bluuebunny/crossref_metadata_2025 huggingface dataset:
Asp433 in the closing gate of ASIC1 determines stability of the open state without changing properties of the selectivity filter or Ca2+ block
Authors: Li Tianbo , Yang Youshan , Canessa Cecilia M.
Published: March 2011

A constriction formed by the crossing of the second transmembrane domains of ASIC1, residues G432 to G436, forms the narrowest segment of the pore in the crystal structure of chicken ASIC1, presumably in the desensitized state, suggesting that it constitutes the “desensitization gate” and the “selectivity filter.” Residues Gly-432 and Asp-433 occlude the pore, preventing the passage of ions from the extracellular side. Here, we examined the role of Asp-433 and Gly-432 in channel kinetics, ion selectivity, conductance, and Ca2+ block in lamprey ASIC1 that is a channel with little intrinsic desensitization in the pH range of maximal activity, pH 7.0. The results show that the duration of open times depends on residue 433, with Asp supporting the longest openings followed by Glu, Gln, or Asn, whereas other residues keep the channel closed. This is consistent with residue Asp-433 forming the pore’s closing gate and the properties of the side chain either stabilizing (hydrophobic amino acids) or destabilizing (Asp) the gate. The data also show residue 432 influencing the duration of openings, but here only Gly and Ala support long openings, whereas all other residues keep channels closed. The negative charge of Asp-433 was not required for block of the open pore by Ca2+ or for determining ion selectivity and unitary conductance. We conclude that the conserved residue Asp-433 forms the closing gate of the pore and thereby determines the duration of individual openings while desensitization, defined as the permanent closure of all or a fraction of channels by the continual presence of H+, modulates the on or off position of the closing gate. The latter effect depends on less conserved regions of the channel, such as TM1 and the extracellular domain. The constriction made by Asp-433 and Gly-432 does not select for ions in the open conformation, implying that the closing gate and selectivity filter are separate structural elements in the ion pathway of ASIC1. The results also predict a significantly different conformation of TM2 in the open state that relieves the constriction made by TM2, allowing the passage of ions unimpeded by the side chain of Asp-433.
Comparison of modelling and experimental results of anode surface melting by femtosecond laser-stimulated electrical discharges in small gaps
Authors: Chen Jian , He LingNa , Farson Dave F , Rokhlin Stanislav I
Published: March 2011

Experiments and particle-in-cell simulations of femtosecond laser-stimulated electrical discharges in submicrometre gaps between scanning tunnelling microscope tip cathodes and gold film anodes are described. In experiments at applied potentials of 35 V and less, discharges were detected either as self-terminating low-current pulses with durations less than 10 ns and magnitudes less than 200 mA or as higher-current, longer-duration current waveforms. The probability of occurrence of low-current pulses increased as applied potential was decreased, being certain at low potentials of 20–25 V. Low-current pulse waveforms and surface melting of gold anodes predicted by the simulations were compared with experiments. Laser stimulation was modelled by introducing partially ionized electrode materials into the simulation domain at a controlled rate. Simulation results showed that the duration of low-current pulses was influenced by the time over which material was added to the gap region, establishing the importance of electrode vaporization on discharge duration. Subsequently, partially ionized electrode materials were preloaded into the gap in controlled amounts in subsequent simulations. Peak currents predicted by these simulations were nearly equal to the low-current pulse measurements but simulated pulse durations were shorter than experiments. Thus, the time axis of simulation current profiles was normalized for equality of charge transfer with experiments. Anode temperatures and melt diameters calculated from normalized simulated heat input profiles were well matched to experimental measurements.
Combined spectroscopic methods for electron-density diagnostics inside atmospheric-pressure glow discharge using He/N2 gas mixture
Authors: Urabe Keiichiro , Sakai Osamu , Tachibana Kunihide
Published: March 2011

We investigated the spatiotemporal structures of electron density inside an atmospheric-pressure glow discharge in a gaseous medium of He with small N2 impurity using a parallel-plate dielectric barrier discharge configuration. To reveal the spatial distributions of temporal-peak electron density, we combined the measurement results of two spectroscopic diagnostics applied to the same plasma source: CO2-laser heterodyne interferometry and millimetre-wave transmission methods. Laser absorption and optical emission spectroscopy methods were also performed to analyse the detailed plasma characteristics, and we calculated the total ionization frequency to discuss the influence of N2 impurity on the discharge. The experimental and calculated results suggest that the localization of the electron density near the dielectric barriers was caused by the formation of a high excited-species density region near the temporal cathode, and the total ionization frequency was maximized around 0.25% of the N2 impurity ratio.
Magnetic resonance imaging studies of spontaneous capillary water imbibition in aerated gypsum
Authors: Song Kyung-Min , Mitchell Jonathan , Jaffel Hamouda , Gladden Lynn F
Published: March 2011

In this paper we investigate both capillary water imbibition and the sorptivity of aerated gypsum plaster, and how these sorption characteristics are related to the pore structure of the material. These characteristics are examined by monitoring mass change using the conventional gravimetric method and by obtaining water content profiles using non-destructive magnetic resonance imaging (MRI) techniques during capillary imbibition of water. Here, three different gypsum samples are investigated: one non-aerated reference gypsum sample and two aerated gypsum samples produced with different volumetric air fractions. The capillary water absorption into the reference sample follows t
1/2 kinetics (Fickian diffusion), where t is the time of ingress. However, in the aerated gypsum samples there are deviations from t
1/2 kinetics. The MRI results show unambiguously that two wetting fronts advance through the aerated structure; an observation that cannot be made from the gravimetric data alone. The water content profiles of the aerated gypsum samples are therefore analysed by treating them as the sum of two separate absorption processes using sharp front analysis. The capillary water absorption properties of this material are well described as a parallel combination of fast absorption into fine matrix pores and slow absorption into a modified structure of matrix pores inter-connected to air voids introduced into the slurry by aeration.
Optical absorption and photoluminescent studies of cerium-doped cobalt tungstate nanomaterials
Authors: Naik S J , Subramanian Uma , Tangsali R B , Salker A V
Published: March 2011

