bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adaptation to climate change: trade‐offs among responses to multiple stressors in an intertidal crustacean
Authors: Kelly Morgan W. , DeBiasse Melissa B. , Villela Vidal A. , Roberts Hope L. , Cecola Colleen F. 
Published: May 2016

AbstractTrade‐offs may influence both physiological and evolutionary responses to co‐occurring stressors, but their effects on both plastic and adaptive responses to climate change are poorly understood. To test for genetic and physiological trade‐offs incurred in tolerating multiple stressors, we hybridized two populations of the intertidal copepod Tigriopus californicus that were divergent for both heat and salinity tolerance. Starting in the F2 generation, we selected for increased tolerance of heat, low salinity, and high salinity in replicate lines. After five generations of selection, heat‐selected lines had greater heat tolerance but lower fecundity, indicating an energetic cost to tolerance. Lines selected for increased salinity tolerance did not show evidence of adaptation to their respective environments; however, hypo‐osmotic selection lines showed substantial loss of tolerance to hyperosmotic stress. Neither of the salinity selection regimes resulted in diminished heat tolerance at ambient salinity; however, simultaneous exposure to heat and hypo‐osmotic stress led to decreased heat tolerance, implying a physiological trade‐off in tolerance to the two stressors. When we quantified the transcriptomic response to heat and salinity stress via RNA sequencing, we observed little overlap in the stress responses, suggesting the observed synergistic effects of heat and salinity stress were driven by competing energetic demands, rather than shared stress response pathways.
Has Scots pine (Pinus sylvestris) co‐evolved with Dothistroma septosporum in Scotland? Evidence for spatial heterogeneity in the susceptibility of native provenances
Authors: Perry Annika , Brown Anna V. , Cavers Stephen , Cottrell Joan E. , Ennos Richard A. 
Published: May 2016

AbstractSpatial heterogeneity in pathogen pressure leads to genetic variation in, and evolution of, disease‐related traits among host populations. In contrast, hosts are expected to be highly susceptible to exotic pathogens as there has been no evolution of defence responses. Host response to pathogens can therefore be an indicator of a novel or endemic pathosystem. Currently, the most significant threat to native British Scots pine (Pinus sylvestris) forests is Dothistroma needle blight (DNB) caused by the foliar pathogen Dothistroma septosporum which is presumed to be exotic. A progeny–provenance trial of 6‐year‐old Scots pine, comprising eight native provenances each with four families in six blocks, was translocated in April 2013 to a clear‐fell site in Galloway adjacent to a DNB‐infected forest. Susceptibility to D. septosporum, measured as DNB severity (estimated percentage nongreen current‐year needles), was assessed visually over 2 years (2013–2014 and 2014–2015; two assessments per year). There were highly significant differences in susceptibility among provenances but not among families for each annual assessment. Provenance mean susceptibility to D. septosporum was negatively and significantly associated with water‐related variables at site of origin, potentially due to the evolution of low susceptibility in the host in response to high historical pathogen pressure.
Comparison of human glutamate carboxypeptidases II and III reveals their divergent substrate specificities
Authors: Navrátil Michal , Tykvart Jan , Schimer Jiří , Pachl Petr , Navrátil Václav , Rokob Tibor András , Hlouchová Klára , Rulíšek Lubomír , Konvalinka Jan 
Published: May 2016

