bluuebunny/crossref_metadata_2025 huggingface dataset:
A highly flexible and conductive graphene-wrapped carbon nanofiber membrane for high-performance electrocatalytic applications
Authors: Huang Yunpeng , Zhang Longsheng , Lu Hengyi , Lai Feili , Miao Yue-E , Liu Tianxi
Published: May 2016

Graphene-wrapped electrospun carbon nanofiber membranes with greatly improved electrical conductivity have been synthesized through an effective surface-induced assembly strategy.
The effect of different levels of crude protein on the pathophysiology of Haemonchus contortus infection in 2-year-old Boer dry does under confined conditions
Authors: Can T. V. , Hohenhaus M. A. , Murray P. J.
Published: May 2016

The effect of dietary protein supplementation on the pathophysiology of a single Haemonchus contortus infection in 2-year-old Boer dry does under confined conditions was examined. Twenty-four does were randomly confined in individual pens and allocated into three groups balanced by their liveweight. The goats in the Control group were offered a basal diet whereas goats in Treatments 1 and 2 were fed the basal diet plus 25% and 50% dietary protein increments, respectively. Each animal was orally administrated 100 H. contortus L3 larvae/kg liveweight on Day 0 of the experiment. The goat liveweights and FAMACHA scores were recorded at weekly intervals. Packed cell volumes, eosinophil percentage, haemoglobin concentration, total serum protein, globulin, and albumin concentrations were recorded on Days 0 and 14, and then at weekly intervals during the experiments. Faecal egg counts were measured on Days 0, 21, and then at weekly intervals thereafter. Antigen-specific IgA, IgG, and IgM titres were determined from Enzyme-linked immunosorbent assays tests on Days 0, 28, and at the termination of the experiment. The results of this study showed that a single H. contortus L3 infection did not cause pathogenic effects in 2-year-old Boer dry does. Dietary protein supplementation significantly lowered faecal egg count and significantly enhanced IgG titres (P < 0.05). However, the higher protein diets did not have any significant effects on liveweight, packed cell volumes, haemoglobin concentration, biological parameters (total serum protein, albumin, and globulin concentrations), and peripheral antibodies (IgA and IgM titres) between the treatments. Further investigations are required to clarify the role of protein supplementation to control H. contortus infection in goats.
Concentrating pre-mRNA processing factors in the histone locus body facilitates efficient histone mRNA biogenesis
Authors: Tatomer Deirdre C. , Terzo Esteban , Curry Kaitlin P. , Salzler Harmony , Sabath Ivan , Zapotoczny Grzegorz , McKay Daniel J. , Dominski Zbigniew , Marzluff William F. , Duronio Robert J.
Published: May 2016

The histone locus body (HLB) assembles at replication-dependent histone genes and concentrates factors required for histone messenger RNA (mRNA) biosynthesis. FLASH (Flice-associated huge protein) and U7 small nuclear RNP (snRNP) are HLB components that participate in 3′ processing of the nonpolyadenylated histone mRNAs by recruiting the endonuclease CPSF-73 to histone pre-mRNA. Using transgenes to complement a FLASH mutant, we show that distinct domains of FLASH involved in U7 snRNP binding, histone pre-mRNA cleavage, and HLB localization are all required for proper FLASH function in vivo. By genetically manipulating HLB composition using mutations in FLASH, mutations in the HLB assembly factor Mxc, or depletion of the variant histone H2aV, we find that failure to concentrate FLASH and/or U7 snRNP in the HLB impairs histone pre-mRNA processing. This failure results in accumulation of small amounts of polyadenylated histone mRNA and nascent read-through transcripts at the histone locus. Thus, the HLB concentrates FLASH and U7 snRNP, promoting efficient histone mRNA biosynthesis and coupling 3′ end processing with transcription termination.
Num1 anchors mitochondria to the plasma membrane via two domains with different lipid binding specificities
Authors: Ping Holly A. , Kraft Lauren M. , Chen WeiTing , Nilles Amy E. , Lackner Laura L.
Published: May 2016

The mitochondria–ER cortex anchor (MECA) is required for proper mitochondrial distribution and functions by tethering mitochondria to the plasma membrane. The core component of MECA is the multidomain protein Num1, which assembles into clusters at the cell cortex. We show Num1 adopts an extended, polarized conformation. Its N-terminal coiled-coil domain (Num1CC) is proximal to mitochondria, and the C-terminal pleckstrin homology domain is associated with the plasma membrane. We find that Num1CC interacts directly with phospholipid membranes and displays a strong preference for the mitochondria-specific phospholipid cardiolipin. This direct membrane interaction is critical for MECA function. Thus, mitochondrial anchoring is mediated by a protein that interacts directly with two different membranes through lipid-specific binding domains, suggesting a general mechanism for interorganelle tethering.
Nuclear bodies: Built to boost
Authors: Sawyer Iain A. , Dundr Miroslav
Published: May 2016

The classic archetypal function of nuclear bodies is to accelerate specific reactions within their crowded space. In this issue, Tatomer et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201504043) provide the first direct evidence that the histone locus body acts to concentrate key factors required for the proper processing of histone pre-mRNAs.
Human T cell responses to Japanese encephalitis virus in health and disease
Authors: Turtle Lance , Bali Tanushka , Buxton Gemma , Chib Savita , Chan Sajesh , Soni Mohammed , Hussain Mohammed , Isenman Heather , Fadnis Prachi , Venkataswamy Manjunatha M. , Satishkumar Vishali , Lewthwaite Penny , Kurioka Ayako , Krishna Srinivasa , Shankar M. Veera , Ahmed Riyaz , Begum Ashia , Ravi Vasanthapuram , Desai Anita , Yoksan Sutee , Fernandez Stefan , Willberg Christian B. , Kloverpris Henrik N. , Conlon Christopher , Klenerman Paul , Satchidanandam Vijaya , Solomon Tom
Published: May 2016

