bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histogenesis of cutaneous malignant melanoma: The vast majority do not develop from melanocytic nevus but arise de novo as melanoma in situ
Authors: Saida Toshiaki 
Published: January 2019

AbstractIt has been considered that most cutaneous malignant melanomas arise from pre‐existing melanocytic nevus. Many clinical and histopathological studies seem to support this concept. Dysplastic nevus originally proposed by Clark's group is a key entity of the intermediate lesion between benign nevus and melanoma. The latest edition of the WHO Classification of Skin Tumours (2018) has excluded Clark nevus (dysplastic nevus of mild atypia) from dysplastic nevus, the latter being now classified into the low‐ and high‐grade by the degrees of nuclear atypia. The World Health Organization classification regards dysplastic nevus of both grades as the intermediate lesion between common acquired nevus and the radial growth‐phase melanoma. An extensive genetic study recently performed by Bastian's group indicated the existence of intermediate lesions between nevus and melanoma. In spite of these findings, some investigators doubt the concept of the intermediate lesions including dysplastic nevus and insist that the majority of melanomas arise de novo as melanoma in situ, not in association with a preceding nevus. The concept of de novo genesis of melanoma may be supported by a recent meta‐analysis study revealing that 71% of melanomas likely arose de novo and 29% from pre‐existing nevus. In this review article, from the viewpoint of de novo genesis of melanoma, the author critically discusses the relevant findings of melanoma genesis and proposes a new framework to interpret the morphological and genetic data alternatively. Clarification of the oncogenic process of melanoma has great impact not only on clinical dermatology but also on basic oncology.
Endophytes from wild cereals protect wheat plants from drought by alteration of physiological responses of the plants to water stress
Authors: Llorens Eugenio , Sharon Or , Camañes Gemma , García‐Agustín Pilar , Sharon Amir 
Published: January 2019

SummaryEndophytes contribute to plant performance, especially under harsh conditions. We therefore hypothesized that wild plants have retained beneficial endophytes that are less abundant or not present in related crop plants. To test this hypothesis, we selected two endophytes that were found in Sharon goatgrass, an ancestor of wheat, and tested their effect on bread wheat. Both endophytes infected wheat and improved sustainability and performance under water‐limited conditions. To determine how the endophytes modify plant development, we measured parameters of plant growth and physiological status and performed a comparative metabolomics analysis. Endophyte‐treated wheat plants had reduced levels of stress damage markers and reduced accumulation of stress‐adaptation metabolites. Metabolomics profiling revealed significant differences in the response to water stress of endophyte‐treated plants compared with untreated plants. Our results demonstrate the potential of endophytes from wild plants for improvement of related crops and show that the beneficial effects of two endophytes are associated with alteration of physiological responses to water‐limited conditions.
Access by Design, Benefits if Convenient: A Closer Look at the Pandemic Influenza Preparedness Framework's Standard Material Transfer Agreements
Authors: ROURKE MICHELLE F. 
Published: January 2019

