bluuebunny/crossref_metadata_2025 huggingface dataset:
Contralateral biopsies in patients with testicular germ cell tumours: patterns of care in Germany and recent data regarding prevalence and treatment of testicular intra‐epithelial neoplasia
Authors: Ruf C.G. , Gnoss A. , Hartmann M. , Matthies C. , Anheuser P. , Loy V. , Pichlmeier U. , Dieckmann K.‐P.
Published: August 2014

The precursor of testicular germ cell tumours (GCTs), called testicular intra‐epithelial neoplasia (TIN/CIS), is safely diagnosed immunohistologically. Testicular biopsy provides a valuable tool for early detection of GCTs in risk groups. Although this knowledge is undisputed, testicular biopsies are utilized poorly. The patterns of care regarding the use of biopsies remain unknown. Uncertainty exists about the prevalence and specific treatment of TIN/CIS. We asked clinical urologists in Germany whether or not they employed contralateral biopsies in GCT patients. We evaluated the prevalence of contralateral TIN/CIS in a retrospective analysis of 780 consecutive GCT patients. All had contralateral double biopsies. Discordance of TIN/CIS findings among biopsy pairs as well as age, histology of the primary tumour and clinical stage was noted. Evaluation of data comprised descriptive statistical methods. To evaluate treatment options for TIN/CIS, we performed a literature search. 52.1% of German urologists always perform the biopsy, 17% do it mostly, 27.3% in select cases, 3.5% never. Curiously, there was a geographic north‐south gradient regarding biopsy use. Contralateral TIN/CIS was found in 5%. The median ages of patients with TIN/CIS and those without were 31.8 and 34.9 years respectively (p = 0.02). The discordance rate among biopsy pairs was of 33%. Two‐site biopsies provide a 17% gain in diagnostic sensitivity. Local radiotherapy with 20 Gy is the safest treatment of TIN/CIS failing in 2%. Chemotherapy has significantly lower efficacy. Contralateral testicular biopsies in GCT patients are well accepted among German urologists. The prevalence of contralateral TIN/CIS found in this series is in accordance with previous reports. Double biopsies should be the diagnostic standard because of their diagnostic superiority. Local radiotherapy with 20 Gy is the safest way of eradicating TIN/CIS. Failures occur in only 2%, usually many years after irradiation. Cisplatin‐based chemotherapy is dose dependent and less effective.
Contrasting Water‐Use Efficiency (WUE) Responses of a Potato Mapping Population and Capability of Modified Ball‐Berry Model to Predict Stomatal Conductance and WUE Measured at Different Environmental Conditions
Authors: Kaminski K. P. , Kørup K. , Kristensen K. , Nielsen K. L. , Liu F. , Topbjerg H. B. , Kirk H. G. , Andersen M. N.
Published: August 2014

Potatoes (Solanum tuberosum L.) are drought‐sensitive and more efficient water use, while maintaining high yields is required. Here, water‐use efficiency (WUE) of a mapping population comprising 144 clones from a cross between 90‐HAF‐01 (Solanum tuberosum1) and 90‐HAG‐15 (S. tuberosum2 × S. sparsipilum) was measured on well‐watered plants under controlled‐environment conditions combining three levels of each of the factors: [CO2], temperature, light, and relative humidity in growth chambers. The clones were grouped according to their photosynthetic WUE (pWUE) and whole‐plant WUE (wpWUE) during experiments in 2010. Two offspring groups according to pWUE and wpWUE were identified on the basis of experiments conducted in 2010, which in experiments in 2011 again showed significant differences in pWUE (46 %, P < 0.001) and wpWUE (34 %, P < 0.001). The high‐WUE group had a higher net photosynthesis rate (34 %) and dry matter accumulation (55 %, P < 0.001) rather than leaf‐level transpiration rate (−4 %, no significant difference) or whole‐plant water use (16 %). The pWUE correlated negatively to the ratio between leaf‐internal and leaf‐external [CO2] (R2 = −0.86 in 2010 and R2 = −0.83 in 2011, P < 0.001). The leaf chlorophyll content was lower in the high‐WUE group indicating that the higher net photosynthesis rate was not due to higher leaf‐N status. Less negative value of carbon isotope discrimination (δ13C) in the high‐WUE group was only found in 2011. A modified Ball‐Berry model was fitted to measured stomatal conductance (gs) under the systematically varied environmental conditions to identify parameter differences between the two groups, which could explain their contrasting WUE. Compared to the low‐WUE group, the high‐WUE group showed consistently lower values of the parameter m, which is inversely related to WUE. Differences related specifically to the dependence of gs on humidity and net photosynthesis rate were only found in 2010. The lower ratio between leaf‐internal and leaf‐external [CO2] and higher WUE of the high‐WUE group was consistent over a wide range of air vapour pressure deficits from 0.5 to 3.5 kPa. The mapping population was normally distributed with respect to WUE suggesting a multigenic nature of this trait. The WUE groups identified can be further employed for quantitative trait loci (QTL) analysis by use of gene expression studies or genome resequencing. The differences in population WUE indicate a genetic potential for improvement of this trait.
Revealing Structural Relaxation of Optical Glass Through the Temperature Dependence of Young's Modulus
Authors: Liu Weidong , Ruan Haihui , Zhang Liangchi
Published: August 2014

