bluuebunny/crossref_metadata_2025 huggingface dataset:
The persimmon genome reveals clues to the evolution of a lineage-specific sex determination system in plants
Authors: Akagi Takashi , Shirasawa Kenta , Nagasaki Hideki , Hirakawa Hideki , Tao Ryutaro , Comai Luca , Henry Isabelle M.
Published: May 2019

Most angiosperms bear hermaphroditic flowers, but a few species have evolved outcrossing strategies, such as dioecy, the presence of separate male and female individuals. We previously investigated the mechanisms underlying dioecy in diploid persimmon (D. lotus) and found that male flowers are specified by repression of the autosomal gene MeGI by its paralog, the Y-encoded pseudo-gene OGI. This mechanism is thought to be lineage-specific, but its evolutionary path remains unknown. Here, we developed a full draft of the diploid persimmon genome (D. lotus), which revealed a lineage-specific genome-wide paleoduplication event. Together with a subsequent persimmon-specific duplication(s), these events resulted in the presence of three paralogs, MeGI, OGI and newly identified Sister of MeGI (SiMeGI), from the single original gene. Evolutionary analysis suggested that MeGI underwent adaptive evolution after the paleoduplication event. Transformation of tobacco plants with MeGI and SiMeGI revealed that MeGI specifically acquired a new function as a repressor of male organ development, while SiMeGI presumably maintained the original function. Later, local duplication spawned MeGI’s regulator OGI, completing the path leading to dioecy. These findings exemplify how duplication events can provide flexible genetic material available to help respond to varying environments and provide interesting parallels for our understanding of the mechanisms underlying the transition into dieocy in plants.

Author summary

Plant sexuality has fascinated scientists for decades. Most plants can self-reproduce but not all. For example, a small subset of species have evolved a system called dioecy, with separate male and female individuals. Dioecy has evolved multiple times independently and, while we do not understand the molecular mechanisms underlying dioecy in many of these species yet, a picture is starting to emerge with recent progress in several dioecious species. Here, we focused on the evolutionary events leading to dioecy in persimmon. Our previous work had identified a pair of genes regulating sex in this species, called OGI and MeGI. We drafted the whole genome sequence of diploid persimmon to investigate their evolutionary history. We discovered a lineage-specific genome duplication event, and observed that MeGI underwent adaptive evolution after this duplication. Transgenic analyses validated that MeGI newly acquired a male-suppressor function, while the other copy of this gene, SiMeGI, did not. The regulator of MeGI, OGI, resulted from a second smaller-scale duplication event, finalizing the system. This study sheds light on the role of duplication as a mechanism that promote flexible genes functions, and how it can affect important biological functions, such as the establishment of a new sexual system.
Stochastic modeling of aging cells reveals how damage accumulation, repair, and cell-division asymmetry affect clonal senescence and population fitness
Authors: Song Ruijie , Acar Murat
Published: May 2019

Background

Asymmetry during cellular division, both in the uneven partitioning of damaged cellular components and of cell volume, is a cell biological phenomenon experienced by many unicellular organisms. Previous work based on a deterministic model claimed that such asymmetry in the partitioning of cell volume and of aging-associated damage confers a fitness benefit in avoiding clonal senescence, primarily by diversifying the cellular population. However, clonal populations of unicellular organisms are already naturally diversified due to the inherent stochasticity of biological processes.

Results

Applying a model of aging cells that accounts for natural cell-to-cell variations across a broad range of parameter values, here we show that the parameters directly controlling the accumulation and repair of damage are the most important factors affecting fitness and clonal senescence, while the effects of both segregation of damaged components and division asymmetry are frequently minimal and generally context-dependent.

Conclusions

We conclude that damage segregation and division asymmetry, perhaps counterintuitively, are not necessarily beneficial from an evolutionary perspective.
Linkage between tree species richness and soil microbial diversity improves phosphorus bioavailability
Authors: Wu Huili , Xiang Wenhua , Ouyang Shuai , Forrester David I. , Zhou Bo , Chen Lingxiu , Ge Tida , Lei Pifeng , Chen Liang , Zeng Yelin , Song Xinzhang , Peñuelas Josep , Peng Changhui
Published: May 2019

Increased availability of soil phosphorus (P) has recently been recognised as an underlying driving factor for the positive relationship between plant diversity and ecosystem function. The effects of plant diversity on the bioavailable forms of P involved in biologically mediated rhizospheric processes and how the link between plant and soil microbial diversity facilitates soil P bioavailability, however, remain poorly understood.

This study quantified four forms of bioavailable P (CaCl2‐P, citric‐P, enzyme‐P and HCl‐P) in mature subtropical forests using a novel biologically based approach, which emulates how rhizospheric processes influence the release and supply of available P. Soil microbial diversity was measured by Illumina high‐throughput sequencing.

Our results suggest that tree species richness significantly affects soil microbial diversity (p < 0.05), increases litter decomposition, fine‐root biomass and length and soil organic carbon and thus increases the four forms of bioavailable P. A structural equation model that links plants, soil microbes and P forms indicated that soil bacterial and fungal diversity play dominant roles in mediating the effects of tree species richness on soil P bioavailability.

An increase in the biodiversity of plants, soil bacteria and fungi could maintain soil P bioavailability and alleviate soil P limitations. Our results imply that biodiversity strengthens plant and soil feedback and increases P recycling.

