bluuebunny/crossref_metadata_2025 huggingface dataset:
Dispute Settlement Reports 2015
Authors: World Trade Organization
Published: August 2017

The Dispute Settlement Reports of the World Trade Organization (WTO) include Panel and Appellate Body reports, as well as arbitration awards, in disputes concerning the rights and obligations of WTO members under the provisions of the Marrakesh Agreement Establishing the World Trade Organization. These are the WTO authorized and paginated reports in English. They are an essential addition to the library of all practicing and academic trade lawyers, and needed by students worldwide taking courses in international economic or trade law. DSR 2015: Volume 10 reports on United States - Measures Concerning the Importation, Marketing and Sale of Tuna and Tuna Products - Recourse to Article 21.5 of the DSU by Mexico (WT/DS381).
Dispute Settlement Reports 2015
Authors: World Trade Organization
Published: August 2017

The Dispute Settlement Reports of the World Trade Organization (WTO) include Panel and Appellate Body reports, as well as arbitration awards, in disputes concerning the rights and obligations of WTO members under the provisions of the Marrakesh Agreement Establishing the World Trade Organization. DSR 2015: Volume 11 reports on: United States - Measures Concerning the Importation, Marketing and Sale of Tuna and Tuna Products - Recourse to Article 21.5 of the DSU by Mexico (WT/DS381), United States - Countervailing Duty Measures on Certain Products from China - Arbitration under Article 21.3(c) of the DSU (WT/DS437/16), United States - Anti-Dumping Measures on Certain Shrimp from Viet Nam - Arbitration under Article 21.3(c) of the DSU(WT/DS429/12), Peru - Additional Duty on Imports of Certain Agricultural Products - Arbitration under Article 21.3(c) of the DSU (WT/DS457/15) and United States - Certain Country of Origin Labelling (COOL) Requirements - Recourse to Article 22.6 of the DSU (WT/DS384, WT/DS386).
Dispute Settlement Reports 2014
Authors: World Trade Organization
Published: August 2017

The Dispute Settlement Reports of the World Trade Organization (WTO) include Panel and Appellate Body reports, as well as arbitration awards, in disputes concerning the rights and obligations of WTO members under the provisions of the Marrakesh Agreement Establishing the World Trade Organization. These are the WTO authorized and paginated reports in English. An essential addition to the library of all practicing and academic trade lawyers and needed by students worldwide taking courses in international economic or trade law. DSR 2014: Volume 4 reports on China - Measures Related to the Exportation of Rare Earths, Tungsten, and Molybdenum (WT/DS431, WT/DS432, WT/DS433).
Dispute Settlement Reports 2015
Authors: World Trade Organization
Published: August 2017

The Dispute Settlement Reports of the World Trade Organization (WTO) include Panel and Appellate Body reports, as well as arbitration awards, in disputes concerning the rights and obligations of WTO members under the provisions of the Marrakesh Agreement Establishing the World Trade Organization. These are the WTO authorized and paginated reports in English. An essential addition to the library of all practicing and academic trade lawyers and needed by students worldwide taking courses in international economic or trade law. DSR 2015: Volume 4 reports on United States - Certain Country of Origin Labelling (COOL) Requirements (Recourse to Article 21.5 of the DSU by Canada and Mexico) (WT/DS384, WT/DS386).
Dietary polyphenol intake and risk of type 2 diabetes in the Polish arm of the Health, Alcohol and Psychosocial factors in Eastern Europe (HAPIEE) study
Authors: Grosso Giuseppe , Stepaniak Urszula , Micek Agnieszka , Kozela Magdalena , Stefler Denes , Bobak Martin , Pajak Andrzej
Published: August 2017

This study aimed to test the association between dietary content of total and individual classes of polyphenols and incident cases of type 2 diabetes in Polish adults participating to the Health, Alcohol and Psychosocial factors In Eastern Europe study. At baseline, diet by 148-item FFQ and health information were collected from 5806 participants free of diabetes. Self-reported incident type 2 diabetes was ascertained at 2–4-year follow-up visit. OR and 95 % CI of type 2 diabetes comparing the various categories of polyphenol intake to the lowest one (reference category) and as 1sdincrease modelled as continuous variable were calculated by performing age-, energy-, and multivariate-adjusted logistic regression models. During the follow-up, 456 incident cases of type 2 diabetes occurred. When comparing extreme quartiles, intake of total polyphenol was inversely associated with the risk of type 2 diabetes (OR 0·43; 95 % CI 0·30, 0·61); 1sdincrease was associated with a reduced risk of diabetes (OR 0·68; 95 % CI 0·59, 0·79). Among the main classes of polyphenols, flavonoids, phenolic acids, and stilbenes were independent contributors to this association. Both subclasses of phenolic acids were associated with decreased risk of type 2 diabetes, whereas among subclasses of flavonoids, high intake of flavanols, flavanones, flavones and anthocyanins was significantly associated with decreased risk of type 2 diabetes. Total dietary polyphenols and some classes of dietary polyphenols were associated with lower risk of type 2 diabetes.
Maternal intake oftrans-unsaturated or interesterified fatty acids during pregnancy and lactation modifies mitochondrial bioenergetics in the liver of adult offspring in mice
Authors: de Velasco Patricia C. , Chicaybam Gustavo , Ramos-Filho Dionizio M. , dos Santos Raísa M. A. R. , Mairink Caroline , Sardinha Fátima L. C. , El-Bacha Tatiana , Galina Antonio , Tavares-do-Carmo Maria das Graças
Published: August 2017

