiator for the CROP of MeOx. Initiation and propagation kinetic measurements were undertaken and the ratio kp/ki was found to be too high to provide a controlled polymerisation. Using iodine as co-initiator allowed a decrease of the kp/ki ratio that gave better control of the polymerisation. DOSY NMR and viscosity characterisations were undertaken, and both techniques lead to the demonstration of a lower hydrodynamic volume of the star polymers versus the linear counterparts, for compounds of the same molecular weight.
Cryopreservation and long-term maintenance of bovine embryo-derived cell lines
Authors: Pashaiasl Maryam , Khodadadi Khodadad , Richings Nadine M. , Holland Michael K. , Verma Paul J.
Published: July 2012

The aim of this study was to develop methods for cryopreservation and long-term maintenance of putative bovine embryonic stem cells (ESCs). Putative bovine ESC (bESC) lines (n = 3) isolated in conventional medium were used to compare slow-freezing and vitrification. After warming, vitrified cells (96.9%) demonstrated significantly (P < 0.05) better survival than frozen–thawed cells (81.5%) and formed significantly more colonies with good morphology (vitrification: 93/93, 100.0%; slow-freezing: 74/106, 69.81%; P < 0.05). The effect of inhibitors of differentiation (PD184352, SU5402, CHIR99021) on ESC maintenance was assessed on putative bESC lines established in N2B27–3i medium (n = 8) or conventional medium (n = 1) after culture over 30 passages (>240 days). All cell lines expressed ALP, SSEA1, SSEA4, OCT4, REX1 and SSEA1. OCT4 expression was confirmed by relative real-time PCR and was upregulated in early passages of putative bESCs cultured in N2B27–3i (2.9 ± 0.89-fold higher at Passage (P) 2–4), whereas the converse was observed later (P22–26; 2.2 ± 0.1-fold increase in conventional medium). Putative bESC lines isolated in N2B27–3i medium (n = 3) or conventional medium (n = 1) were vitrified at P18 and, after warming, were cultured for a further 12 passages. These cells survived vitrification and expressed OCT4, REX1, SSEA1, ALP, SSEA1 and SSEA4. These results demonstrate that putative bESC lines that express pluripotent markers can be cultured long term and retain expression of pluripotent markers after vitrification.
Involvement of microRNA-335-5p in cytoskeleton dynamics in mouse oocytes
Authors: Cui Xiang-Shun , Sun Shao-Chen , Kang Yong-Kook , Kim Nam-Hyung
Published: July 2012

MicroRNA is a short RNA molecule expressed in eukaryotic cells that is involved in multiple processes, including translational repression, target degradation and gene silencing. However, its specific role(s) in these processes remains largely unknown, especially in terms of germ cell development. The present study identified a microRNA, namely miR-335-5p, that is involved in mouse oocyte meiosis. MiR-335-5p was highly expressed in oocytes, but levels decreased markedly shortly after fertilisation. Microinjection of miR-335-5p or its inhibitor into oocytes resulted in a higher proportion of 2-cell-like MII oocytes and oocytes at the germinal vesicle breakdown and/or MI stage, indicating failure of asymmetric oocyte division. This may be due to regulation of actin because perturbation of miR-335-5p resulted in reduced expression of actin nucleator Daam1, a member of the Formin family. Moreover, injection of miR-335-5p or its inhibitor resulted in aberrant spindle morphology, namely an elongated spindle and multiple poles spindle. After injection of oocytes, levels of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) decreased, suggesting that miR-335-5p may regulate spindle formation via the mitogen-activated protein kinase pathway. Overexpression and inhibition of miR-335-5p had no effect on embryo development. Together, the results of the present study indicate that miR-335-5p is a novel regulator expressed in oocytes that is involved in cytoskeleton dynamics.
K-Ras and B-Raf oncogenes inhibit colon epithelial polarity establishment through up-regulation of c-myc
Authors: Magudia Kirti , Lahoz Aurelia , Hall Alan
Published: July 2012