This paper deals with optical absorption and photoluminescence properties of nanorange (22–65 nm) luminescent materials Co1−x
Ce
x
WO4 (where x = 0.01, 0.015, 0.02, 0.025 and 0.03) sintered in air at various temperatures. These compounds were prepared by the solution-based co-precipitation method and characterized by x-ray powder diffraction and thermal analysis. Optimum conditions for high luminescence emission were obtained.
Mixing categories
Authors: Oprea John , Strom Jeff
Published: March 2011

We show that
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c
a
t

(
X
)
≤

c
a
t

1

(
X
)
+

c
a
t

1

(
X
)

\mathrm {cat}(X) \leq \mathrm {cat}_1(X) + \mathrm {cat}^1(X)

, where

c
a
t

1

(
X
)

\mathrm {cat}_1(X)

is Fox’s

1
1

-dimensional category and

c
a
t

1

(
X
)

\mathrm {cat}^1(X)

is the

A

\mathcal {A}

-category of Clapp and Puppe with

\mathcal {A}=\{\mbox {1

-dimensional spaces}\}.
Dougall’s bilateral ₂𝐻₂-series and Ramanujan-like 𝜋-formulae
Authors: Chu Wenchang
Published: March 2011

The modified Abel lemma on summation by parts is employed to investigate the partial sum of Dougall’s bilateral

2

H
2

_2H_2

-series. Several unusual transformations into fast convergent series are established. They lead surprisingly to numerous infinite series expressions for

π
\pi

, including several formulae discovered by Ramanujan (1914) and recently by Guillera (2008).
Not Yet A Garrison State: Reconsidering Eisenhower's Military–Industrial Complex
Authors: Engel Jeffrey A.
Published: March 2011

Dwight Eisenhower's farewell address continues to resonate, beyond this admirable special edition of Enterprise & Society. The term he employed to describe the influence of corporations and financial interests over national defense policy, the “military–industrial complex,” usefully summarized phenomenon of his time. It also depicts an ongoing and arguably even structural phenomenon within contemporary American society. Ike would therefore appear in retrospect one part keen observer, another prophet. As the articles in this forum collectively suggest, the ideas embedded within his now-famous phrase continue to frame contemporary scholarship fifty years after his final Oval Office speech, though with a far narrower lens than Ike envisioned, and with less dire societal results than he feared. The military–industrial complex is both more real, and less frightening, than he foretold. At least, so far.
Methods for Characterization of Residual Starch in Distiller's Dried Grains with Solubles (DDGS)
Authors: Srichuwong Sathaporn , Jane Jay‐lin
Published: March 2011

The objective of this study was to establish methods for determining the content and components of residual starch in distiller's dried grains with solubles (DDGS), a coproduct from dry‐grind corn ethanol production. Four DDGS prepared in our laboratory and one DDGS obtained from a commercial ethanol manufacturer were used for the study. Quantitative analysis of total residual sugar (TRS) in DDGS was performed by determining d‐glucose produced by enzymatic hydrolysis of oligosaccharides and residual starch remaining in hexane‐defatted DDGS after being dispersed in 90% DMSO. The TRS consisted of free glucose, oligosaccharides, and residual starch. The commercial manufacturer's DDGS contained more TRS (15.8%, w/w db) than the laboratory‐processed DDGS (2.4–2.9%, w/w db). The content of residual starch remaining in the commercial DDGS (5.5% w/w db) was also larger than the laboratory‐processed DDGS (1.9–2.5% w/w db). Analyses of molecular weight distribution showed that the residual starch in DDGS consisted of short‐chain amylose and amylopectin, respectively, as the major and minor components. The short‐chain amylose molecules constituted 86.5–94.1% of the residual starch. The major population of the short‐chain amyloses had an average degree of polymerization (DP) of 85, closely resembling the length of enzyme‐resistant fragments of amylose‐lipid complexes.
Molecular Cloning of ATR5Emoy2 from Hyaloperonospora arabidopsidis, an Avirulence Determinant That Triggers RPP5-Mediated Defense in Arabidopsis
Authors: Bailey Kate , Çevik Volkan , Holton Nicholas , Byrne-Richardson Jane , Sohn Kee Hoon , Coates Mary , Woods-Tör Alison , Aksoy H. Murat , Hughes Linda , Baxter Laura , Jones Jonathan D. G. , Beynon Jim , Holub Eric B. , Tör Mahmut
Published: March 2011