The quality of dietary lipids in the maternal diet can programme the offspring to diseases in later life. We investigated whether the maternal intake of palm oil or interesterified fat, substitutes fortrans-unsaturated fatty acids (FA), induces metabolic changes in the adult offspring. During pregnancy and lactation, C57BL/6 female mice received normolipidic diets containing partially hydrogenated vegetable fat rich intrans-unsaturated fatty acids (TG), palm oil (PG), interesterified fat (IG) or soyabean oil (CG). After weaning, male offspring from all groups received the control diet until day 110. Plasma glucose and TAG and liver FA profiles were ascertained. Liver mitochondrial function was accessed with high-resolution respirometry by measuring VO2, fluorimetry for detection of hydrogen peroxide (H2O2) production and mitochondrial Ca2+uptake. The results showed that the IG offspring presented a 20 % increase in plasma glucose and both the IG and TG offspring presented a 2- and 1·9-fold increase in TAG, respectively, when compared with CG offspring. Liver MUFA and PUFA contents decreased in the TG and IG offspring when compared with CG offspring. Liver MUFA content also decreased in the PG offspring. These modifications in FA composition possibly affected liver mitochondrial function, as respiration was impaired in the TG offspring and H2O2production was higher in the IG offspring. In addition, mitochondrial Ca2+retention capacity was reduced by approximately 40 and 55 % in the TG and IG offspring, respectively. In conclusion, maternal consumption oftrans-unsaturated and interesterified fat affected offspring health by compromising mitochondrial bioenergetics and lipid metabolism in the liver.
First detection ofEchinococcus multilocularisin rodent intermediate hosts in Turkey
Authors: AVCIOGLU HAMZA , GUVEN ESIN , BALKAYA IBRAHIM , KIRMAN RIDVAN , BIA MOHAMMED MEBAREK , GULBEYEN HATICE , KURT ALI , YAYA SALI , DEMIRTAS SADIK
Published: August 2017

Echinococcus multilocularisis the causative agent of alveolar echinococcosis (AE), a potentially fatal zoonotic disease. Large parts of Turkey are considered as endemic forE. multilocularis. The aim of this study was to determine the occurrence of metacestode ofE. multilocularisin wild rodents in Erzurum, an endemic region for human AE in Turkey. During the sampling period, a total of 498 rodents were trapped in twenty counties of Erzurum Province. Suspected lesions were observed on the livers of 48 rodents, and then partial fragment of mitochondrial 12S rRNA gene was PCR-amplified. Five liver samples exhibitedE. multilocularisinfection. The prevalence ofE. multilocularisforMicrotusspp. was 1·3%. All of the infected rodents had fertile metacestodes. Infected rodents were morphologically and molecularly analysed and were confirmed to beMicrotus iraniby the mitochondrial cytochromebgene sequence analysis. This is the first report of the presence ofE. multilocularisin rodent intermediate hosts in Turkey. Our findings of infectedM. iraniwith protoscoleces show that this rodent can act as suitable intermediate host forE. multilocularis’ life cycle in Turkey. However, there was a complete lack of data on the infection of carnivores from the country. An extensive survey is recommended to determine the prevalence ofE. multilocularisin definitive hosts in this endemic region.
Intravenous immunoglobulins in children with new onset dilated cardiomyopathy
Authors: Heidendael Josephine F. , Den Boer Suzanne L. , Wildenbeest Joanne G. , Dalinghaus Michiel , Straver Bart , Pajkrt Dasja
Published: August 2017

Background

Dilated cardiomyopathy is a rare but serious disorder in children. No effective diagnostic or treatment tools are readily available. This study aimed to evaluate the efficacy of intravenous immunoglobulins in children with new onset dilated cardiomyopathy.

Methods and results

In this retrospective cohort study, 94 children with new onset dilated cardiomyopathy were followed during a median period of 33 months. All patients with secondary dilated cardiomyopathy – for example, genetic, auto-immune or structural defects – had been excluded. Viral tests were performed in all patients and 18 (19%) children met the criteria for the diagnosis “probable or definite viral myocarditis”. Intravenous immunoglobulins were administered to 21 (22%) patients. Overall transplant-free survival was 75% in 5 years and did not differ between treatment groups. The treatment was associated with a higher recovery rate within 5 years, compared with non-treated children (70 versus 43%, log rank=0.045). After correction for possible confounders the hazard ratio for recovery with intravenous immunoglobulins was not significant (hazard ratio: 2.1; 95% CI: 1.0–4.6; p=0.056). Administration of intravenous immunoglobulins resulted in a greater improvement in the shortening fraction of the left ventricle.

