bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic traits predict the effects of warming on phytoplankton competition
Authors: Bestion Elvire , García‐Carreras Bernardo , Schaum Charlotte‐Elisa , Pawar Samraat , Yvon‐Durocher Gabriel
Published: March 2018

Understanding how changes in temperature affect interspecific competition is critical for predicting changes in ecological communities with global warming. Here, we develop a theoretical model that links interspecific differences in the temperature dependence of resource acquisition and growth to the outcome of pairwise competition in phytoplankton. We parameterised our model with these metabolic traits derived from six species of freshwater phytoplankton and tested its ability to predict the outcome of competition in all pairwise combinations of the species in a factorial experiment, manipulating temperature and nutrient availability. The model correctly predicted the outcome of competition in 72% of the pairwise experiments, with competitive advantage determined by difference in thermal sensitivity of growth rates of the two species. These results demonstrate that metabolic traits play a key role in determining how changes in temperature influence interspecific competition and lay the foundation for mechanistically predicting the effects of warming in complex, multi‐species communities.
Predictive power of food web models based on body size decreases with trophic complexity
Authors: Jonsson Tomas , Kaartinen Riikka , Jonsson Mattias , Bommarco Riccardo
Published: March 2018

Food web models parameterised using body size show promise to predict trophic interaction strengths (IS) and abundance dynamics. However, this remains to be rigorously tested in food webs beyond simple trophic modules, where indirect and intraguild interactions could be important and driven by traits other than body size. We systematically varied predator body size, guild composition and richness in microcosm insect webs and compared experimental outcomes with predictions of IS from models with allometrically scaled parameters. Body size was a strong predictor of IS in simple modules (r2 = 0.92), but with increasing complexity the predictive power decreased, with model IS being consistently overestimated. We quantify the strength of observed trophic interaction modifications, partition this into density‐mediated vs. behaviour‐mediated indirect effects and show that model shortcomings in predicting IS is related to the size of behaviour‐mediated effects. Our findings encourage development of dynamical food web models explicitly including and exploring indirect mechanisms.
Drivers of vegetative dormancy across herbaceous perennial plant species
Authors: Shefferson Richard P. , Kull Tiiu , Hutchings Michael J. , Selosse Marc‐André , Jacquemyn Hans , Kellett Kimberly M. , Menges Eric S. , Primack Richard B. , Tuomi Juha , Alahuhta Kirsi , Hurskainen Sonja , Alexander Helen M. , Anderson Derek S. , Brys Rein , Brzosko Emilia , Dostálik Slavomir , Gregg Katharine , Ipser Zdeněk , Jäkäläniemi Anne , Jersáková Jana , Dean Kettle W. , McCormick Melissa K. , Mendoza Ana , Miller Michael T. , Moen Asbjørn , Øien Dag‐Inge , Püttsepp Ülle , Roy Mélanie , Sather Nancy , Sletvold Nina , Štípková Zuzana , Tali Kadri , Warren Robert J. , Whigham Dennis F.
Published: March 2018

Vegetative dormancy, that is the temporary absence of aboveground growth for ≥ 1 year, is paradoxical, because plants cannot photosynthesise or flower during dormant periods. We test ecological and evolutionary hypotheses for its widespread persistence. We show that dormancy has evolved numerous times. Most species displaying dormancy exhibit life‐history costs of sprouting, and of dormancy. Short‐lived and mycoheterotrophic species have higher proportions of dormant plants than long‐lived species and species with other nutritional modes. Foliage loss is associated with higher future dormancy levels, suggesting that carbon limitation promotes dormancy. Maximum dormancy duration is shorter under higher precipitation and at higher latitudes, the latter suggesting an important role for competition or herbivory. Study length affects estimates of some demographic parameters. Our results identify life historical and environmental drivers of dormancy. We also highlight the evolutionary importance of the little understood costs of sprouting and growth, latitudinal stress gradients and mixed nutritional modes.
Association study of functional polymorphisms of dopaminergic pathway in epilepsy‐related factors of temporal lobe epilepsy in Brazilian population
Authors: Alcantara J. A. , Vincentis S. , Kerr D. S. , dos Santos B. , Alessi R. , van der Linden Jr H. , Chaim T. , Serpa M. H. , Busatto G. F. , Gattaz W. F. , Demarque R. , Valente K. D.
Published: March 2018

Background and purpose

There are few data about the role of neurotransmission modulated by dopamine in epilepsy, especially temporal lobe epilepsy (TLE). This is the first study that aimed to analyze the dopaminergic polymorphisms in an etiologically homogeneous group of patients with TLE with hippocampal sclerosis. Selected polymorphisms were: (i) the most expressed D2‐like receptors in the limbic system (DRD2/ANKK1 TAQ‐1A, D4_VNTR and D4_rs1800955); (ii) the dopamine transporter (DAT) 3′‐untranslated region and intron 8; and (iii) two degrading enzymes regulating the synaptic activity, i.e. the main metabolizer of dopamine, catechol‐O‐methyltransferase, and monoamine oxidase A.

Methods

We assessed 119 patients with unequivocal TLE with hippocampal sclerosis and 112 healthy volunteers. Individuals were genotyped for the polymorphisms of the gene encoding dopaminergic pathway transporter DAT haplotype, dopaminergic receptors, catechol‐O‐methyltransferase and monoamine oxidase A. We also evaluated epilepsy‐related factors (e.g. seizure frequency, age of onset, duration and status epilepticus).

