bluuebunny/crossref_metadata_2025 huggingface dataset:
Waterfowl populations are resilient to immediate and lagged impacts of wildfires in the boreal forest
Authors: Lewis Tyler L. , Schmutz Joel A. , Amundson Courtney L. , Lindberg Mark S.
Published: June 2016

Wildfires are the principal disturbance in the boreal forest, and their size and frequency are increasing as the climate warms. Impacts of fires on boreal wildlife are largely unknown, especially for the tens of millions of waterfowl that breed in the region. This knowledge gap creates significant barriers to the integrative management of fires and waterfowl, leading to fire policies that largely disregard waterfowl.

Waterfowl populations across the western boreal forest of North America have been monitored annually since 1955 by the Waterfowl Breeding Population and Habitat Survey (BPOP), widely considered the most extensive wildlife survey in the world. Using these data, we examined impacts of forest fires on abundance of two waterfowl guilds – dabblers and divers. We modelled waterfowl abundance in relation to fire extent (i.e. amount of survey transect burned) and time since fire, examining both immediate and lagged fire impacts.

From 1955 to 2014, >1100 fires in the western boreal forest intersected BPOP survey transects, and many transects burned multiple times. Nonetheless, fires had no detectable impact on waterfowl abundance; annual transect counts of dabbler and diver pairs remained stable from the pre‐ to post‐fire period.

The absence of fire impacts on waterfowl abundance extended from the years immediately following the fire to those more than a decade afterwards. Likewise, the amount of transect burned did not influence waterfowl abundance, with similar pair counts from the pre‐ to post‐fire period for small (1–20% burned), medium (21–60%) and large (>60%) burns.

Policy implications. Waterfowl populations appear largely resilient to forest fires, providing initial evidence that current policies of limited fire suppression, which predominate throughout much of the boreal forest, have not been detrimental to waterfowl populations. Likewise, fire‐related management actions, such as prescribed burning or targeted suppression, seem to have limited impacts on waterfowl abundance and productivity. For waterfowl managers, our results suggest that adaptive models of waterfowl harvest, which annually guide hunting quotas, do not need to emphasize fires when integrating climate change effects.
MicroRNA‐217 suppresses homocysteine‐induced proliferation and migration of vascular smooth muscle cells via N‐methyl‐D‐aspartic acid receptor inhibition
Authors: Duan Hongyan , Li Yongqiang , Yan Lijie , Yang Haitao , Wu Jintao , Qian Peng , Li Bing , Wang Shanling
Published: June 2016

Hyperhomocysteine has become a critical risk for atherosclerosis and can stimulate proliferation and migration of vascular smooth muscle cells (VSMCs). N‐methyl‐D‐aspartic acid receptor (NMDAR) is a receptor of homocysteine and mediates the effects of homocysteine on VSMCs. Bioinformatics analysis has shown NMDAR is a potential target of microRNA‐217 (miR‐217), which exerts multiple functions in cancer tumorigenesis and carotid plaque progression. In this study, we sought to investigate the role of miR‐217 in VSMCs phenotype transition under homocysteine exposure and elucidate its effect on atherosclerotic plaque formation. After treating with several doses of homocysteine (0–8 × 10−4 mol/L) for 24 hours, the expression of miR‐217 in HA‐VSMCs and rat aortic VSMCs was not altered. Intriguingly, the expression of NMDAR mRNA and protein was reduced by homocysteine in a dose‐dependent manner. Transfection of miR‐217 mimic significantly inhibited the proliferation and migration of VSMCs with homocysteine treatment, while transfection of miR‐217 inhibitor promoted VSMCs migration. Moreover, miR‐217 mimic down‐regulated while miR‐217 inhibitor up‐regulated NMDAR protein expression but not NMDAR mRNA expression. Through luciferase reporter assay, we showed that miR‐217 could directly bind to the 3′‐UTR of NMDAR. MiR‐217 mimic transfection also released the inhibition of cAMP‐response element‐binding protein (CREB)‐PGC‐1α signalling induced by homocysteine. Additionally, restoration of PGC‐1α expression via AdPGC‐1α infection markedly suppressed VSMCs proliferation through the degradation of NADPH oxidase (NOX1) and reduction of reactive oxygen species (ROS). Collectively, our study identified the role of miR‐217 in regulating VSMCs proliferation and migration, which might serve as a target for atherosclerosis therapy.
The importance of the Cisto‐Lavanduletalia coastal habitat on population persistence of the narrow endemic Dianthus morisianus (Caryophyllaceae)
Authors: Fenu Giuseppe , Cogoni Donatella , Navarro Francisco B , Concas Erica , Bacchetta Gianluigi
Published: June 2016

