bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardioprotective cytokine interleukin‐33 is up‐regulated by statins in human cardiac tissue
Authors: Pentz Richard , Kaun Christoph , Thaler Barbara , Stojkovic Stefan , Lenz Max , Krychtiuk Konstantin A. , Zuckermann Andreas , Huber Kurt , Wojta Johann , Hohensinner Philipp J. , Demyanets Svitlana
Published: September 2018

Interleukin (IL)‐33 is a member of the IL‐1 family and is able to act cardioprotective. The aim of this study was to investigate the regulation of IL‐33 by 3‐hydroxy‐3‐methylglutaryl‐coenzyme‐A (HMG‐CoA) reductase inhibitors (statins) and bisphosphonates (BPs) in human cardiac tissue. The lipophilic fluvastatin, simvastatin, atorvastatin, and lovastatin as well as the nitrogenous BPs alendronate and ibandronate, but not hydrophilic pravastatin increased IL‐33 mRNA and intracellular IL‐33 protein levels in both human adult cardiac myocytes (HACM) and fibroblasts (HACF). Additionally, fluvastatin reduced soluble ST2 secretion from HACM. IL‐33 was also up‐regulated by the general inhibitor of prenylation perillic acid, a RhoA kinase inhibitor Y‐27632, and by latrunculin B, but statin‐induced IL‐33 expression was inhibited by mevalonate, geranylgeranyl pyrophosphate (GGPP) and RhoA activator U‐46619. The IL‐33 promoter was 2.3‐fold more accessible in statin‐treated HACM compared to untreated cells (P = 0.037). In explanted hearts of statin‐treated patients IL‐33 protein was up‐regulated as compared with the hearts of non‐statin‐treated patients (P = 0.048). As IL‐33 was previously shown to exert cardioprotective effects, one could speculate that such up‐regulation of IL‐33 expression in human cardiac cells, which might happen mainly through protein geranylgeranylation, could be a novel mechanism contributing to known cardioprotective effects of statins and BPs.
Functional protection against cardiac diseases depends on ATP‐sensitive potassium channels
Authors: Ye Peng , Zhu Yan‐Rong , Gu Yue , Zhang  Dai‐Min , Chen Shao‐Liang
Published: September 2018

ATP‐sensitive potassium channels (KATP) channels are widely distributed in various tissues, including pancreatic beta cells, muscle tissue and brain tissue. KATP channels play an important role in cardioprotection in physiological/pathological situations. KATP channels are inhibited by an increase in the intracellular ATP concentration and are stimulated by an increase in the intracellular MgADP concentration. Activation of KATP channels decreases ischaemia/reperfusion injury, protects cardiomyocytes from heart failure, and reduces the occurrence of arrhythmias. KATP channels are involved in various signalling pathways, and their participation in protective processes is regulated by endogenous signalling molecules, such as nitric oxide and hydrogen sulphide. KATP channels may act as a new drug target to fight against cardiovascular disease in the development of related drugs in the future. This review highlights the potential mechanisms correlated with the protective role of KATP channels and their therapeutic value in cardiovascular diseases.
Oral health‐related quality of life and standard of treatment in aggressive periodontitis patients more than 5 years after therapy
Authors: Bäumer Amelie , Kappesz Dieter , Ozga Ann‐Kathrin , Mertens Christian , Eickholz Peter , Pretzl Bernadette
Published: September 2018

Objectives

To assess OHRQoL in patients with aggressive periodontitis (AgP) after periodontal treatment using the Oral Health Impact Profile‐49 (OHIP‐49) and compare to patients’ dental status.

Material and methods

More than 5 years after therapy, 71 patients were examined and answered the OHIP‐questionnaire. The dental and periodontal status were assessed according to the SSO (Swiss Dental Society) criteria. Descriptive statistics were performed with SPSS, correlation analysis and tests for differences using R 3.2.2.

Results

More than 90% of all patients showed no probing depths (PD) >5 mm, a bleeding on probing (BOP) index below 35%, and a sufficient function. Four patients showed no visible plaque, PDs ≤ 3 mm, a BOP below 10%, and an optimum function. Non‐smoking and compliant patients exhibited a more favourable status.

The OHIP‐49 added up to 24.9 points, representing a comparatively high satisfaction of AgP‐patients with their oral status. The subscale which most patients reported impairment in was “functional limitation.” A correlation between quality standard and the OHIP‐49G could only be shown in the psychological disability subscale.

Conclusion

After treatment, a moderate to high quality level can be retained over more than 5 years. Most patients are satisfied with their oral health. Correlations between the objective and subjective view could not be found, apart from the subscale “psychological disability.”
Omega‐3 polyunsaturated fatty acids exert anti‐oxidant effects through the nuclear factor (erythroid‐derived 2)‐related factor 2 pathway in immortalized mouse Schwann cells
Authors: Tatsumi Yasuaki , Kato Ayako , Sango Kazunori , Himeno Tatsuhito , Kondo Masaki , Kato Yoshiro , Kamiya Hideki , Nakamura Jiro , Kato Koichi
Published: September 2018

Aims/Introduction

Recent studies advocate that omega‐3 polyunsaturated fatty acids (ω‐3 PUFAs) have direct anti‐oxidative and anti‐inflammatory effects in the vasculature; however, the role of ω‐3 PUFAs in Schwann cells remains undetermined.