Structural relaxation is one of the most important features of a glass material at an elevated temperature. This study aims to obtain an insight into the structural relaxation process of a typical optical glass. Experimentally, a high‐temperature impulse excitation technique was used to explore the mechanism through monitoring the variation of the Young's modulus of the material. Theoretically, the Tool–Narayanaswamy–Moynihan (TNM) model was employed to describe the variation of modulus with time and temperature. It was found that the parameterized TNM model obtained by modulus data could be used to achieve a more subtle description of the variation of coefficient of thermal expansion during structural relaxation, which is vital for thermoforming a glass product.
Structure, Phase Transition, and Electronic Properties of K1−xNaxNbO3 Solid Solutions from First‐Principles Theory
Authors: Liu Shi‐Yu , Liu Shiyang , Li De‐Jun , Shen Yaogen , Dang Hongli , Liu Yingdi , Xue Wenhua , Wang Sanwu
Published: August 2014

With extensive first‐principles calculations, we investigated the geometric structure, phase transition, and electronic properties of orthorhombic, monoclinic, and tetragonal K1−xNaxNbO3 (KNN) as functions of the Na content. We found that KNN undergoes an orthorhombic‐to‐monoclinic‐to‐orthorhombic phase transition when the Na content is gradually increased. We also found that the polarization vector of the monoclinic phase can be rotated more easily than those of the orthorhombic and tetragonal phases, giving rise to an enhanced piezoelectric response of the monoclinic KNN. Furthermore, our calculations provide an interpretation for the experimentally observed unusual broad peak of the KNN piezoelectric parameters.
Preparation and Luminescence Properties of Eu2+ and Mn2+ Coactivated Tricalcium Phosphate Phosphors
Authors: Zhou Wenli , Han Jin , Pan Fengjuan , Zhang Jilin , Xie Qingji , Lian Shixun , Yu Liping , Wang Jing
Published: August 2014

Eu2+ and Mn2+ coactivated β–Ca3(PO4)2 (TCP) phosphors have been prepared by high‐temperature solid‐state reaction. The site occupation and photoluminescence properties of Eu2+ and Mn2+ have been identified and discussed in detail. The energy transfer from Eu2+ to Mn2+ in TCP: Eu2+, Mn2+ phosphors has been validated and demonstrated to be a resonant type via a dipole‐quadrupole mechanism, and the critical distance (RC) calculated by concentration quenching method is 21.76 Å. A color‐tunable emission from violet‐blue to red in TCP: Eu2+, Mn2+ phosphors can be realized via the energy transfer from Eu2+ to Mn2+ ions.
Finding the True Voice of the Customer inCPGSupply Chains: Shopper‐Centric Supply Chain Management
Authors: Zondag Marcel M. , Ferrin Bruce
Published: August 2014

Demand and supply integration is the subject of increasing scholarly attention. The theoretical emphasis on combining market and supply chain data as the basis for strategic and operational decision making is particularly relevant in the context of Consumer Packaged Goods (CPG) supply chains, and offers the basis for advancing our understanding and knowledge in this field. Point‐of‐sale (POS) data are commonly used as the demand signal inCPGsupply chains. Using empirical data, this research demonstrates thatPOSdata can be influenced by nondemand factors. We present a number of issues raised by this finding.
Reduction in behavior problems with omega‐3 supplementation in children aged 8–16 years: a randomized, double‐blind, placebo‐controlled, stratified, parallel‐group trial
Authors: Raine Adrian , Portnoy Jill , Liu Jianghong , Mahoomed Tashneem , Hibbeln Joseph R.
Published: August 2014

Background

While limited evidence suggests that omega‐3 supplementation may reduce antisocial behavior in children, studies have not reported on posttreatment follow‐up and most treatment periods have been of short duration. This study tests the hypothesis that omega‐3 supplementation over 6 months will reduce behavior problems in children both at the end of treatment and at 6 months post treatment.

Methods

In this randomized, double‐blind, placebo‐controlled, stratified, parallel‐group trial, a community sample of 8–16 year old children were randomized into a treatment group (N = 100) and a placebo‐control group (N = 100). The supplementation consisted of a fruit drink containing 1 g/day of omega‐3 or a placebo consisting of the same fruit drink without omega‐3. Participants, caregivers, and research assistants were blinded to group assignment. The primary outcome measures of externalizing and internalizing behavior problems were reported by both caregivers and their children in a laboratory setting at 0 months (baseline), 6 months (end of treatment) and 12 months (6 months post treatment), together with the secondary outcome measures of parental antisocial behavior. Data were analyzed on an intention‐to‐treat basis including all participants. Trial registration: ClinicalTrials.gov: http://clinicaltrials.gov/ct2/show/NCT02016079?term=mauritius&rank=2

Results

Significant group × time interactions were observed with the treatment group showing long‐term improvements in child behavior problems. The average posttreatment effect size was d = −.59. Effects were documented for parent reports, but with the exception of proactive and reactive aggression, child‐report data were nonsignificant. Parents whose children took omega‐3 showed significant posttreatment reductions in their own antisocial and aggressive behavior. This improvement in caregiver behavior partly mediated the improvements observed in child behavior.

