bluuebunny/crossref_metadata_2025 huggingface dataset:
The key protein of endosomal mRNP transport Rrm4 binds translational landmark sites of cargo mRNAs
Authors: Olgeiser Lilli , Haag Carl , Boerner Susan , Ule Jernej , Busch Anke , Koepke Janine , König Julian , Feldbrügge Michael , Zarnack Kathi
Published: September 2018

RNA-binding proteins (RBPs) determine spatiotemporal gene expression by mediating active transport and local translation of cargo mRNAs. Here, we cast a transcriptome-wide view on the transported mRNAs and cognate RBP binding sites during endosomal messenger ribonucleoprotein (mRNP) transport in Ustilago maydis. Using individual-nucleotide resolution UV crosslinking and immunoprecipitation (iCLIP), we compare the key transport RBP Rrm4 and the newly identified endosomal mRNP component Grp1 that is crucial to coordinate hyphal growth. Both RBPs bind predominantly in the 3’ untranslated region of thousands of shared cargo mRNAs, often in close proximity. Intriguingly, Rrm4 precisely binds at stop codons, which constitute landmark sites of translation, suggesting an intimate connection of mRNA transport and translation. Towards uncovering the code of recognition, we identify UAUG as specific binding motif of Rrm4 that is bound by its third RRM domain. Altogether, we provide first insights into the positional organisation of co-localising RBPs on individual cargo mRNAs.
Tau Secretion and Propagation Is Regulated by p300/CBP via Autophagy-Lysosomal Pathway in Tauopathy
Authors: Chen Xu , Li Yaqiao , Wang Chao , Tang Yinyan , Mok Sue-Ann , Tsai Richard M. , Rojas Julio C. , Karydas Anna , Miller Bruce L. , Boxer Adam L. , Gestwicki Jason E. , Cuervo Ana Maria , Arkin Michelle , Gan Li
Published: September 2018

The trans-neuronal propagation of tau has been implicated in the progression of tau-mediated neurodegeneration. Tau secretion from neurons is the first step in tau transmission, but little is known about the cellular mechanism. Here, we report that p300/CBP, the lysine acetyltransferase that acetylates tau and regulates its homeostasis and toxicity, serves as a key regulator of tau secretion by inhibiting the autophagy-lysosomal pathway (ALP). Increased p300/CBP activity was associated with impaired function of this pathway in a tau transgenic mouse model. p300/CBP hyperactivation increased tau secretion by blocking autophagic flux. Conversely, inhibiting p300/CBP genetically or pharmacologically promoted autophagic flux, and reduced tau accumulation, tau secretion, and tau propagation in fibril-induced tau spreading models in vitro and in vivo. Our findings show that p300/CBP-induced impairment in the ALP underlies excessive unconventional secretion and pathogenic spread of tau.
Gut microbiome of an unindustrialized population have characteristic enrichment of SNPs in species and functions with the succession of seasons
Authors: Qin Jiyue , Tan Chongyang , Ning Kang
Published: September 2018

Most studies investigating human gut microbiome dynamics are conducted in modern populations. However, unindustrialized populations are arguably better subjects in answering human-gut microbiome coevolution questions due to their lower exposure to antibiotics and higher dependence on natural resources. Hadza hunter-gatherers in Tanzania have been found to exhibit high biodiversity and seasonal patterns in their gut microbiome composition at family level, where some taxa disappear in one season and reappear at later time. However, such seasonal changes have previously been profiled only according to species abundances, with genome-level variant dynamics unexplored. As a result it is still elusive how microbial communities change at the genome-level under environmental pressures caused by seasonal changes. Here, a strain-level SNP analysis of Hadza gut metagenome is performed for 40 Hadza fecal samples collected in three seasons. First, we benchmarked three SNP calling tools based on simulated sequencing reads, and selected VarScan2 that has highest accuracy and sensitivity after a filtering step. Second, we applied VarScan2 on Hadza gut microbiome, with results showing that: with more SNP presented in wet season in general, eight prevalent species have significant SNP enrichments in wet season of which only three species have relatively high abundances. This indicates that SNP characteristics are independent of species abundances, and provides us a unique lens towards microbial community dynamics. Finally, we identify 83 genes with the most characteristic SNP distributions between wet season and dry season. Many of these genes are from Ruminococcus obeum, and mainly from metabolic pathways like carbon metabolism, pyruvate metabolism and glycolysis, as shown by KEGG annotation. This implies that the seasonal changes might indirectly impact the mutational patterns for specific species and functions for gut microbiome of an unindustrialized population, indicating the role of these variants in their adaptation to the changing environment and diets.

Importance

By analyzing the changes of SNP enrichments in different seasons, we have found that SNP characteristics are independent of species abundances, and could provide us a unique lens towards microbial community dynamics at the genomic level. Many of the genes in microbiome also presented characteristic SNP distributions between wet season and dry season, indicating the role of variants in specific species in their adaptation to the changing environment for an unindustrialized population.
A Nodal/Eph signalling relay drives the transition from apical constriction to apico-basal shortening in ascidian endoderm invagination
Authors: Fiuza Ulla-Maj , Negishi Takefumi , Rouan Alice , Yasuo Hitoyoshi , Lemaire Patrick
Published: September 2018

Gastrulation is the first major morphogenetic event during animal embryogenesis. Ascidian gastrulation starts with the invagination of 10 endodermal precursor cells between the 64- and late 112-cell stages. This process occurs in the absence of endodermal cell division and in two steps, driven by myosin-dependent contractions of the acto-myosin network. First, endoderm precursors constrict their apex. Second, they shorten apico-basally, while retaining small apical surfaces, thereby causing invagination. The mechanisms controlling the endoderm mitotic delay, the step 1 to step 2 transition, and apico-basal shortening have remained elusive. Here, we demonstrate the conserved role during invagination of Nodal and Eph signalling in two distantly related ascidian species (Phallusia mammillataandCiona intestinalis). We show that the transition to step 2 is controlled by Nodal relayed by Eph signalling and that Eph signalling has a Nodal-independent role in mitotic delay. Interestingly, both Nodal and Eph signals are dispensable for endodermal germ layer fate specification.

