bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical, histopathological, and immunological evaluation of a series of patients with erythema nodosum
Authors: De Simone Clara , Caldarola Giacomo , Scaldaferri Franco , Petito Valentina , Perino Francesca , Arena Vincenzo , Papini Manuela , Caproni Marzia , Peris Ketty
Published: February 2016

Background

The pathogenesis of erythema nodosum (EN) is still poorly understood, and studies evaluating the involvement of a cytokine network are very scarce.

Objectives

To investigate clinical and pathological features, the cytokine profiles, and the balance of T‐regulatory (Treg) and T‐helper (Th)17 cells in serum and lesional skin of patients with EN.

Methods

Patients with a diagnosis of EN were consecutively enrolled, and their clinical and histopathological features were recorded. A panel of cytokines was evaluated in both serum and lesional skin using enzyme‐linked immunosorbent assay. Real‐time polymerase chain reaction was performed to evaluate the Treg/Th17 cell balance.

Results

Histopathological examination of skin biopsy specimens from all patients (four women and one man) showed classical features of EN. The most widely expressed cytokines were innate immunity cytokines (mainly tumor necrosis factor alpha, interleukin‐8 and ‐6) and growth factors (mainly granulocyte colony‐stimulating factor and monocyte chemoattractant protein‐1). The Treg/Th17 balance was highly different between patients.

Conclusions

The present study emphasizes the crucial role of neutrophils in the pathogenesis of EN, as high levels of cytokines and growth factors mainly involved in neutrophil recruitment and activation were detected.
Variations in genes involved in regulation of the nuclear factor – κB pathway and the risk of acute myeloid leukaemia
Authors: Rybka J. , Gębura K. , Wróbel T. , Wysoczańska B. , Stefanko E. , Kuliczkowski K. , Bogunia‐Kubik K.
Published: February 2016

Genes involved in regulation of the nuclear factor – kappa B (NF‐κB) pathway are suggested to play a role in the pathogenesis of acute myeloid leukaemia (AML). The present study aimed to assess the association between the NF‐κB1, TRAF3 and TLRs genes single nucleotide polymorphisms (SNPs) and disease susceptibility as well as progression in patients with AML. For this purpose 62 patients and 126 healthy individuals were genotyped for NF‐κB1 (rs28362491), TRAF3 (rs11160707; rs12147254), TLR2 (rs201786064), TLR4 (rs4986790; rs4986791) and TLR9 (rs5743836; rs187084) alleles. Three SNPs were found to be associated with the risk for the AML development. The TRAF3 (rs12147254) AA homozygosity (RR = 2.770, P = 0.0392), TLR9 (rs5743836) C wild‐type allele (RR = 2.542, P = 0.0096) as well as TLR9 (rs187084) T allele (RR = 13.396, P < 0.0001) and its homozygosity (RR = 11.805, P < 0.0001) were more frequent among patients with AML than healthy individuals. The associations of the rs187084 SNP were significant for both sexes. Moreover, patients who relapsed were more frequently characterized with the presence of the rs187084 TLR9 TT genotype (P = 0.045) or the rs12147254 TRAF3 A variant (P = 0.066). In conclusion, polymorphisms within the TLR9 and TRAF3 genes are associated with predisposition to AML and may affect the progression of the disease in the Polish population.
Body mass index trajectories from 2 to 18 years – exploring differences between European cohorts
Authors: Graversen L. , Howe L. D. , Sørensen T. I. A. , Sovio U. , Hohwü L. , Tilling K. , Laitinen J. , Taanila A. , Pouta A. , Järvelin M‐R. , Obel C.
Published: February 2016

Background

In recent decades, there has been an increase in the prevalence of childhood overweight in most high‐income countries. Within northern Europe, prevalence tends to be higher in the UK compared with the Scandinavian countries. We aimed to study differences in body mass index (BMI) trajectories between large cohorts of children from UK and Scandinavian populations.

Methods

We compared BMI trajectories in participants from the English Avon Longitudinal Study of Parents and Children born in 1991–1993 (ALSPAC) (N = 6517), the Northern Finland Birth Cohorts born in 1966 (NFBC1966) (N = 3321) and 1986 (NFBC1986) (N = 4764), and the Danish Aarhus Birth Cohort born in 1990–1992 (ABC) (N = 1920). We used multilevel models to estimate BMI trajectories from 2 to 18 years. We explored whether cohort differences were explained by maternal BMI, height, education or smoking during pregnancy and whether differences were attributable to changes in the degree of skew in the BMI distribution.

Results

Differences in mean BMI between the cohorts were small but emerged early and persisted in most cases across childhood. Girls in ALSPAC had a higher BMI than all other cohorts throughout childhood, e.g. compared with the NFBC1986 BMI was 2.2–3.5% higher. For boys, the difference emerging over time (comparing the two NFBC's) exceeded the differences across populations (comparing NFBC1986, ABC and ALSPAC). BMI distribution demonstrated increasing right skew with age.

