bluuebunny/crossref_metadata_2025 huggingface dataset:
Time and space adaptivity of the wave equation discretized in time by a second-order scheme
Authors: Gorynina Olga , Lozinski Alexei , Picasso Marco
Published: July 2018

The aim of this paper is to obtain a posteriori error bounds of optimal order in time and space for the linear second-order wave equation discretized by the Newmark scheme in time and the finite element method in space. An error estimate is derived in the $L^{\infty }$-in-time/energy-in-space norm. Numerical experiments are reported for several test cases and confirm equivalence of the proposed estimator and the true error.
Local BPS Invariants: Enumerative Aspects and Wall-Crossing
Authors: Choi Jinwon , van Garrel Michel , Katz Sheldon , Takahashi Nobuyoshi
Published: July 2018

We study the BPS invariants for local del Pezzo surfaces, which can be obtained as the signed Euler characteristic of the moduli spaces of stable one-dimensional sheaves on the surface $S$. We calculate the Poincaré polynomials of the moduli spaces for the curve classes $\beta $ having arithmetic genus at most 2. We formulate a conjecture that these Poincaré polynomials are divisible by the Poincaré polynomials of $((-K_S).\beta -1)$-dimensional projective space. This conjecture motivates the upcoming work on log BPS numbers [8].
Properties of the epigenetic clock and age acceleration
Authors: Khoury Louis El , Gorrie-Stone Tyler , Smart Melissa , Hughes Amanda , Bao Yanchun , Andrayas Alexandria , Burrage Joe , Hannon Eilis , Kumari Meena , Mill Jonathan , Schalkwyk Leonard C
Published: July 2018

Background

The methylation status of numerous CpG sites in the human genome varies with age. The Horvath epigenetic clock used a wide variety of published DNA methylation data to produce an age prediction that has been widely used to, predict age in unknown samples, and draw conclusions about speed of ageing in various tissues, environments, and diseases. Despite its utility, there are a number of assumptions in the model that require examination. We explore the characteristics of the model in whole blood and multiple brain regions from older people, who are not well represented in the original training data, and in blood from a cross-sectional population study.

Results

We find that the model systematically underestimates age in tissues from older people. A decrease in slope of the predicted ages were observed at approximately 60 years, indicating that some loci in the model may change differently with age, and that age acceleration measures will themselves be age-dependent. This is seen most strongly in the cerebellum but is also present in other examined tissues, and is consistently observed in multiple datasets. An apparent association of Alzheimer’s disease with age acceleration disappears when age is used as a covariate. Association tests in the literature use a variety of methods for calculating age acceleration and often do not use age as a covariate. This is a potential cause of misleading findings.

Conclusions

Associations of phenotypes with age acceleration should be evaluated cautiously, and chronological age should be included as a covariate in all analyses.
Sirt7 regulates circadian phase coherence of hepatic circadian clock via a body temperature/Hsp70-Sirt7-Cry1 axis
Authors: Liu Zuojun , Qian Minxian , Tang Xiaolong , Hu Wenjing , Zhang Shuju , Meng Fanbiao , Sun Shimin , Cao Xinyue , Pang Qiuxiang , Zhao Bosheng , Liu Baohua
Published: July 2018

The biological clock is generated in the hypothalamic suprachiasmatic nucleus (SCN), which synchronizes peripheral oscillators to coordinate physiological and behavioral activities throughout the body. Disturbance of circadian phase coherence between the central and peripheral could disrupt rhythms and thus cause diseases and aging. Here, we identified hepatic Sirt7 as an early element responsive to light, which ensures the phase coherence in mouse liver. Loss of Sirt7 leads to advanced liver circadian phase; restricted feeding in daytime entrains hepatic clock more rapidly in Sirt7-/- mice compared to wild-types. Molecularly, a light-driven body temperature (BT) oscillation induces rhythmic expression of Hsp70, which binds to and promotes the ubiquitination and proteasomal degradation of Sirt7. Sirt7 rhythmically deacetylates Cry1 on K565/579 and promotes Fbxl3-mediated degradation, thus coupling hepatic clock to the central pacemaker. Together, our data identify a novel BT/Hsp70-Sirt7-Cry1 axis, which transmits biological timing cues from the central to the peripheral and ensures circadian phase coherence in livers.
Relationship between ACTN3 and ACE polymorphisms and FIFA World averaged rating
Authors: Ilinsky Valery , Zakharova Natalia
Published: July 2018

Polymorphisms in ACTN3 and ACE genes were previously reported to be associated with power and endurance performance. We estimated the relationship between their population frequencies in several countries and FIFA World averaged rating (FWAR). The entropy was used as the measure of uncertainty. The FWAR distribution entropy (in nats) was 1.38. The FWAR conditional distribution entropy given ACTN3 RR and ACE II frequencies was 1.27 and 1.24, respectively. Almost same FWAR conditional entropy (1.25) was after adjustment on GDP. Population frequencies of polymorphisms in power and endurance performance genes might be a cause of high or low FWAR (low frequency -- less football players) or an effect of ethnic origin and geographical location of countries, related to GDP.
Characterization of fluorescent proteins, promoters, and selectable markers for applications in the Lyme disease spirocheteBorrelia burgdorferi
Authors: Takacs Constantin N. , Kloos Zachary A. , Scott Molly , Rosa Patricia A. , Jacobs-Wagner Christine
Published: July 2018