RPP5 is the seminal example of a cytoplasmic NB-LRR receptor-like protein that confers downy mildew resistance in Arabidopsis thaliana. In this study, we describe the cloning and molecular characterization of the gene encoding ATR5Emoy2, an avirulence protein from the downy mildew pathogen Hyaloperonospora arabidopsidis isolate Emoy2. ATR5Emoy2 triggers defense response in host lines expressing the functional RPP5 allele from Landsberg erecta (Ler-0). ATR5Emoy2 is embedded in a cluster with two additional ATR5-like (ATR5L) genes, most likely resulting from gene duplications. ATR5L proteins do not trigger RPP5-mediated resistance and the copy number of ATR5L genes varies among H. arabidopsidis isolates. ATR5Emoy2 and ATR5L proteins contain a signal peptide, canonical EER motif, and an RGD motif. However, they lack the canonical translocation motif RXLR, which characterizes most oomycete effectors identified so far. The signal peptide and the N-terminal regions including the EER motif of ATR5Emoy2 are not required to trigger an RPP5-dependent immune response. Bioinformatics screen of H. arabidopsidis Emoy2 genome revealed the presence of 173 open reading frames that potentially encode for secreted proteins similar to ATR5Emoy2, in which they share some motifs such as EER but there is no canonical RXLR motif.
Experimental Verification of Seed Transmission of Zucchini yellow mosaic virus
Authors: Simmons H. E. , Holmes E. C. , Gildow F. E. , Bothe-Goralczyk M. A. , Stephenson A. G.
Published: March 2011

Within two decades of its discovery, Zucchini yellow mosaic virus (ZYMV) achieved a global distribution. However, whether or not seed transmission occurs in this economically significant crop pathogen is controversial, and the relative impact of seed transmission on the epidemiology of ZYMV remains unclear. Using reverse transcription–polymerase chain reaction, we observed a seed transmission rate of 1.6% in Cucurbita pepo subsp. texana and show that seed-infected C. pepo plants are capable of initiating horizontal ZYMV infections, both mechanically and via an aphid vector (Myzus persicae). We also provide evidence that ZYMV-infected seeds may act as effective viral reservoirs, partially accounting for the current geographic distribution of ZYMV. Finally, the observation that ZYMV infection of C. pepo seeds results in virtually symptomless infection, coupled with our finding that an antibody test failed to detect vertically transmitted ZYMV in infected seed, highlights the urgent need to standardize current detection methods for seed infection.
Clinical Assessment of the Ultrasonographic Measurement of Antral Area for Estimating Preoperative Gastric Content and Volume
Authors: Bouvet Lionel , Mazoit Jean-Xavier , Chassard Dominique , Allaouchiche Bernard , Boselli Emmanuel , Benhamou Dan
Published: March 2011

Background

This prospective observational study aimed to assess the feasibility and performance of the ultrasonographic measurement of antral cross-sectional area (CSA) for the preoperative assessment of gastric contents and volume in adult patients and for the diagnosis of risk stomach (defined by the presence of solid particles and/or gastric fluid volume >0.8 ml/kg).

Methods

A preoperative ultrasonographic measurement of the antral CSA was performed for each patient by a physician (L.B.) blinded to the history of the patient. Immediately after tracheal intubation, an 18-French multiorifice Salem tube was inserted and gastric contents were aspirated in five different patient positions; during this time, the patient's epigastrium was massaged and the tube was moved backward and forward in the stomach. The relationship between the antral area and the volume of aspirated gastric contents was analyzed, as was the performance of ultrasonographic measurement of antral area for the diagnosis of risk stomach.

Results

The measurement of antral CSA was performed on 180 of 183 patients. A significant positive relationship between antral CSA and aspirated fluid volume was found. The cutoff value of antral CSA of 340 mm(2) for the diagnosis of risk stomach was associated with a sensitivity of 91% and a specificity of 71%. The area under the receiver operating characteristic curve for the diagnosis of risk stomach was 90%.

Conclusions

The ultrasonographic measurement of antral CSA could be an important help for the anesthesiologist in minimizing the risk of pulmonary aspiration of gastric contents due to general anesthesia.
Propofol Restores Transient Receptor Potential Vanilloid Receptor Subtype-1 Sensitivity via Activation of Transient Receptor Potential Ankyrin Receptor Subtype-1 in Sensory Neurons
Authors: Zhang Hongyu , Wickley Peter J. , Sinha Sayantani , Bratz Ian N. , Damron Derek S.
Published: March 2011

Background

Cross talk between peripheral nociceptors belonging to the transient receptor potential vanilloid receptor subtype-1 (TRPV1) and ankyrin subtype-1 (TRPA1) family has been demonstrated recently. Moreover, the intravenous anesthetic propofol has directly activates TRPA1 receptors and indirectly restores sensitivity of TRPV1 receptors in dorsal root ganglion (DRG) sensory neurons. Our objective was to determine the extent to which TRPA1 activation is involved in mediating the propofol-induced restoration of TRPV1 sensitivity.

Methods

Mouse DRG neurons were isolated by enzymatic dissociation and grown for 24 h. F-11 cells were transfected with complementary DNA for both TRPV1 and TRPA1 or TRPV1 only. The intracellular Ca concentration was measured in individual cells via fluorescence microscopy. After TRPV1 desensitization with capsaicin (100 nM), cells were treated with propofol (1, 5, and 10 μM) alone or with propofol in the presence of the TRPA1 antagonist, HC-030031 (0.5 μM), or the TRPA1 agonist, allyl isothiocyanate (AITC; 100 μM); capsaicin was then reapplied.

Results

In DRG neurons that contain both TRPV1 and TRPA1, propofol and AITC restored TRPV1 sensitivity. However, in DRG neurons containing only TRPV1 receptors, exposure to propofol or AITC after desensitization did not restore capsaicin-induced TRPV1 sensitivity. Similarly, in F-11 cells transfected with both TRPV1 and TRPA1, propofol and AITC restored TRPV1 sensitivity. However, in F-11 cells transfected with TRPV1 only, neither propofol nor AITC was capable of restoring TRPV1 sensitivity.