Materials and methods

Immortalized mouse Schwann (IMS32) cells were incubated with the ω‐3 PUFAs docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). The messenger ribonucleic acid levels of several anti‐oxidant enzymes (heme oxygenase‐1 [Ho‐1], nicotinamide adenine dinucleotide [phosphate] H quinone oxidoreductase 1, catalase, superoxide dismutase and glutathione peroxidase) were identified using real‐time reverse transcription polymerase chain reaction. Ho‐1 and nicotinamide adenine dinucleotide [phosphate] H quinone oxidoreductase 1 protein levels were evaluated using Western blotting. Nuclear factor (erythroid‐derived 2)‐related factor 2 (Nrf2) of the nuclear fraction was also quantified using western blotting. Catalase activity and glutathione content were determined by colorimetric assay kits. Nrf2 promoter‐luciferase activity was evaluated by a dual luciferase assay system.

Results

Treatment with tert‐butyl hydroperoxide decreased cell viability dose‐dependently. DHA or EPA pretreatment significantly alleviated tert‐butyl hydroperoxide‐induced cytotoxicity. DHA or EPA increased the messenger ribonucleic acid levels of Ho‐1, nicotinamide adenine dinucleotide (phosphate) H quinone oxidoreductase 1 and catalase dose‐dependently. Ho‐1 protein level, catalase activity, Nrf2 promoter‐luciferase activity and intracellular glutathione content were significantly increased by DHA and EPA.

Conclusions

These findings show that DHA and EPA can induce Ho‐1 and catalase through Nrf2, thus protecting Schwann cells against oxidative stress. ω‐3 PUFAs appear to exert their neuroprotective effect by increasing defense mechanisms against oxidative stress in diabetic neuropathies.
Extrinsic and intrinsic constraints interact to drive extra‐pair paternities in the Alpine marmot
Authors: Bichet Coraline , Lepetit David , Cohas Aurélie
Published: September 2018

To reproduce, animals have to form pairs and large variations in the degree of mate switching are observed. Extrinsic and intrinsic factors can constrain individual's mate switching. Among intrinsic factors, genes involved in pair‐bonding, such as Avpr‐1a, receive increasing attention. The length of microsatellites present in the regulatory region of Avpr‐1a determines the neural densities and distributions of the vasopressin receptors known to impact pair‐bonding behaviours. For the first time, we investigated whether and how the genetic makeup at Avpr‐1a, an intrinsic factor, and the social context, an extrinsic factor, experienced by wild Alpine marmot (Marmota marmota) females affect the proportion of extra‐pair young. This proportion was positively correlated with the length of their Avpr‐1a regulatory region but only when the social constraints were relaxed, that is when mature male subordinates were present. When ignoring the interactive effect between the length of their Avpr‐1a regulatory region and the social constraints, the genetic makeup at Avpr‐1a was not associated with the proportion of extra‐pair young. Under natural conditions, the genetic regulation of pair‐bonding could be hidden by extrinsic factors constraining mate choice.
Single‐operator cholangioscopy for the treatment of concomitant gallbladder stones and secondary common bile duct stones
Authors: Liu Dan‐qing , Zhang Hang , Xiao Le , Zhang Bing‐yin , Liu Wei‐hui
Published: September 2018

Background and Aim

This study aims to assess the clinical validity and safety of single‐operator cholangioscopy system (SOCS) for the treatment of concomitant gallbladder stones and secondary common bile duct (CBD) stones.

Methods

This retrospective study included 10 consecutive patients who had small‐sized stones (< 1 cm) in both the gallbladder and CBD; the patients underwent SOCS treatment from June 2016 to December 2016. The clinical validity of this minimally invasive surgery was determined by the operation success rate, stone removal rate, postoperative hospital stay, hospitalization cost, and contrast images before and after the operation. The clinical safety was evaluated by perioperative complications and outcomes, gallbladder stone recurrence, and gallbladder contractility function.

Results

Both the technique success rate and the stone removal rate when using SOCS was 100%. There were no serious complications that occurred during the operation; three patients developed acute cholecystitis, and four patients underwent hyperamylasemia after the surgery. The average postoperative hospital stay was 5.8 ± 1.32 days, and the average hospitalization cost was 7466 ± 566.1 dollars. In the follow‐up period, which ranged from 3 to 8 months, there was no stone residuals or recurrences in the gallbladder and CBD, and no patient showed a recurrence of biliary colic. In addition, the gallbladder contractility function was proven to be normal within 3 to 6 months after the operation.

Conclusions

SOCS could successfully manage concomitant gallbladder stones and secondary CBD stones and precisely protect normal biliary function.
Variability of the cortisol awakening response and morning salivary oxytocin in late adolescence
Authors: Van Dam Jago M. , Garrett Amy J. , Schneider Luke A. , Buisman‐Pijlman Femke T. A. , Short Michelle A. , Hodyl Nicolette A. , Edwards Hannah K. , Goldsworthy Mitchell R. , Pitcher Julia B.
Published: September 2018