Lyme disease is the most widely reported vector-borne disease in the United States. Its incidence is rapidly increasing and disease symptoms can be debilitating. The need to understand the biology of the disease agent, the spirocheteBorrelia burgdorferi, is thus evermore pressing. Despite important advances inB. burgdorferigenetics, the array of molecular tools available for use in this organism remains limited, especially for cell biological studies. Here, we adapt a palette of bright and mostly monomeric fluorescent proteins for versatile use and multi-color imaging inB. burgdorferi. We also characterize two novel antibiotic selection markers and establish the feasibility of their use in conjunction with extant markers. Lastly, we describe a set of constitutively active promoters of low and intermediate strengths that allow fine-tuning of gene expression levels. These molecular tools complement and expand current experimental capabilities inB. burgdorferi, which will facilitate future investigation of this important human pathogen. To showcase the usefulness of these reagents, we used them to investigate the subcellular localization of BB0323, aB. burgdorferilipoprotein essential for survival in the host and vector environments. We show that BB0323 accumulates at the cell poles and future division sites ofB. burgdorfericells, highlighting the complex subcellular organization of this spirochete.

IMPORTANCE

Genetic manipulation of the Lyme disease spirocheteB. burgdorferiremains cumbersome, despite significant progress in the field. The scarcity of molecular reagents available for use in this pathogen has slowed research efforts to study its unusual biology. Of interest,B. burgdorferidisplays complex cellular organization features that have yet to be understood. These include an unusual morphology and a highly fragmented genome, both of which are likely to play important roles in the bacterium’s transmission, infectivity, and persistence. Here, we complement and expand the array of molecular tools available for use inB. burgdorferiby generating and characterizing multiple fluorescent proteins, antibiotic selection markers, and constitutively active promoters of different strengths. These tools will facilitate investigations in this important human pathogen, as exemplified by the polar and midcell localization of the cell envelope regulator BB0323, which we uncovered using these reagents.
Increased oxidative stress tolerance by Superoxide dismutase overexpression inMesorhizobium loti
Authors: Gonzalez Pablo J , Lozano Mauricio , Lascano Hernán R. , Lagares Antonio , Melchiorre Mariana N.
Published: July 2018

Drought and salinity conditions are the major factors affecting nitrogen fixation by legume-rhizobium symbiosis. A global response to these stress conditions is the increase of intracellular ROS leading to activation of antioxidant system to ensure cellular homeostasis. Under the hypothesis that overexpression ofsodgene inM. lotiimprove tolerance to oxidative stress we decide to investigate the response of constitutive overexpression of theMesorhizobium lotiMAFF303099sodgene on tolerance to oxidative stress under free-living conditions. The genemlr7636was overexpressed constitutively under thenptIIpromoter of pFAJ1708 plasmid. Our study revealed that thesodoverexpressing mutant had five-fold increased SOD activity in periplasmic space and a better tolerance to superoxide and hydrogen peroxide in bacterial killing assays.

IMPORTANCE

In this study, we report that the homologous superoxide dismutase overexpression inMesorhizobium lotiimproves its tolerance to oxidative stress under free-living conditions.
Multi-way methods for understanding longitudinal intervention effects on bacterial communities
Authors: Måge Ingrid , Steppeler Christina , Berget Ingunn , Paulsen Jan Erik , Rud Ida
Published: July 2018

Background

This paper presents a strategy for statistical analysis and interpretation of longitudinal intervention effects on bacterial communities. Data from such experiments often suffers from small sample size, high degree of irrelevant variation, and missing data points. Our strategy is a combination of multi-way decomposition methods, multivariate ANOVA, multi-block regression, hierarchical clustering and phylogenetic network graphs. The aim is to provide answers to relevant research questions, which are bothstatistically validandeasy to interpret.

Results

The strategy is illustrated by analysing an intervention design where two mice groups were subjected to a treatment that caused inflammation in the intestines. Total microbiota in fecal samples was analysed at five time points, and the clinical end point was the load of colon cancer lesions. By using different combinations of the aforementioned methods, we were able to show that:

The treatment had a significant effect on the microbiota, and we have identified clusters of bacteria groups with different time trajectories.

Individual differences in the initial microbiota had a large effect on the load of tumors, but not on the formation of early-stage lesions (flat ACFs).

The treatment resulted in an increase inBacteroidaceae,PrevotellaceaeandParaprevotellaceae, and this increase could be associated with the formation of cancer lesions.

Conclusion

The results show that by applying several data analytical methods in combination, we are able to view the system from different angles and thereby answer different research questions. We believe that multiway methods and multivariate ANOVA should be used more frequently in the bioinformatics fields, due to their ability to extract meaningful components from data sets with many collinear variables, few samples and a high degree of noise or irrelevant variation.
Ultra-fine temporal resolution in auditory processing is preserved in aged mice without peripheral hearing loss
Authors: Osterhagen Lasse , Hildebrandt K. Jannis
Published: July 2018

Age-related hearing loss (presbycusis) is caused by damage to the periphery as well as deterioration of central auditory processing. Gap detection is a paradigm to study age-related temporal processing deficits, which is assumed to be determined primarily by the latter. However, peripheral hearing loss is a strong confounding factor when using gap detection to measure temporal processing. In this study, we used mice from the CAST line, which is known to maintain excellent peripheral hearing, to rule out any contribution of peripheral hearing loss to gap detection performance. We employed an operant Go/No-go paradigm to obtain psychometric functions of gap in noise (GIN) detection at young and middle age. Besides, we measured auditory brainstem responses (ABR) and multiunit recordings in the auditory cortex (AC) in order to disentangle the processing stages of gap detection. We found detection thresholds around 0.6 ms in all measurement modalities. Detection thresholds did not increase with age. In the ABR, GIN stimuli are coded as onset responses to the noise that follows the gap, strikingly similar to the ABR of noise bursts in silence (NBIS). The simplicity of the neural representation of the gap together with the preservation of detection threshold in aged CAST mice suggests that GIN detection in the mouse is primarily determined by peripheral, not central processing.

