bluuebunny/crossref_metadata_2025_split huggingface dataset:
Major histocompatibility complex and mate choice in the polygynous primate: the Sichuan snub‐nosed monkey (Rhinopithecus roxellana)
Authors: YANG Banghe , REN Baoping , XIANG Zuofu , YANG Jingyuan , YAO Hui , GARBER Paul A. , LI Ming 
Published: November 2014

AbstractThe highly polymorphic genes within the major histocompatibility complex (MHC) not only play a major role in immunity resistance, but also seem to provide hints for mate choice in some animal populations. In the present study we investigated MHC‐related mate choice in a small natural population (group size 40–55 individuals) of a polygynous primate, the Sichuan snub‐nosed monkey (Rhinopithecus roxellana). We found that there was no evidence either for MHC‐disassortative mating, or for females to mate with males based on MHC heterozygosity or specific alleles. Nevertheless, of the 11 alleles identified, we found that the frequencies of 2 alleles, Rhro‐DRB2 (P < 0.01) and Rhro‐DRB5 (P < 0.05) were higher in offspring than in their parents. These findings suggest that MHC‐DRB in this population of R. roxellana is unlikely to be associated with mating preferences. Limited female opportunities for mate choice are likely due, in part, to the harem breeding structure present in R. roxellana, and the relatively small number of resident adult males in our study band (N = 4–6). In addition, we suggest that differences in the frequency of particular alleles across generations may be linked to parasite resistance in a fluctuating environment; however, confirmation of this finding requires further study.
Ionizing radiation exposure in patients with inflammatory bowel disease: Are we overexposing our patients?
Authors: Estay Camila , Simian Daniela , Lubascher Jaime , Figueroa Carolina , O'Brien Andrés , Quera Rodrigo 
Published: November 2014

ObjectiveImaging techniques are accurate and reliable in diagnosing inflammatory bowel disease (IBD). However, the main disadvantage of computed tomography (CT) compared with magnetic resonance imaging (MRI) is radiation exposure and the potential risk of cancer, especially since IBD patients are at increased risk of malignancies. This study aims to quantify and characterize effective radiation exposure of IBD patients.MethodsA cohort of IBD patients were retrospectively enrolled in the Clínica las Condes IBD registry between 2011 and 2013. High cumulative radiation exposure (CED) was defined as ≥−50 mSv.ResultsA total of 325 IBD patients were enrolled in our registry, including 243 (74.8%) with UC and 82 (25.2%) with CD. The patients with CD were more commonly to reach a high CED seen compared with those with UC (19.5% vs 2.5%). Higher exposure to radiation was associated with longer duration of disease, ileal involvement, stricturing behavior, treatments with steroids and biological agents and CD‐related hospitalization or surgery. Abdominopelvic CT and enteroclysis CT accounted for 93.6% of total CED.ConclusionsA high percentage of IBD patients are exposed to high CED. Radiation‐free cross‐sectional examinations, such as MRI, should be used, especially in young patients, those who have undergone prior surgery and those with severe IBD.
Genomic Resources Notes Accepted 1 August 2014–30 September 2014
Authors:   Genomic Resources Development Consortium, Arthofer Wolfgang , Banbury B. L. , Carneiro Miguel , Cicconardi Francesco , Duda Thomas F. , Harris R. B. , Kang David S. , Leaché A. D. , Nolte Viola , Nourisson Coralie , Palmieri Nicola , Schlick‐Steiner Birgit C. , Schlötterer Christian , Sequeira Fernando , Sim Cheolho , Steiner Florian M. , Vallinoto Marcelo , Weese David A. 
Published: November 2014

AbstractThis article documents the public availability of (i) transcriptome sequence data, assembly and annotation, and single nucleotide polymorphisms (SNPs) for the cone snail Conus miliaris; (ii) a set of SNP markers for two biotypes from the Culex pipiens mosquito complex; (iii) transcriptome sequence data, assembly and annotation for the mountain fly Drosophila nigrosparsa; (iv) transcriptome sequence data, assembly and annotation and SNPs for the Neotropical toads Rhinella marina and R. schneideri; and (v) partial genomic sequence assembly and annotation for 35 spiny lizard species (Genus Sceloporus).
The prevalence of EGFR mutations in non‐small cell lung cancer in an unselected Caucasian population
Authors: Skov Birgit G , Høgdall Estrid , Clementsen Paul , Krasnik Mark , Larsen Klaus Richter , Sørensen Jens Benn , Skov Torsten , Mellemgaard Anders 
Published: November 2014