KRAS, BRAF, and PI3KCA are the most frequently mutated oncogenes in human colon cancer. To explore their effects on morphogenesis, we used the colon cancer–derived cell line Caco-2. When seeded in extracellular matrix, individual cells proliferate and generate hollow, polarized cysts. The expression of oncogenic phosphatidylinositol 3-kinase (PI3KCA H1047R) in Caco-2 has no effect, but K-Ras V12 or B-Raf V600E disrupts polarity and tight junctions and promotes hyperproliferation, resulting in large, filled structures. Inhibition of mitogen-activated protein/extracellular signal–regulated kinase (ERK) kinase blocks the disruption of morphology, as well as the increased levels of c-myc protein induced by K-Ras V12 and B-Raf V600E. Apical polarity is already established after the first cell division (two-cell stage) in Caco-2 three-dimensional cultures. This is disrupted by expression of K-Ras V12 or B-Raf V600E but can be rescued by ribonucleic acid interference–mediated depletion of c-myc. We conclude that ERK-mediated up-regulation of c-myc by K-Ras or B-Raf oncogenes disrupts the establishment of apical/basolateral polarity in colon epithelial cells independently of its effect on proliferation.
A conserved KASH domain protein associates with telomeres, SUN1, and dynactin during mammalian meiosis
Authors: Morimoto Akihiro , Shibuya Hiroki , Zhu Xiaoqiang , Kim Jihye , Ishiguro Kei-ichiro , Han Min , Watanabe Yoshinori
Published: July 2012

In yeasts and worms, KASH (Klarsicht/ANC-1/Syne/homology) domain and SUN (Sad-1/UNC-84) domain nuclear envelope (NE) proteins play a crucial role in meiotic chromosome movement and homologue pairing. However, although the vertebrate SUN domain protein SUN1 is involved in these processes, its partner has remained identified. Based on subcellular localization screening in mouse spermatocytes, we identified a novel germ cell–specific protein, KASH5, that localized exclusively at telomeres from the leptotene to diplotene stages in both spermatocytes and oocytes. KASH5 possesses hitherto unknown KASH-related sequences that directly interacted with SUN1 and mediated telomere localization. Thus, KASH5 is a mammalian meiosis-specific KASH domain protein. We show that meiotic chromosome movement depended on microtubules and that KASH5 interacted with the microtubule-associated dynein–dynactin complex. These results suggest that KASH5 connects the telomere-associated SUN1 protein to the cytoplasmic force–generating mechanism involved in meiotic chromosome movement. Our study strongly suggests that the meiotic homologue-pairing mechanism mediated by the SUN–KASH NE bridge is highly conserved among eukaryotes.
Autophagy regulation through Atg9 traffic
Authors: Reggiori Fulvio , Tooze Sharon A.
Published: July 2012

Rapid membrane expansion is the key to autophagosome formation during nutrient starvation. In this issue, Yamamoto et al. (2012. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201202061) now provide a mechanism for vesicle-mediated initiation of autophagosome biogenesis. They show that Atg9 vesicles, produced de novo during starvation, are ∼30–60 nm in size and contain ∼30 molecules of Atg9. These vesicles assemble to form an autophagosome, and subsequently, the Atg9 embedded in the outer membrane is recycled to avoid degradation.
Effects of the antidepressant fluoxetine on the subcellular localization of 5-HT
1A
receptors and SERT
Authors: Descarries Laurent , Riad Mustaph
Published: July 2012

Serotonin (5-HT) 5-HT
1A
autoreceptors (5-HT
1A
autoR) and the plasmalemmal 5-HT transporter (SERT) are key elements in the regulation of central 5-HT function and its responsiveness to antidepressant drugs. Previous immuno-electron microscopic studies in rats have demonstrated an internalization of 5-HT
1A
autoR upon acute administration of the selective agonist 8-OH-DPAT or the selective serotonin reuptake inhibitor antidepressant fluoxetine. Interestingly, it was subsequently shown in cats as well as in humans that this internalization is detectable by positron emission tomography (PET) imaging with the 5-HT
1A
radioligand [
18
F]MPPF. Further immunocytochemical studies also revealed that, after chronic fluoxetine treatment, the 5-HT
1A
autoR, although present in normal density on the plasma membrane of 5-HT cell bodies and dendrites, do not internalize when challenged with 8-OH-DPAT. Resensitization requires several weeks after discontinuation of the chronic fluoxetine treatment. In contrast, the SERT internalizes in both the cell bodies and axon terminals of 5-HT neurons after chronic but not acute fluoxetine treatment. Moreover, the total amount of SERT immunoreactivity is then reduced, suggesting that SERT is not only internalized, but also degraded in the course of the treatment. Ongoing and future investigations prompted by these finding are briefly outlined by way of conclusion.
Serotonin receptor expression along the dorsal–ventral axis of mouse hippocampus
Authors: Tanaka Kenji F. , Samuels Benjamin Adam , Hen René
Published: July 2012

