bluuebunny/crossref_metadata_2025_split huggingface dataset:
A modular Golden Gate toolkit for Yarrowia lipolytica synthetic biology
Authors: Larroude Macarena , Park Young‐Kyoung , Soudier Paul , Kubiak Monika , Nicaud Jean‐Marc , Rossignol Tristan 
Published: May 2019

SummaryThe oleaginous yeast Yarrowia lipolytica is an established host for the bio‐based production of valuable compounds and an organism for which many genetic tools have been developed. However, to properly engineer Y. lipolytica and take full advantage of its potential, we need efficient, versatile, standardized and modular cloning tools. Here, we present a new modular Golden Gate toolkit for the one‐step assembly of three transcription units that includes a selective marker and sequences for genome integration. Perfectly suited to a combinatorial approach, it contains nine different validated promoters, including inducible promoters, which allows expression to be fine‐tuned. Moreover, this toolbox incorporates six different markers (three auxotrophic markers, two antibiotic‐resistance markers and one metabolic marker), which allows the fast sequential construction and transformation of multiple elements. In total, the toolbox contains 64 bricks, and it has been validated and characterized using three different fluorescent reporter proteins. Additionally, it was successfully used to assemble and integrate a three‐gene pathway allowing xylose utilization by Y. lipolytica. This toolbox provides a powerful new tool for rapidly engineering Y. lipolytica strains and is available to the community through Addgene.
Phenological stages of arrowroot (Maranta arundinacea L.) according to the Biologische Bundesanstalt Bundessortenamt und Chemische Industrie scale
Authors: Brito Vitor , Godoy‐Casagrande Vitor , Narcisa‐Oliveira Jeniffer , Tomielis Ismael , Cereda Marney , Steinfort Ursula , Costa Reginaldo 
Published: May 2019

AbstractThe present study aimed to characterise and establish the phenological stages of arrowroot (Maranta arundinacea L.) by employing the extended BBCH (Biologische Bundesanstalt Bundessortenamt und Chemische Industrie) scale system and reporting a detailed biometric evaluation. An experiment with individual plants grown in separate pots was set up in a greenhouse for the identification and characterisation of phenological stages (the phenotypic characterisation and tuberisation process was accompanied by histological analyses every 2 months) and for biometric evaluation (plant height, root volume, dry biomass, leaf area and accumulated starch). We identified 36 secondary stages within eight principal stages of arrowroot growth which comprise: (0) sprouting; (1) leaf development–main stem; (2) formation of lateral stems; (3) elongation–main stem; (4) rhizome formation and tuberisation; (5) inflorescence emergence; (6) flowering, and (9) senescence. Results were categorised and recorded by way of photographs and technical drawings. The total growth cycle in this experiment was 230 days, concluding at the point of harvest. It was possible to observe the phenological events that characterised the changes at each stage (colouration, flag leaf emission, inflorescence and the rhizome tuberisation process). The BBCH system was efficient in identifying arrowroot phenological data. It constitutes a tool for agricultural calendar delineation and contributes to the standardisation of research on the species.
Resilience as a focus of suicide research and prevention
Authors: Sher L. 
Published: May 2019

Suicide is a major medical and social problem. Decades of suicide research have mostly focused on risk factors for suicidal behaviour while overlooking protective factors such as resilience that may help to address this important public health issue. Resilience is the capacity and dynamic process of adaptively overcoming stress and adversity while maintaining normal psychological and physical functioning. Studies conducted over the past 10–15 years suggest that resilience is a protective factor against suicide risk. Resilience is becoming a focus of suicide research and prevention. Building resilience should be a part of universal, selective, and indicated suicide prevention interventions. Promoting resilience may reduce suicide risk in the general population, in groups at elevated suicide risk, and among high‐risk individuals. Building resilience in the general population may reduce the incidence of stress‐related disorders and, consequently, suicidal behaviour. Improving resilience should be a part of a treatment plan of every psychiatric patient. Mental health professionals will probably have the best success in reducing suicide risk in psychiatric patients if they actively concentrate on increasing stress resilience using both psychosocial and pharmacological interventions. It is critically important to move forward the development of pharmacological and psychological interventions for enhancing resilience.
Comparing alcohol taxation throughout the European Union
Authors: Angus Colin , Holmes John , Meier Petra S. 
Published: May 2019

