bluuebunny/crossref_metadata_2025 huggingface dataset:
Antinociceptive properties of esculetin in non‐inflammatory and inflammatory models of pain in rats
Authors: Rzodkiewicz Przemyslaw , Gasinska Emilia , Maslinski Slawomir , Bujalska‐Zadrozny Magdalena
Published: November 2014

Some studies suggest that 5‐lipoxygenase (5‐LOX) inhibition or leukotriene receptor antagonism may effectively attenuate different kinds of pain. In the present study, we investigated whether esculetin (which, among other actions, potently inhibits 5‐LOX) possesses analgesic activity in acute non‐inflammatory pain and acute inflammatory pain models in rats. We also examined the effects of zileuton, a selective 5‐LOX inhibitor, on esculetin activity. Plasma concentrations of leukotriene B4 (LTB4) after administration of esculetin were also determined. Esculetin (1.25–20 mg/kg, i.p.) dose‐dependently alleviated hyperalgesia and exhibited antinociceptive effects in both experimental models. The greatest effect of esculetin was observed with a dose of 20 mg/kg. In carrageenan‐induced inflammatory pain in rats, 20 mg/kg esculetin reversed or mitigated hyperalgesia, increasing the threshold to mechanical stimuli from a control value of −23.8 ± 1.8% to 15.2 ± 2.2% (P < 0.01) and that to thermal stimuli from −52.5 ± 6.1% to −9.5 ± 3.9% (P < 0.01). In non‐inflammatory pain, after esculetin (20 mg/kg) administration the threshold values to mechanical and thermal stimuli increased to 75.9 ± 4.2% and 59.2 ± 4.3%, respectively (P < 0.01 for both). Zileuton (30 mg/kg, p.o.) alone slightly but significantly increased the pain threshold in the non‐inflammatory and inflammatory acute pain models. Pretreatment with 30 mg/kg, p.o., zileuton significantly enhanced the analgesic activity of 5 mg/kg, i.p., esculetin in both pain models. Moreover, esculetin (10 mg/kg, i.p.) decreased LTB4 concentrations in the blood from 244 ± 29 pg/mL in the control group to 185 ± 11 pg/mL (P < 0.005). The results of the present study suggest the involvement of the 5‐LOX pathway in esculetin analgesia.
The production of nitric oxide by marine ammonia‐oxidizing archaea and inhibition of archaeal ammonia oxidation by a nitric oxide scavenger
Authors: Martens‐Habbena Willm , Qin Wei , Horak Rachel E. A. , Urakawa Hidetoshi , Schauer Andrew J. , Moffett James W. , Armbrust E. Virginia , Ingalls Anitra E. , Devol Allan H. , Stahl David A.
Published: November 2014

Nitrification is a critical process for the balance of reduced and oxidized nitrogen pools in nature, linking mineralization to the nitrogen loss processes of denitrification and anammox. Recent studies indicate a significant contribution of ammonia‐oxidizing archaea (AOA) to nitrification. However, quantification of the relative contributions of AOA and ammonia‐oxidizing bacteria (AOB) to in situ ammonia oxidation remains challenging. We show here the production of nitric oxide (NO) by Nitrosopumilus maritimus SCM1. Activity of SCM1 was always associated with the release of NO with quasi‐steady state concentrations between 0.05 and 0.08 μM. NO production and metabolic activity were inhibited by the nitrogen free radical scavenger 2‐phenyl‐4,4,5,5,‐tetramethylimidazoline‐1‐oxyl‐3‐oxide (PTIO). Comparison of marine and terrestrial AOB strains with SCM1 and the recently isolated marine AOA strain HCA1 demonstrated a differential sensitivity of AOB and AOA to PTIO and allylthiourea (ATU). Similar to the investigated AOA strains, bulk water column nitrification at coastal and open ocean sites with sub‐micromolar ammonia/ammonium concentrations was inhibited by PTIO and insensitive to ATU. These experiments support predictions from kinetic, molecular and biogeochemical studies, indicating that marine nitrification at low ammonia/ammonium concentrations is largely driven by archaea and suggest an important role of NO in the archaeal metabolism.
Economic deviance (Respond to this article at http://www.therai.org.uk/at/debate)
Authors: Carrier James G.
Published: November 2014

Making sense of what went wrong during the recent financial crises requires us to go beyond the conventional view of deviance. We need a more systematic and social view of financial deviance, and have long had the intellectual tools to do so. They include Durkheim and Merton's work, invoked here to pose pertinent questions about the deviant behaviour of corporations and institutions.
From plate to pet: Promotion of trans‐species companionship by Korean animal activists
Authors: Dugnoille Julien
Published: November 2014