Conclusions

These data demonstrate that propofol restores TRPV1 sensitivity in primary DRG neurons and in cultured F-11 cells transfected with both the TRPV1 and TRPA1 receptors via a TRPA1-dependent process. Propofol's effects on sensory neurons may be clinically important and may contribute to peripheral sensitization to nociceptive stimuli in traumatized tissue.
Magnesium—Essentials for Anesthesiologists
Authors: Herroeder Susanne , Schönherr Marianne E. , De Hert Stefan G. , Hollmann Markus W. , Warner David S.
Published: March 2011

Magnesium plays a fundamental role in many cellular functions, and thus there is increasing interest in its role in clinical medicine. Although numerous experimental studies indicate positive effects of magnesium in a variety of disease states, large clinical trials often give conflicting results. However, there is clear evidence for magnesium to benefit patients with eclampsia or torsades de pointes arrhythmias. In addition, magnesium seems to have antinociceptive and anesthetic as well as neuroprotective effects, yet well-designed large clinical trials are required to determine its actual efficacy in pain management or in the state of stroke or subarachnoid hemorrhage. The current review aims to provide an overview of current knowledge and available evidence with respect to physiologic aspects of magnesium and proposed indications and recommendations for its use in the clinical setting.
Efficacy of Tranexamic Acid in Pediatric Craniosynostosis Surgery
Authors: Goobie Susan M. , Meier Petra M. , Pereira Luis M. , McGowan Francis X. , Prescilla Randy P. , Scharp Laurie A. , Rogers Gary F. , Proctor Mark R. , Meara John G. , Soriano Sulpicio G. , Zurakowski David , Sethna Navil F.
Published: March 2011

Background

Extensive blood loss is common in pediatric craniosynostosis reconstruction surgery. Tranexamic acid (TXA) is increasingly used to reduce perioperative blood loss in various settings, but data on its efficacy are limited in children. The purpose of this randomized, double-blind, placebo-controlled, parallel trial was to evaluate the efficacy of TXA in pediatric craniosynostosis correction surgery. The primary and secondary outcome variables were reduction in perioperative blood loss and reduction in blood transfusion, respectively.

Methods

Forty-three children, ages 2 months to 6 yr, received either placebo or TXA in a loading dose of 50 mg·kg(-1), followed by an infusion of 5 mg·kg·h(-1) during surgery. TXA plasma concentrations were measured.

Results

The TXA group had significantly lower perioperative mean blood loss (65 vs. 119 ml·kg(-1), P < 0.001) and lower perioperative mean blood transfusion (33 vs. 56 ml· kg(-1), P = 0.006) compared to the placebo group. The mean difference between the TXA and placebo groups for total blood loss was 54 ml·kg(-1) (95% CI for the difference, 23-84 ml·kg(-1)) and for packed erythrocytes transfused was 23 ml·kg(-1) (95% CI for the difference, 7-39 ml·kg(-1)). TXA administration also significantly diminished (by two thirds) the perioperative exposure of patients to transfused blood (median, 1 unit vs. 3 units; P < 0.001). TXA plasma concentrations were maintained above the in vitro thresholds reported for inhibition of fibrinolysis (10 μg·ml(-1)) and plasmin-induced platelet activation (16 μg·ml(-1)) throughout the infusion.

Conclusions

TXA is effective in reducing perioperative blood loss and transfusion requirement in children undergoing craniosynostosis reconstruction surgery.
The fission yeast meiosis-specific Dmc1 recombinase mediates formation and branch migration of Holliday junctions by preferentially promoting strand exchange in a direction opposite to that of Rad51
Authors: Murayama Yasuto , Tsutsui Yasuhiro , Iwasaki Hiroshi
Published: March 2011

Homologous recombination proceeds via the formation of several intermediates including Holliday junctions (HJs), which are important for creating crossover products. DNA strand exchange is a core reaction that produces these intermediates that is directly catalyzed by RecA family recombinases, of which there are two types in eukaryotes: universal Rad51 and meiosis-specific Dmc1. We demonstrated previously that Rad51 promotes four-strand exchange, mimicking the formation and branch migration of HJs. Here we show that Dmc1 from fission yeast has a similar activity, which requires ATP hydrolysis and is independent of an absolute requirement for the Swi5–Sfr1 complex. These features are critically different from three-strand exchange mediated by Dmc1, but similar to those of four-strand exchange mediated by Rad51, suggesting that strand exchange reactions between duplex–duplex and single-duplex DNAs are mechanistically different. Interestingly, despite similarities in protein structure and in reaction features, the preferential polarities of Dmc1 and Rad51 strand exchange are different (Dmc1 promotes exchange in the 5′-to-3′ direction and Rad51 promotes exchange in the 3′-to-5′ direction relative to the ssDNA region of the DNA substrate). The significance of the Dmc1 polarity is discussed within the context of the necessity for crossover production.
Reduced fidelity of branch point recognition and alternative splicing induced by the anti-tumor drug spliceostatin A
Authors: Corrionero Anna , Miñana Belén , Valcárcel Juan
Published: March 2011