Policy Points
Securing access to pathogen samples for research purposes is crucial for pandemic preparedness and responding to infectious disease outbreaks.
The Pandemic Influenza Preparedness Framework (PIP Framework) is the only pathogen‐specific international access and benefit‐sharing (ABS) instrument.
This analysis reveals that during an influenza pandemic, the PIP Framework will safeguard access to virus samples but may not be as effective in delivering the associated benefits, like vaccines and antivirals, to countries in need.
The PIP Framework's deficiencies must be addressed before an influenza pandemic and before this ABS model is extended to other human pathogens.
ContextThe World Health Organization (WHO) adopted the Pandemic Influenza Preparedness Framework (PIP Framework) after being forced to grapple with the demands of developing countries for the fairer distribution of vaccines and antivirals created using influenza viruses isolated from within their territories. Though adopted as a nonbinding resolution, the PIP Framework has been praised for its novel legal approach to access and benefit‐sharing (ABS), using Standard Material Transfer Agreements (SMTAs) to create binding terms and conditions on both providers and users of PIP biological materials. The PIP Framework's SMTA1 regulates the movement of influenza viruses with human pandemic potential through the WHO's Global Influenza Surveillance and Response System (GISRS) as it operates to monitor the spread of seasonal influenza and detect the emergence of pandemic strains. Member States give consent to the WHO to transfer their materials to third parties under the terms of a negotiated SMTA2. The SMTA2 details benefits such as vaccines and antivirals to be made available to the WHO for distribution in the event of an influenza pandemic.MethodsI analyzed the PIP Framework, its SMTAs, and secondary sources to determine whether the PIP Framework will effectively function as an ABS instrument during an influenza pandemic.FindingsThe SMTAs do not create any direct or binding agreements between Member States and third‐party recipients of influenza viruses. In the lead‐up to and during a pandemic, the SMTA1 secures access to influenza viruses for the WHO, and the SMTA2 secures access for commercial users of virus samples, but the SMTA2 may be ineffective in securing tangible benefits for the sovereign providers of those materials.ConclusionsAs the international community starts to consider how to best regulate access to nonpandemic influenza pathogen samples, it is imperative that we first address the shortcomings of the only pathogen‐specific international ABS instrument available, and we should do so before it is put to the ultimate test.
Genotype‐free estimation of allele frequencies reduces bias and improves demographic inference from RADSeq data
Authors: Warmuth Vera M. , Ellegren Hans 
Published: January 2019

AbstractRestriction‐site associated DNA sequencing (RADSeq) facilitates rapid generation of thousands of genetic markers at relatively low cost; however, several sources of error specific to RADSeq methods often lead to biased estimates of allele frequencies and thereby to erroneous population genetic inference. Estimating the distribution of sample allele frequencies without calling genotypes was shown to improve population inference from whole genome sequencing data, but the ability of this approach to account for RADSeq‐specific biases remains unexplored. Here we assess in how far genotype‐free methods of allele frequency estimation affect demographic inference from empirical RADSeq data. Using the well‐studied pied flycatcher (Ficedula hypoleuca) as a study system, we compare allele frequency estimation and demographic inference from whole genome sequencing data with that from RADSeq data matched for samples using both genotype‐based and genotype free methods. The demographic history of pied flycatchers as inferred from RADSeq data was highly congruent with that inferred from whole genome resequencing (WGS) data when allele frequencies were estimated directly from the read data. In contrast, when allele frequencies were derived from called genotypes, RADSeq‐based estimates of most model parameters fell outside the 95% confidence interval of estimates derived from WGS data. Notably, more stringent filtering of the genotype calls tended to increase the discrepancy between parameter estimates from WGS and RADSeq data, respectively. The results from this study demonstrate the ability of genotype‐free methods to improve allele frequency spectrum‐ (AFS‐) based demographic inference from empirical RADSeq data and highlight the need to account for uncertainty in NGS data regardless of sequencing method.
Regularized S‐map for inference and forecasting with noisy ecological time series
Authors: Cenci Simone , Sugihara George , Saavedra Serguei 
Published: January 2019

AbstractIt is well known that fluctuations of species abundances observed in ecological time series emerge from an interplay between deterministic nonlinear dynamics and stochastic forces. Importantly, nonlinearity and stochasticity introduce significant challenges to the analysis of ecological time series, such as the inference of the effect of species interactions on community dynamics and forecasting of species abundances.Local linear fits with state‐space‐dependent kernel functions, known as S‐maps, provide an efficient method to infer Jacobian coefficients (a proxy for the local effect of species interactions) and to make reliable forecasts from nonlinear time series. Yet, while it has been shown that the S‐map outperforms existing methods for nonparametric inference and forecasting, the methodology is sensitive to process noise. To overcome this limitation, we integrate the S‐map with different regularization schemes.To validate our approach, we test our methodology against different levels of noise and nonlinearity using three standard population dynamics models. We show that an appropriate choice of the regularization scheme, alongside an accurate choice of the kernel functions, can significantly improve the in‐sample inference of Jacobian coefficients and the out‐of‐sample forecast of species abundances in the presence of process noise. We further validate our methodology using two empirical time series of marine microbial communities.Our results illustrate that the regularized S‐map is an efficient method for nonparametric inference and forecasting from noisy, nonlinear, ecological time series. Yet, attention must be paid on the regularization scheme and the structure of the kernel for whether inference or forecasting is the ultimate goal of a research study.
Exploring synchronous, remote collaborative interaction between learners using multi‐touch tables and video conferencing in UK primary schools
Authors: Beauchamp Gary , Joyce‐Gibbons Andrew , Mc Naughton James , Young Nick , Crick Tom 
Published: January 2019