Summary statement

Identification of a regulatory developmental signalling sub-network driving endoderm cell shape changes during ascidian endoderm invagination, not involved in cell fate specification.
Planned delivery route of preterm breech singletons, and neonatal and 2‐year outcomes: a population‐based cohort study
Authors: Lorthe E , Sentilhes L , Quere M , Lebeaux C , Winer N , Torchin H , Goffinet F , Delorme P , Kayem G ,   the EPIPAGE‐2 Obstetric Writing Group
Published: September 2018

Objective

To assess whether planned route of delivery is associated with perinatal and 2‐year outcomes for preterm breech singletons.

Design

Prospective nationwide population‐based EPIPAGE‐2 cohort study.

Setting

France, 2011.

Sample

Three hundred and ninety women with breech singletons born at 26–34 weeks of gestation after preterm labour or preterm prelabour rupture of membranes.

Methods

Propensity‐score analysis.

Main outcome measures

Survival at discharge, survival at discharge without severe morbidity, and survival at 2 years of corrected age without neurosensory impairment.

Results

Vaginal and caesarean deliveries were planned in 143 and 247 women, respectively. Neonates with planned vaginal delivery and planned caesarean delivery did not differ in survival (93.0 versus 95.7%, P = 0.14), survival at discharge without severe morbidity (90.4 versus 89.9%, P = 0.85), or survival at 2 years without neurosensory impairment (86.6 versus 91.6%, P = 0.11). After applying propensity scores and assigning inverse probability of treatment weighting, as compared with planned vaginal delivery, planned caesarean delivery was not associated with improved survival (odds ratio, OR 1.31; 95% confidence interval, 95% CI 0.67–2.59), survival without severe morbidity (OR 0.75, 95% CI 0.45–1.27), or survival at 2 years without neurosensory impairment (OR 1.04, 95% CI 0.60–1.80). Results were similar after matching on propensity score.

Conclusions

No association between planned caesarean delivery and improved outcomes for preterm breech singletons born at 26–34 weeks of gestation after preterm labour or preterm prelabour rupture of membranes was found. The route of delivery should be discussed with women, balancing neonatal outcomes with the higher risks of maternal morbidity associated with caesarean section performed at low gestational age.
Improving the effectiveness of lifestyle interventions for gestational diabetes prevention: a meta‐analysis and meta‐regression
Authors: Guo X‐Y , Shu J , Fu X‐H , Chen X‐P , Zhang L , Ji M‐X , Liu X‐M , Yu T‐T , Sheng J‐Z , Huang H‐F
Published: September 2018

Background

Diet and exercise during pregnancy have been used to prevent gestational diabetes mellitus (GDM) with some success.

Objective

To examine the effectiveness of lifestyle intervention on GDM prevention and to identify key effectiveness moderators to improve the prevention strategy.

Search strategy

Pubmed, Scopus, Cochrane, and cross‐references were searched.

Selection criteria

Randomised controlled trials (RCTs) evaluating lifestyle interventions during pregnancy for GDM prevention.

Data collection and analysis

Two independent reviewers extracted data. A random‐effects model was used to analyse the relative risk (RR) and 95% confidence interval (95% CI). Meta‐regressions and subgroup analyses were used to investigate important moderators of effectiveness.

Main results

Forty‐seven RCTs involving 15 745 participants showed that diet and exercise during pregnancy were preventive of GDM (RR 0.77, 95% CI 0.69–0.87). Four key aspects were identified to improve the preventive effect: targeting the high‐risk population; an early initiation of the intervention; the correct intensity and frequency of exercise; and gestational weight gain management. Although 24 RCTs targeted women who were overweight or obese, body mass index (BMI) failed to predict the effectiveness of an intervention. Instead, interventions are most effective in high‐incidence populations rather than simply in women who are overweight or obese. Furthermore, exercise of moderate intensity for 50–60 minutes twice a week could lead to an approximately 24% reduction in GDM.

Conclusion

The best strategy to prevent GDM is to target the high‐risk population predicted by risk evaluation models and to control the gestational weight gain of women through intensified diet and exercise modifications early in their pregnancy.

Tweetable abstract

Four key effectiveness moderators of lifestyle interventions for GDM prevention.
Microsatellite High‐Resolution Melting (SSR‐HRM) to Track Olive Genotypes: From Field to Olive Oil
Authors: Gomes Sónia , Breia Richard , Carvalho Teresa , Carnide Valdemar , Martins‐Lopes Paula
Published: September 2018