Japanese encephalitis (JE) virus (JEV) is an important cause of encephalitis in children of South and Southeast Asia. However, the majority of individuals exposed to JEV only develop mild symptoms associated with long-lasting adaptive immunity. The related flavivirus dengue virus (DENV) cocirculates in many JEV-endemic areas, and clinical data suggest cross-protection between DENV and JEV. To address the role of T cell responses in protection against JEV, we conducted the first full-breadth analysis of the human memory T cell response using a synthetic peptide library. Ex vivo interferon-γ (IFN-γ) responses to JEV in healthy JEV-exposed donors were mostly CD8+ and targeted nonstructural (NS) proteins, whereas IFN-γ responses in recovered JE patients were mostly CD4+ and targeted structural proteins and the secreted protein NS1. Among patients, a high quality, polyfunctional CD4+ T cell response was associated with complete recovery from JE. T cell responses from healthy donors showed a high degree of cross-reactivity to DENV that was less apparent in recovered JE patients despite equal exposure. These data reveal divergent functional CD4+ and CD8+ T cell responses linked to different clinical outcomes of JEV infection, associated with distinct targeting and broad flavivirus cross-reactivity including epitopes from DENV, West Nile, and Zika virus.
Electrophysiological characterization of the archaeal transporter NCX_Mj using solid supported membrane technology
Authors: Barthmes Maria , Liao Jun , Jiang Youxing , Brüggemann Andrea , Wahl-Schott Christian
Published: May 2016

Sodium–calcium exchangers (NCXs) are membrane transporters that play an important role in Ca2+ homeostasis and Ca2+ signaling. The recent crystal structure of NCX_Mj, a member of the NCX family from the archaebacterium Methanococcus jannaschii, provided insight into the atomistic details of sodium–calcium exchange. Here, we extend these findings by providing detailed functional data on purified NCX_Mj using solid supported membrane (SSM)–based electrophysiology, a powerful but unexploited tool for functional studies of electrogenic transporter proteins. We show that NCX_Mj is highly selective for Na+, whereas Ca2+ can be replaced by Mg2+ and Sr2+ and that NCX_Mj can be inhibited by divalent ions, particularly Cd2+. By directly comparing the apparent affinities of Na+ and Ca2+ for NCX_Mj with those for human NCX1, we show excellent agreement, indicating a strong functional similarity between NCX_Mj and its eukaryotic isoforms. We also provide detailed instructions to facilitate the adaption of this method to other electrogenic transporter proteins. Our findings demonstrate that NCX_Mj can serve as a model for the NCX family and highlight several possible applications for SSM-based electrophysiology.
Dosimetric comparison of carbon ion and X-ray radiotherapy for Stage IIIA non–small cell lung cancer
Authors: Kubo Nobuteru , Saitoh Jun-ichi , Shimada Hirofumi , Shirai Katsuyuki , Kawamura Hidemasa , Ohno Tatsuya , Nakano Takashi
Published: May 2016

The present study compared the dose–volume histograms of patients with Stage IIIA non–small cell lung cancer (NSCLC) treated with carbon ion radiotherapy with those of patients treated with X-ray radiotherapy. Patients with Stage IIIA NSCLC ( n  = 10 patients for each approach) were enrolled. Both radiotherapy plans were calculated with the same targets and organs at risk on the same CT. The treatment plan for the prophylactic lymph node and primary tumor (PTV1) delivered 40 Gy for X-ray radiotherapy and 40 Gy (relative biological effectiveness; RBE) for carbon ion radiotherapy. The total doses for the primary tumor and clinically positive lymph nodes (PTV2) were 60 Gy for X-ray radiotherapy and 60 Gy (RBE) for carbon ion radiotherapy. The homogeneity indexes for PTV1 and PTV2 were superior for carbon ion radiotherapy in comparison with X-ray radiotherapy (PTV1, 0.57 vs 0.65, P  = 0.009; PTV2, 0.07 vs 0.16, P  = 0.005). The normal lung mean dose, V5, V10 and V20 for carbon ion radiotherapy were 7.7 Gy (RBE), 21.4%, 19.7% and 17.0%, respectively, whereas the corresponding doses for X-ray radiotherapy were 11.9 Gy, 34.9%, 26.6% and 20.8%, respectively. Maximum spinal cord dose, esophageal maximum dose and V50, and bone V10, V30 and V50 were lower with carbon ion radiotherapy than with X-ray radiotherapy. The present study indicates that carbon ion radiotherapy provides a more homogeneous target dose and a lower dose to organs at risk than X-ray radiotherapy for Stage IIIA non–small cell lung cancer.
Cell division cycle‐associated protein 1 as a new melanoma‐associated antigen
Authors: Tokuzumi Aki , Fukushima Satoshi , Miyashita Azusa , Nakahara Satoshi , Kubo Yosuke , Yamashita Junji , Harada Miho , Nakamura Kayo , Kajihara Ikko , Jinnin Masatoshi , Ihn Hironobu
Published: May 2016