Using
in situ
hybridization, we describe, for the first time, the profiles of expression of serotonin receptors (Htr/5-HTR) along the dorsal–ventral axis of mouse hippocampus. cRNA probes for most Htrs, excluding Htr6, were used. All hippocampal subregions and the entorhinal cortex cells providing input into the hippocampus were examined. The study shows that some, but not all, Htrs are expressed in the cells of the hippocampal circuitry. At both the subfield and the cell type levels, a somewhat overlapping pattern is observed. Four serotonin receptors, Htr1a, Htr2a, Htr2c and Htr7, display an expression pattern that changes along the dorsal–ventral axis of the hippocampus. Given the proposed functional differentiation of the hippocampus along its long axis, with the dorsal pole more involved in cognitive functions and the ventral pole more involved in mood and anxiety, our results suggest that serotonin receptors enriched in the ventral pole probably contribute to mood- and anxiety-related behaviours.
Selective deletion of forebrain glycogen synthase kinase 3β reveals a central role in serotonin-sensitive anxiety and social behaviour
Authors: Latapy Camille , Rioux Véronique , Guitton Matthieu J. , Beaulieu Jean-Martin
Published: July 2012

Serotonin (5-HT) neurotransmission is thought to underlie mental illnesses, such as bipolar disorder, depression, autism and schizophrenia. Independent studies have indicated that 5-HT or drugs acting on 5-HT neurotransmission regulate the serine/threonine kinase glycogen synthase kinase 3β (GSK3β). Furthermore, GSK3β inhibition rescues behavioural abnormalities in 5-HT-deficient mice with a loss-of-function mutation equivalent to the human variant (R441H) of tryptophan hydroxylase 2. In an effort to define neuroanatomical correlates of GSK3β activity in the regulation of behaviour, we generated CamKIIcre-floxGSK3β mice in which the
gsk3b
gene is postnatally inactivated in forebrain pyramidal neurons. Behavioural characterization showed that suppression of GSK3β in these brain areas has anxiolytic and pro-social effects. However, while a global reduction of GSK2β expression reduced responsiveness to amphetamine and increased resilience to social defeat, these behavioural effects were not found in CamKIIcre-floxGSK3β mice. These findings demonstrate a dissociation of behavioural effects related to GSK3 inhibition, with forebrain GSK3β being involved in the regulation of anxiety and sociability while social preference, resilience and responsiveness to psychostimulants would involve a function of this kinase in subcortical areas such as the hippocampus and striatum.
The neurobiology of depression—revisiting the serotonin hypothesis. I. Cellular and molecular mechanisms
Authors: Albert Paul R. , Benkelfat Chawki , Descarries Laurent
Published: July 2012

The serotonin (5-HT) hypothesis of depression dates from the 1960s. It originally postulated that a deficit in brain serotonin, corrected by antidepressant drugs, was the origin of the illness. Nowadays, it is generally accepted that recurring mood disorders are brain diseases resulting from the combination, to various degrees, of genetic and other biological as well as environmental factors, evolving through the lifespan. All areas of neuroscience, from genes to behaviour, molecules to mind, and experimental to clinical, are actively engaged in attempts at elucidating the pathophysiology of depression and the mechanisms underlying the efficacy of antidepressant treatments. This first of two special issues ofPhilosophical Transactions Bseeks to provide an overview of current developments in the field, with an emphasis on cellular and molecular mechanisms, and how their unravelling opens new perspectives for future research.
Maternal licking regulates hippocampal glucocorticoid receptor transcription through a thyroid hormone–serotonin–NGFI-A signalling cascade
Authors: Hellstrom Ian C. , Dhir Sabine K. , Diorio Josie C. , Meaney Michael J.
Published: July 2012