EGFR mutation frequencies in unselected Caucasian populations are unknown. This study assesses the prevalence of EGFR mutations in an unselected population‐based cohort, and the correlation between mutation and gender, age, ethnicity, smoking habits, and pathological data. NSCLC patients diagnosed in a well‐defined Danish population were included. The type of the diagnostic material, and data on smoking were registered. The mutation analyses were investigated by Therascreen EGFR RGQ‐PCR Kit or Sanger sequencing. A total of 658 men and 598 women were included. 6.2% were never smokers, 38.9% were ex‐smokers, and 54.9% were current smokers. One thousand one hundred and sixty‐one (92.4%) patients had sufficient material for mutation analysis. Cytological material was used for 38% of the mutation analyses. 5.4% had mutation in the EGFR gene (4.3% men/6.7% women). 87% were activating mutations. 8.0% of adenocarcinomas, and 1.9% of squamous cell carcinomas were mutated. 29.4%, 4.4% and 2.9% of never, ex‐ and current smokers were mutated (p < 0.001). No difference in mutation rate was observed between patients with cytology only, histology only or both cytology and histology available. 5.4% of the patients had EGFR mutation. Adenocarcinomas were mutated more often (8.0%) than squamous cell carcinomas (1.9%). Mutations were found in never smokers as well as in former and current smokers. No difference in gender and age regarding mutation status was observed. EGFR mutations analysis was possible in almost all patients with no difference between cytology and histology specimens.
Paraesthesia after Local Anaesthetics: An Analysis of Reports to the FDA Adverse Event Reporting System
Authors: Piccinni Carlo , Gissi Davide B. , Gabusi Andrea , Montebugnoli Lucio , Poluzzi Elisabetta 
Published: November 2014

AbstractThis study was aimed to evaluate the possible alert signals of paraesthesia by local anaesthetics, focusing on those used in dentistry. A case/non‐case study of spontaneous adverse events recorded in FAERS (FDA Adverse Event Reporting System) between 2004 and 2011 was performed. Cases were represented by the reports of reactions grouped under the term ‘Paraesthesias and dysaesthesias’ involving local anaesthetics (ATC: N01B*); non‐cases were all other reports of the same drugs. Reporting odds ratios (ROR) with the relevant 95% confidence intervals (95CI) were calculated. Alert signal was considered when number of cases >3 and lower limit of ROR 95CI > 1. To estimate the specificity of signals for dentistry, the analysis was restricted to the specific term “Oral Paraesthesia” and to reports concerning dental practice. Overall, 528 reports of ‘Paraesthesias and dysaesthesias’ were retrieved, corresponding to 573 drug–reaction pairs (247 lidocaine, 99 bupivacaine, 85 articaine, 30 prilocaine, 112 others). The signal was significant only for articaine (ROR=18.38; 95CI = 13.95–24.21) and prilocaine (2.66; 1.82–3.90). The analysis of the specific term “Oral Paraesthesia” retrieved 82 reports corresponding to 90 drug–reaction pairs (37 articaine, 19 lidocaine, 14 prilocaine, 7 bupivacaine, 13 others) and confirmed the signal for articaine (58.77; 37.82–91.31) and prilocaine (8.73; 4.89–15.57). The analysis of reports concerning dental procedures retrieved a signal for articaine, both for any procedures (8.84; 2.79–27.97) and for non‐surgical ones (15.79; 1.87–133.46). In conclusion, among local anaesthetics, only articaine and prilocaine generated a signal of paraesthesia, especially when used in dentistry.
An Eliminativist Approach to Vulnerability
Authors: Wrigley Anthony 
Published: November 2014

AbstractThe concept of vulnerability has been subject to numerous different interpretations but accounts are still beset with significant problems as to their adequacy, such as their contentious application or the lack of genuine explanatory role for the concept. The constant failure to provide a compelling conceptual analysis and satisfactory definition leaves the concept open to an eliminativist move whereby we can question whether we need the concept at all. I highlight problems with various kinds of approach and explain why a satisfactory account of vulnerability is unlikely ever to be offered if we wish the concept to play a genuinely explanatory role in bioethical contexts. I outline why an eliminativist position should be taken with regard to this concept in light of these concerns but mitigate some of the severity of this position by arguing that we can still make sense of retaining our widespread use of the term by viewing it as nothing more than a useful pragmatic linguistic device that acts as a marker to draw attention to certain kinds of issue. These issues will be entirely governed by other, better understood ethical concepts and theories.
The role of skeletal‐muscle‐based thermogenic mechanisms in vertebrate endothermy
Authors: Rowland Leslie A. , Bal Naresh C. , Periasamy Muthu 
Published: November 2014