Conclusions

Findings provide initial evidence that omega‐3 supplementation can produce sustained reductions in externalizing and internalizing behavior problems. Results are the first to report improvements in caregiver behavior, and to establish this improvement as a part‐mechanism for the efficacy of omega‐3.
Slr0151 in Synechocystis sp. PCC 6803 is required for efficient repair of photosystem II under high‐light condition
Authors: Yang Haomeng , Liao Libing , Bo Tingting , Zhao Lei , Sun Xuwu , Lu Xuefeng , Norling Birgitta , Huang Fang
Published: August 2014

Cyanobacteria are ancient photosynthetic prokaryotes that have adapted successfully to adverse environments including high‐light irradiation. Although it is known that the repair of photodamaged photosystem II (PSII) in the organisms is a highly regulated process, our knowledge of the molecular components that regulate each step of the process is limited. We have previously identified a hypothetical protein Slr0151 in the membrane fractions of cyanobacterium Synechocystis sp. PCC 6803. Here, we report that Slr0151 is involved in PSII repair of the organism. We generated a mutant strain (Δslr0151) lacking the protein Slr0151 and analyzed its characteristics under normal and high‐light conditions. Targeted deletion of slr0151 resulted in decreased PSII activity in Synechocystis. Moreover, the mutant exhibited increased photoinhibition due to impairment of PSII repair under high‐light condition. Further analysis using in vivo radioactive labeling and 2‐D blue native/sodium dodecylsulfate polyacrylamide gel electrophoresis indicated that the PSII repair cycle was hindered at the levels of D1 synthesis and disassembly and/or assembly of PSII in the mutant. Protein interaction assays demonstrated that Slr0151 interacts with D1 and CP43 proteins. Taken together, these results indicate that Slr0151 plays an important role in regulating PSII repair in the organism under high‐light stress condition.
The Effects of Oil Price Uncertainty on Global Real Economic Activity
Authors: JO SOOJIN
Published: August 2014

This paper investigates the effect of oil price uncertainty on global real economic activity using a quarterly vector autoregressive model with stochastic volatility in mean. Stochastic volatility allows oil price uncertainty to vary separately from changes in the level of oil prices, and allows one to incorporate an extraneous indicator of oil price uncertainty such as realized volatility that greatly improves the precision of the estimated uncertainty series. The estimation results show that an oil price uncertainty shock has negative effects on world industrial production all else equal. For example, it is shown that a doubling of oil price volatility is associated with a cumulative decline as high as 0.3 percentage points in world industrial production.
Lumpy Investment and Corporate Tax Policy
Authors: MIAO JIANJUN , WANG PENGFEI
Published: August 2014

In the presence of both convex and nonconvex capital adjustment costs in a dynamic general equilibrium model, corporate tax policy generates both intensive and extensive margin effects via the channel of marginal Q. Its impact is determined largely by the strength of the extensive margin effect, which, in turn, depends on the cross‐sectional distribution of firms. Depending on the initial distribution of firms, the economy displays asymmetric responses to tax changes. Moreover, an anticipated increase in the future investment tax credit reduces investment and adjustment rate initially.
Information from Relationship Lending: Evidence from Loan Defaults in China
Authors: CHANG CHUN , LIAO GUANMIN , YU XIAOYUN , NI ZHENG
Published: August 2014

Using a proprietary database from a large Chinese state‐owned bank, we examine whether information evolved from banking relationships predicts commercial loan default by industrial firms. We find that the bank's relationship information is significantly linked to the incidence of default, and that its contribution to prediction accuracy is larger than any hard information. Furthermore, the effect of relationship information is stronger among firms that have a more sustained banking relationship. Our findings indicate that, at least in the emerging markets, a bank's relationship information still matters for large firms, despite the fact that hard information for such firms is abundant.
Quantification and micron‐scale imaging of spatial distribution of trace beryllium in shrapnel fragments and metallurgic samples with correlative fluorescence detection method and secondary ion mass spectrometry (SIMS)
Authors: ABRAHAM J.L. , CHANDRA S. , AGRAWAL A.
Published: August 2014

Recently, a report raised the possibility of shrapnel‐induced chronic beryllium disease from long‐term exposure to the surface of retained aluminum shrapnel fragments in the body. Since the shrapnel fragments contained trace beryllium, methodological developments were needed for beryllium quantification and to study its spatial distribution in relation to other matrix elements, such as aluminum and iron, in metallurgic samples. In this work, we developed methodology for quantification of trace beryllium in samples of shrapnel fragments and other metallurgic sample‐types with main matrix of aluminum (aluminum cans from soda, beer, carbonated water and aluminum foil). Sample preparation procedures were developed for dissolving beryllium for its quantification with the fluorescence detection method for homogenized measurements. The spatial distribution of trace beryllium on the sample surface and in 3D was imaged with a dynamic secondary ion mass spectrometry instrument, CAMECA IMS 3f secondary ion mass spectrometry ion microscope. The beryllium content of shrapnel (∼100 ppb) was the same as the trace quantities of beryllium found in aluminum cans. The beryllium content of aluminum foil (∼25 ppb) was significantly lower than cans. SIMS imaging analysis revealed beryllium to be distributed in the form of low micron‐sized particles and clusters distributed randomly in X–Y‐ and Z dimensions, and often in association with iron, in the main aluminum matrix of cans. These observations indicate a plausible formation of Be–Fe or Al–Be alloy in the matrix of cans. Further observations were made on fluids (carbonated water) for understanding if trace beryllium in cans leached out and contaminated the food product. A direct comparison of carbonated water in aluminum cans and plastic bottles revealed that beryllium was below the detection limits of the fluorescence detection method (∼0.01 ppb). These observations indicate that beryllium present in aluminum matrix was either present in an immobile form or its mobilization into the food product was prevented by a polymer coating on the inside of cans, a practice used in food industry to prevent contamination of food products. The lack of such coating in retained shrapnel fragments renders their surface a possible source of contamination for long‐term exposure of tissues and fluids and induction of disease, as characterized in a recent study. Methodological developments reported here can be extended to studies of beryllium in electronics devices and components.
Thrombosis formation on atherosclerotic lesions and plaque rupture
Authors: Badimon L. , Vilahur G.
Published: August 2014