Conclusion

Population‐level differences between cohorts were small, tended to emerge very early, persisted across childhood, and demonstrated an increase in the right‐hand tail of the BMI distribution.
Does more education mean less fun? A comparison of two animal presentations
Authors: Mann‐Lang J. B. , Ballantyne R. , Packer J.
Published: February 2016

Animal presentations have the potential to reach zoo and aquarium visitors with powerful conservation messages that inspire environmentally responsible behaviour. However, there is limited information available on the style of presentation that would be most effective in achieving the greatest impact. This research study was designed to investigate the impact of two differently designed dolphin presentations on conservation‐learning outcomes and overall enjoyment of visitors. The results showed that increasing the educational content of the presentation enhanced visitor learning considerably, without detracting from their enjoyment of the presentation. The research provides evidence for the value of animal presentations in the conservation‐education programmes of zoos and aquariums, and provides suggestions of how to increase the impact of such presentations.
Representation of age and ageing identities in popular music texts
Authors: Kelly Jacinta , Watson Roger , Pankratova Marina , Pedzeni Ann‐marie
Published: February 2016

Aims

To critically examine the representation of ageing identities in popular music texts.

Background

Having a positive outlook provides both short‐term benefits and has been proven to help people live longer. Music is capable of conveying positive and negative emotion towards ageing, however, only a limited number of unpublished studies exist on how age and ageing is represented in popular music.

Design

Qualitative discourse analysis.

Methods

In July 2014, a search without time limits was completed of the music lyrics databases,The Music Lyric Database, Songfacts, The Macronium and Absolute lyricsfor English language music texts relating to age and ageing.

Results

Findings revealed (N = 76) relevant music texts offering up negative and positive discourses of age and ageing, with negative predominating. Identities of age and ageing were categorized as ‘contented and celebrated aged’, ‘pitiful and petulant pensioners’ and ‘frail and flagging old folks’.

Conclusion

From this study, it is evident that mainly negative representations of age and ageing are available in popular music texts. It is imagined that the negative representations of age and ageing can be dispiriting, confidence and esteem lowering for older people and their potential impact might be considered carefully by artists. However, while evidence exists that negative and positive emotions can influence health and well‐being, further qualitative research is needed to explore what impact precisely the negative texts have on those experiencing ageing.
Hikers in Flip‐Flops: Luck Egalitarianism, Democratic Equality and the Distribuenda of Justice
Authors: Gheaus Anca
Published: February 2016

Abstract

The article has two aims. First, to show that a version of luck egalitarianism that includes relational goods amongst its distribuenda can, as a matter of internal logic, account for one of the core beliefs of relational egalitarianism. Therefore, there will be important extensional overlap, at the level of domestic justice, between luck egalitarianism and relational egalitarianism. This is an important consideration in assessing the merits of and relationship between the two rival views. Second, to provide some support for including relational goods, including those advocated by relational egalitarianism, on the distribuenda of justice and therefore to put in a good word for the overall plausibility of this conception of justice. I show why relational egalitarians, too, have reason to sympathise with this proposal.
Effect of Renal Sympathetic Denervation on Specific MicroRNAs as an Indicator of Reverse Remodeling Processes in Hypertensive Heart Disease
Authors: Dörr Oliver , Liebetrau Christoph , Möllmann Helge , Gaede Luise , Troidl Christian , Lankes Simone , Guckel Denise , Boeder Niklas , Voss Sandra , Bauer Timm , Hamm Christian , Nef Holger
Published: February 2016

A total of 90 consecutive patients undergoing renal sympathetic denervation (RSD) were included in this study. A significant reduction in office systolic blood pressure (SBP) of 21.1 mm Hg (P<.001) was documented 6 months after RSD. At this time point, circulating concentrations of microRNA (miR)‐133a were significantly increased (sevenfold; P<.001) compared with baseline values. Correlation analysis showed a significant relationship between baseline SBP values and SBP reduction (P<.001) as well as between miR‐133a baseline levels and the increase in miR‐133a expression (P<.001) after the 6‐month follow‐up. The effect of RSD on miR‐133a expression was significantly greater in patients at high risk for hypertensive heart disease. In addition to the effective blood pressure reduction in response to RSD, this study demonstrates an effect of RSD on miR reflecting cardiovascular reverse remodeling processes. Thus, these results provide information on a beneficial effect of RSD on cardiac recovery in patients at high risk for hypertensive heart disease.
Protection from cigarette smoke‐induced vascular injury by recombinant human relaxin‐2 (serelaxin)
Authors: Pini Alessandro , Boccalini Giulia , Baccari Maria Caterina , Becatti Matteo , Garella Rachele , Fiorillo Claudia , Calosi Laura , Bani Daniele , Nistri Silvia
Published: February 2016

Smoking is regarded as a major risk factor for the development of cardiovascular diseases (CVD). This study investigates whether serelaxin (RLX, recombinant human relaxin‐2) endowed with promising therapeutic properties in CVD, can be credited of a protective effect against cigarette smoke (CS)‐induced vascular damage and dysfunction. Guinea pigs exposed daily to CS for 8 weeks were treated with vehicle or RLX, delivered by osmotic pumps at daily doses of 1 or 10 μg. Controls were non‐smoking animals. Other studies were performed on primary guinea pig aortic endothelial (GPAE) cells, challenged with CS extracts (CSE) in the absence and presence of 100 ng/ml (17 nmol/l) RLX. In aortic specimens from CS‐exposed guinea pigs, both the contractile and the relaxant responses to phenylephrine and acetylcholine, respectively, were significantly reduced in amplitude and delayed, in keeping with the observed adverse remodelling of the aortic wall, endothelial injury and endothelial nitric oxide synthase (eNOS) down‐regulation. RLX at both doses maintained the aortic contractile and relaxant responses to a control‐like pattern and counteracted aortic wall remodelling and endothelial derangement. The experiments with GPAE cells showed that CSE significantly decreased cell viability and eNOS expression and promoted apoptosis by sparkling oxygen free radical‐related cytotoxicity, while RLX counterbalanced the adverse effects of CSE. These findings demonstrate that RLX is capable of counteracting CS‐mediated vascular damage and dysfunction by reducing oxidative stress, thus adding a tile to the growing mosaic of the beneficial effects of RLX in CVD.
Comparative movements of four large fish species in a lowland river
Authors: Koehn J. D. , Nicol S. J.
Published: February 2016