A plain language summary is available for this article.
Is phenotypic plasticity an explanation for the invasiveness of goldenrods (SolidagoandEuthamia) in Europe?
Authors: Szymura Magdalena , Szymura Tomasz H. , Rajsz Adam , Świerszcz Sebastian
Published: May 2019

High phenotypic plasticity contributes to invasiveness of alien species. Goldenrods of American origin (Solidago canadensis,S. giganteaandEuthamia graminifolia) have successfully invaded Europe, and this success can be related to their high phenotypic plasticity. The aim of our study was to test the hypothesis of higher phenotypic plasticity of invasive goldenrods by comparing them with native taxa: closely relatedSolidago virgaureaand similar ecologically, invasive in other regionsTanacetum vulgare. The species studied were grown in a common garden on three different substrates with different fertilizers. After 3 years, the height and number of ramets, biomass production and allocation, phenology and nitrate reductase activity (NRA) were measured. The highest level of phenotypic plasticity was exhibited by the competitively weak native speciesS. virgaurea. The invasive species produced relatively high biomass and exhibited a moderate level of phenotypic plasticity. Variability in the studied traits did not always correlate with differences in substrates. The invasion success of non‐native goldenrods is not caused by their having a higher phenotypic plasticity than native species. Rather, the non‐natives should be considered as “Jack of all traits, and master of some”.
Skunks in an English Woodland: Should England Embrace For‐Profit Higher Education?
Authors: Ahlburg Dennis A.
Published: May 2019

The British government is encouraging the growth of for‐profit alternative providers of higher education (HE). While it is true that for‐profits have opened HE access to previously under‐served groups and have been more agile in reacting to market demand, they have done so at a considerable cost to students and the taxpayer because they do not share in the cost of the failure of HE to ensure a payoff for many of their students. The US experience with for‐profits should be a cautionary tale for those supporting their expansion in Britain. Policy is needed to craft a regulatory framework that produces the benefits that for‐profits can provide, but minimises the costs that often accompany them. At present, it is far from clear that expanding alternative providers—that is, for‐profits—would ‘work better’ for students.
How Russia's Internet Research Agency Built its Disinformation Campaign
Authors: Dawson Andrew , Innes Martin
Published: May 2019

In this article we analyse features of the information influence operations run by the St. Petersburg based Internet Research Agency, targeted at Europe. Informed by publicly available ‘open source’ data, the analysis delineates three key tactics that underpinned their disinformation campaign: account buying; ‘follower fishing’; and narrative switching. Both individually and collectively these were designed to build the reach, impact and influence of the ideologically loaded messages that social media account operators authored and amplified. The particular value of the analysis is that whilst a lot of recent public and political attention has focussed upon Kremlin backed disinformation in respect of the 2016 United States presidential election, far less work has addressed their European activities.
Model Building and Slicing in Food 3D Printing Processes: A Review
Authors: Guo Chaofan , Zhang Min , Bhandari Bhesh
Published: May 2019

Three‐dimensional (3D) printing has been successfully applied to food processing, and widely appreciated by food science researchers. Recently, a lot of researches and review works have been done focusing on the ink's properties, printer design, and printing parameters. However, few articles specifically describe 3D models and slicing methods used in food printing. This work introduced the requirements for 3D printing models in some specific areas, discussed the critical parameter settings in the model slicing processes, and discussed the possible use of numerical techniques in the model building and printing of food 3D printing. The objective of this review is to increase researchers' focus on 3D printing models and slices in order to optimize the printing process and to provide some useful information for future research.
International Perspectives on Substantiating the Efficacy of Herbal Dietary Supplements and Herbal Medicines Through Evidence on Traditional Use
Authors: Lenssen Karin G. M. , Bast Aalt , de Boer Alie
Published: May 2019

The efficacy of botanicals in medicines can be substantiated with evidence on traditional use, whereas in foodstuffs, this is often not possible. In Europe, for example, the evaluation and subsequent authorization of health claims on herbal dietary supplements (HDS) have been put on hold by the European Commission. This study aims to analyze the role of evidence on traditional use in international legal frameworks of foods and pharmaceuticals. Both legal sources as well as scientific studies offering insights into these regulatory frameworks were included into the analysis. The international approach toward evidence on traditional use for substantiating efficacy of botanicals varies highly. For herbal medicines, substantiating efficacy with evidence on traditional use is possible in all studied jurisdictions, except for Japan and the United States. HDS efficacy can only be substantiated with evidence on traditional use in India and New Zealand, although the enforcing authorities do not describe which data are required. Australia and Canada regulate botanicals in a separate “borderline” category from foods and pharmaceuticals. Both jurisdictions allow for substantiating efficacy with evidence on traditional use. This study's second objective was to assess the applicability of the international approaches in the European legal framework, in light of the ongoing political debate regarding the use of traditional evidence. Implementation of the analyzed international approaches would require major revisions of the current European legal framework. This review of international approaches might, however, aid in deciding upon future approaches for substantiating health claims with evidence on traditional use.
Characteristics and outcomes of patient presentations made by police to an Australian emergency department
Authors: Crilly Julia , Zhang Ping , Lincoln Cathy , Scuffham Paul , Timms Jo , Becker Ken , van Buuren Nelle , Fisher Andrew , Murphy Danny , Green David
Published: May 2019

Objective

To describe and compare characteristics and outcomes of patient presentations brought in by police (BIBP) with those not BIBP (NBIBP) to one Australian ED.