Atherosclerosis is a silent chronic vascular pathology that is the cause of the majority of cardiovascular ischaemic events. The evolution of vascular disease involves a combination of endothelial dysfunction, extensive lipid deposition in the intima, exacerbated innate and adaptive immune responses, proliferation of vascular smooth muscle cells and remodelling of the extracellular matrix, resulting in the formation of an atherosclerotic plaque. High‐risk plaques have a large acellular lipid‐rich necrotic core with an overlying thin fibrous cap infiltrated by inflammatory cells and diffuse calcification. The formation of new fragile and leaky vessels that invade the expanding intima contributes to enlarge the necrotic core increasing the vulnerability of the plaque. In addition, biomechanical, haemodynamic and physical factors contribute to plaque destabilization. Upon erosion or rupture, these high‐risk lipid‐rich vulnerable plaques expose vascular structures or necrotic core components to the circulation, which causes the activation of tissue factor and the subsequent formation of a fibrin monolayer (coagulation cascade) and, concomitantly, the recruitment of circulating platelets and inflammatory cells. The interaction between exposed atherosclerotic plaque components, platelet receptors and coagulation factors eventually leads to platelet activation, aggregation and the subsequent formation of a superimposed thrombus (i.e. atherothrombosis) which may compromise the arterial lumen leading to the presentation of acute ischaemic syndromes. In this review, we will describe the progression of the atherosclerotic lesion along with the main morphological characteristics that predispose to plaque rupture, and discuss the multifaceted mechanisms that drive platelet activation and subsequent thrombus formation. Finally, we will consider the current scientific challenges and future research directions.
Rectal Lactobacillus Species and Their Influence on the Vaginal Microflora: A Model of Male-to-Female Transsexual Women
Authors: Petricevic Ljubomir , Kaufmann Ulrike , Domig Konrad J. , Kraler Manuel , Marschalek Julian , Kneifel Wolfgang , Kiss Herbert
Published: August 2014

Introduction

Based on Lactobacillus species co-colonizing the vagina and rectum, it has been hypothesized that the rectum may be an important reservoir for vaginal colonization by lactobacilli. There are no data on this issue in male-to-female transsexual women.

Aim

We undertook this observational study to characterize the Lactobacillus species present in the neovagina and rectum of male-to-female transsexual women and to determine the degree of neovaginal-rectal co-colonization in order to gain a better understanding of the potential role of the gut as a reservoir for genital lactobacilli.

Methods

Sixty-one male-to-female transsexual women with penile skin lined neovagina without clinical signs of infection were recruited on an ongoing basis from among male-to-female transsexual outpatients. Neovaginal and rectal smears were taken for molecular Lactobacillus species profiling by denaturing gradient gel electrophoresis (PCR-DGGE).

Main Outcome Measures

Matching Lactobacillus species between neovagina and rectum.

Results

Forty-three of the 61 male-to-female transsexual women (70.5%) simultaneously harbored the same lactobacilli in both the neovagina and rectum. We found 276 neovaginal and 258 rectal DGGE bands representing 11 Lactobacillus species, with 201 matches of the same Lactobacillus species in neovagina and rectum. 37 of the 61 women (61%) had two or more matching Lactobacillus species.

Conclusion

These data support the hypothesis that the rectum may play an important role as source of Lactobacillus species that colonies neovagina of male-to-female transsexual women. In view of the specific anatomical circumstances of the study population, these findings may be extended to the general population of women.
Stardust Interstellar Preliminary Examination IV: Scanning transmission X‐ray microscopy analyses of impact features in the Stardust Interstellar Dust Collector
Authors: Butterworth Anna L. , Westphal Andrew J. , Tyliszczak Tolek , Gainsforth Zack , Stodolna Julien , Frank David R. , Allen Carlton , Anderson David , Ansari Asna , Bajt Saša , Bastien Ron K. , Bassim Nabil , Bechtel Hans A. , Borg Janet , Brenker Frank E. , Bridges John , Brownlee Donald E. , Burchell Mark , Burghammer Manfred , Changela Hitesh , Cloetens Peter , Davis Andrew M. , Doll Ryan , Floss Christine , Flynn George , Grün Eberhard , Heck Philipp R. , Hillier Jon K. , Hoppe Peter , Hudson Bruce , Huth Joachim , Hvide Brit , Kearsley Anton , King Ashley J. , Lai Barry , Leitner Jan , Lemelle Laurence , Leroux Hugues , Leonard Ariel , Lettieri Robert , Marchant William , Nittler Larry R. , Ogliore Ryan , Ong Wei Ja , Postberg Frank , Price Mark C. , Sandford Scott A. , Sans͂ Tresseras Juan‐Angel , Schmitz Sylvia , Schoonjans Tom , Silversmit Geert , Simionovici Alexandre S. , Solé Vicente A. , Srama Ralf , Stadermann Frank J. , Stephan Thomas , Sterken Veerle J. , Stroud Rhonda M. , Sutton Steven , Trieloff Mario , Tsou Peter , Tsuchiyama Akira , Vekemans Bart , Vincze Laszlo , Von Korff Joshua , Wordsworth Naomi , Zevin Daniel , Zolensky Michael E. ,   >30,000 Stardust@home dusters
Published: August 2014