Conclusion

In our population of children with new onset dilated cardiomyopathy, of either viral or idiopathic origin, intravenous immunoglobulins were administered to a minority of the patients and did not influence transplant-free survival, but were associated with better improvement of systolic left ventricular function and with better recovery. Our results support the concept that children with new onset dilated cardiomyopathy might benefit from intravenous immunoglobulins.
NSF Grant: AGU and Partners Aim at Gender Issues in Geosciences
Authors: Williams Billy
Published: August 2017

Funding through July 2021 supports a project in the Earth, space, and environmental sciences to promote gender equity and train scientists to recognize and counteract sexual harassment.
Chemical dispersants enhance the activity of oil- and gas condensate-degrading marine bacteria
Authors: Tremblay Julien , Yergeau Etienne , Fortin Nathalie , Cobanli Susan , Elias Miria , King Thomas L , Lee Kenneth , Greer Charles W
Published: August 2017

Application of chemical dispersants to oil spills in the marine environment is a common practice to disperse oil into the water column and stimulate oil biodegradation by increasing its bioavailability to indigenous bacteria capable of naturally metabolizing hydrocarbons. In the context of a spill event, the biodegradation of crude oil and gas condensate off eastern Canada is an essential component of a response strategy. In laboratory experiments, we simulated conditions similar to an oil spill with and without the addition of chemical dispersant under both winter and summer conditions and evaluated the natural attenuation potential for hydrocarbons in near-surface sea water from the vicinity of crude oil and natural gas production facilities off eastern Canada. Chemical analyses were performed to determine hydrocarbon degradation rates, and metagenome binning combined with metatranscriptomics was used to reconstruct abundant bacterial genomes and estimate their oil degradation gene abundance and activity. Our results show important and rapid structural shifts in microbial populations in all three different oil production sites examined following exposure to oil, oil with dispersant and dispersant alone. We found that the addition of dispersant to crude oil enhanced oil degradation rates and favored the abundance and expression of oil-degrading genes from a Thalassolituus sp. (that is, metagenome bin) that harbors multiple alkane hydroxylase (alkB) gene copies. We propose that this member of the Oceanospirillales group would be an important oil degrader when oil spills are treated with dispersant.
Feathermoss and epiphytic Nostoc cooperate differently: expanding the spectrum of plant–cyanobacteria symbiosis
Authors: Warshan Denis , Espinoza Josh L , Stuart Rhona K , Richter R Alexander , Kim Sea-Yong , Shapiro Nicole , Woyke Tanja , C Kyrpides Nikos , Barry Kerrie , Singan Vasanth , Lindquist Erika , Ansong Charles , Purvine Samuel O , M Brewer Heather , Weyman Philip D , Dupont Christopher L , Rasmussen Ulla
Published: August 2017

Dinitrogen (N2)-fixation by cyanobacteria in symbiosis with feathermosses is the primary pathway of biological nitrogen (N) input into boreal forests. Despite its significance, little is known about the cyanobacterial gene repertoire and regulatory rewiring needed for the establishment and maintenance of the symbiosis. To determine gene acquisitions and regulatory changes allowing cyanobacteria to form and maintain this symbiosis, we compared genomically closely related symbiotic-competent and -incompetent Nostoc strains using a proteogenomics approach and an experimental set up allowing for controlled chemical and physical contact between partners. Thirty-two gene families were found only in the genomes of symbiotic strains, including some never before associated with cyanobacterial symbiosis. We identified conserved orthologs that were differentially expressed in symbiotic strains, including protein families involved in chemotaxis and motility, NO regulation, sulfate/phosphate transport, and glycosyl-modifying and oxidative stress-mediating exoenzymes. The physical moss–cyanobacteria epiphytic symbiosis is distinct from other cyanobacteria–plant symbioses, with Nostoc retaining motility, and lacking modulation of N2-fixation, photosynthesis, GS-GOGAT cycle and heterocyst formation. The results expand our knowledge base of plant–cyanobacterial symbioses, provide a model of information and material exchange in this ecologically significant symbiosis, and suggest new currencies, namely nitric oxide and aliphatic sulfonates, may be involved in establishing and maintaining the cyanobacteria–feathermoss symbiosis.
ROCKII inhibition promotes the maturation of human pancreatic beta-like cells
Authors: Ghazizadeh Zaniar , Kao Der-I , Amin Sadaf , Cook Brandoch , Rao Sahana , Zhou Ting , Zhang Tuo , Xiang Zhaoying , Kenyon Reyn , Kaymakcalan Omer , Liu Chengyang , Evans Todd , Chen Shuibing
Published: August 2017

Diabetes is linked to loss of pancreatic beta-cells. Pluripotent stem cells offer a valuable source of human beta-cells for basic studies of their biology and translational applications. However, the signalling pathways that regulate beta-cell development and functional maturation are not fully understood. Here we report a high content chemical screen, revealing that H1152, a ROCK inhibitor, promotes the robust generation of insulin-expressing cells from multiple hPSC lines. The insulin expressing cells obtained after H1152 treatment show increased expression of mature beta cell markers and improved glucose stimulated insulin secretion. Moreover, the H1152-treated beta-like cells show enhanced glucose stimulated insulin secretion and increased capacity to maintain glucose homeostasis after transplantation. Conditional gene knockdown reveals that inhibition of ROCKII promotes the generation and maturation of glucose-responding cells. This study provides a strategy to promote human beta-cell maturation and identifies an unexpected role for the ROCKII pathway in the development and maturation of beta-like cells.
JunB promotes Th17 cell identity and restrains alternative CD4+ T-cell programs during inflammation
Authors: Carr Tiffany M. , Wheaton Joshua D. , Houtz Geoffrey M. , Ciofani Maria
Published: August 2017

