bluuebunny/crossref_metadata_2025_split huggingface dataset:
The nutritional quality of foods carrying health-related claims in Germany, The Netherlands, Spain, Slovenia and the United Kingdom
Authors: Kaur A , Scarborough P , Hieke S , Kusar A , Pravst I , Raats M , Rayner M 
Published: July 2016

Abstract

Backgroung/Objectives:
Compares the nutritional quality of pre-packaged foods carrying health-related claims with foods that do not carry health-related claims.

Subject/Methods:
Cross-sectional survey of pre-packaged foods available in Germany, The Netherlands, Spain, Slovenia and the United Kingdom in 2013. A total of 2034 foods were randomly sampled from three food store types (a supermarket, a neighbourhood store and a discounter). Nutritional information was taken from nutrient declarations present on food labels and assessed through a comparison of mean levels, regression analyses and the application of a nutrient profile model currently used to regulate health claims in Australia and New Zealand (Food Standards Australia New Zealand’s Nutrient Profiling Scoring Criterion, FSANZ NPSC).

Results:
Foods carrying health claims had, on average, lower levels, per 100 g, of the following nutrients, energy—29.3 kcal (P<0.05), protein—1.2 g (P<0.01), total sugars—3.1 g (P<0.05), saturated fat—2.4 g (P<0.001), and sodium—842 mg (P<0.001), and higher levels of fibre—0.8 g (P<0.001). A similar pattern was observed for foods carrying nutrition claims. Forty-three percent (confidence interval (CI) 41%, 45%) of foods passed the FSANZ NPSC, with foods carrying health claims more likely to pass (70%, CI 64%, 76%) than foods carrying nutrition claims (61%, CI 57%, 66%) or foods that did not carry either type of claim (36%, CI 34%, 38%).

Conclusions:
Foods carrying health-related claims have marginally better nutrition profiles than those that do not carry claims; these differences would be increased if the FSANZ NPSC was used to regulate health-related claims. It is unclear whether these relatively small differences have significant impacts on health.
Cryo-EM structure of aerolysin variants reveals a novel protein fold and the pore-formation process
Authors: Iacovache Ioan , De Carlo Sacha , Cirauqui Nuria , Dal Peraro Matteo , van der Goot F. Gisou , Zuber Benoît 
Published: July 2016

AbstractOwing to their pathogenical role and unique ability to exist both as soluble proteins and transmembrane complexes, pore-forming toxins (PFTs) have been a focus of microbiologists and structural biologists for decades. PFTs are generally secreted as water-soluble monomers and subsequently bind the membrane of target cells. Then, they assemble into circular oligomers, which undergo conformational changes that allow membrane insertion leading to pore formation and potentially cell death. Aerolysin, produced by the human pathogen Aeromonas hydrophila, is the founding member of a major PFT family found throughout all kingdoms of life. We report cryo-electron microscopy structures of three conformational intermediates and of the final aerolysin pore, jointly providing insight into the conformational changes that allow pore formation. Moreover, the structures reveal a protein fold consisting of two concentric β-barrels, tightly kept together by hydrophobic interactions. This fold suggests a basis for the prion-like ultrastability of aerolysin pore and its stoichiometry.
αE-catenin inhibits YAP/TAZ activity to regulate signalling centre formation during tooth development
Authors: Li Chun-Ying , Hu Jimmy , Lu Hongbing , Lan Jing , Du Wei , Galicia Nicole , Klein Ophir D. 
Published: July 2016