Immune checkpoint inhibitors have increased the median survival of melanoma patients. To improve their effects, antigen‐specific therapies utilizing melanoma‐associated antigens should be developed. Cell division cycle‐associated protein 1 (CDCA1), which has a specific function at the kinetochores for stabilizing microtubule attachment, is overexpressed in various cancers. CDCA1, which is a member of cancer–testis antigens, does not show detectable expression levels in normal tissues. Quantitative reverse transcription polymerase chain reaction and immunoblotting analyses revealed that CDCA1 was expressed in all of the tested melanoma cell lines, 74% of primary melanomas, 64% of metastatic melanomas and 25% of nevi. An immunohistochemical analysis and a Cox proportional hazards model showed that CDCA1 could be a prognostic marker in malignant melanoma (MM) patients. CDCA1‐specific siRNA inhibited the cell proliferation of SKMEL2 and WM115 cells, but did not reduce the migration or invasion activity. These results suggest that CDCA1 may be a new therapeutic target of melanoma.
Dermoscopy of nail fold and elbow in the differential diagnosis of early psoriatic arthritis sine psoriasis and early rheumatoid arthritis
Authors: Errichetti Enzo , Zabotti Alen , Stinco Giuseppe , Quartuccio Luca , Sacco Stefania , De Marchi Ginevra , Piccirillo Angelo , De Vita Salvatore
Published: May 2016

Differentiation between psoriatic arthritis (PsA) sine psoriasis and rheumatoid arthritis (RA) may be a challenge, especially in the early stages, hence the need for new instrumental markers to assist their diagnosis. In this study, we investigated possible dermoscopic differences in vascular appearance of nail fold and elbow (a classic site of repeated trauma) in these two conditions. Fifteen patients with PsA sine psoriasis, 12 patients with RA and 12 controls were included in the study. Regarding the nail fold vascular appearance in PsA sine psoriasis and RA cohorts, the presence of diffuse reddish background with or without sparse dotted vessels was significant in the former, whereas the evidence of parallel dotted/short linear vessels (“fish school‐like” pattern) or irregular/ramified, blurry, purple vessels were significant in the latter; none of these patterns were detected in the control group. Regarding the elbow, the pattern significantly associated with PsA sine psoriasis consisted of diffusely distributed, red, dotted vessels. On the other hand, RA patients and controls displayed similar dermoscopic findings, with three possible vascular patterns being observed: (i) irregular, blurry, purple vessels; (ii) avascular appearance; and (iii) sparse, dotted, purple vessels. In conclusion, dermoscopy may be a useful supportive tool for differentiating early PsA sine psoriasis from RA.
Early cognitive and linguistic profiles of different types of 7‐ to 8‐year‐old readers
Authors: Potocki Anna , Ecalle Jean , Magnan Annie
Published: May 2016

The aim of this study was to investigate the early characteristics of four profiles of readers established in second grade (7–8 years of age): good readers, specific poor decoders, specific poor comprehenders and general poor readers. These profiles were compared retrospectively on a range of measures administered 2 years earlier, in kindergarten. These measures were based on factors known to be predictors of either decoding skills or comprehension performance. The results showed that children experiencing comprehension difficulties in second grade have early deficits in vocabulary, inferencing, working memory and morphology, while the children with decoding difficulties have limited letter knowledge and rapid naming performance. Phonological skills and verbal short‐term memory appeared to be deficient in all three profiles of struggling readers. These results are discussed in terms of the early identification of at‐risk children in kindergarten and the remedial programmes that could be provided to them at an early stage.
The Influence of Prefermentative Addition of Gallic Acid on the Phenolic Composition and Chromatic Characteristics of Cabernet Sauvignon Wines
Authors: Liu Yue , Zhang Bo , He Fei , Duan Chang‐Qing , Shi Ying
Published: May 2016

In this study, the prefermentative addition of gallic acid in Cabernet Sauvignon red winemaking was performed. The influence of gallic acid addition on wine phenolic composition, the ratio of copigmentation, and the color parameters were monitored throughout the winemaking process. The results showed that the prefermentative addition of gallic acid enhanced the extraction of total anthocyanins and the copigmentation effect, producing wines with more darkness, redness, yellowness, and saturation. Moreover, the addition of gallic acid contributed to the concentration of total phenolic acids. However, it had a negative effect on the concentrations of flavonols and flavan‐3‐ols in the final wines. Thus, the prefermentative addition of gallic acid at appropriate levels might be a promising enological technology to obtain wines with high color quality and aging potential.
Assessing the Potential Content of Ethyl Carbamate in White, Red, and Rosé Wines as a Key Factor for Pursuing Urea Degradation by Purified Acid Urease
Authors: Cerreti Martina , Fidaleo Marcello , Benucci Ilaria , Liburdi Katia , Tamborra Pasquale , Moresi Mauro
Published: May 2016