Exogenously administered oxytocin interacts with the hypothalamic‐pituitary‐adrenal (HPA) axis to modulate endogenous cortisol levels, suggesting a synergistic role for these two hormones in the response to stress, cognitive performance and the development of psycho‐behavioural disorders. The cortisol awakening response (CAR) is considered a reliable measure of HPA axis function in humans. However, the CAR appears to vary considerably from day to day and may be strongly influenced by the anticipated demands of the day ahead. The level of variation intrinsic to the CAR is unclear because few studies have examined the CAR in the absence of daily environmental variation. It is not known whether oxytocin has a similar or complementary awakening response. Therefore, over three consecutive days, we examined 12 adolescents (aged 15‐17 years) in a highly‐controlled sleep laboratory. Saliva was collected on days 4‐6 of a 9‐day laboratory visit. Cortisol and oxytocin levels were determined by an enzyme‐linked immunosorbent assay from saliva sampled at 0, 15, 30 and 45 minutes, and 8 and 12 hours post‐awakening. CAR magnitude varied between days and was associated with sleep duration and pre‐awakening sleep stage. Conversely, oxytocin levels dropped dramatically in the first 15 minutes post‐awakening and were highly consistent across participants and days. Older participants had higher awakening oxytocin concentrations. Although cortisol increases and oxytocin rapidly declines upon awakening, their diurnal variation does not appear to be related at basal, peripheral levels, consistent with a previous finding that exogenously administered oxytocin only modulates cortisol under conditions of stress.
Associations among two vitamin D receptor (VDR) gene polymorphisms (ApaI and TaqI) in acne vulgaris: A pilot susceptibility study
Authors: Swelam Mervat M. , El‐Barbary Rasha A. H. , Saudi Wael M. , Fathi Marwa S. , Soliman Dina A. , Abd Elrehem Heba H.
Published: September 2018

Background

Acne vulgaris (AV) pathogenesis is multifactorial. Vitamin D (VitD) plays an important role in sebocytes' differentiation and function. Most VitD functions are mediated by the nuclear VitD receptor (VDR) following binding of its biologically active form (1,25 dihydroxyvitamin D3). Genetic variations in VDR gene may cause significant receptor dysfunction and have been found to be associated with many inflammatory skin diseases. Two adjacent single nucleotide polymorphisms of VDR, ApaI (rs7975232) and TaqI (rs731236), were commonly studied.

Objective

To evaluate the association between VDR ApaI and TaqI gene polymorphism and AV.

Methods

This case control study included 30 Egyptian acne patients who attended Dermatology Outpatient Clinic of Al‐Zahraa University and Misr University for Science and Technology Hospitals. Thirty age‐ and sex‐matched healthy individuals participated as controls. VDR gene ApaI and TaqI polymorphisms were examined by polymerase chain reaction restriction fragment length polymorphism. Serum 25(OH)D was measured in all participants.

Results

Patients had significant decrease in ApaI A allele and AATT combined genotype (60%, 3.3%) than controls (78.3%, 20%), respectively, and significant increase in TaqI tt genotype and t allele (46.7%, 63.3%) than controls (13.3%, 41.7%), respectively. Patients showed significantly lower serum 25(OH)D3 concentration than controls.

Conclusion

Polymorphisms of ApaI and TaqI may have a role in the pathogenesis of AV as A allele and AATT combined genotype could be considered protective against acne development and tt genotype and t allele may increase the risk of AV development. VitD deficiency can be considered as a risk factor for AV development.
Exploring Hiring Practitioner Preferences for and Assessment Practices of Prospective Candidates
Authors: Huber Amy
Published: September 2018

While the decision–making strategies involved in the design process have long been a topic of scholarly exploration, less attention has been devoted to probing the likely antecedents to other decisions that potentially influence design practice. One such decision is the formation of a project team, which is likely influenced by those who are hired to work in a firm. While some interior design scholars have outlined the skills and characteristics viewed as most desirable by hiring practitioners, there remains relatively little information regarding the assessment of those attributes and how decision–making strategies may sway the hiring process. This study sought the perceptions of those hiring entry–level interior design candidates. More specifically, it aimed to determine preferences among the commonly cited factors of employability; namely, if hiring practitioners were more apt to prefer soft skills, hard skills, or specific experiences. The study then sought to discern whether those attributes are assessed through either System 1 (i.e., gut–level abbreviated processes often reliant on heuristics) or System 2 strategies (i.e., rational, conscious processes utilizing a broad array of evidence). Findings stemming from a survey of ( n = 106) senior–level interior design practitioners suggest that they are likely to prioritize soft skills when screening candidates. Moreover, practitioners may utilize System 1 processes, heuristics, and relatively subjective strategies—to assess these attributes. Findings offer practical implications while contributing to the body of knowledge regarding the employability of interior design university graduates by empirically examining how hiring practitioners prioritize of a range of cognitive, emotional, and behavioral patterns.
Nomological consistency: A comprehensive test of the equivalence of different trait indicators for the same constructs
Authors: Thielmann Isabel , Hilbig Benjamin E.
Published: September 2018

Objective

Across all subfields of psychology, it is common practice to use different indicators of allegedly the same personality constructs, resting upon the (often implicit) assumption that the indicators measure equivalent constructs. However, there is a lack of approaches allowing for a strict and comprehensive test of the equivalence assumption. We propose investigating nomological consistency to test the equivalence assumption across inventories allegedly measuring the same set of constructs. Nomological consistency refers to the degree to which different indicators of constructs in a theoretical or structural model (such as the Big Five) show similar (non‐)associations with a set of external criteria, thus testing the consistency of the nomological net spanned by different indicators.

Method

In a large‐scale study based on a convenience sample (N = 2,846; 64.9% female), we provide an empirical demonstration of nomological consistency across three commonly used Big Five inventories by comparing the pattern of associations of the Big Five constructs across inventories with five external criteria using a multifaceted analytic approach.