AbstractEmbryonic signalling centres are specialized clusters of non-proliferating cells that direct the development of many organs. However, the mechanisms that establish these essential structures in mammals are not well understood. Here we report, using the murine incisor as a model, that αE-catenin is essential for inhibiting nuclear YAP localization and cell proliferation. This function of αE-catenin is required for formation of the tooth signalling centre, the enamel knot (EK), which maintains dental mesenchymal condensation and epithelial invagination. EK formation depends primarily on the signalling function of αE-catenin through YAP and its homologue TAZ, as opposed to its adhesive function, and combined deletion of Yap and Taz rescues the EK defects caused by loss of αE-catenin. These findings point to a developmental mechanism by which αE-catenin restricts YAP/TAZ activity to establish a group of non-dividing and specialized cells that constitute a signalling centre.
A conserved abundant cytoplasmic long noncoding RNA modulates repression by Pumilio proteins in human cells
Authors: Tichon Ailone , Gil Noa , Lubelsky Yoav , Havkin Solomon Tal , Lemze Doron , Itzkovitz Shalev , Stern-Ginossar Noam , Ulitsky Igor 
Published: July 2016

AbstractThousands of long noncoding RNA (lncRNA) genes are encoded in the human genome, and hundreds of them are evolutionarily conserved, but their functions and modes of action remain largely obscure. Particularly enigmatic lncRNAs are those that are exported to the cytoplasm, including NORAD—an abundant and highly conserved cytoplasmic lncRNA. Here we show that most of the sequence of NORAD is comprised of repetitive units that together contain at least 17 functional binding sites for the two mammalian Pumilio homologues. Through binding to PUM1 and PUM2, NORAD modulates the mRNA levels of their targets, which are enriched for genes involved in chromosome segregation during cell division. Our results suggest that some cytoplasmic lncRNAs function by modulating the activities of RNA-binding proteins, an activity which positions them at key junctions of cellular signalling pathways.
A whole-genome sequence and transcriptome perspective on HER2-positive breast cancers
Authors: Ferrari Anthony , Vincent-Salomon Anne , Pivot Xavier , Sertier Anne-Sophie , Thomas Emilie , Tonon Laurie , Boyault Sandrine , Mulugeta Eskeatnaf , Treilleux Isabelle , MacGrogan Gaëtan , Arnould Laurent , Kielbassa Janice , Le Texier Vincent , Blanché Hélène , Deleuze Jean-François , Jacquemier Jocelyne , Mathieu Marie-Christine , Penault-Llorca Frédérique , Bibeau Frédéric , Mariani Odette , Mannina Cécile , Pierga Jean-Yves , Trédan Olivier , Bachelot Thomas , Bonnefoi Hervé , Romieu Gilles , Fumoleau Pierre , Delaloge Suzette , Rios Maria , Ferrero Jean-Marc , Tarpin Carole , Bouteille Catherine , Calvo Fabien , Gut Ivo Glynne , Gut Marta , Martin Sancha , Nik-Zainal Serena , Stratton Michael R. , Pauporté Iris , Saintigny Pierre , Birnbaum Daniel , Viari Alain , Thomas Gilles 
Published: July 2016

AbstractHER2-positive breast cancer has long proven to be a clinically distinct class of breast cancers for which several targeted therapies are now available. However, resistance to the treatment associated with specific gene expressions or mutations has been observed, revealing the underlying diversity of these cancers. Therefore, understanding the full extent of the HER2-positive disease heterogeneity still remains challenging. Here we carry out an in-depth genomic characterization of 64 HER2-positive breast tumour genomes that exhibit four subgroups, based on the expression data, with distinctive genomic features in terms of somatic mutations, copy-number changes or structural variations. The results suggest that, despite being clinically defined by a specific gene amplification, HER2-positive tumours melt into the whole luminal–basal breast cancer spectrum rather than standing apart. The results also lead to a refined ERBB2 amplicon of 106 kb and show that several cases of amplifications are compatible with a breakage–fusion–bridge mechanism.
Chronic hyperglycemia induced via the heterozygous knockout of Pdx1 worsens neuropathological lesion in an Alzheimer mouse model
Authors: Guo Chuang , Zhang Shuai , Li Jia-Yi , Ding Chen , Yang Zhao-Hui , Chai Rui , Wang Xu , Wang Zhan-You 
Published: July 2016