In Korea cats and dogs are both pets and food. This article looks at how Korean activists bring the issue of animal welfare to the attention of Korean society in the context of cat and dog meat consumption. It explores the ways in which activists deploy rescue narratives in order to attract families willing to adopt rescued animals, thus transforming people's perception of livestock animals into that of potential lifetime companions. Combined here are the Confucian virtue of impartial benevolence and 18th‐century Western moral philosophy.
Boredom and crisis in the humanitarian realm (Respond to this article at http://www.therai.org.uk/at/debate)
Authors: De Lauri Antonio
Published: November 2014

‘Humanitarian boredom’ produces its own perspective on the world, providing a ‘point of entry’ to the observation of humanitarianism in practice. In this paper, while problematizing both a general understanding of boredom and a romantic idea of humanitarianism, the author focuses on boredom as experienced by humanitarian workers during crises in the humanitarian realm.
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

The 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

Objective

Imaging 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.

Methods

A 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.

Results

A 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.

Conclusions

A 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

This 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.
Problematising participatory video with youth inCanada: the intersection of therapeutic, deficit and individualising discourses
Authors: Rogers Matt
Published: November 2014

This paper draws on critical discourse analysis to explore power dynamics in a participatory video project that took place in an alternative education centre inNewBrunswick,Canada. The paper addresses growing concerns at the paucity of critical scholarship devoted to participatory video research. Often championed for its democratic, critical and counter‐hegemonic potential, participatory video has steadily gained favour in academic, developmental and educational contexts. However, practitioners implementing participatory approaches often fail to engage with issues of power. This oversight has meant that taken‐for‐granted assumptions about participatory video have often gone unquestioned. Appreciating this concern, this paper explores how power operates through individualising and deficit discourses in participatory video work with youth and how these discourses might reinforce oppressive thinking, consequently adversely impacting those who participate. This critique accents the importance of challenging taken‐for‐granted assumptions about participatory video by showing how the method can be shaped by, and play into, marginalising discourses. For practitioners, this is a reminder that power operates through all research and educational practices – even those claiming to be participatory, critical and counter‐hegemonic. The paper adds to a growing body of scholarship that draws attention to complexities associated with participatory video and relocates it within the framework of critical participatory research.
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

This 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

The 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

Thermogenesis 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.
The Impact of Bandung City's Rapid Development on children's Independent Mobility and Access to Friendly Play Environments
Authors: Drianda Riela Provi , Kinoshita Isami , Said Ismail
Published: November 2014

This study explored the extent to which the enormous development in Bandung City, Indonesia has some bearing on local children as the youngest inhabitants. In particular, it focused on the issue of children's independent mobility and the availability of friendly play environments in children's neighbourhoods. The result of this study showed that the development of Bandung City has created a disparity in access regarding children's opportunities for mobility as well as participation in friendly play environments. This study identified that many children were allowed to visit two places — local shops and the local mosque — without accompanying elders. This study also recognised children's desires to have appropriately designed play spaces, such as parks that are equipped with play equipment and rich in nature. Thus, this study argues the necessity to preserve the remaining and add a significant number of new, free, outdoor play spaces in the city.
What's Wrong with Being Poor? The Problems of Poverty, as Young People Describe them
Authors: Farthing Rys
Published: November 2014

This article explores how young people living in low‐income neighbourhoods problematise their own lives, using data generated as part of a participatory policy project with five groups of young people, aged 11–21. Three common problems were identified; housing, education and crime, as well as one common silence around their own agency. This silence is perhaps substituted by a focus on collective agency and politics, suggesting that perhaps young people can see poverty as a more collective problem than previous research may highlight.
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

Aims

To 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.

Methods

In 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.

Results

Canagliflozin 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.

Conclusions

In 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

The 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

Toll‐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

While 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)
Global changes, livestock and vulnerability: the social construction of markets as an adaptive strategy
Authors: Gautier Denis , Locatelli Bruno , Corniaux Christian , Alary Véronique
Published: November 2014