Glutamate carboxypeptidase III (GCPIII) is best known as a homologue of glutamate carboxypeptidase II [GCPII; also known as prostate‐specific membrane antigen (PSMA)], a protease involved in neurological disorders and overexpressed in a number of solid cancers. However, mouse GCPIII was recently shown to cleave β‐citrylglutamate (BCG), suggesting that these two closely related enzymes have distinct functions. To develop a tool to dissect, evaluate and quantify the activities of human GCPII and GCPIII, we analysed the catalytic efficiencies of these enzymes towards three physiological substrates. We observed a high efficiency of BCG cleavage by GCPIII but not GCPII. We also identified a strong modulation of GCPIII enzymatic activity by divalent cations, while we did not observe this effect for GCPII. Additionally, we used X‐ray crystallography and computational modelling (quantum and molecular mechanical calculations) to describe the mechanism of BCG binding to the active sites of GCPII and GCPIII, respectively. Finally, we took advantage of the substantial differences in the enzymatic efficiencies of GCPII and GCPIII towards their substrates, using enzymatic assays for specific detection of these proteins in human tissues. Our findings suggest that GCPIII may not act merely as a complementary enzyme to GCPII, and it more likely possesses a specific physiological function related to BCG metabolism in the human body.DatabaseThe X‐ray structure of GCPII Glu424Ala in complex with BCG has been deposited in the RCSB Protein Data Bank under accession code 5F09.
Mutually Beneficial Foreign Language Learning: Creating Meaningful Interactions Through Video‐Synchronous Computer‐Mediated Communication
Authors: Kato Fumie , Spring Ryan , Mori Chikako 
Published: May 2016

AbstractProviding learners of a foreign language with meaningful opportunities for interactions, specifically with native speakers, is especially challenging for instructors. One way to overcome this obstacle is through video‐synchronous computer‐mediated communication tools such as Skype software. This study reports quantitative and qualitative data from a Skype partner program that emphasized meaningful communication between American students learning Japanese in the United States and Japanese students learning English in Japan. Analysis of pre‐ and posttests showed significant improvement in the listening and speaking abilities of the Japanese participants and in the speaking abilities of the American participants.
Evidence of pathogenicity of a mutation in 3′ untranslated region causing mild haemophilia A
Authors: Pezeshkpoor B. , Berkemeier A‐ C. , Czogalla K. J. , Oldenburg J. , El‐Maarri O. 
Published: May 2016

IntroductionDespite the high mutation detection rate, in a small group of haemophilia A patients, using current screening methods, no causal mutation in F8 can be detected. In such cases, the causal mutation might be in the non‐coding sequences of F8.AimRarely, mutations in non‐coding sequences reveal a pivotal role. Here, we analysed a mild haemophilia A patient harbouring a mutation in the 3′ untranslated region (UTR) of F8 and elucidated the molecular mechanism leading to haemophilia phenotype.MethodsTo find the causal mutation, the complete F8 genomic region was analysed by next generation sequencing. The effect of the identified alteration on F8 expression was evaluated in silico and analysed for the splicing effect at mRNA level. Moreover, in vitro studies using a luciferase reporter system were performed to functionally analyse the mutation.ResultsWe identified an alteration in the 3′ UTR (c.*56G>T) as the only change in F8 gene. Pedigree analysis showed a segregation pattern for three affected members for the presumptive mutation. Moreover, the variant was predicted in silico to create a new donor splice site, which was also detected at mRNA level, resulting in a 159 bp deletion in 3′ UTR of F8. Finally, the variant showed reduced expression of the gene reporter firefly luciferase in cell line expression analysis.ConclusionOur results advocate the patient specific c.*56G>T base change in the 3′ UTR to be a disease‐associated mutation leading to alternative splicing explaining the mild haemophilia A phenotype.
Experience of a new high‐purity factor X concentrate in subjects with hereditary factor X deficiency undergoing surgery
Authors: Escobar M. A. , Auerswald G. , Austin S. , Huang J. N. , Norton M. , Millar C. M. 
Published: May 2016