Variations in parental care direct phenotypic development across many species. Variations in maternal pup licking/grooming (LG) in the rat regulate the development of individual differences in hypothalamic–pituitary–adrenal responses to stress. The adult offspring of mothers that show an increased frequency of pup LG have increased hippocampal glucocorticoid receptor (GR) expression and more modest pituitary–adrenal responses to stress. This parental effect is mediated by the epigenetic programming of a GR exon 1 promoter (exon 17) through the binding of the transcription factor nerve growth factor-inducible factor A (NGFI-A). In this paper, we report that: (i) the association of NGFI-A with the exon 17GR promoter is dynamically regulated by mother–pup interactions; (ii) this effect is mimicked by artificial tactile stimulation comparable to that provided by pup LG; (iii) that serotonin (5-HT) induces an NGFI-A-dependent increase in GR transcription in hippocampal neurons and NGFI-A overexpression is sufficient for this effect; and (iv) that thyroid hormones and 5-HT are key mediators of the effects of pup LG and tactile stimulation on NGFI-A binding to the exon 17GR promoter in hippocampus. These findings suggest that pup LG directly activates 5-HT systems to initiate intracellular signalling pathways in the hippocampus that regulate GR transcription.
Lipid Profiling of the Arabidopsis Hypersensitive Response Reveals Specific Lipid Peroxidation and Fragmentation Processes: Biogenesis of Pimelic and Azelaic Acid
Authors: Zoeller Maria , Stingl Nadja , Krischke Markus , Fekete Agnes , Waller Frank , Berger Susanne , Mueller Martin J.
Published: July 2012

Lipid peroxidation (LPO) is induced by a variety of abiotic and biotic stresses. Although LPO is involved in diverse signaling processes, little is known about the oxidation mechanisms and major lipid targets. A systematic lipidomics analysis of LPO in the interaction of Arabidopsis (Arabidopsis thaliana) with Pseudomonas syringae revealed that LPO is predominantly confined to plastid lipids comprising galactolipid and triacylglyceride species and precedes programmed cell death. Singlet oxygen was identified as the major cause of lipid oxidation under basal conditions, while a 13-lipoxygenase (LOX2) and free radical-catalyzed lipid oxidation substantially contribute to the increase upon pathogen infection. Analysis of lox2 mutants revealed that LOX2 is essential for enzymatic membrane peroxidation but not for the pathogen-induced free jasmonate production. Despite massive oxidative modification of plastid lipids, levels of nonoxidized lipids dramatically increased after infection. Pathogen infection also induced an accumulation of fragmented lipids. Analysis of mutants defective in 9-lipoxygenases and LOX2 showed that galactolipid fragmentation is independent of LOXs. We provide strong in vivo evidence for a free radical-catalyzed galactolipid fragmentation mechanism responsible for the formation of the essential biotin precursor pimelic acid as well as of azelaic acid, which was previously postulated to prime the immune response of Arabidopsis. Our results suggest that azelaic acid is a general marker for LPO rather than a general immune signal. The proposed fragmentation mechanism rationalizes the pathogen-induced radical amplification and formation of electrophile signals such as phytoprostanes, malondialdehyde, and hexenal in plastids.
Review article: overlap syndromes and autoimmune liver disease
Authors: Trivedi P. J. , Hirschfield G. M.
Published: July 2012

Background

Autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) all nestle within the family of autoimmune liver diseases, whereby the result of immune‐mediated liver injury gives rise to varied clinical presentations. Some patients demonstrate a phenotype whereby there is evidence of either PBC or PSC together with overlapping features of AIH. Due to an absence of well‐validated diagnostic criteria and a lack of large therapeutic trials, treatment of overlap conditions is empiric and extrapolated from data derived from the primary autoimmune liver diseases.

Aims

To review overlaps in the context of autoimmune liver diseases.