AbstractCompelling evidence has indicated that dysregulated glucose metabolism links Alzheimer’s disease (AD) and diabetes mellitus (DM) via glucose metabolic products. Nevertheless, because of the lack of appropriate animal models, whether chronic hyperglycemia worsens AD pathologies in vivo remains to be confirmed. Here, we crossed diabetic mice (Pdx1+/− mice) with Alzheimer mice (APP/PS1 transgenic mice) to generate Pdx1+/−/APP/PS1. We identified robust increases in tau phosphorylation, the loss of the synaptic spine protein, amyloid-β (Aβ) deposition and plaque formation associated with increased microglial and astrocyte activation proliferation, which lead to exacerbated memory and cognition deficits. More importantly, we also observed increased glucose intolerance accompanied by Pdx1 reduction, the formation of advanced glycation end-products (AGEs), and the activation of the receptor for AGEs (RAGE) signaling pathways during AD progression; these changes are thought to contribute to the processing of Aβ precursor proteins and result in increased Aβ generation and decreased Aβ degradation. Protein glycation, increased oxidative stress and inflammation via hyperglycemia are the primary mechanisms involved in the pathophysiology of AD. These results indicate the pathological relationship between these diseases and provide novel insights suggesting that glycemic control may be beneficial for decreasing the incidence of AD in diabetic patients and delaying AD progression.
Exploring the induction of preproinsulin-specific Foxp3+ CD4+ Treg cells that inhibit CD8+ T cell-mediated autoimmune diabetes by DNA vaccination
Authors: Stifter Katja , Schuster Cornelia , Schlosser Michael , Boehm Bernhard Otto , Schirmbeck Reinhold 
Published: July 2016

AbstractDNA vaccination is a promising strategy to induce effector T cells but also regulatory Foxp3+ CD25+ CD4+ Treg cells and inhibit autoimmune disorders such as type 1 diabetes. Little is known about the antigen requirements that facilitate priming of Treg cells but not autoreactive effector CD8+ T cells. We have shown that the injection of preproinsulin (ppins)-expressing pCI/ppins vector into PD-1- or PD-L1-deficient mice induced Kb/A12-21-monospecific CD8+ T cells and autoimmune diabetes. A pCI/ppinsΔA12-21 vector (lacking the critical Kb/A12-21 epitope) did not induce autoimmune diabetes but elicited a systemic Foxp3+ CD25+ Treg cell immunity that suppressed diabetes induction by a subsequent injection of the diabetogenic pCI/ppins. TGF-β expression was significantly enhanced in the Foxp3+ CD25+ Treg cell population of vaccinated/ppins-primed mice. Ablation of Treg cells in vaccinated/ppins-primed mice by anti-CD25 antibody treatment abolished the protective effect of the vaccine and enabled diabetes induction by pCI/ppins. Adoptive transfer of Treg cells from vaccinated/ppins-primed mice into PD-L1−/− hosts efficiently suppressed diabetes induction by pCI/ppins. We narrowed down the Treg-stimulating domain to a 15-residue ppins76–90 peptide. Vaccine-induced Treg cells thus play a crucial role in the control of de novo primed autoreactive effector CD8+ T cells in this diabetes model.
Promising Tools in Prostate Cancer Research: Selective Non-Steroidal Cytochrome P450 17A1 Inhibitors
Authors: Bonomo Silvia , Hansen Cecilie H. , Petrunak Elyse M. , Scott Emily E. , Styrishave Bjarne , Jørgensen Flemming Steen , Olsen Lars 
Published: July 2016