IntroductionMaintaining haemostasis in surgery is challenging for hereditary rare bleeding disorders in which multi‐coagulation‐factor concentrates are the only therapeutic option. Hereditary factor X (FX) deficiency affects 1:500 000 to 1:1 000 000 individuals, and no specific replacement FX concentrate has been available. A high‐purity, plasma‐derived FX concentrate (pdFX) has been developed for patients with hereditary FX deficiency.AimOur objective was to assess the safety and efficacy of pdFX in subjects with FX deficiency undergoing surgery.MethodsSubjects with hereditary mild‐to‐severe FX deficiency (basal plasma FX activity [FX:C] <20 IU dL−1) undergoing surgery received pdFX preoperatively to raise FX:C to 70–90 IU dL−1 and postoperatively to maintain levels >50 IU dL−1 until the subject was no longer at risk of bleeding due to surgery. Efficacy of pdFX was assessed by blood loss during surgery, requirement for blood transfusion, postoperative bleeding from the surgical or other sites, and changes in haemoglobin levels. Safety was assessed by adverse events (AEs), development of inhibitors, and clinically significant changes in laboratory parameters.ResultsFive subjects (aged 14–59 years) underwent seven surgical procedures (four major and three minor). Treatment duration was 1–15 days. For each procedure, pdFX treatment was assessed as “excellent” in preventing bleeding and achieving haemostasis. No blood transfusions were required, no AEs related to pdFX were observed, and no clinically significant trends were found in any laboratory parameters.ConclusionThese data demonstrate that pdFX is safe and effective as replacement therapy in five subjects with mild‐to‐severe FX deficiency undergoing surgery on seven occasions.
Evaluation of chemical components of debittered olives undergone preservation and polyphenol oxidation
Authors: Ramírez Eva , García Pedro , Brenes Manuel , Romero Concepción 
Published: May 2016

SummaryOlives can reduce their bitterness by oleuropein oxidation via an enzymatic reaction. In this study, olives of the Manzanilla and Hojiblanca varieties preserved in acidified brine were submitted to oxidation tests under overpressure of oxygen (0.3 bars) for 3 days. It was found that the oxidation of fruit preserved for more than 3–4 months showed a reduction in the concentration of oleuropein, but with great variability (28–100%). By contrast, when olives were preserved for only one month, the oxidation treatment was able to decrease more than 90% of the content of oleuropein in the fruit. These oxidised olives were stored again in the acidified medium for 6 months and no spoilage or organoleptic problems were detected. Oxidation gave rise to darker olives (L* parameter diminished from 40 to 34). Moreover, the oxidised fruit was enriched with free phenols such as hydroxytyrosol and tyrosol as a consequence of the acid hydrolysis of phenolic glucosides during the preservation step.
The Impact of NASD Rule 2711 and NYSE Rule 472 on Analyst Behavior: The Strategic Timing of Recommendations Issued on Weekends
Authors: Dong Yi , Hu Nan 
Published: May 2016

AbstractAmendments to NASD Rule 2711 and NYSE Rule 472, enacted in May 2002, mandate that sell‐side analysts disclose the distribution of their security recommendations by buy, hold and sell category. This regulation enhances the transparency of analysts’ information and mitigates the long‐recognized optimistic bias in their recommendations. However, we find that analysts are more likely to issue sell recommendations or downgrade revisions on weekends when investors have limited attention after these rule changes. This pattern is more pronounced for prestigious analysts, who are more likely to influence stock prices. Market reaction tests reveal an incomplete immediate response and a greater drift to unfavorable recommendations issued on weekends. Finally, analysts who are more likely to release unfavorable recommendations on weekends exhibit higher future forecast accuracy. Our findings suggest that, while these regulatory changes effectively reduce analysts’ optimistic bias, they are also associated with an increased prevalence of a different form of distortion in the capital market.
Genetic divergence and isolation by thermal environment in geothermal populations of an aquatic invertebrate
Authors: Johansson M. P. , Quintela M. , Laurila A. 
Published: May 2016

AbstractTemperature is one of the most influential forces of natural selection impacting all biological levels. In the face of increasing global temperatures, studies over small geographic scales allowing investigations on the effects of gene flow are of great value for understanding thermal adaptation. Here, we investigated genetic population structure in the freshwater gastropod Radix balthica originating from contrasting thermal habitats in three areas of geothermal activity in Iceland. Snails from 32 sites were genotyped at 208 AFLP loci. Five AFLPs were identified as putatively under divergent selection in Lake Mývatn, a geothermal lake with an almost 20 °C difference in mean temperature across a distance of a few kilometres. In four of these loci, variation across all study populations was correlated with temperature. We found significant population structure in neutral markers both within and between the areas. Cluster analysis using neutral markers classified the sites mainly by geography, whereas analyses using markers under selection differentiated the sites based on temperature. Isolation by distance was stronger in the neutral than in the outlier loci. Pairwise differences based on outlier FST were significantly correlated with temperature at different spatial scales, even after correcting for geographic distance or neutral pairwise FST differences. In general, genetic variation decreased with increasing environmental temperature, possibly suggesting that natural selection had reduced the genetic diversity in the warm origin sites. Our results emphasize the influence of environmental temperature on the genetic structure of populations and suggest local thermal adaptation in these geothermal habitats.
Coeliac disease and the gluten‐free diet: a review of the burdens; factors associated with adherence and impact on health‐related quality of life, with specific focus on adolescence
Authors: White L. E. , Bannerman E. , Gillett P. M. 
Published: May 2016