The need to support food labelling has driven to the development of PCR‐based techniques suitable for food analysis. DNA‐based markers have been successfully employed for varietal tracing in Protected Designation of Origin (PDO) olive oils. In this study, we report a fast, sensitive, and easy‐to‐use strategy for PDO olive varietal identification. To achieve this aim four different DNA extraction methods were tested and compared, based on initial volume, extraction time, the gDNA concentration, and quality ratios. The optimized DNA extraction protocol from extra virgin olive oils, based on CTAB–hexane–chloroform extraction, proved to be the most effective. High‐resolution melting (HRM) DNA assay was developed based on nuclear microsatellites (gSSR) and plastid DNA (cpDNA) aiming an accurate identification of the olive varieties present in the olive oil samples. After PCR reproducibility evaluation, six molecular markers: three SSRs and three cpDNA loci were chosen based on their discrimination power. The SSR‐HRM strategy assays were designed to target UDO99‐011, UDO99‐039, UDO99‐024, and ssrOeUA‐DCA16 loci. All SSR‐PCR products generated from these primers were analyzed by capillary electrophoresis (CE) for HRM data validation. The SSR coupled with HRM melting curve analysis generated 14 HRM profiles sufficient to genotype all varieties, highlighting their potential use for varietal discrimination. The locus ssrOeUA‐DCA16 generated a specific melting curve that allow a high‐throughput discrimination of the Picual and Cobrançosa varieties in olive oil samples. Further, the UDO99‐024 was also tested by SSR‐HRM assay in commercial olive oil samples with promising results. Considering time, cost, and performance SSR‐HRM proved to be a reliable method suitable for varietal tracing of olive oils.

Practical Application

Olive oil authenticity is a form of protecting producers and consumers against fraudulent practices. Herein, we present a DNA barcode suitable for the identification of olive varieties, allowing an accurate identification of the olive varieties in olive oil samples using SSR‐HRM assay. Its applicability in commercial olive oil samples is viable. This methodology can be used as a tool for Extra Virgin Olive Oil (EVOO) adulterations detection.
Analysis of the current preschool vision screening in Denmark
Authors: Sandfeld Lisbeth , Weihrauch Hanne , Tubæk Gitte
Published: September 2018

Purpose

To analyse the current vision screening programme for children attending school with respect to identifying children with significant refractive errors.

Methods

A total of 950 children from the municipality of Roskilde, Denmark, were invited to participate in a cross‐sectional study of vision screening. 447 children aged 4.5–7 years participated in the study. The children completed a vision screening and a full eye examination. The vision screening consisted of visual acuity at distance (VA), visual acuity at distance with +2.0 glasses (VA+2), visual acuity at near (VAnear) and Lang II stereotest. A LogMAR‐based picture chart was used for the vision testing. Significant refractive errors were defined as hyperopia ≥+3.5 D, myopia >1.0 D, astigmatism ≥1.25 D and anisometropia >1.0 D.

Results

Using receiver operating characteristic (ROC) curves, we could compare the efficiency of VA, VA+2, VAnear, VA in combination with VA+2 and VA in combination with VAnear. Area under the curve (AUC) for VA, VA combined with VA+2 and VA combined with VAnear was 0.841, 0.857 and 0.857, respectively, that is all classified as ‘very good’ screening tools, whereas VA+2 and VAnear as single screening tools were classified as ‘good’ with AUC of 0.704 and 0.775, respectively. Using the optimal cut‐off limit from the ROC curves, VA above 0.05 LogMAR as cut‐off limit showed a sensitivity of 85.2% with a specificity of 74.9%. A slightly higher sensitivity could be found when combining screening tests, but with declining specificities.

Conclusion

Visual acuity at distance with the use of LogMAR‐based charts is the optimal screening tool of choice; only minor improvements can be obtained combining with other tests.
Food Import Dependency in Cuba: Still the ‘Achilles’ Heel of the Revolution'?
Authors: BOTELLA‐RODRÍGUEZ ELISA
Published: September 2018

The ‘Special Period in Peacetime’ plunged Cuba into an austerity programme of great severity. The crisis forced agriculture to shift dramatically from a model based on trade dependency (sugar exports providing most of the foreign currency) to one prioritising food import substitution. This alternative brought about major transformations in the country's agriculture. It revolutionised food production and decentralised land ownership. This article asks whether or not these changes reduced food dependency in Cuba. It provides an updated picture of Cuba's food import dependency, with a particular emphasis on the increased role of small farmers in food production during the 2000s.
Design, synthesis, and biological activity evaluation of campthothecin‐HAA‐Norcantharidin conjugates as antitumor agents in vitro
Authors: Wang Xian H. , Huang Mei , Zhao Chang K. , Li Chan , Xu Lang
Published: September 2018

Three components of Camptothecin, hydroxyacetic acid, and functionalized norcantharidins were constructed together to form a novel series of camptothecin derivatives in a good yield. The synthesized campthothecin‐HAA‐norcantharidin conjugate pro‐drugs could suppress cancer cell growth in vitro. These conjugated pro‐drug molecules possess therapeutic potential as novel bi‐functional conjugates platforms for cancer treatment.
Prioritizing recovery funding to maximize conservation of endangered species
Authors: Martin Tara G. , Kehoe Laura , Mantyka‐Pringle Chrystal , Chades Iadine , Wilson Scott , Bloom Robin G. , Davis Stephen K. , Fisher Ryan , Keith Jeff , Mehl Katherine , Diaz Beatriz Prieto , Wayland Mark E. , Wellicome Troy I. , Zimmer Karl P. , Smith Paul A.
Published: September 2018

The absence of a rigorous mechanism for prioritizing investment in endangered species management is a major implementation hurdle affecting recovery. Here, we present a method for prioritizing strategies for endangered species management based on the likelihood of achieving species’ recovery goals per dollar invested. We demonstrate our approach for 15 species listed under Canada's Species at Risk Act that co‐occur in Southwestern Saskatchewan. Without management, only two species have >50% probability of meeting recovery objectives; whereas, with management, 13 species exceed the >50% threshold with the implementation of just five complementary strategies at a cost of $126m over 20 years. The likelihood of meeting recovery objectives rarely exceeded 70% and two species failed to reach the >50% threshold. Our findings underscore the need to consider the cost, benefit, and feasibility of management strategies when developing recovery plans in order to prioritize implementation in a timely and cost‐effective manner.
Amplifying plant disease risk through assisted migration
Authors: Simler Allison B. , Williamson Matthew A. , Schwartz Mark W. , Rizzo David M.
Published: September 2018

