bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of hemicatenane-specific binding proteins by fractionation of Hela nuclei extracts
Authors: Rouis Oumayma , Broussard Cédric , Guillonneau François , Boulé Jean-Baptiste , Delagoutte Emmanuelle
Published: November 2019

DNA hemicatenanes (HCs) are DNA structures in which one strand of a double stranded helix passes through the two strands of another double stranded DNA. Frequently mentioned as DNA replication, recombination and repair intermediates, they have been proposed to participate in the spatial organization of chromosomes and in the regulation of gene expression. To explore potential roles of HCs in genome metabolism, proteins capable of binding specifically HCs were purified by fractionating nuclear extracts from Hela cells. This approach identified three RNA-binding proteins: the Tudor-Staphylococcal Nuclease Domain 1 (SND1) protein and two proteins from the Drosophila behavior human splicing family, the ParaSpeckle Protein Component 1 and the Splicing Factor Proline- and Glutamine- rich protein. Since these proteins were partially pure after fractionation, truncated forms of these proteins were expressed in E. coli and purified to near homogeneity. The specificity of their interaction with HCs was re-examined in vitro. The two truncated purified SND1 proteins exhibited a high specificity for HCs, suggesting a role of SND1 protein in targeting the basic transcription machinery to HC structures.
cando.py: Open source software for predictive bioanalytics of large scale drug-protein-disease data
Authors: Mangione William , Falls Zackary , Chopra Gaurav , Samudrala Ram
Published: November 2019

Elucidating drug-protein interactions is essential for understanding the beneficial effects of small molecule therapeutics in human disease states. Traditional drug discovery methods focus on optimizing the efficacy of a drug against a single biological target of interest. However, evidence supports the multitarget theory, i.e., drugs work by exerting their therapeutic effects via interaction with multiple biological targets. Analyzing drug interactions with a library of proteins provides further insight into disease systems while also allowing for prediction of putative therapeutics against specific indications. We present a Python package for analysis of drug-proteome and drug-disease relationships implementing the Computational Analysis of Novel Drug Opportunities (CANDO) platform [1–7]. The CANDO package allows for rapid drug similarity assessment, most notably via the bioinformatic docking protocol where billions of drug-protein interactions are rapidly scored and the similarity of drug-proteome interaction signatures is calculated. The package also implements a variety of bench-marking protocols to determine how well drugs are related to each other in terms of the indications/diseases for which they are approved. Drug predictions are generated through consensus scoring of the most similar compounds to drugs known to treat a particular indication. Support for comparing and ranking novel chemical entities, as well as machine learning modules for both benchmarking and putative drug candidate prediction is also available. The CANDO Python package is available on GitHub at https://github.com/ram-compbio/CANDO, through the Conda Python package installer, and at http://compbio.org/software/.
Leishmania infection induces a limited differential gene expression in the sand fly midgut
Authors: Coutinho-Abreu Iliano V. , Serafim Tiago D. , Meneses Claudio , Kamhawi Shaden , Oliveira Fabiano , Valenzuela Jesus G.
Published: November 2019

Background

Phlebotomine sand flies are the vectors of Leishmania worldwide. To develop in the sand fly midgut, Leishmania multiplies and undergoes multiple stage differentiations leading to the infective form, the metacyclic promastigotes. To gain a better understanding of the influence of Leishmania infection in midgut gene expression, we performed RNA-Seq comparing uninfected Lutzomyia longipalpis midguts and Leishmania infantum-infected Lutzomyia longipalpis midguts at seven time points which cover the various developmental Leishmania stages including early time points when blood digestion is taking place and late time points when the parasites are undergoing metacyclogenesis.

Results

Out of over 13,841 transcripts assembled de novo, only 113 sand fly transcripts, about 1%, were differentially expressed. Further, we observed a low overlap of differentially expressed sand fly transcripts across different time points suggesting a specific influence of each Leishmania stage on midgut gene expression. Two main patterns of sand fly gene expression modulation were noticed. At early time points (days 1-4), more transcripts were down-regulated by Leishmania infection at large fold changes (> −32 fold). Among the down-regulated genes, the transcription factor Forkhead/HNF-3 and hormone degradation enzymes were differentially regulated on day 4 and appear to be the upstream regulators of nutrient transport, digestive enzymes, and peritrophic matrix proteins. Conversely, at later time points (days 6 onwards), most of the differentially expressed transcripts were up-regulated by small fold changes (< 32 fold), and the molecular function of such genes are associated with the metabolism of lipids and detoxification of xenobiotics (P450).