We report the quantitative characterization by synchrotron soft X‐ray spectroscopy of 31 potential impact features in the aerogel capture medium of the Stardust Interstellar Dust Collector. Samples were analyzed in aerogel by acquiring high spatial resolution maps and high energy‐resolution spectra of major rock‐forming elements Mg, Al, Si, Fe, and others. We developed diagnostic screening tests to reject spacecraft secondary ejecta and terrestrial contaminants from further consideration as interstellar dust candidates. The results support an extraterrestrial origin for three interstellar candidates: I1043,1,30 (Orion) is a 3 pg particle with Mg‐spinel, forsterite, and an iron‐bearing phase. I1047,1,34 (Hylabrook) is a 4 pg particle comprising an olivine core surrounded by low‐density, amorphous Mg‐silicate and amorphous Fe, Cr, and Mn phases. I1003,1,40 (Sorok) has the track morphology of a high‐speed impact, but contains no detectable residue that is convincingly distinguishable from the background aerogel. Twenty‐two samples with an anthropogenic origin were rejected, including four secondary ejecta from impacts on the Stardust spacecraft aft solar panels, nine ejecta from secondary impacts on the Stardust Sample Return Capsule, and nine contaminants lacking evidence of an impact. Other samples in the collection included I1029,1,6, which contained surviving solar system impactor material. Four samples remained ambiguous: I1006,2,18, I1044,2,32, and I1092,2,38 were too dense for analysis, and we did not detect an intact projectile in I1044,3,33. We detected no radiation effects from the synchrotron soft X‐ray analyses; however, we recorded the effects of synchrotron hard X‐ray radiation on I1043,1,30 and I1047,1,34.
An increasing opine carbon bias in artificial exudation systems and genetically modified plant rhizospheres leads to an increasing reshaping of bacterial populations
Authors: Mondy Samuel , Lenglet Aurore , Beury‐Cirou Amelie , Libanga Celestin , Ratet Pascal , Faure Denis , Dessaux Yves
Published: August 2014

To investigate how exudation shapes root‐associated bacterial populations, transgenic Arabidopsis thaliana plants that exuded the xenotopic compound octopine at low and high rates were grown in a nonsterile soil. Enumerations of both cultivable and octopine‐degrading bacteria demonstrated that the ratios of octopine degraders increased along with octopine concentration. An artificial exudation system was also set up in which octopine was brought at four ratios. The density of octopine‐degrading bacteria directly correlated with the input of octopine. Bacterial diversity was analysed by rrs amplicon pyrosequencing. Ensifer and Pseudomonas were significantly more frequently detected in soil amended with artificial exudates. However, the density of Pseudomonas increased as a response to carbon supplementation while that of Ensifer only correlated with octopine concentrations possibly in relation to two opposed colonization strategies of rhizosphere bacteria, that is, copiotrophy and oligotrophy.
HemR is an OmpR/PhoB‐like response regulator from Leptospira, which simultaneously effects transcriptional activation and repression of key haem metabolism genes
Authors: Morero Natalia R. , Botti Horacio , Nitta Kazuhiro R. , Carrión Federico , Obal Gonzalo , Picardeau Mathieu , Buschiazzo Alejandro
Published: August 2014

Several Leptospira species cause leptospirosis, the most extended zoonosis worldwide. In bacteria, two‐component systems constitute key signalling pathways, some of which are involved in pathogenesis. The physiological roles of two‐component systems in Leptospira are largely unknown, despite identifying several dozens within their genomes. Biochemical confirmation of an operative phosphorelaying two‐component system has been obtained so far only for the Hklep/Rrlep pair. It is known that hklep/rrlep knockout strains of Leptospira biflexa result in haem auxotrophy, although their de novo biosynthesis machinery remains fully functional. Haem is essential for Leptospira, but information about Hklep/Rrlep effector function(s) and target(s) is still lacking. We are now reporting a thorough molecular characterization of this system, which we rename HemK/HemR. The DNA HemR‐binding motif was determined, and found within the genomes of saprophyte and pathogenic Leptospira. In this way, putative HemR‐regulated genes were pinpointed, including haem catabolism‐related (hmuO – haem oxygenase) and biosynthesis‐related (the hemA/C/D/B/L/E/N/G operon). Specific HemR binding to these two promoters was quantified, and a dual function was observed in vivo, inversely repressing the hmuO, while activating the hemA operon transcription. The crystal structure of HemR receiver domain was determined, leading to a mechanistic model for its dual regulatory role.
Diverse chemotypes disrupt ion homeostasis in the malaria parasite
Authors: Lehane Adele M. , Ridgway Melanie C. , Baker Eileen , Kirk Kiaran
Published: August 2014

The antimalarial spiroindolones disrupt Plasmodium falciparum Na+ regulation and induce an alkalinization of the parasite cytosol. It has been proposed that they do so by inhibiting PfATP4, a parasite plasma membrane P‐type ATPase postulated to export Na+ and import H+ equivalents. Here, we screened the 400 antiplasmodial compounds of the open access ‘Malaria Box’ for their effects on parasite ion regulation. Twenty eight compounds affected parasite Na+ and pH regulation in a manner consistent with PfATP4 inhibition. Six of these, with chemically diverse structures, were selected for further analysis. All six showed reduced antiplasmodial activity against spiroindolone‐resistant parasites carrying mutations in pfatp4. We exposed parasites to incrementally increasing concentrations of two of the six compounds and in both cases obtained resistant parasites with mutations in pfatp4. The finding that diverse chemotypes have an apparently similar mechanism of action indicates that PfATP4 may be a significant Achilles' heel for the parasite.
Acid infusion into the esophagus increases the number of meal‐induced transient lower esophageal sphincter relaxations (TLESRs) in healthy volunteers
Authors: Halicka J. , Banovcin P. , Halickova M. , Demeter M. , Hyrdel R. , Tatar M. , Kollarik M.
Published: August 2014

Background

Transient lower esophageal sphincter relaxation (TLESR) is the major mechanism of gastroesophageal reflux (GER) but the regulation of TLESR by stimuli in the esophagus is incompletely understood. If stimuli in the esophagus can influence TLESR, then such regulation may perpetuate or limit GER. We addressed the hypothesis that acid in the esophagus enhances TLESRs.

