bluuebunny/crossref_metadata_2025 huggingface dataset:
Wilderness tourism – alleviating poverty through empowering local people
Authors: Ajagunna Ibrahim , Pinnock Fritz , Kerr Robert
Published: May 2014

Purpose

– This paper aims to examine how “wilderness tourism” is being successfully used to promote tourism development in the economically depressed community of Bangor Ridge in Jamaica. Through this promotion, its sponsor, Sun Venture Tours, has been able to create employment for local residents and in so doing, contribute to community development and poverty alleviation. The company has also been able to demonstrate that local entrepreneurs have the capacity to address issues in their communities with little or no reliance on government.

Design/methodology/approach

– The paper employs a qualitative research methodology using both primary and secondary data. The study focuses specifically on Bangor Ridge in Jamaica with Costa Rica and Belize used as comparators.

Findings

– This paper concludes that the exclusion of heritage assets from the government's development strategies for tourism in Jamaica has resulted in economic and social stagnation and a decline in economic opportunities for rural communities on the island where unemployment and poverty are rife. It argues that there is a strong case for consultation among all stakeholders as to the value of the country's natural assets and the future of tourism in Jamaica. The paper observes that tourism cannot be sustained unless Jamaica's natural assets are preserved and carefully utilized.

Originality/value

– This paper explores topical issues and provides a case study that clearly illustrates how government could redirect its interest in terms of support to local communities whose assets form the basis for tourism products on the island.
Contextual influences on employment of people with dual diagnosis: spinal cord injury and traumatic brain injury
Authors: Boyle Claire L. , Nott Melissa T. , Baguley Ian J. , Ranka Judy L.
Published: May 2014

Background/aim

Research into the paid employment of people with spinal cord injury or traumatic brain injury is prevalent; however, little research has examined the factors that may support employment for adults with a concomitant spinal cord injury and traumatic brain injury (dual diagnosis). This study aimed to determine the level of paid employment reported by people with dual diagnosis and to explore contextual factors that supported paid employment.

Methods

This cross‐sectional cohort study recruited 30 participants with dual diagnosis from a specialist spinal rehabilitation unit. Interviews were conducted during the first five years post‐rehabilitation discharge to determine level of paid employment and contextual factors that supported employment.

Results

At interview, 47% of participants were in paid employment. Employment type at interview indicated a shift away from more physically intensive jobs. Employed and unemployed participants reported a high level of social support and reported experiencing few physical or attitudinal barriers in their day to day lives. These environmental factors did not differentiate between employed and unemployed participants (z range = −0.98 to −0.17; P value range = 0.33–0.86). The most common facilitator of employment identified by participants was the personal factor – motivation (93% of employed participants).

Conclusion

When considering the impact of contextual factors on paid employment for people with a dual diagnosis of spinal cord injury/traumatic brain injury, personal factors may be of greater influence than environmental factors. Study participants experienced few physical or attitudinal barriers and reported highly supportive interpersonal relationships.
Trademarks andBritish dominance in consumer goods, 1876–1914
Authors: da Silva Lopes Teresa , Guimaraes Paulo
Published: May 2014

LateVictorianBritain was very important in the development ofBritish dominance in light consumer goods industries, such as fermented liquors and spirits; detergents and perfumery; bicycles and other carriages; paper, stationery, and bookbinding; and games of all kinds and sports goods. Firms developed technology‐based innovations and marketing‐based innovations, creating abnormal peaks of trademark registrations in certain industries. This article investigates those peaks and shows that factors usually pointed out as explainingBritish economic decline in heavy industries did not impact on the development of light consumer goods industries, and on the contrary encouraged their fast growth during this period. Trademark registrations are shown to provide new insights into the debate onBritish relative decline, when combined with other industry and firm‐level data.
External debt and commitment mechanisms:Danish borrowing inHolland, 1763–1825
Authors: van Bochove Christiaan
Published: May 2014

External borrowing constituted an important part of sovereign finances in early modernEurope. As payments could not be enforced through third parties, sovereigns had to convince lenders of their commitment to service their loans. Although the literature has dealt with this problem extensively, little is known about what supported lending in early modernEurope. This article therefore asks whether and how commitment mechanisms identified in the sovereign borrowing literature made external borrowing safer in early modernEurope. It attempts to answer this question by analysing the loans that a small and peripheral state (Denmark) issued inEurope's foremost international investment hub (eighteenth‐centuryHolland). Primary sources demonstrate thatDenmark inspired confidence in investors and serviced its loans well; a new dataset with securities prices reveals yields to maturity in accordance with this. Economic spillovers (domestic economic damage) and reputation (loss of access to external loans) are identified as the mechanisms that kept theDanish sovereigns committed to honouring their debts. TheDanish case shows, however, that these commitment mechanisms could only be adopted after the growth and integration of northernEurope's economies. This suggests that commitment mechanisms are not as universally applicable as the literature often seems to claim.
An Assessment of Patient Navigator Activities in Breast Cancer Patient Navigation Programs Using a Nine‐Principle Framework
Authors: Gunn Christine M. , Clark Jack A. , Battaglia Tracy A. , Freund Karen M. , Parker Victoria A.
Published: May 2014

Objective

To determine how closely a published model of navigation reflects the practice of navigation in breast cancer patient navigation programs.

