Lipoprotein-associated phospholipase A2, and subsequent cardiovascular events and mortality among patients with coronary heart disease

Objective: The objective of this study is to evaluate the relevance of Lp-PLA₂ to risk prediction among coronary heart disease (CHD) patients.

Methods: Lp-PLA₂ activity was measured in 2538 CHD patients included in the Bezafibrate Infarction Prevention (BIP) study.

Results: Adjusting for patient characteristics and traditional risk factors, 1 standard deviation of Lp-PLA₂ was associated with a hazard ratio (HR) of 1.12 (95% confidence interval (CI): 1.00–1.25) for mortality and 1.03 (0.93–1.14) for cardiovascular events. Lp-PLA₂ did not significantly improve model discrimination, or calibration nor result in noteworthy reclassification.

Conclusions: Our results do not support added value of Lp-PLA₂ for predicting cardiovascular events or mortality among CHD patients beyond traditional risk factor.     

Riboflavin as an independent and accurate biomarker for adherence in a randomized double-blind and placebo-controlled clinical trial

Background: Medication adherence is critical for success of clinical trials.

Objective: To assess oral riboflavin is an adherence marker.

Methods: Riboflavin was incorporated into active treatment and placebo pills for a clinical trial lasting for 2 years.

Results: The accuracy (area under the receiver operating curve) of urinary riboflavin was 0.91 as a binary classifier of adherence, and was similar or better than for two active study ingredients daidzein (0.92) and genistein (0.87) (all p?<?0.0001). Decreased adherence over time was similar in the two study groups.

Conclusion: Riboflavin is an accurate and useful biomarker for study pill ingestion.     

Habitat preference of female Corncrakes Crex crex: implications for the conservation of breeding sites in a secretive species

Capsule: Forb-rich and diverse, annually mown vegetation is the preferred Corncrake Crex crex breeding habitat in floodplains.

Aims: To identify habitat preferences of female Corncrakes and characteristics of breeding sites in floodplain habitats and derive recommendations for management.

Methods: We tracked six female Corncrakes and compared vegetation characteristics at 78 male calling sites with regard to breeding records and diurnal call activity of males, because we expect the latter to indicate female occurrence. Additionally, we analysed how practice and timing of land use in the preceding year affected vegetation structure.

Results: Females preferred areas with high cover of forbs and a distinct relief heterogeneity, which was associated with overall vegetation diversity. All calling sites with breeding records and diurnal call incidence of males showed high forb and low sedge cover, low litter heights and a close location to ditches. Favourable conditions were best provided by mowing in the preceding year.

Conclusion: In eutrophic habitats, female Corncrakes preferred a vegetation structure created by annual mowing. Because nests and unfledged chicks are threatened by mowing operations, we recommend an alternating management regime based on the identification of breeding sites using male diurnal calling activity.     

Habitat use and tree selection of a declining Afro-Palaearctic migrant at sub-Saharan staging and wintering sites

Capsule: Wood Warblers Phylloscopus sibilatrix showed significant selection for tree species and woodland characteristics at staging and wintering sites in sub-Saharan Africa.

Aims: To investigate home range size, habitat and tree species selection of Wood Warblers at a staging site in Burkina Faso (Koubri) and a wintering site in Ghana (Pepease).

Methods: Comparing habitat recorded at locations of radio-tagged birds and at control points, we investigated whether there was habitat and tree species selection. We also compared home range size of individual birds between the two sites.

Results: Home range size did not differ between the two sites. There was significant selection for tree species at both Koubri and Pepease: Anogeissus leiocarpus and Albizia zygia, respectively. At Koubri, there was significant avoidance of the most common tree species (Azadirachta indica, Mangifera indica (both non-native), Vitellaria paradoxa and Acacia spp.). In addition, there was a preference for taller trees and greater tree density at both sites. However, the probability of a point being used declined with increasing number of taller (>14?m) trees.

Conclusion: Fine-scale selection of woodland habitats suggests that Wood Warblers are likely to suffer the consequences of ongoing land-use change in their West African wintering grounds.     

Nocturnal bird migration in the Bay of Biscay as observed by a thermal-imaging camera

Capsule: Bird migration was recorded by an infrared device at three sites in the southeastern Bay of Biscay, indicating seasonal east–west differences in migration flow.

Aims: The main aims of this study were to quantify and describe nocturnal migration dynamics in proximity of a sea barrier, and to assess seasonal and geographical drivers of migration patterns.