Results

Although results showed some level of consistency across the Big Five inventories under scrutiny, there was also a relevant extent of nomological inconsistency.

Conclusions

Testing nomological consistency allows for a more conclusive judgment on the equivalence of different indicators across inventories.
Paediatric electroencephalograph: The benefits of guidelines
Authors: Thompson (nee Milner) Brooke E , Newsom David , White Andrew
Published: September 2018

Aim

The electroencephalogram (EEG) is an important but often over‐relied upon investigation in evaluating paroxysmal events of childhood. The UK National Institute for Health and Care Excellence (NICE) guidelines for epilepsy help clinicians decide which children should/should not have an EEG. Would introduction of these guidelines in our hospital change the ordering practices of our hospital clinicians? Would introduction reduce unnecessary tests and improve rapidity of obtaining an EEG?

Methods

Paediatric EEG requests, results and, where possible, the patient hospital chart were reviewed before and after introduction of an EEG request form (Appendix I) which provided ordering advice as per the NICE epilepsy guideline. Patient age, sex, distance from hospital and ethnicity were reviewed. Also evaluated was clinical indication and time from ordering to performing the EEG.

Results

Prior to the new EEG form, 56% of the EEG requests fulfilled the NICE criteria; after its introduction, this increased to 83%. EEGs ordered within the NICE guidelines were abnormal on 61% of occasions, but when ordered outside of the guidelines they were abnormal only 4% of the time (P < 0.0001). After its introduction there was poor use of the new form in practice (only 29% of requests). However, the EEGs were more likely to meet ordering criteria and fewer tests were required, leading to more rapid turn‐around times.

Conclusion

This study demonstrates the value of using guidelines to improve timeliness and reduce over‐utilisation of EEGs in general paediatric practice.
Albuminuria and low bone mineral density in paediatric patients with type 1 diabetes
Authors: Souza Karla S Costa de , Gomes Iago de Souza , Oliveira Yonara M da Costa , Loureiro Melina Bezerra , Silva Heglayne Pereira Vital da , Melo Thamara Rodrigues de , Santos Marcos Gonzaga dos , Bortolin Raul Hernandes , Maciel Neto José J , Arrais Ricardo F , Almeida Maria das G , Ururahy Marcela Abbott Galvão , Rezende Adriana A de
Published: September 2018

Aim

To evaluate glycaemic control and its influence on albuminuria and bone mineral density (BMD) in children and adolescents with type 1 diabetes (T1D).

Methods

We collectively assessed 84 T1D children/adolescents (T1D group), aged between 6 and 17 years, and then divided them into two groups according to their glycaemic profile (T1D with good glycaemic control (T1DG group) and T1D with poor glycaemic control (T1DP group)). Serum glucose, glycated haemoglobin, serum urea, serum creatinine, urinary albumin‐to‐creatinine ratio (ACR), estimated glomerular filtration rate and BMD levels were assessed.

Results

Of the patients studied, 77% presented with poor glycaemic control. Patients with T1DP showed an increased ACR (P < 0.001) and a low BMD (P = 0.025) when compared to the T1DG group. In addition, five patients in the T1DP group presented with concomitant albuminuria and a low BMD for their chronological age. Significant negative correlations were identified between the ACR and glycated haemoglobin (r = 0.655, P < 0.001), BMD and glycated haemoglobin (r = −0.262, P = 0.047) and BMD and the ACR (r = −0.631, P = <0.001). In linear regression analysis, the ACR showed a negative effect on BMD (P = 0.044) in the T1D patient group.

Conclusion

Poor glycaemic control was correlated with albuminuria, suggestive of a negative effect on bone tissue, leading to a low BMD in children and adolescents with T1D.
Pratylenchus zeae and P. brachyurus reproduction in green manure maize/soybean consortium systems
Authors: Santana‐Gomes Simone de Melo , Dias‐Arieira Claudia Regina , Cardoso Michelly Ragazzi , Puerari Heriksen Higashi , Schwengber Raiane Pereira , Baldisera Sephora Serrano
Published: September 2018

Root lesion nematodes are pathogens that have been causing relevant losses in crops; therefore, assertive management procedures to control them must be put in practice. Thus, the aim of the present study is to assess Pratylenchus zeae and P. brachyurus reproduction in green manure maize/soybean consortium and in single management systems. Initially, maize was cultivated for 60 days in naturally infested soil to enable nematode multiplication. Next, soil and roots in the pots were homogenized and the initial population was determined. The sampled soil was placed in pots containing green manure. Stizolobium aterrimum, Cajanus cajan, Canavalia ensiformis, Crotalaria spectabilis and C. juncea were sown alone or in maize/soybean consortium. Only one crop was used as control. The experiment was repeated in two different periods. Overall, the single and the consortium treatments reduced the nematode population per root gram, as well as the total population in the root system in experiments with P. zeae. The consortium treatments did not reduce the nematode population in treatments with P. brachyurus. On the other hand, the single crop treatments were efficient in controlling both nematode phytoparasites.
Effect of prespecified therapy escalation on plasma NT‐proBNP concentrations in dogs with stable congestive heart failure due to myxomatous mitral valve disease
Authors: Hezzell Melanie J. , Block Chloë L. , Laughlin Danielle S. , Oyama Mark A.
Published: September 2018

Background

Treatment targeted to achieve reduction in N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) improves outcomes in human congestive heart failure (CHF) patients.