Data Source

Observational field notes describing patient navigator activities collected from 10 purposefully sampled, foundation‐funded breast cancer navigation programs in 2008–2009.

Study Design

An exploratory study evaluated a model framework for patient navigation published by Harold Freeman by using an a priori coding scheme based on model domains.

Data Collection

Field notes were compiled and coded. Inductive codes were added during analysis to characterize activities not included in the original model.

Principal Findings

Programs were consistent with individual‐level principles representing tasks focused on individual patients. There was variation with respect to program‐level principles that related to program organization and structure. Program characteristics such as the use of volunteer or clinical navigators were identified as contributors to patterns of model concordance.

Conclusions

This research provides a framework for defining the navigator role as focused on eliminating barriers through the provision of individual‐level interventions. The diversity observed at the program level in these programs was a reflection of implementation according to target population. Further guidance may be required to assist patient navigation programs to define and tailor goals and measurement to community needs.
Taking Explanation Seriously in Political Science
Authors: Daigneault Pierre-Marc , Béland Daniel
Published: May 2014

The concept of ‘explanation’ has attracted considerable attention in the social sciences, and particularly within political science. However, scholars are not always familiar with what explaining political phenomena means, let alone with what it entails for developing sound causal arguments. This article introduces Craig Parsons’ typology of explanation before assessing its value for the causal analysis of political behaviour and processes. As argued, despite its limitations, this typology clearly maps four types of explanation in political science (institutional, ideational, structural and psychological) while helping scholars to combine them more rigorously when needed. This is why Parsons’ typology has the potential to move political scientists to the ‘next level’ as far as ‘explanation’ is concerned.
Intralipid therapy does not improve level of consciousness in overdoses with sedating drugs: A case series
Authors: Downes Michael A , Calver Leonie A , Isbister Geoffrey K
Published: May 2014

Objective

To assess the effect of intralipid emulsion therapy (ILE) in sedating drugs presenting to an urban emergency department.

Methods

Following the introduction of a clinical protocol for the use of ILE a retrospective chart review was undertaken, which describes the use of ILE in treating sedating drug overdose in a facility with a tertiary referral level clinical toxicology unit. Demographic data as well as details of drug ingested, physiological parameters and disposition were extracted from the medical record.

Results

Over a 7 month period nine cases were treated with intralipid, of which two were male and the median age was 33 years (17–52 years). Endotracheal intubation was required in seven cases and of the other two, one required a nasopharyngeal airway for several hours while being observed in a critical care area. One patient was managed in the intensive care unit without intubation. The median duration of ventilation in the seven patients was 31 h (22–82 h), and median length of stay for all nine cases was 63 h (24–133 h).

Conclusion

This study does not support any clinically significant effect of intralipid in sedating drug overdose.
Field trapping of the flathead oak borer Coroebus undatus (Coleoptera: Buprestidae) with different traps and volatile lures
Authors: Fürstenau Benjamin , Quero Carmen , Riba Josep Ma , Rosell Gloria , Guerrero Angel
Published: May 2014

The flathead oak borer Coroebus undatus F. (Coleoptera: Buprestidae) is one of the primary pests of cork oak Quercus suber L. in the Mediterranean region causing great economic losses to the cork industry. Very little is known about its biology and behavior and, so far, no control measures have been established. We present the results of a pilot study aimed to develop an efficient trapping method for monitoring this harmful pest. In a 3‐year field study, purple‐colored prism traps baited with a mixture of green leaf volatiles (GLVs) from the host have been shown the most effective combination to catch C. undatus adults (solely females) compared to other trap and lure types tested. Wavelength and reflectance measurements revealed that purple traps exhibit reflectance peak values similar to those found in the abdominal and elytral cuticle of both sexes, suggesting the involvement of visual cues for mate location in this species. The data presented are the first to demonstrate captures of adults of the genus Coroebus by an attractant‐based trapping method.
Learning and development opportunities as a tool for the retention of volunteers: a motivational perspective
Authors: Newton Cameron , Becker Karen , Bell Sarah
Published: May 2014

The growing reliance on volunteers in Australia has heightened the need for non‐profit organisations to retain these valuable resources. However, the current literature on volunteer retention is limited. One potential way volunteers can be retained is by providing learning and development opportunities (LDOs). This study investigates the relationship between volunteer perceptions of LDOs, their motivations for volunteering, and retention. Analyses revealed significant main effects for LDOs and volunteer motivations on retention and several interactive effects demonstrating that LDOs can have differential effects on retention depending on the reasons for volunteering.
Discovery and validation of genic single nucleotide polymorphisms in the Pacific oyster Crassostrea gigas
Authors: Wang Jiafeng , Qi Haigang , Li Li , Que Huayong , Wang Di , Zhang Guofan
Published: May 2014