Translocation of species, populations, or genotypes beyond their historic ranges (i.e., assisted migration [AM]) is an oft‐debated climate adaptation strategy. Well‐intentioned AM actions could alter disease dynamics for target species and recipient sites, resulting in unanticipated detrimental economic and ecological impacts. Although disease risks are occasionally mentioned in AM debates, current regulations or best practices that reduce or mitigate these complex risks are generally lacking in North America. We use the “Disease Triangle”, a foundational framework in pathology, to illustrate pathways through which AM may impact disease emergence, to identify knowledge gaps, and to suggest best practices to reduce disease risks. We highlight empirical examples in which altering pathogen distributions, host communities, and environment have historically resulted in costly and ecologically damaging diseases in plants. Although guidelines to reduce disease risks in AM are generally lacking, policies governing endangered species, invasive species, and disease management can provide starting points for a more comprehensive policy. We use examples from the United States to identify key strengths and weaknesses that can inform regulations to reduce disease risks associated with AM. We argue that consideration of disease motivates policy development that incorporates improved risk assessments, agency coordination, and accountability mechanisms.
Elevated end‐diastolic wall stress after acute myocardial infarction predicts adverse cardiovascular outcomes and longer hospital length of stay
Authors: Mosleh Wassim , Elango Kalaimani , Shah Tanvi , Chaudhari Milind , Gandhi Sumeet , Kattel Sharma , Karki Roshan , Khalil Charl , Frodey Kevin , Dahal Suraj , Okeeffe Cale , Aljebaje Zaid , Nagahama Makoto , Punnanithinont Natdanai , Sharma Umesh C.
Published: September 2018

Background

Acute myocardial infarction (MI) leads to ventricular remodeling in response to oxygen demand. Such changes include left ventricular (LV) dilatation and increased myocardial wall stress. Prior studies showed that wall stress is a vital parameter of cardiac remodeling. However, outcome data are lacking. We aim to investigate wall stress post‐MI in relation to biomarkers of cardiac remodeling and cardiovascular outcomes.

Methods

Patients presenting with ST‐elevation MI (STEMI) requiring primary percutaneous intervention (PCI) were enrolled prospectively. LVEF and volume‐based end‐diastolic (EDWS) and end‐systolic (ESWS) wall stress were measured from predischarge echocardiograms. Serum samples were collected for measurement of serum biomarkers. We identified 81 patients meeting inclusion criteria (64% men, 36% women) with a mean age of 61. The primary outcome was major adverse cardiovascular events (MACE) defined as 1‐year composite endpoint of cardiac mortality, recurrent MI, revascularization, or stroke. Length of hospitalization (LOH) was recorded.

Results

Major adverse cardiovascular events‐positive patients (n = 12) had significantly higher EDWS levels (15.87 vs 12.33, P = 0.045), and galectin‐3 levels (19.07 vs 11.75, P = 0.015), and lower LVEF (40.0% vs 48.4%, P = 0.023) compared to MACE‐negative patients. Patients with LOH > 72 hours (n = 33) had significantly higher EDWS, galectin‐3, and peak troponin, and lower LVEF compared to patients with LOH < 72 hours. EDWS positively correlated with LOH and galectin‐3. EDWS was an independent predictor of MACE by binomial regression analysis.

Conclusion

End‐diastolic walls tress is a potential prognostic tool for risk stratifying STEMI patients, providing an assessment of the functional consequences of myocardial remodeling. It is predictive of MACE independent of LVEF, associated with longer hospitalizations, and correlates with galectin‐3, a biomarker of cardiac remodeling.
Agri‐environmental schemes affect the trophic niche size and diet of common carabid species in agricultural landscapes
Authors: Mader Viktoria , Diehl Eva , Wolters Volkmar , Birkhofer Klaus
Published: September 2018

1. Carabids are abundant in agroecosystems and provide biocontrol services by feeding on weed seeds and pests. We compare the effects of two fundamentally different agri‐environmental schemes (AES) on the numeric and trophic responses of four common carabid species:Anchomenus dorsalis,Poecilus cupreus,Pseudoophonus rufipesandPterostichus melanarius.

2. In six cereal fields under organic farming and six sown flowering fields, 10 290 individuals of the four species were sampled to quantify their numeric response. The activity density of all species was higher in organically managed cereal fields compared to flowering fields.

3. We analysed naturally occurring stable isotope ratios of carbon and nitrogen in 138 carabid individuals to quantify isotopic niches and the diet contribution of soil‐ versus plant‐based resources. Resources from the soil (‘brown’) energy channel were more important than resources from the plant (‘green’) energy channel in the diet of all species, particularly inP. melanarius.

4. Isotopic niches were larger forP. rufipesandP. melanariusin flowering fields than in organically managed cereal fields. Moreover, differences between AES types were observed in the diet contribution derived from both energy channels:A. dorsalisandP. cupreusincorporated higher proportions of plant‐based resources in organically managed cereal fields compared to flowering fields.