A multi‐year radio‐telemetry data set was used to comparatively examine the concurrent movements of the adults of three large‐bodied Australian native freshwater fishes (Murray cod Maccullochella peelii, trout cod Maccullochella macquariensis and golden perch Macquaria ambigua) and the introduced carp Cyprinus carpio. The study was conducted over a reach scale in the regulated Murray River in south‐eastern Australia. Differences were identified in the movements among these species. The predominant behaviour was the use of small movements (<1 km) for all species, and although larger‐scale movements (>1 km) did occur, the frequency varied considerably among species. Large‐scale movements were least evident for M. macquariensis and more common for M. ambigua and C. carpio with these two species also having a greater propensity to change locations. Macquaria ambigua displayed the largest movements and more M. ambigua moved on a ‘continual’ basis. Although a degree of site fidelity was evident for all species, the highest levels were exhibited by M. macquariensis and M. peelii. Homing was also evident to some degree in all species, but was greatest for M. peelii.
Prediction of postoperative liver failure using gadoxetic acid‐enhanced magnetic resonance imaging in patients with hepatocellular carcinoma
Authors: Jin Young‐Joo , Lee Seung Ho , Cho Soon Gu , Kim Jun Ho , Lee Jin‐Woo , Lee Kun Young , Shin Woo Young
Published: February 2016

Background

We intended to determine the usefulness of gadoxetic acid‐enhanced magnetic resonance (MR) imaging on preoperative prediction of the risk of postoperative liver failure (PLF) using measurement of relative liver enhancement (RLE) in patients who underwent surgical resection of hepatocellular carcinoma (HCC).

Methods

A total of 121 HCC patients who had underwent gadoxetic acid‐enhanced MRI before surgery between January 2012 and April 2015 at our hospital was retrospectively analyzed. RLE was calculated as the ratio of signal intensity measurements of the liver parenchyma in each liver segment before and 20 min after intravenous administration of gadoxetic acid. PLF was defined based on the “50–50 criteria” (prothrombin time <50% and serum bilirubin >5 mg/dL on 5 days after surgery).

Results

Of the 121 patients, 74 (61.2%) patients had liver cirrhosis, clinically. Median tumor size 2.8 cm (range, 1–14 cm), 106 (87.6%) patients had a single HCC, and 101 (83.5%) patients had HCC within Milan criteria. Based on the “50–50 criteria”, PLF was observed in 7 (5.8%) patients. Mean RLE was significantly lower in patients with PLF than those without it (55.9% vs 85.5%, P < 0.01). In a multivariate analysis, decreased RLE was a significant independent risk factor for PLF in HCC patients (odds ratio 0.97, P = 0.03). Optimal cut‐off RLE value was 82.36.

Conclusions

RLE was significantly lower in patients with PLF than those without it. Measurement of RLE using gadoxetic acid‐enhanced MR imaging before surgery can be useful for prediction of PLF in HCC patients who receive surgical treatment.
Simplified Complete Denture: A Systematic Review of the Literature
Authors: Ye Ye , Sun Jian
Published: February 2016

Purpose

Many procedures are used to construct traditional (T) complete dentures; however, a simplified (S) method requiring fewer steps and less time is available. This systematic review intends to summarize the modeling of simplified methods for complete dentures and evaluate the differences between the T method and S method. With this review, we hope to lay the foundation for proposing a standardized fabrication method for “simplified dentures.”

Methods

The MEDLINE (via PubMed) and EMBASE databases were searched for articles on simplified complete dentures published in English before April 2014. Eleven articles were included. One was about one‐step complete dentures, two were about SET (simplified treatment of edentulous patients), and the others were about the normal simplified method, which includes impression, occlusal registration, and try‐in. Seven were randomized controlled clinical trials (RCTs). The time, cost, patient satisfaction, clinical effects, masticatory performance, masticatory ability, and professional evaluation reported in these studies were compared.

Results

We summarized the different techniques of fabricating complete dentures and discussed the RCTs of the normal complete technique. None of the RCTs identified significant differences between the S and T groups in terms of patient ratings for general satisfaction, OHIP‐edentulous scale, denture quality, or masticatory ability. At the same time, the T method was significantly more expensive and required more time to complete than the S method.

Conclusions

Current scientific evidence suggests that the S method can replace or partly replace the T method. Moreover, specific rules should be devised to restrict the simplified construction, and detailed research should be conducted.
Developmental Trajectories of Maladaptive Perfectionism in Middle Childhood
Authors: Hong Ryan Y. , Lee Stephanie S. M. , Chng Ren Ying , Zhou Yuqi , Tsai Fen‐Fang , Tan Seok Hui
Published: February 2016