The economic and ecological importance of the oyster necessitates further research on the molecular mechanisms, which both regulate the commercially important traits of the oyster and help it to survive in the variable marine environment. Single nucleotide polymorphisms (SNPs) have been widely used to assess genetic variation and identify genes underlying target traits. In addition, high‐resolution melting (HRM) analysis is a potentially powerful method for validating candidate SNPs. In this study, we adopted a rapid and efficient pipeline for the screening and validation of SNPs in the genic region of Crassostrea gigas based on transcriptome sequencing and HRM analysis. Transcriptomes of three wild oyster populations were sequenced using Illumina sequencing technology. In total, 50–60 million short reads, corresponding to 4.5–5.4 Gbp, from each population were aligned to the oyster genome, and 5.8 × 105 SNPs were putatively identified, resulting in a predicted SNP every 47 nucleotides on average. The putative SNPs were unevenly distributed in the genome and high‐density (≥2%), nonsynonymous coding SNPs were enriched in genes related to apoptosis and responses to biotic stimuli. Subsequently, 1,671 loci were detected by HRM analysis, accounting for 64.7% of the total selected candidate primers, and finally, 1,301 polymorphic SNP markers were developed based on HRM analysis. All of the validated SNPs were distributed into 897 genes and located in 672 scaffolds, and 275 of these genes were stress inducible under unfavourable salinity, temperature, and exposure to air and heavy metals. The validated SNPs in this study provide valuable molecular markers for genetic mapping and characterization of important traits in oysters.
Do male and female patients with chronic neck pain really have different health‐related physical fitness, depression, anxiety and quality of life parameters?
Authors: Yalcinkaya Hatice , Ucok Kagan , Ulasli Alper M. , Coban Necip F. , Aydin Sedat , Kaya Idris , Akkan Gokhan , Tugrul Senay Tugba
Published: May 2014

Aim

The purpose of this study was to investigate whole body physical fitness parameters such as maximal aerobic capacity (VO2max), muscle strength, trunk flexibility, daily physical activity, pulmonary function, body composition, anxiety and depression, as well as other disease‐related changes in patients with chronic neck pain (CNP), and to compare them with healthy controls.

Method

Eighty patients (40 male, 40 female) with CNP and 80 (40 male, 40 female) controls were included in this study. VO2max, handgrip and back‐leg strengths, trunk flexibility, daily physical activity, pulmonary function test (PFT), body composition and pressure pain threshold (PPT) measurements were carried out. Neck disability index (NDI), Beck anxiety inventory (BAI), Beck depression inventory (BDI), Pittsburg sleep quality index (PSQI), and Short‐Form health survey (SF‐36) questionnaires were applied to all participants.

Results

Handgrip and back‐leg strengths and suboccipital and paraspinal‐C7 PPTs and health‐related quality of life (HRQoL) were lower, and PSQI, BAI and BDI were higher, in female patients with CNP, compared to healthy controls; whereas, VO2max and HRQoL were lower, and body fat percantage and PSQI were higher, in male patients with CNP, compared to healthy controls. Trunk flexibility and PFT values were not significantly different between the patients and the controls in both genders.

Conclusion

We suggest that, on the basis of gender, consideration of not only the neck region but also whole body physical fitness, anxiety and depression parameters in patients with CNP might be helpful to the development of more benefical strategies for illness management.
The Role of Inflammation for a Successful Implantation
Authors: Dekel Nava , Gnainsky Yulia , Granot Irit , Racicot Karen , Mor Gil
Published: May 2014

Approximately half of all human embryo implantations result in failed pregnancy. Multiple factors may contribute to this failure, including genetic or metabolic abnormalities of the embryo. However, many of these spontaneous early abortion cases are attributed to poor uterine receptivity. Furthermore, although many fertility disorders have been overcome by a variety of assisted reproductive techniques, implantation remains the rate‐limiting step for the success of the in vitro fertilization (IVF) treatments. We, as well as others, have demonstrated that endometrial biopsies performed either during the spontaneous, preceding cycle, or during the IVF cycle itself, significantly improve the rate of implantation, clinical pregnancies, and live births. These observations suggest that mechanical injury of the endometrium may enhance uterine receptivity by provoking the immune system to generate an inflammatory reaction. In strong support of this idea, we recently found that dendritic cells (DCs), an important cellular component of the innate immune system, play a critical role in successful implantation in a mouse model. In this review, we discuss the hypothesis that the injury‐derived inflammation in the biopsy‐treated patients generates a focus for uterine DCs and Mac accumulation that, in turn, enhance the endometrial expression of essential molecules that facilitate the interaction between the embryo and the uterine epithelium.
Allergic rhinitis is a risk factor for traffic safety
Authors: Vuurman E. F. P. M. , Vuurman L. L. , Lutgens I. , Kremer B.
Published: May 2014

Background

Allergic rhinitis (AR) affects up to 30% of the adult population and symptomatic patients continue to engage in daily life activities, including car driving. Previous studies have shown that AR can impair cognitive functions, especially during longer‐lasting tasks. Other reports suggest negative effects on psychomotor functions such as driving, but no clear evidence has been presented yet.

Objectives

Primary objective was to determine the effect of AR per se on actual driving performance and compare it with the effects of treated AR.

Methods

Nineteen patients with documented AR history underwent a unique and validated 1‐h on‐the‐road driving test outside the pollen season. In a 4‐leg repeated measures design, patients underwent a nasal provocation test with either pollen or inactive control prior to the driving test. In the three conditions with pollen provocation, patients were pretreated with either cetirizine 10 mg, fluticasone furoate 27.5 μg, or placebo to alleviate the provoked AR symptoms.