Methods

We evaluated the effect of acid infusion into the distal esophagus on TLESRs evoked by a standard meal in a paired randomized study in healthy subjects. TLESRs were evaluated by using high resolution manometry (HRM).

Key Results

We found that acid in the esophagus enhanced meal‐induced TLESRs. Compared to control infusion the number of TLESRs (median [interquartile range]) was increased during 2 h following the acid infusion (11 [9–14] vs 17 [12.5–20], p < 0.01). The average duration of individual TLESRs was not affected. The time‐course analysis revealed that a robust increase in TLESRs occurred already in the first hour when the number of TLESRs nearly doubled (6 [5.5–7.5] vs 11 [7.5–12.5], p < 0.05). In contrast to the enhancement of TLESRs, the number of swallows was not changed.

Conclusions & Inferences

The acid infusion into the esophagus increases the number of meal‐induced TLESRs in healthy subjects. Our results provide evidence for the concept that the stimuli in the esophagus can influence TLESRs. The regulation of TLESR by stimuli in the esophagus may contribute to pathogenesis of GER in some patients.
MPK6 controls H2O2‐induced root elongation by mediating Ca2+ influx across the plasma membrane of root cells in Arabidopsis seedlings
Authors: Han Shuan , Fang Lin , Ren Xuejian , Wang Wenle , Jiang Jing
Published: August 2014

Mitogen‐activated protein kinases (MPKs) play critical roles in signalling and growth, and Ca2+ and H2O2 control plant growth processes associated with abscisic acid (ABA). However, it remains unclear how MPKs are involved in H2O2‐ and Ca2+‐mediated root elongation.

Root elongation in seedlings of the loss‐of‐function mutant Atmpk6 (Arabidopsis thaliana MPK6) was less sensitive to moderate H2O2 or ABA than that in wild‐type (WT) plants. The enhanced elongation was a result of root cell expansion. This effect disappeared when ABA‐induced H2O2 accumulation or the cytosolic Ca2+ increase were defective.

Molecular and biochemical evidence showed that increased expression of the cell wall peroxidase PRX34 in Atmpk6 root cells enhanced apoplastic H2O2 generation; this promoted a cytosolic Ca2+ increase and Ca2+ influx across the plasma membrane. The plasma membrane damage caused by high levels of H2O2 was ameliorated in a Ca2+‐dependent manner.

These results suggested that there was intensified PRX34‐mediated H2O2 generation in the apoplast and increased Ca2+ flux into the cytosol of Atmpk6 root cells; that is, the spatial separation of apoplastic H2O2 from cytosolic Ca2+ in root cells prevented H2O2‐induced inhibition of root elongation in Atmpk6 seedlings.
Monitoring and benchmarking government policies and actions to improve the healthiness of food environments: a proposed Government Healthy Food Environment Policy Index
Authors: Swinburn B. , Vandevijvere S. , Kraak V. , Sacks G. , Snowdon W. , Hawkes C. , Barquera S. , Friel S. , Kelly B. , Kumanyika S. , L'Abbé M. , Lee A. , Lobstein T. , Ma J. , Macmullan J. , Mohan S. , Monteiro C. , Neal B. , Rayner M. , Sanders D. , Walker C. ,   INFORMAS
Published: August 2014

Government action is essential to increase the healthiness of food environments and reduce obesity, diet‐related non‐communicable diseases (NCDs), and their related inequalities. This paper proposes a monitoring framework to assess government policies and actions for creating healthy food environments. Recommendations from relevant authoritative organizations and expert advisory groups for reducing obesity and NCDs were examined, and pertinent components were incorporated into a comprehensive framework for monitoring government policies and actions. A Government Healthy Food Environment Policy Index (Food‐EPI) was developed, which comprises a ‘policy’ component with seven domains on specific aspects of food environments, and an ‘infrastructure support’ component with seven domains to strengthen systems to prevent obesity and NCDs. These were revised through a week‐long consultation process with international experts. Examples of good practice statements are proposed within each domain, and these will evolve into benchmarks established by governments at the forefront of creating and implementing food policies for good health. A rating process is proposed to assess a government's level of policy implementation towards good practice. The Food‐EPI will be pre‐tested and piloted in countries of varying size and income levels. The benchmarking of government policy implementation has the potential to catalyse greater action to reduce obesity and NCDs.
Monitoring the health‐related labelling of foods and non‐alcoholic beverages in retail settings
Authors: Rayner M. , Wood A. , Lawrence M. , Mhurchu C. N. , Albert J. , Barquera S. , Friel S. , Hawkes C. , Kelly B. , Kumanyika S. , L'Abbé M. , Lee A. , Lobstein T. , Ma J. , Macmullan J. , Mohan S. , Monteiro C. , Neal B. , Sacks G. , Sanders D. , Snowdon W. , Swinburn B. , Vandevijvere S. , Walker C. ,   INFORMAS
Published: August 2014

Food labelling on food packaging has the potential to have both positive and negative effects on diets. Monitoring different aspects of food labelling would help to identify priority policy options to help people make healthier food choices. A taxonomy of the elements of health‐related food labelling is proposed. A systematic review of studies that assessed the nature and extent of health‐related food labelling has been conducted to identify approaches to monitoring food labelling. A step‐wise approach has been developed for independently assessing the nature and extent of health‐related food labelling in different countries and over time. Procedures for sampling the food supply, and collecting and analysing data are proposed, as well as quantifiable measurement indicators and benchmarks for health‐related food labelling.
Immunotherapy – risk/benefit in food allergy
Authors: Kostadinova Atanaska I. , Willemsen Linette E. M. , Knippels Léon M. J. , Garssen Johan
Published: August 2014