The ethyl carbamate (EC) content of a wine after a given temperature‐time storage was theoretically predicted from the potential concentration of ethyl carbamate (PEC), as determined via an accelerated EC formation test. Such information was used to decide whether an enzymatic treatment was needed to reduce the wine urea level before bottling/aging. To this end, 6 white, red, and rosé wines, manufactured in Italy as such or enriched with urea, were tested for their PEC content either before or after enzymatic treatment using a purified acid urease preparation derived from Lactobacillus fermentum. The treatment was severely affected by the total phenolic content (TP) of the wine, the estimated pseudo‐first‐order kinetic rate constant for NH3 formation reducing by a factor of approximately 2000 as the TP increased from 0 to 1.64 g L‐1. Such a sensitivity to TP was by far greater than that pertaining to a killed cell‐based enzyme preparation used previously. Urea hydrolysis was successful at reducing EC concentration in wines with low levels of TP and other EC precursors.
Novel Synthesis of Phytosterol Ester from Soybean Sterol and Acetic Anhydride
Authors: Yang Fuming , Oyeyinka Samson A. , Ma Ying
Published: May 2016

Phytosterols are important bioactive compounds which have several health benefits including reduction of serum cholesterol and preventing cardiovascular diseases. The most widely used method in the synthesis of its ester analogous form is the use of catalysts and solvents. These methods have been found to present some safety and health concern. In this paper, an alternative method of synthesizing phytosterol ester from soybean sterol and acetic anhydride was investigated. Process parameters such as mole ratio, temperature and time were optimized. The structure and physicochemical properties of phytosterol acetic ester were analyzed. By the use of gas chromatography, the mole ratio of soybean sterol and acetic anhydride needed for optimum esterification rate of 99.4% was 1:1 at 135 °C for 1.5 h. FTIR spectra confirmed the formation of phytosterol ester with strong absorption peaks at 1732 and 1250 cm–1, which corresponds to the stretching vibration of C=O and C—O—C, respectively. These peaks could be attributed to the formation of ester links which resulted from the reaction between the hydroxyl group of soybean sterol and the carbonyl group of acetic anhydride. This paper provides a better alternative to the synthesis of phytosterol ester without catalyst and solvent residues, which may have potential application in the food, health‐care food, and pharmaceutical industries.
A universal and reliable assay for molecular sex identification of three‐spined sticklebacks (Gasterosteus aculeatus)
Authors: Toli E.‐A. , Calboli F.C.F. , Shikano T. , Merilä J.
Published: May 2016

In heterogametic species, biological differences between the two sexes are ubiquitous, and hence, errors in sex identification can be a significant source of noise and bias in studies where sex‐related sources of variation are of interest or need to be controlled for. We developed and validated a universal multimarker assay for reliable sex identification of three‐spined sticklebacks (Gasterosteus aculeatus). The assay makes use of genotype scores from three sex‐linked loci and utilizes Bayesian probabilistic inference to identify sex of the genotyped individuals. The results, validated with 286 phenotypically sexed individuals from six populations of sticklebacks representing all major genetic lineages (cf. Pacific, Atlantic and Japan Sea), indicate that in contrast to commonly used single‐marker‐based sex identification assays, the developed multimarker assay should be 100% accurate. As the markers in the assay can be scored from agarose gels, it provides a quick and cost‐efficient tool for universal sex identification of three‐spined sticklebacks. The general principle of combining information from multiple markers to improve the reliability of sex identification is transferable and can be utilized to develop and validate similar assays for other species.
Assessing the cost‐efficiency of environmental DNA sampling
Authors: Smart Adam S. , Weeks Andrew R. , van Rooyen Anthony R. , Moore Alana , McCarthy Michael A. , Tingley Reid
Published: May 2016

Environmental DNA (eDNA) sampling can be a highly sensitive method for detecting aquatic taxa; however, the cost‐efficiency of this technique relative to traditional methods has not been rigorously assessed.

We show how methods that account for imperfect and stochastic detection can be used to (i) determine the optimal allocation of survey effort with eDNA sampling for a fixed budget (i.e. identify the optimal combination of water samples vs. site visits), and (ii) assess the cost‐efficiency of eDNA sampling relative to traditional survey techniques. We illustrate this approach by comparing eDNA sampling and bottle‐trapping for an exotic newt species (Lissotriton v. vulgaris) recently detected in Melbourne, Australia.

Bottle traps produced much lower detection rates than eDNA sampling, but the cost‐efficiency of the two methods can be similar because bottle‐trapping is cheaper per sample. The relative cost‐efficiency of the two sampling methods was sensitive to the available survey budget, the costs of eDNA primer/probe development and sample processing and the number of positive quantitative PCR assays (qPCRs) used to designate a water sample as positive for newt DNA. Environmental DNA sampling was more cost‐efficient than bottle‐trapping for small to intermediate budgets when primer/probe development and sample processing costs were low, and 1/4 or 2/4 positive qPCRs were used to label a water sample as positive for newt eDNA. However, bottle traps were generally more cost‐efficient than eDNA sampling when primer/probe development and sample processing costs were high, regardless of qPCR threshold or survey budget.

Traditional sampling methods may achieve lower detection probabilities compared to eDNA sampling, but the totality of costs can make eDNA sampling less efficient than traditional techniques in some circumstances. Our approach provides a quantitative framework for determining how many water samples and site visits are required to maximize detection probabilities with eDNA sampling, and can calculate the cost‐efficiency of any sampling method.
Visual outcome in Sturge–Weber syndrome: a systematic review and Dutch multicentre cohort
Authors: Koenraads Yvonne , van Egmond‐Ebbeling Michelle B. , de Boer Joke H. , Imhof Saskia M. , Braun Kees P. J. , Porro Giorgio L. ,   the SWS study group
Published: May 2016