AbstractBackground and AimsThe World Health Organization recommends increasing alcohol taxes as a ‘best‐buy’ approach to reducing alcohol consumption and improving population health. Alcohol may be taxed based on sales value, product volume or alcohol content; however, duty structures and rates vary, both among countries and between beverage types. From a public health perspective, the best duty structure links taxation level to alcohol content, keeps pace with inflation and avoids substantial disparities between different beverage types. This data note compares current alcohol duty structures and levels throughout the 28 European Union (EU) Member States and how these vary by alcohol content, and also considers implications for public health.Design and SettingDescriptive analysis using administrative data, European Union, July 2018.MeasurementsBeverage‐specific alcohol duty rates per UK alcohol unit (8 g ethanol) in pounds sterling at a range of different alcoholic strengths.FindingsOnly 50% of Member States levy any duty on wine and several levy duty on spirits and beer at or close to the EU minimum level. There is at least a 10‐fold difference in the effective duty rate per unit between the highest‐ and lowest‐duty countries for each beverage type. Duty rates for beer and spirits stay constant with strength in the majority of countries, while rates for wine and cider generally fall as strength increases. Duty rates are generally higher for spirits than other beverage types and are generally lowest in eastern Europe and highest in Finland, Sweden, Ireland and the United Kingdom.ConclusionsDifferent European Union countries enact very different alcohol taxation policies, despite a partially restrictive legal framework. There is only limited evidence that alcohol duties are designed to minimize public health harms by ensuring that drinks containing more alcohol are taxed at higher rates. Instead, tax rates appear to reflect national alcohol production and consumption patterns.
Geomorphic, sedimentary and hydraulic reconstruction of a glacial lake outburst flood in northern Alberta, Canada
Authors: Norris Sophie L. , Margold Martin , Utting Daniel J. , Froese Duane G. 
Published: May 2019

Glacial lake outburst floods occurred frequently during the last deglaciation of the Laurentide Ice Sheet. Within the Interior Plains, these floods carved large spillway systems; however, due to a lack of abundant sediment, deposits within prairie spillways are rarely preserved. Here, we present geomorphic and sedimentary evidence and hydraulic modelling of the eastern Beaver River Spillway, formed by the catastrophic drainage of the ice‐dammed glacial Lake Algar, in north central Alberta. During this flood, coarse‐grained sediment eroded from local till formed large pendant bars. Within the first ~50 km of the spillway (Reach 1), pendant bars contain downstream orientated foresets overlain by horizontally bedded coarser gravels. The remaining pendant bars (Reach 2), present downflow of a moraine barrier, differ, comprising massive, matrix‐supported, inversely graded gravels capped by a boulder layer. We use a HEC‐GeoRAS/HEC‐RAS system in conjunction with palaeostage indicators to estimate the steady‐state water surface elevation. Modelling results show that peak discharge within Reach 1 of the eastern Beaver River Spillway was approximately 14 000–21 000 m3 s−1. For Reach 2, 30 km downstream, the peak discharge was estimated at 23 000–40 000 m3 s−1 (nbulked 18 000–26 000 m3 s−1). The downstream discharge increase, consistent with the sedimentary change in pendant bar deposits, is attributed to sediment bulking of the flood flow. This provides the opportunity to observe a range of flow conditions, and associated sedimentology, from a single flood event. The reconstructed flow conditions, coupled with lake volume estimates from the ponding above the moraine barrier suggest a minimum flow duration of 3–5 days.
Assessing the utility of conserving evolutionary history
Authors: Tucker Caroline M. , Aze Tracy , Cadotte Marc W. , Cantalapiedra Juan L. , Chisholm Chelsea , Díaz Sandra , Grenyer Richard , Huang Danwei , Mazel Florent , Pearse William D. , Pennell Matthew W. , Winter Marten , Mooers Arne O. 
Published: May 2019