Hypothesis

A pre‐specified therapeutic algorithm that increased diuretic or pimobendan usage will reduce plasma NT‐proBNP concentrations in dogs with CHF secondary to myxomatous mitral valve disease (MMVD).

Animals

Twenty‐six dogs with clinically stable CHF secondary to MMVD.

Methods

Prospective, controlled before‐and‐after study. Dogs were examined up to 3 times over 21 days. Treatment was prescribed based on NT‐proBNP as follows: <1500 pmol/L at baseline, no treatment adjustment at any point during the study (group 1); ≥1500 pmol/L and creatinine ≤3.0 mg/dL at baseline or SC visits, treatment escalated according to the algorithm (group 2); ≥1500 pmol/L at baseline, no treatment adjustment (group 3).

Results

N‐terminal pro‐B‐type natriuretic peptide decreased significantly in group 2 (mean change = −1736 pmol/L (95% CI, −804 to −2668),P < .001) but not in groups 1 or 3 (623 pmol/L [–631 to 1877 pmol/L],P = .14 and 685 pmol/L [–304 to 1068 pmol/L],P = .46, respectively). Serum BUN and creatinine did not change significantly between visit 0 and visit 2 in group 1 (median = 23 mg/dL [range 13‐32] versus 19 mg/dL [12‐38],P = .72 and 1.15 mg/dL [0.70‐1.40] versus 0.95 mg/dL [0.70‐1.10],P = .10, respectively) or group 2 (28 mg/dL [18‐87] versus 43.5 mg/dL [21‐160],P = .092 and 1.10 mg/dL [0.90‐2.50] versus 1.55 mg/dL [0.90‐3.30],P = .062, respectively).

Conclusions and Clinical Importance

Use of this treatment escalation algorithm allows effective targeting of treatment for CHF in dogs against an objective criterion.
Newborn foal with atypical myopathy
Authors: Karlíková Radana , Široká Jitka , Mech Marek , Friedecký David , Janečková Hana , Mádrová Lucie , Hrdinová Františka , Drábková Zuzana , Dobešová Olga , Adam Tomáš , Jahn Petr
Published: September 2018

The case of atypical myopathy (AM) in newborn Haflinger foal with clinical signs of depression and weakness appearing 6 hours after birth resulting in recumbency 12 hours after birth is described. The foal's dam was diagnosed with AM in the 6th month of gestation based on clinical signs of a myopathy, elevated serum activity of creatine kinase, metabolomic analysis and the presence of methylenecyclopropyl acetyl carnitine (MCPA‐carnitine) in the blood. At the time of delivery, the mare was grazing on a pasture near sycamore trees but was free of clinical signs of AM. Metabolomic analysis of the foal's blood revealed increased concentrations of acylcarnitines and MCPA‐carnitine consistent with metabolic profiles of blood from AM affected horses. Two theories could explain this observation (a) hypoglycin A or its metabolites accumulated in the mare's placenta with consequent transfer to fetus or (b) these compounds were secreted into mare's milk.
Echocardiographic evaluation of the right ventricular dimension and systolic function in dogs with pulmonary hypertension
Authors: Vezzosi Tommaso , Domenech Oriol , Costa Giulia , Marchesotti Federica , Venco Luigi , Zini Eric , del Palacio Maria Josefa Fernández , Tognetti Rosalba
Published: September 2018

Background

Right ventricular (RV) enlargement and dysfunction are associated with prognosis in humans with pulmonary hypertension (PH).

Hypothesis/Objectives

To assess RV size and systolic function in dogs with PH and to determine if they are associated with disease severity and right‐sided congestive heart failure (R‐CHF).

Animals

89 dogs with PH and 74 healthy dogs.

Methods

Prospective observational study. PH was classified according to the tricuspid regurgitation pressure gradient. RV end‐diastolic area (RVEDA) index was calculated as RVEDA divided by body surface area. RV systolic function was assessed with the tricuspid annular plane systolic excursion (TAPSE) and the RV fractional area change (FAC) normalized for body weight (TAPSEn and FACn, respectively).

Results

RVEDA index was higher in dogs with moderate PH (10.8 cm2/m2; range, 6.2‐14.4 cm2/m2) and severe PH (12.4 cm2/m2; range, 7.7‐21.4 cm2/m2) than in those with mild PH (8.4 cm2/m2; range, 4.8‐11.6 cm2/m2) and control dogs (8.5 cm2/m2; range, 2.8‐11.6 cm2/m2; P < .001). RVEDA index was significantly higher in dogs with R‐CHF (13.7 cm2/m2; range, 11.0‐21.4 cm2/m2) than in dogs without R‐CHF (9.4 cm2/m2; range, 4.8‐17.1 cm2/m2; P < .001). The severity of tricuspid regurgitation (TR) was the only independent predictor of the RVEDA index (P < .001). TAPSEn and FACn were not significantly different among varying degrees of PH severity and between dogs with and without R‐CHF.