Results

The driving performance of patients when symptomatic and not treated was significantly impaired compared to the placebo condition. When engaging in a secondary memory task during driving, their performance deteriorated further. The magnitude of impairment was relevant and comparable to that seen at a blood alcohol level of 0.05%, the legal limit in many countries. Treatment of AR symptoms partially counteracted the effect of AR on driving.

Conclusions

Untreated AR can impair driving ability and put patients at risk. Drug therapy reduces this impairment, and AR patients should therefore be advised to always treat their condition.
Year in Review, Public Anthropology, 2013: Webs of Meaning, Critical Interventions
Authors: Benson Peter
Published: May 2014

In this essay, I provide an overview of public anthropology from the year 2013, examining how anthropologists engaged public, socially relevant issues and brought anthropological understandings and expertise into public debates, conversations, and forums. In particular, I focus on the ways that the publication of anthropology is changing to reflect trends toward open‐access electronic publishing and new formats for scholarly and public discussion. I then highlight how anthropologists engaged with a set of specific issues and topics, including debates about same‐sex marriage in the United States; the trial of Efraín Ríos Montt, the former dictator of Guatemala who was tried and convicted of genocide last year; and the publication of a controversial new memoir by the anthropologist Napoleon Chagnon. Taken together, the sections of this essay disclose the significant ways that anthropologists have engaged with and contributed to public debates and contested issues.
Generic security concern influencing individual response to natural hazards: evidence from Shanghai, China
Authors: Xie Xin Lu , Lo Alex Y , Zheng Yan , Pan Jiahua , Luo Jing
Published: May 2014

Shanghai is a megacity located in a hazard‐prone region, but one in which local residents have not actively engaged in disaster risk management. This paper aims to identify factors of perception that influence residents' propensity to adopt risk‐mitigating measures. It presents results of a structured questionnaire survey administered to Shanghai residents. Results show that risk‐mitigating measures are deemed to be important if people: (1) have frequently experienced extreme weather; (2) believe that extreme weather events are severe in Shanghai; and (3) are concerned about other public risks confronting international society, such as energy security and terrorism. It is important to note that the third point has resulted in greater impacts than the other two factors. A cultural explanation is offered in this paper. Public risk awareness emanates from a generic concern over the security of the human world. This generic concern acts as a socio‐cultural backdrop that contextualises the ways in which individuals respond to natural hazards. The significance of this factor indicates the need for broadening the analytical scope of risk perception research in China. These findings are useful for local policymakers, emergency managers and community and aid organisations seeking to develop creative strategies for risk education and communication.
Diverse mechanisms underlying the regulation of ion channels by carbon monoxide
Authors: Peers C , Boyle J P , Scragg J L , Dallas M L , Al‐Owais M M , Hettiarachichi N T , Elies J , Johnson E , Gamper N , Steele D S
Published: May 2014

Carbon monoxide (CO) is firmly established as an important, physiological signalling molecule as well as a potent toxin. Through its ability to bind metal‐containing proteins, it is known to interfere with a number of intracellular signalling pathways, and such actions can account for its physiological and pathological effects. In particular, CO can modulate the intracellular production of reactive oxygen species, NO and cGMP levels, as well as regulate MAPK signalling. In this review, we consider ion channels as more recently discovered effectors of CO signalling. CO is now known to regulate a growing number of different ion channel types, and detailed studies of the underlying mechanisms of action are revealing unexpected findings. For example, there are clear areas of contention surrounding its ability to increase the activity of high conductance, Ca2+‐sensitive K+ channels. More recent studies have revealed the ability of CO to inhibit T‐type Ca2+ channels and have unveiled a novel signalling pathway underlying tonic regulation of this channel. It is clear that the investigation of ion channels as effectors of CO signalling is in its infancy, and much more work is required to fully understand both the physiological and the toxic actions of this gas. Only then can its emerging use as a therapeutic tool be fully and safely exploited.

Linked Articles

This article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-6
CCDI: a new ligand that modulates mammalian type 1 ryanodine receptor (RyR1)
Authors: Tian Chengju , Shao Chun Hong , Padanilam Christina , Ezell Edward , Singh Jaipaul , Kutty Shelby , Bidasee Keshore R
Published: May 2014

Background and Purpose

Ryanodine receptors (RyRs) are Ca2+‐release channels on the sarco(endo)plasmic reticulum that modulate a wide array of physiological functions. Three RyR isoforms are present in cells: RyR1, RyR2 and RyR3. To date, there are no reports on ligands that modulate RyR in an isoform‐selective manner. Such ligands are not only valuable research tools, but could serve as intermediates for development of therapeutics.

Experimental approach

Pyrrole‐2‐carboxylic acid and 1,3‐dicyclohexylcarbodiimide were allowed to react in carbon tetrachloride for 24 h at low temperatures and pressures. The chemical structures of the two products isolated were elucidated using NMR spectrometry, mass spectrometry and elemental analyses. [3H]‐ryanodine binding, lipid bilayer and time‐lapsed confocal imaging were used to determine their effects on RyR isoforms.