Methods: A thermal-imaging camera was used at two coastal study sites (Punta Galea, Cape Higuer) in spring and three study sites (coast: Punta Galea, Cape Higuer; inland: Iregua Valley) in autumn for four hours from sunset over 90 nights in 2014 and 2015.

Results: Migration was strong at both coastal sites in early spring. Autumn migration was weak at the western coast, but strong at the eastern coast and inland. Tailwind had no significant effect on migration intensity, but migration ceased during strong cross- or headwinds despite clear skies. The majority of the targets were passerines.

Conclusions: The patterns observed suggest spring migration occurs on a broader front, potentially involving sea crossing further to the west, while autumn migration concentrates more eastwards over land. In both seasons, there was no significant response to wind conditions.     

A first test of unattended,acoustic recorders for monitoring Capercaillie Tetrao urogallus lekking activity

Capsule: Automated acoustic recording can be used as a valuable survey technique for Capercaillie Tetrao urogallus leks, improving the quality and quantity of field data for this endangered bird species. However, more development work and testing against traditional methods are needed to establish optimal working practices.

Aims: This study aims to determine whether Capercaillie vocalizations can be recognized in lek recordings, whether this can be automated using readily available software, and whether the number of calls resulting varies with location, weather conditions, date and time of day.

Methods: Unattended recording devices and semi-automated call classification software were used to record and analyse the display calls of Capercaillie at three known lek sites in Scotland over a two-week period.

Results: Capercaillie calls were successfully and rapidly identified within a data set that included the vocalizations of other bird species and environmental noise. Calls could be readily recognized to species level using a combination of unsupervised software and manual analysis. The number of calls varied by time and date, by recorder/microphone location at the lek site, and with weather conditions. This information can be used to better target future acoustic monitoring and improve the quality of existing traditional lek surveys.

Conclusion: Bioacoustic methods provide a practical and cost-effective way to determine habitat occupancy and activity levels by a vocally distinctive bird species. Following further testing alongside traditional counting methods, it could offer a significant new approach towards more effective monitoring of local population levels for Capercaillie and other species of conservation concern.     

Kleptoparasitism in gulls Laridae at an urban and a coastal foraging environment: an assessment of ecological predictors

Capsule: Kleptoparasitism in gulls occurred at a greater rate at an urban compared with a coastal site. Population density and prey size predicted the rate of kleptoparasitism at the urban site.

Aims: To investigate and assess the ecological variables associated with kleptoparasitism among gulls at urban and rural sites.

Methods: Field observations were conducted at Brancaster (coastal rural) and Billingsgate Market (urban) to examine differences in the rate of kleptoparasitism in mixed-species flocks of gulls. Four key variables (prey size, population density, season and species) were assessed as predictors of kleptoparasitism.

Results: Generalized linear models revealed significant effects on kleptoparasitism rate of site, population density and prey size, and two-way interactions between these main terms. Population density and prey size differed significantly between sites, but population density appeared to predict the rate of kleptoparasitism.

Conclusion: Kleptoparasitism may well aid invasion and increase the range of environments a gull can tolerate by helping them meet their energy needs in novel environments where normal foraging behaviours are difficult to implement.     

Inhibitory effect of Tanshinone IIA on inverted formin-2 protects HaCaT cells against oxidative injury via regulating mitochondrial stress

Context: Epidermal cells play an important role in regulating the regeneration of skin after burns and wounds.

Objective: The aim of our study is to explore the role of Tanshinone IIA (Tan IIA) in the apoptosis of epidermal HaCaT cells induced by H₂O₂, with a focus on mitochondrial homeostasis and inverted formin-2 (INF2).

Materials and methods: Cellular viability was determined using the MTT assay, TUNEL staining, western blot analysis and LDH release assay. Adenovirus-loaded INF2 was transfected into HaCaT cells to overexpress INF2 in the presence of Tan IIA treatment. Mitochondrial function was determined using JC-1 staining, mitochondrial ROS staining, immunofluorescence and western blotting.

Results: Oxidative stress promoted the death of HaCaT cells and this effect could be reversed by Tan IIA. At the molecular levels, Tan IIA treatment sustained mitochondrial energy metabolism, repressed mitochondrial ROS generation, stabilized mitochondrial potential, and blocked the mitochondrial apoptotic pathway. Furthermore, we demonstrated that Tan IIA modulated mitochondrial homeostasis via affecting INF2-related mitochondrial stress. Overexpression of INF2 could abolish the protective effects of Tan IIA on HaCaT cells viability and mitochondrial function. Besides, we also reported that Tan IIA regulated INF2 expression via the ERK pathway; inhibition of this pathway abrogated the beneficial effects of Tan IIA on HaCaT cells survival and mitochondrial homeostasis.