Methods

General and specific review of published articles using PubMed, Medline and Ovid search engines, alongside pre‐existing clinical management protocols, guidelines, and the authors' own knowledge of the published literature.

Results

The challenges in diagnosis, clinical presentation, determining natural history and outcome of overlaps are presented, as well as present‐day management suggestions, some based on evidence, others on consensus and opinion.

Conclusions

Overlapping autoimmune features, be they clinical, serological, histological or radiological are not infrequent, but appropriate diagnosis remains hindered by a lack of standardised diagnostic criteria. Optimum care for those with suspected overlap should thus focus on attention to detail over the fundamental aspects of timely secure diagnosis of the dominant disease entity. Clinicians should counsel patients carefully with regard to the risks and benefits of treatment, bearing in mind the paucity of randomised and controlled outcome data for medical interventions.
The pre‐emptive analgesic effect of a cyclooxygenase‐2 inhibitor in a rat model of acute postoperative pain
Authors: Chen J. J. , Hung K. C. , Lu K. , Yu S. W. , Chang C. C. , Liu C. C. , Spielberger J. , Ku P. Y. , Tan P. H.
Published: July 2012

We examined the pre‐emptive analgesic effect of a cyclooxygenase (COX)‐2 inhibitor in a rat surgical pain model and characterised the changes in cutaneous COX‐2 around a surgical site. Thermal hyperalgesia and mechanical allodynia were tested in the rats for three days after incision and skin tissues were collected for analysis of COX‐2. There was decreased expression of cutaneous COX‐2 one day after surgical incision. Pre‐incision injection of the COX‐2 inhibitor significantly inhibited expression of COX‐2 and also reduced thermal hyperalgesia (but not mechanical allodynia) compared with the post‐incision COX‐2‐inhibitor injection group, one day after incision.
Observational study on safety and tolerability of duloxetine in the treatment of female stress urinary incontinence in German routine practice
Authors: Michel Martin C. , Minarzyk Anette , Schwerdtner Inka , Quail Deborah , Methfessel Hans D. , Weber Hans‐Joachim
Published: July 2012

Aims

To evaluate the safety and tolerability of duloxetine during routine clinical care in women with stress urinary incontinence (SUI) in Germany, and in particular, to identify previously unrecognized safety issues as uncommon adverse reactions, and the influence of confounding factors present in clinical practice on the safety profile of duloxetine.

Methods

Office‐based urologists, gynaecologists and primary care physicians were asked to document women newly started on treatment for moderate to severe symptoms of SUI. Six thousand eight hundred and fifty‐four patients from urologist/gynaecologist practices and 5879 primary care patients were assessed. In a two‐armed, observational study with parallel 12 week (urologists and gynaecologists) or 24 week (primary care physicians) design, patients were treated with duloxetine or other conservative treatment. The main outcome measure was the occurrence of adverse events (AEs).

Results

Baseline characteristics differed slightly between patient groups and studies. Duloxetine doses in most patients were lower than recommended. Overall, AE frequency with duloxetine was lower than in controlled studies (15.9% (95% CI 14.9, 16.9) and 9.1% (95% CI 8.2, 10.0) in the 12 and 24 week treatment groups, respectively), but exhibited a similar qualitative spectrum. In the logistic regression models, the following factors were associated with greater AE risk: investigator specialization (gynaecologist vs. urologist and primary care physician), initial duloxetine dose (80 vs. 20 mg day−1) and use of any concomitant medication. Within the 24 week study, a positive screen for depressive disorder was surprisingly common, but no case of attempted suicide was reported in either study.