5. Similar numeric, but different trophic responses suggest that AES type may alter arthropod food webs beyond simple changes in carabid densities. Such ‘hidden’ modifications in the resource utilisation of generalist predators deserve more attention to adequately evaluate the ecological consequences of AES.
The neuronal migration hypothesis of dyslexia: A critical evaluation 30 years on
Authors: Guidi Luiz G. , Velayos‐Baeza Antonio , Martinez‐Garay Isabel , Monaco Anthony P. , Paracchini Silvia , Bishop Dorothy V. M. , Molnár Zoltán
Published: September 2018

The capacity for language is one of the key features underlying the complexity of human cognition and its evolution. However, little is known about the neurobiological mechanisms that mediate normal or impaired linguistic ability. For developmental dyslexia, early postmortem studies conducted in the 1980s linked the disorder to subtle defects in the migration of neurons in the developing neocortex. These early studies were reinforced by human genetic analyses that identified dyslexia susceptibility genes and subsequent evidence of their involvement in neuronal migration. In this review, we examine recent experimental evidence that does not support the link between dyslexia and neuronal migration. We critically evaluate gene function studies conducted in rodent models and draw attention to the lack of robust evidence from histopathological and imaging studies in humans. Our review suggests that the neuronal migration hypothesis of dyslexia should be reconsidered, and the neurobiological basis of dyslexia should be approached with a fresh start.
Comparison of coded‐wire tagging with parentage‐based tagging and genetic stock identification in a large‐scale coho salmon fisheries application in British Columbia, Canada
Authors: Beacham Terry D. , Wallace Colin , Jonsen Kim , McIntosh Brenda , Candy John R. , Willis David , Lynch Cheryl , Moore Jean‐Sébastien , Bernatchez Louis , Withler Ruth E.
Published: September 2018

Wild Pacific salmon, including Coho salmon Onchorynchus kisutch, have been supplemented with hatchery propagation for over 50 years in support of increased ocean harvest and conservation of threatened populations. In Canada, the Wild Salmon Policy for Pacific salmon was established with the goal of maintaining and restoring healthy and diverse Pacific salmon populations, making conservation of wild salmon and their habitats the highest priority for resource management decision‐making. A new approach to the assessment and management of wild coho salmon, and the associated hatchery production and fishery management is needed. Implementation of parentage‐based tagging (PBT) may overcome problems associated with coded‐wire tag‐based (CWT) assessment and management of coho salmon fisheries, providing at a minimum information equivalent to that derived from the CWT program. PBT and genetic stock identification (GSI) were used to identify coho salmon sampled in fisheries (8,006 individuals) and escapements (1,692 individuals) in British Columbia to specific conservation units (CU), populations, and broodyears. Individuals were genotyped at 304 single nucleotide polymorphisms (SNPs) via direct sequencing of amplicons. Very high accuracy of assignment to population (100%) via PBT for 543 jack (age 2) assigned to correct age and collection location and 265 coded‐wire tag (CWT, age 3) coho salmon assigned to correct age and release location was observed, with a 40,774—individual, 267—population baseline available for assignment. Coho salmon from un‐CWTed enhanced populations contributed 65% of the catch in southern recreational fisheries in 2017. Application of a PBT‐GSI system of identification to individuals in 2017 fisheries and escapements provided high‐resolution estimates of stock composition, catch, and exploitation rate by CU or population, providing an alternate and more effective method in the assessment and management of Canadian‐origin coho salmon relative to CWTs, and an opportunity for a genetic‐based system to replace the current CWT system for coho salmon assessment.
Agomelatine pretreatment prevents development of hyperglycemia and hypoinsulinemia in streptozotocin‐induced diabetes in mice
Authors: Ozcan Mete , Canpolat Sinan , Bulmus Ozgur , Ulker Nazife , Tektemur Ahmet , Tekin Suat , Ozcan Sibel , Serhatlioglu Ihsan , Kacar Emine , Ayar Ahmet , Kelestimur Haluk
Published: September 2018

The main objective of this study was to investigate potential effectiveness of agomelatine pretreatment in the prevention of diabetes itself and encephalopathy, with a focus on brain tissue oxidative stress and inflammatory processes in streptozotocin (STZ)‐induced diabetic mice. Interleukine‐1β (IL‐1β) and TACR1 (NK1), which is a tachykinine receptor, were used for the investigation of inflammation in the brain regions including raphe nucleus, periaqueductal gyrus (PAG), amygdala, and nucleus accumbens. The effects of agomelatine on total antioxidant capacity were also evaluated. In the in vitro part of the study, the effects of agomelatine on cell viability were investigated in dorsal root ganglion (DRG) neurons. Fasting blood glucose levels were measured 72 h after STZ injection to determine the diabetic condition. Agomelatine pretreatment prevented both hyperglycemia and hypoinsulinemia in STZ‐treated mice. When STZ was injected to induce diabetes in mice, neither hyperglycemia nor hypoinsulinemia was developed in agomelatine pretreated mice and 6 weeks after development of diabetes, agomelatine treatment significantly decreased levels of IL‐1β mRNA in raphe nucleus and nucleus accumbens. TACR1 mRNA levels were lower in raphe nucleus, PAG, and amygdala of agomelatine‐treated diabetic mice. The increase in total antioxidant capacity after agomelatine administration may responsible for its beneficial effect in the prevention of diabetes. We showed that agomelatine reversed high glucose–induced cell viability decreases in DRG neurons. Both the antihyperglycemic and antioxidant effects of agomelatine might have contributed to the DRG neuron viability improvement. In conclusion, agomelatine seems to both prevent development of diabetes and reverse the encephalopathic changes caused by diabetes.
Characterization of sulfuretin as a depigmenting agent
Authors: Zhou Zhike , Hou Jun , Xiong Juanjuan , Li Min
Published: September 2018