AbstractCytochrome P450 17A1 (CYP17A1) is an important target in the treatment of prostate cancer because it produces androgens required for tumour growth. The FDA has approved only one CYP17A1 inhibitor, abiraterone, which contains a steroidal scaffold similar to the endogenous CYP17A1 substrates. Abiraterone is structurally similar to the substrates of other cytochrome P450 enzymes involved in steroidogenesis, and interference can pose a liability in terms of side effects. Using non-steroidal scaffolds is expected to enable the design of compounds that interact more selectively with CYP17A1. Therefore, we combined a structure-based virtual screening approach with density functional theory (DFT) calculations to suggest non-steroidal compounds selective for CYP17A1. In vitro assays demonstrated that two such compounds selectively inhibited CYP17A1 17α-hydroxylase and 17,20-lyase activities with IC50 values in the nanomolar range, without affinity for the major drug-metabolizing CYP2D6 and CYP3A4 enzymes and CYP21A2, with the latter result confirmed in human H295R cells.
TolC plays a crucial role in immune protection conferred by Edwardsiella tarda whole-cell vaccines
Authors: Wang Chao , Peng Bo , Li Hui , Peng Xuan-xian 
Published: July 2016

AbstractAlthough vaccines developed from live organisms have better efficacy than those developed from dead organisms, the mechanisms underlying this differential efficacy remain unexplored. In this study, we combined sub-immunoproteomics with immune challenge to investigate the action of the outer membrane proteome in the immune protection conferred by four Edwardsiella tarda whole-cell vaccines prepared via different treatments and to identify protective immunogens that play a key role in this immune protection. Thirteen spots representing five outer membrane proteins and one cytoplasmic protein were identified and it was found that their abundance was altered in relation with the immune protective abilities of the four vaccines. Among these proteins, TolC and OmpA were found to be the key immunogens conferring the first and second highest degrees of protection, respectively. TolC was detected in the two effective vaccines (live and inactivated-30-F). The total antiserum and anti-OmpA titers were higher for the two effective vaccines than for the two ineffective vaccines (inactivated-80-F and inactivated-100). Further evidence demonstrated that the live and inactivated-30-F vaccines demonstrated stronger abilities to induce CD8+ and CD4+ T cell differentiation than the other two evaluated vaccines. Our results indicate that the outer membrane proteome changes dramatically following different treatments, which contributes to the effectiveness of whole-cell vaccines.
Implementing rapid, robust, cost-effective, patient-centred, routine genetic testing in ovarian cancer patients
Authors: George Angela , Riddell Daniel , Seal Sheila , Talukdar Sabrina , Mahamdallie Shazia , Ruark Elise , Cloke Victoria , Slade Ingrid , Kemp Zoe , Gore Martin , Strydom Ann , Banerjee Susana , Hanson Helen , Rahman Nazneen 
Published: July 2016

AbstractAdvances in DNA sequencing have made genetic testing fast and affordable, but limitations of testing processes are impeding realisation of patient benefits. Ovarian cancer exemplifies the potential value of genetic testing and the shortcomings of current pathways to access testing. Approximately 15% of ovarian cancer patients have a germline BRCA1 or BRCA2 mutation which has substantial implications for their personal management and that of their relatives. Unfortunately, in most countries, routine implementation of BRCA testing for ovarian cancer patients has been inconsistent and largely unsuccessful. We developed a rapid, robust, mainstream genetic testing pathway in which testing is undertaken by the trained cancer team with cascade testing to relatives performed by the genetics team. 207 women with ovarian cancer were offered testing through the mainstream pathway. All accepted. 33 (16%) had a BRCA mutation. The result informed management of 79% (121/154) women with active disease. Patient and clinician feedback was very positive. The pathway offers a 4-fold reduction in time and 13-fold reduction in resource requirement compared to the conventional testing pathway. The mainstream genetic testing pathway we present is effective, efficient and patient-centred. It can deliver rapid, robust, large-scale, cost-effective genetic testing of BRCA1 and BRCA2 and may serve as an exemplar for other genes and other diseases.
The impact of conservation-driven translocations on blood parasite prevalence in the Seychelles warbler
Authors: Fairfield Eleanor A. , Hutchings Kimberly , Gilroy Danielle L. , Kingma Sjouke A. , Burke Terry , Komdeur Jan , Richardson David S. 
Published: July 2016