In Mediterranean coastal dune habitats, the facilitative mechanisms among plants could be crucial for the persistence of several plants for which survival is linked to a fragile equilibrium with the surrounding microenvironment. The aim of this study was to verify whether there exists a facilitative effect on Dianthus morisianus Vals., a narrow endemic plant of Sardinia, and to analyze the potential importance of facilitative effects via the analysis of the interaction outcome with the nurse plants. Forty‐five plots of 1 × 1 m were randomly placed within the habitat where D
. morisianus grows preferentially, composed of sclerophyllous shrubs (Cisto‐Lavanduletalia sensu Habitats Directive). All D
. morisianus plants recorded within the plots were assigned to one of the three microhabitats identified: (i) open areas in the inter‐shrub discontinuities, (ii) under shrubs canopy influence and (iii) inside the shrubs. For each D
. morisianus plant, the reproductive or vegetative status and both morphological and reproductive traits, as well as the possible physical damage (grazing and trampling), were measured. Inside the Cisto‐Lavanduletalia habitat there was a greater number of reproductive plants, whereas in the open patches the vegetative plants prevailed. Morphological and reproductive parameters varied significantly among microhabitats and showed higher values inside the shrubs. As expected, grazing and trampling negatively affected mainly plants growing in the open and below microhabitats. A strong facilitative interaction between D
. morisianus and the coastal Cisto
‐
Lavanduletalia habitat was found: this habitat had a crucial positive effect on the persistence of D
. morisianus and preserved this threatened plant; therefore, it is essential to primarily conserve the Cisto‐Lavanduletalia habitat.
A Longitudinal Investigation of Willingness to Pay for Health Insurance in Germany
Authors: Bock Jens‐Oliver , Hajek André , Brenner Hermann , Saum Kai‐Uwe , Matschinger Herbert , Haefeli Walter Emil , Schöttker Ben , Quinzler Renate , Heider Dirk , König Hans‐Helmut
Published: June 2016

Objective

To investigate factors affecting willingness to pay (WTP) for health insurance of older adults in a longitudinal setting in Germany.

Data Sources

Survey data from a cohort study in Saarland, Germany, from 2008–2010 and 2011–2014 (n1 = 3,124;n2 = 2,761) were used.

Study Design

Panel data were taken at two points from an observational, prospective cohort study.

Data Collection

WTPestimates were derived using a contingent valuation method with a payment card. Participants provided data on sociodemographics, lifestyle factors, morbidity, and health care utilization.

Principal Findings

Fixed effects regression models showed higher individual health care costs to increaseWTP, which in particular could be found for members of private health insurance. Changes in income and morbidity did not affectWTPamong members of social health insurance, whereas these predictors affectedWTPamong members of private health insurance.

Conclusions

The fact that individual health care costs affectedWTPpositively might indicate that demanding (expensive) health care services raises the awareness of the benefits of health insurance. Thus, measures to increaseWTPin old age should target at improving transparency of the value of health insurances at the moment when individual health care utilization and corresponding costs are still relatively low.
Distinguishing liver haemangiomas from metastatic tumours using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid‐enhanced diffusion‐weighted imaging at 1.5T MRI
Authors: Saito Kazuhiro , Yoshimura Nobutaka , Shirota Natsuhiko , Saguchi Toru , Sugimoto Katsutoshi , Tokuuye Koichi
Published: June 2016

Introduction

The aim of this study to evaluate the effectiveness of enhanced diffusion‐weighted imaging (DWI) for distinguishing liver haemangiomas from metastatic tumours (mets).

Methods

This study included 23 patients with 27 haemangiomas and 26 patients with 46 mets. Breath‐holding diffusion‐weighted imaging (DWI) (b‐values of 0, 50, 100, 150, 200, 400 and 800 s/mm2) were obtained before and 20 min after injection of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd‐EOB‐DTPA). Lesion contrast‐to‐noise ratios (CNRs) were calculated. The data were processed using the bi‐exponential model of intravoxel incoherent motion (IVIM). Receiver operating characteristic analysis was performed to compare the diagnostic performance when distinguishing haemangioma from mets.

Results

The CNRs of haemangioma and mets at post‐contrast enhancement increased. All IVIM parameters for liver haemangioma and mets showed no significant differences between pre‐ and post‐contrast enhancement. The highest Az value of CNR and IVIM parameters occurred at a post‐contrast b‐value of 0 s/mm2 and true diffusion (D). The highest qualitative evaluation occurred at a b‐value of 800 s/mm2. The sensitivity and specificity, with a CNR of 100 or higher at a post‐contrast b‐value of 0 s/mm2 and considered to be haemangioma, were 89% and 67% (<10 mm, 91%, 77%) respectively. The sensitivity and specificity, when D was higher than 1.4 × 10−3 mm2/s, were 74% and 83% (<10 mm, 64%, 77%) respectively. The sensitivity and specificity of qualitative evaluation by enhanced DWI were 74% and 76% (<10 mm, 64%, 80%) respectively.

Conclusions

The accuracy of the CNR was highest with b = 0; however, examination at high b‐values had advantages in the qualitative evaluation of some small‐size lesions.
stratag: An r package for manipulating, summarizing and analysing population genetic data
Authors: Archer Frederick I. , Adams Paula E. , Schneiders Brita B.
Published: June 2016

We introduce the r package stratag as a user‐friendly population genetics toolkit. stratag provides easy access to a suite of standard genetic summaries as well as the ability to rapidly manipulate stratified genetic data for custom analyses. Tests of population subdivision with most common measures of population subdivision (e.g., FST, GST, ΦST, Χ2) can be conducted within a single function. The package also provides wrapper functions that allow users to configure and run popular external programs such as genepop, structure, and fastsimcoal from within r, and smoothly interface with popular r packages adegenet and pegas. stratag is intended to be an open‐source dynamic package that will grow with future needs and user input.
SNP discovery in candidate adaptive genes using exon capture in a free‐ranging alpine ungulate
Authors: Roffler Gretchen H. , Amish Stephen J. , Smith Seth , Cosart Ted , Kardos Marty , Schwartz Michael K. , Luikart Gordon
Published: June 2016