Methods

A retrospective observational study. All patient presentations to a tertiary hospital ED made during the period 8 October 2012 to 7 April 2013 were included. Routinely collected ED information data and medical record review data were used. ED care delivery for people BIBP from the watch house (WH) or other location was compared. Univariate comparison and multivariate logistic regression analyses were performed to identify the different characteristics and ED outcomes between BIBP and NBIBP groups.

Results

A total of 35 127 ED presentations occurred within the 6 month period; 392 (1.1%) were BIBP. Compared with those NBIBP, those BIBP were diagnosed with ‘psychiatric’ and ‘toxicology‐related’ illnesses in higher proportions. Overlap in health conditions (primarily for physical health reasons) between those BIBP and NBIBP existed. Presentations BIBP from the WH reflected ‘physical health emergencies’ whereas presentations BIBP from other locations reflected ‘behavioural emergencies’. Compared to those NBIBP, those BIBP had a longer wait to be seen (by about 5 min), longer ED length of stay (LOS) if not admitted (by about 20 min) but shorter ED LOS if admitted (by about 59 min). When adjusted for sex, age group and diagnosis, ED LOS (if admitted) and admission rate were statistically significant. For those BIBP, mental health related orders and alcohol breath tests were common.

Conclusions

Patients BIBP were different to those NBIBP. Despite comprising a small proportion of overall ED attendances, they are a group where mental health and drug and alcohol issues are over‐represented. Differences in ED care delivery for those BIBP highlights potential opportunities for pre‐hospital healthcare interventions.
Examining emergency department inequities: Do they exist?
Authors: Curtis Elana , Paine Sarah‐Jane , Jiang Yannan , Jones Peter , Tomash Inia , Raumati Inia , Reid Papaarangi
Published: May 2019

Objectives

Ethnic inequities in health outcomes have been well documented with Indigenous peoples experiencing a high level of healthcare need, yet low access to, and through, high‐quality healthcare services. Despite Māori having a high ED use, few studies have explored the potential for ethnic inequities in emergency care within New Zealand (NZ). Healthcare delivery within an ED context is characterised by time‐pressured, relatively brief, complex and demanding environments. When clinical decision‐making occurs in this context, provider prejudice, stereotyping and bias are more likely. The examining emergency department inequities (EEDI) research project aims to investigate whether clinically important ethnic inequities between Māori and non‐Māori exist.

Methods

EEDI is a retrospective observational study examining ED admissions in NZ between 2006 and 2012 (5 976 126 ED events). EEDI has been designed from a Kaupapa Māori Research position.

Results

The primary data source is the existing Shorter Stays in Emergency Department National Research Project (SSED) dataset that will be combined with clinical information extracted from NZ's National Minimum Dataset. The key predictor variable is patient ethnicity with other covariates including: sex, age‐group, area deprivation, mode of presentation, referral method, Australasian Triage Scale and the Multimorbidity Measure (M3 Index) for co‐morbidities. Generalised linear regression models will be used to investigate the associations between pre‐admission variables and the measures of ED care, and to examine the contribution of each measure of ED care on ethnic inequities in mortality.

Conclusion

The present study will provide the largest, most comprehensive investigation of ED outcomes by ethnicity to date in NZ.
Evaluation of Food Safety and Quality Parameters for Shelf Life Extension of Pulsed Light Treated Strawberries
Authors: Cao Xinang , Huang Runze , Chen Haiqiang
Published: May 2019

Strawberry is a healthy fruit with numerous health‐benefit compounds. Unfortunately, it is highly perishable and occasionally can be contaminated with foodborne pathogens. The overall goal of this study is to evaluate pulsed light (PL) processing for disinfection of strawberries, extension of shelf life, and preservation of quality attributes and compounds that are beneficial to health. Preliminary screening of PL conditions based on visual appearance of strawberries was conducted, and 3 PL treatments were identified for full evaluation. Salmonella inoculum was artificially deposited onto the skin of strawberries via spot‐inoculation or dip‐inoculation. The 3 PL treatments slightly reduced the level of inoculated Salmonella on strawberries, ranging from approximately 0.4 to 0.8 log reduction. They also slowed down the visible mold development on strawberries by 2 to 4 days compared with the untreated control. Regarding the natural yeasts and molds, the quality attributes (weight loss and firmness), and the bioactive compounds (total anthocyanin, total phenolics, and total antioxidant activity). The 3 PL treatment showed no significant or negligible difference comparing to the control group. Overall, the 3 PL treatments demonstrated potential in extending the shelf life of strawberries. The quality attributes or the bioactive compounds of strawberries showed no significant or minimal change after these PL treatments.