The developmental trajectories of maladaptive perfectionism, along with their consequences and origins, were examined in middle childhood. A sample of Singaporean children and their parents (N = 302) were recruited for a longitudinal study when the children were 7 years old. Subsequent follow‐up assessments were made at ages 8, 9, and 11. A multimethod approach was adopted where parent reports, child reports, and observational data on a dyadic interaction task were obtained. Using latent class growth modeling, four distinct classes were obtained for critical self‐oriented perfectionism (SOP‐C), whereas two classes emerged for socially prescribed perfectionism (SPP). Children with high and/or increasing SOP‐C and SPP trajectories constituted 60% and 78% of the sample, respectively. For both SOP‐C and SPP, trajectories with high initial status were associated with higher internalizing and externalizing symptoms. Parental intrusiveness and negative parenting predicted high and/or increasing SOP‐C trajectories, whereas the child temperament dimension of surgency predicted high SPP trajectory. Both SOP‐C and SPP trajectories tended to co‐occur, suggesting a mutually reinforcing process. This study yields important findings that help advance current understanding of the emergence and developmental pathways of maladaptive perfectionism in children.
JNK–TLR9 signal pathway mediates allergic airway inflammation through suppressing melatonin biosynthesis
Authors: Wu Hui‐Mei , Shen Qi‐Ying , Fang Lei , Zhang Shi‐Hai , Shen Pei‐Ting , Liu Ya‐Jing , Liu Rong‐Yu
Published: February 2016

Toll‐like receptors (TLRs) play pivotal role in the pathogenesis of allergic airway diseases such as asthma. TLR9 is one of the most extensively studied TLRs as an approach to treat asthma. In this study, we investigated the role of TLR9 in the allergic airway inflammation and the underlying mechanism. Wild‐type (WT) mice and TLR9−/− mice were sensitized and challenged with OVA to establish allergic airway disease model. We found that the expression of TLR9 was elevated concomitantly with airway inflammation post‐OVA challenge, and TLR9 deficiency effectively inhibited airway inflammation, including serum OVA‐specific immunoglobulin E (IgE), pulmonary inflammatory cell recruitment, mucus secretion, and bronchoalveolar lavage fluid (BALF) inflammatory cytokine production. Meanwhile, the protein expression of hydroxyindole‐o‐methyltransferase (HIOMT) in lung tissues, the level of melatonin in serum, and BALF were reduced in OVA‐challenged WT mice, while these reductions were significantly restored by TLR9 deficiency. Additionally, we showed that although TLR9 deficiency had no effect on OVA‐induced phosphorylation of JNK, inhibition of JNK by specific inhibitor SP600125 significantly decreased OVA‐induced expression of TLR9, suggesting that JNK is the upstream signal molecular of TLR9. Furthermore, SP600125 treatment promoted resolution of allergic airway inflammation in OVA‐challenged WT mice, but not further ameliorated allergic airway inflammation in OVA‐challenged TLR9−/− mice. Similarly, SP600125 significantly restored the protein expression of HIOMT and the level of melatonin in OVA‐challenged WT mice, while such effect was not further enhanced by TLR9 deficiency. Collectively, our results indicated that JNK–TLR9 signal pathway mediates allergic airway inflammation through suppressing melatonin biosynthesis.
Influence of medium‐chain fatty acids and short‐chain organic acids on jejunal morphology and intra‐epithelial immune cells in weaned piglets
Authors: Ferrara F. , Tedin L. , Pieper R. , Meyer W. , Zentek J.
Published: February 2016

Medium‐chain fatty acids (MCFA) and short‐chain organic acids (SOA) are often used as feed additives in piglet diets. There are limited studies in pigs describing the impact of MCFA or SOA on gut morphology and the local immune system. The aim of this study was to investigate whether the supplementation of SOA (0.41% fumaric acid and 0.32% lactic acid), or the combination of SOA with MCFA (0.15% caprylic and capric acid) would have effects on gut morphology and intestinal immune cells in weaned piglets. A total number of 72 weaned piglets were randomly allocated into three experimental groups. Tissue samples of six animals per group were used to investigate the potential impact of the feed additives on villus length and crypt depth of the jejunum and to quantify intra‐epithelial lymphocytes (IEL). CD3‐positive IEL were determined via immunohistochemistry (IHC) and flow cytometry (FC), whereas CD2−, CD5−, CD8β−, CD16− and γδ TCR‐positive IEL were only analysed by FC. The supplementation of MCFA and SOA did not significantly affect morphometric data. The FC data indicated that SOA significantly increased the quantity of CD2−CD8− γδ T cells in the jejunum epithelium. Both IHC and FC analyses of pig jejunum confirmed that the majority of IEL expressed the surface marker CD3 and could be classified as cytotoxic T lymphocytes. In conclusion, the data indicated that SOA increased the proportion of CD2−CD8− γδ T cells in the jejunal epithelium. Thus, SOA might enable a beneficial effect on the local immunity by increasing the constitutive number of potential effector cells to defeat infectious diseases.
Microclimate buffering and fertility island formation during Juniperus communis ontogenesis modulate competition–facilitation balance
Authors: Allegrezza M. , Corti G. , Cocco S. , Pesaresi S. , Chirico G.B. , Saracino A. , Bonanomi G.
Published: February 2016

Aims

Facilitation has been reported in a wide range of plant communities, with evidence of positive interactions between beneficiary and nurse plants shifting during their ontogenetic development. This study explored the hypothesis that shrubs of Juniperus communis subsp. nana (thereafter Juniperus) play a crucial role in the successional sequence of plant communities acting as nurse for different species, but only after reaching a certain size. In addition, we examined whether plant–plant interaction changes during ontogenesis of these shrubs in the presence of contrasting disturbance regimes in terms of substrate stability.