Identification of genes underlying genomic signatures of natural selection is key to understanding adaptation to local conditions. We used targeted resequencing to identify SNP markers in 5321 candidate adaptive genes associated with known immunological, metabolic and growth functions in ovids and other ungulates. We selectively targeted 8161 exons in protein‐coding and nearby 5′ and 3′ untranslated regions of chosen candidate genes. Targeted sequences were taken from bighorn sheep (Ovis canadensis) exon capture data and directly from the domestic sheep genome (Ovis aries v. 3; oviAri3). The bighorn sheep sequences used in the Dall's sheep (Ovis dalli dalli) exon capture aligned to 2350 genes on the oviAri3 genome with an average of 2 exons each. We developed a microfluidic qPCR‐based SNP chip to genotype 476 Dall's sheep from locations across their range and test for patterns of selection. Using multiple corroborating approaches (lositan and bayescan), we detected 28 SNP loci potentially under selection. We additionally identified candidate loci significantly associated with latitude, longitude, precipitation and temperature, suggesting local environmental adaptation. The three methods demonstrated consistent support for natural selection on nine genes with immune and disease‐regulating functions (e.g. Ovar‐DRA, APC, BATF2, MAGEB18), cell regulation signalling pathways (e.g. KRIT1, PI3K, ORRC3), and respiratory health (CYSLTR1). Characterizing adaptive allele distributions from novel genetic techniques will facilitate investigation of the influence of environmental variation on local adaptation of a northern alpine ungulate throughout its range. This research demonstrated the utility of exon capture for gene‐targeted SNP discovery and subsequent SNP chip genotyping using low‐quality samples in a nonmodel species.
Hypersensitivities to sesame and other common edible seeds
Authors: Patel A. , Bahna S. L.
Published: June 2016

Several seeds have been increasingly incorporated in various food items, with consequent risk of hypersensitivity reactions that are often severe. Identification of the specific seed as the culprit is often not explored or is difficult to verify. In this article, we reviewed the English literature from January 1930 to March 2016 using PubMed and Google Scholar searching for publications relevant to hypersensitivity to common edible seeds, namely sesame, sunflower seed, poppy seed, pumpkin seed, flaxseed, and mustard seed. Considering the worldwide consumption of those seeds, the number of published articles on the subject was relatively small and was mainly as case reports rather than large series. Allergy to sesame was more reported than to other seeds, with an estimated prevalence of 0.1–0.2%. In this review, we summarize the information relevant to each of the six seeds and their oils regarding the manifestations, routes of exposure, identified major allergens, and cross‐reactivity with other seeds or other foods. We also addressed the important role of a thorough history taking in suspecting seed allergy, the limited reliability of routine diagnostic procedures, and the importance of verification by appropriate challenge tests. At present, management is basically dietary avoidance and the use of symptomatic medications that may include epinephrine auto‐injectors. We did not encounter any well‐designed studies on immunotherapy for seed allergy, but it is hoped that such a gap be filled by the development of safe effective protocols in the near future.
Mould‐sensitized adults have lower Th2 cytokines and a higher prevalence of asthma than those sensitized to other aeroallergens
Authors: Matheson M. C. , Reece J. C. , Kandane‐Rathnayake R. K. , Tang M. L. K. , Simpson J. A. , Feather I. H. , Southey M. C. , Tsimiklis H. , Hopper J. L. , Morrison S. C. , Giles G. G. , Walters E. H. , Dharmage S. C.
Published: June 2016

Background

Evidence suggests that specific allergen sensitizations are associated with different allergic diseases which may reflect different underlying immune profiles. We aimed to examine the cytokine profiles of individuals sensitized to eight common aeroallergens.

Methods

We used data from the Tasmanian Longitudinal Health Study a population‐based cohort study of 45‐year‐olds. Serum cytokines (IL‐4, IL‐5, IL‐6, IL‐8, IL‐10, TNF‐α) were measured in 1157 subjects using the LINCOplex assays. Participants underwent skin prick testing for house dust mite, cat, grasses and moulds. Multivariable linear regression was used to compare serum cytokine levels between sensitized and nonatopic subjects.

Results

The prevalence of allergic sensitization to any aeroallergen was 51% (95% CI 47–54). Being sensitized to any aeroallergen was strongly associated with current asthma (OR = 3.7, 95% CI 2.6–5.3), and being sensitized to any moulds was associated with a very high risk of current asthma (OR = 6.40, 95% CI 4.06–10.1). The geometric mean (GM) levels of Th2 cytokines (IL‐4, IL‐5 and IL‐6) for adults sensitized to Cladosporium were significantly lower than the levels for nonatopic individuals (IL‐4 ratio of GMs = 0.25, 95% CI 0.10–0.62, P = 0.003; IL‐5 GM = 0.55, 95% CI 0.30–0.99, P = 0.05; and IL‐6 GM = 0.50, 95% CI 0.24–1.07, P = 0.07). Individuals sensitized to other aeroallergens all showed elevated Th2 cytokine levels.

Conclusion

Our study is the first large population‐based study to demonstrate reduced Th2 cytokines levels in people sensitized to mould. Underlying biological mechanisms driving allergic inflammatory responses in adults sensitized to moulds may differ from those sensitized to other aeroallergens. These findings suggest that it may be necessary to tailor treatments in individuals sensitized to moulds compared with other aeroallergens in order to optimize outcomes.
Evaluation of allowable time and histopathological changes in warm ischemia of the uterus in cynomolgus monkey as a model for uterus transplantation
Authors: Adachi Masataka , Kisu Iori , Nagai Toshihiro , Emoto Katsura , Banno Kouji , Umene Kiyoko , Nogami Yuya , Tsuchiya Hideaki , Itagaki Iori , Kawamoto Ikuo , Nakagawa Takahiro , Ogasawara Kazumasa , Aoki Daisuke
Published: June 2016

Introduction

The objective of this study was to examine the allowable warm ischemic time and pathological changes due to ischemia and reperfusion injury in the uterus of the cynomolgus monkey as a model for uterus transplantation.