AbstractThis study explores remote, non‐collocated collaboration via multi‐touch table (SynergyNet) and video conferencing software (Skype). Twenty‐four participants (aged 10‐11 years) in two locations—primary school classrooms located 300 miles apart in the UK—engaged in simultaneous collaborative activity to solve a History mystery task. Audio‐video data recorded in the first minute of the activity were analysed to explore the emergence of collaborative working practices both within groups in the same location (resizing for shared reading) and between the groups communicating via video conferencing software and through the “flick” multi‐touch gesture (sharing clues between groups). The results indicated that most groups focused first on the establishment of intra‐group collaboration before reaching out to their remotely located partners. However, when the second data set was analysed, audio data from delayed interviews conducted after the original study, participants reported that the discussion between groups supported by the “flick” gesture was the most important and memorable feature of the activity. The study relates these findings to the existing literature on collaborative learning using multi‐touch tables and considers how teachers are best able to help support the emergence of collaborative practices.
Pterostilbene prevents hepatocyte epithelial‐mesenchymal transition in fructose‐induced liver fibrosis through suppressing miR‐34a/Sirt1/p53 and TGF‐β1/Smads signalling
Authors: Song Lin , Chen Tian‐Yu , Zhao Xiao‐Juan , Xu Qiang , Jiao Rui‐Qing , Li Jian‐Mei , Kong Ling‐Dong 
Published: January 2019

Background and PurposeExcessive fructose consumption is a risk factor for liver fibrosis. Pterostilbene protects against liver fibrosis. Here, we investigated the potential role and the mechanisms underlying the hepatocyte epithelial‐mesenchymal transition (EMT) in fructose‐induced liver fibrosis and protection by pterostilbene.Experimental ApproachCharacteristic features of liver fibrosis in 10% fructose‐fed rats and EMT in 5 mM fructose‐exposed BRL‐3A cells with or without pterostilbene and the change of miR‐34a/Sirt1/p53 and transforming growth factor‐β1 (TGF‐β1)/Smadssignalling were examined. MiR‐34a inhibitor, miR‐34a minic, orp53siRNA were used to explore the role of miR‐34a/Sirt1/p53 signalling in fructose‐induced EMT and the action of pterostilbene.Key ResultsPterostilbene prevented fructose‐induced liver injury with fibrosis in rats. Fructose caused hepatocyte undergoing EMT, gaining fibroblast‐specific protein 1 and vimentin, and losing E‐cadherin, effects attenuated by pterostilbene. Moreover, fructose induced miR‐34a overexpression in hepatocytes with down‐regulated Sirt1, increased p53 and ac‐p53, and activated TGF‐β1/Smads signalling, whereas these disturbances were suppressed by miR‐34a inhibitor. Additionally, miR‐34a inhibitor andp53siRNA prevented TGF‐β1‐driven hepatocyte EMT under fructose exposure. Pterostilbene down‐regulated miR‐34a, up‐regulated Sirt1, and suppressed p53 activation and TGF‐β1/Smads signalling in fructose‐stimulated animals and cells but showed no additional effects with miR‐34a inhibitor on miR‐34a/Sirt1/p53 signalling in fructose‐exposed hepatocytes.Conclusions and ImplicationsThese results strongly suggest that activation of miR‐34a/Sirt1/p53 signalling is required for fructose‐induced hepatocyte EMT mediated by TGF‐β1/Smads signalling, contributing to liver fibrosis in rats. Pterostilbene exhibits a protective effect against liver fibrosis at least partly through inhibiting miR‐34a/Sirt1/p53 signalling activation.
Anti‐cancer effects of CQBTO, a chloroquine, and benzo(e)triazine oxide conjugate
Authors: Guo Ziyang , Pei Hailong , Nie Jing , Hu Wentao , Zhang Jian , Ding Jiahan , Pan Shuxian , Li Bingyan , Hei Tom K. , Chen Weiqiang , Zhou Guangming 
Published: January 2019