Location

Sibillini National Park, central Italy. The vegetation is semi‐natural dry grasslands (92/43/EEC Habitats Directive: Habitat 6210 ‐ Festuco‐Brometalia).

Methods

Field measurements were carried out to assess the effects of Juniperus on (1) the distribution of co‐existing vascular species, (2) the above‐ and below‐ground microclimate, and (3) changes in soil fertility and hydrology.

Results

The capacity of Juniperus shrubs to facilitate heterospecific plants considerably increases during its ontogenetic development, i.e. small shrubs mainly compete for resources with local vegetation, whereas large shrubs act as nurse plants for herbaceous and especially for woody species. The facilitation effect was slight, albeit significantly higher in the disturbed area than in the more stable one. Juniperus was able to promote the formation of an island of fertility under its canopy by accumulating a considerable amount of organic matter, N, P, Ca2+, Mg2+ and K+ in a few decades. Juniperus shrubs improve soil hydrological properties and mitigate the daily range of soil temperature, reducing the exposure of co‐existing plants to high temperatures and water loss through soil evaporation, particularly during the growing periods in spring and summer.

Conclusions

This study demonstrates that biogenic amelioration of soil quality, coupled with the mitigation of below‐canopy microclimatic conditions, control the establishment and growth of co‐existing plants during Juniperus shrub development.
Growth Performance, Biochemical Responses, and Skeletal Muscle Development of Juvenile Nile Tilapia, Oreochromis niloticus, Fed with Increasing Levels of Arginine
Authors: Neu Dacley , Boscolo Wilson , Zaminhan Micheli , Almeida Fernanda , Sary Cesar , Furuya Wilson
Published: February 2016

Tilapia, Oreochromis niloticus, is among the fish species with high potential for aquaculture in intensive farming, and Brazil is among the largest producers worldwide. Some of the amino acid requirements in practical diets for tilapia are still unknown. Thus, this study determined the dietary arginine requirements for Nile tilapia juveniles based on growth performance, hematological and biochemical responses, and muscle growth. Three hundred Nile tilapia juveniles (2.95 ± 0.79 g) were distributed into 20–500 L fiberglass aquaria and fed five extruded isoproteic (28% crude protein) and isoenergetic (3160 kcal/kg) diets formulated to contain 0.95, 1.10, 1.25, 1.40, and 1.55% arginine. Based on the quadratic regression analysis, the best results in weight gain, feed conversion, protein efficiency ratio, and protein retention were estimated in fish fed diets containing 1.36, 1.34, 1.36, and 1.37% arginine, respectively. The best amino acid body retention values were estimated in fish fed diets containing 1.31–1.37% arginine. Muscle growth occurred mainly by hyperplasia in fish fed 0.95% arginine, whereas reduction in the hyperplasia time and signs of hypertrophy occurred in fish fed 1.10–1.55% arginine diets. It was concluded that a diet with 1.36% of arginine (with 1.53% lysine in diet) meets the requirements of Nile tilapia juveniles.
BsdABsd2‐dependent vacuolar turnover of a misfolded version of the UapA transporter along the secretory pathway: prominent role of selective autophagy
Authors: Evangelinos Minoas , Martzoukou Olga , Chorozian Koar , Amillis Sotiris , Diallinas George
Published: February 2016

Transmembrane proteins translocate cotranslationally in the endoplasmic reticulum (ER) membrane and traffic as vesicular cargoes, via the Golgi, in their final membrane destination. Misfolding in the ER leads to protein degradation basically through the ERAD/proteasome system. Here, we use a mutant version of the purine transporter UapA (ΔR481) to show that specific misfolded versions of plasma membrane cargoes undergo vacuolar turnover prior to localization in the plasma membrane. We show that non‐endocytic vacuolar turnover of ΔR481 is dependent on BsdABsd2, an ER transmembrane adaptor of HulARsp5 ubiquitin ligase. We obtain in vivo evidence that BsdABsd2 interacts with HulARsp5 and ΔR481, primarily in the ER. Importantly, accumulation of ΔR481 in the ER triggers delivery of the selective autophagy marker Atg8 in vacuoles along with ΔR481. Genetic block of autophagy (atg9Δ, rabOts) reduces, but does not abolish, sorting of ΔR481 in the vacuoles, suggesting that a fraction of the misfolded transporter might be redirected for vacuolar degradation via the Golgi. Our results support that multiple routes along the secretory pathway operate for the detoxification of Aspergillus nidulans cells from misfolded membrane proteins and that BsdA is a key factor for marking specific misfolded cargoes.
Short‐term survival of Steller sea lion (Eumetopias jubatus) pups: Investigating the effect of health status on survival
Authors: Pendleton Grey W. , Hastings Kelly K. , Rea Lorrie D. , Jemison Lauri A. , O'Corry‐Crowe Greg M. , Beckmen Kimberlee B.
Published: February 2016