T helper 17 (Th17) cell plasticity contributes to both immunity and autoimmunity; however, the factors that control lineage flexibility are mostly unknown. Here we show the activator protein-1 (AP-1) factor JunB is an essential regulator of Th17 cell identity. JunB activates expression of Th17 lineage-specifying genes and coordinately represses genes controlling Th1 and regulatory T-cell fate. JunB supports Th17 cell identity by regulating key AP-1 complex constituents. In particular, JunB limits the expression of the subset repressor IRF8, and impedes access of JunD to regulatory regions of alternative effector loci. Although dispensable for homeostatic Th17 cell development, JunB is required for induction and maintenance of Th17 effector responses in the inflammatory contexts of both acute infection and chronic autoimmunity in mice. Through regulatory network analysis, we show that JunB is a core regulator of global transcriptional programs that promote Th17 cell identity and restrict alternative CD4+ T-cell potential.
Temporal profiling of depression vulnerability in a preclinical model of sustained depression
Authors: Riga D. , Schmitz L. J. M. , Hoogendijk W. J. G. , Smit A. B. , Spijker S.
Published: August 2017

Major Depression is a prevalent mental disorder that is characterized by negative mood and reduced motivation, and frequently results in social withdrawal and memory-related deficits. Repeated stressors, such as adverse life events, increase the risk for development of the disorder. Consequently, individual variability in stress response greatly weighs on depression-vulnerability and -resilience. Here, we employed the social defeat-induced persistent stress (SDPS) paradigm to identify depression-prone individuals and to examine the temporal development of depression in the months following exposure to brief defeat stress. Male Wistar rats were socially defeated (5 defeat episodes) and single-housed for a prolonged period of time (~24 weeks). We assessed the emergence of a sustained depressive-like state by repeatedly evaluating social motivation (social approach avoidance) and spatial memory (object place recognition) in SDPS rats during the isolation period. Individual variability in the effects of SDPS yielded two extreme subpopulations: an SDPS-prone group that showed gradual affective and cognitive deterioration in terms of social approach and memory retention, and a SDPS-resilient group that did not develop this phenotype. Notably, in SDPS-prone individuals, the affective deficits preceded later cognitive impairments, providing a novel temporal profile of the development of pathology in this preclinical model of sustained depression.
The saliva microbiome profiles are minimally affected by collection method or DNA extraction protocols
Authors: Lim Yenkai , Totsika Makrina , Morrison Mark , Punyadeera Chamindie
Published: August 2017

Saliva has attracted attention as a diagnostic fluid due to the association of oral microbiota with systemic diseases. However, the lack of standardised methods for saliva collection has led to the slow uptake of saliva in microbiome research. The aim of this study was to systematically evaluate the potential effects on salivary microbiome profiles using different methods of saliva collection, storage and gDNA extraction. Three types of saliva fractions were collected from healthy individuals with or without the gDNA stabilising buffer. Subsequently, three types of gDNA extraction methods were evaluated to determine the gDNA extraction efficiencies from saliva samples. The purity of total bacterial gDNA was evaluated using the ratio of human β-globin to bacterial 16S rRNA PCR while 16S rRNA gene amplicon sequencing was carried out to identify the bacterial profiles present in these samples. The quantity and quality of extracted gDNA were similar among all three gDNA extraction methods and there were no statistically significant differences in the bacterial profiles among different saliva fractions at the genus-level of taxonomic classification. In conclusion, saliva sampling, processing and gDNA preparation do not have major influence on microbiome profiles.
Differential diagnostic performance of acoustic radiation force impulse imaging in small (≤20 mm) breast cancers: Is it valuable?
Authors: Wang Si-Da , Wang Lei , Li Zhi-Xian , Wei Kang-Lai , Liao Xin-Hong , Chen Yuan-Yuan , Huang Xue
Published: August 2017

To evaluate acoustic radiation force impulse (ARFI) inthe differential diagnosis of small (≤20 mm) solid breast lesions and identify the most efficient ARFI parameters. Conventional ultrasonography and ARFIwere performed in 120 patients with 121 small solid breast lesions. The area ratios (ARs) of the lesion on virtual touch tissue compared to B-mode were calculated. The shear wave velocity of the inner (SWVi) and boundary (SWVb) of the lesions and surrounding fatty tissue (SWVf) was measured. The ratio of SWVi to SWVf (SWVrat) was calculated. AR, SWVi, SWVb, and SWVrat were significantly larger in malignant lesions (all P < 0.001). A cutoff AR of 1.17 yielded the highest area under the receiver operating characteristic curveamong the various parameters (91.2% sensitivity, 85.9% specificity, 88.4% accuracy) for the differential diagnosis of small breast lesions, but this value did not significantly differ from SWVi (P = 0.1144). This AR cutoff indowngradingcategory 4a to category 3 would avoid 83.3% unnecessary biopsies, and improved diagnostic specificity up to 73.4% without decreasing sensitivity. AR and SWVi are efficient parameters for the differential diagnosis of small breast lesions, whichwill improve diagnostic specificity and reduce unnecessary biopsies.
Automatic Categorization and Scoring of Solid, Part-Solid and Non-Solid Pulmonary Nodules in CT Images with Convolutional Neural Network
Authors: Tu Xiaoguang , Xie Mei , Gao Jingjing , Ma Zheng , Chen Daiqiang , Wang Qingfeng , Finlayson Samuel G. , Ou Yangming , Cheng Jie-Zhi
Published: August 2017