AbstractAimAutophagy is a self‐protective process, and it confers cancer cells resistance against radio‐chemotherapeutics. To induce cancer cell death, a series of compounds of 3‐((4‐((7‐chloroquinolin‐4‐yl)amino)butyl)amino)‐7‐substituted benzo[e][1,2,4]triazine 1‐oxide or CQBTO containing two critical chemical groups were designed and synthesized. One compound, benzo[e][1,2,4]triazine 1‐oxide, yielded free radicals to trigger autophagy, and the other one, chloroquine (CQ), was an inhibitor of autophagy. We hypothesized that the compounds could kill cancer cells effectively by inducing incomplete autophagy.MethodsIn vitro cultured non‐small cell lung carcinoma cells and primary lung tumors in mice in vivo were used to test the lethal effects of CQBTO on cancer cells and toxicity to normal tissues. Cell viability was examined using the CCK8 assay. Genomic instability was determined with the cytochalasin B‐blocked micronucleus assay. Cell cycle distribution was analyzed by propidium iodide staining and flow cytometry. Western blotting and immunofluorescence were used to detect the induction and localization of LC3, a biomarker for autophagy.ResultsCompared with CQ, three CQBTO compounds were lethal to lung cancer cells, and CQBTO‐3 was the most effective. The LD50 for CQBTO‐3 was 21 μΜ in A549 cells and 21.5 μΜ in Calu‐1 cells, which was lower than that of CQBTO‐2 or CQBTO‐1. Induction of LC3 foci and an increase in the LC3II/LC3I ratio demonstrated the induction of autophagy by CQBTO‐3 in A549 cells, whereas no obvious micronuclei or cell cycle arrest was observed. No detectable toxicity to normal mice was observed. CQBTO‐3 improved the quality of mouse life, reduced the number and size of existing tumors, and suppressed tumor formation.ConclusionCQBTO‐3 is a potential chemical compound for lung cancer treatment.
Epigenetic regulation of myelination in health and disease
Authors: Lu Guozhen , Zhang Ming , Wang Jian , Zhang Kaixiang , Wu Shengxi , Zhao Xianghui 
Published: January 2019

AbstractMyelin is lipid‐rich structure that is necessary to avoid leakage of electric signals and to ensure saltatory impulse conduction along axons. Oligodendrocytes in central nervous system (CNS) and Schwann cells in peripheral nervous system (PNS) are responsible for myelin formation. Axonal demyelination after injury or diseases greatly impairs normal nervous system function. Therefore, understanding how the myelination process is programmed, coordinated, and maintained is crucial for developing therapeutic strategies for remyelination in the nervous system. Epigenetic mechanisms have been recognized as a fundamental contributor in this process. In recent years, histone modification, DNA modification, ATP‐dependent chromatin remodeling, and non‐coding RNA modulation are very active area of investigation. We will present a conceptual framework that integrates crucial epigenetic mechanisms with the regulation of oligodendrocyte and Schwann cell lineage progression during development and myelin degeneration in pathological conditions. It is anticipated that a refined understanding of the molecular basis of myelination will aid in the development of treatment strategies for debilitating disorders that involve demyelination, such as multiple sclerosis in the CNS and neuropathies in the PNS.
C‐reactive protein (CRP) rs3093059C predicts poor mizolastine response in chronic spontaneous urticaria patients with elevated serum CRP level
Authors: Yan Siyu , Chen Wangqing , Peng Cong , Zhu Wu , Chen Mingliang , Zhang Jianglin , Su Juan , Li Fangfang , Liu Zhaoqian , Zhang Wei , Li Qingling , Li Jie , Chen Xiang 
Published: January 2019