ABSTRACTIt is often claimed that conserving evolutionary history is more efficient than species‐based approaches for capturing the attributes of biodiversity that benefit people. This claim underpins academic analyses and recommendations about the distribution and prioritization of species and areas for conservation, but evolutionary history is rarely considered in practical conservation activities. One impediment to implementation is that arguments related to the human‐centric benefits of evolutionary history are often vague and the underlying mechanisms poorly explored. Herein we identify the arguments linking the prioritization of evolutionary history with benefits to people, and for each we explicate the purported mechanism, and evaluate its theoretical and empirical support. We find that, even after 25 years of academic research, the strength of evidence linking evolutionary history to human benefits is still fragile.Most – but not all – arguments rely on the assumption that evolutionary history is a useful surrogate for phenotypic diversity. This surrogacy relationship in turn underlies additional arguments, particularly that, by capturing more phenotypic diversity, evolutionary history will preserve greater ecosystem functioning, capture more of the natural variety that humans prefer, and allow the maintenance of future benefits to humans. A surrogate relationship between evolutionary history and phenotypic diversity appears reasonable given theoretical and empirical results, but the strength of this relationship varies greatly. To the extent that evolutionary history captures unmeasured phenotypic diversity, maximizing the representation of evolutionary history should capture variation in species characteristics that are otherwise unknown, supporting some of the existing arguments. However, there is great variation in the strength and availability of evidence for benefits associated with protecting phenotypic diversity. There are many studies finding positive biodiversity–ecosystem functioning relationships, but little work exists on the maintenance of future benefits or the degree to which humans prefer sets of species with high phenotypic diversity or evolutionary history. Although several arguments link the protection of evolutionary history directly with the reduction of extinction rates, and with the production of relatively greater future biodiversity via increased adaptation or diversification, there are few direct tests. Several of these putative benefits have mismatches between the relevant spatial scales for conservation actions and the spatial scales at which benefits to humans are realized. It will be important for future work to fill in some of these gaps through direct tests of the arguments we define here.
Causes and effects of haploinsufficiency
Authors: Johnson Adam F. , Nguyen Ha T. , Veitia Reiner A. 
Published: May 2019

ABSTRACTHaploinsufficiency is a form of genetic dominance and is the underlying mechanism of numerous human inherited conditions in which the causal genes are sensitive to altered dosage. This review examines the poorly understood relationships between haploinsufficiency, dosage sensitivity and genetic dominance, whose common theme is the existence of nonlinear relationships between genotype and phenotype. We present an up‐to‐date account of the bases of haploinsufficiency from the perspective of theoretical and experimental models. We also discuss human conditions caused by haploinsufficiency, including developmental syndromes and cancer. Connections between the understanding of these conditions' genetic mechanisms and advances in treatments are also described.
Exosomal microRNAs derived from colon cancer cells promote tumor progression by suppressing fibroblast TP53 expression
Authors: Yoshii Shunsuke , Hayashi Yoshito , Iijima Hideki , Inoue Takanori , Kimura Keiichi , Sakatani Akihiko , Nagai Kengo , Fujinaga Tetsuji , Hiyama Satoshi , Kodama Takahiro , Shinzaki Shinichiro , Tsujii Yoshiki , Watabe Kenji , Takehara Tetsuo 
Published: May 2019

AbstractThe tumor microenvironment offers favorable conditions for tumor progression, and activated fibroblasts, known as cancer‐associated fibroblasts, play a pivotal role. TP53‐deficient cancer cells are known to induce strong fibroblast activation. We aimed to elucidate the oncogenic role of exosomes derived from TP53‐deficient colon cancer cells in fibroblast proliferation and tumor growth. Cancer cell‐derived exosomes (CDEs) were isolated from the conditioned media of cancer cells using a sequential ultracentrifugation method. The effects of exosomes on tumor growth were evaluated using human cell lines (TP53‐WT colon cancer, HCT116; TP53‐mutant colon cancer, HT29; and fibroblasts, CCD‐18Co and WI‐38) and an immune‐deficient nude mouse xenograft model. HCT116 (HCT116sh p53) cells deficient in TP53 accelerated cocultured fibroblast proliferation compared to TP53‐WT HCT116 (HCT116sh control) cells in vitro. Exosomes from HCT116sh p53 cells suppressed TP53 expression of fibroblasts and promoted their proliferation. Xenografts of HCT116sh p53 cells grew significantly faster than those of HCT116sh control cells in the presence of co‐injected fibroblasts, but this difference was diminished by CDE inhibition. Microarray analysis identified upregulation of several microRNAs (miR‐1249‐5p, miR‐6737‐5p, and miR‐6819‐5p) in TP53‐deficient CDEs, which were functionally proven to suppress TP53 expression in fibroblasts. Exosomes derived from TP53‐mutant HT29 cells also suppressed TP53 expression in fibroblasts and accelerated their growth. The proliferative effect of HT29 on cocultured fibroblasts was diminished by inhibition of these miRNAs in fibroblasts. Our results suggest that CDEs play a pivotal role in tumor progression by fibroblast modification. Cancer cell‐derived exosomes might, therefore, represent a novel therapeutic target in colon cancer.
Targeting PIN1 exerts potent antitumor activity in pancreatic ductal carcinoma via inhibiting tumor metastasis
Authors: Chen Linying , Xu Xiao , Wen Xinxin , Xu Shenmin , Wang Long , Lu Wenxian , Jiang Mingting , Huang Jing , Yang Dayun , Wang Jichuang , Zheng Min , Zhou Xiao Zhen , Lu Kun Ping , Liu Hekun 
Published: May 2019