Conclusions and Clinical Importance

The RVEDA index can be used to evaluate RV size in dogs. It can provide additional information in dogs with PH and predict R‐CHF. Severity of TR is the main determinant of RV enlargement in dogs with PH.
Evaluation of the ability of colistin, amoxicillin (components of Potencil®), and fluoroquinolones to attenuate bacterial endotoxin‐ and Shiga exotoxin‐mediated cytotoxicity—In vitro studies
Authors: Szuster‐Ciesielska Agnieszka , Urban‐Chmiel Renata , Wernicki Andrzej , Mascaron Laurent , Wasak Marek , Bousquet Eric
Published: September 2018

Escherichia coli is one of the major pathogens in humans and animals causing localized and systemic infections, which often lead to acute inflammation, watery diarrhea, and hemorrhagic colitis. Bacterial lipopolysaccharide (LPS) and Shiga exotoxins (Stx) are mostly responsible for such clinical signs. Therefore, highly effective treatment of E. coli infections should include both eradication of bacteria and neutralization of their toxins. Here, for the first time, we compared the in vitro ability of common antibiotics to decrease LPS‐ and Stx‐mediated cytotoxicity: colistin, amoxicillin (used separately or combined), enrofloxacin, and its metabolite ciprofloxacin. Three experimental scenarios were realized as follows: (a) the direct effect of antibiotics on endotoxin, (b) the effect of antibiotic treatment on LPS‐mediated cytotoxicity in an experiment mimicking “natural infection,” (c) the effect of antibiotics to decrease Stx2e‐mediated cytotoxicity. Two cell lines, A549 and Vero cells, were used to perform cytotoxic assays with the methyl tetrazolium (MTT) and lactate dehydrogenase leakage (LDH) methods, respectively. Colistin and amoxicillin, especially used in combination, were able to attenuate LPS toxic effect, which was reflected by increase in A549 cell viability. In comparison with other antibiotics, the combination of colistin and amoxicillin exhibited the highest boster or additive effect in protecting cells against LPS‐ and Stx2e‐induced toxicity. In summary, in comparison with fluoroquinolones, the combination of colistin and amoxicillin at concentrations similar to those achieved in plasma of treated animals exhibited the highest ability to attenuate LPS‐ and Stx2e‐mediated cytotoxicity.
The assembly of a plant network in alpine vegetation
Authors: Losapio Gianalberto , de la Cruz Marcelino , Escudero Adrián , Schmid Bernhard , Schöb Christian
Published: September 2018

Questions

Positive and negative associations among species influence the structure of plant communities. Yet how these plant associations are assembled at the community level is poorly understood. We propose a new approach that combines spatial ecology, network theory and trait‐based ecology to examine the assembly of plant–plant associations at the community level.

Location

Gemmipass, Swiss Alps.

Methods

We fully mapped an alpine plant community at the individual plant level, recording both plant coordinates and functional traits for each individual. We identified non‐random species associations using spatial point‐pattern analysis and partialled out the effect of abiotic heterogeneity. We then analysed the plant network structure and used plant traits to predict species associations.

Results

We identified 36 significant spatial associations between plant species, 34 positive and two negatives. Dominant, stress‐tolerant species such as Dryas octopetala, Linaria alpina and Leontodon montanus were highly connected in the network, whereas rare, water‐ and nutrient‐demanding species such as Saxifraga aizoides, Galium anisophyllon and Thymus praecox were less connected compared to random expectation. The plant network was clustered, meaning that species were overall more connected among each other than expected by chance.

Conclusions

Positive associations among species characterized the studied plant community. Besides the primary effect of associations of the “foundation” species D. octopetala with other species, these “subordinate” plants were also associated with each other. Our study reveals the assembly of plant communities as driven by positive associations among stress‐tolerant pioneer species, highlighting their role in supporting the cohesiveness of alpine plant communities.
Victorian roots and branches: “The statistical century” as foundation to the digital humanities
Authors: Babb Genie
Published: September 2018

Victorian Studies and the Digital Humanities (DH) are a natural fit; Victorian texts are in the public domain and thus available for full digitization and subjection to all kinds of applications. This essay focuses on arguably the most controversial: the use of statistical methodologies to analyze literary texts. Often aimed at the “distant reading” practices of Franco Moretti, the pros and cons of these methods have been widely debated among literary scholars, but with little reference to their historical roots. Historical accounts of DH have instead focused on technological developments, citing the massive, computerized concordance of the works of Thomas Aquinas, envisioned in 1949 by Father Roberto Busa and realized by IBM over the next 20 years, as the moment DH was born. Such accounts, as useful as they are, neglect important connections between the computational methodologies of DH and the emergence of modern statistical methodology during the nineteenth century. The advantage of seeing DH as part of the history of statistics is that it helps us understand and evaluate statistically based DH methodologies in their own terms and not simply as methodologies associated with particular neoliberal institutions in the present. This essay argues that understanding the history of statistics as well as examining current practice helps address the criticisms leveled at computational methodologies and the question of compatibility with traditional humanistic methodologies such as close reading. It begins with a brief history of the emergence of modern statistics in the nineteenth century and the impact on Victorian literature and popular culture and then examines recent DH scholarship that utilizes statistical methodologies to analyze Victorian texts.
Beyond Shakespeare's land of ire: Revisiting Ireland in English Renaissance drama
Authors: O'Neill Stephen
Published: September 2018