Conclusions: Overall, our results indicated that oxidative stress-mediated HaCaT cells apoptosis could be reversed by Tan IIA treatment via reducing INF2-related mitochondrial stress in a manner dependent on the ERK signaling pathway.     

Dynamic variation of histone H3 trimethyl Lys4 (H3K4me3) and heterochromatin protein 1 (HP1) with employment length in nickel smelting workers

Objective: To investigate the dynamic variation in H3K4me3 and HP1 with employment length in nickel smelting workers.

Methods: Blood samples were collected from 140 nickel smelting workers and 140 age-matched office workers to test for H3K4me3, and HP1 levels.

Results: H3K4me3 was statistically significantly different (p?<?0.05) between the two groups and positively correlated with employment length (r_s?=_?0.267). HP1 was not correlated with employment length (p?=?0.066) but was significantly different between the two groups.

Conclusions: Chronic exposure to nickel can induce oxidative damage, and increase H3K4me3 expression and inhibit HP1 expression.     

Hen harrier Circus cyaneus nest sites on the Isle of Mull are associated with habitat mosaics and constrained by topography

Capsule: Hen Harriers Circus cyaneus on the Isle of Mull, UK, are associated with habitat mosaics consisting of moorland, scrub and forestry but avoid grazed land, suggesting that forested habitats could be managed sympathetically for the Hen Harrier in the future should the current UK population increase.

Aims: To use distribution modelling to investigate nesting habitat associations using a long-term data set for the Hen Harrier on Mull.

Methods: We develop area-interaction models using a least absolute shrinkage and selection operator penalty to explore the distribution of 102 Hen Harrier nest sites in relation to habitat and topography. Our model is then successfully validated in tests using data for 70 nest sites from subsequent years.

Results: Our model is effective in predicting suitable areas for Hen Harrier nest sites and indicates that Hen Harriers on Mull are found in habitat mosaics below 200 m above sea level. Hen Harrier nest intensity is positively associated with increasing proportions of moorland and scrub, open canopy forestry and closed canopy forestry. Nest intensity is negatively associated with increasing proportions of grazed land.

Conclusion: Hen Harriers avoid grazed areas but are relatively tolerant of other habitat combinations. These findings are supported by previous observations of Hen Harrier habitat use and have implications for the recovery of some Hen Harrier populations in Special Protection Areas and future forest management. Open canopy forest and forest mosaics could potentially be incorporated into landscape-scale conservation plans for Hen Harriers using the population on Mull as an example.     

The diversity and community dynamics of hazelwood lichens and bryophytes along a major gradient of human impact

Background: Oceanic hazelwoods in western Scotland are hypothesised to be unmanaged post-glacial relicts, representing an unusual type of old-growth forest habitat in Europe. They are characterised by an exceptionally high epiphytic diversity, including their status as ‘hotspots’ for indicators of woodland ecological continuity.

Aims: The aim of this study was to evaluate the effects of climate, pollution and management on the occurrence of epiphytic lichens and bryophytes on Corylus avellana.

Methods: Thirteen hazelwood study sites were systematically sampled along a climate, pollution and management gradient in Britain. Epiphyte composition and richness were examined in a strict hierarchical framework, and compared against site-, stool- and stem-scale environmental predictors.

Results: The study showed that along the gradient from ‘clean-air’ relict sites to ‘polluted’ coppiced sites: (i) epiphytic local stem-scale diversity declined, (ii) there was a loss of late-successional species including foliose cyano- and tripartite lichens and bryophytes and (iii) stem sizes were reduced, providing a further limit to the accumulation of species richness within a site.

Conclusions: Relict hazelwoods in western Scotland are confirmed as an example of the most intact epiphyte communities. In particular, we show that the transition to coppicing can be clearly linked to ecological processes causing species loss.     

Future breeding and foraging sites of a southern edge population of the locally endangered Black Guillemot Cepphus grylle

Capsule: One of the southernmost populations of the Black Guillemot Cepphus grylle is currently endangered, and the risk may be exacerbated by climate change.

Aims: We evaluated the future vulnerability of the Black Guillemot by predicting the impact of climate change on the geographic distribution of its breeding and foraging range in the Baltic Sea.

Methods: We used MaxEnt, a species distribution modelling technique, to predict the current and future breeding grounds and foraging sites.