Food allergy is a growing health concern in the westernized world with approx. 6% of children suffering from it. A lack of approved treatment has led to strict avoidance of the culprit food proteins being the only standard of care. Nowadays in‐depth research is conducted to evaluate the possible use of allergen‐specific immunotherapy (SIT) as an active therapeutic option for food allergy. Various routes of administration for the immunotherapy are investigated, including subcutaneous, oral, sublingual, and epicutaneous, and some appear to be successful in inducing a temporary tolerant state. Most research has been conducted with oral immunotherapy due to its efficacious and relatively safe profile. Increasing interest is dedicated to safer and more convenient approaches, such as sublingual and epicutaneous SIT; however, doubts exist about their possible capacity to induce temporary tolerant state and permanent oral tolerance. The high frequency of allergic adverse reactions of the various approaches and the inability to achieve permanent oral tolerance have highlighted the need of refinements in the strategies. A promising strategy for preventing IgE cross‐linking and thus enhancing safety of SIT, while still activating T cells, is the use of tolerogenic peptides. The implementation of such an immunotherapy approach has the potential of not only increasing the chance of achieving a permanent state of tolerance, but also improving the safety and tolerability of the therapy. Immunotherapy for food allergy is still not ready for the clinic, but current and upcoming studies are dedicated to collect enough evidence for the possible implementation of allergen‐SIT as a standard treatment for food allergy.
How to reintroduce cow′s milk?
Authors: Dupont Christophe
Published: August 2014

In a child that is allergic to milk, the natural next step, following the elimination diet, is the reintroduction of cow's milk. Several questions may arise. When feasible, this reintroduction has many benefits for the child and his family. However, the disease needs to be well defined by physicians and explained to parents. They need to understand that there are different types of allergy to cow's milk, specifically IgE‐ and non‐IgE‐mediated, and each of these may exhibit both a variable duration and frequently an incomplete recovery. Deciding where to first reintroduce cow's milk to a child who has previously followed a milk‐free diet, whether it be at home or in a hospital, also frequently presents an issue. Following this first reintroduction, the progressive increase of milk into the diet needs to be managed properly, as not all children will go back to a normal dairy products intake. Recent studies show that most children with milk allergy tolerate products containing baked milk and that their consumption might speed up recovery. Hence, the purpose of the milk challenge in a child on a milk‐free diet is becoming, even in a child still reactive to milk, the first step of gradual and individually adapted reintroduction of milk or dairy products. When reintroduction of cow's milk does not work, immunotherapy becomes an option, and this is carried out in specialized centers.
TheQQSorphan gene of Arabidopsis modulates carbon and nitrogen allocation in soybean
Authors: Li Ling , Wurtele Eve Syrkin
Published: August 2014

The genome of each species contains as high as 8% of genes that are uniquely present in that species. Little is known about the functional significance of these so‐called species specific or orphan genes. TheArabidopsis thalianagene Qua‐Quine Starch (QQS) is species specific. Here, we show that alteringQQSexpression in Arabidopsis affects carbon partitioning to both starch and protein. We hypothesizedQQSmay be conserved in a feature other than primary sequence, and as such could function to impact composition in another species. To test the potential ofQQSin affecting composition in an ectopic species, we introducedQQSinto soybean. Soybean T1 lines expressingQQShave up to 80% decreased leaf starch and up to 60% increased leaf protein; T4 generation seeds from field‐grown plants contain up to 13% less oil, while protein is increased by up to 18%. These data broaden the concept ofQQSas a modulator of carbon and nitrogen allocation, and demonstrate that this species‐specific gene can affect the seed composition of an agronomic species thought to have diverged from Arabidopsis 100 million years ago.
Rootstock‐to‐scion transfer of transgene‐derived small interfering RNAs and their effect on virus resistance in nontransgenic sweet cherry
Authors: Zhao Dongyan , Song Guo‐qing
Published: August 2014

Small interfering RNAs (siRNAs) are silencing signals in plants. Virus‐resistant transgenic rootstocks developed through siRNA‐mediated gene silencing may enhance virus resistance of nontransgenic scions via siRNAs transported from the transgenic rootstocks. However, convincing evidence of rootstock‐to‐scion movement of siRNAs of exogenous genes in woody plants is still lacking. To determine whether exogenous siRNAs can be transferred, nontransgenic sweet cherry (scions) was grafted on transgenic cherry rootstocks (TRs), which was transformed with an RNA interference (RNAi) vector expressing short hairpin RNAs of the genomic RNA3 of Prunus necrotic ringspot virus (PNRSV‐hpRNA). Small RNA sequencing was conducted using bud tissues of TRs and those of grafted (rootstock/scion) trees, locating at about 1.2 m above the graft unions. Comparison of the siRNA profiles revealed that the PNRSV‐hpRNA was efficient in producing siRNAs and eliminating PNRSV in the TRs. Furthermore, our study confirmed, for the first time, the long‐distance (1.2 m) transfer of PNRSV‐hpRNA‐derived siRNAs from the transgenic rootstock to the nontransgenic scion in woody plants. Inoculation of nontransgenic scions with PNRSV revealed that the transferred siRNAs enhanced PNRSV resistance of the scions grafted on the TRs. Collectively, these findings provide the foundation for ‘using transgenic rootstocks to produce products of nontransgenic scions in fruit trees'.
What Caused the Formation of the Absorption Maximum at 421 nm in vivo Spectra of Rhodopseudomonas palustris
Authors: Zhao Chungui , Yue Huiying , Cheng Qianru , Chen Shicheng , Yang Suping
Published: August 2014