There has been much critical work on the symbolic centrality of Ireland to English Renaissance literature and drama. To focus on the latter, Shakespeare's histories have been read topically in terms of the contemporaneous Irish wars and also more historically, in terms of English colonialism in Ireland. Topical readings have been followed by allegorical approaches with, for instance, attention to Othello's “ghostly Irish subtext” (Hadfield, ) or Troilus and Cressida's memories of Elizabethan conflict in Ireland (Parker, ). Such interpretations suggest scholarly imaginativeness, the discovery of surprising meaning about a text we thought we knew, albeit within a Shakespeare‐centric frame. They further suggest the capacity of Ireland to enter a play's imaginary—as problem, as image, as other world. At stake here, then, are interrelated questions about what Ireland is doing in English Renaissance drama, where and when we expect to find it, and how we read it. This essay re‐examines the question of why and how Ireland features in plays by Shakespeare and other early modern dramatists. This deceptively simple question is intended to revisit some assumptions that underpin current critical understandings. Why Ireland features in plays has been largely understood as a function of historical contexts and processes: critics and scholars have turned to these as an important site of explanation, with the early modern colonialist discourse on Ireland given special prominence as a determinant of meaning. However, this focus has sidelined other considerations. This article argues for a broadening of context, beyond a focus on topical resonance, to allow for a consideration of dramatic genre and form, the imitative nature of dramatic writing, and the theatre companies themselves, as important factors that shaped how a text and context like Ireland and the Irish found its way into a play. This approach treats representations as a series of reciprocal markings, intertextual echoes, and foregrounds the capacity of a play to make meaning within its own frame. The objective here is less about discounting the political and ideological work of Renaissance plays than about exploring their possibilities to (re)imagine the early modern “land of ire.”
Sexual conflict and the maintenance of genetic variation in natural populations
Authors: Meisel Richard P.
Published: September 2018

Understanding the factors that maintain genetic variation in natural populations is a foundational goal of evolutionary biology. To this end, population geneticists have developed a variety of models that can produce stable polymorphisms. In one of the earliest models, Owen () demonstrated that differences in selection pressures acting on males and females could maintain multiple alleles of a gene at a stable equilibrium. If the selection pressures act in opposite directions in males and females, we refer to this as (inter‐) sexual conflict or sexual antagonism (Arnqvist & Rowe, ). Testing if sexual conflict maintains genetic variation in natural populations is a tremendous challenge—it requires both identifying loci that harbor sexually antagonistic alleles and determining whether those alleles are maintained as stable polymorphisms (Mank, ). Doing so genome‐wide is even harder because it is not tractable to identify sexually antagonistic alleles and test for stable polymorphisms at all loci. Dutoit et al. () confront this challenge in a paper published in this issue of Molecular Ecology. Using gene expression and population genomic data from the collared flycatcher, Dutoit et al. () identify associations and correlations between genomic signatures of balanced polymorphisms and sexual conflict.
A case of Marfan syndrome with ischemic stroke due to middle cerebral artery dissection
Authors: Ozawa Tadashi , Toyohara Akihiro , Kim Younhee , Mashiko Takafumi , Koide Reiji , Shimazaki Haruo , Higaki Ayuho , Namba Katsunari , Fujimoto Shigeru
Published: September 2018

Marfan syndrome is known to cause aneurysm and dissection of the aorta and cerebral artery. Although there are many reports of dissection of the aorta, there are few of intracranial artery dissection. We report a 32‐year‐old man with Marfan syndrome. He was presented to our hospital with sudden left hemiparesis and dysarthria. The initial diffusion‐weighted image revealed high‐intensity lesions in the right corona radiata. Magnetic resonance angiography revealed the disruption of the blood flow signal in the proximal M1 portion of the right middle cerebral artery. The clinical course of acute occlusion and gradual recanalization was confirmed, and we diagnosed the dissection of the right middle cerebral artery. Anticoagulant therapy was started, and the neurological symptoms disappeared about 1 week after the onset. In Marfan syndrome, dissection of the intracranial cerebral artery is rare, so further investigation is required.
Spontaneous epimutations in plants
Authors: Johannes Frank , Schmitz Robert J.
Published: September 2018

Contents

Summary
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I.
Introduction
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II.
What is the rate and molecular spectrum of spontaneous epimutations?
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III.
Do spontaneous epimutations have phenotypic consequences?
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IV.
Conclusion and discussion
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Acknowledgements
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References
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Heritable gains or losses of cytosine methylation can arise stochastically in plant genomes independently of DNA sequence changes. These so‐called ‘spontaneous epimutations’ appear to be a byproduct of imperfect DNA methylation maintenance and epigenome reinforcement events that occur in specialized cell types. There is continued interest in the plant epigenetics community in trying to understand the broader implications of these stochastic events, as some have been shown to induce heritable gene expression changes, shape patterns of methylation diversity within and among plant populations, and appear to be responsive to multi‐generational environmental stressors. In this paper we synthesized our current knowledge of the molecular basis and functional consequences of spontaneous epimutations in plants, discuss technical and conceptual challenges, and highlight emerging research directions.
Arabidopsis UBC13 differentially regulates two programmed cell death pathways in responses to pathogen and low‐temperature stress
Authors: Wang Lipu , Wen Rui , Wang Jinghe , Xiang Daoquan , Wang Qian , Zang Yuepeng , Wang Zheng , Huang Shuai , Li Xin , Datla Raju , Fobert Pierre R. , Wang Hong , Wei Yangdou , Xiao Wei
Published: September 2018

UBC13 is required for Lys63‐linked polyubiquitination and innate immune responses in mammals, but its functions in plant immunity remain to be defined.

Here we used genetic and pathological methods to evaluate roles of Arabidopsis UBC13 in response to pathogens and environmental stresses.