Key results

The major product, 2‐cyclohexyl‐3‐cyclohexylimino‐2, 3, dihydro–pyrrolo[1,2‐c]imidazol‐1‐one (CCDI) dose‐dependently potentiated Ca2+‐dependent binding of [3H]‐ryanodine to RyR1, with no significant effects on [3H]‐ryanodine binding to RyR2 or RyR3. CCDI also reversibly increased the open probability (Po) of RyR1 with minimal effects on RyR2 and RyR3. CCDI induced Ca2+ transients in C2C12 skeletal myotubes, but not in rat ventricular myocytes. This effect was blocked by pretreating cells with ryanodine. The minor product 2‐cyclohexyl‐pyrrolo[1,2‐c]imidazole‐1,3‐dione had no effect on either [3H]‐ryanodine binding or Po of RyR1, RyR2 and RyR3.

Conclusions and implications

A new ligand that preferentially modulates RyR1 was identified. In addition to being an important research tool, the pharmacophore of this small molecule could serve as a template for the synthesis of other isoform‐selective modulators of RyRs.
Rectification of impaired adipose tissue methylation status and lipolytic response contributes to hepatoprotective effect of betaine in a mouse model of alcoholic liver disease
Authors: Dou Xiaobing , Xia Yongliang , Chen Jing , Qian Ying , Li Songtao , Zhang Ximei , Song Zhenyuan
Published: May 2014

Background and Purpose

Overactive lipolysis in adipose tissue contributes to the pathogenesis of alcoholic liver disease (ALD); however, the mechanisms involved have not been elucidated. We previously reported that chronic alcohol consumption produces a hypomethylation state in adipose tissue. In this study we investigated the role of hypomethylation in adipose tissue in alcohol‐induced lipolysis and whether its correction contributes to the well‐established hepatoprotective effect of betaine in ALD.

Experimental Approach

Male C57BL/6 mice were divided into four groups and started on one of four treatments for 5 weeks: isocaloric pair‐fed (PF), alcohol‐fed (AF), PF supplemented with betaine (BT/AF) and AF supplemented with betaine (BT/AF). Betaine, 0.5% (w v−1), was added to the liquid diet. Both primary adipocytes and mature 3T3‐L1 adipocytes were exposed to demethylation reagents and their lipolytic responses determined.

Key Results

Betaine alleviated alcohol‐induced pathological changes in the liver and rectified the impaired methylation status in adipose tissue, concomitant with attenuating lipolysis. In adipocytes, inducing hypomethylation activated lipolysis through a mechanism involving suppression of protein phosphatase 2A (PP2A), due to hypomethylation of its catalytic subunit, leading to increased activation of hormone‐sensitive lipase (HSL). In line with in vitro observations, reduced PP2A catalytic subunit methylation and activity, and enhanced HSL activation, were observed in adipose tissue of alcohol‐fed mice. Betaine attenuated this alcohol‐induced PP2A suppression and HSL activation.

Conclusions and Implications

In adipose tissue, a hypomethylation state contributes to its alcohol‐induced dysfunction and an improvement in its function may contribute to the hepatoprotective effects of betaine in ALD.
The conservative view: is it necessary to implant a stent into the dopamine transporter?
Authors: Schmid D , Koenig X , Bulusu S , Schicker K , Freissmuth M , Sitte H H , Sandtner W
Published: May 2014

Linked Articles

This article is a reply to De Felice LJ and Cameron KN (2015). Comments on ‘A quantitative model of amphetamine action on the serotonin transporter’, by Sandtner et al., Br J Pharmacol 171: 1007–1018. Br J Pharmacol 172: this issue, doi: 10.1111/bph.12767, commenting on Sandtner W, Schmid D, Schicker K, Gerstbrein K, Koenig X, Mayer FP, Boehm S, Freissmuth M and Sitte HH (2014). A quantitative model of amphetamine action on the 5‐HT transporter. Br J Pharmacol 171: 1007–1018. doi: 10.1111/bph.12520
Interactions of hydrogen sulfide with myeloperoxidase
Authors: Pálinkás Zoltán , Furtmüller Paul G , Nagy Attila , Jakopitsch Christa , Pirker Katharina F , Magierowski Marcin , Jasnos Katarzyna , Wallace John L , Obinger Christian , Nagy Péter
Published: May 2014

Background and Purpose

The actions of hydrogen sulfide in human physiology have been extensively studied and, although it is an essential mediator of many biological functions, the underlying molecular mechanisms of its actions are ill‐defined. To elucidate the roles of sulfide in inflammation, we have investigated its interactions with human myeloperoxidase (MPO), a major contributor to inflammatory oxidative stress.

Experimental Approach

The interactions of sulfide and MPO were investigated using electron paramagnetic resonance, electronic circular dichroism, UV‐vis and stopped‐flow spectroscopies.

Key Results

We found favourable reactions between sulfide and the native‐ferric enzyme as well as the MPO redox intermediates, ferrous MPO, compound I and compound II. Sulfide was a potent reversible inhibitor of MPO enzymic activity with an IC50 of 1 µM. In addition, the measured second‐order rate constants for the reactions of sulfide with compound I [k = (1.1 ± 0.06) × 106 M−1 s−1] and compound II [k = (2.0 ± 0.03) × 105 M−1 s−1] suggest that sulfide is a potential substrate for MPO in vivo.