Abbreviaions

GIN

gap in noise

ABR

auditory brainstem response

AC

auditory cortex

NBIS

noise burst in silence

IIN

inhibitory interneuron
One‐ and three‐year outcomes in patients treated with intermittent hemodialysis for acute kidney injury: prospective observational multicenter post‐hoc FINNAKI study
Authors: Eskola Maija , Vaara Suvi T. , Korhonen Anna‐Maija , Sauranen Jukka , Koivuviita Niina , Honkanen Eero , Pettilä Ville , Haapio Mikko ,   for the FINNAKI Study Group
Published: July 2018

Background

Studies reporting renal and overall survival after acute kidney injury (AKI) treated exclusively with intermittent modalities of renal replacement therapy (IRRT) are rare. This study focused on outcomes of AKI patients treated with IRRT both in intensive care units (ICUs) and non‐ICU dialysis units.

Methods

This prospective observational study was carried on during a 5‐month period in 17 ICUs and 17 non‐ICUs. ICU and non‐ICU patients (total n = 138; 65 ICU, 73 non‐ICU) requiring RRT for AKI and chosen to receive IRRT were included. Patient and RRT characteristics as well as outcomes at 90 days, 1 year, and 3 years were registered.

Results

Characteristics of ICU and non‐ICU patients differed markedly. Pre‐existing chronic kidney disease (CKD) and chronic heart failure were significantly more common among non‐ICU patients. At 1 year, RRT dependence was significantly more common in the non‐ICU group. At 3 years, there was no significant difference between the groups either in RRT dependence or mortality.

Conclusion

Outcome of AKI patients treated with IRRT is dismal with regard to 3‐year kidney function and mortality. Although pre‐existing CKD emerged as a major risk factor for end‐stage renal disease after AKI, the poor kidney survival was also seen in patients without prior CKD.
Survey of 23 Nordic university hospitals showed that 77% lacked written procedures for measuring and interpreting blood pressure in infants
Authors: Granlund Peder Annæus , Ødegaard Jostein Strand , Skjerven Håvard Ove , Lødrup Carlsen Karin C. , Hanséus Katarina , Rögnvaldsson Ingolfur , Sunnegårdh Jan , Turanlahti Maila I. , Holmstrøm Henrik
Published: July 2018

Aim

This study determined the use of standardised procedures for infant noninvasive blood pressure (NIBP) measurements in the Nordic countries and aimed to identify factors included in the standardisation and interpretation of NIBP measurements in infants.

Methods

A cross‐sectional electronic questionnaire survey was sent to 84 physicians in all 23 university hospitals in Sweden, Norway, Denmark, Finland and Iceland and was completed from February to March 2017. The survey contained respondent characteristics, the presence and description of standardised procedures for NIBP measurements, daily practice of NIBP measurements and methodological considerations and interpretation of NIBP measurements in a healthy six‐month‐old child.

Results

We received responses from 55 of 84 physicians working in all 23 Nordic university hospitals, in paediatric cardiology (n = 22), general paediatrics (n = 16), paediatric nephrology (n = 14) and other fields (n = 3). Less than a quarter (23%) said their hospital issued specific NIBP procedures relating to infants and they referred to 19 different sources of information. The factors that were most commonly assessed for interpretation were age (100%), arousal state (78%) and cuff size (76%).

Conclusion

Most of the university hospital units treating children lacked age‐specific written procedures for measuring and interpreting infant NIBP, and there is a strong need for common Nordic guidelines.
Differential prognostic impact of GELTAMO‐IPI in cell of origin subtypes of Diffuse Large B Cell Lymphoma as defined by the Hans algorithm
Authors: Montalbán Carlos , Díaz‐López Antonio , Martín Alejandro , Baile Mónica , Sanchez José M. , Sancho Juan M. , García Olga , Novelli Silvana , Monter‐Rovira Anna , Salar Antonio , Bastos Mariana , Gutiérrez Antonio , Bento Leyre , Córdoba Raul , Arquero Teresa , González de Villambrosia Sonia , Barranco Gilberto , De Oña Raquel , López Guillermo Armando , Rodriguez Salazar María J. , Domínguez Juan F. , Fernández Rubén , Queizan José A. , Rodríguez José , Abraira Victor , García Juan F. ,   the GELTAMO‐IPI Project Investigators
Published: July 2018