Visual functions in Sturge–Weber syndrome (SWS) may be impaired by glaucoma, diffuse choroidal haemangioma (DCH) or leptomeningeal angioma. The aim of this study was to gain better insight in the visual deficits of SWS patients. A systematic literature search using PubMed and Embase medical databases was performed to identify articles describing visual acuity (VA) and/or visual field (VF) findings in SWS patients. In addition, a Dutch multicentre cohort with 33 SWS patients was collected and the combined results of VA and VF findings are presented. Visual acuity results of 25 studies and VF results of 12 studies were suitable for data extraction. Description of the combination of both VA and VF findings was scarce. Homonymous hemianopia (HH) was present in 42% of SWS patients. Seventy per cent of eyes had a (near) normal vision, while VA of eyes with glaucoma or DCH was severely impaired in 28% and 67%, respectively. In the Dutch cohort, only 18% (6/33) of patients had (near) normal findings of both visual parameters. In addition, half of the patients with glaucoma suffered from a combination of a HH and VA impairment. In conclusion, although SWS patients are exposed to severe functional visual impairment due to the possible cumulative consequences of glaucoma, DCH and cerebral injury, description of the combination of both VA and VF results is scarce in the literature. Particularly, the combination of visual impairment due to glaucoma or DCH, and HH might be invalidating.
Degree of corneal anaesthesia after topical application of 0.4% oxybuprocaine hydrochloride and 0.5% proparacaine hydrochloride ophthalmic solution in clinically normal cattle
Authors: Little WB , Jean G St. , Sithole F , Little E , Jean K Yvorchuk‐St.
Published: May 2016

Objectives

The use of corneal anaesthesia is necessary for a range of clinical purposes. Therefore, we assessed and compared the efficacy of corneal anaesthesia after application of 0.4% oxybuprocaine hydrochloride and 0.5% proparacaine hydrochloride ophthalmic solution in clinically normal cattle.

Methods

The 24 clinically normal cows were allocated into two groups. Cows in group 1 (n = 12) received 0.2 mLof 0.4% oxybuprocaine hydrochloride with fluorescein ophthalmic solution in one eye and 0.2 mLof sterile saline (0.9%NaCl) with fluorescein in the contralateral eye (control). Group 2 (n = 12) received 0.2 mLof 0.4% oxybuprocaine hydrochloride with fluorescein ophthalmic solution in one eye and 0.2 mLof 0.5% proparacaine hydrochloride with fluorescein in the contralateral eye (control). In each group, corneal touch threshold was determined by Cochet‐Bonnet aesthesiometer for both eyes immediately prior to topical administration of solutions, at 1 min and 5 min after administration of topical solutions and every 5 min thereafter for a total of 75 min.

Results

Significant corneal anaesthesia was noted immediately following topical application of both oxybuprocaine and proparacaine as compared with controls, with maximal corneal anaesthesia noted 1 min after administration. Both oxybuprocaine and proparacaine produced significant corneal anaesthesia for the duration of the 75‐min study. Neither oxybuprocaine hydrochloride nor proparacaine hydrochloride treatment resulted in visible adverse effects.

Conclusion

There are limited data available demonstrating the efficacy and duration of corneal anaesthetic agents in cattle. Both oxybuprocaine hydrochloride and proparacaine hydrochloride should be considered practical options for providing corneal anaesthesia in cattle in a clinical setting.
Ultrasonographically visible hepatic location in clinically normal horses
Authors: Johns IC , Miles A
Published: May 2016

Objective

Ultrasound is widely used for evaluating horses with suspected liver dysfunction. Although a change in size is considered suggestive of pathology, no clear guidelines exist to define the hepatic ultrasonographically visible locations (HUVL) in horses. The aim of the study was to describe theHUVLin normal horses and determine whether this is altered by signalment, height, weight and body condition score (BCS).

Design

Prospective observational study.

Procedure

Bilateral ultrasonographic evaluation was performed in 58 clinically normal horses with no history of hepatic disease. The most cranial/caudal intercostal spaces (ICS), total number ofICSin which the liver was visualised and the ventral extent of the liver were recorded.

Results

Liver was visualised on the right in 56/58 horses (97%), the left in 41/58 (71%) and on both sides in 39/58 (67%). The most cranialICSwas 5 (right) or 4 (left) and the most caudal was 16 (right) or 11 (left). Liver was visualised inICS0–11 (right) andICS0–5 (left). Liver was not visualised ventral to the costochondral junction. There was no significant effect of sex, breed, height, weight orBCSonHUVL. Liver was visible in significantly fewerICSon the right in horses aged 24 years and older (medianICS3.5) compared with younger horses (medianICS7; P = 0.016).

Conclusion

These findings suggest that the liver should be consistently visualised on the right side, but absence of ultrasonographically visible liver on the left is unlikely to be clinically relevant. Liver dimensions may be decreased in older horses.
Influence of management practices on plant assemblages of road–field boundaries in an agricultural landscape
Authors: Chaudron Clémence , Perronne Rémi , Bonthoux Sébastien , Di Pietro Francesca
Published: May 2016

Questions

Plant communities of road verges adjoining arable fields are often managed for conservation purposes. How do the diversity and composition of plant communities differ within and between berms, embankments and field margins? What is the influence of management practices on the diversity and composition of plant communities within and between these elements? Considering species frequently occurring in these three elements (hereafter generalist species), do road–field management practices influence their abundance in field margins?

Location

Central‐western France.