Practical Application

Pulsed light (PL) processing for strawberry decontamination and shelf life extension was evaluated. Results demonstrated that PL processing could have the potency to improve strawberry shelf life without significantly affecting the quality and bioactive compounds of strawberries.
Effect of Emulsifier Type, Maltodextrin, and β‐Cyclodextrin on Physical and Oxidative Stability of Oil‐In‐Water Emulsions
Authors: Kibici Duygu , Kahveci Derya
Published: May 2019

The effect of emulsifiers, emulsion stabilizer (maltodextrin, MD), and β‐cyclodextrin (BCD) on physical and oxidative properties of oil‐in‐water (O/W) emulsions (5%, 20%, 40% of oil, w/w) was investigated. Four different emulsifiers were selected based on their structure: two types of protein‐based emulsifiers (sodium caseinate, SC; and whey protein isolate, WPI), and two types low molecular weight emulsifiers (LMEWs: lecithin, LEC; and Citrem, CITREM). Physical and oxidative stability of emulsions prepared with these emulsifiers together with MD were compared based on their creaming index (CI), viscosity, droplet size, zeta potential, peroxide and p‐anisidine values. LMWE‐stabilized emulsions (with LEC or CITREM) had better creaming stability with lower droplet sizes whereas protein‐stabilized emulsions (with SC or WPI) had higher viscosities. Droplet size was the lowest when CITREM was used, which increased with increasing oil concentration for all emulsifiers. Formulation with the lowest CI value and droplet size was considered to be more prone to oxidation; therefore, a 1:1 (w/w) combination of CITREM with BCD was used to stabilize the emulsions to improve the oxidative as well as physical stability. Added BCD significantly increased the storage stability of emulsions by reducing CI and droplet size values with a simultaneous increase in the viscosity, both at room temperature and at storage conditions (at 4 and 55 oC). However, the oxidative as well as physical stability of BCD added emulsions were not improved, neither toward heat‐ nor light‐induced lipid oxidation.

Practical Application

This work investigated the effects of emulsifiers and dextrins on the stability of oil‐in‐water (O/W) emulsions. Both maltodextrin (MD) and β‐cyclodextrin (BCD) addition resulted in enhanced physical stability, the latter being more effective. The findings can be applied to formulate emulsions with improved shelf life within the limits of allowed daily intake (ADI) level of BCD (5 mg/kg bw per day).
Quality and quantity of genetic relatedness data affect the analysis of social structure
Authors: Foroughirad Vivienne , Levengood Alexis L. , Mann Janet , Frère Céline H.
Published: May 2019

Kinship plays a fundamental role in the evolution of social systems and is considered a key driver of group living. To understand the role of kinship in the formation and maintenance of social bonds, accurate measures of genetic relatedness are critical. Genotype‐by‐sequencing technologies are rapidly advancing the accuracy and precision of genetic relatedness estimates for wild populations. The ability to assign kinship from genetic data varies depending on a species’ or population's mating system and pattern of dispersal, and empirical data from longitudinal studies are crucial to validate these methods. We use data from a long‐term behavioural study of a polygynandrous, bisexually philopatric marine mammal to measure accuracy and precision of parentage and genetic relatedness estimation against a known partial pedigree. We show that with moderate but obtainable sample sizes of approximately 4,235 SNPs and 272 individuals, highly accurate parentage assignments and genetic relatedness coefficients can be obtained. Additionally, we subsample our data to quantify how data availability affects relatedness estimation and kinship assignment. Lastly, we conduct a social network analysis to investigate the extent to which accuracy and precision of relatedness estimation improve statistical power to detect an effect of relatedness on social structure. Our results provide practical guidance for minimum sample sizes and sequencing depth for future studies, as well as thresholds for post hoc interpretation of previous analyses.
Association between chondrocalcinosis and osteoarthritis: A systematic review and meta‐analysis
Authors: Wang Yilun , Wei Jie , Zeng Chao , Xie Dongxing , Li Hui , Yang Tuo , Ding Xiang , Cui Yang , Xiong Yilin , Li Jiatian , Lei Guanghua
Published: May 2019

Aim

To systematically examine the existing literature on the associations between chondrocalcinosis (CC) and osteoarthritis (OA) at different joints, and to quantify such associations through meta‐analysis.

Methods

PubMed, Embase and Scopus databases were searched through from inception to June 2017. Cohort, case‐control or cross‐sectional studies were included if they examined the association between CC and OA. Data on the odds ratios (OR) and their 95% confidence intervals (CI) of the prevalence or progression of OA between the CC group and non‐CC group with respect to the same joint were extracted.

Results

A total of 14 studies were identified. Twelve studies were eligible for assessing the association between knee CC and knee OA. The combined data showed a positive association between them (OR = 2.84; 95% CI, 2.12‐3.81; P < 0.001). Three studies were eligible for assessing the association between hip CC and hip OA. The data on the OR could only be extracted from one study (OR = 0.92; 95% CI, 0.68‐1.24; P = 0.59). Two studies were eligible for assessing the association between hand CC and hand OA, and the data on the OR could only be extracted from one study which reported significant associations between CC and OA at the metacarpophalangeal joint (OR = 4.75; 95% CI, 2.12‐10.64; P < 0.001) and the wrist joint (OR = 4.44; 95% CI, 3.56‐5.54; P < 0.001).

Conclusion

This study established a strong association between knee CC and knee OA. However, the associations between CC and OA at the hip or hand still remain controversial and warrant further study.
Alcohol‐induced blackouts at age 20 predict the incidence, maintenance and severity of alcohol dependence at age 25: a prospective study in a sample of young Swiss men
Authors: Studer Joseph , Gmel Gerhard , Bertholet Nicolas , Marmet Simon , Daeppen Jean‐Bernard
Published: May 2019

Background and Aims

Alcohol‐induced blackout (AIB) is a common alcohol‐related adverse event occurring during teenage years. Although research provides evidence that AIB predicts acute negative consequences, less is known about the associations of AIB with chronic consequences, such as alcohol dependence (AD). This study estimated the associations between an experience of AIB at age 20 and the incidence, maintenance and severity of AD at age 25 among Swiss men.