AbstractThe human prolyl isomerase PIN1, best known for its association with carcinogenesis, has recently been indicated in the disease of pancreatic ductal adenocarcinoma (PDAC). However, the functions of PIN1 and the feasibility of targeting PIN1 in PDAC remain elusive. For this purpose, we examined the expression of PIN1 in cancer, related paracarcinoma and metastatic cancer tissues by immunohistochemistry and analyzed the associations with the pathogenesis of PDAC in 173 patients. The functional roles of PIN1 in PDAC were explored in vitro and in vivo using both genetic and chemical PIN1 inhibition. We showed that PIN1 was upregulated in pancreatic cancer and metastatic tissues. High PIN1 expression is significantly association with poor clinicopathological features and shorter overall survival and disease‐free survival. Further stratified analysis showed that PIN1 phenotypes refined prognostication in PDAC. Inhibition of PIN1 expression with RNA interference or with all trans retinoic acid decreased not only the growth but also the migration and invasion of PDAC cells through regulating the key molecules of multiple cancer‐driving pathways, simultaneously resulting in cell cycle arrest and mesenchymal‐epithelial transition in vitro. Furthermore, genetic and chemical PIN1 ablation showed dramatic inhibition of the tumorigenesis and metastatic spread and then reduced the tumor burden in vivo. We provided further evidence for the use of PIN1 as a promising therapeutic target in PDAC. Genetic and chemical PIN1 ablation exerted potent antitumor effects through blocking multiple cancer‐driving pathways in PDAC. More potent and specific PIN1 targeted inhibitors could be exploited to treat this aggressive cancer.
Design and synthesis of phenylpiperazine derivatives as potent anticancer agents for prostate cancer
Authors: Demirci Serpil , Hayal Taha Bartu , Kıratlı Binnur , Şişli Hatice Burcu , Demirci Selami , Şahin Fikrettin , Doğan Ayşegül 
Published: May 2019

AbstractNovel thiourea (5a, 5b) and thiazolidinone derivatives (6a, 6b) were synthesized by hybridizing molecules starting from the compound 6‐(4‐phenylpiperazin‐1‐yl)pyridin‐3‐amine (4) which is known to show anticancer activity. The synthesis of the leading compound was carried out by using 1‐(5‐nitropyridin‐2‐yl)‐4‐phenylpiperazine (3) which was obtained by a novel method of the reaction of 2‐chloro‐5‐nitropyridine (1) and N‐phenylpiperazine (2). The structures of the compounds were confirmed using FTIR, 1H NMR, 13C NMR, HRMS spectroscopic methods and elemental analysis. The organic molecules were tested for their anticancer activities against prostate cancer (PC) cell lines: DU 145, PC‐3 and LNCaP. As the compound 5a exerted the highest cytotoxic activity, IC50 concentrations of compound 5a were further investigated in terms of morphology, colony‐forming ability, RNA expression, fragmented DNA and cell cycle distributions of PC cell lines. Overall data revealed that compound 5a treatment induces apoptosis and DNA fragmentation in PC cell lines and inhibits cell cycle progression resulting in the accumulation of cells in either the G1 or the S phases.
Structural changes over time in individual‐based networks involving a harvester ant, seeds, and invertebrates
Authors: Anjos Diego V. , Luna Pedro , Borges Carla C. R. , Dáttilo Wesley , Del‐Claro Kleber 
Published: May 2019