We present a computer-aided diagnosis system (CADx) for the automatic categorization of solid, part-solid and non-solid nodules in pulmonary computerized tomography images using a Convolutional Neural Network (CNN). Provided with only a two-dimensional region of interest (ROI) surrounding each nodule, our CNN automatically reasons from image context to discover informative computational features. As a result, no image segmentation processing is needed for further analysis of nodule attenuation, allowing our system to avoid potential errors caused by inaccurate image processing. We implemented two computerized texture analysis schemes, classification and regression, to automatically categorize solid, part-solid and non-solid nodules in CT scans, with hierarchical features in each case learned directly by the CNN model. To show the effectiveness of our CNN-based CADx, an established method based on histogram analysis (HIST) was implemented for comparison. The experimental results show significant performance improvement by the CNN model over HIST in both classification and regression tasks, yielding nodule classification and rating performance concordant with those of practicing radiologists. Adoption of CNN-based CADx systems may reduce the inter-observer variation among screening radiologists and provide a quantitative reference for further nodule analysis.
Mass production of polymer nano-wires filled with metal nano-particles
Authors: Lomadze Nino , Kopyshev Alexey , Bargheer Matias , Wollgarten Markus , Santer Svetlana
Published: August 2017

Despite the ongoing progress in nanotechnology and its applications, the development of strategies for connecting nano-scale systems to micro- or macroscale elements is hampered by the lack of structural components that have both, nano- and macroscale dimensions. The production of nano-scale wires with macroscale length is one of the most interesting challenges here. There are a lot of strategies to fabricate long nanoscopic stripes made of metals, polymers or ceramics but none is suitable for mass production of ordered and dense arrangements of wires at large numbers. In this paper, we report on a technique for producing arrays of ordered, flexible and free-standing polymer nano-wires filled with different types of nano-particles. The process utilizes the strong response of photosensitive polymer brushes to irradiation with UV-interference patterns, resulting in a substantial mass redistribution of the polymer material along with local rupturing of polymer chains. The chains can wind up in wires of nano-scale thickness and a length of up to several centimeters. When dispersing nano-particles within the film, the final arrangement is similar to a core-shell geometry with mainly nano-particles found in the core region and the polymer forming a dielectric jacket.
TLR4-Mediated Placental Pathology and Pregnancy Outcome in Experimental Malaria
Authors: Barboza Renato , Lima Flávia Afonso , Reis Aramys Silva , Murillo Oscar Javier , Peixoto Erika Paula Machado , Bandeira Carla Letícia , Fotoran Wesley Luzetti , Sardinha Luis Roberto , Wunderlich Gerhard , Bevilacqua Estela , Lima Maria Regina D’Império , Alvarez José Maria , Costa Fabio Trindade Maranhão , Gonçalves Lígia Antunes , Epiphanio Sabrina , Marinho Claudio Romero Farias
Published: August 2017

Malaria-associate pregnancy has a significant impact on infant morbidity and mortality. The detrimental effects of malaria infection during pregnancy have been shown to correlate with immune activation in the placental tissue. Herein we sought to evaluate the effect of Toll-like receptors (TLRs) activation on placental malaria (PM) development by using the Plasmodium berghei NK65GFP infection model. We observed that activation of the innate immune system by parasites leads to PM due to local inflammation. We identified TLR4 activation as the main pathway involved in the inflammatory process in the placental tissue since the absence of functional TLR4 in mice leads to a decrease in the pro-inflammatory responses, which resulted in an improved pregnancy outcome. Additionally, a similar result was obtained when infected pregnant mice were treated with IAXO-101, a TLR4/CD14 blocker. Together, this study illustrates the importance of TLR4 signalling for the generation of the severe inflammatory response involved in PM pathogenesis. Therefore, our results implicate that TLR4 blockage could be a potential candidate for therapeutic interventions to reduce malaria-induced pathology both in the mother and the fetus.
In vivo therapeutic efficacy of frog skin-derived peptides against Pseudomonas aeruginosa-induced pulmonary infection
Authors: Chen Chen , Mangoni Maria Luisa , Di Y. Peter
Published: August 2017

Pseudomonas aeruginosa is an opportunistic and frequently drug-resistant pulmonary pathogen especially in cystic fibrosis sufferers. Recently, the frog skin-derived antimicrobial peptide (AMP) Esc(1–21) and its diastereomer Esc(1–21)-1c were found to possess potent in vitro antipseudomonal activity. Here, they were first shown to preserve the barrier integrity of airway epithelial cells better than the human AMP LL-37. Furthermore, Esc(1–21)-1c was more efficacious than Esc(1–21) and LL-37 in protecting host from pulmonary bacterial infection after a single intra-tracheal instillation at a very low dosage of 0.1 mg/kg. The protection was evidenced by 2-log reduction of lung bacterial burden and was accompanied by less leukocytes recruitment and attenuated inflammatory response. In addition, the diastereomer was more efficient in reducing the systemic dissemination of bacterial cells. Importantly, in contrast to what reported for other AMPs, the peptide was administered at 2 hours after bacterial challenge to better reflect the real life infectious conditions. To the best of our knowledge, this is also the first study investigating the effect of AMPs on airway-epithelia associated genes upon administration to infected lungs. Overall, our data highly support advanced preclinical studies for the development of Esc(1–21)-1c as an efficacious therapeutic alternative against pulmonary P. aeruginosa infections.
Nosema ceranae, Fipronil and their combination compromise honey bee reproduction via changes in male physiology
Authors: Kairo Guillaume , Biron David G. , Ben Abdelkader Faten , Bonnet Marc , Tchamitchian Sylvie , Cousin Marianne , Dussaubat Claudia , Benoit Boris , Kretzschmar André , Belzunces Luc P. , Brunet Jean-Luc
Published: August 2017