Methods

Three adjacent elements located between district roads and winter cereal fields – i.e. berm, embankment and field margin – were sampled in 40 road–field boundaries situated in an agricultural area. Management practices on each element were characterized (i.e. mowing frequency and/or mowing period, inputs of herbicide and nitrogen fertilizers). We compared species diversity and taxonomic composition within and between elements. We tested the influence of management practices on (i) species richness and species evenness in each element, (ii) abundance‐based compositional dissimilarity between pairs of elements using a model averaging procedure, and (iii) abundance of generalist species in field margins using generalized Cochran‐Mantel‐Haenszel tests.

Results

Compositional dissimilarity between elements was mainly due to changes of dominant species. An early mowing of the berm increased berm species richness, while late mowing increased species richness of adjacent elements. An increase in embankment mowing frequency decreased species evenness in the embankment while input of herbicide on the embankment decreased the substitution rate between embankment and field margin. Finally, late mowing of the berm and one cut of the embankment both increased abundance of some generalist weeds in field margins.

Conclusions

In our agricultural landscape, mowing berms once in early summer is appropriate to promote plant species richness, while late mowing may potentially conflict with integrated weed management in adjacent arable fields. We suggest that programmes managing road verges should take into account the effects on plant assemblages within road verge elements and adjacent arable fields, as well as the potential increase in weed risk.
Effect of flecainide derivatives on sarcoplasmic reticulum calcium release suggests a lack of direct action on the cardiac ryanodine receptor
Authors: Bannister Mark L , Alvarez‐Laviada Anita , Thomas N Lowri , Mason Sammy A , Coleman Sharon , du Plessis Christo L , Moran Abbygail T , Neill‐Hall David , Osman Hasnah , Bagley Mark C , MacLeod Kenneth T , George Christopher H , Williams Alan J
Published: May 2016

Background and Purpose

Flecainide is a use‐dependent blocker of cardiac Na+ channels. Mechanistic analysis of this block showed that the cationic form of flecainide enters the cytosolic vestibule of the open Na+ channel. Flecainide is also effective in the treatment of catecholaminergic polymorphic ventricular tachycardia but, in this condition, its mechanism of action is contentious. We investigated how flecainide derivatives influence Ca2+‐release from the sarcoplasmic reticulum through the ryanodine receptor channel (RyR2) and whether this correlates with their effectiveness as blockers of Na+ and/or RyR2 channels.

Experimental Approach

We compared the ability of fully charged (QX‐FL) and neutral (NU‐FL) derivatives of flecainide to block individual recombinant human RyR2 channels incorporated into planar phospholipid bilayers, and their effects on the properties of Ca2+ sparks in intact adult rat cardiac myocytes.

Key Results

Both QX‐FL and NU‐FL were partial blockers of the non‐physiological cytosolic to luminal flux of cations through RyR2 channels but were significantly less effective than flecainide. None of the compounds influenced the physiologically relevant luminal to cytosol cation flux through RyR2 channels. Intracellular flecainide or QX‐FL, but not NU‐FL, reduced Ca2+ spark frequency.

Conclusions and Implications

Given its inability to block physiologically relevant cation flux through RyR2 channels, and its lack of efficacy in blocking the cytosolic‐to‐luminal current, the effect of QX‐FL on Ca2+ sparks is likely, by analogy with flecainide, to result from Na+ channel block. Our data reveal important differences in the interaction of flecainide with sites in the cytosolic vestibules of Na+ and RyR2 channels.
The actions of relaxin on the human cardiovascular system
Authors: Sarwar Mohsin , Du Xiao‐Jun , Dschietzig Thomas B , Summers Roger J
Published: May 2016

The insulin‐like peptide relaxin, originally identified as a hormone of pregnancy, is now known to exert a range of pleiotropic effects including vasodilatory, anti‐fibrotic, angiogenic, anti‐apoptotic and anti‐inflammatory effects in both males and females. Relaxin produces these effects by binding to a cognate receptor RXFP1 and activating a variety of signalling pathways including cAMP, cGMP and MAPKs as well as by altering gene expression of TGF‐β, MMPs, angiogenic growth factors and endothelin receptors. The peptide has been shown to be effective in halting or reversing many of the adverse effects including fibrosis in animal models of cardiovascular disease including ischaemia/reperfusion injury, myocardial infarction, hypertensive heart disease and cardiomyopathy. Relaxin given to humans is safe and produces favourable haemodynamic changes. Serelaxin, the recombinant form of relaxin, is now in extended phase III clinical trials for the treatment of acute heart failure. Previous clinical studies indicated that a 48 h infusion of relaxin improved 180 day mortality, yet the mechanism underlying this effect is not clear. This article provides an overview of the cellular mechanism of effects of relaxin and summarizes its beneficial actions in animal models and in the clinic. We also hypothesize potential mechanisms for the clinical efficacy of relaxin, identify current knowledge gaps and suggest new ways in which relaxin could be useful therapeutically.

Linked Articles

This article is part of a themed section on Recent Progress in the Understanding of Relaxin Family Peptides and their Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.10/issuetoc
In permanent atrial fibrillation, PDE3 reduces force responses to 5‐HT, but PDE3 and PDE4 do not cause the blunting of atrial arrhythmias
Authors: Berk Emanuel , Christ Torsten , Schwarz Simon , Ravens Ursula , Knaut Michael , Kaumann Alberto J
Published: May 2016

Background and Purpose

5‐HT increases force and L‐type Ca2+ current (ICa,L) and causes arrhythmias through 5‐HT4 receptors in human atrium. In permanent atrial fibrillation (peAF), atrial force responses to 5‐HT are blunted, arrhythmias abolished but ICa,L responses only moderately attenuated. We investigated whether, in peAF, this could be due to an increased function of PDE3 and/or PDE4, using the inhibitors cilostamide (300 nM) and rolipram (1 μM) respectively.