Material and methods

Six female cynomolgus monkeys were used in the study. The uterus was resected from the vaginal canal and connected through the bilateral ovarian and uterine arteries and veins only. One animal was used as a control. In the other five animals, the bilateral uterine and ovarian vessels were clamped for 0.5, 1, 2, 4 and 8 h, respectively. Biopsy of the smooth muscle tissue of corpus uteri was performed after each ischemic time and after subsequent reperfusion for 3 h. Biopsy samples were observed by light and electron microscopy. Menstruation recovery was monitored.

Results

There were no particular findings in both light and electron microscopy after ischemia for up to 2 h and after subsequent reperfusion. There were no marked changes after ischemia for 4 h, but dilated nuclear pores and rough endoplasmic reticulum swelling were found after reperfusion. These changes also occurred, along with mitochondrial swelling and cristae loss after ischemia for 8 h, and plasma membrane loss, nuclear fragmentation and chromatin condensation were found after reperfusion. Periodical menstruation restarted in all animals with ischemia up to 4 h, but the animal with ischemia for 8 h had amenorrhea and uterine atrophy.

Conclusions

The uterus of the cynomolgus monkey tolerates warm ischemia for up to 4 h.
Supranutritional dietary selenium depressed expression of selenoprotein genes in three immune organs of broilers
Authors: Tang Jiayong , Huang Xiaofeng , Wang Longqiong , Li Qiang , Xu Jinyang , Jia Gang , Liu Guangmang , Chen Xiaoling , Shang Haiying , Zhao Hua
Published: June 2016

The objective of this study was to investigate the effects of supranutritional dietary selenium (Se) on selenoproteins expression in three immune organs of chickens. A total of 160 1‐day‐old male Cobb broilers were randomly divided into two groups and fed a Se‐deficient corn‐soybean basal diet supplemented with 0.3 (adequate) and 3.0 (excess) mg/kg Se for 42 days. Immune organs were collected, and effects of supranutritional Se on messenger RNA abundance of 23 selenoprotein genes and eight inflammation‐related genes were compared at day 42. Also enzyme activities were measured at days 14, 28 and 42. The results showed supranutritional dietary Se depressed growth performance of chicken and down‐regulated nine and three selenoprotein genes in thymus and spleen, respectively, and only Sepp1 was up‐regulated in the bursa of Fabricius. Also three, three and seven inflammation‐related genes were up‐regulated in three organs, respectively. Supranutritional Se elevated (P < 0.05) activities of superoxidase dismutase, total antioxidant capacity and glutathione peroxidase, mainly in early stages. In summary, supranutritional Se resulted in down‐regulation of selenoprotein genes and up‐regulation of inflammation‐related genes in three immune organs of chicken, which indicated potential roles of those selenoprotein genes in immune organs of the chicken.
Inflammation induced by inhaled lipopolysaccharide depends on particle size in healthy volunteers
Authors: Doyen Virginie , Pilcer Gabrielle , Dinh Phong Huy Duc , Corazza Francis , Bernard Alfred , Bergmann Pierre , Lefevre Nicolas , Amighi Karim , Michel Olivier
Published: June 2016

Aims

In drug development, the anti‐inflammatory properties of new molecules in the lung are currently tested using the inhaled lipopolysaccharide (LPS) model. The total and regional lung bioavailability of inhaled particles depends significantly on their size. The objective of the present study was to compare inflammatory responses in healthy volunteers after the inhalation of LPS of varying droplet size.

Methods

Three nebulizers were characterized by different droplet size distributions [mean mass median aerodynamic diameters: Microcirrus (2.0 μm), MB2 (3.2 μm) and Pari (7.9 μm)]. Participants inhaled three boluses of a 20 μg (technetium 99 m‐labelled) solution of LPS, randomly delivered by each nebulizer. We measured the lung deposition of the nebulized LPS by gamma‐scintigraphy, while blood and sputum biomarkers were evaluated before and after challenges.

Results

MB2 and Pari achieved greater lung deposition than Microcirrus [171.5 (±72.9) and 217.6 (±97.8) counts pixel–1, respectively, vs. 67.9 (±20.6) counts pixel–1; P < 0.01]. MB2 and Pari caused higher levels of blood C‐reactive protein and more total cells and neutrophils in sputum compared with Microcirrus (P < 0.05). C‐reactive protein levels correlated positively with lung deposition (P < 0.01).

Conclusions

Inhalation of large droplets of LPS gave rise to greater lung deposition and induced a more pronounced systemic and bronchial inflammatory response than small droplets. The systemic inflammatory response correlated with lung deposition. NCT01081392.
Brain‐derived neurotrophic factor, impaired glucose metabolism, and bipolar disorder course
Authors: Mansur Rodrigo B , Santos Camila M , Rizzo Lucas B , Asevedo Elson , Cunha Graccielle R , Noto Mariane N , Pedrini Mariana , Zeni‐Graiff Maiara , Cordeiro Quirino , Vinberg Maj , Kapczinski Flavio , McIntyre Roger S , Brietzke Elisa
Published: June 2016

Objectives

The neurotrophin brain‐derived neurotrophic factor (BDNF) has been proposed as a potential biomarker in bipolar disorder (BD). However, current evidence is limited and results have been highly heterogeneous. This study aimed to assess the moderating effect of impaired glucose metabolism (IGM) on plasma levels of BDNF in individuals with BD, and on the relationship between BDNF and variables of illness course.