Conclusion and Implications

Endogenous levels of sulfide are likely to inhibit the activity of circulating and endothelium‐bound MPO. The fully reversible inhibition suggests a mediatory role of sulfide on the oxidant‐producing function of the enzyme. Furthermore, the efficient HOCl oxidation of sulfide to give polysulfides (recently recognized as important components of sulfide biology) together with MPO‐catalysed sulfide oxidation and the lack of interaction between MPO and sulfide oxidation products, predict a modulatory role of MPO in sulfide signalling.

Linked Articles

This article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-6
Deep vs. shallow controlling factors of the crustal thermal field – insights from 3D modelling of theBeaufort‐MackenzieBasin (ArcticCanada)
Authors: Sippel J. , Scheck‐Wenderoth M. , Lewerenz B. , Klitzke P.
Published: May 2014

Significant lateral variations in observed temperatures in theBeaufort‐MackenzieBasin raise the question on the temperature‐controlling factors. Based on the structural configuration of the sediments and underlying crust in the area, we calculate the steady‐state 3D conductive thermal field. Integrated data include the base of the relic permafrost layer representing the 0 °C‐isotherm, public‐domain temperature data (from 227 wells) and thermal conductivity data. For >75% of the wells the predicted temperatures deviate by <10 K from the observed temperatures, which validates the overall model setup and adopted thermal properties. One important trend reproduced by the model is a decrease in temperatures from the western to the eastern basin. While in the west, a maximum temperature of 185 °C is reached at 5000 m below sea level, in the east the maximum temperature is 138 °C. The main cause for this pattern lies in lateral variations in thermal conductivity indicating differences in the shale and sand contents of the different juxtaposed sedimentary units. North‐to‐south temperature trends reveal the superposition of deep and shallow effects. At the southern margin, where the insulating effect of the low‐conductive sediments is missing, temperatures are lowest. Farther north, where the sub‐sedimentary continental crust is thick enough to produce considerable heat and a thick pile of sediments efficiently stores heat, temperatures tend to be highest. Temperatures decrease again towards the northernmost distal parts of the basin, where thinned continental and oceanic crust produce less radiogenic heat. Wells with larger deviations of the purely conductive model from the temperature observations (>15 K at 10% of the wells) and their basin‐wide pattern of misfit tendency (too cold vs. too warm temperature predictions) point to a locally restricted coupling of heat transport to groundwater flow.
Novel 3‐Substituted Ocotillol‐Type Triterpenoid Derivatives as Antibacterial Candidates
Authors: Bi Yi , Ma Cong , Zhang Hengyuan , Zhou Zhiwen , Yang Jian , Zhang Zhenlei , Meng Qingguo , Lewis Peter J. , Xu Jinyi
Published: May 2014

Plant‐derived triterpenoid saponins are involved in the plant defense system by targeting bacterial membranes. A series of ocotillol‐type triterpenoid derivatives were synthesized starting from PPD, one of the main components of Panax ginseng and their antibacterial activity against several representative bacteria were evaluated. Compounds 5 and 11 exhibited excellent antibacterial activity with MIC values of 1 μg/mL against Staphylococcus aureus and 8 μg/mL and 4 μg/mL against Bacillus subtilis, respectively. Furthermore, when compounds 5 and 11 were combined with two commercial antibiotics kanamycin and chloramphenicol, they showed strong synergistic activity at sub‐MIC levels against S. aureus USA300 and B. subtilis 168. Moreover, chloramphenicol turned from a bacteriostatic to a bactericidal agent when combined with compound 11 against B. subtilis 168.
The effectiveness of age on HbA1c as a criterion for the diagnosis of diabetes in Chinese different age subjects
Authors: Yang Liyong , Shen Ximei , Yan Sunjie , Xu Feipeng , Wu Peiwen
Published: May 2014

Objective

To analyse the effectiveness of age on HbA1c as a criterion for the diagnosis of diabetes in Chinese different age subjects.

Methods

This retrospective study enrolled a total of 1147 outpatients with untreated newly diagnosed diabetes (aged 18–80 years, 42·55% women) from the Fujian Province, China, and 427 age and gender‐matched (control) subjects without diabetes. Receiver operating characteristic curve (ROC) was plotted to determine the performance of HbA1c against results of oral glucose tolerance test (OGTT) performed at the same time according to specific age groups. The ORs and 95%CIs between diabetes and other metabolic disorders were analysed.

Results

(i) HbA1c provided an age‐specific diagnosis for diabetes: there was a high diagnostic titter of HbA1c in the 18‐ to 39‐year age group; conversely, there was a low diagnostic titter of HbA1c in the ≥70‐year‐old age groups. (ii) After adjusted for age, individuals with diabetes by OGTT criteria but not by WHO HbA1c criteria had an increased chance of having abnormal weight, hypertriglyceridaemia, HDL hypocholesterolaemia and insulin resistance. (iii) The diagnostic cut‐off points of HbA1c for diabetes in different age groups (18–39, 40–49, 50–59, 60–69 and ≥70 years) were 6·1, 6·3, 6·4, 6·5 and 6·4, respectively. The age‐specific HbA1c criteria exhibited the higher positive rate, sensitivity and lower false‐negative rate when compared with WHO HbA1c criteria.