We estimated survival probabilities for Steller sea lion (Eumetopias jubatus) pups from 3 wk to 6 wk old and from 6 wk to 1 yr at three rookeries in southeastern Alaska. We also investigated the effect of mass, body condition, health variables, and the genetic origin on 3–6 wk survival. Survival differed substantially among rookeries and between sexes, with survival lowest at Hazy Islands, intermediate at White Sisters, and highest at Graves Rocks and survival lower for males than females. Body mass, body condition, and hematocrit were positively related to survival and blood %H2O and haptoglobin level (for females; no relationship for males) were negatively related to survival. Taking predictor variables collectively, sea lion pups at Hazy Islands, which had the lowest survival probability, had the lowest mass, hematocrit, and hemoglobin, and had high levels of blood %H2O, and hookworm infection. Values from Graves Rocks, which had the highest survival, were the opposite of those from Hazy Island (e.g., high mass, body condition, hematocrit, and hemoglobin), while those from White Sisters (intermediate survival) had varying means (e.g., high hematocrit and hemoglobin and low hookworms, but also low body condition); these patterns suggest that physiological factors potentially underlie rookery differences in survival.
Production of small cysteine‐rich effector proteins in Escherichia coli for structural and functional studies
Authors: Zhang Xiaoxiao , Nguyen Neal , Breen Susan , Outram Megan A. , Dodds Peter N. , Kobe Bostjan , Solomon Peter S. , Williams Simon J.
Published: February 2016

Although the lifestyles and infection strategies of plant pathogens are diverse, a prevailing feature is the use of an arsenal of secreted proteins, known as effectors, which aid in microbial infection. In the case of eukaryotic filamentous pathogens, such as fungi and oomycetes, effector proteins are typically dissimilar, at the protein sequence level, to known protein families and functional domains. Consequently, we currently have a limited understanding of how fungal and oomycete effectors promote disease. Protein biochemistry and structural biology are two methods that can contribute greatly to the understanding of protein function. Both techniques are dependent on obtaining proteins that are pure and functional, and generally require the use of heterologous recombinant protein expression systems. Here, we present a general scheme and methodology for the production and characterization of small cysteine‐rich (SCR) effectors utilizing Escherichia coli expression systems. Using this approach, we successfully produced cysteine‐rich effectors derived from the biotrophic fungal pathogen Melampsora lini and the necrotrophic fungal pathogen Parastagonospora nodorum. Access to functional recombinant proteins facilitated crystallization and functional experiments. These results are discussed in the context of a general workflow that may serve as a template for others interested in understanding the function of SCR effector(s) from their plant pathogen(s) of interest.
Heat stress of two tropical seagrass species during low tides – impact on underwater net photosynthesis, dark respiration and diel in situ internal aeration
Authors: Pedersen Ole , Colmer Timothy D. , Borum Jens , Zavala‐Perez Andrea , Kendrick Gary A.
Published: February 2016

Seagrasses grow submerged in aerated seawater but often in low O2 sediments. Elevated temperatures and low O2 are stress factors.

Internal aeration was measured in two tropical seagrasses, Thalassia hemprichii and Enhalus acoroides, growing with extreme tides and diel temperature amplitudes. Temperature effects on net photosynthesis (PN) and dark respiration (RD) of leaves were evaluated.

Daytime low tide was characterized by high pO2 (54 kPa), pH (8.8) and temperature (38°C) in shallow pools. As PN was maximum at 33°C (9.1 and 7.2 μmol O2 m−2 s−1 in T. hemprichii and E. acoroides, respectively), the high temperatures and reduced CO2 would have diminished PN, whereas RD increased (Q10 of 2.0–2.7) above that at 33°C (0.45 and 0.33 μmol O2 m−2 s−1, respectively). During night‐time low tides, O2 declined resulting in shoot base anoxia in both species, but incoming water containing c. 20 kPa O2 relieved the anoxia. Shoots exposed to 40°C for 4 h showed recovery of PN and RD, whereas 45°C resulted in leaf damage.

These seagrasses are ‘living near the edge’, tolerant of current diel O2 and temperature extremes, but if temperatures rise both species may be threatened in this habitat.
Plant pneumatics: stem air flow is related to embolism – new perspectives on methods in plant hydraulics
Authors: Pereira Luciano , Bittencourt Paulo R. L. , Oliveira Rafael S. , Junior Mauro B. M. , Barros Fernanda V. , Ribeiro Rafael V. , Mazzafera Paulo
Published: February 2016

Wood contains a large amount of air, even in functional xylem. Air embolisms in the xylem affect water transport and can determine plant growth and survival. Embolisms are usually estimated with laborious hydraulic methods, which can be prone to several artefacts.

Here, we describe a new method for estimating embolisms that is based on air flow measurements of entire branches. To calculate the amount of air flowing out of the branch, a vacuum was applied to the cut bases of branches under different water potentials.

We first investigated the source of air by determining whether it came from inside or outside the branch. Second, we compared embolism curves according to air flow or hydraulic measurements in 15 vessel‐ and tracheid‐bearing species to test the hypothesis that the air flow is related to embolism.

Air flow came almost exclusively from air inside the branch during the 2.5‐min measurements and was strongly related to embolism. We propose a new embolism measurement method that is simple, effective, rapid and inexpensive, and that allows several measurements on the same branch, thus opening up new possibilities for studying plant hydraulics.
SET domain–mediated lysine methylation in lower organisms regulates growth and transcription in hosts
Authors: Nwasike Chukwuazam , Ewert Sinead , Jovanovic Srdan , Haider Shozeb , Mujtaba Shiraz
Published: February 2016