Nowadays, livestock producers in Sahel have to deal not only with climate variability but also with changes in land use and policies that restrict access to pasture and increase their vulnerability. At the same time, the growth of urban livestock markets both nationwide and in neighbouring countries is creating opportunities for producers. However, few studies have examined the role of markets in the adaptive strategies of livestock producers in West Africa, the changes in strategies for capturing market opportunities and the social interactions that lead to changes in market access and functioning. This paper addresses the question of how livestock producers and traders have transformed their producing and marketing strategies in response to climate variability and land access constraints. Our proposed conceptual framework on markets, vulnerability and adaptation considers that adaptive strategies include the social construction of markets through which market access is based on social networks and follows the norms and rules embedded in the complexity of these networks. This proactive strategy of stakeholders, through a socially constructed market access, allows traders to harness opportunities and livestock producers to adapt to climatic and land access constraints. We apply the framework in a case study in the region of Niono and Ségou in the Niger Inner delta in Mali. Results show that livestock producers and traders have changed their livestock‐raising and marketing strategies in response to the challenges faced by livestock producers and the emerging market opportunities. This study highlights the importance of considering the social construction of livestock market systems and marketing behaviours as adaptive strategies of livestock producers to multiple changes. Although livestock markets can support the adaptive strategies of several types of producers, their functioning as institutions has been understudied and scantily addressed in policy.
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

Development 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.
Modern carbonate sedimentary facies on the outer shelf and slope around New Caledonia
Authors: Yamano Hiroya , Cabioch Guy , Pelletier Bernard , Chevillon Christophe , Tachikawa Hiroyuki , Lefêvre Jérôme , Marchesiello Patrick
Published: November 2014

We investigated surface carbonate sediments at 33 sites on the outer shelf and slope around New Caledonia (163°–167°E, 20°–23°S), at water depths of 75–720 m. Four carbonate sedimentary facies are recognized on the basis of sediment size fractions and predominant constituents: Facies 1, encrusted grains (rhodoliths and macroids), bryozoa, and benthic foraminifera; Facies 2, bryozoa, benthic foraminifera, and mud; Facies 3, plankton and mud; and Facies 4, ahermatypic corals. Facies distributions were constrained primarily by water depth, and secondarily by local seafloor geomorphology that, in some areas, allows transport of sediments to deeper water. Because the dominant facies (Facies 1 and 3), as well as lagoon and basin facies, are distributed worldwide at similar latitudes, facies around New Caledonia can be considered as representative of carbonate sedimentary facies distributed in tropical–subtropical regions.
In vitro evaluation of a novel biofilm remover
Authors: Hofer D , Meier A , Sener B , Guggenheim B , Attin T , Schmidlin PR
Published: November 2014

Objective

To evaluate a novel device for its efficacy in removing experimental biofilm from root surfaces and its potential for concomitantly removing/roughening the surface substance.

Methods and Materials

A novel acrylic rotary device (biofilm remover, BR) was tested in vitro in three experiments: surface loss, surface roughness [positive controls: Perioset (PS) and Proxoshape (PR)] and biofilm removal [positive controls: ultrasonic (US) and PS]. Surface loss/surface roughness was evaluated for dentin samples instrumented for three 20 s periods. The calcium removed during instrumentation was analysed after each interval and cumulatively, using atomic absorption spectrophotometry (AAS). Surface roughness was measured using profilometric analysis. Biofilm removal was evaluated on dentin specimens coated with a 64.5 h 6‐species in vitro formed biofilm, after one 20 s treatment. Surface loss was analysed using anova with Scheffé post hoc test, and surface roughness/biofilm removal was analysed using Mann–Whitney test (all P ≤ 0.05).

Results

Significantly less substance loss [μg (±1 SD)] was observed with the novel device at all time points, both interval and cumulative (1.0 (±0.5) versus 9.3 (±3.2) PS and 9.9 (±1.9) PR at 60 s). Surface roughness [μm (95% CI)] was significantly lower for BR than for PS and PR [0.00 (−0.01, 0.08) 0.20 (0.16, 0.27) and 0.21 (0.19, 0.24) at 60 s]. Significantly less biofilm bacteria remained after treatment with both BR 4.5 (−0.1, 16.2) and US 1.9 (−0.2, 14.3), compared to PS 52 (27.9, 82.1).

Conclusions

The novel biofilm remover was less damaging to dentin surfaces, while removing biofilm at least as effectively as devices used in this study.
Dental pulp stem cell responses to novel antibiotic‐containing scaffolds for regenerative endodontics
Authors: Kamocki K. , Nör J. E. , Bottino M. C.
Published: November 2014

Aim

To evaluate both the drug‐release profile and the effects on human dental pulp stem cells' (hDPSC) proliferation and viability of novel bi‐mix antibiotic‐containing scaffolds intended for use as a drug delivery system for root canal disinfection prior to regenerative endodontics.