Design

Prospective cohort study with 5.5 years separating baseline and follow‐up.

Setting

Switzerland.

Participants

Swiss male drinkers (n = 5469, age 20 at baseline) drawn from the Cohort Study on Substance Use Risk Factors (C‐SURF).

Measurements

Self‐report questionnaires assessing AIB, AD, alcohol (drinking volume, binge drinking), cigarette and cannabis use, several risk factors (sensation‐seeking, family history of problematic alcohol use, age of first alcohol intoxication) and socio‐demographic variables.

Findings

Generalized estimating equation models with and without adjustment for risk factors, including alcohol use and socio‐demographics, showed that AIB at age 20 significantly predicted the incidence of AD at age 25 in men without AD at age 20 [odds ratio (OR) = 2.52, 95% confidence interval (CI), unadjusted = 2.04, 3.11, P < 0.001; fully adjusted, OR = 1.47, 95% CI = 1.13, 1.91, P = 0.004], maintenance of AD in men with AD at age 20 (unadjusted, OR = 1.82, 95% CI = 1.12, 2.95, P = 0.015; fully adjusted, OR = 1.66, 95% CI = 1.00, 2.76, P = 0.048] and AD severity [unadjusted incidence rate ratio (IRR) = 1.89, 95% CI = 1.69, 2.11, P < 0.001; fully adjusted, IRR = 1.20, 95% CI = 1.10, 1.31, P < 0.001].

Conclusions

Among Swiss men, alcohol‐induced blackout at age 20 predicts the development, maintenance and severity of alcohol dependence at age 25.
Waiting times in aged care: What matters?
Authors: Yu Serena , Byles Julie
Published: May 2019

Objective

To assess consumer‐level socioeconomic factors associated with waiting times for access to aged care services, specifically community‐based care and permanent residential care.

Methods

Administrative data on assessment outcomes and admissions to services were linked with survey data at the person‐level and were used to implement a competing risks regression model. We estimated the association between health needs, and socioeconomic variables and subsequent waiting periods for individuals with approval for access.

Results

The main consumer‐level factors driving waiting time were the individual's assessed needs, including health status, whether they lived alone and age. We found no evidence that socioeconomic status was associated with waiting times for community‐based care; however, admission to residential care reflected socioeconomic factors including education levels and geographical isolation.

Conclusion

This paper provides baseline evidence for factors affecting wait times in aged care, essential for evaluating subsequent policy reforms aimed at reducing wait times and increasing equity of access and consumer choice.
Estimation of aboveground biomass in conserved areas of Stipa tenacissima L. stands in the high steppes of western Algeria by mean of the Landsat 8 imagery‐based vegetation indices
Authors: Benseghir Louaï , Kadi‐Hanifi Halima , Bachari Nour El Islam
Published: May 2019

The main aim of this paper was to evaluate the use of OLI spectral data as a tool to assess the steppe vegetation in a conservation context. The field sampling was conducted for two specific areas of treatment (a) an exclosure area and (b) a free grazing area. After testing several vegetation indices (VIs), the optimal results were obtained for the Normalised Difference Vegetation Index (NDVI)‐based aboveground biomass model with r2 = 0.61 and r2 = 0.72 for total and perennial biomass, respectively. No difference between observed and predicted total and perennial biomass was found (p = 0.700 and p = 0.306, respectively). The comparison between the two treatments using the field sampling revealed a significant difference on total plant cover (p = 0.016) and total biomass (p = 0.005), with a plant cover of 50.6% and a biomass of 325.771 kg dry matter per hectare (kg DM ha−1) on average in grazed area and 66.9%, 1,407.869 kg DM ha−1 in exclosure. Finally, a concordance is noted between the results obtained by the NDVI‐based biomass model and the field sampling‐based biomass.
Retinal layer thickness in preclinical Alzheimer's disease
Authors: van de Kreeke Jacoba A. , Nguyen Hoang‐Ton , den Haan Jurre , Konijnenberg Elles , Tomassen Jori , den Braber Anouk , ten Kate Mara , Collij Lyduine , Yaqub Maqsood , van Berckel Bart , Lammertsma Adriaan A. , Boomsma Dorret I. , Tan Hendra Stevie , Verbraak Frank D. , Visser Pieter Jelle
Published: May 2019

Purpose

There is urgent need for non‐invasive diagnostic biomarkers in the preclinical phase of Alzheimer's Disease (AD). Several studies suggest that retinal thickness is reduced in AD. Here, we aim to test the diagnostic value of retinal thickness in preclinical AD, as defined by cognitively normal individuals with amyloid pathology on PET.

Methods

One hundred and sixty five cognitively healthy monozygotic twins aged ≥ 60 were included from the Netherlands Twin Register taking part in the European Medical Information Framework for Alzheimer's Disease PreclinAD study. Participants underwent [18F] flutemetamol PET that was visually rated for presence or absence of cortical amyloid beta (Aβ). Binding potential (BPND) was calculated as continuous measure for Aβ. Spectral Domain OCT was used to asses total and individual inner retinal layer thickness in the macular region (ETDRS circles) as well as peripapillary retinal nerve fibre layer (pRNFL) thickness. Differences between Aβ+ and Aβ− individuals and associations between BPND and retinal thickness were analyzed.