Results

There was no difference between the groups for the studied polymorphisms. The polymorphism DRD4_VNTR was associated with family history of epilepsy (P = 0.003), DRD2_rs1800497 was related to status epilepticus (P = 0.022), and intron 8 VNTR DAT was related to higher seizure frequency (P = 0.019) and family history of epilepsy (P = 0.011).

Conclusions

Our findings demonstrated that polymorphisms of the dopaminergic pathway are associated with significant clinical features of this form of epilepsy, such as seizure frequency, family history of epilepsy and status epilepticus.
Impact of intravenous thrombolysis and emergent carotid stenting on reperfusion and clinical outcomes in patients with acute stroke with tandem lesion treated with thrombectomy: a collaborative pooled analysis
Authors: Gory B. , Haussen D. C. , Piotin M. , Steglich‐Arnholm H. , Holtmannspötter M. , Labreuche J. , Kyheng M. , Taschner C. , Eiden S. , Nogueira R. G. , Papanagiotou P. , Boutchakova M. , Siddiqui A. H. , Lapergue B. , Dorn F. , Cognard C. , Killer M. , Mangiafico S. , Ribo M. , Psychogios M. N. , Spiotta A. M. , Labeyrie M. A. , Biondi A. , Mazighi M. , Turjman F. ,   the Thrombectomy In TANdem lesions (TITAN) investigators
Published: March 2018

Background and purpose

Tandem anterior circulation lesions in the setting of acute ischemic stroke (AIS) are a complex endovascular situation that has not been specifically addressed in trials. We determined the predictors of successful reperfusion and good clinical outcome at 90 days after mechanical thrombectomy (MT) in patients with AIS with tandem lesions in a pooled collaborative study.

Methods

This was a retrospective analysis of consecutive patients presenting to 18 comprehensive stroke centers with AIS due to tandem lesion of the anterior circulation who underwent MT.

Results

A total of 395 patients were included. Successful reperfusion (modified thrombolysis in cerebral infarction score 2b–3) was achieved in 76.7%. At 90 days, 52.2% achieved a good outcome (modified Rankin Scale score 0–2), 13.8% suffered a parenchymal hematoma and 13.2% were dead. Lower National Institutes of Health Stroke Scale score [odds ratio (OR), 1.26; 95% confidence intervals (CI), 1.07–1.48, P = 0.004], Alberta Stroke Program Early CT Score ≥7 (OR, 2.00; 95% CI, 1.07–3.43, P = 0.011), intravenous thrombolysis (OR, 1.47; 95% CI, 1.01–2.12, P = 0.042) and stenting of the extracranial carotid lesion (OR, 1.63; 95% CI, 1.04–2;53, P = 0.030) were independently associated with successful reperfusion. Lower age (OR, 1.58; 95% CI, 1.26–1.97, P < 0.001), absence of hypercholesterolemia (OR, 1.77; 95% CI, 1.10–2.84, P = 0.018), lower National Institutes of Health Stroke Scale scores (OR, 2.04; 95% CI, 1.53–2.72, P < 0.001), Alberta Stroke Program Early CT Score ≥7 (OR, 2.75; 95% CI, 1.24–6.10, P = 0.013) and proximal middle cerebral artery occlusion (OR, 1.59; 95% CI, 1.03–2.44, P = 0.035) independently predicted a good 90‐day outcome.

Conclusions

Intravenous thrombolysis and emergent stenting of the extracranial carotid lesion were predictors of a successful reperfusion after MT of patients with AIS with tandem lesion of the anterior circulation.
A comprehensive approach to identifying repurposed drugs to treat SCN8A epilepsy
Authors: Atkin Talia A. , Maher Chani M. , Gerlach Aaron C. , Gay Bryant C. , Antonio Brett M. , Santos Sonia C. , Padilla Karen M. , Rader JulieAnn , Krafte Douglas S. , Fox Matthew A. , Stewart Gregory R. , Petrovski Slavé , Devinsky Orrin , Might Matthew , Petrou Steven , Goldstein David B.
Published: March 2018

Objective

Many previous studies of drug repurposing have relied on literature review followed by evaluation of a limited number of candidate compounds. Here, we demonstrate the feasibility of a more comprehensive approach using high‐throughput screening to identify inhibitors of a gain‐of‐function mutation in the SCN8A gene associated with severe pediatric epilepsy.

Methods

We developed cellular models expressing wild‐type or an R1872Q mutation in the Nav1.6 sodium channel encoded by SCN8A. Voltage clamp experiments in HEK‐293 cells expressing the SCN8A R1872Q mutation demonstrated a leftward shift in sodium channel activation as well as delayed inactivation; both changes are consistent with a gain‐of‐function mutation. We next developed a fluorescence‐based, sodium flux assay and used it to assess an extensive library of approved drugs, including a panel of antiepileptic drugs, for inhibitory activity in the mutated cell line. Lead candidates were evaluated in follow‐on studies to generate concentration‐response curves for inhibiting sodium influx. Select compounds of clinical interest were evaluated by electrophysiology to further characterize drug effects on wild‐type and mutant sodium channel functions.

Results

The screen identified 90 drugs that significantly inhibited sodium influx in the R1872Q cell line. Four drugs of potential clinical interest—amitriptyline, carvedilol, nilvadipine, and carbamazepine—were further investigated and demonstrated concentration‐dependent inhibition of sodium channel currents.