Methods

We measured and compared the plasma levels of BDNF in individuals with BD (n=57) and healthy controls (n=26). IGM was operationalized as pre‐diabetes or type 2 diabetes mellitus. Information related to current and past psychiatric/medical history, as well as prescription of pharmacological treatments was also captured.

Results

Individuals with BD had lower levels of BDNF, relative to healthy controls, after adjustment for age, gender, current medications, smoking, alcohol use, and IGM (P=.046). There was no effect of IGM (P=.860) and no interaction between BD diagnosis and IGM (P=.893). Peripheral BDNF levels were positively correlated with lifetime depressive episodes (P<.001), psychiatric hospitalizations (P=.001) and suicide attempts (P=.021). IGM moderated the association between BDNF and the number of previous mood episodes (P<.001), wherein there was a positive correlation in euglycemic participants and a negative correlation in individuals with IGM.

Conclusions

BD is independently associated with lower levels of BDNF; IGM may modify the relationship between BDNF and BD course, suggesting an interactive effect of BDNF with metabolic status on illness progression.
The contemporary landscape of occupational bladder cancer within the United Kingdom: a meta‐analysis of risks over the last 80 years
Authors: Cumberbatch Marcus G. , Windsor‐Shellard Ben , Catto James W. F.
Published: June 2016

Objective

To profile the contemporary risks of occupational bladder in the UK, as this is a common malignancy that arises through occupational carcinogen exposure.

Materials and methods

A systematic review using PubMed, Medline, Embase and Web of Science was performed in March 2016. We selected reports of British workers in which bladder cancer or occupation were the main focus, with sufficient cases or with confidence intervals (CIs). We used the most recent data in populations with multiple reports. We combined odds ratios and risk ratios (RRs) to provide pooled RRs of incidence and disease‐specific mortality (DSM). We tested for heterogeneity and publication bias. We extracted bladder cancer mortality from Office of National Statistics death certificates. We compered across regions and with our meta‐analysis.

Results

We identified 25 articles reporting risks in 702 941 persons. Meta‐analysis revealed significantly increased incidence for 12/37 and DSM for five of 37 occupational classes. Three classes had reduced bladder cancer risks. The greatest risk of bladder cancer incidence occurred in chemical process (RR 1.87, 95% CI 1.50–2.34), rubber (RR 1.82, 95% CI 1.4–2.38), and dye workers (RR 1.8, 95% CI 1.07–3.04). The greatest risk of DSM occurred in electrical (RR 1.49, 95% CI 1.19–1.87) and chemical process workers (RR 1.35, 95% CI 1.09–1.68). Bladder cancer mortality was higher in the North of England, probably reflecting smoking patterns and certain industries. Limitations include the lack of sufficient robust data, missing occupational tasks, and no adjustment for smoking.

Conclusion

Occupational bladder cancer occurs in many workplaces and the risks for incidence and DSM may differ. Regional differences may reflect changes in industry and smoking patterns. Relatively little is known about bladder cancer within British industry, suggesting official data underestimate the disease.
The receptor for advanced glycation end products is required for β‐catenin stabilization in a chemical‐induced asthma model
Authors: Yao Lihong , Zhao Haijin , Tang Haixiong , Liang Junjie , Liu Laiyu , Dong Hangming , Zou Fei , Cai Shaoxi
Published: June 2016

Background and Purpose

Cytoplasmic retention of β‐catenin will lead to its nuclear translocation and subsequent interaction with the transcription factor TCF/LEF that regulates target gene expression. We have previously demonstrated aberrant expression of β‐catenin in a model of asthma induced by toluene diisocyanate (TDI). The aim of this study was to examine whether the receptor for advanced glycation end products (RAGE) can regulate β‐catenin expression in TDI‐induced asthma.

Experimental Approach

Male BALB/c mice were sensitized and challenged with TDI to generate a chemically‐induced asthma model. Inhibitors of RAGE, FPS‐ZM1 and the RAGE antagonist peptide (RAP), were injected i.p. after each challenge. Airway resistance was measured in vivo and bronchoalveolar lavage fluid was analysed. Lungs were examined by histology and immunohistochemistry. Western blotting and quantitative PCR were also used.

Key Results

Expression of RAGE and of its ligands HMGB1, S100A12, S100B, HSP70 was increased in TDI‐exposed lungs. These increases were inhibited by FPS‐ZM1 or RAP. Either antagonist blunted airway reactivity, airway inflammation and goblet cell metaplasia, and decreased release of Th2 cytokines. TDI exposure decreased level of membrane β‐catenin, phosphorylated Akt (Ser473), inactivated GSK3β (Ser9), dephosphorylated β‐catenin at Ser33/37/Thr41, which controls its cytoplasmic degradation, increased phosphorylated β‐catenin at Ser552, raised cytoplasmic and nuclear levels of β‐catenin and up‐regulated its targeted gene expression (MMP2, MMP7, MMP9, VEGF, cyclin D1, fibronectin), all of which were reversed by RAGE inhibition.

Conclusion and Implications

RAGE was required for stabilization of β‐catenin in TDI‐induced asthma, identifying protective effects of RAGE blockade in this model.
γ‐Tocotrienol reversal of epithelial‐to‐mesenchymal transition in human breast cancer cells is associated with inhibition of canonical Wnt signalling
Authors: Ahmed R. A. , Alawin O. A. , Sylvester P. W.
Published: June 2016

Objectives

Frizzled‐7 (FZD7) receptor‐dependent activation of the canonical Wnt/β‐catenin pathway plays a crucial role in epithelial‐to‐mesenchymal transition (EMT) and breast cancer metastasis. FZD7 and its co‐receptor, low‐density lipoprotein receptor‐related protein 6 (LRP6), are highly expressed in MDA‐MB‐231 and T‐47D breast cancer cells, and endogenous ligands for FZD7 include Wnt3a and Wnt5a/b. γ‐Tocotrienol, a natural isoform of vitamin E, inhibits human breast cancer cell proliferation and EMT. Here, studies have been conducted to investigate the role of the canonical Wnt pathway in mediating inhibitory effects of γ‐tocotrienol on EMT in human breast cancer cells.