Results

No differences were found in retinal layer thickness in the macula or pRNFL between Aβ+ and Aβ− individuals. A positive associations between BPND and macular total retinal thickness was observed in the inner ring (p = 0.018), but this was not statistically significant after correction for multiple testing (p = 0.144). Brain/eye parameters had moderate to high intra‐twin correlations (p < 0.001) except visual rating score of Aβ, which did not correlate (r = 0.21, p = 0.068).

Conclusion

Variation in retinal thickness likely reflects genetic differences between individuals, but cannot discriminate between healthy and preclinical AD cases, making its use as biomarker in these early stages limited.
Activation of the prostaglandin E2 EP2 receptor attenuates renal fibrosis in unilateral ureteral obstructed mice and human kidney slices
Authors: Jensen Michael Schou , Mutsaers Henricus A. M. , Tingskov Stine Julie , Christensen Michael , Madsen Mia Gebauer , Olinga Peter , Kwon Tae‐Hwan , Nørregaard Rikke
Published: May 2019

Aim

Renal fibrosis plays a pivotal role in the development and progression of chronic kidney disease, which affects 10% of the adult population. Previously, it has been demonstrated that the cyclooxygenase‐2 (COX‐2)/prostaglandin (PG) system influences the progression of renal injury. Here, we evaluated the impact of butaprost, a selective EP2 receptor agonist, on renal fibrosis in several models of kidney injury, including human tissue slices.

Methods

We studied the anti‐fibrotic efficacy of butaprost using Madin‐Darby Canine Kidney (MDCK) cells, mice that underwent unilateral ureteral obstruction and human precision‐cut kidney slices. Fibrogenesis was evaluated on a gene and protein level by qPCR and Western blotting.

Results

Butaprost (50 μM) reduced TGF‐β‐induced fibronectin (FN) expression, Smad2 phosphorylation and epithelial‐mesenchymal transition in MDCK cells. In addition, treatment with 4 mg/kg/day butaprost attenuated the development of fibrosis in mice that underwent unilateral ureteral obstruction surgery, as illustrated by a reduction in the gene and protein expression of α‐smooth muscle actin, FN and collagen 1A1. More importantly, a similar anti‐fibrotic effect of butaprost was observed in human precision‐cut kidney slices exposed to TGF‐β. The mechanism of action of butaprost appeared to be a direct effect on TGF‐β/Smad signalling, which was independent of the cAMP/PKA pathway.

Conclusion

In conclusion, this study demonstrates that stimulation of the EP2 receptor effectively mitigates renal fibrogenesis in various fibrosis models. These findings warrant further research into the clinical application of butaprost, or other EP2 agonists, for the inhibition of renal fibrosis.
Carbon monoxide releasing molecule enhances coagulation and decreases fibrinolysis in canine plasma exposed to Crotalus viridis venom in vitro and in vivo
Authors: Johnson Tyler E. , Wells Raegan J. , Bell Amy , Nielsen Vance G. , Olver Christine S.
Published: May 2019

Carbon monoxide releasing molecule‐2 (CORM‐2), an emerging therapeutic in human medicine, enhances plasmatic coagulation and attenuates fibrinolysis in vitro in human, rabbit and horse plasma and ameliorates hypocoagulation and hyperfibrinolysis secondary to venom exposure in human plasma in vitro. Fibrinogenases in rattlesnake venom cause decreased clot strength, and in the presence of tissue plasminogen activator (tPA) in vitro, a markedly increased rate of clot lysis. CO interacts with a haem group on fibrinogen, changing its configuration so that the fibrin clot is strengthened and more resistant to fibrinolysis. We hypothesized that CORM‐2 enhances coagulation and attenuates fibrinolysis in canine plasma exposed to C viridis venom. We measured the effects of C viridis venom on clot strength, rates of coagulation and fibrinolysis in both pooled canine plasma and plasma from individual naturally envenomed dogs, with and without CORM‐2, using thromboelastography (TEG). We tested venom effects on coagulation using tissue factor (TF) activated TEG and on both coagulation and fibrinolysis using TF‐activated TEG with added tPA. We found that 17.9 µg/mL of venom causes a mean 26.4% decrease in clot strength, a 61.8% decrease in maximum rate of thrombus generation, 75% faster clot lysis, a 226% increase in maximum rate of lysis and a 92% decrease in total clot life span (CLS). CORM‐2 ameliorated these effects, increasing CLS in the presence of venom by 603%. Additionally, we showed that CORM‐2 has similar effects in vitro on plasma from naturally envenomed dogs, showing promise as an adjunct therapy for snake envenomation.
Gestational exposure to low‐dose zearalenone disrupting offspring spermatogenesis might be through epigenetic modifications
Authors: Men Yuhao , Zhao Yong , Zhang Pengfei , Zhang Hongfu , Gao Yishan , Liu Jing , Feng Yanni , Li Lan , Shen Wei , Sun Zhongyi , Min Lingjiang
Published: May 2019