Significance

A comprehensive drug repurposing screen identified potential new candidates for the treatment of epilepsy caused by the R1872Q mutation in the SCN8A gene.
The frequency and management of seizures during psychological treatment among patients with psychogenic nonepileptic seizures and epilepsy
Authors: Kemp Steven , Graham Christopher D. , Chan Rebecca , Kitchingman Hayley , Vickerman Kirsty , Reuber Markus
Published: March 2018

Objective

Growing evidence suggests that psychological treatments are effective for improving outcomes in both epilepsy and psychogenic nonepileptic seizures (PNES). However, the risk of in‐session seizures may cause concerns about safety and about seizures disrupting treatment. This study explores the risk of in‐session seizures in patients with epilepsy and those with PNES, the timings of seizures during psychological therapy, and the responses of therapists to seizures.

Methods

Consecutive patients with epilepsy or PNES attending 2 neurology centers in the United Kingdom for psychological treatment to help with their seizure disorders were studied. Information about seizures during outpatient psychological therapy sessions was gathered using a 12‐item pro forma.

Results

Ninety‐seven patients with epilepsy and 195 with PNES were evaluated. One in 32 patients with epilepsy and 1 in 8 with PNES had at least 1 in‐session seizure. A seizure occurred in 1 in 136 treatment sessions provided to patients with epilepsy, and 1 in 36 sessions provided to those with PNES. The risk of in‐session seizures was significantly greater in patients with PNES than in patients with epilepsy (odds ratio [OR] 4.4, 95% confidence interval [CI] 1.3‐15.2). Seizures tended to occur in the first half of treatment programs and individual sessions and only disrupted sessions briefly. Only one patient with PNES required in‐patient observation not involving overnight admission.

Significance

In‐session seizures do occur and are much more common in patients with PNES than in those with epilepsy. Seizures rarely caused major disruption to psychological treatment, and could almost invariably be managed by the treating therapist without help from additional medical staff. Nonetheless, this research suggests that psychological therapy providers should anticipate the occurrence of in‐session seizures and have safe management plans in place. The greater frequency of in‐session seizures in PNES may add to our understanding of the mechanisms triggering these seizures.
Final safety, tolerability, and seizure outcomes in patients with focal epilepsy treated with adjunctive perampanel for up to 4 years in an open‐label extension of phase III randomized trials: Study 307
Authors: Krauss Gregory L. , Perucca Emilio , Kwan Patrick , Ben‐Menachem Elinor , Wang Xue‐Feng , Shih Jerry J. , Patten Anna , Yang Haichen , Williams Betsy , Laurenza Antonio
Published: March 2018

Objective

To evaluate long‐term safety/tolerability and seizure outcomes in patients with focal seizures treated with adjunctive perampanel in the open‐label extension (OLEx) Study 307 (ClinicalTrials.gov identifier: NCT00735397).

Methods

Patients could enter the OLEx after completing one of the double‐blind, phase III studies. Safety/tolerability and seizure outcomes (median percent reduction in seizure frequency per 28 days, and 50% responder and seizure freedom rates) were analyzed during the OLEx in cohorts with the same minimum perampanel exposure for all focal seizures and secondarily generalized seizures (SGS). An additional sensitivity analysis accounted for early dropouts from the OLEx.

Results

Of 1480 patients randomized across the double‐blind studies, 1218 enrolled in the OLEx. The majority of patients (65.4%‐80.9%) received a last daily dose of perampanel 12 mg and completed long‐term assessment on the same, or one fewer, concomitant antiepileptic drug compared with baseline. The long‐term safety/tolerability profile was consistent with the double‐blind studies. Treatment‐emergent adverse events (TEAEs) leading to discontinuation in >1% of patients were dizziness, irritability, and fatigue; TEAEs of clinical interest were stable for 4 years. In all cohorts, seizure outcome improvements were sustained over time. Median percent seizure reductions per 28 days reached 62.0% and 70.6% for patients with ≥3 (n = 436) or ≥4 (n = 78) years of exposure, respectively; corresponding 50% responder rates were 59.6% and 67.9%. The largest median percent seizure reduction per 28 days occurred in SGS for patients with SGS at baseline: 88.0% and 100.0% for patients with ≥3 (n = 190) or ≥4 (n = 28) years of exposure, respectively; in these cohorts 40.0% and 53.6% of patients, respectively, attained freedom from SGS. Median percent seizure reductions per 28 days were similar when early dropouts were accounted for.

Significance

Long‐term (≤4 years) adjunctive perampanel treatment did not raise new safety/tolerability signals and was associated with markedly improved seizure control, particularly in patients with SGS at baseline.
Pathogenicity of Diaporthe spp. on two blueberry cultivars (Vaccinium corymbosum)
Authors: Cardinaals J. , Wenneker M. , Voogd J. G. B. , van Leeuwen G. C. M.
Published: March 2018