Loss of UBC13 failed to activate the expression of numerous cold‐responsive genes and resulted in hypersensitivity to low‐temperature stress, indicating that UBC13 is involved in plant response to low‐temperature stress. Furthermore, the ubc13 mutant displayed low‐temperature‐induced and salicylic acid‐dependent lesion mimic phenotypes. Unlike typical lesion mimic mutants, ubc13 did not enhance disease resistance against virulent bacterial and fungal pathogens, but diminished hypersensitive response and compromised effector‐triggered immunity against avirulent bacterial pathogens. UBC13 differently regulates two types of programmed cell death in response to low temperature and pathogen. The lesion mimic phenotype in the ubc13 mutant is partially dependent on SNC1. UBC13 interacts with an F‐box protein CPR1 that regulates the homeostasis of SNC1. However, the SNC1 protein level was not altered in the ubc13 mutant, implying that UBC13 is not involved in CPR1‐regulated SNC1 protein degradation.

Taken together, our results revealed that UBC13 is a key regulator in plant response to low temperature and pathogens.
Competition for epidermal space in the evolution of leaves with high physiological rates
Authors: Baresch Andrés , Crifò Camilla , Boyce C. Kevin
Published: September 2018

Leaves with high photosynthetic capacity require high transpiration capacity. Consequently, hydraulic conductance, stomatal conductance, and assimilation capacities should be positively correlated. These traits make independent demands on anatomical space, particularly due to the propensity for veins to have bundle sheath extensions that exclude stomata from the local epidermis. We measured density and area occupation of bundle sheath extensions, density and size of stomata and subsidiary cells, and venation density for a sample of extant angiosperms and fossil and living nonangiosperm tracheophytes. For most nonangiosperms, even modest increases in vein density and stomatal conductance would require substantial reconfigurations of anatomy. One characteristic of the angiosperm syndrome (e.g. small cell sizes, etc.) is hierarchical vein networks that allow expression of bundle sheath extensions in some, but not all veins, contrasting with all‐or‐nothing alternatives available with the single‐order vein networks in most nonangiosperms. Bundle sheath modulation is associated with higher vein densities in three independent groups with hierarchical venation: angiosperms, Gnetum (gymnosperm) and Dipteris (fern). Anatomical and developmental constraints likely contribute to the stability in leaf characteristics – and ecophysiology – seen through time in different lineages and contribute to the uniqueness of angiosperms in achieving the highest vein densities, stomatal densities, and physiological rates.
Downregulation of mitochondrial alternative oxidase affects chloroplast function, redox status and stress response in a marine diatom
Authors: Murik Omer , Tirichine Leila , Prihoda Judit , Thomas Yann , Araújo Wagner L. , Allen Andrew E. , Fernie Alisdair R. , Bowler Chris
Published: September 2018

Diatom dominance in contemporary aquatic environments indicates that they have developed unique and effective mechanisms to cope with the rapid and considerable fluctuations that characterize these environments. In view of their evolutionary history from a secondary endosymbiosis, inter‐organellar regulation of biochemical activities may be of particular relevance. Diatom mitochondrial alternative oxidase (AOX) is believed to play a significant role in supplying chloroplasts with ATP produced in the mitochondria.

Using the model diatom Phaeodactylum tricornutum we generated AOX knockdown lines, and followed sensitivity to stressors, photosynthesis and transcriptome and metabolome profiles of wild‐type and knockdown lines.

We show here that expression of the AOX gene is upregulated by various stresses including H2O2, heat, high light illumination, and iron or nitrogen limitation. AOX knockdown results in hypersensitivity to stress. Knockdown lines also show significantly reduced photosynthetic rates and their chloroplasts are more oxidized. Comparisons of transcriptome and metabolome profiles suggest a strong impact of AOX activity on gene expression, which is carried through to the level of the metabolome.

Our data provide evidence for the involvement of mitochondrial AOX in processes central to the cell biology of diatoms, revealing that cross‐talk between mitochondria and chloroplasts is crucial for maintaining sensitivity to changing environments.
The p33 protein of Citrus tristeza virus affects viral pathogenicity by modulating a host immune response
Authors: Sun Yong‐Duo , Folimonova Svetlana Y.
Published: September 2018

Accumulation of reactive oxygen species (ROS) is a general plant basal defense strategy against viruses. In this study, we show that infection by Citrus tristeza virus (CTV) triggered ROS burst in Nicotiana benthamiana and in the natural citrus host, the extent of which was virus‐dose dependent.

Using Agrobacterium‐mediated expression of CTV‐encoded proteins in N. benthamiana, we found that p33, a unique viral protein, contributed to the induction of ROS accumulation and programmed cell death. The role of p33 in CTV pathogenicity was assessed based on gene knockout and complementation in N. benthamiana.

In the citrus–CTV pathosystem, deletion of the p33 open reading frame in a CTV variant resulted in a significant decrease in ROS production, compared to that of the wild type CTV, which correlated with invasion of the mutant virus into the immature xylem tracheid cells and abnormal differentiation of the vascular system. By contrast, the wild type CTV exhibited phloem‐limited distribution with a minor effect on the vasculature.

We conclude that the p33 protein is a CTV effector that negatively affects virus pathogenicity and suggest that N. benthamiana recognizes p33 to activate the host immune response to restrict CTV into the phloem tissue and minimize the disease syndrome.