Conclusions

This provided evidence indicating that there may be drawbacks in the use of HbA1c in the diagnosis of diabetes. Thus, we proposed that the impact of introducing HbA1c for diabetes diagnosis should be considered in terms of age. Cohort studies are needed to further confirm the suitability of age‐specific HbA1c criteria for the diagnosis of diabetes.
Historical linguistics as a sequence optimization problem: the evolution and biogeography ofUto‐Aztecan languages
Authors: Wheeler Ward C. , Whiteley Peter M.
Published: May 2014

Language origins and diversification are vital for mapping human history. Traditionally, the reconstruction of language trees has been based on cognate forms among related languages, with ancestral protolanguages inferred by individual investigators. Disagreement among competing authorities is typically extensive, without empirical grounds for resolving alternative hypotheses. Here, we apply analytical methods derived fromDNAsequence optimization algorithms toUto‐Aztecan languages, treating words as sequences of sounds. Our analysis yields novel relationships and suggests a resolution to current conflicts about theProto‐Uto‐Aztecan homeland. The techniques used forUto‐Aztecan are applicable to written and unwritten languages, and should enable more empirically robust hypotheses of language relationships, language histories, and linguistic evolution.
BASI, A Potent Small Molecular Inhibitor, Inhibits Glioblastoma Progression by Targeting microRNA‐mediated β‐Catenin Signaling
Authors: Shi Zhen‐Dong , Qian Xiao‐Min , Zhang Jun‐Xia , Han Lei , Zhang Kai‐Liang , Chen Lu‐Yue , Zhou Xuan , Zhang Jian‐Ning , Kang Chun‐Sheng
Published: May 2014

Background and Aims

The nuclear localization of β‐catenin, a mediator of canonical Wnt signaling, has been indicated in a variety of cancers and is frequently related to tumor progression and metastasis. Therefore, targeting β‐catenin is an attractive therapeutic strategy for cancers.

Methods

Herein, we identified a natural, small molecule inhibitor of β‐catenin signaling, BASI, and evaluated its therapeutic efficacy both in vitro and in orthotopic mouse models of glioma.

Results

BASI significantly suppressed proliferation and invasion and induced apoptosis in glioblastoma cells and resulted in the remarkable attenuation of orthotopic tumor growth in vivo. Furthermore, we found that BASI altered the expression of several microRNAs, which mediated the posttranscriptional silencing of β‐catenin expression either directly or indirectly through a von Hippel‐Lindau (VHL)‐mediated β‐catenin degradation pattern.

Conclusions

Taken together, our findings offer preclinical validation of BASI as a promising new type of β‐catenin inhibitor with a mechanism of inhibition that has broad potential for the improved treatment of glioblastoma.
Tumour repopulation and the role of abortive division in squamous cell carcinomas during chemotherapy
Authors: Marcu L. G.
Published: May 2014

Objectives

In head and neck cancers, tumour cell repopulation during chemotherapy is one reason for treatment failure. Some of the mechanisms responsible for this repopulation are cell recruitment and abortive division. Due to lack of quantitative data in the literature regarding these mechanisms, the aim of this study was to investigate the interplay between recruitment and abortive division during cisplatin chemotherapy and to quantify the impact of these mechanisms on tumour control.

Materials and methods

An in silico Monte Carlo tumour model was developed to simulate tumour behaviour during chemotherapy. The virtual tumour had the composition and kinetic properties of a biological tumour. Effect of cisplatin on cell cycle and repopulation mechanisms were simulated and interpreted.

Results

Abortive division contributed to cell production within the tumour during chemotherapy. There was a strong relationship between recruitment and tumour growth due to abortive division. This observation was supported by the value of proliferative/stem ratio, which increased from 1.3 to 36, even when using small recruitment parameters.

Conclusions

While abortive division contributed towards tumour repopulation during chemotherapy, this mechanism could be controlled by daily doses of cisplatin. On the other hand, stem cells require an additional cytotoxic agent to overcome repopulation due to cell recruitment. Consequently, repopulation via abortive division during chemotherapy did not entail alterations in treatment schedule, nor dose escalation, to control the tumour.
Differential characteristics and in vitro angiogenesis of bone marrow‐ and peripheral blood‐derived endothelial progenitor cells: evidence from avian species
Authors: Shah Q. A. , Tan X. , Bi S. , Liu X. , Hu S.
Published: May 2014

Objectives

This study was conducted to compare phenotypes and in vitro angiogenic capacity of putative endothelial progenitor cells (EPCs) derived from bone marrow (BM) and peripheral blood (PB), from an avian species.

Materials and methods

Mononuclear cells were isolated from chicken BM and PB (BMMNCs and PBMNCs) and cultured in EGM‐2 medium. Cells at days 7–14 were used for the experiments. Expression of progenitor and endothelial markers, number of Dil–ac–LDL/lectin dual‐positive cells and adipogenic and osteogenic differentiation were determined. Migration and in vitro angiogenic ability between BMMNC‐ and PBMNC‐derived cells were compared.