Methodology

Polydioxanone (PDS)‐based fibrous scaffolds containing both metronidazole (MET) and ciprofloxacin (CIP) at selected ratios were synthesized via electrospinning. Fibre diameter was evaluated based on scanning electron microscopy (SEM) images. Pure PDS scaffolds and a saturated CIP/MET solution (i.e. 50 mg of each antibiotic in 1 mL) (hereafter referred to as DAP) served as both negative (nontoxic) and positive (toxic) controls, respectively. High‐performance liquid chromatography (HPLC) was performed to investigate the amount of drug(s) released from the scaffolds. WST‐1® proliferation assay was used to evaluate the effect of the scaffolds on cell proliferation. LIVE/DEAD® assay was used to qualitatively assess cell viability. Data obtained from drug release and proliferation assays were statistically analysed at the 5% significance level.

Results

A burst release of CIP and MET was noted within the first 24 h, followed by a sustained maintenance of the drug(s) concentration for 14 days. A concentration‐dependent trend was noticed upon hDPSCs' exposure to all CIP‐containing scaffolds, where increasing the CIP concentration resulted in reduced cell proliferation (P < 0.05) and viability. In groups exposed to pure MET or pure PDS scaffolds, no changes in proliferation were observed.

Conclusions

Synthesized antibiotic‐containing scaffolds had significantly lower effects on hDPSCs proliferation when compared to the saturated CIP/MET solution (DAP).
Microwave‐Assisted Production of Amorphous Calcium Magnesium Phosphate: Study From Co‐Precipitation to Sintered Products
Authors: Zhou Huan , Kong Shiqin , Liu Zhiwei , Shi Xiaohao , Luo Mingzhi , Deng Linhong
Published: November 2014

Under microwave irradiation, agglomerates of nanospherical amorphous calcium magnesium phosphate (ACMP) particles were precipitated from a source solution with Ca2+, Mg2+, and PO43−. These precipitates were achieved when Mg2+ was added no less than three times concentrated of Ca2+. Otherwise, the as‐precipitated powder would only be a mixture of brushite (DCPD) and calcium sodium phosphate (CNP) with poor Mg2+ substitution. As compared to the mixture of DCPD and CNP, the as‐formed ACMP presented great densification during sintering. Moreover, the as‐sintered products were bioactive with final composition of magnesium pyrophosphate (MPP), β‐tricalcium phosphate (β‐TCP), and calcium pyrophosphate (CPP).
From the state to the family or to the market? Consequences of reduced residential eldercare in Sweden
Authors: Ulmanen Petra , Szebehely Marta
Published: November 2014

This article analyses the changing roles of the state, family and market in providing care for older people in Sweden, in relation to Scandinavian welfare ideals of universalism and de‐familisation. Since 2000 every fourth residential care bed has disappeared and the increase in homecare services has not compensated for the decline. Instead family care (defined here as help from adult children and other non‐cohabiting family or friends) has increased in all social groups: help by daughters mainly among older people with shorter education and help by sons among those highly educated. Use of privately purchased services has also increased but continues to play a marginal role. Family care remains more common among older people with less education whereas privately purchased services are more common among those with higher education. This dualisation of care challenges universalism, and working‐class daughters continue to be most affected by eldercare cutbacks.
Ending poverty in Mongolia: From socialism to social development
Authors: Smith Richard J.
Published: November 2014

While recent literature on social welfare has included Asian countries, less is known about low‐income and former socialist countries in Central Asia. This article combines a documentary‐historical method with a value‐critical approach to analyze Mongolia's social policy response to poverty. Mongolia is unique in Asia because it transformed from nomadic pastoralism to socialism without a phase of capitalist industrial development. The case study found that Mongolia lost social welfare when it transitioned from socialism, a statist model, to market liberalism and multiparty democracy. In the 21st century, Mongolia has been aspiring to promote social development by redirecting mining revenues to a human development fund. Mongolia is potentially an exemplar of social development strategies affirmed at the United Nations Conference for Social Development (Rio+20) regarding a green economy for inclusive growth and poverty elimination. Future social welfare research should consider the importance of sustainability.