Zearalenone (ZEA), a F‐2 mycotoxin produced by Fusarium, has been found to be an endocrine disruptor through oestrogen receptor signalling pathway to impair spermatogenesis. The disruption on reproductive systems by ZEA exposure might be transgenerational. In our previous report, we have found that low dose (lower than no‐observed effect level, NOEL) of ZEA impaired mouse spermatogenesis and decreased mouse semen quality. The purpose of the current investigation was to explore the impacts of low‐dose ZEA on spermatogenesis in the offspring after prenatal exposure and the underlying mechanisms. And it demonstrated that prenatal low‐dose ZEA exposure disrupted the meiosis process to inhibit the spermatogenesis in offspring and even to diminish the semen quality by the decrease in spermatozoa motility and concentration. The DNA methylation marker 5hmC was decreased, the histone methylation markers H3K9 and H3K27 were elevated, and oestrogen receptor alpha was reduced in the offspring testis after prenatal low‐dose ZEA exposure. The data suggest that the disruption in spermatogenesis by prenatal low‐dose ZEA exposure may be through the modifications on epigenetic pathways (DNA methylation and histone methylation) and the interactions with oestrogen receptor signalling pathway. Moreover, in the current study, the male offspring were indirectly exposed to low‐dose ZEA through placenta and the spermatogenesis in offspring was disrupted which suggested that the toxicity of ZEA on reproductive systems was very severe. Therefore, we strongly recommend that greater attention should be paid to this mycotoxin to minimize its adverse impact on human spermatogenesis.
Cefoperazone/sulbactam therapeutic drug monitoring in patients with liver cirrhosis: Potential factors affecting the pharmacokinetic/pharmacodynamic target attainment
Authors: Dong Yuzhu , Li Ying , Zhang Ying , Zhang Tao , Zhu Li , Dong Yaling , Wang Taotao
Published: May 2019

Objectives

Cefoperazone/sulbactam trough concentration (Cmin) varies widely in cirrhotic patients. The objective of this study was to describe the characteristics of Cmin and to identify factors associated with the pharmacokinetic/pharmacodynamic (PK/PD) target attainment of cefoperazone/sulbactam in cirrhotic patients.

Methods

Data were collected retrospectively from cirrhotic patients who received cefoperazone/sulbactam treatment. The Cmin was measured using a validated liquid chromatography‐tandem mass spectrometry. The PK/PD target of 100% fT > MIC was used for cefoperazone/sulbactam. Multivariate logistic regression and classification and regression tree (CART) analysis were performed to identify the factors affecting the PK/PD target attainment in these patients.

Results

Cefoperazone and sulbactam Cmin were measured simultaneously in 103 plasma samples from 70 cirrhotic patients. Cefoperazone and sulbactam Cmin were 89.27 ± 44.38 mg/L and 10.09 ± 13.01 mg/L, respectively. The PK/PD target of 100% fT > MIC was achieved in 47.1% (33/70) patients for cefoperazone and in 28.6% (20/70) patients for sulbactam. The CART analysis revealed that cefoperazone Cmin was likely to reach the PK/PD target in patients with serum bilirubin levels between 26.15 μmol/L and 99.15 μmol/L. Inversely, lower cefoperazone Cmin was observed in patients with bilirubin levels ≤26.15 μmol/L and serum albumin >38.45 g/L or in patients with bilirubin levels >99.15 μmol/L and creatinine clearance (CrCl) >139.13 mL/min. Additionally, patients had higher sulbactam Cmin when CrCl was below 62.85 mL/min.

Conclusions

This study shows that current cefoperazone/sulbactam dosage regimens may result in inadequate plasma concentrations in cirrhotic patients. We recommend monitoring the Cmin of cefoperazone/sulbactam to ensure efficacy of cefoperazone/sulbactam treatment.
Functional characterization of 27 CYP3A4 protein variants to metabolize regorafenib in vitro
Authors: Li Ying‐Hui , Lin Qian‐Meng , Pang Ni‐Hong , Zhang Xiao‐Dan , Huang Huan‐Le , Cai Jian-Ping , Hu Guo-Xin
Published: May 2019

Aim

Regorafenib is a tyrosine kinase inhibitor that is mainly metabolized by CYP3A4. The genetic polymorphism of CYP3A4 would contribute to differences in metabolism of regorafenib. Previously, we had discovered several novel CYP3A4 variants. However, the catalytic characteristics of these 27 CYP3A4 variants on oxidizing regorafenib have not being determined. The purpose of this study was to investigate the catalytic characteristics of 27 CYP3A4 protein variants on the oxidative metabolism of regorafenib in vitro.

Method

Wild‐type CYP3A4.1 or other variants was incubated with 0.5‐20 μmol/L regorafenib for 30 minutes. After sample processing, regorafenib‐N‐oxide, a primary metabolite, was detected by ultra‐performance liquid chromatography‐tandem mass spectrometry system.

Result

CYP3A4.20 had no detectable enzyme activity compared with wild‐type CYP3A4.1; five variants (CYP3A4.5, .16, .19, .24, .29) exhibited similar clearance value with CYP3A4.1; four variants (CYP3A4.14, .15, .28, .31) displayed increased enzymatic activities, while remaining variants showed markedly decreased intrinsic clearance values.