AbstractAdherence and non‐adherence to a gluten‐free diet (GFD) may impact negatively on health‐related quality of life (HRQoL). Understanding the factors that influence compliance could help inform management and also guide support. With a particular focus on adolescence, this narrative review critiques current literature on the burdens associated with following a GFD and the factors associated with adherence. Studies highlight a variety of burdens faced by individuals with coeliac disease, including the cost, access and availability of gluten‐free (GF) foods, as well as the dilemmas experienced when eating out, travelling and socialising with friends. A number of studies report that adolescents face stigmatisation and feel isolated in social situations and at school. Additional burdens that are highlighted are a lack of knowledge regarding CD and GFD difficulties in interpreting food labels, as well as dissatisfaction with the organoleptic properties of GF foods. Factors associated with poor adherence in adolescence include older age, an absence of immediate symptoms, difficulties eating out and poor palatability of GF foods. Conversely, better emotional support and stronger organisation skills have been associated with superior adherence. Significant associations have been reported between HRQoL measures and adherence, although the findings are inconsistent. Limitations in research methodologies exist and data are restricted to just a few countries. Further research specific to adolescence is required to identify independent predictors of adherence.
A Hybrid Approach for Assessing the Multi‐Scale Impacts of Urban Resource Use: Transportation in Phoenix, Arizona
Authors: Clark Susan Spierre , Chester Mikhail V. 
Published: May 2016

SummaryLife cycle assessment (LCA) and urban metabolism (UM) are popular approaches for urban system environmental assessment. However, both approaches have challenges when used across spatial scales. LCA tends to decompose systemic information into micro‐level functional units that mask complexity and purpose, whereas UM typically equates aggregated material and energy flows with impacts and is not ideal for revealing the mechanisms or alternatives available to reduce systemic environmental risks. This study explores the value of integrating UM with LCA, using vehicle transportation in the Phoenix metropolitan area as an illustrative case study. Where other studies have focused on the use of LCA providing upstream supply‐chain impacts for UM, we assert that the broader value of the integrated approach is in (1) the ability to cross scales (from micro to macro) in environmental assessment and (2) establishing an analysis that captures function and complexity in urban systems. The results for Phoenix show the complexity in resource supply chains and critical infrastructure services, how impacts accrue well beyond geopolitical boundaries where activities occur, and potential system vulnerabilities.
Biochemical and electrophysiological characterization of N‐glycans on NMDA receptor subunits
Authors: Kaniakova Martina , Lichnerova Katarina , Skrenkova Kristyna , Vyklicky Ladislav , Horak Martin 
Published: May 2016