Spliceostatin A (SSA) is a stabilized derivative of a Pseudomonas bacterial fermentation product that displays potent anti-proliferative and anti-tumor activities in cancer cells and animal models. The drug inhibits pre-mRNA splicing in vitro and in vivo and binds SF3b, a protein subcomplex of U2 small nuclear ribonucleoprotein (snRNP), which is essential for recognition of the pre-mRNA branch point. We report that SSA prevents interaction of an SF3b 155-kDa subunit with the pre-mRNA, concomitant with nonproductive recruitment of U2 snRNP to sequences 5′ of the branch point. Differences in base-pairing potential with U2 snRNA in this region lead to different sensitivity of 3′ splice sites to SSA, and to SSA-induced changes in alternative splicing. Indeed, rather than general splicing inhibition, splicing-sensitive microarray analyses reveal specific alternative splicing changes induced by the drug that significantly overlap with those induced by knockdown of SF3b 155. These changes lead to down-regulation of genes important for cell division, including cyclin A2 and Aurora A kinase, thus providing an explanation for the anti-proliferative effects of SSA. Our results reveal a mechanism that prevents nonproductive base-pairing interactions in the spliceosome, and highlight the regulatory and cancer therapeutic potential of perturbing the fidelity of splice site recognition.
Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications
Authors: Polo Sophie E. , Jackson Stephen P.
Published: March 2011

Genome integrity is constantly monitored by sophisticated cellular networks, collectively termed the DNA damage response (DDR). A common feature of DDR proteins is their mobilization in response to genotoxic stress. Here, we outline how the development of various complementary methodologies has provided valuable insights into the spatiotemporal dynamics of DDR protein assembly/disassembly at sites of DNA strand breaks in eukaryotic cells. Considerable advances have also been made in understanding the underlying molecular mechanisms for these events, with post-translational modifications of DDR factors being shown to play prominent roles in controlling the formation of foci in response to DNA-damaging agents. We review these regulatory mechanisms and discuss their biological significance to the DDR.
Review article: reflux and its consequences – the laryngeal, pulmonary and oesophageal manifestations
Authors: Dettmar P. W. , Castell D. O. , Heading R. C. , Dettmar P. W. , Ell S. , Fagan M. J. , McGlashan J. A. , Morice A. H. , Watson M.
Published: March 2011

Background  Gastro‐oesophageal reflux disease (GERD) is one of the commonest diseases of Western populations, affecting 20 to 30% of adults. GERD is multifaceted and the classical oesophageal symptoms such as heartburn and regurgitation often overlap with atypical symptoms that impact upon the respiratory system and airways. This is referred to as extra‐oesophageal reflux disease (EERD), or laryngopharyngeal reflux (LPR), which manifests as chronic cough, laryngitis, hoarseness, voice disorders and asthma.

Aim  The ‘Reflux and its consequences’ conference was held in Hull in 2010 and brought together a multidisciplinary group of experts all with a common interest in the many manifestations of reflux disease to present recent research and clinical progress in GERD and EERD. In particular new techniques for diagnosing reflux were showcased at the conference.

Methods  Both clinical and non‐clinical key opinion leaders were invited to write a review on key areas presented at the `Reflux and its consequences' conference for inclusion in this supplement.

Results and conclusion  Eleven chapters contained in this supplement reflected the sessions of the conference and included discussion of the nature of the refluxate (acid, pepsin, bile acids and non‐acid reflux); mechanisms of tissue damage and protection in the oesophagus, laryngopharynx and airways. Clinical conditions with a reflux aetiology including asthma, chronic cough, airway disease, LPR, and paediatric EERD were reviewed. In addition methods for diagnosis of reflux disease and treatment strategies, especially with reference to non‐acid reflux, were considered.

Aliment Pharmacol Ther 2011; 33 (Suppl. 1), 1–71
Insulin autoantibodies with high affinity to the bovine milk protein alpha casein
Authors: Adler K , Mueller D B , Achenbach P , Krause S , Heninger A-K , Ziegler A G , Bonifacio E
Published: March 2011

Insulin autoantibodies (IAA) can appear in children within months of introducing solid foods to the diet and before clinical type 1 diabetes. The aim of this study was to determine whether infant dietary antigens could be immunizing agents of IAA. To this end, IAA binding to [125I]insulin was competed with food preparations and extracts of foods encountered in the infant diet (milk formulas, bovine milk, wheat flour, fowl meal). Bovine milk powder extracts inhibited IAA-positive samples from six of 53 children (age 0·3–14·0 years) participating in German prospective cohorts. Inhibition in these sera ranged from 23 to 100%. Competition was abolished when hydrolyzed milk powder was used. Competition with protein components of bovine milk found that two of the six milk-reactive sera were inhibited strongly by alpha- and beta-casein; none were inhibited by the milk proteins bovine serum albumin or lactoglobulins. The two casein-reactive sera had high affinity to alpha-casein (1·7 × 109; 3·1 × 109 l/mol), and lesser affinity to beta-casein (4·0 × 108; 7·0 × 107 l/mol) and insulin (2·6 × 108; 1·6 × 108 l/mol). No children with milk-reactive IAA developed autoantibodies to other islet autoantigens or diabetes (median follow-up 9·8 years). These results suggest that autoimmunity to insulin can occur infrequently via cross-reactivity to food proteins, but this form of IAA immunization does not appear to be associated with progression to diabetes.
Enhanced lymphocyte interferon (IFN)-γ responses in a PTEN mutation-negative Cowden disease kindred
Authors: Stevenson R , Fatehullah A , Jagan I , Deevi R K , Bingham V , Irvine A E , Armstrong M , Morrison P J , Dimmick I , Stewart R , Campbell F C
Published: March 2011