Materials and methods

MDA‐MB‐231, T‐47D and MCF‐10A cells were maintained in serum‐free defined media containing selected doses of γ‐tocotrienol. Cell viability was determined using the MTT colorimetric assay, Western blot analysis was used to measure protein expression and the wound‐healing assay was employed to study cell mobility and migration. Immunohistochemical fluorescence staining visualized expression and localization of EMT cell markers.

Results

γ‐Tocotrienol was found to induce dose‐responsive inhibition of MDA‐MB‐231 and T‐47D cell growth at doses that had no effect on immortalized normal MCF‐10A mammary epithelial cells. These growth inhibitory effects were associated with suppression in canonical Wnt signalling, reversal of EMT and significant reduction in breast cancer cell motility.

Conclusions

γ‐Tocotrienol suppression of metastatic breast cancer cell proliferation and EMT was associated with suppression of the canonical Wnt/β‐catenin signalling pathway.
Outcomes of bisphosphonate therapy in kidney transplant recipients: a systematic review and meta‐analysis
Authors: Toth‐Manikowski Stephanie M. , Francis Jean M. , Gautam Amitabh , Gordon Craig E.
Published: June 2016

Mineral and bone disorders that precede kidney transplantation are exacerbated in the post‐transplant setting by tertiary hyperparathyroidism and immunosuppressive regimens. Bone mineral density (BMD) decreases following transplantation, leading to increased fracture risk. The effect of bisphosphonates on fracture is unknown. The aim of this study was to update estimates of change in BMD and fracture rates in bisphosphonate‐treated kidney transplant recipients through meta‐analysis. Studies comparing bisphosphonate therapy to standard of care were included if follow‐up duration was more than 6 months. We performed random‐effects meta‐analysis to determine the effect of bisphosphonates on lumbar spine and femoral neck BMD and fracture rates. Bisphosphonates improved femoral neck and lumbar spine BMD compared with controls (0.055 g/cm2, 95% CI 0.012–0.099 and 0.053 g/cm2, 95% CI 0.032–0.074, respectively) without adversely affecting serum creatinine or calcium. This corresponded to an unweighted improvement in BMD of 6.0% and 7.4%, respectively. There was no difference in fracture incidence in the two groups. Bisphosphonate therapy in kidney transplant recipients is associated with a statistically significant improvement in BMD at the lumbar spine and femoral neck. There was no difference in fracture incidence. Bisphosphonates did not adversely affect allograft dysfunction or serum calcium levels.
Incidence and impact of anti‐HLA‐DP antibodies in renal transplantation
Authors: Hörmann Mareike , Dieplinger Georg , Rebellato Lorita M. , Briley Kimberly P. , Bolin Paul , Morgan Claire , Haisch Carl E. , Everly Matthew J.
Published: June 2016

Background

The role of anti‐HLA‐DP antibodies in renal transplantation is poorly defined. This study describes the impact of donor (donor‐specific antibody [DSA]) and non‐donor‐specific antibodies against HLA‐DP antigens in renal transplant patients.

Methods

Of 195 consecutive patients transplanted between September 2009 and December 2011, 166 primary kidney recipients and their donors were typed (high‐resolution) for DP antigens. Sera taken pre‐transplant and at 1, 3, 6, 9, and 12 months, and annually post‐transplant were retrospectively tested for anti‐DP antibodies using single‐antigen beads.

Results

In 81 (49%) patients, anti‐DP antibodies were found; 64% (n=52) of patients were positive in the pre‐transplant samples and 36% (n=29) were positive exclusively post‐transplant. The median time from transplantation to antibody was 20.9 months. Fifty‐five percent (n=16) of the de novo anti‐DP antibodies were accompanied by another de novo DSA. Anti‐DP antibody‐positive patients had a higher rate of rejection (compared with anti‐DP antibody‐negative patients, P=.01). The estimated glomerular filtration rate declined more with anti‐DP antibodies (−5.5% vs +26%).

Conclusions

Antibodies against HLA‐DP antigens are common. De novo anti‐DP antibodies commonly appear after acute rejection and accompany DSA, which makes it difficult to determine whether anti‐DP antibodies are the cause or the consequence of graft injury.
Feasibility of exercise stress echocardiography for cardiac risk assessment in chronic kidney disease patients prior to renal transplantation
Authors: Nerlekar Nitesh , Mulley William , Rehmani Hassan , Ramkumar Satish , Cheng Kevin , Vasanthakumar Sheran A. , Rashid Hashrul , Barton Timothy , Nasis Arthur , Meredith Ian T. , Moir Stuart , Mottram Philip M.
Published: June 2016

Background

Pharmacologic stress testing is utilized in preference to exercise stress echocardiography (ESE) for cardiac risk evaluation in potential renal transplant recipients due to the perceived lower feasibility of ESE for achieving adequate workload and target heart rate (THR) in this population.