The Grupo Español de Linfomas y Trasplantes de Médula Ósea International Prognostic Index (GELTAMO‐IPI) stratifies four risk groups in diffuse large B cell lymphoma (DLBCL) patients treated with immunochaemotherapy: low (LR), low‐intermediate (LIR), high‐intermediate (HIR), and high (HR). The present study explores the effect of GELTAMO‐IPI in the DLBCL subtypes defined by the immunohistochaemistry‐based Hans algorithm, Germinal Centre B (GCB) and non‐GCB. A multivariate Cox regression model including GELTAMO‐IPI risk groups, cell of origin (COO) subtypes and their product was developed to evaluate interaction between the two variables. The COO subtype was available in 839 patients (380 GCB; 459 non‐GCB) and both the GELTAMO‐IPI and the COO subtype in 780 (353 GCB; 427 non‐GCB). There were no differences in 5‐year overall survival (OS) between the two subtypes. The Cox model revealed interaction between the GELTAMO‐IPI risk groups and the COO subtypes (P = 0·005), indicating that GELTAMO‐IPI has a different effect in the two subtypes. Three risk groups were stratified in both COO subtypes: in the GCB subtype, LR, LIR and the combined HIR+HR had 5‐year OS of 100%, 75% and 52%, respectively. In the non‐GCB subtype, LR, the combined LIR+HIR and HR had a 5‐year OS of, 97%, 82% and 35% respectively. GELTAMO‐IPI identifies a genuine poor outcome group of patients in the DLBCL non‐GCB subtype.
The dual inhibitor of the phosphoinositol‐3 and PIM kinases, IBL‐202, is effective against chronic lymphocytic leukaemia cells under conditions that mimic the hypoxic tumour microenvironment
Authors: Crassini Kyle , Shen Yandong , O'Dwyer Michael , O'Neill Michael , Christopherson Richard , Mulligan Stephen , Best O. Giles
Published: July 2018

Despite significant advances in treatment, chronic lymphocytic leukaemia (CLL) remains an incurable disease. Ibrutinib and idelalisib, which inhibit Bruton Tyrosine kinase (BTK) and phosphoinositol‐3 (PI3) kinase‐δ respectively, have become important treatment options for the disease and demonstrate the potential of targeting components of the B‐cell receptor‐signalling pathway. IBL‐202 is a dual inhibitor of the PIM and PI3 kinases. Synergy between the pan‐PIM inhibitor, pPIMi, and idelalisib against a range of haematological cell lines and primary CLL cells supports the rationale for preclinical studies of IBL‐202 in CLL. Importantly, IBL‐202, but not idelalisib, was cytotoxic against CLL cells under in vitro conditions that mimic the hypoxic tumour microenvironment. The significant effects of IBL‐202 on CD49d and CXCR4 expression and migration, cycle and proliferation of CLL cells suggest the drug may also interfere with the migratory and proliferative capacity of the leukaemic cells. Collectively, these data demonstrate that dual inhibition of the PIM and PI3 kinases by IBL‐202 may be an effective strategy for targeting CLL cells, particularly within the environmental niches known to confer drug‐resistance.
The area–heterogeneity tradeoff applied to spatial protection of rockfish (Sebastes spp.) species richness
Authors: Frid Alejandro , McGreer Madeleine , Gale Katie SP , Rubidge Emily , Blaine Tristan , Reid Mike , Olson Angeleen , Hankewich Sandie , Mason Ernest , Rolston Dave , Tallio Ernest
Published: July 2018

The “area–heterogeneity tradeoff” hypothesis predicts unimodal effects of habitat heterogeneity on species richness, implying that habitats with intermediate heterogeneity may be priority for spatial protection. Alternatively, if heterogeneity effects are positive, then protecting the most heterogeneous habitats may take precedence. We tested for unimodal effects of habitat heterogeneity on the species density (area‐corrected richness) of rockfishes (Sebastes spp.): long‐lived, benthic fishes vulnerable to overexploitation. Inconsistent with predictions, topographic structural complexity had a strong linear effect on species density; other heterogeneity measures had weaker, positive effects and the only unimodal effect (depth range) was weak. The clear implication is that, to protect the highest density of rockfish species, marine protected areas should include the most topographically complex substrates. Our results can also help refine and test species distribution models needed to inform spatial planning where in situ surveys are lacking. The area–heterogeneity tradeoff generates useful predictions for which support may be context‐dependent.
Conditions for successful range shifts under climate change: The role of species dispersal and landscape configuration
Authors: Årevall Jonatan , Early Regan , Estrada Alba , Wennergren Uno , Eklöf Anna C.
Published: July 2018

Aim

Ongoing climate change is currently modifying the geographical location of areas that are climatically suitable for species. Understanding a species’ ability to successfully shift its geographical range would allow us to assess extinction risks and predict future community compositions. We investigate how habitat configuration impedes or promotes climate‐driven range shifts, given different speeds of climate change and dispersal abilities.

Location

Theoretical, but illustrated with European examples.

Methods

We model how a species’ ability to track a directional shift in climatic conditions is affected by (a) species’ dispersal abilities; (b) speed of climatic shift; and (c) spatial arrangement of the habitat. Our modelling framework includes within‐and between‐patch population dynamics and uses ecologically realistic habitat distributions and dispersal scenarios (verified with data from a set of European mammal species) and, as such, is an improvement of classical range shift models.

Results

In landscapes with a homogeneous distribution of suitable habitats, all but the least dispersive species will be able to range shift. However, species with high dispersal ability will have lower population densities after range shift. In heterogeneous landscapes species’ ability to range shift is far more variable and heavily dependent on the habitat configuration. This means that landscape configuration in combination with the speed of climate change and species dispersal abilities give rise to nonlinear effects on population sizes and survival after a climatic shift.