Conclusions

Our results from German clinical practice show that women with SUI were often treated with duloxetine doses lower than recommended. This was associated with a low incidence of AEs. Suicide attempts were not reported.
Treatment outcome of CRLF2‐rearranged childhood acute lymphoblastic leukaemia: a comparative analysis of the AIEOP‐BFM and UK NCRI‐CCLG study groups
Authors: Attarbaschi Andishe , Morak Maria , Cario Gunnar , Cazzaniga Giovanni , Ensor Hannah M. , te Kronnie Truus , Bradtke Jutta , Mann Georg , Vendramini Elena , Palmi Chiara , Schwab Claire , Russell Lisa J. , Schrappe Martin , Conter Valentino , Mitchell Christopher D. , Strehl Sabine , Zimmermann Martin , Pötschger Ulrike , Harrison Christine J. , Stanulla Martin , Panzer‐Grümayer Renate , Haas Oskar A. , Moorman Anthony V. ,   on behalf of the Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP)‐Berlin‐Frankfurt‐Münster (BFM) Study Group and National Cancer Research Institute (NCRI)‐Children's Cancer and Leukaemia (CCLG) Study Group
Published: July 2012

The prognostic relevance of
CRLF2

‐rearrangements in childhood acute B‐cell precursor lymphoblastic leukaemia (ALL), was assessed by a comparative analysis of 114 non‐Down‐syndrome patients (99
P2RY8‐CRLF2+
, 15
IGH@‐CRLF2+
), 76 from the AIEOP‐BFM ALL 2000 and 38 from the MRC ALL97 trials. The 6‐year cumulative relapse incidence of
P2RY8‐CRLF2+
patients treated on the two trials was not statistically different: 0·37 ± 0·06 vs. 0·25 ± 0·08 (P = 0·194). In contrast, 0/9
IGH@‐CRLF2+ AIEOP‐BFM, but 5/6 ALL97 patients relapsed. Conclusively,
P2RY8‐CRLF2+
patients had an intermediate protocol‐independent outcome while the different prognosis of
IGH@‐CRLF2+ patients could be related to the different structures of the applied treatment protocols.
Normal ageing is associated with an increase in Th2 cells, MCP-1 (CCL1) and RANTES (CCL5), with differences in sCD40L and PDGF-AA between sexes
Authors: Mansfield A S , Nevala W K , Dronca R S , Leontovich A A , Shuster L , Markovic S N
Published: July 2012

We have observed T helper type 2 (Th2) polarization of systemic immunity in patients with metastatic malignant melanoma. We hypothesized that similar changes in systemic immunity occur with ageing and may be permissive for the development of melanoma. We analysed the peripheral blood of 389 healthy blood donors. All subjects were profiled for peripheral blood T cell and B cell subsets, and 58 of these subjects were profiled for antigen-specific cytotoxic T cell subsets [cytomegalovirus (CMV), influenza and melanoma antigen recognized by T cells 1 (MART-1)]. Ninety-five separate healthy subjects underwent profiling of 42 plasma cytokines. Ageing was associated positively with CD4+CD294+ Th2 cells, and associated negatively with CD3+ T cells, cytotoxic T cells and T helper cells. Ageing was also associated negatively with CMV-, influenza- and MART-1-specific naive and CD8+ T cells. There were significant increases in plasma monocyte chemotactic protein 1 (MCP-1) (CCL1) and regulated upon activation normal T cell expressed and secreted (RANTES) (CCL5) with age. We observed differences in cytokine profiles between males and females; specifically, women had higher levels of sCD40L and PDGF-AA. In summary, we demonstrated in healthy blood donors that ageing was associated with an increase in cellular Th2 bias and a decline in total numbers of T cells. Additionally, there was an increase in MCP-1 and RANTES with ageing. Women had higher levels of sCD40L and PDGF-AA than men.
Dysregulated immunophenotypic attributes of plasmacytoid but not myeloid dendritic cells in HIV-1 infected individuals in the absence of highly active anti-retroviral therapy
Authors: Benlahrech A , Yasmin A , Westrop S J , Coleman A , Herasimtschuk A , Page E , Kelleher P , Gotch F , Imami N , Patterson S
Published: July 2012