Identification of immune modifiers of inherited cancer syndromes may provide a rationale for preventive therapy. Cowden disease (CD) is a genetically heterogeneous inherited cancer syndrome that arises predominantly from germline phosphatase and tensin homologue deleted on chromosome 10 (PTEN) mutation and increased phosphoinositide 3-kinase/mammalian target of rapamycin (PI3K/mTOR) signalling. However, many patients with classic CD diagnostic features are mutation-negative for PTEN (PTEN M-Neg). Interferon (IFN)-γ can modulate the PI3K/mTOR pathway, but its association with PTEN M-Neg CD remains unclear. This study assessed IFN-γ secretion by multi-colour flow cytometry in a CD kindred that was mutation-negative for PTEN and other known susceptibility genes. Because IFN-γ responses may be regulated by killer cell immunoglobulin-like receptors (KIR) and respective human leucocyte antigen (HLA) ligands, KIR/HLA genotypes were also assessed. Activating treatments induced greater IFN-γ secretion in PTEN M-Neg CD peripheral blood lymphocytes versus healthy controls. Increased frequency of activating KIR genes, potentially activating KIR/HLA compound genotypes and reduced frequency of inhibitory genotypes, were found in the PTEN M-Neg CD kindred. Differences of IFN-γ secretion were observed among PTEN M-Neg CD patients with distinct KIR/HLA compound genotypes. Taken together, these findings show enhanced lymphocyte secretion of IFN-γ that may influence the PI3K/mTOR CD causal molecular pathway in a PTEN mutation-negative CD kindred.
On the computation of the electrical potential inside a horizontally‐layered half‐space
Authors: Maineult Alexis , Schott Jean‐Jacques
Published: March 2011

A new formulation is proposed for the electrical potential developed inside a horizontally‐layered half‐space for a direct current point‐source at the surface. The recursion formula for the kernel coefficient in the potential integral is simpler than the generally used two‐coefficient recursion. The numerical difficulties that may occur during the computation of the integrals and near the source axis are examined and solutions are proposed. The set of equations permits a stable and accurate computation of the tabular potential everywhere in the medium.
HLA‐C as a mediator of natural killer and T‐cell activation: spectator or key player?
Authors: Blais Marie‐Eve , Dong Tao , Rowland‐Jones Sarah
Published: March 2011

The biochemical properties of the HLA‐C antigen differ substantially from those of HLA‐A and ‐B molecules. For this reason, HLA‐C diversity and expression at the cell surface are much lower than its counterparts and in consequence HLA‐C‐restricted responses have been infrequently detected and described. In this review we summarise the key differences between HLA‐C and other class I molecules and provide an update on natural killer and T‐cell responses restricted by HLA‐C. We also discuss the different clinical settings associated with HLA‐C alleles which mainly consist of autoimmune disorders, cancers and chronic infections.
Hepatitis C virus persistence after sustained virological response to antiviral therapy in patients with or without past exposure to hepatitis B virus
Authors: Pham T. N. Q. , Coffin C. S. , Churchill N. D. , Urbanski S. J. , Lee S. S. , Michalak T. I.
Published: March 2011

Summary.  Hepatitis C virus (HCV) and hepatitis B virus (HBV) frequently coinfect and persist long after clinical resolution. We assessed the incidence of low‐level (occult) HCV infection (OCI) after sustained virological response (SVR) to standard anti‐HCV therapy in individuals with or without past exposure to HBV to recognize whether HBV could influence the prevalence of OCI, HCV level and hepatic histology. Plasma and peripheral blood mononuclear cells (PBMC) were collected from 24 individuals at 6‐ to 12‐month intervals for up to 72 months after SVR. Liver histology was available for nine patients. HCV and HBV genomes were detected with sensitivity <10 genome copies/mL. In individuals without HBV exposure (n = 15), comprehensive analyses of sequential plasma and PBMC samples revealed HCV RNA in all 15 cases (75% plasma and 61% PBMC). In the group with HBV exposure (n = 9), evidenced by circulating anti‐HBc and/or HBV DNA detection by a highly sensitive assay, HCV RNA was identified in all cases (83% plasma and 59% PBMC), at levels similar to those in HBV nonexposed individuals. In both groups of patients, most liver biopsies included those reactive for viral genomes displayed low‐grade inflammation (8 of 9) and fibrosis (7 of 9). Sequence polymorphisms at the 5`‐UTR between PBMC and liver or plasma, as well as circulating HCV virion‐like particles, were observed in patients with or without HBV exposure. In conclusion, the prevalence of OCI after SVR is comparable in individuals with or without past exposure to HBV. HCV loads and liver alterations in OCI appear to be unaffected by low‐level HBV DNA carriage.
Frequency and clinical outcomes of flares related to nucleos(t)ide analogue therapy in patients with chronic hepatitis B
Authors: Zhang N.‐P. , Reijnders J. G. P. , Perquin M. , Hansen B. E. , Janssen H. L. A.
Published: March 2011

Summary.  Flares in chronic hepatitis B are often detrimental but sometimes lead to sustained immune control and disease remission. The aim of this study was to estimate the frequency of hepatitis flares which occur during and/or after cessation of nucleos(t)ide analogue (NA) therapy, and to assess their outcomes. In a single centre cohort study we investigated 227 patients who received a total of 351 NA treatment courses. NA therapy was discontinued after 149 treatment courses. In total, 27 flares were observed during 9779 on‐treatment patient‐months. The frequency was estimated as 3.2 per 100 person‐years (95% CI 2.2–4.7). Lamivudine (LAM)‐treated patients demonstrated the highest frequency (4.9/100 person‐years, 95% CI 3.2–7.4). Twenty (74%) of 27 on‐therapy flares were associated with development of genotypic resistance, which all occurred during LAM therapy. NA withdrawal flares occurred after a median post‐treatment follow‐up of 3.5 months in 17 (11%) of 149 treatment discontinuations. No flares were observed in patients who switched to another antiviral agent (n = 51). None of the on‐therapy and withdrawal flares related to NA therapy were associated with sustained disease remission, and seven flares resulted in decompensated liver disease. In this study, flares related to NA therapy never led to immune control and sustained disease remission, and sometimes resulted in decompensated liver disease.
Salmonella detoxifying enzymes are sufficient to cope with the host oxidative burst
Authors: Aussel Laurent , Zhao Weidong , Hébrard Magali , Guilhon Aude‐Agnès , Viala Julie P. M. , Henri Sandrine , Chasson Lionel , Gorvel Jean‐Pierre , Barras Frédéric , Méresse Stéphane
Published: March 2011