Main conclusions

Our analyses point out the importance of accounting for the interplay of species dispersal and the landscape configuration when estimating future climate impact on species. These results link ecologically important attributes of both species and their landscapes to outcomes of species range shift, and thereby long‐term persistence of ecological communities.
Psoriasis in Israel: demographic, epidemiology, and healthcare services utilization
Authors: Shalom Guy , Zisman Devy , Babaev Meir , Horev Amir , Tiosano Shmuel , Schonmann Yochai , Comaneshter Doron , Cohen Arnon D.
Published: July 2018

Background

Updated data regarding the epidemiology of psoriasis and related healthcare utilization are lacking.

Objective

To investigate the epidemiology, comorbidities, healthcare services utilization, and drug use in a large group of patients with psoriasis from Clalit Health Services (CHS) database.

Methods

A controlled cross‐sectional study was performed. Case patients were defined when there was at least one documented diagnosis of psoriasis registered by a CHS dermatologist between the years 1998–2016. The extracted data included metabolic, cardiovascular and psychiatric comorbidities; community clinic visits; in‐ and outpatient services utilization profiles and drug use data, which included pharmacy claims of topical and systemic treatments, including phototherapy and climatotherapy. Comparative analysis was performed by a univariate and multivariate analysis, adjusting for age, gender, obesity, and smoking.

Results

The study included 118,680 patients with psoriasis (prevalence of 2.69%) and 118,680 age‐ and gender‐matched controls. Patients with psoriasis had increased prevalence of metabolic, cardiovascular, and psychiatric illnesses. Psoriasis was significantly associated with an increased healthcare utilization. The mean (SD) number of annual dermatologist clinic visits and emergency room visits was 7.2 ± 12.4 and 2.9 ± 7.7 in psoriasis patients as compared to 2.9 ± 7.9 and 2.7 ± 7.4 in the control group (P < 0.001). Topical steroids were the most applied treatment in psoriasis patients (15.5%), and topical vitamin D analogs were second in use (14.6%). Traditional systemic treatment for psoriasis was used in 3.8% of the patients, and biologic treatments were used in 1.6% of the patients.

Conclusions

Our study quantifies healthcare services utilization and drug use in patients with psoriasis.
Accuracy of policy function approximations for strongly concave recursive problems
Authors: Maldonado Wilfredo L. , Candido Osvaldo , Pereira Luis Felipe V. N.
Published: July 2018

Under the hypotheses of strong concavity of the aggregator function and concavity of the stochastic operator which define the objective function of the stochastic dynamic programming problem (SDPP), we prove that the policy function approximation of the problem is a Hölder continuous function with respect to the value function approximation. From this, explicit error bounds for computation of the solution of such problems are provided. To illustrate the results we apply the error control formula to the solution of two SDPPs with aggregator functions: the neoclassical Ramsey economic growth model and the Lucas asset pricing model.
Hypocholesterolaemic and hepatoprotective effects of virgin avocado oil in diet‐induced hypercholesterolaemia rats
Authors: Tan Chin Xuan , Chong Gun Hean , Hamzah Hazilawati , Ghazali Hasanah Mohd
Published: July 2018

Hypercholesterolaemia is a chronic disease associated with the development of nonalcoholic fatty liver disease and atherosclerosis. This study aimed to investigate the hypocholesterolaemic and hepatoprotective effects of virgin avocado oil (VAO) using diet‐induced hypercholesterolaemia rats. Male Sprague Dawley rats were fed high‐cholesterol diet for 4 weeks to induce hypercholesterolaemia. After confirming the establishment of hypercholesterolaemia model, the VAO (450 and 900 mg kg−1 body weight per day) and simvastatin (10 mg kg−1 body weight per day) were given orally while maintaining the high‐cholesterol diet for another 4 weeks. Changes in anthropometric, lipid profile, liver biomarkers and liver histology were determined. At the end of the experiment, the serum low‐density lipoprotein cholesterol (LDL‐C) and triglyceride (TG) levels were significantly reduced, while the high‐density lipoprotein cholesterol (HDL‐C) level was significantly increased in high‐dose VAO‐ (900 mg kg−1 body weight per day) and simvastatin‐treated rats when compared with their respective baseline values. The liver damage index was also markedly reduced in all treated rats. Current findings demonstrated the potential hypocholesterolaemic and hepatoprotective benefits of VAO in the preclinical study.
Intellectual Perfectionism about Schooling
Authors: Kotzee Ben
Published: July 2018

In education, character education is a burgeoning field; however, it is also the target of considerable criticism. Amongst criticisms of character education, the political criticism that character education is a form of indoctrination stands out. In particular, the charge is made against character education that it breaches the principle of liberal neutrality about the good. In this article I discuss liberal approaches to character education. I outline the two most prominent liberal approaches to character education in school, liberal neutralism and liberal perfectionism, as we find it in the work of Clayton (neutralism) and Levinson (liberal perfectionism). I hold that the two standard liberal approaches do not distinguish carefully enough between two possible forms of character education – moral character education and intellectual character education. Drawing on recent work in virtue epistemology, I hold that the liberal position tacitly demands intellectual character education. Regarding moral character education, however, I hold that the picture appears different. In the final analysis, I advocate a new form of perfectionism regarding character education that I call ‘intellectual perfectionism’. According to intellectual perfectionism, schools should be perfectionist regarding children's intellects, but neutralist regarding their morals.
Scary clowns: adaptive function of anemonefish coloration
Authors: Merilaita Sami , Kelley Jennifer L.
Published: July 2018