Sulfuretin is a major flavonoid found in Rhus verniciflua and carries anti‐oxidative and anti‐inflammatory properties, but its potential use in the control of skin pigmentation is unknown. The purpose of the present study was to elucidate sulfuretin as a new active compound inhibiting melanogenesis and the underlying mechanism. The effects of sulfuretin on melanin production, tyrosinase activity, cAMP level, and MITF expression were examined in murine melanoma B16 cells challenged with forskolin or α‐MSH. The inhibitory effect of sulfuretin on melanogenesis was further validated on neonatal human melanocytes. When tested in melanoma B16 cells treated with forskolin or α‐MSH, sulfuretin inhibited the cellular melanogenesis. Sulfuretin also showed direct inhibitory effect on tyrosinase activity in vitro. In human primary melanocytes, the inhibitory effect of sulfuretin on melanin synthesis was also confirmed. Our current results support the depigmenting effect of sulfuretin and suggest a clinical strategy for using sulfuretin in the topical treatment of hyperpigmentation disorders.
EngineeringC*‐integral and COD estimates for nonidealized circumferential through‐wall cracked pipes at elevated temperature
Authors: Won Min‐Gu , Kim Kyunghoon , Huh Nam‐Su , Kim Woo‐Gon , Lee Hyeong‐Yeon
Published: September 2018

In this study, creep fracture mechanics parameters,C*‐integral and crack opening displacement (COD) rate, are estimated for a nonidealized circumferential through‐wall crack (TWC) in pipes. The GE/EPRI and enhanced reference stress (ERS) methods are employed. As for creep condition, the Norton and RCC‐MRx creep models are considered for secondary and primary‐secondary creep strain, respectively. The bending moment, axial tension, and internal pressure are applied to a pipe with a nonidealized circumferential TWC, as individual loads. Three‐dimensional elastic‐creep finite element (FE) analyses are performed, and the predictions from the GE/EPRI and ERS methods are compared with FE results. For the Norton creep model, both methods show good agreement with the FE results. For the RCC‐MRx creep model, only the ERS method can be used, and it provides accurate predictions comparing with FE results. Based on the comparison results, the use of the present engineeringC*‐integral and COD estimation methods for nonidealized circumferential TWC is validated.
Performance and urban space: An ambivalent affair
Authors: Sachs Olsen Cecilie
Published: September 2018

Artistic performance is increasingly seen as a crucial creative means of empowerment in the midst of urban transformation. However, the varied abilities of performance to challenge, or not, existing power structures are often lost in analyses that either celebrate the utopian potential of performance for challenging hegemonic oppression, or critique performance for being inevitably complicit with hegemonic sociopolitical ideologies due to its material conditions. By introducing a neo‐Marxist critical framework that focuses on the interplay between socio‐material conditions and performance, this paper promotes a nuanced analytic strategy for examining the relation between performance and urban space.
Flow cytometric quantitation of EpCAM‐positive extracellular vesicles by immunomagnetic separation and phospholipid staining method
Authors: Takao Masashi , Nagai Yutaka , Ito Masami , Ohba Tetsuhiko
Published: September 2018

Extracellular vesicles (EV) have attracted attention as circulating biomarkers for many diseases, particularly cancer. Conventional immunofluorescence staining has been used for the detection of target antigens on EV by flow cytometry. However, the staining intensity depends on the amount of antigen expressed on the vesicles and is often only around the noise level. Instead of immunofluorescence, we combined immunomagnetic separation using nanosize MACS® MicroBeads with phospholipid staining of EV (IMS‐PS method). EpCAM‐positive EV were prepared from the culture supernatants of OVCAR3 (EpCAM‐high), A431 (EpCAM‐low) or Colon‐26 (non‐human control) cells as cancer models and were examined by the IMS‐PS method using EpCAM mAb‐coated MicroBeads. By employing Polaric‐500c6F as the dye for staining EV phospholipids and using appropriate flow cytometry settings, autofluorescence was excluded, whereas pretreatment of the MicroBeads with conventional blocking agents reduced nonspecific binding to non‐target vesicles. These modifications resulted in a linear relation between the number of EV detected and the sample volume, regardless of the level of EpCAM expression on the vesicles. A431 EV spiked into healthy volunteer plasma were enumerated with good accuracy. The IMS‐PS method may be useful for clinical evaluation of EV with low levels of antigen expression that are difficult to detect by conventional immunofluorescence.
Going deeper: three‐dimensional study of γδ T cells in mouse reproductive tract using tissue clearing methods
Authors: Mikolajewicz Katarzyna , Chodaczek Grzegorz
Published: September 2018

Several tissue clearing methods have been developed for three‐dimensional imaging of thick specimens. Here, we applied CUBIC and ScaleS approaches to whole‐mounted vaginal wall to reveal spatial distribution of γδ T lymphocytes, the key cells engaged in the epithelial homeostasis control and immune surveillance. Both methods rendered the tissue transparent and enabled detection of the green fluorescent protein (GFP)‐expressing γδ T cells in vaginal samples of Tcrd‐H2BeGFP transgenic mice. Upon additional immunolabeling, however, only CUBIC preserved the GFP signal and allowed for cell localization assessment during the estrous cycle. Using a combination of single‐ and two‐photon microscopy, we found that during the diestrus phase the number of γδ T cells in the vaginal wall increased compared to estrus, while the proportion of cells residing in epithelium and stroma remained constant, irrespective of the cycle phase, and was close to 3:1, respectively. Moreover, the distance from epithelial γδ T cells to laminin‐positive basal membrane and collagen‐rich stroma also increased in diestrus in spite of thinning of epithelium upon shedding cornified cells. Our data indicate that γδ T cells sense sex hormone fluxes which influence their number and position them closer to the vaginal lumen in the diestrus phase.
Replacement of neuraminidase inhibitor‐susceptible influenza A(H1N1) with resistant phenotype in 2008 and circulation of susceptible influenza A and B viruses during 2009‐2013, South Africa
Authors: Treurnicht Florette K. , Buys Amelia , Tempia Stefano , Seleka Mpho , Cohen Adam L. , Walaza Sibongile , Glass Allison J. , Rossouw Inéz , McAnerney Johanna , Blumberg Lucille , Cohen Cheryl , Venter Marietjie
Published: September 2018