Diaporthe vaccinii causes twig blight and fruit rot and is currently listed as a quarantine organism for the European Union. In the Netherlands, two species from the same genus, Diaporthe eres and Diaporthe rudis, are regularly isolated from blighted twigs of Vaccinium corymbosum. This study compared the pathogenicity of these two species to D. vaccinii. To develop a pathogenicity test a field experiment was performed at an experimental station, testing isolates of D. rudis and D. eres. Most of the isolates tested did not cause statistically significantly larger lesions compared to the control treatment (P > 0.05). In a greenhouse experiment a similar test was conducted, comparing D. vaccinii with the closely related species D. eres. Two cultivars of blueberry, Duke and Liberty, were inoculated using two D. vaccinii and two D. eres isolates. Stem canker lesions caused by D. vaccinii were larger than these caused by D. eres isolates. The majority of the lesions caused by D. vaccinii did not pass the first node of the inoculated shoot, which might be an explanation for the ‘mild’ symptoms of D. vaccinii in V. corymbosum, which appear not to cause crop losses. The results of this study suggest that D. vaccinii may not be a major threat to blueberry production in Europe. Further data is required to be able to conclude whether the quarantine status of D. vaccinii is still appropriate.
Linking phenotypic correlations from a diverse set of laboratory tests to field behaviors in the crayfish, Orconectes virilis
Authors: Edwards David D. , Rapin Kathryn E. , Moore Paul A.
Published: March 2018

The presence of phenotypic behavioral correlations and their connection to fitness consequences of organisms have received considerable debate within the literature. Yet, little work has been carried out to connect any behavioral correlates found within a set of laboratory studies to natural behavior observed under complex environmental conditions. To help fill this gap, individual crayfish, collected from the same local population, completed five different behavioral assays in a laboratory setting in a random order. These data were used to reveal any possible correlations for behavioral scores across all of the laboratory tests. Subsequently, these same individuals were placed into the field and video recorded for 24 hr. A separate set of field behaviors, related to the laboratory assays, were quantified from the field videos. The normalized laboratory and field behaviors were used in three stepwise statistical analyses. First, normalized data were loaded into a PCA to generate a priori hypotheses on potential behavioral correlates. These hypotheses were subsequently tested using general multiple linear regression. Finally, structural equation modeling was performed to elucidate any behavioral modules from the laboratory assays that correlated with behavioral patterns present from the fieldwork. Three laboratory‐based behavioral modules were connected to three separate field assays: exploration–avoidance, bold–shy, and aggressiveness. Yet, some behaviors exhibited in the laboratory assays were uncorrelated with any behaviors found in the field and vice versa. Results from this study provide evidence that although many different behavioral correlates may exist within laboratory settings, these same modules may not translate directly into predicting behavior under natural settings.
Exploring short‐ and long‐run links from bank competition to risk
Authors: Davis E. Philip , Karim Dilruba
Published: March 2018

The current literature offers diverse findings on the bank competition‐risk relationship. We seek to advance understanding by looking at both short‐ and long‐run relationships for banks from 27 EU countries, using a six‐year period before and since 2007 and employing both the H‐statistic and the Lerner index as measures of competition. We thus highlight further nuances in the competition–risk relationship that are absent from the current literature. Both measures have a positive short‐run relationship with risk, while long‐run effects differ. Underlying this, the competition measures differ in their relationship to the volatility of profits, with important policy implications.
Parallel evolution and adaptation to environmental factors in a marine flatfish: Implications for fisheries and aquaculture management of the turbot (Scophthalmus maximus)
Authors: do Prado Fernanda Dotti , Vera Manuel , Hermida Miguel , Bouza Carmen , Pardo Belén G. , Vilas Román , Blanco Andrés , Fernández Carlos , Maroso Francesco , Maes Gregory E. , Turan Cemal , Volckaert Filip A. M. , Taggart John B. , Carr Adrian , Ogden Rob , Nielsen Einar Eg ,   The Aquatrace Consortium, Martínez Paulino
Published: March 2018

Unraveling adaptive genetic variation represents, in addition to the estimate of population demographic parameters, a cornerstone for the management of aquatic natural living resources, which, in turn, represent the raw material for breeding programs. The turbot (Scophthalmus maximus) is a marine flatfish of high commercial value living on the European continental shelf. While wild populations are declining, aquaculture is flourishing in southern Europe. We evaluated the genetic structure of turbot throughout its natural distribution range (672 individuals; 20 populations) by analyzing allele frequency data from 755 single nucleotide polymorphism discovered and genotyped by double‐digest RAD sequencing. The species was structured into four main regions: Baltic Sea, Atlantic Ocean, Adriatic Sea, and Black Sea, with subtle differentiation apparent at the distribution margins of the Atlantic region. Genetic diversity and effective population size estimates were highest in the Atlantic populations, the area of greatest occurrence, while turbot from other regions showed lower levels, reflecting geographical isolation and reduced abundance. Divergent selection was detected within and between the Atlantic Ocean and Baltic Sea regions, and also when comparing these two regions with the Black Sea. Evidence of parallel evolution was detected between the two low salinity regions, the Baltic and Black seas. Correlation between genetic and environmental variation indicated that temperature and salinity were probably the main environmental drivers of selection. Mining around the four genomic regions consistently inferred to be under selection identified candidate genes related to osmoregulation, growth, and resistance to diseases. The new insights are useful for the management of turbot fisheries and aquaculture by providing the baseline for evaluating the consequences of turbot releases from restocking and farming.
Spatio‐temporal connectivity and host resistance influence evolutionary and epidemiological dynamics of the canola pathogen Leptosphaeria maculans
Authors: Bousset Lydia , Sprague Susan J. , Thrall Peter H. , Barrett Luke G.
Published: March 2018