Conclusion

This study is the first to investigate the function of 27 CYP3A4 protein variants on the metabolism of regorafenib in vitro, and it may provide some valuable information for further research in clinic.
Does blended instruction enhance English language learning in developing countries? Evidence from Mexico
Authors: Xu Di , Glick Danny , Rodriguez Fernando , Cung Bianca , Li Qiujie , Warschauer Mark
Published: May 2019

Despite steady investment in English language education made by developing countries over the past few decades, results continue to be constrained by lack of high‐quality instructors and language learning resources. Thus, using technology in language instruction has increasingly been recognized as a potential approach for addressing these constraints. This study uses administrative data from a large public university in Mexico to examine the impact of a technology‐enhanced blended program on students' English course grades and course completion rates. Specifically, we focus on a campus‐wide policy change in all compulsory English language courses that replaces half of the traditional face‐to‐face class time with an interactive online learning environment developed by a leading technology‐mediated English language learning and assessment provider. Our results suggest that, compared to traditional face‐to‐face instruction, blended learning had a significant, positive impact on students' course grades and course completion rates. In addition, the enrollment‐teacher ratio increased after replacing half of the face‐to‐face instructional time with online learning, suggesting that blended learning environments hold promise for providing high‐quality and cost‐effective language instruction.
A general framework for propagule dispersal in mangroves
Authors: Van der Stocken Tom , Wee Alison K. S. , De Ryck Dennis J. R. , Vanschoenwinkel Bram , Friess Daniel A. , Dahdouh‐Guebas Farid , Simard Marc , Koedam Nico , Webb Edward L.
Published: May 2019

Dispersal allows species to shift their distributions in response to changing climate conditions. As a result, dispersal is considered a key process contributing to a species' long‐term persistence. For many passive dispersers, fluid dynamics of wind and water fuel these movements and different species have developed remarkable adaptations for utilizing this energy to reach and colonize suitable habitats. The seafaring propagules (fruits and seeds) of mangroves represent an excellent example of such passive dispersal. Mangroves are halophytic woody plants that grow in the intertidal zones along tropical and subtropical shorelines and produce hydrochorous propagules with high dispersal potential. This results in exceptionally large coastal ranges across vast expanses of ocean and allows species to shift geographically and track the conditions to which they are adapted. This is particularly relevant given the challenges presented by rapid sea‐level rise, higher frequency and intensity of storms, and changes in regional precipitation and temperature regimes. However, despite its importance, the underlying drivers of mangrove dispersal have typically been studied in isolation, and a conceptual synthesis of mangrove oceanic dispersal across spatial scales is lacking. Here, we review current knowledge on mangrove propagule dispersal across the various stages of the dispersal process. Using a general framework, we outline the mechanisms and ecological processes that are known to modulate the spatial patterns of mangrove dispersal. We show that important dispersal factors remain understudied and that adequate empirical data on the determinants of dispersal are missing for most mangrove species. This review particularly aims to provide a baseline for developing future research agendas and field campaigns, filling current knowledge gaps and increasing our understanding of the processes that shape global mangrove distributions.
Effects of ecotourism on forest loss in the Himalayan biodiversity hotspot based on counterfactual analyses
Authors: Brandt Jodi S. , Radeloff Volker , Allendorf Teri , Butsic Van , Roopsind Anand
Published: May 2019

Ecotourism is developing rapidly in biodiversity hotspots worldwide, but there is limited and mixed empirical evidence that ecotourism achieves positive biodiversity outcomes. We assessed whether ecotourism influenced forest loss rates and trajectories from 2000 to 2017 in Himalayan temperate forests. We compared forest loss in 15 ecotourism hubs with nonecotourism areas in 4 Himalayan countries. We used matching statistics to control for local‐level determinants of forest loss, for example, population density, market access, and topography. None of the ecotourism hubs was free of forest loss, and we found limited evidence that forest‐loss trajectories in ecotourism hubs were different from those in nonecotourism areas. In Nepal and Bhutan, differences in forest loss rates between ecotourism hubs and matched nonecotourism areas did not differ significantly, and the magnitude of the estimated effect was small. In India, where overall forest loss rates were the lowest of any country in our analysis, forest loss rates were higher in ecotourism hubs than in matched nonecotourism areas. In contrast, in China, where overall forest loss rates were highest, forest loss rates were lower in ecotourism hubs than where there was no ecotourism. Our results suggest that the success of ecotourism as a forest conservation strategy, as it is currently practiced in the Himalaya, is context dependent. In a region with high deforestation pressures, ecotourism may be a relatively environmentally friendly form of economic development relative to other development strategies. However, ecotourism may stimulate forest loss in regions where deforestation rates are low.
Compliance with and ecosystem function of biodiversity offsets in North American and European freshwaters
Authors: Theis Sebastian , Ruppert Jonathan L.W. , Roberts Karling N. , Minns Charles K. , Koops Marten , Poesch Mark S.
Published: May 2019

Land‐use change via human development is a major driver of biodiversity loss. To reduce these impacts, billions of dollars are spent on biodiversity offsets. However, studies evaluating offset project effectiveness that examine components such as the overall compliance and function of projects remain rare. We reviewed 577 offsetting projects in freshwater ecosystems that included the metrics project size, type of aquatic system (e.g., wetland and creek), offsetting measure (e.g., enhancement, restoration, and creation), and an assessment of the projects’ compliance and functional success. Project information was obtained from scientific and government databases and gray literature. Despite considerable investment in offsetting projects, crucial problems persisted. Although compliance and function were related to each other, a high level of compliance did not guarantee a high degree of function. However, large projects relative to area had better function than small projects. Function improved when projects targeted productivity or specific ecosystem features and when multiple complementary management targets were in place. Restorative measures were more likely to achieve targets than creating entirely new ecosystems. Altogether the relationships we found highlight specific ecological processes that may help improve offsetting outcomes.