The honey bee is threatened by biological agents and pesticides that can act in combination to induce synergistic effects on its physiology and lifespan. The synergistic effects of a parasite/pesticide combination have been demonstrated on workers and queens, but no studies have been performed on drones despite their essential contribution to colony sustainability by providing semen diversity and quality. The effects of the Nosema ceranae/fipronil combination on the life traits and physiology of mature drones were examined following exposure under semi-field conditions. The results showed that the microsporidia alone induced moderate and localized effects in the midgut, whereas fipronil alone induced moderate and generalized effects. The parasite/insecticide combination drastically affected both physiology and survival, exhibiting an important and significant generalized action that could jeopardize mating success. In terms of fertility, semen was strongly impacted regardless of stressor, suggesting that drone reproductive functions are very sensitive to stress factors. These findings suggest that drone health and fertility impairment might contribute to poorly mated queens, leading to the storage of poor quality semen and poor spermathecae diversity. Thus, the queens failures observed in recent years might result from the continuous exposure of drones to multiple environmental stressors.
Tip-dated phylogeny of whirligig beetles reveals ancient lineage surviving on Madagascar
Authors: Gustafson Grey T. , Prokin Alexander A. , Bukontaite Rasa , Bergsten Johannes , Miller Kelly B.
Published: August 2017

The temporal origin of Madagascar’s extraordinary endemic diversity is debated. A preference for Cenozoic dispersal origins has replaced the classical view of Mesozoic vicariance in the wake of molecular dating. However, evidence of ancient origins is mounting from arthropod groups. Using phylogenetic ‘tip-dating’ analysis with fossils, we show that a whirligig beetle species,Heterogyrus milloti, inhabiting forest streams in southeastern Madagascar is the last survivor of a once dominant and widespread Mesozoic group. With a Late Triassic to Early Jurassic origin (226–187 Ma) it is the hitherto oldest dated endemic lineage of animal or plant on Madagascar. Island biotas’ sensitivity to extinction is well known, but islands can also provide refuge from continental extinction.Heterogyrus millotiis an irreplaceable link to the freshwater biota of the Mesozoic and serves as a reminder of what may be lost without critical conservation efforts on Madagascar.
Novel STAT binding elements mediate IL-6 regulation of MMP-1 and MMP-3
Authors: Cutler Samuel J. , Doecke James D. , Ghazawi Ibtisam , Yang Jinbo , Griffiths Lyn R. , Spring Kevin J. , Ralph Stephen J. , Mellick Albert S.
Published: August 2017

Dynamic remodelling of the extracellular matrix (ECM) is a key feature of cancer progression. Enzymes that modify the ECM, such as matrix metalloproteinases (MMPs), have long been recognised as important targets of anticancer therapy. Inflammatory cytokines are known to play a key role in regulating protease expression in cancer. Here we describe the identification of gamma-activated site (GA﻿S)-like, signal transducer and activator of transcription (STAT) binding elements (SBEs) within the proximal promoters of theMMP-1andMMP-3genes, which in association with AP-1 components (c-Fos or Jun), bind STAT-1 in ahomodimerlike complex (HDLC). We further demonstrate that MMP expression and binding of this complex to SBEs can either be enhanced by interleukin (IL)-6, or reduced by interferon gamma (IFN-γ), and that IL-6 regulation of MMPs is not STAT-3 dependent. Collectively, this data adds to existing understanding of the mechanism underlying cytokine regulation of MMP expression via STAT-1, and increases our understanding of the links between inflammation and malignancy in colon cancer.
Asymmetry of the temporal code for space by hippocampal place cells
Authors: Souza Bryan C. , Tort Adriano B. L.
Published: August 2017

Hippocampal place cells convey spatial information through spike frequency (“rate coding”) and spike timing relative to the theta phase (“temporal coding”). Whether rate and temporal coding are due to independent or related mechanisms has been the subject of wide debate. Here we show that the spike timing of place cells couples to theta phase before major increases in firing rate, anticipating the animal’s entrance into the classical, rate-based place field. In contrast, spikes rapidly decouple from theta as the animal leaves the place field and firing rate decreases. Therefore, temporal coding has strong asymmetry around the place field center. We further show that the dynamics of temporal coding along space evolves in three stages as the animal traverses the place field: phase coupling, sharp precession and phase decoupling. These results suggest that independent mechanisms may govern rate and temporal coding.
Rapid peat accumulation favours the occurrence of both fen and bog microbial communities within a Mediterranean, free-floating peat island
Authors: Concheri Giuseppe , Stevanato Piergiorgio , Zaccone Claudio , Shotyk William , D’Orazio Valeria , Miano Teodoro , Piffanelli Pietro , Rizzi Valeria , Ferrandi Chiara , Squartini Andrea
Published: August 2017