The oxidative burst produced by the NADPH oxidase (Phox) is an essential weapon used by host cells to eradicate engulfed pathogens. In Salmonella typhimurium, oxidative stress resistance has been previously proposed to be mediated by the pathogenicity island 2 type III secretion system (T3SS‐2), periplasmic superoxide dismutases and cytoplasmic catalases/peroxidases. Here, we fused an OxyR‐dependent promoter to the gfp to build the ahpC‐gfp transcriptional fusion. This reporter was used to monitor hydrogen peroxide levels as sensed by Salmonella during the course of an infection. We showed that the expression of this fusion was under the exclusive control of reactive oxygen species produced by the host. The ahpC‐gfp expression was noticeably modified in the absence of bacterial periplasmic superoxide dismutases or cytoplasmic catalases/peroxidases. Surprisingly, inactivation of the T3SS‐2 had no effect on the ahpC‐gfp expression. All together, these results led to a model in which Salmonella resistance relies on its arsenal of detoxifying enzymes to cope with Phox‐mediated oxidative stress.
Impact of patterns of proteinuria on renal allograft function and survival: a prospective cohort study
Authors: Suhail S.M. , Kee T.S.Y. , Woo K.T. , Tan H.K. , Yang W.S. , Chan C.M. , Foo M.W.Y. , Li H.H. , Siddique M.M. , Wong K.S.
Published: March 2011

Suhail SM, Kee TSY, Woo KT, Tan HK, Yang WS, Chan CM, Foo MWY, Li HH, Siddique MM, Wong KS. Impact of patterns of proteinuria on renal allograft function and survival: a prospective cohort study. Clin Transplant 2011: 25: E297–E303. © 2011 John Wiley & Sons A/S.

Abstract:  Background:  Proteinuria is an important complication in renal transplant recipients. The aim of this prospective study was to evaluate the long‐term impact of transplant proteinuria patterns on allograft function and survival.

Methods:  We analyzed urinary protein of a cohort of 83 renal transplants with proteinuria ≥0.5 g/d by sodium dodecyl sulfate–polyacrylamide gel electrophoresis and radial immunogel diffusion assay. After initial stratification and analysis, the cohort was followed up for 16 yr. The graft outcome and survival were analyzed using Cox regression model to determine their association with different patterns of initial transplant proteinuria.

Results:  Group with predominantly glomerular (middle‐ and high‐molecular‐weight with or without low‐molecular‐weight) proteinuria (61%) had higher serum creatinine (p < 0.001) than the group with predominantly tubular (low‐molecular‐weight) proteinuria (39%). The incidences of chronic graft dysfunction and graft loss had increased in the glomerular proteinuria group (p < 0.001, hazard ratio 3.6, 95% confidence interval 1.7–7.5 and p < 0.001, hazard ratio 4.9, 95% confidence interval 1.9–12.1, respectively). Patient death did not differ (p = 0.434, hazard ratio 1.5, 95% confidence interval 0.5–4.5).

Conclusion:  Proteinuria in renal transplants can be differentiated into glomerular and tubular types based on molecular weight. Glomerular proteinuria is associated with significant increase in graft dysfunction and graft loss.
The relationship between isoprene emission, CO2 assimilation and water use efficiency across a range of poplar genotypes
Authors: Guidolotti Gabriele , Calfapietra Carlo , Loreto Francesco
Published: March 2011

Poplars (Populus sp.) are among the strongest isoprene (Iso)‐emitting plants. Ten poplar genotypes belonging to four different species were grown under the same environmental conditions in a common garden experiment, to study the influence of the genetic variability on Iso emission and on the relationship between Iso and photosynthesis. Photosynthesis ranged from 13 to 20 µmol CO2 m−2 s−1, whereas Iso emission ranged from 18.2 to 45.2 nmol m−2 s−1. There was no clear association between Iso emission and photosynthesis. In most genotypes, photosynthetic capacity developed earlier than Iso emission capacity. The emission of Iso was inversely correlated with the intercellular CO2 concentration (Ci) and positively correlated with instantaneous water use efficiency. It is speculated that, by regulating Ci, stomatal opening also indirectly controls Iso emission in poplars. A positive linear correlation between the fraction of recently assimilated carbon emitted as Iso and Iso emission rate was found. The slope of this relationship indicated that each nanomole of Iso emitted requires a fixed fraction of photosynthetic carbon regardless of the intra‐ and interspecific variability in the Populus genus, and of leaf ontogeny. A comparison with data from recent studies showed that the slope of this relationship increases in drought‐stressed leaves. However, this might be explained by an increasing contribution of carbon sources for Iso biosynthesis from stored photosynthates. If this is true, then the amount of carbon directly shunted from photosynthesis into Iso is constant in all poplars and is not influenced by abiotic stresses.
Ectopic Endometrial Tissue in Mesonephric Duct Remnants in Bitches
Authors: Bartel C , Berghold P , Walter I
Published: March 2011