Clownfishes, with their showy coloration, are well known for their symbiosis with sea anemones and for their hierarchical reproductive system, but the function of their coloration is unclear. We used a phylogeny of 27 clownfish species to test whether fish coloration (i) serves a protective function that involves their anemone hosts, or (ii) signals species identity in species with overlapping host ranges that can potentially share the same host. We tested for an association between fish colour pattern traits, host morphology and host toxicity and examined coloration in relation to host sharing and geographic proximity. Fish with fewer stripes occupied fewer anemone species, and hosts with shorter tentacles, than fish with multiple stripes. There was a negative relationship between anemone toxicity and tentacle length and these protective traits together were correlated with the evolution of stripes. Host sharing or range overlap was not associated with coloration divergence. We propose that ancestral anemonefishes had multiple stripes that served for hiding/camouflage among the hosts’ long tentacles, whereas increased specialization towards fewer and more toxic hosts (with shorter tentacles) led to the use of coloration as an aposematic signal. The intriguing notion that an aposematic signal could advertise the defence of another species may reflect the unique symbiotic relationship between anemonefishes and their hosts.
Right aortic arch with bilateral arterial duct and nonconfluent pulmonary arteries without associated cardiac defects: Prenatal diagnosis and successful postnatal treatment
Authors: Cordisco Adalgisa , Murzi Bruno , Chiappa Enrico
Published: July 2018

We describe a rare case of right aortic arch with bilateral arterial duct and disconnected left pulmonary artery. Prenatal diagnosis allowed to plan delivery at the referral center and to maintain perfusion of the disconnected pulmonary artery through prostaglandin E1 infusion until surgical reconnection was performed. Early postnatal treatment avoided functional loss of the left lung that would have happened if malformation had not been identified before birth.
Immune response of the Pacific white shrimp, Litopenaeus vannamei, previously reared in biofloc and after an infection assay with Vibrio harveyi
Authors: Aguilera‐Rivera Diana , Escalante‐Herrera Karla , Gaxiola Gabriela , Prieto‐Davó Alejandra , Rodríguez‐Fuentes Gabriela , Guerra‐Castro Edlin , Hernández‐López Jorge , Chávez‐Sánchez María Cristina , Rodríguez‐Canul Rossanna
Published: July 2018

The effectiveness of the immune defense of Litopenaeus vannamei previously reared in biofloc or in a traditional clear seawater rearing system was assessed after a bacterial challenge with a pathogenic strain of Vibrio harveyi. The changes caused by its previous rearing system condition or the challenge were assessed in terms of metabolites (glucose, cholesterol, acylglycerides, protein), hemocyanin, the antioxidant defense system (superoxide dismutase, and catalase), and gene expression related to immune response (superoxide dismutase, alpha2 macroglobulin, prophenoloxidase, hemocyanin, and penaeidin‐3a). The biofloc rearing system was associated with a significant increase in protein, the antioxidant defense system, and the superoxide dismutase, alpha2 macroglobulin, and prophenoloxidase genes. For shrimp previously reared in biofloc, a positive interaction with the presence or absence (control) of V. harveyi significantly affected the hemocyanin concentration, and the interaction between the two rearing systems in shrimp challenged with the bacteria produced a higher transcription of the hemocyanin gene. Likewise, biofloc and clear seawater maintained a higher transcription of prophenoloxidase gene after the bacterial challenge. In the absence of the bacteria, shrimp of the biofloc group produced a higher transcription of the penaeidin‐3a gene. V. harveyi caused hepatopancreatic lesions and mortalities only in shrimp previously reared in clear seawater. These results suggest that biofloc helps to prevent the development of disease by improving the shrimp immune response.
Covariates streamline age‐specific early life survival estimates of two chelonian species
Authors: Arsovski D. , Olivier A. , Bonnet X. , Drilholle S. , Tomović L. , Béchet A. , Golubović A. , Besnard A.
Published: July 2018

Delayed maturity and high survival rates of immatures and adults characterize long‐lived species’ life histories. Understanding how these traits interact in stochastic environments is essential to understand early life in long‐lived species and to assist conservation planning. Unfortunately, available information of demographic traits in immatures are often fragmentary and the logistical difficulties of capturing and recapturing this cohort leave little room for improvement. Published immature chelonian survival estimates vary broadly, are often not age‐specific, and lack precision. In an attempt to overcome this issue, we developed a novel modelling approach based on Capture‐Recapture data to obtain robust age‐specific survival probabilities in two chelonian species (the freshwater European pond turtle, Emys orbicularis, and the terrestrial Hermann's tortoise, Testudo hermanni). More specifically, we show that implementing a linear relationship between survival probabilities and age does not distort survival estimates and improves precision. Both species display a progressive increase in survival with age, reaching a plateau at the ages of four to five. As maturity occurs later in both species (8–12 years‐old), the survival plateau might be governed by the final hardening of the carapace, which brings obvious survival benefits. Taking advantage of the flexibility of multievent models we encourage a systematic field approach even when very large samples from immatures cannot be amassed. Only so can demographic traits in chelonians, and more generally in long‐lived species, be properly explored.
Import‐Export and ‘And’
Authors: Mandelkern Matthew
Published: July 2018