The unique environment of a 4m-thick, free-floating peat island within the Posta Fibreno lake (Central Italy) was analyzed using DNA-based techniques to assess bacterial and fungal community members identity and abundance. Two depths were sampled at 41 and 279 cm from the surface, the former corresponding to an emerged portion of Sphagnum residues accumulated less than 30 yrs ago, and the latter mainly consisting of silty peat belonging to the deeply submerged part of the island, dating back to 1520–1660 AD. The corresponding communities were very diverse, each of them dominated by a different member of the Delta-proteobacteria class for prokaryotes. Among Eukaryotes, Ascomycota prevailed in the shallow layer while Basidiomycota were abundant in the deep sample. The identity of taxa partitioning between acidic surface layer and neutral core is very reminiscent of the differences reported between bogs and fens respectively, supporting the view of Posta Fibreno as a relic transitional floating mire. Moreover, some microbial taxa show an unusual concurrent species convergence between this sub-Mediterranean site and far Nordic or circumpolar environments. This study represents the first report describing the biotic assemblages of such a peculiar environment, and provides some insights into the possible mechanisms of its evolution.
Functional validation of GPIHBP1 and identification of a functional mutation in GPIHBP1 for milk fat traits in dairy cattle
Authors: Yang Jie , Liu Xuan , Wang Dan , Ning Chao , Wang Haifei , Zhang Qin , Jiang Li
Published: August 2017

In a previous genome-wide association study (GWAS) on milk production traits in a Chinese Holstein population, we revealed that GPIHBP1 is a novel promising candidate gene for milk fat content traits. In this study, we performed over-expression and RNAi experiments on GPIHBP1 in bovine primary mammary epithelial cells. The results showed that the expression of several important milk fat-related genes (LPL, CD36, VLDLR, ACACA and FASN) increased or decreased when the expression of GPIHBP1 was up- or down-regulated. To identify the potential functional SNP involved, we explored the genetic variants of GPIHBP1 and found that a G/A mutation (chr14:2553998) in the promoter region of GPIHBP1 significantly reduced promoter activity and had an effect on transcription factor binding sites. This finding was consistent with the lower expression of GPIHBP1 observed in the mammary gland tissue of cows harboring the homozygous AA mutation compared with wild-type homozygous GG or heterozygous AG. Furthermore, association analysis showed that cows with the AA genotype outperformed those with the GG and AG genotypes in terms of the milk fat percentage. Our study demonstrates that GPIHBP1 could be a strong candidate gene for milk fat content traits and, in particular, the G to A mutation at chr14:2553998 within GPIHBP1 could be a functional mutation related to its effects.
A portable microfluidic platform for rapid molecular diagnostic testing of patients with myeloproliferative neoplasms
Authors: Wang Hua , zhang Xinju , Xu Xiao , Zhang Qunfeng , Wang Hengliang , Li Dong , Kang Zhihua , Wu Zhiyuan , Tang Yigui , An Zhenhua , Guan Ming
Published: August 2017

The ability to simultaneously detect JAK2 V617F and MPL W515K/L mutations would substantially improve the early diagnosis of myeloproliferative neoplasms (MPNs) and decrease the risk of arterial thrombosis. The goal of this study is to achieve a point of care testing platform for simultaneous analysis of major genetic alterations in MPN. Here, we report a microfluidic platform including a glass capillary containing polypropylene matrix that extracts genomic DNA from a drop of whole blood, a microchip for simultaneous multi-gene mutation screening, and a handheld battery-powered heating device. The µmLchip system was successfully used for point-of-care identification of the JAK2 V617F and MPL W515K/L mutations. The µmLchip assays were then validated by mutation analysis with samples from 100 MPN patients who had previously been analyzed via unlabeled probe melting curve analysis or real-time PCR. The results from the µmLchip were in perfect agreement with those from the other methods, except for one discrepant result that was negative in the unlabeled probe melting curve analysis but positive in the µmLchip. After T-A cloning, sequences of cloned PCR products revealed JAK2 V617F mutation in the sample. The portable microfluidic platform may be very attractive in developing point-of-care diagnostics for MPL W515K/L and JAK2 V617F mutations.
Medial prefrontal cortical thinning mediates shifts in other-regarding preferences during adolescence
Authors: Sul Sunhae , Güroğlu Berna , Crone Eveline A. , Chang Luke J.
Published: August 2017

Adolescence is a time of significant cortical changes in the ‘social brain’, a set of brain regions involved in sophisticated social inference. However, there is limited evidence linking the structural changes in social brain to development of social behavior. The present study investigated how cortical development of the social brain relates to other-regarding behavior, in the context of fairness concerns. Participants aged between 9 to 23 years old responded to multiple rounds of ultimatum game proposals. The degree to which each participant considers fairness of intention (i.e., intention-based reciprocity) vs. outcome (i.e., egalitarianism) was quantified using economic utility models. We observed a gradual shift in other-regarding preferences from simple rule-based egalitarianism to complex intention-based reciprocity from early childhood to young adulthood. The preference shift was associated with cortical thinning of the dorsomedial prefrontal cortex and posterior temporal cortex. Meta-analytic reverse-inference analysis showed that these regions were involved in social inference. Importantly, the other-regarding preference shift was statistically mediated by cortical thinning in the dorsomedial prefrontal cortex. Together these findings suggest that development of the ability to perform sophisticated other-regarding social inference is associated with the structural changes of specific social brain regions in late adolescence.
Administration of mesenchymal stromal cells before renal ischemia/reperfusion attenuates kidney injury and may modulate renal lipid metabolism in rats
Authors: Erpicum Pauline , Rowart Pascal , Poma Laurence , Krzesinski Jean-Marie , Detry Olivier , Jouret François
Published: August 2017