AbstractIn mammals, excitatory synapses contain two major types of ionotropic glutamate receptors: α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptors and N‐methyl‐d‐aspartate receptors (NMDARs). Both receptor types are comprised of several subunits that are post‐translationally modified by N‐glycosylation. However, the precise N‐glycans that are attached to these receptor types are largely unknown. Here, we used biochemistry to confirm that native NMDARs are extensively N‐glycosylated; moreover, we found that the NMDAR GluN2B subunit differs from GluN1 subunits with respect to endoglycosidase H sensitivity. Next, we used a complete panel of lectins to determine the glycan composition of NMDARs in both cerebellar tissue and cultured cerebellar granule cells. Our experiments identified 23 lectins that pulled down both the GluN1 and GluN2B NMDAR subunits. We then performed an electrophysiological analysis using representative lectins and found that pre‐incubating cerebellar granule cells with the AAL, WGA, or ConA alters the receptor's biophysical properties; this lectin‐mediated effect was eliminated when the cells were deglycosylated with peptide‐N‐glycosidase F. Similar lectin‐mediated effects were observed using HEK293 cells that express recombinant GluN1/GluN2B receptors. Finally, using mutant recombinant GluN subunits expressed in HEK293 cells, we found that 11 out of 12 predicted N‐glycosylation sites in GluN1 and 7 out of 7 N‐glycosylation sites in GluN2B are occupied by N‐glycans. These data provide new insight into the role that N‐glycosylation plays in regulating the function of NMDA receptors in the central nervous system. All animal experiments were performed in accordance with relevant institutional ethics guidelines and regulations with respect to protecting animal welfare.
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We examined the N‐glycan composition of NMDA receptors (NMDARs) using deglycosylating enzymes, lectin‐based biochemistry, and electrophysiology. Our results revealed that cerebellar NMDARs associate with 23 different lectins that have unique specificities for glycan structures. Furthermore, we found that 11 out of 12 predicted N‐glycosylation sites in GluN1 and 7 out of 7 N‐glycosylation sites in GluN2B are occupied by N‐glycans. These data shed light on the glycan composition of NMDARs, revealing potential targets for the development of novel therapeutic approaches.
Capital Investment, Innovative Capacity, and Stock Returns
Authors: KUMAR PRAVEEN , LI DONGMEI 
Published: May 2016

ABSTRACTWe study the dynamic implications of capital investment in innovative capacity (IC) on future stock returns, investment, and profitability by modeling the unique effects of IC investment on uncertain option generation/exercise and postexercise revenue. The model highlights the diverse effects of IC investment on expected returns in different postinvestment regimes and yields the novel prediction that, under the neoclassical assumption of nonincreasing revenue returns, IC investment is positively related to subsequent cumulative stock returns with a lag. The model also predicts a positive effect of IC investment on future investment and profitability. We find strong empirical support for these predictions.
Selective intestinal decontamination with norfloxacin enhances a regulatory T cell‐mediated inflammatory control mechanism in cirrhosis
Authors: Juanola Oriol , Gómez‐Hurtado Isabel , Zapater Pedro , Moratalla Alba , Caparrós Esther , Piñero Paula , González‐Navajas José M. , Giménez Paula , Such José , Francés Rubén 
Published: May 2016

AbstractBackground & AimsNorfloxacin exerts immunomodulatory effects in cirrhosis beyond its bactericidal activity. We aimed at identifying the role of regulatory T (Treg) cells in the norfloxacin mechanism that compensates the inflammatory environment in cirrhosis.Patients & MethodsConsecutively admitted patients with cirrhosis and ascitic fluid (AF) with: spontaneous bacterial peritonitis (SBP), non‐infected AF, and norfloxacin as secondary SBP prophylaxis (SID group). Tregs were defined by flow‐cytometry as CD4+CD25+FoxP3+ cells. Dendritic cells (DCs) were purified for co‐stimulatory signalling evaluation and norfloxacin and IL‐10 levels were measured in serum. Wildtype and recombination activating gene 1 (Rag1)‐deficient mice with CCl4‐induced cirrhosis were used for adoptive‐transfer experiments using naïve CD4+ T cells and Tregs.ResultsEighty‐four patients were included. Treg percentage was significantly increased in SID patients compared with SBP or non‐infected AF patients. A positive correlation was observed between Tregs and serum norfloxacin and IL‐10 levels. DCs from SID patients showed a significantly decreased expression of CD80 and CD86 compared with SBP and non‐infected AF patients and correlated with norfloxacin levels. Modulation of co‐stimulatory signalling by norfloxacin was not detected in Rag1‐deficient mice and Rag1‐deficient mice reconstituted with naïve T‐cells. However, reconstitution with naïve T‐cells and Tregs was associated with significantly downregulated CD80 and CD86 expression in the presence of norfloxacin. Norfloxacin immunomodulatory effect on IL‐2 and IFN‐gamma reduction and on the increase of IL‐10 was significantly achieved only when the Tregs were restored in Rag1‐deficient mice.ConclusionsThese results provide a plausible mechanism for the immunomodulatory effects of norfloxacin in cirrhosis beyond its bactericidal effect.