Import‐Export says that a conditional of the form is always equivalent to the corresponding conditional . I argue that Import‐Export does not sit well with a classical approach to conjunction: given some plausible and widely accepted principles about conditionals, Import‐Export together with classical conjunction leads to absurd consequences. My main goal is to draw out these surprising connections. In concluding, I argue that the best response to these facts is to reject Import‐Export and adopt instead a limited version of that principle which better fits natural language data, still accounts for the intuitions that motivate Import‐Export, and sits more easily with a classical conjunction.
Basidiospores as sources of inoculum in the spread of Ganoderma boninense in oil palm plantations in Papua New Guinea
Authors: Pilotti C. A. , Gorea E. A. , Bonneau L.
Published: July 2018

Basal and upper stem rot of oil palm is caused by the agaricomycete Ganoderma boninense. This study investigated the transmission of basal stem rot from Ganoderma‐infected oil palm stumps to young oil palm seedlings. Low seedling mortalities (2.5%) were observed in a field trial after 24 months, but G. boninense could be detected in the rachis, bole and roots of a significant proportion of seedlings that were outwardly healthy. A high level of genetic heterogeneity amongst G. boninense isolates within the trial area was revealed. Furthermore, germinated seedlings growing in close proximity to infected palms in a mature oil palm field contained multiple isolates of G. boninense indicating that colonization of roots by basidiospores and dikaryons, arising from mating between basidiospores, is a common occurrence in oil palm plantations. The probability that basidiospores are a direct source of inoculum in addition to diseased trunk tissue is discussed as a means of explaining the observed heterogeneity in populations of G. boninense on oil palm. Such a scenario presents challenges for the long‐term management of basal stem rot.
MCRiceRepGP: a framework for the identification of genes associated with sexual reproduction in rice
Authors: Golicz Agnieszka A. , Bhalla Prem L. , Singh Mohan B.
Published: July 2018

Rice is an important cereal crop, being a staple food for over half of the world's population, and sexual reproduction resulting in grain formation underpins global food security. However, despite considerable research efforts, many of the genes, especially long intergenic non‐coding RNA (lincRNA) genes, involved in sexual reproduction in rice remain uncharacterized. With an increasing number of public resources becoming available, information from different sources can be combined to perform gene functional annotation. We report the development of MCRiceRepGP, a machine learning framework which integrates heterogeneous evidence and employs multicriteria decision analysis and machine learning to predict coding and lincRNA genes involved in sexual reproduction in rice. The rice genome was reannotated using deep‐sequencing transcriptomic data from reproduction‐associated tissue/cell types identifying previously unannotated putative protein‐coding genes and lincRNAs. MCRiceRepGP was used for genome‐wide discovery of sexual reproduction associated coding and lincRNA genes. The protein‐coding and lincRNA genes identified have distinct expression profiles, with a large proportion of lincRNAs reaching maximum expression levels in the sperm cells. Some of the genes are potentially linked to male‐ and female‐specific fertility and heat stress tolerance during the reproductive stage. MCRiceRepGP can be used in combination with other genome‐wide studies, such as genome‐wide association studies, giving greater confidence that the genes identified are associated with the biological process of interest. As more data, especially about mutant plant phenotypes, become available, the power of MCRiceRepGP will grow, providing researchers with a tool to identify candidate genes for future experiments. MCRiceRepGP is available as a web application (http://mcgplannotator.com/MCRiceRepGP/).
A novel mutation +5904 C>T of RUNX1 site in the erythroid cell‐specific regulatory element decreases the ABO antigen expression in Chinese population
Authors: Ying Y. , Hong X. , Xu X. , Ma K. , He J. , Zhu F.
Published: July 2018

Background

An erythroid cell‐specific regulatory element (+5·8‐kb) in the first intron of ABO is responsible for the antigen differential expression and the regulatory activity of the element was affected by the nucleotide mutation in the +5·8‐kb region. Currently, many individuals with ABO subgroups were found in the Chinese population, but there was little information about the function of +5·8‐kb region in these individuals. Here, we studied the mechanism of the mutation in the +5·8‐kb region responsible for reducing of antigen expression in 30 ABO subtype Chinese individuals without mutation in the coding region or splicing site.

Materials and methods

The nucleotide sequence of the partial intron 1 covering the +5·8‐kb site was amplified and directly sequenced. The haplotype with the novel mutation was obtained by the TOPO TA cloning. Both of the ABO promoter and the +5·8 kb regulatory element were subcloned into the basic luciferase reporter plasmid using the double endonuclease digestion. The promoter activity was examined by the dual‐luciferase report vector with K562 cells.

Results

A novel nucleotide substitution +5904 C>T located at RUNX1‐binding site in the +5·8 kb site was identified from three individuals with B subtypes. +5890 T>G were found in three Bel and one Ael phenotypes. Cotransfection and luciferase assays demonstrated that the +5904 C>T could obviously reduce activity of the +5·8 kb site.

Conclusion

The study suggested that the transcriptional activity of the +5·8 kb site could be downregulated by the single point mutation of RUNX1 motif, leading to reduction in A or B antigen expression.
Metabolic signaling directs the reciprocal lineage decisions of αβ and γδ T cells
Authors: Yang Kai , Blanco Daniel Bastardo , Chen Xiang , Dash Pradyot , Neale Geoffrey , Rosencrance Celeste , Easton John , Chen Wenan , Cheng Changde , Dhungana Yogesh , KC Anil , Awad Walid , Guo Xi-Zhi J. , Thomas Paul G. , Chi Hongbo
Published: July 2018