AbstractIntroduced populations often lose the parasites they carried in their native range, but little is known about which processes may cause parasite loss during host movement. Conservation-driven translocations could provide an opportunity to identify the mechanisms involved. Using 3,888 blood samples collected over 22 years, we investigated parasite prevalence in populations of Seychelles warblers (Acrocephalus sechellensis) after individuals were translocated from Cousin Island to four new islands (Aride, Cousine, Denis and Frégate). Only a single parasite (Haemoproteus nucleocondensus) was detected on Cousin (prevalence = 52%). This parasite persisted on Cousine (prevalence = 41%), but no infection was found in individuals hatched on Aride, Denis or Frégate. It is not known whether the parasite ever arrived on Aride, but it has not been detected there despite 20 years of post-translocation sampling. We confirmed that individuals translocated to Denis and Frégate were infected, with initial prevalence similar to Cousin. Over time, prevalence decreased on Denis and Frégate until the parasite was not found on Denis two years after translocation, and was approaching zero prevalence on Frégate. The loss (Denis) or decline (Frégate) of H. nucleocondensus, despite successful establishment of infected hosts, must be due to factors affecting parasite transmission on these islands.
Germline replacement by blastula cell transplantation in the fish medaka
Authors: Li Mingyou , Hong Ni , Xu Hongyan , Song Jianxing , Hong Yunhan 
Published: July 2016

AbstractPrimordial germ cell (PGC) specification early in development establishes the germline for reproduction and reproductive technologies. Germline replacement (GR) is a powerful tool for conservation of valuable or endangered animals. GR is achievable by germ cell transplantation into the PGC migration pathway or gonads. Blastula cell transplantation (BCT) can also lead to the chimeric germline containing PGCs of both donor and host origins. It has remained largely unknown whether BCT is able to achieve GR at a high efficiency. Here we report efficient GR by BCT into blastula embryos in the fish medaka (Oryzias latipes). Specifically, dnd depletion completely ablated host PGCs and fertility, and dnd overexpression remarkably boosted PGCs in donor blastulae. BCT between normal donor and host produced a germline transmission rate of ~4%. This rate was enhanced up to ~30% upon PGC boosting in donors. Most importantly, BCT between PGC-boosted donors and PGC-ablated hosts led to more than 90% fertility restoration and 100% GR. Therefore, BCT features an extremely high efficiency of fertility recovery and GR in medaka. This finding makes medaka an ideal model to analyze genetic and physiological donor-host compatibilities for BCT-mediated surrogate production and propagation of endangered lower vertebrates and biodiversity.
Advanced nanoporous TiO2 photocatalysts by hydrogen plasma for efficient solar-light photocatalytic application
Authors: An Ha-Rim , Park So Young , Kim Hyeran , Lee Che Yoon , Choi Saehae , Lee Soon Chang , Seo Soonjoo , Park Edmond Changkyun , Oh You-Kwan , Song Chan-Geun , Won Jonghan , Kim Youn Jung , Lee Jouhahn , Lee Hyun Uk , Lee Young-Chul 
Published: July 2016