AbstractChronic spontaneous urticaria (CSU) is a frequent disorder with recurrent itchy wheals and/or angioedema, and nearly 35% patients respond poorly to non‐sedating H1 antihistamine treatment. CRP gene encodes the C‐reactive protein, which is involved in the pathogenesis of CSU. To investigate the impacts of CRP polymorphisms on the susceptibility and therapeutic efficacy in the South Han CSU patients, we enrolled 145 CSU patients in our study. After 4‐week non‐sedating H1 antihistamine monotherapy treatment, more than 50% reduction of the severity score is considered as effective, or else non‐effective. The CRP rs3093059T/C and rs2794521G/A genotypes of patients were determined by Sequenom MassARRAY. Functional studies including relative luciferase assay and β‐hexosaminidase assay were conducted in HEK293T cells or RBL‐2H3 cells to explore the function of variants. Forty (62.50%) CSU patients were effective when treated with mizolastine, and 55 (72.4%) patients were effective in the desloratadine group. We found that the patients carried with rs3093059TT genotype were significantly associated with good response (OR = 4.20, P = 0.015), had lower serum CRP, IL‐6 and TNF‐α levels than the CT/CC genotypes. In vitro, the rs3093059C allele exhibited significantly higher luciferase activity than wild allele (P < 0.001). From the β‐hexosaminidase assay, we observed the inhibiting degranulation effects by mizolastine and this effect is weakened when with a higher dose CRP in RBL‐2H3 cells. Our findings suggested that CSU patients carrying the rs3093059C allele may respond poorly to mizolastine with elevated serum CRP level.
High abundance of an invasive species gives it an outsized ecological role
Authors: McDowell William G. , Byers James E. 
Published: January 2019

Abstract

Many communities are shifting composition, with losses of native species and increases of non‐indigenous species (NIS). At its extreme, such alteration of ecological guilds can result in simplification with a single NIS performing an ecological role once carried out by a suite of natives. This alteration has occurred in many rivers of the south‐eastern U.S.A., where the invasive filter‐feeding freshwater clam Corbicula fluminea has proliferated following the nearly complete extirpation of native mussels.

We investigated the factors controlling the distribution and abundance of Corbicula, as well as estimated the ecological service it provides via water filtration. With a nested design, we surveyed multiple transects within four to six sites within each of four rivers that spanned three large catchments in the Georgia piedmont, collecting data on Corbicula density and physical habitat characteristics associated with its presence.

We found Corbicula present in over half of the 1,536 sampled 0.044 m2 sampled plots, 90 of the 93 transects that spanned the width of the river, and all 1–2 km sample sites, underscoring the clam's ubiquity in the study region. At the river scale, Corbicula densities ranged from 50–212 Corbicula m−2, although individual sites ranged from 7–483 Corbicula m−2. Corbicula was more abundant in areas with higher proportions of gravel, and less abundant with higher proportions of bedrock. A hierarchical model with river, site, and these two substrate variables explained 32% of the variation in Corbicula density.

Using observed densities and published per capita feeding rates, we calculated system‐wide collective filtration rates provided by Corbicula. In the four rivers surveyed and based on estimated residence times for median flows for the summer of 2012, Corbicula is estimated to filter water as many as seven times during median flows and 18 times during minimum flows before water flows out of a 10‐km reach. Due to high abundances and per biomass filtration rates, Corbicula plays an important role in these rivers.

Invasive species, biotic homogenisation, and the loss of functional redundancy may mean that many more rivers are similar to our studied rivers, with a single, often invasive, species dominating ecosystem function. Understanding the influence of biotic homogenisation on ecosystem function is of foremost importance to evaluate the resilience of natural systems.