Results: We found that although the foraging range is expected to increase in the southern Baltic Sea in future, these areas will no longer be suitable as breeding grounds due to a changing climate, creating a spatial mismatch.

Conclusion: Our predictions indicate where threats to the species may be most severe and can be used to guide conservation planning. We advocate conservation measures which integrate potential future threats and focus on breeding sites across the current and future potential geographic range of the Black Guillemot.     

Tumor delivery of liposomal doxorubicin prepared with poly-L-glutamic acid as a drug-trapping agent

Context: Poly-l-glutamic acid (PGA) is an anionic polymer with a large number of carboxyl groups that can interact electrostatically with cationic drugs such as doxorubicin (DOX).

Objective: For stable encapsulation of DOX into liposomes, we prepared triethylamine (TEA)-PGA-liposomes using PGA as an internal trapping agent.

Methods: We prepared TEA-PGA-liposomes by remote loading of DOX with a TEA gradient into preformed liposomes prepared with 1, 2, or 4?mg/mL PGA (molecular weights 4800, 9800, and 20 500), and evaluated their biodistribution and antitumor effects on Lewis lung carcinoma (LLC) tumor-bearing mice.

Results: TEA-PGA-liposomes using the higher the molecular weight or concentration of PGA showed a slower release of DOX from the liposomes. TEA-PGA-liposomes prepared with a high concentration of PGA could enhance DOX accumulation in tumors and prolonged DOX circulation in the serum, indicating that DOX may be retained stably in the liposomal interior by interaction with PGA. Furthermore, injection of TEA-PGA-liposomes prepared with 4?mg/mL of PGA₉₈₀₀ or 2?mg/mL PGA₂₀₅₀₀ strongly inhibited tumor growth in LLC tumor-bearing mice.

Conclusions: PGA may be a potential trapping agent for liposomal DOX for tumor drug delivery.     

Downregulation of IDH2 exacerbates H2O2-mediated cell death and hypertrophy

Objectives: Reactive oxygen species-mediated cell death contributes to the pathophysiology of cardiovascular disease and myocardial dysfunction. We recently showed that mitochondrial NADP⁺-dependent isocitrate dehydrogenase (IDH2) functions as an antioxidant and anti-apoptotic protein by supplying NADPH to antioxidant systems.

Methods: In the present study, we demonstrated that H₂O₂-induced apoptosis and hypertrophy of H9c2 cardiomyoblasts was markedly exacerbated by small interfering RNA (siRNA) specific for IDH2.

Results: Attenuated IDH2 expression resulted in the modulation of cellular and mitochondrial redox status, mitochondrial function, and cellular oxidative damage. MitoTEMPO, a mitochondria-targeted antioxidant, efficiently suppressed increased caspase-3 activity, increased cell size, and depletion of cellular GSH levels in IDH2 siRNA-transfected cells that were treated with H₂O₂.

Discussion: These results indicated that the disruption of cellular redox balance might be responsible for the enhanced H₂O₂-induced apoptosis and hypertrophy of cultured cardiomyocytes by the attenuated IDH2 expression.     

Association of IL-10 (-819T/C, -592A/C and -1082A/G) and IL-6 -174G/C gene polymorphism and the risk of pneumonia-induced sepsis

Context: Association between inherited variants and the risks of sepsis is controversial.

Objective: To evaluate the risk of pneumonia-induced sepsis by examining its linkage with polymorphisms of IL-6 and IL-10.

Materials and methods: Samples were obtained from 188 pneumonia-induced sepsis patients, 162 pneumonia patients and 200 healthy controls.

Results: Subjects with IL-10 -1082 AA genotypes and IL-6 -174?CC genotype had a higher risk of sepsis and increased mRNA levels.

Conclusion: The variants of IL-10 -1082 A allele and IL-6 -174 C allele contributed to an increased risk of pneumonia-induced sepsis.     

Transplanting the leafy liverwort Herbertus hutchinsiae: a suitable conservation tool to maintain oceanic-montane liverwort-rich heath?

Background: Translocating plants for conservation purposes can be a useful tool to enhance existing populations, restore lost populations or create new ones, but has rarely been done for bryophytes, especially liverworts.

Aims: Here, the leafy liverwort Herbertus hutchinsiae, a representative species of oceanic-montane liverwort-rich heath, was translocated to unoccupied habitat within its current range, to establish whether its restricted distribution is due to habitat or dispersal limitation.