Genetic, physiological and physical homogenization of agricultural landscapes creates ideal environments for plant pathogens to proliferate and rapidly evolve. Thus, a critical challenge in plant pathology and epidemiology is to design durable and effective strategies to protect cropping systems from damage caused by pathogens. Theoretical studies suggest that spatio‐temporal variation in the diversity and distribution of resistant hosts across agricultural landscapes may have strong effects on the epidemiology and evolutionary potential of crop pathogens. However, we lack empirical tests of spatio‐temporal deployment of host resistance to pathogens can be best used to manage disease epidemics and disrupt pathogen evolutionary dynamics in real‐world systems. In a field experiment, we simulated how differences in Brassica napus resistance deployment strategies and landscape connectivity influence epidemic severity and Leptosphaeria maculans pathogen population composition. Host plant resistance, spatio‐temporal connectivity [stubble loads], and genetic connectivity of the inoculum source [composition of canola stubble mixtures] jointly impacted epidemiology (disease severity) and pathogen evolution (population composition). Changes in population composition were consistent with directional selection for the ability to infect the host (infectivity), leading to changes in pathotype (multilocus phenotypes) and infectivity frequencies. We repeatedly observed decreases in the frequency of unnecessary infectivity, suggesting that carrying multiple infectivity genes is costly for the pathogen. From an applied perspective, our results indicate that varying resistance genes in space and time can be used to help control disease, even when resistance has already been overcome. Furthermore, our approach extends our ability to test not only for the efficacy of host varieties in a given year, but also for durability over multiple cropping seasons, given variation in the combination of resistance genes deployed.
Understanding managers’ and scientists’ perspectives on opportunities to achieve more evolutionarily enlightened management in conservation
Authors: Cook Carly N. , Sgrò Carla M.
Published: March 2018

Despite wide acceptance that conservation could benefit from greater attention to principles and processes from evolutionary biology, little attention has been given to quantifying the degree to which relevant evolutionary concepts are being integrated into management practices. There has also been increasing discussion of the potential reasons for a lack of evolutionarily enlightened management, but no attempts to understand the challenges from the perspective of those making management decisions. In this study, we asked conservation managers and scientists for their views on the importance of a range of key evolutionary concepts, the degree to which these concepts are being integrated into management, and what would need to change to support better integration into management practices. We found that while managers recognize the importance of a wide range of evolutionary concepts for conservation outcomes, they acknowledge these concepts are rarely incorporated into management. Managers and scientists were in strong agreement about the range of barriers that need to be overcome, with a lack of knowledge reported as the most important barrier to better integration of evolutionary biology into conservation decision‐making. Although managers tended to be more focused on the need for more training in evolutionary biology, scientists reported greater engagement between managers and evolutionary biologists as most important to achieve the necessary change. Nevertheless, the challenges appear to be multifaceted, and several are outside the control of managers, suggesting solutions will need to be multidimensional.
The outcomes of epidural anaesthesia in horses with perineal and tail melanomas: Complications associated with ataxia and the risks of rope recovery
Authors: Bird A. R. , Morley S. J. , Sherlock C. E. , Mair T. S.
Published: March 2018

Melanoma is a common neoplasm in horses, with a high rate of incidence in the perineum and ventral tail. Surgical excision is often recommended to remove such masses and can be achieved in the standing horse either via local infiltration of local anaesthetic, or via epidural administration of a local anaesthetic and/or an adrenergic α2receptor agonist. The clinical records of all horses with tail and/or perineal melanomas that received epidural anaesthesia at a single equine hospital, over a 7‐year period, were reviewed to determine the drugs administered and complications associated with the epidural injection. Twenty‐five cases were identified, five of which received epidural anaesthesia on two occasions. Epidural anaesthesia was insufficient to allow surgical melanoma excision in two horses; repeated epidural injection allowed sufficient loss of sensation in one of these horses and additional regional infiltration of local anaesthetic allowed completion of surgery in the other. Three horses developed significant ataxia associated with epidural anaesthesia, two of which became recumbent. Both recumbent horses were placed under general anaesthesia, and in one of these, rope‐assisted anaesthetic recovery resulted in additional complications associated with facial nerve paresis, fractured ribs and a fracture of the first coccygeal vertebra, with associated neurological dysfunction of the rectum, anus, tail and surrounding skin.
A longitudinal study of fractures in 1488 Thoroughbred racehorses receiving intrasynovial medication: 2006–2011
Authors: Smith L. C. R. , Wylie C. E. , Palmer L. , Ramzan P. H. L.
Published: March 2018

Background

There is a need for investigation of associations between intrasynovial medication and fracture risk in racehorses.

Objectives

To document the proportion and type of fracture occurring following intrasynovial medication.

Study design

Retrospective longitudinal study.

Methods

Review of clinical records from all Thoroughbred flat racehorses receiving intrasynovial medication under the care of a first‐opinion veterinary practice between 2006 and 2011. Fractures pre‐ and post‐medication were categorised by location, type, and severity; analysis of fractures sustained within 56‐days of medication was undertaken. Survival analyses using Cox proportional hazards models were conducted for associations between medication used (corticosteroid vs. non‐corticosteroid), age at first medication, sex and total number of medications and fracture.