Results

PBMNCs developed typical EPC appearance, with initial spindle shape followed by a cobblestone form, whereas BMMNC‐derived cells retained their constitutive spindle‐like morphology throughout the study. Cells derived from both sources expressed CD133, CD31 and VEGFR‐2, although PBMNCs‐derived cells had lower CD133 expression. Nevertheless, number of Dil–ac–LDL/lectin dual‐positive cells did not differ between groups. Adipogenic and osteogenic lineages were verified in BMMNC‐ but not in PBMNC‐derived cells. PBMNC‐derived cells formed tubular networks on Matrigel. However, BMMNC‐derived cells formed few tube‐like structures, which were not morphologically comparable to those developed by their counterparts.

Conclusion

Our results suggest that so called EPCs derived from BMMNCs are not ‘true’ EPCs, supporting previous findings on mammals that BM may not serve as an optimal isolation source of EPCs.
Hypermethylation of p15 Gene in Diffuse – Large B‐Cell Lymphoma: Association with Less Aggressiveness of the Disease
Authors: Krajnović Milena , Jovanović Maja Peruničić , Mihaljević Biljana , Anđelić Boško , Tarabar Olivera , Knežević‐Ušaj Slavica , Krtolica Koviljka
Published: May 2014

In this study, methylation‐specific polymerase chain reaction was used to investigate the potential prognostic significance of the methylation status of p15, p16, MGMT, and DAPK genes in 51 specimens of diffuse large B‐cell lymphoma (DLBCL). Hypermethylation of p15 gene was significantly more prevalent in patients without relapse (p = 0.001) and there was a trend toward more frequent presence of p15 methylation in patients without death outcome within 5‐year follow‐up period (p = 0.086) Also, there was a trend toward accumulation of p15 methylation with favorable clinicopathological parameters including: age ≤ 60 years (p = 0.091), normal levels of lactate dehydrogenase (p = 0.090), Eastern Cooperative Oncology Group performance status < 2 (p = 0.095), and low/intermediate low International Prognostic Index (p = 0.076). In the female group and group of the patients without bulky tumor mass, treated with chemotherapeutic regimens including rituximab, methylation of p15 was significantly related to longer overall survival (p = 0.036 and 0.027, respectively). Our results suggest that promoter methylation of p15 gene could have prognostic value in DLBCL patients treated with rituximab when used in combination with gender and tumor size.
Amphibians over the edge: silent extinction risk of Data Deficient species
Authors: Howard Sam D. , Bickford David P.
Published: May 2014

Aim

To apply mathematical models to the task of predicting extinction risk for species currently listed as ‘Data Deficient’ (DD) by the International Union for the Conservation of Nature (IUCN). We demonstrate this approach by applying it globally to amphibians, the vertebrate group recognized as being most extinction threatened and having the largest proportion of DD species. We combine model predictions with current extinction risk knowledge to highlight regions of greatest disparity between known and predicted risk, where potential species extinctions may be overlooked.

Location

Global.

Methods

Using global amphibian distribution data obtained from the IUCN and species trait data, we apply machine learning randomForest models to predict extinction risk of DD species from life history traits, environmental variables and habitat loss. These models are trained using data for species that have been assigned to an extinction risk category (other than DD) by the IUCN. We then combine predictions for DD species with IUCN assessment data in a GIS framework to highlight anomalies between current knowledge of amphibian extinction risk and our model predictions.

Results

We show that DD amphibian species are likely to be more threatened with extinction than their fully assessed counterparts. Regions in South America, central Africa and North Asia are particularly at risk due to lack of species knowledge and higher extinction risk than currently recognized.

Main conclusions

Application of predictive models ranking regions and species most in need of primary research allows prioritization of limited resources in an informed context, minimizing risk of unnoticed species' extinction.
Diffusion tensor imaging in pediatric Chiari type I malformation
Authors: Eshetu Tadesse , Meoded Avner , Jallo George I , Carson Benjamin S , Huisman Thierry AGM , Poretti Andrea
Published: May 2014

Aim

Chiari type I malformation (C1M) may be symptomatic or asymptomatic as an incidental finding. In this retrospective study, we applied diffusion tensor imaging (DTI) to study the brainstem and cerebellar white matter tracts in C1M.

Method

Diffusion tensor imaging (DTI) data were acquired on a 1.5T MR‐scanner using balanced pairs of diffusion gradients along 20 non‐collinear directions. Measurements from regions of interest in each pontine corticospinal tract, medial leminscus, and middle cerebellar peduncle (MCP) and in the lower brainstem were obtained for fractional anisotropy and mean, axial, and radial diffusivity. Values in symptomatic and asymptomatic children, and children with and without hydromyelia were compared using analysis of variance.

Results

Fifteen children with C1M (10 males, five females; six symptomatic [four with hydromyelia] and nine asymptomatic) were included. Median age was 6 years 5 months (range 2y 10mo–15y 4mo). No significant differences in DTI scalars were found in the lower brainstem. In both MCPs, axial diffusivity values were lower in symptomatic than in asymptomatic children (p=0.049 and p=0.035 respectively) and higher in children with hydromyelia versus without hydromyelia (p=0.018 and p=0.006 respectively). In the left MCP, mean diffusivity values were lower in symptomatic than in asymptomatic children (p=0.047).

Interpretation

Our results show that microstructural tissue alterations may be present in C1M. Additionally, our study suggests a specific role for the MCPs in C1M. Further large‐scale studies are warranted.