Su(var)3‐9, Enhancer‐of‐zeste, Trithorax (SET) domain–mediated lysine methylation, one of the major epigenetic marks, has been found to regulate chromatin‐mediated gene transcription. Published studies have established further that methylation is not restricted to nuclear proteins but is involved in many cellular processes, including growth, differentiation, immune regulation, and cancer progression. The biological complexity of lysine methylation emerges from its capacity to cause gene activation or gene repression owing to the specific position of methylated‐lysine moieties on the chromatin. Accumulating evidence suggests that despite the absence of chromatin, viruses and prokaryotes also express SET proteins, although their functional roles remain relatively less investigated. One possibility could be that SET proteins in lower organisms have more than one biological function, for example, in regulating growth or in manipulating host transcription machinery in order to establish infection. Thus, elucidating the role of an SET protein in host–pathogen interactions requires a thorough understanding of their functions. This review discusses the biological role of lysine methylation in prokaryotes and lower eukaryotes, as well as the underlying structural complexity and functional diversity of SET proteins.
Management of Postherniorrhaphy Chronic Neuropathic Groin Pain: A Role for Dorsal Root Ganglion Stimulation
Authors: Liem Liong , Mekhail Nagy
Published: February 2016

Chronic neuropathic groin pain is a sequela of hernia surgery that occurs at unacceptably high rates, causing widespread impacts on quality of life. Although the medical community is beginning to recognize the role of surgical technique in the initiation and maintenance of postherniorrhaphy neuropathic pain, little information exists regarding pain management strategies for this condition. This review presents a summary of the pain condition state, its treatment options, and treatment recommendations. Both literature review and clinical experience were used to develop a proposed a treatment algorithm for the treatment of postherniorrhaphy pain.

The development of chronic pain may be prevented via a number of perioperative measures. For pain that is already established, some surgical approaches including inguinal neurectomy can be effective, in addition to standard pharmacological treatments and local infiltrations. An unmet need may still exist with these options, however, leaving a role for neuromodulation for the treatment of intractable cases. A pain management algorithm for iterative interventions including stimulation of the dorsal root ganglion (DRG) is described. It is expected that cross‐disciplinary awareness of surgeons for nonsurgical pain management options in the treatment of chronic neuropathic postherniorrhaphy pain will contribute to better clinical outcomes.
Anorexia Nervosa, Major Depression, and Suicide Attempts: Shared Genetic Factors
Authors: Thornton Laura M. , Welch Elisabeth , Munn‐Chernoff Melissa A. , Lichtenstein Paul , Bulik Cynthia M.
Published: February 2016

The extent to which genetic and environmental factors influenced anorexia nervosa (AN), major depressive disorder (MDD), and suicide attempts (SA) were evaluated. Participants were 6,899 women from the Swedish Twin Study of Adults: Genes and Environment. A Cholesky decomposition assessed independent and overlapping genetic and environmental contributions to AN, MDD, and SA. Genetic factors accounted for a substantial amount of liability to all three traits; unique environmental factors accounted for most of the remaining liability. Shared genetic factors may underlie the coexpression of these traits. Results underscore the importance of assessing for signs of suicide among individuals with AN.
Development and validation of the Axiom®Apple480K SNP genotyping array
Authors: Bianco Luca , Cestaro Alessandro , Linsmith Gareth , Muranty Hélène , Denancé Caroline , Théron Anthony , Poncet Charles , Micheletti Diego , Kerschbamer Emanuela , Di Pierro Erica A. , Larger Simone , Pindo Massimo , Van de Weg Eric , Davassi Alessandro , Laurens François , Velasco Riccardo , Durel Charles‐Eric , Troggio Michela
Published: February 2016

Cultivated apple (Malus × domestica Borkh.) is one of the most important fruit crops in temperate regions, and has great economic and cultural value. The apple genome is highly heterozygous and has undergone a recent duplication which, combined with a rapid linkage disequilibrium decay, makes it difficult to perform genome‐wide association (GWA) studies. Single nucleotide polymorphism arrays offer highly multiplexed assays at a relatively low cost per data point and can be a valid tool for the identification of the markers associated with traits of interest. Here, we describe the development and validation of a 487K SNP Affymetrix Axiom® genotyping array for apple and discuss its potential applications. The array has been built from the high‐depth resequencing of 63 different cultivars covering most of the genetic diversity in cultivated apple. The SNPs were chosen by applying a focal points approach to enrich genic regions, but also to reach a uniform coverage of non‐genic regions. A total of 1324 apple accessions, including the 92 progenies of two mapping populations, have been genotyped with the Axiom®Apple480K to assess the effectiveness of the array. A large majority of SNPs (359 994 or 74%) fell in the stringent class of poly high resolution polymorphisms. We also devised a filtering procedure to identify a subset of 275K very robust markers that can be safely used for germplasm surveys in apple. The Axiom®Apple480K has now been commercially released both for public and proprietary use and will likely be a reference tool for GWA studies in apple.
How do I perform hematopoietic progenitor cell selection?
Authors: Avecilla Scott T. , Goss Cheryl , Bleau Sharon , Tonon Jo‐ann , Meagher Richard C.
Published: February 2016