Experimental Approach

Contractile force, arrhythmic contractions and ICa,L were assessed in right atrial trabeculae and myocytes, obtained from patients with sinus rhythm (SR), paroxysmal atrial fibrillation (pAF) and peAF.

Key Results

Maximum force responses to 5‐HT were reduced to 15% in peAF, but not in pAF. Cilostamide, but not rolipram, increased both the blunted force responses to 5‐HT in peAF and the inotropic potency of 5‐HT fourfold to sevenfold in trabeculae of patients with SR, pAF and peAF. Lusitropic responses to 5‐HT were not decreased in peAF. Responses of ICa,L to 5‐HT did not differ and were unaffected by cilostamide or rolipram in myocytes from patients with SR or peAF. Concurrent cilostamide and rolipram increased 5‐HT's propensity to elicit arrhythmias in trabeculae from patients with SR, but not with peAF.

Conclusions and Implications

PDE3, but not PDE4, reduced inotropic responses to 5‐HT in peAF, independently of lusitropy and ICa,L, but PDE3 activity was the same as that in patients with SR and pAF. Atrial remodelling in peAF abolished the facilitation of 5‐HT to induce arrhythmias by inhibition of PDE3 plus PDE4.
Effects of xanthine oxidase inhibition with febuxostat on the development of nephropathy in experimental type 2 diabetes
Authors: Komers Radko , Xu Bei , Schneider Jennifer , Oyama Terry T
Published: May 2016

Background and Purpose

Elevated serum uric acid (UA) is a risk factor for the development of kidney disease. Inhibitors of xanthine oxidase (XOi), an enzyme involved in UA synthesis, have protective effects at early stages of experimental diabetic nephropathy (DN). However, long‐term effects of XOi in models of DN remain to be determined.

Experimental Approach

The development of albuminuria, renal structure and molecular markers of DN were studied in type 2 diabetic Zucker obese (ZO) rats treated for 18 weeks with the XOi febuxostat and compared with vehicle‐treated ZO rats, ZO rats treated with enalapril or a combination of both agents, and lean Zucker rats without metabolic defects.

Results

Febuxostat normalized serum UA and attenuated the development of albuminuria, renal structural changes, with no significant effects on BP, metabolic control or systemic markers of oxidative stress (OS). Most of these actions were comparable with those of enalapril. Combination treatment induced marked decreases in BP and was more effective in ameliorating structural changes, expression of profibrotic genes and systemic OS than either monotherapy. Febuxostat attenuated renal protein expression of TGF‐ß, CTGF, collagen 4, mesenchymal markers (FSP1 and vimentin) and a tissue marker of OS nitrotyrosine. Moreover, febuxostat attenuated TGF‐ß‐ and S100B‐induced increased expression of fibrogenic molecules in renal tubular cells in vitro in UA‐free media in an Akt kinase‐dependent manner.

Conclusions and Implications

Febuxostat is protective and enhances the actions of enalapril in experimental DN. Multiple mechanisms might be involved, such as a reduction of UA, renal OS and inhibition of profibrotic signalling.
Modeling the efficacy of the extent of surgical resection in the setting of radiation therapy for glioblastoma
Authors: Hathout Leith , Ellingson Benjamin , Pope Whitney
Published: May 2016

Standard therapy for glioblastoma (GBM) includes maximal surgical resection and radiation therapy. While it is established that radiation therapy provides the greatest survival benefit of standard treatment modalities, the impact of the extent of surgical resection (EOR) on patient outcome remains highly controversial. While some studies describe no correlation between EOR and patient survival even up to total resection, others propose either qualitative (partial versus subtotal versus complete resection) or quantitative EOR thresholds, below which there is no correlation with survival. This work uses a mathematical model in the form of a reaction–diffusion partial differential equation to simulate tumor growth and treatment with radiation therapy and surgical resection based on tumor‐specific rates of diffusion and proliferation. Simulation of 36 tumors across a wide spectrum of diffusion and proliferation rates suggests that while partial or subtotal resections generally do not provide a survival advantage, complete resection significantly improves patient outcomes. Furthermore, our model predicts a tumor‐specific quantitative threshold below which EOR has no effect on patient survival and demonstrates that this threshold increases with tumor aggressiveness, particularly with the rate of proliferation. Thus, this model may serve as an aid for determining both when surgical resection is indicated as well as the surgical margins necessary to provide clinically significant improvements in patient survival. In addition, by assigning relative benefits to radiation and surgical resection based on tumor invasiveness and proliferation, this model confirms that (with the exception of the least aggressive tumors) the survival benefit of radiation therapy exceeds that of surgical resection.
Sensitivities to various epidermal growth factor receptor‐tyrosine kinase inhibitors of uncommon epidermal growth factor receptor mutations L861Q and S768I: What is the optimal epidermal growth factor receptor‐tyrosine kinase inhibitor?
Authors: Banno Eri , Togashi Yosuke , Nakamura Yu , Chiba Masato , Kobayashi Yoshihisa , Hayashi Hidetoshi , Terashima Masato , de Velasco Marco A. , Sakai Kazuko , Fujita Yoshihiko , Mitsudomi Tetsuya , Nishio Kazuto
Published: May 2016