Contents

Common congenital embryonic remnants of the canine female genital tract are Gartner cysts originating from mesonephric duct remnants. They can increase in size and lead to adverse effects in fertility and health. In the present study, three cases of mesonephric remnants in bitches were analysed. The mesonephric remnants featured an inner lining endometrium comprising surface epithelium, glands and stroma. This ectopic endometrium was further characterized by immunohistochemistry (oestrogen and progesterone receptors, proliferation activity, cytokeratin, alpha smooth muscle actin, and vimentin) and lectin histochemistry compared with normal uterine endometrium. Furthermore, hypertrophic cells at the serosal site of the uteri were detected and analysed in the same way compared with normal serosa. The ectopic endometrium of case no. 2 mesonephric remnant was comparable with normal endometrium whereas in nos 1 and 3 uteri the ectopic endometrium was reduced in thickness. In all mesonephric remnants, surface and glandular epithelial cells of the ectopic endometrium gave positive immunoreactions for cytokeratin, oestrogen and progesterone receptors and showed lectin‐binding patterns comparable with normal endometrium. Some of the stromal cells of the ectopic endometria were smooth muscle actin and vimentin positive. Mitotic activity of the ectopic endometria was comparable with normal endometria. Hypertrophic epithelial cells of the serosal side showed positive reactions to anti‐oestrogen receptor and anti‐cytokeratin immunohistochemistry as well as lectin binding patterns and mitotic activity comparable with the normal canine serosa. The present study is the first considerable immunohistochemical characterization of canine mesonephric remnants and discusses the appearance of ectopic endometrium in mesonephric remnants.
Pro‐inflammatory cytokines are raised in extrahepatic portal venous obstruction, with minimal hepatic encephalopathy
Authors: Srivastava Anshu , Yadav Santosh Kumar , Yachha Surender Kumar , Thomas Michael Albert , Saraswat Vivek Anand , Gupta Rakesh Kumar
Published: March 2011

Background and Aims:  Minimal hepatic encephalopathy (MHE) and hyperammonemia are seen in patients with extrahepatic portal venous obstruction (EHPVO). Inflammation has been shown to play an important role in the pathogenesis of hepatic encephalopathy in cirrhotics. This study assessed serum pro‐inflammatory cytokines and their correlation with hyperammonemia, 1H‐magnetic resonance (MR) spectroscopy‐derived brain glutamine, and diffusion tensor imaging (DTI)‐derived metrics in patients with EPHVO, with and without MHE.

Methods:  Neuropsychological tests, DTI, 1H‐MR spectroscopy, and estimation of blood ammonia and pro‐inflammatory cytokines (tumor necrosis factor‐α[TNF‐α] and interleukin‐6 [IL‐6]) were done in 20 patients with EHPVO and eight healthy controls.

Results:  Pro‐inflammatory cytokines (TNF‐α and IL‐6), blood ammonia, brain glutamine, and mean diffusivity were increased in both patient groups, as compared to controls. Patients with MHE (n‐12) had significantly higher TNF‐α, IL‐6, blood ammonia, brain glutamine, and mean diffusivity, signifying brain edema, than controls. A significant, positive correlation was seen between TNF‐α and IL‐6 and between blood ammonia and TNF‐α, IL‐6, and brain glutamine. Significant, positive correlations of TNF‐α, IL‐6, and blood ammonia with mean diffusivity values were seen in various brain regions, including spectroscopy voxel‐derived mean diffusivity.

Conclusion:  Patients with extrahepatic portal vein obstruction have inflammation and hyperammonemia made evident by higher blood TNF‐α, IL‐6, ammonia, and brain glutamine levels. A significant correlation between hyperammonemia, pro‐inflammatory cytokines, and cerebral edema on DTI in various brain regions suggests that both these factors play a role in the pathogenesis of MHE in these patients.
Different sex‐related influences of eating habits on the prevalence of reflux esophagitis in Japanese
Authors: Mizuta Atsushi , Adachi Kyoichi , Furuta Kenji , Ohara Shunji , Morita Terumi , Koshino Kenji , Tanaka Shino , Moriyama Mika , Sumikawa Masuko , Sanpei Mari , Kinoshita Yoshikazu
Published: March 2011

Background and Aim:  Many types of food have been shown to affect lower esophageal sphincter pressure and esophageal motor function, and thus, the prevalence of reflux esophagitis. The present study was performed to clarify the different eating habits that predominantly affect the prevalence of reflux esophagitis in Japanese.

Methods:  The study included 2303 individuals (males: 1599, females: 704, mean age: 49.9 years) who underwent upper gastrointestinal endoscopy for gastric cancer screening. The daily dietary contents of the patients were analyzed using a self‐administered questionnaire.

Results:  A total of 201 patients had endoscopically‐proven reflux esophagitis, and the percentage of males with reflux esophagitis was significantly higher than their female counterparts (11.3% vs 2.8%). The body mass indexes of individuals with reflux esophagitis were significantly higher than those without, both for males and females. Total energy intake was the most important risk factor for the occurrence of reflux esophagitis in males, but the food content was not a significant risk factor. Dietary habit did not affect the prevalence of reflux esophagitis in the female patients. The age and height of females with reflux esophagitis significantly exceeded those of females without reflux esophagitis, and were independent risk factors for the occurrence of reflux esophagitis only in the female patients.

Conclusion:  There is a sex‐related difference in the influence of eating habits on the prevalence of reflux esophagitis in Japanese.