1. Harvester ants perform important ecological functions, such as seed predation and redistribution of nutrients in the soil, through a complex of ecological interactions. Most studies are static descriptions of network structure, while their temporal organisations and the factors that modulate it have been neglected.2. This study describes the temporal organisation and the influence of climatic variables (e.g. temperature and rainfall) on network structure between a harvester ant species and its food resources (seeds and invertebrates) in the Brazilian savanna over a 1‐year period. In addition, considering the ant–seed networks, the relationship between the size of seeds collected by ants and the distance travelled was examined, as well as how this relationship behaves over time.3. For all network types (ant–seed, ant–invertebrate, and combined) there was great structural variation throughout the year. Among climatic variables, only rainfall influenced the properties of ant–invertebrate networks, presenting a positive influence on diversity of interactions and a negative influence on network specialisation. Finally, this study shows that harvester ants tend to collect larger seeds in the vicinity of the nest (< 5 m) and smaller seeds at greater distances, and this relationship appears to be constant over time.4. This study highlights that ecological networks are useful tools with which to understand the temporal organisation of ecological functions. In addition, climatic changes, mainly in the rainfall regime, may interfere directly in the availability of resources and ultimately in the interactions between harvester ants and their food resources.
Role of magnetic resonance spectroscopy in cerebral glutathione quantification for youth mental health: A systematic review
Authors: Fisher Emily , Gillam John , Upthegrove Rachel , Aldred Sarah , Wood Stephen J. 
Published: May 2019

AbstractAimOxidative stress is strongly implicated in many psychiatric disorders, which has resulted in the development of new interventions to attempt to perturb this pathology. A great deal of attention has been paid to glutathione, which is the brain's dominant antioxidant and plays a fundamental role in removing free radicals and other reactive oxygen species. Measurement of glutathione concentration in the brain in vivo can provide information on redox status and potential for oxidative stress to develop. Glutathione might also represent a marker to assess treatment response.MethodsThis paper systematically reviews studies that assess glutathione concentration (measured using magnetic resonance spectroscopy) in various mental health conditions.ResultsThere is limited evidence showing altered brain glutathione concentration in mental disorders; the best evidence suggests glutathione is decreased in depression, but is not altered in bipolar disorder. The review then outlines the various methodological options for acquiring glutathione data using spectroscopy.ConclusionsAnalysis of the minimum effect size measurable in existing studies indicates that increased number of participants is required to measure subtle but possibly important differences and move the field forward.
Range‐wide population genomics of the Mexican fruit fly: Toward development of pathway analysis tools
Authors: Dupuis Julian R. , Ruiz‐Arce Raul , Barr Norman B. , Thomas Donald B. , Geib Scott M. 
Published: May 2019

AbstractRecurrently invading pests provide unique challenges for pest management, but also present opportunities to utilize genomics to understand invasion dynamics and inform regulatory management through pathway analysis. In the southern United States, the Mexican fruit fly Anastrepha ludens is such a pest, and its incursions into Texas and California represent major threats to the agricultural systems of those regions. We developed a draft genome assembly for A. ludens, conducted range‐wide population genomics using restriction site‐associated DNA sequencing, and then developed and demonstrated a panel of highly differentiated diagnostic SNPs for source determination of intercepted flies in this system. Using 2,081 genomewide SNPs, we identified four populations across the range of A. ludens, corresponding to western Mexico, eastern Mexico/Texas, Guatemala/Belize/Honduras, and Costa Rica/Panama, with some intergradation present between clusters, particularly in Central America. From this population genomics framework, we developed a diagnostic panel of 28 highly differentiated SNPs that were able to recreate the genomewide population structure in this species. We demonstrated this panel on a set of test specimens, including specimens intercepted as part of regular trapping surveillance in Texas and California, and we were able to predict populations of origin for these specimens. This methodology presents a highly applied use of genomic techniques and can be implemented in any group of recurrently invading pests.