Most patients with non‐small cell lung cancer (NSCLC) harboring common epidermal growth factor receptor (EGFR) mutations, such as deletions in exon 19 or the L858R mutation in exon 21, respond dramatically to EGFR tyrosine kinase inhibitors (EGFR‐TKI), and their sensitivities to various EGFR‐TKI have been well characterized. Our previous article showed the in vitro sensitivities of EGFR exon 18 mutations to EGFR‐TKI, but little information regarding the sensitivities of other uncommon EGFR mutations is available. First, stable transfectant Ba/F3 cell lines harboring EGFR L858R (Ba/F3‐L858R), L861Q (Ba/F3‐L861Q) or S768I (Ba/F3‐S768I) mutations were created and their drug sensitivities to various EGFR‐TKI were examined. Both the Ba/F3‐L861Q and Ba/F3‐S768I cell lines were less sensitive to erlotinib, compared with the Ba/F3‐L858R cell line, but their sensitivities to afatinib were similar to that of the Ba/F3‐L858R cell line. The Ba/F3‐L861Q cell line was similarly sensitive and the Ba/F3‐S768I cell line was less sensitive to osimertinib, compared with the Ba/F3‐L858R cell line. The results of western blot analyses were consistent with these sensitivities. Next, similar experiments were also performed using the KYSE270 (L861Q) and KYSE 450 (S768I) cell lines, and their results were compatible with those of the transfectant Ba/F3 cell lines. Our findings suggest that NSCLC harboring the EGFR L861Q mutation might be sensitive to afatinib or osimertinib and that NSCLC harboring the EGFR S768I mutation might be sensitive to afatinib. Overall, afatinib might be the optimal EGFR‐TKI against these uncommon EGFR mutations.
Reference ranges for serum periostin in a population without asthma or chronic obstructive pulmonary disease
Authors: Caswell‐Smith R. , Hosking A. , Cripps T. , Holweg C. , Matthews J. , Holliday M. , Maillot C. , Fingleton J. , Weatherall M. , Braithwaite I. , Beasley R. ,   the Periostin Study Team
Published: May 2016

Background

The clinical utility of serum periostin as a type 2 biomarker in asthma is limited by lack of reference range values derived from a population without respiratory disease.

Objective

To derive age‐ and sex‐related reference intervals for serum periostin from an adult population without asthma or COPD.

Methods

Serum periostin levels were measured in 480 individuals, comprising 60 female and 60 male adults in each of the 18‐ to 30‐year, 31‐ to 45‐year, 46‐ to 60‐year and 61‐ to 75‐year age groups. Key exclusion criteria included a doctor's diagnosis of asthma, chronic bronchitis or COPD, and a history of wheezing or use of respiratory inhalers in the last 12 months. The distribution of periostin and logarithm‐transformed periostin levels was derived, and 90% confidence intervals for an individual prediction were calculated.

Results

The distribution of serum periostin was right skewed with a mean (SD) periostin of 51.2 (11.9) ng/mL, median (IQR) 50.1 (43.1 to 56.9) ng/mL and range 28.1 to 136.4 ng/mL. There was no association between logarithm periostin and age or sex, although levels were low in current smokers. The 90% confidence limits for periostin were 35.0 and 71.1 ng/mL.

Conclusions and Clinical Relevance

Serum periostin levels in adults without asthma or COPD are similar to those in adults with asthma. Serum periostin measurements do not need to be adjusted to take account of a patient's age or sex, although levels are lower in current smokers. Reference values for serum periostin levels in adults without asthma or COPD are provided.
Conformational IgE epitopes of peanut allergens Ara h 2 and Ara h 6
Authors: Chen X. , Negi S. S. , Liao S. , Gao V. , Braun W. , Dreskin S. C.
Published: May 2016

Background

Cross‐linking of IgE antibody by specific epitopes on the surface of mast cells is a prerequisite for triggering symptoms of peanut allergy. IgE epitopes are frequently categorized as linear or conformational epitopes. Although linear IgE‐binding epitopes of peanut allergens have been defined, little is known about conformational IgE‐binding epitopes.

Objective

To identify clinically relevant conformational IgE epitopes of the two most important peanut allergens, Ara h 2 and Ara h 6, using phage peptide library.

Methods

A phage 12mer peptide library was screened with allergen‐specific IgE from 4 peanut‐allergic patients. Binding of the mimotopes to IgE from a total of 29 peanut‐allergic subjects was measured by ELISA. The mimotope sequences were mapped on the surface areas of Ara h 2 and Ara h 6 using EpiSearch.

Results

Forty‐one individual mimotopes were identified that specifically bind anti‐ Ara h 2/Ara h 6 IgE as well as rabbit anti‐Ara h 2 and anti‐Ara h 6 IgG. Sequence alignment showed that none of the mimotope sequences match a linear segment of the Ara h 2 or Ara h 6 sequences. EpiSearch analysis showed that all the mimotopes mapped to surface patches of Ara h 2 and Ara h 6. Eight of the mimotopes were recognized by more than 90% of the patients, suggesting immunodominance. Each patient had distinct IgE recognition patterns but the recognition frequency was not correlated to the concentration of peanut specific IgE or to clinical history.

Conclusions

The mimotopes identified in this study represent conformational epitopes. Identification of similar surface patches on Ara h 2 and Ara h 6 further underscores the similarities between these two potent allergens.