Dendritic cells (DC) in HIV-1-infected individuals are decreased and their dysfunction has been implicated in HIV-1 immunopathogenesis. The mechanism of their dysfunction remains unclear, thus we analysed the expression of membrane molecules associated with immune regulation and DC activation in myeloid (mDC) and plasmacytoid DC (pDC) in therapy-naive and highly active anti-retroviral therapy (HAART)-treated HIV-1+ patients. DC from healthy controls, untreated HIV-1+ and HAART-treated patients were assessed by flow cytometry for expression of: anergy and apoptosis inducing molecules [programmed death (PD)-1 and its ligands PD-L1 and PD-L2], inhibitory and regulatory T cell-inducing molecules [immunoglobulin-like transcript (ILT)-3 and ILT-4], interferon (IFN)-α inhibitory receptor (ILT-7) and co-stimulatory molecules (CD80, CD83, and CD86). pDC from untreated HIV-1+ patients expressed significantly lower levels of ILT-7 compared to healthy controls, while HAART-treated patients showed normal expression. pDC were also found to express moderately higher levels of PD-L1 and ILT-3 and lower levels of PD-L2 receptors in untreated patients compared to controls and HAART-treated patients. No significant changes were observed in mDC. There were no associations between the percentages and levels of expression of these molecules by pDC and viral load or CD4 T cell count. In conclusion, pDC but not mDC from HIV-1+ patients with active viraemia display higher levels of apoptosis and T regulatory-inducing molecules and may be predisposed to chronically produce IFN-α through down-regulation of ILT-7. HAART restored normal expression levels of these receptors.
Skin- and gut-homing molecules on human circulating γδ T cells and their dysregulation in inflammatory bowel disease
Authors: Mann E R , McCarthy N E , Peake S T C , Milestone A N , Al-Hassi H O , Bernardo D , Tee C T , Landy J , Pitcher M C , Cochrane S A , Hart A L , Stagg A J , Knight S C
Published: July 2012

Changes in phenotype and function of γδ T cells have been reported in inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). Dysregulation of lymphocyte migration plays a key role in IBD pathogenesis; however, data on migratory properties of γδ T cells are scarce. Human circulating γδ T cells from healthy controls (n = 27), patients with active CD (n = 15), active UC (n = 14) or cutaneous manifestations of IBD (n = 2) were characterized by flow cytometry. Circulating γδ T cells in healthy controls were CD3hi and expressed CD45RO. They expressed gut-homing molecule β7 but not gut-homing molecule corresponding chemokine receptors (CCR)9, or skin-homing molecules cutaneous lymphocyte-associated antigen (CLA) and CCR4, despite conventional T cells containing populations expressing these molecules. CCR9 expression was increased on γδ T cells in CD and UC, while skin-homing CLA was expressed aberrantly on γδ T cells in patients with cutaneous manifestations of IBD. Lower levels of CD3 expression were found on γδ T cells in CD but not in UC, and a lower proportion of γδ T cells expressed CD45RO in CD and UC. Enhanced expression of gut-homing molecules on circulating γδ T cells in IBD and skin-homing molecules in cutaneous manifestations of IBD may be of clinical relevance.
Innate and adaptive immune gene expression profiles as biomarkers in human type 1 diabetes
Authors: Han D , Cai X , Wen J , Matheson D , Skyler J S , Kenyon N S , Chen Z
Published: July 2012

The mRNA levels of a set of immune-related genes were analysed with peripheral blood samples from at-risk, new-onset and long-term type 1 diabetes (T1D) patients, in comparison to those from healthy controls. The selected set includes T lymphocyte genes [CD3G and cytotoxic T lymphocyte-associated antigen 4 (CTLA4)], B lymphocyte genes (CD19 and CD20) and myeloid cell-related genes [CD11b, Toll-like receptor (TLR)-9, arginase (ARG1)]. Also included is a subset of the S100 family members that has been documented recently as regulatory elements of innate immunity. Samples from patients with long-term T1D had a reduced level of mRNA for most of selected innate and adaptive immune genes. No such reduction was detected in samples collected from at-risk or new-onset T1D patients. Analyses of regulatory gene expression ratios revealed a dynamic disproportion of CTLA4 versus CD3G expression in samples from at-risk, new-onset and long-term T1D patients. These changes could serve as immunological biomarkers for the status of the immune system during T1D progression and therapeutic interventions.
Cervical squamous intraepithelial lesions and associated cervical infections in an HIV‐positive population in Rural Mpumalanga, South Africa
Authors: Swanepoel P. J. , Michelow P. , Du Plessis R. , Proudfoot I. G. , Tarr G. A. , Bockel S. L. , Swanepoel C. J.
Published: July 2012