Graft‐versus‐host disease remains the most important source of morbidity and mortality associated with allogeneic stem cell transplantation. The implementation of hematopoietic progenitor cell (HPC) selection is employed by some stem cell processing facilities to mitigate this complication. Current cell selection methods include reducing the number of unwanted T cells (negative selection) and/or enriching CD34+ hematopoietic stem/progenitors (positive selection) using immunomagnetic beads subjected to magnetic fields within columns to separate out targeted cells. Unwanted side effects of cell selection as a result of T‐cell reduction are primary graft failure, increased infection rates, delayed immune reconstitution, possible disease relapse, and posttransplant lymphoproliferative disease. The Miltenyi CliniMACS cell isolation system is the only device currently approved for clinical use by the Food and Drug Administration. It uses magnetic microbeads conjugated with a high‐affinity anti‐CD34 monoclonal antibody capable of binding to HPCs in marrow, peripheral blood, or umbilical cord blood products. The system results in significantly improved CD34+ cell recoveries (50%‐100%) and consistent 3‐log CD3+ T‐cell reductions compared to previous generations of CD34+ cell selection procedures. In this article, the CliniMACS procedure is described in greater detail and the authors provide useful insight into modifications of the system. Successful implementation of cell selection procedures can have a significant positive clinical effect by greatly increasing the pool of donors for recipients requiring transplants. However, before a program implements cell selection techniques, it is important to consider the time and financial resources required to properly and safely perform these procedures.
Congenital dystrophic epidermolysis bullosa (DEB) in Sprague Dawley rats: a case series
Authors: Eden Kristin B. , Peterson Ashley , Payne Harold R. , Corapi Wayne V. , Mansell Joanne , Hoffman Aline Rodrigues
Published: February 2016

Background

Epidermolysis bullosa is a rare skin disease caused by defects in the basement membrane and/or other dermoepidermal junction components.

Hypothesis/Objectives

We describe a series of spontaneous cases of dystrophic epidermolysis bullosa (DEB) in a colony of Sprague Dawley rats investigated with histopathology, transmission electron microscopy (TEM) and inheritance pattern.

Animals

Four, 4‐day‐old pups from a litter of Sprague Dawley rats developed blistering, haemorrhagic skin lesions and were euthanized. Age‐matched controls from the same litter were normal. Several months later two more litters presented with identical findings. All three litters had the same sire, suggesting a genetic component.

Methods

Skin from affected and control animals was evaluated histologically and with TEM. Unaffected sibling pairs from affected litters were bred in order to potentially reproduce the disease and determine the mode of inheritance.

Results

Histologically, there was significant dermoepidermal clefting below the basement membrane with variable amounts of haemorrhage and cellular debris within the clefts. Ultrastructurally, clefting occurred below the basement membrane with an intact lamina densa and normal hemidesmosomes. Anchoring filaments were strikingly absent. Litters produced from phenotypically unaffected sibling pairs resulted in a total of four more litters with approximately a quarter of pups affected.

Conclusions and clinical importance

Based on the gross lesions, histopathological features and TEM determination of separation below the lamina densa and lack of normal anchoring fibrils, these cases are most consistent with DEB. This is the first report of naturally occurring, localized and reproducible recessive DEB in Sprague Dawley rats.
Intracellular soluble α‐synuclein oligomers reduce pyramidal cell excitability
Authors: Kaufmann Timothy J. , Harrison Paul M. , Richardson Magnus J. E. , Pinheiro Teresa J. T. , Wall Mark J.
Published: February 2016

Key points

The presynaptic protein α‐synuclein forms aggregates during Parkinson's disease.

Accumulating evidence suggests that the small soluble oligomers of α‐synuclein are more toxic than the larger aggregates appearing later in the disease.

The link between oligomer toxicity and structure still remains unclear.

In the present study, we have produced two structurally‐defined oligomers that have a similar morphology but differ in secondary structure.

These oligomers were introduced into neocortical pyramidal cells during whole‐cell recording and, using a combination of experimentation and modelling, electrophysiological parameters were extracted.

Both oligomeric species had similar effects on neuronal properties reducing input resistance, time constant and increasing capacitance. The net effect was a marked reduction in neuronal excitability that could impact on network activity.

The presynaptic protein α‐synuclein (αSyn) aggregates during Parkinson's disease (PD) to form large proteinaceous amyloid plaques, the spread of which throughout the brain clinically defines the severity of the disease. During early stages of aggregation, αSyn forms soluble annular oligomers that show greater toxicity than much larger fibrils. These oligomers produce toxicity via a number of possible mechanisms, including the production of pore‐forming complexes that permeabilize membranes. In the present study, two well‐defined species of soluble αSyn oligomers were produced by different protocols: by polymerization of monomer and by sonication of fibrils. The two oligomeric species produced were morphologically similar, with both having an annular structure and consisting of approximately the same number of monomer subunits, although they differed in their secondary structure. Oligomeric and monomeric αSyn were injected directly into the soma of pyramidal neurons in mouse neocortical brain slices during whole‐cell patch clamp recording. Using a combined experimental and modelling approach, neuronal parameters were extracted to measure, for the first time in the neocortex, specific changes in neuronal electrophysiology. Both species of oligomer had similar effects: (i) a significant reduction in input resistance and the membrane time constant and (ii) an increase in the current required to trigger an action potential with a resultant reduction in the firing rate. Differences in oligomer secondary structure appeared to produce only subtle differences in the activity of the oligomers. Monomeric αSyn had no effect on neuronal parameters, even at high concentrations. The oligomer‐induced fall in neuronal excitability has the potential to impact both network activity and cognitive processing.
Dynamic hyperarticulation of coda voicing contrasts
Authors: Seyfarth Scott , Buz Esteban , Jaeger T. Florian
Published: February 2016

This study investigates the capacity for targeted hyperarticulation of contextually-relevant contrasts. Participants communicated target words with final /s/ or /z/ when a voicing minimal-pair (e.g., target dose, minimal-pair doze) either was or was not available as an alternative in the context. The results indicate that talkers enhance the durational cues associated with the word-final voicing contrast based on whether the context requires it, and that this can involve both elongation as well as shortening, depending on what enhances the contextually-relevant contrast. This suggests that talkers are capable of targeted, context-sensitive temporal enhancements.