Mesenchymal stromal cells (MSC) have been demonstrated to attenuate renal ischemia/reperfusion (I/R) damage in rodent models. The mechanisms of such nephro-protection remain largely unknown. Furthermore, the optimal timing of MSC administration has been poorly investigated. Here, we compare the impact of MSC injection 7 days before (MSCD − 7) versus 1 day after (MSCD + 1) renal I/R in rats. Control groups received equivalent volumes of saline at similar time-points (SD − 7 and SD + 1). Right nephrectomy was performed, and left renal ischemia lasted 45 min. After 48-hour reperfusion, we observed significantly improved renal function parameters, reduced apoptotic index and neutrophil/macrophage infiltration in kidney parenchyma, and lower expression of tubular damage markers and pro-inflammatory cytokines in MSCD − 7 in comparison to MSCD + 1 and saline control groups. Next, comparative high-throughput RNA sequencing of MSCD − 7 vs. SD − 7 non-ischemic right kidneys highlighted significant down-regulation of fatty acid biosynthesis and up-regulation of PPAR-α pathway. Such a preferential regulation towards lipid catabolism was associated with decreased levels of lipid peroxidation products, i.e. malondialdehyde and 4-hydroxy-2-nonenal, in MSCD − 7 versus SD − 7 ischemic kidneys. Our findings suggest that MSC pretreatment may exert protective effects against renal I/R by modulating lipid metabolism in rats.
Dissecting the genomic activity of a transcriptional regulator by the integrative analysis of omics data
Authors: Ferrero Giulio , Miano Valentina , Beccuti Marco , Balbo Gianfranco , De Bortoli Michele , Cordero Francesca
Published: August 2017

In the study of genomic regulation, strategies to integrate the data produced by Next Generation Sequencing (NGS)-based technologies in a meaningful ensemble are eagerly awaited and must continuously evolve. Here, we describe an integrative strategy for the analysis of data generated by chromatin immunoprecipitation followed by NGS which combines algorithms for data overlap, normalization and epigenetic state analysis. The performance of our strategy is illustrated by presenting the analysis of data relative to the transcriptional regulator Estrogen Receptor alpha (ERα) in MCF-7 breast cancer cells and of Glucocorticoid Receptor (GR) in A549 lung cancer cells. We went through the definition of reference cistromes for different experimental contexts, the integration of data relative to co-regulators and the overlay of chromatin states as defined by epigenetic marks in MCF-7 cells. With our strategy, we identified novel features of estrogen-independent ERα activity, including FoxM1 interaction, eRNAs transcription and a peculiar ontology of connected genes.
Effects of environmental enrichment upon ethanol-induced conditioned place preference and pre-frontal BDNF levels in adolescent and adult mice
Authors: Pautassi Ricardo Marcos , Suárez Andrea B. , Hoffmann Lucas Barbosa , Rueda André Veloso , Rae Mariana , Marianno Priscila , Camarini Rosana
Published: August 2017

Environmental enrichment (EE) provides a non-pharmacological tool to alter drug-induced reward, yet its effects on ethanol-induced reward remain controversial. We analyzed adolescent vs. adult (mice) differences in the influence of EE on ethanol-induced conditioned place preference (CPP). The effects of these treatments on brain-derived neurotrophic factor (BDNF) levels in the prefrontal cortex were examined in a separate group of animals. Ethanol-induced CPP was found in adults, and it was similar in EE and in animals reared under standard housing conditions (SC). Adolescents kept under EE, but not those in SC, exhibited CPP. Among SC, but not among EE, adolescents, BDNF levels were significantly lower in those treated with ethanol than in those given vehicle. These results indicate that, compared to adults, adolescent exhibited reduced sensitivity to ethanol’s rewarding effects, yet the youth but not the adults exhibited sensitivity to the promoting effect of EE upon CPP by ethanol. Ethanol significantly reduced BDNF levels in adolescents reared under standard housing conditions, but not in adult mice nor in adolescents given EE housing conditions. The present results add to the plethora of adolescent-specific responses to ethanol or to environmental stimuli that may put the youth at risk for escalation of ethanol intake.
Human cytomegalovirus escapes immune recognition by NK cells through the downregulation of B7-H6 by the viral genes US18 and US20
Authors: Charpak-Amikam Yoav , Kubsch Tobias , Seidel Einat , Oiknine-Djian Esther , Cavaletto Noemi , Yamin Rachel , Schmiedel Dominik , Wolf Dana , Gribaudo Giorgio , Messerle Martin , Cicin-Sain Luka , Mandelboim Ofer
Published: August 2017

Human cytomegalovirus (HCMV) is a major human pathogen, causing serious diseases in immunocompromised populations and congenially infected neonates. One of the main immune cells acting against the virus are Natural Killer (NK) cells. Killing by NK cells is mediated by a small family of activating receptors such as NKp30 that interact with the cellular ligand B7-H6. The outcome of B7-H6-NKp30 interaction was, so far, mainly studied with regard to NK recognition and killing of tumors. Here, we demonstrated that the expression of B7-H6 is upregulated following HCMV infection and that HCMV uses two of its genes: US18 and US20, to interfere with B7-H6 surface expression, in a mechanism involving endosomal degradation, in order to evade NK cell recognition.