Methods

Consecutive patients referred for cardiac risk evaluation prior to potential kidney transplantation were evaluated. All patients attempted ESE before pharmacologic testing was considered. Treadmill ESE utilized BRUCE protocol to maximum capacity. THR was defined as >85% of the maximum predicted heart rate (220‐age). Functional capacity was assessed by metabolic equivalents (METs) and the rate pressure product (RPP).

Results

Of 535 patients (349 male, age 56±11), 372(70%) reached THR. Mean METs were 10±3 with 531(99%) achieving ≥4 METs and 87% ≥7 METs. Mean RPP was 25 821±5820 bpm×mm Hg (83% achieving >20 000 bpm×mm Hg). On multivariate analysis, independent predictors of failure to reach THR were rate‐control medication and diabetes; failure to reach 7 METs: females, diabetics, age≥65, and previous cardiac disease; failure to reach RPP>20 000: rate‐control medication. There were 97% of ESE completed to physiologic endpoints.

Conclusion

In unselected potential renal transplant candidates, cardiac assessment by ESE is well tolerated, with 9‐in‐10 exercising to satisfactory functional capacity. ESE should be considered a feasible alternative to pharmacologic testing in this population.
Development of a curriculum in molecular diagnostics, genomics and personalized medicine for dermatology trainees
Authors: Murphy Michael J. , Shahriari Neda , Payette Michael , Mnayer Laila , Elaba Zendee
Published: June 2016

Background

Results of molecular studies are redefining the diagnosis and management of a wide range of skin disorders. Dermatology training programs maintain a relative gap in relevant teaching.

Objective

To develop a curriculum in molecular diagnostics, genomics and personalized medicine for dermatology trainees at our institution. The aim is to provide trainees with a specialty‐appropriate, working knowledge in clinical molecular dermatology.

Methods

The Departments of Dermatology and Pathology and Laboratory Medicine collaborated on the design and implementation of educational objectives and teaching modalities for the new curriculum.

Results

A multidisciplinary curriculum was developed. It comprises: (i) assigned reading from the medical literature and reference textbook; (ii) review of teaching sets; (iii) two 1 hour lectures; (iv) trainee presentations; (v) 1‐week rotation in a clinical molecular pathology and cytogenetics laboratory; and (vi) assessments and feedback. Residents who participated in the curriculum to date have found the experience to be of value.

Conclusions

Our curriculum provides a framework for other dermatology residency programs to develop their own specific approach to molecular diagnostics education. Such training will provide a foundation for lifelong learning as molecular testing evolves and becomes integral to the practice of dermatology.
Improved transcatheter aortic valve implantation for aortic regurgitation using a snare loop‐assisted device: the first preclinical experience
Authors: Chen Xiang , Zhang Ben , Zhu Yufeng , Tan Hongwen , Zhao Xianxian , Qin Yongwen , Ge Junbo
Published: June 2016

Background

Transcatheter aortic valve implantation (TAVI) is an effective percutaneous treatment for high‐risk patients with severe symptomatic aortic stenosis. However, TAVI is rendered less effective in patients with noncalcified aortic valve disease because noncalcified aortic valves lack an anchor site for the implanted stent, causing the stent to relocate to an unexpected position. In this study, we developed an improved TAVI with a snare loop‐assisted device, and evaluated the feasibility and safety of this strategy in noncalcified aortic valve disease.

Materials and methods

The balloon‐expandable valve stent made of cobalt–chromium alloy was cut into a cylindrically shaped mesh configuration. The prosthetic valve was made of bovine pericardium. Ten healthy sheep (six males and four females with an average weight of 27·8 ± 1·18 kg) were selected to undergo transcatheter implantation of valved stents using the snare loop‐assisted device. Aortic angiography and colour Doppler echocardiography were applied to assess the function of artificial valves immediately and 3 months after the operation.

Results

The snare loop‐assisted TAVI was successfully implanted in all 10 sheep. The aortogram showed that the valve stent was fixed in the expected position. Among these 10 sheep, nine sheep survived for more than 3 months normally and one sheep died of infective endocarditis 1 week after the operation. Ultrasound and aortogram in the 3 months after operation showed proper positions of the prosthetic valves without stenosis and other apparent complications, and normal coronary artery openings.

Conclusions

The snare loop‐assisted TAVI approach can reduce stent shifting during valve stent implantation and improve the success rate of the TAVI in those with noncalcified aortic valves.
Structural host responses of Acacia mangium and Eucalyptus pellita to artificial infection with the root rot pathogen, Ganoderma philippii
Authors: Gill W. , Eyles A. , Glen M. , Mohammed C.
Published: June 2016

Structural host responses of young Acacia mangium and Eucalyptus pellita to infection with the root rot pathogen Ganoderma philippii were described. To our knowledge, this is the first report investigating the histology of root responses infected with G. philippii. The infected roots of A. mangium were characterized by the presence of a continuous multilayered mycelial sheath (~100–200 μm thick), fungal outgrowths and the production of a wound periderm. In contrast, roots of E. pellita were characterized by a mycelial sheath and fungal outgrowths and a wound periderm comprising of only one to four rows of cells.
Screening brassicaceous plants as biofumigants for management of Phytophthora cinnamomi oak disease
Authors: Ríos P. , Obregón S. , González M. , de Haro A. , Sánchez M. E.
Published: June 2016