Results

A total of 1488 horses received intrasynovial medication during the period of study; 8692 synovial spaces were medicated in 3925 sessions. There were 96 fractures that occurred within 56‐days of medication, of which 44 were classified as ‘serious’ (44/1488; 3.0% total population, 95% CI 2.1, 3.8%) and 11 (11/1488, 0.7%, 95% CI 0.3, 1.2%) were euthanased due to severity of injury. Fifty‐four of 96 cases (56.4%, 95% CI 46.3, 66.2%) returned to racing. Targeted imaging of the subsequent injury site was undertaken prior to injury in only 7 (7/96, 7.3%) horses that injured post‐medication. Horses that had received ≥3 previous intrasynovial medication sessions had an increased hazard of sustaining a fracture within 56 days (HR 2.31, 95% CI 1.51, 3.54, P<0.001) compared with those receiving ≤3 medication sessions, adjusted for each increasing year of age (HR 0.67, 95% CI 0.53, 0.86, P = 0.001).

Main limitations

Absence of an unexposed cohort of nonmedicated racehorses.

Conclusions

Serious musculoskeletal injury following intrasynovial medication occurred in 3% (44/1488) horses. Reduction in injury rates may be possible through greater use of premedication diagnostic imaging.
Respiratory disease and sero‐epidemiology of respiratory pathogens in the working horses of Ethiopia
Authors: Laing G. , Christley R. , Stringer A. , Aklilu N. , Ashine T. , Newton R. , Radford A. , Pinchbeck G.
Published: March 2018

Background

Pathogens are frequently implicated in equine respiratory disease. In Ethiopia, respiratory disease is a frequent cause for presentation at veterinary clinics and a priority concern for users of working horses. However, there is little existing literature on possible aetiologies.

Objectives

Determine prevalence of respiratory signs and exposure to major respiratory pathogens through a serological survey.

Study design

Cross‐sectional.

Methods

Systematically selected horses from 19 sites in central Ethiopia were examined clinically and sampled once (August‐December 2013). A face‐to‐face interview collected data on horses’ management and history. Serological testing targeted equine influenza virus (EIV), equine herpesviruses‐1 (EHV‐1) and ‐4 (EHV‐4), equine rhinitis viruses A (ERAV) and B (ERBV), equine arteritis virus (EAV) and Streptococcus equi subspecies equi (S. equi).

Results

Owners reported a recent history of coughing in 38% of horses and nasal discharge in 7%. No animals were observed coughing during examination but 6% had a nasal discharge. Antibodies towards S. equi, were most prevalent (8%, 33/350). Antibodies to EAV were confirmed in one animal (0.3%). Low antibody titres to EHV‐1/4 and ERA/BV suggested prior exposure but antibodies to EIV were not detected. Multivariable, multilevel logistic regression analysis for risk factors associated with S. equi serostatus showed higher odds of seropositivity in younger animals and those working less frequently.

Main limitations

A single serological sample cannot describe dynamic changes in antibodies. Sampling horses at the place of work may result in healthy‐worker bias.

Conclusions

S. equi may be endemic in this population and contributing, in part, to the occurrence of respiratory disease. Low prevalence of antibodies to viruses, with the exception of EIV, indicates these pathogens are present, but unlikely a predominant cause of respiratory signs and noninfectious causes of disease should also be investigated. Working horses in this region would be vulnerable to incursion of equine influenza.
Regulatory T cells in autoimmune skin diseases
Authors: Ujiie Hideyuki
Published: March 2018

CD4+Foxp3+ regulatory T cells (Tregs) are suppressors of immune activation and play a crucial role in the maintenance of peripheral tolerance. Mutations of Foxp3 result in fatal autoimmunity in multiple organs, including the skin, in both humans and mice. Many studies have demonstrated the altered frequency and functions of Tregs, changes in cytokine and chemokine levels related to Tregs and the differences in genetic background regarding Tregs in autoimmune skin disorders. Recent studies have extended our knowledge of certain properties of Tregs, especially skin‐resident Tregs. In addition, some novel therapies have been performed by modulating the number and the function of Tregs. This review focuses on the role of Tregs in some autoimmune skin disorders, including alopecia areata, vitiligo, pemphigoid and pemphigus, and systemic sclerosis, and discusses questions that remain to be addressed.
Skin toxicology and 3Rs—Current challenges for public health protection
Authors: Riebeling Christian , Luch Andreas , Tralau Tewes
Published: March 2018

Driven by the fast paced development of complex test systems in vitro, mass spectrometry and omics, we finally have the tools to unravel the molecular events that underlie toxicological adversity. Yet, timely regulatory adaptation of these new tools continues to pose major challenges even for organs readily accessible such as skin. The reasons for this encompass a need for conservatism as well as the need of tests to serve an existing regulatory framework rather than to produce scientific knowledge. It is important to be aware of this in order to align regulatory skin toxicity with the 3R principles more readily. While most chemical safety testing is still based on animal data, regulatory frameworks have seen a strong push towards non‐animal approaches. The endpoints corrosion, irritation, sensitisation, absorption and phototoxicity, for example, can now be covered in vitro with the corresponding test guidelines (TGs) being made available by the OECD. However, in vitro approaches tend to be more reductionist. Hence, a combination of several tests is usually preferable to achieve satisfying predictivity. Moreover, the test systems and their combined use need to be standardised and are therefore subject not only to validation but also to the ongoing development of so‐called integrated approaches to testing and assessment (IATAs). Concomitantly, skin models are being refined to deliver the complexity required for increased applicability and predictivity. Given the importance of regulatory applicability for 3R‐derived approaches to have a long‐lasting impact, this review examines the state of regulatory implementation and perspectives, respectively.
The failed implementation of performance management in Irish central government
Authors: McGeough Francis , Beck Matthias
Published: March 2018