Background

Data on the susceptibility of influenza viruses from South Africa to neuraminidase inhibitors (NAIs) are scarce, and no extensive analysis was done.

Objectives

We aimed to determine oseltamivir and zanamivir susceptibility of influenza A and B virus neuraminidases (NAs), 2007‐2013, South Africa.

Patients/Methods

We enrolled participants through national influenza‐like illness surveillance, 2007‐2013. Influenza diagnosis was by virus isolation and quantitative polymerase chain reaction (qPCR). Drug susceptibility was determined by chemiluminescence‐based NA‐STAR/NA‐XTD assay. Sanger sequencing was used to determine molecular markers of NAI resistance.

Results

Forty percent (6341/15 985) of participants were positive for influenza viruses using virus isolation (2007‐2009) and qPCR (2009‐2013) methods. A total of 1236/6341 (19.5%) virus isolates were generated of which 307/1236 (25%) were tested for drug susceptibility. During 2007‐2008, the median 50% inhibitory concentration (IC50) of oseltamivir for seasonal influenza A(H1N1) increased from of 0.08 nmol/L (range 0.01‐3.60) in 2007 to 73 nmol/L (range 1.56‐305 nmol/L) in 2008. Influenza A isolates from 2009 to 2013 were susceptible to oseltamivir [A(H3N2) median IC50 = 0.05 nmol/L (range 0.01‐0.08); A(H1N1)pdm09 = 0.11 nmol/L (range 0.01‐0.78)] and zanamivir [A(H3N2) median IC50 = 0.56 nmol/L (range 0.47‐0.66); A(H1N1)pdm09 = 0.35 nmol/L (range 0.27‐0.533)]. Influenza B viruses were susceptible to both NAIs. NAI resistance‐associated substitutions H275Y, E119V, and R150K (N1 numbering) were not detected in influenza A viruses that circulated in 2009‐2013.

Conclusions

We confirm replacement of NAI susceptible by resistant phenotype influenza A(H1N1) in 2008. Influenza A and B viruses (2009‐2013) remained susceptible to NAIs; therefore, these drugs are useful for treating influenza‐infected patients.
Microstructural evolution and mechanical properties of (Mg,Co,Ni,Cu,Zn)O high‐entropy ceramics
Authors: Hong Weichen , Chen Fei , Shen Qiang , Han Young‐Hwan , Fahrenholtz William G. , Zhang Lianmeng
Published: September 2018

The reaction sequence and mechanical properties were studied for (Mg,Co,Ni,Cu,Zn)O high‐entropy ceramics that were synthesized using field‐assisted sintering technology. The evolution from binary oxide starting powders to a single‐phase rock salt structure exhibited a distinct incorporation sequence. For the rock salt oxides, MgO and CoO had the lowest vacancy formation energies and were the first to be incorporated into the high‐entropy ceramic followed by NiO, which had a higher vacancy formation energy. Both CuO and ZnO had different crystal structures, and were incorporated into the single phase structure after the rock salt oxides due to the additional energy barrier associated with the transformations from their original structures to the rock salt structure. Distinctive morphological features including Cu‐rich regions and lattice distortion were observed in the high entropy ceramic. In addition, a trade‐off between densification and grain growth resulted in a maximum in strength (323 MPa) and elastic modulus (108 GPa) after densification at 900°C. This study has revealed new information that can be used to design other high‐entropy ceramics including selection criteria for constituent compounds based on crystal structure and defect formation energy as well as the effects of grain size and porosity on control strength and elastic modulus.
Modulation of apoptosis‐related microRNAs following myocardial infarction in fat‐1 transgenic mice vs wild‐type mice
Authors: Ma Huan , Chen Peipei , Sang Chuanlan , Huang Daozheng , Geng Qingshan , Wang Lei
Published: September 2018

Background

microRNAs (miRNAs) post‐transcriptionally regulate cardiac repair following myocardial infarction (MI). Omega‐3 polyunsaturated fatty acid (ω‐3 PUFAs) may support cardiac healing after MI, but the mechanism is unclear.

Methods

The fat‐1 transgenic mouse expresses a ω‐3 fatty acid desaturase which converts ω‐6 PUFAs to ω‐3 PUFAs in vivo. MI was induced in fat‐1 transgenic (n = 30) and wild‐type (WT) mice (n = 30) using permanent ligation. Other transgenic and WT mice underwent sham procedure (n = 30 and n = 30, respectively). One week after occlusion, cardiac function was measured by echocardiography and the infarct size was assessed using histology and miRNA microarray profiling. Expression of selected miRNA was confirmed using quantitative real‐time PCR.