Methods: Feasibility of establishing new populations outside the current distribution range was assessed, to test the suitability of the species for assisted colonisation. Furthermore, transplants were grown at degraded sites where the species had declined to assess potential for restoration.

Results: Although maximal growth rates occurred within-range, transplants grew at all sites, indicating that the species could be dispersal limited; a conclusion supported by distribution modelling.

Conclusions: Assisted colonisation is thus an option for this species to overcome dispersal limitation and to track future climate space. Reinforcement of populations at degraded sites is only recommended if the pressure causing the degradation has been removed. These findings provide an evidence base for practical conservation management.     

Serum adenosine deaminase,catalase, and carbonic anhydrase activities in patients with renal cell carcinoma

Objectives: To determine whether serum levels of adenosine deaminase (AD), catalase (CAT), and carbonic anhydrase (CA) enzymes may be useful biomarkers in the diagnosis of renal tumors and may lead to early diagnosis of renal tumors.

Material and methods: The study included 33 patients with renal cell carcinoma (RCC) and 31 healthy controls. The activity of serum AD, CA, and CAT was determined and analyzed using the Giusti spectrophotometric method, H₂O₂ substrate, and C0₂ hydration, respectively.

Results: Serum AD and CA activity were significantly higher in patients with RCC than in controls. However, serum CAT activity was significantly lower in patients with RCC than in controls.

Conclusion: These markers might be potentially important as an additional biochemical tool for diagnosing RCC. We believe multidisciplinary studies are needed to plan patients’ preoperative and postoperative treatment and to create follow-up protocols.     

The pharmacologic characterization of allosteric molecules: Gq protein activation

Context: Drugs such as positive allosteric modulators (PAMs) produce complex behaviors when acting on tissues in different physiological contexts in vivo.

Objective: This study describes the use of functional assays of varying receptor sensitivity to unveil the various behaviors of PAMs and thus quantify allosteric effect through system independent scales.

Materials and methods: Muscarinic receptor activation with acetylcholine (ACh) was used to the demonstrate activity of the PAM agonist 1–(4-methoxybenzyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, Benzyl quinolone carboxylic acid (BQCA) in terms of direct agonism, potentiation of ACh affinity, and ACh efficacy. Concentration–response curves were fit to the functional allosteric model to yield indices of agonism (τ_B), effects on affinity (α cooperativity), and efficacy (β cooperativity).

Results: It is shown that a highly sensitive functional assay revealed the direct efficacy of BQCA as an agonist and relatively insensitive cells (produced by chemical alkylation of muscarinic receptor with phenoxybenzamine) revealed a positive allosteric effect of BQCA on ACh efficacy. A wide range of functional assay sensitivities produced a complex pattern of behavior for BQCA all of which was accurately quantified through the system-independent parameters of the functional allosteric model.

Conclusions: The study of complex allosteric molecules in a range of functional assays of varying sensitivity allows the measurement of the complete array of activities of these molecules on receptors and also better predicts which will be seen with these in vivo where a range of tissue sensitivities is encountered.     

Grazing effects on plant diversity in the endemic Erica mackayana heathland community of north-west Spain

Background: Large areas of heathland landscapes in Galicia, north-west Spain, have traditionally been extensively grazed by free-ranging cattle and wild ponies. Recently, a large reduction in the number of these larger herbivores has been observed, with unknown consequences for the habitat.

Aims: To evaluate the effects of grazing and herbivore density on plant diversity, community composition and vegetation structure of the endemic wet heathlands dominated by Erica mackayana in Galicia.

Methods: Field sampling of vascular plants, generalised linear models (GLMs), non-metric multidimensional distance scaling (NMDS).

Results: Grazed sites had significantly higher total and rare species richness and diversity than ungrazed sites. Higher densities of cattle resulted in lower numbers of rare species, while wild pony density had no effect on rare species richness. In grazed sites, vegetation was lower with greater variation in height, resulting in greater heterogeneity of the habitat. Precipitation and summer temperatures were related to plant diversity, mainly beta diversity. Soil organic matter negatively correlated with rare species.

Discussion: Grazing, mostly by wild ponies, was demonstrated to be positively related to plant diversity and vegetation structure. Lack of grazing or high cattle densities resulted in a negative effect on total and rare species richness and diversity. Future climate change may negatively affect heathland plant diversity. Galician wild ponies represent a unique case of sustainable management of a wild species and an invaluable cultural heritage. Moreover, they have a significant role in maintaining the endemic E. mackayana heathlands, what would justify specific conservation actions for these large herbivores.