A spectral peak at ~421 nm appeared in vivo spectrum of Rhodopseudomonas palustris CQV97 cultured in acetate–glutamate medium (M1) but not in acetate–ammonium sulfate medium (M2). However, the spectral origin of 421 nm peak was not clear and frequently attributed to carotenoid component(s). In this study, comparative analysis of the extracted components showed that magnesium protoporphyrin IX monomethylester (MPE) was accumulated as one of the predominate components in M1 culture. The amounts of bacteriochlorophyll a in M1 culture were higher than that in M2, whereas the amounts of carotenoids were nearly identical in both cultures. A simple, rapid and minimum interference with carotenoid and bacteriochlorophyll method to efficiently extract the compounds involving in the formation of 421 nm peak was developed in this study. Assembly of purified MPE with protein components from R. palustris in vitro demonstrated that MPE caused the formation of 421 nm peak. The localization analysis in vivo demonstrated it is MPE associating to protein components and accounting for the peak at ~421 nm. This work clarified the 421 nm peak in vivo mainly originated from MPE accumulation, and will be very helpful to further explore the physiological roles of MPE or its derivatives in photosynthesis.
A case of mixed adenoneuroendocrine carcinoma of the gallbladder arising from an intracystic papillary neoplasm associated with pancreaticobiliary maljunction
Authors: Meguro Yoshiyuki , Fukushima Noriyoshi , Koizumi Masaru , Kasahara Naoya , Hydo Masanobu , Morishima Kazue , Sata Naohiro , Lefor Alan T. , Yasuda Yoshikazu
Published: August 2014

A 54‐year‐old Japanese woman was referred with a gallbladder tumor. Based on the results of the computed tomography scan, endoscopic retrograde cholangiopancreatography, and magnetic resonance cholangiopancreatography, a mucin‐producing neoplasm of the gallbladder associated with pancreaticobiliary maljunction was diagnosed. Extended cholecystectomy, extrahepatic bile duct resection, and choledochojejunostomy were performed, and she remains free of recurrence 24 months after resection. Histopathological examination revealed that the papillary component of the lesion was an intracystic papillary neoplasm with diverse characteristics of pancreaticobiliary epithelium and intestinal epithelium including mucin. In this component, most of the papillary lesion was a high‐grade intraepithelial neoplasm, but also showed slight invasion into the muscular layer. The nodular component consisted of both poorly differentiated biliary type adenocarcinoma and large cell neuroendocrine carcinoma. We report a rare case of a mixed adenoneuroendocrine carcinoma arising from an intracystic papillary neoplasm associated with pancreaticobiliary maljunction. As for the histogenesis of this tumor, based on the histopathologic appearance, transdifferentiation from poorly differentiated biliary type adenocarcinoma to large cell neuroendocrine carcinoma is considered the most possible histogenesis of this tumor.
Role of strawberry volatile organic compounds in the development of Botrytis cinerea infection
Authors: Neri F. , Cappellin L. , Spadoni A. , Cameldi I. , Algarra Alarcon A. , Aprea E. , Romano A. , Gasperi F. , Biasioli F.
Published: August 2014

Botrytis cinerea, the main pathogen of strawberry, has the ability to remain quiescent in unripe tissue and develop disease symptoms in ripe fruit. As strawberry ripening is characterized by an increase of aroma compounds, the role of volatile emission in the development of infection was investigated. Thirty‐five strawberry volatile organic compounds (VOCs) were tested on B. cinerea in vitro and volatile emission was analysed in strawberry harvested at four ripening stages by headspace solid‐phase microextraction/gas chromatography–mass spectrometry and proton transfer reaction–time of flight–mass spectrometry. The coupling of such data sets made it possible to conclude that key strawberry aroma compounds stimulate B. cinerea conidial germination and some typical wound‐volatiles stimulate pathogen conidial germination or mycelial growth. This study is the first report of fungal stimulation by some VOCs naturally occurring in strawberry: the esters ethyl butanoate, cis‐3‐hexenyl acetate, trans‐2‐hexenyl acetate, methyl butanoate and hexyl butanoate, the furanones furaneol and mesifurane, and the alcohol trans‐2‐hexenol. The results of this work provide advances in understanding the functional role of fruit VOCs and suggest, for the first time, that fruit VOCs may influence the development of B. cinerea from the latent phase and that they could favour the invasive growth of B. cinerea after wounding. In particular, ethyl butanoate and furaneol could signal strawberry ripening, and the green leaf volatiles trans‐2‐hexenol, trans‐2‐hexenyl acetate and cis‐3‐hexenyl acetate could signal the presence of damaged tissues that are easier sites for penetration by B. cinerea.
Dopamine agonist‐responsive depression
Authors: Hori Hiroaki , Kunugi Hiroshi
Published: August 2014

Dopaminergic dysfunction is implicated in the pathophysiology of treatment‐resistant depression. In this review, we describe the putative role of dopamine in depression, summarize the evidence for the efficacy of dopamine receptor agonists in the treatment of treatment‐resistant depression, and discuss the underlying mechanisms by which these medications work. Both preclinical and clinical data suggest that adjunctive dopamine agonists could be a promising option for the treatment of such a condition, indicating that there is a dopamine agonist‐responsive subgroup of depression. Future clinical studies are warranted to clarify unresolved issues regarding dopamine agonists such as long‐term efficacy, efficacy as a monotherapy, and efficacy for juvenile and senile depression. Further basic research is also necessary to fully understand how dopamine acts in the brain of depressed patients.