Results

One week following MI, the fat‐1 transgenic myocardium had better cardiac function, a smaller fibrotic area, and fewer apoptotic cardiomyocytes than WT myocardium. Post‐MI profiling showed 33 miRNAs that were significantly up‐regulated, and 35 were down‐regulated, in fat‐1 group compared to the WT group (n = 3 and n = 2 mice, respectively). Among selected apoptosis‐associated miRNAs, 9 miRNAs were up‐regulated (miR‐101a‐3p, miR‐128‐3p,miR‐133a‐5p,miR‐149‐5p,miR‐192‐5p,miR‐1a‐3p,miR‐208a‐3p,miR‐29c‐5p,miR‐30c‐2‐3p), and 3 were down‐regulated (miR‐210‐3p,miR‐21a‐3p,miR‐214‐3p) in fat‐1 transgenic mice compared with WT mice. Kyoto encyclopaedia of genes and genomes (KEGG) pathway analysis indicated likely roles for these miRNAs in MI. Furthermore, Bcl‐2 expression was increased, and caspase‐3 decreased, in infarcted fat‐1 transgenic mouse hearts compared to WT hearts.

Conclusions

ω‐3 PUFAs may have a protective effect on cardiomyocytes following MI through their modulation of apoptosis‐related miRNAs and target genes.
PCAF fine‐tunes hepatic metabolic syndrome, inflammatory disease, and cancer
Authors: Wang Tongxin , Yao Weilei , Shao Yafei , Zheng Ruilong , Huang Feiruo
Published: September 2018

The P300/CBP‐associating factor (PCAF), a histone acetyltransferase, is involved in metabolic and pathogenic diseases, particularly of the liver. The effects of PCAF on fine‐tuning liver diseases are extremely complex and vary according to different pathological conditions. This enzyme has dichotomous functions, depending on differently modified sites, which regulate the activities of various enzymes, metabolic functions, and gene expression. Here, we summarize the most recent findings on the functions and targets of PCAF in various metabolic and immunological processes in the liver and review these new discoveries and models of PCAF biology in three areas: hepatic metabolic syndrome, inflammatory disease, and cancer. Finally, we discuss the potential implications of these findings for therapeutic interventions in liver diseases.
Determination of mold contamination and aflatoxin levels of the meat products/ingredients collected from Turkey market
Authors: Cavus Soner , Tornuk Fatih , Sarioglu Kemal , Yetim Hasan
Published: September 2018

This study aimed to highlight general safety conditions of meat products (n = 24, fresh meat, Turkish sucuk, sausage, and pastirma) and ingredients (n = 20, red paprika, black pepper, coriander, spice mix and fenugreek powder) sold in Turkey regarding mold and aflatoxin contamination. Total 55 mold species belonging to Aspergillus and Penicillium sp. were isolated while A. flavus and A. niger were the most prevalent ones. Aflatoxin B1 (AFB1) was detected in 50% (n = 12) and 65% (n = 13) of the meat products and ingredients while 25% and 43% of sucuk and pastirma samples had mold counts exceeding the limits of Turkish Food Codex, respectively. However, one red paprika sample had AFB1 and total aflatoxin levels over the limitations of Turkish Food Codex and European Commission. It was concluded that Turkish meat products/ingredients were generally safe for consumption.

Practical applications

There is an increasing attention on mycotoxin contamination of foodstuffs in terms of consumer health as well as in international trade. Although especially spices are under the risk of mold growth and formation of mycotoxins, animal products such as beef and milk are also frequently exposed to mycotoxin contamination. In the meanwhile, national and international regulatory agents have established limits for the presence of aflatoxins in foodstuffs. Therefore, this study provides beneficial information about general safety conditions of several meat products and ingredients sold in Turkey market.
Admission temperature and hospital outcomes in extremely preterm infants
Authors: Tay Victoria YJ , Bolisetty Srinivas , Bajuk Barbara , Lui Kei , Smyth John ,   on behalf of the New South Wales and the Australian Capital Territory Neonatal Intensive Care Units' Data Collection
Published: September 2018

Aim

To evaluate trends in admission temperature and its effect on mortality and short‐term morbidities in extremely preterm infants.

Methods

A regional cohort study of infants born at 23–28 weeks’ gestation and admitted to the 10 neonatal intensive care units in New South Wales and the Australian Capital Territory between 1994 and 2012. Hypothermia was defined as skin temperature <36°C on admission to the neonatal intensive care unit. The primary outcome was hospital mortality.

Results

In total, 6267 infants were included. Mean admission temperatures improved significantly from 35.6°C in 1994 to 36.4°C in 2012 (R < 0.88). The incidence of hypothermia was 29.5 and 13.9% between 1994–2005 and 2006–2012, respectively. In comparison with normothermic infants, hypothermic infants had lower gestational age at birth (26 vs. 27 weeks) and lower birthweight (800 vs. 976 g). In‐hospital mortality was higher in hypothermic infants (28.5 vs. 12.9%; odds ratio (OR) 2.69, 95% confidence interval (CI) 2.37–3.06). Severe intraventricular haemorrhage (12.1 vs. 8.5%, OR 1.48, 95% CI 1.25–1.75), necrotising enterocolitis (NEC) (11.0 vs. 7.5%; OR 1.54, 95% CI 1.29–1.83) and severe retinopathy of prematurity (16.5 vs. 8.9%; OR 2.02, 95% CI 1.70–2.39) were significantly higher in hypothermic infants. Multivariate regression analysis showed hypothermia was an independent risk factor for increased mortality (AOR (adjusted odds ratio ) 1.50, 95% CI 1.29–1.74, P < 0.001) and NEC (AOR 1.28, 95% CI 1.05–1.55, P = 0.01).

Conclusions

Admission temperatures improved during the time period. Hypothermia at admission was associated with a significant increase in mortality and NEC.