P. J. Swanepoel, P. Michelow, R. Du Plessis, I. G. Proudfoot, G. A. Tarr, S. L. Bockel, C. J. Swanepoel  Cervical squamous intraepithelial lesions and associated cervical infections in an HIV‐positive population in Rural Mpumalanga, South Africa

Background:  The incidences of genital human papillomavirus (HPV) infection, associated squamous intraepithelial lesions and cervical squamous cell carcinoma are significantly increased in HIV‐positive women. The role of other cervicovaginal infections in the acquisition of the HPV infection, cervical carcinogenesis and genital HIV infection remains largely speculative.

Methods:  A retrospective study was conducted including 1087 HIV‐positive women in rural Mpumalanga province, South Africa, for the period 1 May 2009 to 31 August 2010. For each patient, the age at first presentation, cervical cytological diagnosis, subsequent follow‐up cytology and histology, and microscopically visible infections (including endemic Bilharzia) were tabulated and statistically analysed.

Results:  The prevalence of low‐grade squamous intraepithelial lesion (LSIL), high‐grade squamous intraepithelial lesion (HSIL), squamous cell carcinoma, atypical squamous cells of undetermined significance (ASC‐US) and atypical squamous cells, cannot exclude HSIL (ASC‐H) in the study population were 22.1%, 30.9%, 0.6%, 13.5% and 4.0%, respectively. LSIL, HSIL and squamous cell carcinoma were diagnosed, respectively, at the average ages of 35.7, 37.9 and 37.2 years. Four patients with cervical intraepithelial neoplasia grade 1 (CIN1), 32 with CIN2/CIN3 and two with cervical squamous cell carcinoma were also diagnosed with Bilharzia. Of the other infections only bacterial vaginosis had a positive statistical correlation with HPV‐induced cervical abnormalities (LSIL, HSIL or squamous cell carcinoma).

Conclusion:  This study confirms the high prevalence of progressive HPV‐associated cervical disease in a rural Southern African HIV‐positive population, which is at least equal to or worse than in other African HIV‐positive studies. The high incidence of Bilharzia infection in those cases that underwent cervical cone excision suggests a possible relationship with progressive HPV disease and cervical carcinogenesis. Bacterial vaginosis (perhaps in combination with Bilharzia) may compromise the normal barriers against HPV and HIV infection.
Physiological and ecological hosts ofPopenaias popeii(Bivalvia: Unionidae): laboratory studies identify more hosts than field studies
Authors: LEVINE TODD D. , LANG BRIAN K. , BERG DAVID J.
Published: July 2012

1. Freshwater mussels are critically endangered in North America, making it important to understand their environmental requirements at all life stages. As glochidia (larvae), they attach to fish hosts where they undergo substantial mortality, making this transition important in their life cycle. Larval host fish requirements have typically been described using data from laboratory infestations to determine suitable hosts.

2. Laboratory infestations circumvent many natural barriers that prevent infestation of physiologically compatible fishes by mussel larvae. While such methods are invaluable for identifying ‘physiological hosts,’ they cannot fully describe realised ‘ecological hosts’ in the field.

3. We studiedPopenaias popeiiin the Black River in New Mexico, because it is of conservation concern and it is the only mussel species present, facilitating identification of glochidial infestation. To explore the difference between physiological hosts and ecological hosts, we conducted a 3‐year field study of fishes infested byP. popeiiglochidia.

4. Substantially fewer fish species were infested byP. popeiiin the wild (10 of 20 observed) than had been identified as physiological hosts in laboratory trials (24 of 31). We combined data on fish abundance, proportion of fish hosts infested (prevalence) and the number of glochidia per fish (intensity) and identified three fish species that probably contributed substantially more to mussel recruitment by carrying more glochidia than other host species.

5. Similarities in behaviour among these fishes allowed us to hypothesise routes of infestation, such as benthos‐feeding by catostomids, that allow glochidia to infest these hosts at higher rates than other suitable hosts. Overall, this approach provides a method of quantifying the relative importance of different species of host fish in the mussel lifecycle.