Brassicaceous plants rich in glucosinolates have been used as biofumigants for the management of soilborne pathogens. Efficacy of Brassica plant tissue has mainly been attributed to toxic isothiocyanates released upon the hydrolysis of glucosinolates. Management of Phytophthora cinnamomi, the causal agent of oak root rot in rangeland ecosystems using biofumigation, is promising, but requires further validation. The biofumigation activity of 14 brassicaceous plants was evaluated under experimental conditions. All evaluated plants rich in sinigrin suppressed (100%) the mycelial growth of P. cinnamomi, while plants rich in aromatic or other aliphatic glucosinolates had little or no suppressive effect. Simulating soil amendment in field conditions, the effects on natural soil artificially infested with P. cinnamomi chlamydospores were examined with Brassica juncea, Eruca vesicaria and Lepidium sativum, three species with different glucosinolate profiles. Only B. juncea decreased the viability of chlamydospores significantly in comparison with untreated soil only 1 day after biofumigation, whereas E. vesicaria needed 8 days to reach significance and L. sativum had no effect at all. Despite the decreases in soil inoculum, biofumigation with B. juncea did not prevent the root infections in a highly susceptible host (Lupinus luteus). However, biofumigation with plants rich in sinigrin, such as B. juncea, decreased P. cinnamomi soil inoculum under the experimental minimum threshold for oak disease expression. Although biofumigation should be considered as an effective measure to be incorporated in integrated control of the oak disease, biofumigation by itself would not be effective enough for the substantial suppression of P. cinnamomi inoculum.
A thirteen‐year study on the impact of a severe canker disease of Corymbia calophylla, a keystone tree in Mediterranean‐type forests
Authors: Paap T. , Burgess T. I. , Calver M. , McComb J. A. , Shearer B. L. , Hardy G. E. StJ.
Published: June 2016

Worldwide, forests and woodlands have shown progressive declines in health as a result of global environmental changes in combination with local anthropogenic drivers. This study examined the incidence and progression of a canker disease of marri (Corymbia calophylla) caused by the endemic fungal pathogen Quambalaria coyrecup at three paired forest and anthropogenically disturbed sites in the southwest of Western Australia over 13 years. At the time of plot establishment in 2001, cankers were present on trees at all six sites with 22.7% of the assessed trees cankered. By 2014, cankers had led to the death of 6.7% of the trees, and an additional 10.0% of the trees developed cankers during this time. A further 2.3% of trees died due to causes other than canker, resulting in a final figure of 65.0% of trees remaining alive and free of cankers for the duration of the survey period. Canker incidence was significantly greater on trees present at anthropogenically disturbed sites (along roadsides and in paddocks) than forest trees (35.3% increasing to 50.7%, 10.0% increasing to 14.7%, respectively). Trunk diameter at breast height, tree height and crown ratings were not correlated with canker presence. This long‐term study provides evidence of the increasing severity of this canker pathogen and the impact it is having on the survival of marri.
Transmission of influenza reflects seasonality of wild birds across the annual cycle
Authors: Hill Nichola J. , Ma Eric J. , Meixell Brandt W. , Lindberg Mark S. , Boyce Walter M. , Runstadler Jonathan A.
Published: June 2016

Influenza A Viruses (IAV) in nature must overcome shifting transmission barriers caused by the mobility of their primary host, migratory wild birds, that change throughout the annual cycle. Using a phylogenetic network of viral sequences from North American wild birds (2008–2011) we demonstrate a shift from intraspecific to interspecific transmission that along with reassortment, allows IAV to achieve viral flow across successive seasons from summer to winter. Our study supports amplification of IAV during summer breeding seeded by overwintering virus persisting locally and virus introduced from a wide range of latitudes. As birds migrate from breeding sites to lower latitudes, they become involved in transmission networks with greater connectivity to other bird species, with interspecies transmission of reassortant viruses peaking during the winter. We propose that switching transmission dynamics may be a critical strategy for pathogens that infect mobile hosts inhabiting regions with strong seasonality.
Partitioning of ecosystem respiration of CO2 released during land‐use transition from temperate agricultural grassland to Miscanthus × giganteus
Authors: McCalmont Jon P. , McNamara Niall P. , Donnison Iain S. , Farrar Kerrie , Clifton‐Brown John C.
Published: June 2016

Conversion of large areas of agricultural grassland is inevitable if European and UK domestic production of biomass is to play a significant role in meeting demand. Understanding the impact of these land‐use changes on soil carbon cycling and stocks depends on accurate predictions from well‐parameterized models. Key considerations are cultivation disturbance and the effect of autotrophic root input stimulation on soil carbon decomposition under novel biomass crops. This study presents partitioned parameters from the conversion of semi‐improved grassland to Miscanthus bioenergy production and compares the contribution of autotrophic and heterotrophic respiration to overall ecosystem respiration of CO2 in the first and second years of establishment. Repeated measures of respiration from within and without root exclusion collars were used to produce time‐series model integrations separating live root inputs from decomposition of grass residues ploughed in with cultivation of the new crop. These parameters were then compared to total ecosystem respiration derived from eddy covariance sensors. Average soil surface respiration was 13.4% higher in the second growing season, increasing from 2.9 to 3.29 g CO2‐C m−2 day−1. Total ecosystem respiration followed a similar trend, increasing from 4.07 to 5.4 g CO2‐C m−2 day−1. Heterotrophic respiration from the root exclusion collars was 32.2% lower in the second growing season at 1.20 g CO2‐C m−2 day−1 compared to the previous year at 1.77 g CO2‐C m−2 day−1. Of the total respiration flux over the two‐year time period, aboveground autotrophic respiration plus litter decomposition contributed 38.46% to total ecosystem respiration while belowground autotrophic respiration and stimulation by live root inputs contributed 46.44% to soil surface respiration. This figure is notably higher than mean figures for nonforest soils derived from the literature and demonstrates the importance of crop‐specific parameterization of respiration models.