ABSTRACTThermogenesis is one of the most important homeostatic mechanisms that evolved during vertebrate evolution. Despite its importance for the survival of the organism, the mechanistic details behind various thermogenic processes remain incompletely understood. Although heat production from muscle has long been recognized as a thermogenic mechanism, whether muscle can produce heat independently of contraction remains controversial. Studies in birds and mammals suggest that skeletal muscle can be an important site of non‐shivering thermogenesis (NST) and can be recruited during cold adaptation, although unequivocal evidence is lacking. Much research on thermogenesis during the last two decades has been focused on brown adipose tissue (BAT). These studies clearly implicate BAT as an important site of NST in mammals, in particular in newborns and rodents. However, BAT is either absent, as in birds and pigs, or is only a minor component, as in adult large mammals including humans, bringing into question the BAT‐centric view of thermogenesis. This review focuses on the evolution and emergence of various thermogenic mechanisms in vertebrates from fish to man. A careful analysis of the existing data reveals that muscle was the earliest facultative thermogenic organ to emerge in vertebrates, long before the appearance of BAT in eutherian mammals. Additionally, these studies suggest that muscle‐based thermogenesis is the dominant mechanism of heat production in many species including birds, marsupials, and certain mammals where BAT‐mediated thermogenesis is absent or limited. We discuss the relevance of our recent findings showing that uncoupling of sarco(endo)plasmic reticulum Ca2+‐ATPase (SERCA) by sarcolipin (SLN), resulting in futile cycling and increased heat production, could be the basis for NST in skeletal muscle. The overall goal of this review is to highlight the role of skeletal muscle as a thermogenic organ and provide a balanced view of thermogenesis in vertebrates.
Pharmacodynamic differences between canagliflozin and dapagliflozin: results of a randomized, double‐blind, crossover study
Authors: Sha S. , Polidori D. , Farrell K. , Ghosh A. , Natarajan J. , Vaccaro N. , Pinheiro J. , Rothenberg P. , Plum‐Mörschel L. 
Published: November 2014

AimsTo compare the pharmacodynamic effects of the highest approved doses of the sodium glucose co‐transporter 2 (SGLT2) inhibitors canagliflozin and dapagliflozin on urinary glucose excretion (UGE), renal threshold for glucose excretion (RTG) and postprandial plasma glucose (PPG) excursion in healthy participants in a randomized, double‐blind, two‐period crossover study.MethodsIn each treatment period, participants (n = 54) received canagliflozin 300 mg or dapagliflozin 10 mg for 4 days (20 min before breakfast). A mixed‐meal tolerance test (600 kcal; 75 g glucose) was performed at baseline and on day 4 of each treatment period to assess changes in incremental PPG (PPGΔAUC0–2 h). We measured 24‐h UGE and plasma glucose on day 4 to determine 24‐h mean RTG.ResultsCanagliflozin 300 mg and dapagliflozin 10 mg had similar effects on UGE and RTG for 4 h after dosing, but canagliflozin was associated with higher UGE and greater RTG reductions for the remainder of the day. Mean 24‐h UGE was ∼25% higher with canagliflozin than with dapagliflozin (51.4 vs. 40.8 g), and 24‐h mean RTG was ∼0.4 mmol/l (7 mg/dl) lower with canagliflozin than with dapagliflozin (3.79 vs. 4.17 mmol/l; p < 0.0001). Dapagliflozin had no effect on PPG excursion; canagliflozin delayed and reduced PPG excursion (between‐treatment difference in PPGΔAUC0–2 h from baseline expressed as a percentage of baseline mean, −10.2%; p = 0.0122). Canagliflozin and dapagliflozin were generally well tolerated.ConclusionsIn healthy participants, canagliflozin 300 mg provided greater 24‐h UGE, a lower RTG and smaller PPG excursions than dapagliflozin 10 mg.
Preferential assembly of heteromeric small conductance calcium‐activated potassium channels
Authors: Church Timothy W. , Weatherall Kate L. , Corrêa Sonia A. L. , Prole David L. , Brown Jon T. , Marrion Neil V. 
Published: November 2014