Ireland's Strategic Management Initiative was launched in 1994 and aimed to improve public services delivery. In line with public sector reforms in other countries, it placed strong emphasis on performance management in public sector organisations. Initiatives stressed the need for strategic planning and performance monitoring. The overall impact of these reforms was disappointing, with the Organisation for Economic Co‐operation and Development reporting in 2008 that the Irish public sector lacked a performance culture. This paper utilizes a series of interviews with senior managers in order to identify why performance management did not gain traction and our contribution highlights the complex contextual factors which undermined this agenda.
The development of the management accountant's role revisited: An example from the Swedish Social Insurance Agency
Authors: Holmgren Caicedo Mikael , Mårtensson Maria , Tamm Hallström Kristina
Published: March 2018

This study traces the development of the management accountant (MA) role at the Swedish Social Insurance Agency (SIA). In 2012, the agency began a reformation by implementing the Lean management system in hopes of increasing customer trust. The results of this study show that the authority of the MA rests on decentralization and the proximity of MAs to managers, as previous research has shown, and more specifically on a definitional and a moral prerogative that may or may not be awarded to MAs enabling them to act as de facto managers. The study shows how the role of the SIA's operative level MAs changed into a helpdesk function with the role of assisting other groups to help themselves, in this case operative‐level teams that had begun performing management accounting tasks. Thus, this study bears witness not to the expansion and hybridization of existing MA roles, but to the reduction in authority and de‐hybridization of the MA role, from business partner to a pedagogical role on a consultative basis.
Climate change alters fish community size‐structure, requiring adaptive policy targets
Authors: Queirós Ana M , Fernandes José , Genevier Lily , Lynam Christopher P
Published: March 2018

Size‐based indicators are used worldwide in research that supports the management of commercially exploited wild fish populations, because of their responsiveness to fishing pressure. Observational and experimental data, however, have highlighted the deeply rooted links between fish size and environmental conditions that can drive additional, interannual changes in these indicators. Here, we have used biogeochemical and mechanistic niche modelling of commercially exploited demersal fish species to project time series to the end of the 21st century for one such indicator, the large fish indicator (LFI), under global CO2 emissions scenarios. Our modelling results, validated against survey data, suggest that the LFI's previously proposed policy target may be unachievable under future climate change. In turn, our results help to identify what may be achievable policy targets for demersal fish communities experiencing climate change. While fisheries modelling has grown as a science, climate change modelling is seldom used specifically to address policy aims. Studies such as this one can, however, enable a more sustainable exploitation of marine food resources under changes unmanageable by fisheries control. Indeed, such studies can be used to aid resilient policy target setting by taking into account climate‐driven effects on fish community size‐structure.
Optimization of reprogramming culture conditions for the generation of induced pluripotent stem cells from Col1a1 4F2A‐Oct4‐GFP mice with high efficiency
Authors: Lin Po‐Ying , Hsu Sheng‐Chieh , Chen Hung‐Chi , Len Wen‐Bin , Hsiao Fang‐Chi , Liu Mei‐Chun , Pan Pei‐Ling , Lin Tsai‐Chen , Lee Ying‐Hsuan , Meir Yaa‐Jyuhn James
Published: March 2018

A reprogrammable transgenic mouse strain, called Col1a1 4F2A‐Oct4‐GFP, was bred for the present study. Because the somatic cells of this mouse strain contain only two copies of each Yamanaka factor, these animals are inefficient at producing induced pluripotent stem cells (iPSCs; approx. 0.005%) under traditional culture conditions. With an optimized culture condition, the iPSC production rate of mouse embryonic fibroblasts (MEFs) of Col1a1 4F2A‐Oct4‐GFP mice (MEFCol1a1 4F2A‐Oct4‐GFP) was increased to approximately 8%. Further, promotion of cell proliferation by serum supplementation did not enhance iPSC production. Inhibition of transforming growth factor β (TGF‐β) in the serum by SB431542 neither affected the growth rate of MEFCol1a1 4F2A‐Oct4‐GFP nor promoted iPSC production. However, the use of the gamma‐irradiated STO‐NEO‐LIF (γSNL) cells to serve as feeders for iPSC production resulted in a 5‐fold higher rate of iPSC production than the use of γMEFICR feeders. Interestingly, the use of SB431542 with the γMEFICR‐adopted system could eliminate this difference. RT‐PCR‐based comparative analysis further demonstrated that TGF‐β expression was 10‐fold higher in γMEFICR than in γSNL cells. Consistent with previous reports, mesenchymal to epithelial transition was found to participate in the initial steps of reprogramming in the specific context of MEFCol1a1 4F2A‐Oct4‐GFP. Moreover, we found that the initial seeding density is one of the pivotal factors for determining a high efficiency of iPSC generation. The iPSCs efficiently generated from our MEFCol1a1 4F2A‐Oct4‐GFP resembled mouse embryonic stem cells (mESCs) in aspects of teratoma formation and germline transmission. Depending on the culture conditions, our Col1a1 4F2A‐Oct4‐GFP mouse system can generate bona fide iPSCs with variable efficiencies, which can serve as a tool for interrogating the route taken by cells during somatic reprogramming.
Structural and functional characterisation of multi‐copper oxidase CueO from lignin‐degrading bacterium Ochrobactrum sp. reveal its activity towards lignin model compounds and lignosulfonate
Authors: Granja‐Travez Rommel Santiago , Wilkinson Rachael C. , Persinoti Gabriela Felix , Squina Fabio M. , Fülöp Vilmos , Bugg Timothy D. H.
Published: March 2018