Key Practitioner Message: ● Global standards for tracking poverty alleviation will be integrated with sustainability measures beginning in 2015; ● Mongolia hopes to foster social development and sustainable livelihoods by reinvesting revenues from mining into human capital and health care; ● To sustain future generations, social policy needs to consider the relationship between natural capital, social capital, and financial capital.
MicroRNAs of two medically important mosquito species: Aedes aegypti and Anopheles stephensi
Authors: Hu W. , Criscione F. , Liang S. , Tu Z.
Published: November 2014

MicroRNAs (miRNAs) are endogenous, single‐stranded small RNAs that have important regulatory functions at the post‐transcriptional level. In the present study, we characterize miRNAs in two divergent mosquito species, Aedes aegypti and Anopheles stephensi, through deep sequencing of small RNAs spanning all developmental stages. We discovered eight novel miRNAs in Ae. aegypti and 20 novel miRNAs in An. stephensi, which enabled the first systematic analysis of miRNA evolution in mosquitos. We traced the phylogenetic history of all miRNAs in both species and report a rate of 0.055–0.13 miRNA net gain per million years. Most novel miRNAs originate de novo. Duplications that produced miRNA clusters and families are more common in Ae. aegypti than in An. stephensi. We also identified arm‐switch as a source of new miRNAs. Expression profile analysis identified mosquito‐specific miRNAs that showed strong stage‐specific expression in one or both lineages. For example, the aae‐miR‐2941/2946 family represents the most abundant maternally deposited and zygotically transcribed miRNAs in Ae. aegypti. miR‐2943 is a highly expressed zygotic miRNA in both Ae. aegypti and An. stephensi. Such information provides the basis from which to study the function of these miRNAs in biology common to all mosquitos or unique to one particular lineage.
Toll‐like receptor 8 deletion accelerates autoimmunity in a mouse model of lupus through a Toll‐like receptor 7‐dependent mechanism
Authors: Tran Ngoc Lan , Manzin‐Lorenzi Céline , Santiago‐Raber Marie‐Laure
Published: November 2014

Systemic lupus erythematosus is an autoimmune disorder characterized by increased levels of lymphocyte activation, antigen presentation by dendritic cells, and the formation of autoantibodies. This leads to immune complex‐mediated glomerulonephritis. Toll‐like receptor 7 (T7) and TLR9 localize to the endosomal compartment and play important roles in the generation of autoantibodies against nuclear components, as they recognize RNA and DNA, respectively. In contrast, very little is known about endogenous TLR8 activation in mice. We therefore tested whether TLR8 could affect autoimmune responses in a murine model of lupus. We introduced a Tlr8 null mutation into C57BL/6 mice congenic for the Nba2 (NZB autoimmunity 2) locus and bearing the Yaa (Y‐linked autoimmune acceleration) mutation containing a tlr8 duplicated gene, and monitored disease development, autoantibody production, and glomerulonephritis‐associated mortality. Cellular responses were investigated in female Nba2.TLR8−/− mice bearing no copy of tlr8. The TLR8 deficiency accelerated disease progression and mortality, increased the number of circulating antibodies and activated monocytes, and heightened cellular responses to TLR7 ligation. TLR8‐deficient antigen‐presenting cells exhibited increased levels of MHC class II expression. The ability of dendritic cells to present antigens to allogeneic T cells after TLR7 ligation was also improved by TLR8 deficiency. TLR8 deletion accelerated autoimmunity in lupus‐prone mice in response to TLR7 activation. Antigen‐presenting cell function seemed to play a key role in mediating the effects of TLR8 deficiency.
Contribution of Different Organs to Grain Filling in Durum Wheat under Mediterranean Conditions I. Contribution of Post‐Anthesis Photosynthesis and Remobilization
Authors: Merah O. , Monneveux P.
Published: November 2014

Under Mediterranean conditions, drought affects cereals production principally through a limitation of grain filling. In this study, the respective role of post‐anthesis photosynthesis and carbon remobilization and the contribution of flag leaf, stem, chaff and awns to grain filling were evaluated under Mediterranean conditions in durum wheat (Triticum turgidum var. durum) cultivars. For the purpose, we examined the effects of shading and excision of different parts of the plant and compared carbon isotope discrimination (Δ) in dry matter of flag leaf, stem, chaff, awns and grain at maturity and in sap of stem, flag leaf, chaff and awns, this last measurement providing information on photosynthesis during a short period preceding sampling. Source–sink manipulations and isotopic imprints of different organs on final isotope composition of the grain confirmed the high contribution of both carbons assimilated by ears and remobilized from stems to grain filling, and the relatively low contribution of leaves to grain filling. Grain Δ was highly and significantly associated with grain yield across treatments, suggesting the utilization of this trait as an indicator of source–sink manipulations effects on grain yield. Chaff and awns Δ were better correlated with grain Δ than stem and leaf Δ, indicating that chaff were more involved in grain filling than other organs. Moreover, in chaff, sap Δ was highly significantly correlated with dry matter Δ. These results suggest the use of Δ for a rapid and non‐destructive estimation of the variation in the contribution of different organs to grain filling.