AbstractThe activation of small conductance calcium‐dependent (SK) channels regulates membrane excitability by causing membrane hyperpolarization. Three subtypes (SK1‐3) have been cloned, with each subtype expressed within the nervous system. The locations of channel subunits overlap, with SK1 and SK2 subunits often expressed in the same brain region. We showed that expressed homomeric rat SK1 subunits did not form functional channels, because subunits accumulated in the Golgi. This raised the question of whether heteromeric channels could form with SK1 subunits. The co‐expression of SK1 and SK2 subunits in HEK293 cells preferentially co‐assembled to produce heteromeric channels with a fixed stoichiometry of alternating subunits. The expression in hippocampal CA1 neurons of mutant rat SK1 subunits [rat SK1(LV213/4YA)] that produced an apamin‐sensitive current changed the amplitude and pharmacology of the medium afterhyperpolarization. The overexpression of rat SK1(LV213/4YA) subunits reduced the sensitivity of the medium afterhyperpolarization to apamin, substantiating the preferential co‐assembly of SK1 and SK2 subunits to form heteromeric channels. Species‐specific channel assembly occurred as the co‐expression of human SK1 with rat SK2 did not form functional heteromeric channels. The replacement of two amino acids within the C‐terminus of rat SK2 with those from human SK2 permitted the assembly of heteromeric channels when co‐expressed with human SK1. These data showed that species‐specific co‐assembly was mediated by interaction between the C‐termini of SK channel subunits. The finding that SK channels preferentially co‐assembled to form heteromeric channels suggested that native heteromeric channels will predominate in cells expressing multiple SK channel subunits.
CpGB DNA activates dermal macrophages and specifically recruits inflammatory monocytes into the skin
Authors: Mathes Allison L. , Rice Lisa , Affandi Alsya J. , DiMarzio Michael , Rifkin Ian R. , Stifano Giuseppina , Christmann Romy B. , Lafyatis Robert 
Published: November 2014

AbstractToll‐like receptor 9 (TLR9) drives innate immune responses after recognition of foreign or endogenous DNA containing unmethylated CpG motifs. DNA‐mediated TLR9 activation is highly implicated in the pathogenesis of several autoimmune skin diseases, yet its contribution to the inflammation seen in these diseases remains unclear. In this study, TLR9 ligand, CpGB DNA, was administered to mice via a subcutaneous osmotic pump with treatment lasting 1 or 4 weeks. Gene expression and immunofluorescence analyses were used to determine chemokine expression and cell recruitment in the skin surrounding the pump outlet. CpGB DNA skin treatment dramatically induced a marked influx of CD11b+ F4/80+ macrophages, increasing over 4 weeks of treatment, and induction of IFNγ and TNFα expression. Chemokines, CCL2, CCL4, CCL5, CXCL9 and CXCL10, were highly induced in CpGB DNA‐treated skin, although abrogation of these signalling pathways individually did not alter macrophage accumulation. Flow cytometry analysis showed that TLR9 activation in the skin increased circulating CD11b+ CD115+ Ly6Chi inflammatory monocytes following 1 week of CpGB DNA treatment. Additionally, skin‐resident CD11b+ cells were found to initially take up subcutaneous CpGB DNA and propagate the subsequent immune response. Using diphtheria toxin‐induced monocyte depletion mouse model, gene expression analysis demonstrated that CD11b+ cells are responsible for the CpGB DNA‐induced cytokine and chemokine response. Overall, these data demonstrate that chronic TLR9 activation induces a specific inflammatory response, ultimately leading to a striking and selective accumulation of macrophages in the skin.
The solution structure of the transducin‐α–uncoordinated 119 protein complex suggests occlusion of the Gβ1γ1‐binding sites
Authors: Cheguru Pallavi , Majumder Anurima , Yadav Ravi , Gopalakrishna Kota N. , Gakhar Lokesh , Artemyev Nikolai O. 
Published: November 2014