Development of αβ and γδ T cells requires coupling of environmental signals with metabolic and redox regulation by mTORC1.
In Vivo
Intradermal Delivery of Bacteria by Using Microneedle Arrays
Authors: Chandler Courtney E. , Harberts Erin M. , Laemmermann Tim , Zeng Qin , Opene Belita N. , Germain Ronald N. , Jewell Christopher M. , Scott Alison J. , Ernst Robert K.
Published: July 2018

Infectious diseases propagated by arthropod vectors, such as tularemia, are commonly initiated via dermal infection of the skin. However, due to the technical difficulties in achieving accurate and reproducible dermal deposition, intradermal models are less commonly used.
Expression of Adhesive Pili and the Collagen-Binding Adhesin Ace Is Activated by ArgR Family Transcription Factors in Enterococcus faecalis
Authors: Manias Dawn A. , Dunny Gary M.
Published: July 2018

Cell surface adhesins play critical roles in the formation of biofilms, host colonization, and the pathogenesis of opportunistic infections by
Enterococcus faecalis
. Here, we present new results showing that the expression of two major enterococcal surface adhesins,
ebp
pili, and the collagen-binding protein Ace is positively regulated at the transcription level by two
argR
family transcription factors, AhrC and ArgR2. In the case of pili, the direct target of regulation is the
ebpR
gene, previously shown to activate the transcription of the pilus structural genes, while the activation of
ace
transcription appears to be directly impacted by the two ArgR proteins. These transcription factors may represent new targets for blocking enterococcal infections.
Risk factors associated with injury and concussion in sanctioned amateur and professional mixed martial arts bouts in Calgary, Alberta
Authors: Curran-Sills Gwynn , Abedin Tasnima
Published: July 2018

Background

There is limited literature that examines risk factors for injury and mild traumatic brain injury (mTBI) in mixed martial arts (MMA). An examination of previously unstudied bout and athlete characteristics that may pose health risks while partaking in this sport is warranted.

Hypothesis/purpose

To determine the incidence of injury and concussion, along with the identification of risk factors that contribute to injury and mTBI in amateur and professional MMA bouts in Calgary, Alberta.

Study design

A retrospective cohort study with case–control design.

Methods

Calgary amateur and professional MMA records were examined from 1 January 2010 to 31 December 2015. Descriptive statistics were used to describe the incidence of injury and concussion, along with univariate and multivariable logistic regression to identify risk factors for injury and mTBI.

Results

The injury rate per 100 athlete exposure (AE), the injury rate per 100 min of exposure and the concussion rate per 100 AE were 23.6 (95% CI 20.5 to 27.0), 4.1 (95% CI 3.48 to 4.70) and 14.7 (95% CI 11.8 to 17.2), respectively. The most common location of injury was the head and mTBI was the most common type of injury. Athletes whose bout was finished by a knockout/technical knockout, corner stoppage, draw, no contest or physician, and those whose country of origin was non-Canadian, were more likely to sustain an injury. No risk factors for concussion were shown to be significant.

Conclusion

Engaging in MMA exposes athletes to inherent risk and several recommendations are proposed to reduce these risks. Future prospective investigations are necessary to better delineate the findings in this study.
From pilot project to system solution: innovation, spread and scale for health system leaders
Authors: Shaw James , Tepper Joshua , Martin Danielle
Published: July 2018

Promoting the scale and spread of effective health innovations requires dedicated action from health system leaders. In order to maximise the effects of leadership strategies to promote the spread and scale of health innovations, conceptual clarity and well-defined strategies are essential. In this commentary, we propose definitions of the concepts of ‘innovation’, ‘spread’ and ‘scale’, and explain how these concepts can be used by health system leaders to generate interest, excitement and commitment for specific innovations from a broad community of stakeholders. We then outline two strategies from the community organising literature that leaders can use to promote spread and scale.
Occupational exposure to benzene, toluene, xylene and styrene and risk of prostate cancer in a population-based study
Authors: Blanc-Lapierre Audrey , Sauvé Jean-François , Parent Marie-Elise
Published: July 2018

Objectives

While several monocyclic aromatic hydrocarbons are classified as definite or possible carcinogens to humans, little data exist on their role in prostate cancer (PCa). We examined occupational exposure to benzene, toluene, xylene (BTX) and styrene and PCa risk in a population-based case–control study in Montreal, Canada.

Methods

Cases aged ≤75 years diagnosed with PCa in 2005–2009 (n=1920) and population controls frequency-matched on age (n=1989) provided detailed work histories. Experts evaluated the certainty, frequency and concentration of exposure to monocyclic aromatic hydrocarbons in each job lasting ≥2 years. Logistic regression estimated OR and 95% CIs for PCa risk, adjusting for potential confounders.

Results

Exposures to BTX were highly intercorrelated, except for durations of exposure at substantial levels. Ever exposure to any BTX was associated with overall PCa (OR 1.27, 95% CI 1.05 to 1.53), while the OR for styrene was 1.19. However, increases in risk were largely confined to low-grade tumours, with ORs of 1.33 (95%CI 1.08 to 1.64) and 1.41 (95% CI 0.85 to 2.31) for ever exposure to any BTX and styrene, respectively, and a duration response pattern for any BTX. Risks for low-grade tumours were elevated among men exposed ≥25 years at substantial levels of benzene (OR 2.32) and styrene (OR 2.44). Some cumulative exposure categories showed increased risks but without clear trends.

Conclusion

Exposure to any BTX was associated with higher risks of overall PCa. Prolonged exposures at the substantial level to benzene and styrene increased risks of low-grade tumours. These novel findings were independent from PCa screening.