AbstractWe report an effect involving hydrogen (H2)-plasma-treated nanoporous TiO2(H-TiO2) photocatalysts that improve photocatalytic performance under solar-light illumination. H-TiO2 photocatalysts were prepared by application of hydrogen plasma of assynthesized TiO2(a-TiO2) without annealing process. Compared with the a-TiO2, the H-TiO2 exhibited high anatase/brookite bicrystallinity and a porous structure. Our study demonstrated that H2 plasma is a simple strategy to fabricate H-TiO2 covering a large surface area that offers many active sites for the extension of the adsorption spectra from ultraviolet (UV) to visible range. Notably, the H-TiO2 showed strong ·OH free-radical generation on the TiO2 surface under both UV- and visible-light irradiation with a large responsive surface area, which enhanced photocatalytic efficiency. Under solar-light irradiation, the optimized H-TiO2 120(H2-plasma treatment time: 120 min) photocatalysts showed unprecedentedly excellent removal capability for phenol (Ph), reactive black 5(RB 5), rhodamine B (Rho B) and methylene blue (MB) — approximately four-times higher than those of the other photocatalysts (a-TiO2 and P25) — resulting in complete purification of the water. Such well-purified water (>90%) can utilize culturing of cervical cancer cells (HeLa), breast cancer cells (MCF-7), and keratinocyte cells (HaCaT) while showing minimal cytotoxicity. Significantly, H-TiO2 photocatalysts can be mass-produced and easily processed at room temperature. We believe this novel method can find important environmental and biomedical applications.
A sodium channel inhibitor ISTX-I with a novel structure provides a new hint at the evolutionary link between two toxin folds
Authors: Rong Mingqiang , Liu Jiangxin , Zhang Meilin , Wang Gan , Zhao Gang , Wang Guodong , Zhang Yaping , Hu Kaifeng , Lai Ren 
Published: July 2016

AbstractMembers of arachnida, such as spiders and scorpions, commonly produce venom with specialized venom glands, paralyzing their prey with neurotoxins that specifically target ion channels. Two well-studied motifs, the disulfide-directed hairpin (DDH) and the inhibitor cystine knot motif (ICK), are both found in scorpion and spider toxins. As arachnids, ticks inject a neurotoxin-containing cocktail from their salivary glands into the host to acquire a blood meal, but peptide toxins acting on ion channels have not been observed in ticks. Here, a new neurotoxin (ISTX-I) that acts on sodium channels was identified from the hard tick Ixodes scapularis and characterized. ISTX-I exhibits a potent inhibitory function with an IC50 of 1.6 μM for sodium channel Nav1.7 but not other sodium channel subtypes. ISTX-I adopts a novel structural fold and is distinct from the canonical ICK motif. Analysis of the ISTX-I, DDH and ICK motifs reveals that the new ISTX-I motif might be an intermediate scaffold between DDH and ICK and ISTX-I is a clue to the evolutionary link between the DDH and ICK motifs. These results provide a glimpse into the convergent evolution of neurotoxins from predatory and blood-sucking arthropods.
Effects of Fluoroquinolones and Azithromycin on Biofilm Formation of Stenotrophomonas maltophilia
Authors: Wang Aihua , Wang Qinqin , Kudinha Timothy , Xiao Shunian , Zhuo Chao 
Published: July 2016

AbstractStenotrophomonas maltophilia is an opportunistic pathogen that causes respiratory and urinary tract infections, as well as wound infections in immunocompromised patients. This pathogen is difficult to treat due to increased resistance to many antimicrobial agents. We investigated the in vitro biofilm formation of S. maltophilia, including effects of fluoroquinolones (FQs) and azithromycin on biofilm formation. The organism initiated attachment to polystyrene surfaces after a 4 h incubation period and reached maximal growth at 18–24 h. In the presence of FQs (moxifloxacin, levofloxacin or ciprofloxacin), the biofilm biomass was significantly reduced (P < 0.05). A lower concentration of moxifloxacin (10 μg/mL) exhibited a better inhibiting effect on biofilm formation than 100 μg/mL (P < 0.01), but with no difference in effect compared to the 50 μg/mL concentration (P > 0.05). However, the inhibitory effects of 10 μg/mL of levofloxacin or ciprofloxacin were slightly less pronounced than those of the higher concentrations. A combination of azithromycin and FQs significantly reduced the biofilm inhibiting effect on S. maltophilia preformed biofilms compared to azithromycin or FQs alone. We conclude that early use of clinically acceptable concentrations of FQs, especially moxifloxacin (10 μg/mL), may possibly inhibit biofilm formation by S. maltophilia. Our study provides an experimental basis for a possible optimal treatment strategy for S. maltophilia biofilm-related infections.