Uncoordinated 119 protein (UNC119) is a partner of transducin‐α subunit (Gαt) that is essential for transducin trafficking in rod photoreceptors. The interaction is known to involve binding of the acylated N terminus of Gαt to the hydrophobic pocket of UNC119. To gain insights into the mechanism of transducin trafficking, we isolated a highly pure protein complex between myristoylated chimeric Gαt (Gαt*) and UNC11950–240, and examined the solution structure by small angle X‐ray scattering and chemical crosslinking. The solution structure of the Gαt–UNC11950–240 complex was derived with rigid body/ab initio modeling against the small angle X‐ray scattering data by use of known atomic structures of Gαt and UNC119, and a distance constraint based on the protein crosslinking with p‐phenyldimaleimide. The model of the Gαt–UNC11950–240 complex indicates rotation and bending of the N‐terminal α‐helix of Gαt from its position in the structure of the heterotrimeric G‐protein transducin (Gt). This allows a considerably more compact complex conformation, which also suggests a novel interface involving the switch II/α3–β5 surface of Gαt. Supporting a novel interface, UNC119 was found to bind full‐length Gαt* more strongly than the Gαt N‐terminal peptide. Furthermore, UNC119 competed with the effector molecule phosphodiesterase‐6 γ‐subunit, which is known to bind to the same surface of Gαt. The solution structure of the Gαt–UNC119 complex suggests that the ability of UNC119 to dissociate Gt subunits and release Gαt from the membrane is attributable to disruption and sterical occlusion of the Gβ1γ1‐binding sites on Gαt.
Rhizosphere processes are quantitatively important components of terrestrial carbon and nutrient cycles
Authors: Finzi Adrien C. , Abramoff Rose Z. , Spiller Kimberly S. , Brzostek Edward R. , Darby Bridget A. , Kramer Mark A. , Phillips Richard P. 
Published: November 2014

AbstractWhile there is an emerging view that roots and their associated microbes actively alter resource availability and soil organic matter (SOM) decomposition, the ecosystem consequences of such rhizosphere effects have rarely been quantified. Using a meta‐analysis, we show that multiple indices of microbially mediated C and nitrogen (N) cycling, including SOM decomposition, are significantly enhanced in the rhizospheres of diverse vegetation types. Then, using a numerical model that combines rhizosphere effect sizes with fine root morphology and depth distributions, we show that root‐accelerated mineralization and priming can account for up to one‐third of the total C and N mineralized in temperate forest soils. Finally, using a stoichiometrically constrained microbial decomposition model, we show that these effects can be induced by relatively modest fluxes of root‐derived C, on the order of 4% and 6% of gross and net primary production, respectively. Collectively, our results indicate that rhizosphere processes are a widespread, quantitatively important driver of SOM decomposition and nutrient release at the ecosystem scale, with potential consequences for global C stocks and vegetation feedbacks to climate.
Decentralised forest management: towards a utopian realism
Authors: Nuesiri Emmanuel O 
Published: November 2014

The utopian impulse is the human longing to build the best of all possible worlds imaginable through social theories, policy discourses, legal texts, and institutional structures. The utopian impulse is evident in the meta‐narratives behind human institutions. In developing countries includingCameroon, the utopian impulse has influenced the transition from fortress conservation to contemporary decentralised forestry paradigm. Decentralised forestry not only wishes to save the forest but calls for an equitable and just forestry sector. Decentralised forestry at its core is a utopian vision for a best of all possible worlds imaginable for forest‐dependent people. However, utopia inspires both loyalty and opposition; it enchants and threatens all at once. It is therefore not surprising that contemporary decentralised forestry paradigm, with its lofty rhetoric of social justice as integral to saving the tropical forest, has faced opposition. This article argues that insights from utopian studies would help decentralised forestry advocates to be better prepared to respond to opposition they experience in their work.With commentary by Asiyanbi (2015)
Computer‐predicted peptides that mimic discontinuous epitopes on the A2 domain of factor VIII
Authors: Lebreton A. , Simon N. , Moreau V. , Demolombe V. , Cayzac C. , Nguyen C. , Schved J.‐F. , Granier C. , Lavigne‐Lissalde G. 
Published: November 2014

SummaryDevelopment of antibodies (Abs) against factor VIII (FVIII) is a severe complication of haemophilia A treatment. Recent publications suggest that domain specificity of anti‐FVIII antibodies, particularly during immune tolerance induction (ITI), might be related to the outcome of the treatment. Obtaining suitable tools for a fine mapping of discontinuous epitopes could thus be helpful. The aim of this study was to map discontinuous epitopes on FVIII A2 domain using a new epitope prediction functionality of the PEPOP bioinformatics tool and a peptide inhibition assay based on the Luminex technology. We predicted, selected and synthesized 40 peptides mimicking discontinuous epitopes on the A2 domain of FVIII. A new inhibition assays using Luminex technology was performed to identify peptides able to inhibit the binding of anti‐A2 Abs to A2 domain. We identified two peptides (IFKKLYHVWTKEVG and LYSRRLPKGVKHFD) able to block the binding of anti‐A2 allo‐antibodies to this domain. The three‐dimensional representation of these two peptides on the A2 domain revealed that they are localized on a limited region of A2. We also confirmed that residues 484–508 of the A2 domain define an antigenic site. We suggest that dissection of the antibody response during ITI using synthetic peptide epitopes could provide important information for the management of patients with inhibitors.