The identification of enzymes responsible for oxidation of lignin in lignin‐degrading bacteria is of interest for biotechnological valorization of lignin to renewable chemical products. The genome sequences of two lignin‐degrading bacteria, Ochrobactrum sp., and Paenibacillus sp., contain no B‐type DyP peroxidases implicated in lignin degradation in other bacteria, but contain putative multicopper oxidase genes. Multi‐copper oxidase CueO from Ochrobactrum sp. was expressed and reconstituted as a recombinant laccase‐like enzyme, and kinetically characterized. Ochrobactrum CueO shows activity for oxidation of β‐aryl ether and biphenyl lignin dimer model compounds, generating oxidized dimeric products, and shows activity for oxidation of Ca‐lignosulfonate, generating vanillic acid as a low molecular weight product. The crystal structure of Ochrobactrum CueO (OcCueO) has been determined at 1.1 Å resolution (PDB: 6EVG), showing a four‐coordinate mononuclear type I copper center with ligands His495, His434 and Cys490 with Met500 as an axial ligand, similar to that of Escherichia coli CueO and bacterial azurin proteins, whereas fungal laccase enzymes contain a three‐coordinate type I copper metal center. A trinuclear type 2/3 copper cluster was modeled into the active site, showing similar structure to E. coli CueO and fungal laccases, and three solvent channels leading to the active site. Site‐directed mutagenesis was carried out on amino acid residues found in the solvent channels, indicating the importance for residues Asp102, Gly103, Arg221, Arg223, and Asp462 for catalytic activity. The work identifies a new bacterial multicopper enzyme with activity for lignin oxidation, and implicates a role for bacterial laccase‐like multicopper oxidases in some lignin‐degrading bacteria.

Database

Structural data are available in the PDB under the accession number 6EVG.
p53 mediated regulation of coactivator associated arginine methyltransferase 1 (CARM1) expression is critical for suppression of adipogenesis
Authors: Behera Amit K. , Bhattacharya Aditya , Vasudevan Madavan , Kundu Tapas K.
Published: March 2018

Coactivator‐associated arginine methyltransferase 1 (CARM1/PRMT4) is a type I arginine methyltransferase that mediates transcriptional activation via methylation of histone H3 on R17, R26, and R42. CARM1 is also a coactivator of transcription of various transcription factors such as NF‐kB, MEF2C, β‐catenin, p53, PPAR‐gamma etc. CARM1 has been functionally implicated in maintenance of pluripotency, cellular differentiation, and tumorigenesis; where its expression status plays an important role. Although its expression has been shown to be regulated by a few miRNAs in different contexts at post‐transcriptional level, transcriptional regulation of CARM1 gene is still unexplored. In this report we demonstrate that CARM1 is a p53 responsive gene, where p53 could suppress CARM1 promoter‐driven luciferase expression. CARM1 gene expression was found to be repressed by p53 in 3T3L1 preadipocytes when activated with Nutlin‐3a treatment. Ectopic overexpression of CARM1 could rescue inhibitory effect of p53 on adipogenesis, suggesting a role of p53‐CARM1 axis of regulation operational in the context of adipocyte differentiation. p53 and CARM1 showed antagonistic regulatory influence on PPAR‐gamma expression; which suggests that p53‐mediated suppression of adipogenesis could be partly via repression of CARM1 expression. Taken together these observations provide convincing mechanistic explanation for p53 function in the context of adipocyte differentiation process.
Conserved structural features anchor biofilm‐associated RTX–adhesins to the outer membrane of bacteria
Authors: Guo Shuaiqi , Langelaan David N. , Phippen Sean W. , Smith Steven P. , Voets Ilja K. , Davies Peter L.
Published: March 2018

Repeats‐in‐toxin (RTX) adhesins are present in many Gram‐negative bacteria to facilitate biofilm formation. Previously, we reported that the 1.5‐MDa RTX adhesin (MpIBP) from the Antarctic bacterium, Marinomonas primoryensis, is tethered to the bacterial cell surface via its N‐terminal Region I (RI). Here, we show the detailed structural features of RI. It has an N‐terminal periplasmic retention domain (RIN), a central domain (RIM) that can insert into the β‐barrel of an outer‐membrane pore protein during MpIBP secretion, and three extracellular domains at its C terminus (RIC) that transition the protein into the extender region (RII). RIN has a novel β‐sandwich fold with a similar shape to βγ‐crystallins and tryptophan RNA attenuation proteins. Because RIM undergoes fast and extensive degradation in vitro, its narrow cylindrical shape was rapidly measured by small‐angle X‐ray scattering before proteolysis could occur. The crystal structure of RIC comprises three tandem β‐sandwich domains similar to those in RII, but increasing in their hydrophobicity with proximity to the outer membrane. In addition, the key Ca2+ ion that rigidifies the linkers between RII domains is not present between the first two of these RIC domains. This more flexible RI linker near the cell surface can act as a ‘pivot’ to help the 0.6‐μm‐long MpIBP sweep over larger volumes to find its binding partners. Since the physical features of RI are well conserved in the RTX adhesins of many Gram‐negative bacteria, our detailed structural and bioinformatic analyses serve as a model for investigating the surface retention of biofilm‐forming bacteria, including human pathogens.