Conclusion

Overall, it appears that Leishmania modulates sand fly gene expression early on in order to overcome the barriers imposed by the midgut, yet it behaves like a commensal at later time points, when modest midgut gene expression changes correlate with a massive amount of parasites in the anterior midgut.
Characterizing changes in land cover and forest fragmentation in Dhorpatan Hunting Reserve of Nepal from multi-temporal Landsat observations (1993-2018)
Authors: Sharma Sandeep , Bista Manjit , Mingshi Li
Published: November 2019

Recent centuries have experienced drastic changes in land cover around the world where Himalayan countries like Nepal have undergone changes in the past several decades because of increasing anthropogenic pressure, natural risks and climatic factors. Accordingly, forest fragmentation has also been increasing alarmingly, which is a matter of concern for natural resource management agencies and biodiversity conservation communities. In this study, we assessed land cover change and forest fragmentation trends in Dhorpatan Hunting Reserve of Nepal by implementing landscape fragmentation and recovery process models, and calculating landscape indices based on five-date land cover maps derived from Landsat satellite images from 1993 to 2018. Six land cover types including forest, grass land, barren land, agriculture & built-up, water bodies and snow & glaciers were determined after an intensive field survey. Diverse derived image features were fed to the Support Vector Machines classifier to create land cover maps, followed by a validation procedure using field samples and reference data. Land cover maps showed an increase in forest area from 37.32% (1993) to 39.26% (2018) and snow & glaciers from 1.72% (1993) to 2.15% (2018) while a decrease in grassland area from 38.78% (1993) to 36.41% (2018) and agriculture & built-up area from 2.39% (1993) to 1.80% (2018). Barren land and water body showed negligible changes. The spatial explicit process of forest fragmentation indicated that shrinkage was the most responsible factor of forest loss while expansion was dominant to increment for forest restoration. High dependency of people persists on the reserve for subsistence resources being a cause of forest fragmentation and posing threats to biodiversity. Focus should be made on strategies to decrease the anthropogenic pressure on the reserve. This requires approaches that provide sustainable alternative resources to the local people and innovations that will help them become less reliant on natural resources.
Effect of crocin and naringenin supplementation in cryopreservation medium on post-thawed rooster sperm quality and expression of apoptosis associated genes
Authors: Mehdipour Mahdieh , Kia Hossein Daghigh , Najafi Abouzar
Published: November 2019

The aim of our research was to examine the effects of crocin (0.5 (C0.5), 1 (C1) and 1.5 (C1.5) mM) and naringenin (50 (N50), 100 (N100) and 150 (N150) µM) in cryopreservation extender for freezing rooster semen. Sperm motility, viability, abnormalities, membrane integrity, mitochondrial activity, apoptosis status, lipid peroxidation (LP), GPX, SOD, TAC, the mRNA expression of pro-apoptotic (CASPASE 3) and anti-apoptotic (Bcl-2) genes, fertility and hatchability rate were investigated following freeze-thawing. C1 and N100 resulted in the higher (P < 0.05) total motility and progressive motility in comparison to the control group. C1 and N100 improved viability, membrane integrity and reduced lipid peroxidation. We found much higher values for mitochondria activity with C1 and N100 respect to the control group. The C1 and N100 showed lower percentages of early apoptosis when compared with control group. Also, C1 and N100 had higher TAC when compared with control group. The mRNA expression of BCL-2 in the C1 and N100 group were significantly higher than that of other treatments. The expression of CASPASES 3 was significantly reduced in C1 and N100 group (P < 0.05) when compared to control group. Significantly higher percentage of fertility and hatching rate were observed in C1 and N100 compared to the control group. In conclusion, crocin at 1 mM and naringenin at 100 µM seem to improve the post-thawing rooster semen quality, fertility and could protect the sperm against excessive ROS generation by reducing the pro-apoptotic (CASPASE 3) and increasing anti-apoptotic (Bcl-2) genes.
Effects of fasting induced carbohydrate depletion on murine ischemic skeletal muscle function
Authors: Schmidt Cameron A. , Goldberg Emma J. , Green Tom D. , Karnekar Reema R. , Brault Jeffrey J. , Miller Spencer G. , Amorese Adam J. , Yamaguchi Dean J. , Spangenburg Espen E. , McClung Joseph M.
Published: November 2019

Stored muscle carbohydrate supply and energetic efficiency constrain muscle functional capacity during exercise and are influenced by common physiological variables (e.g. age, diet, and physical activity level). Whether these constraints affect overall functional capacity or the timing of muscle energetic failure during acute ischemia is not known. We interrogated skeletal muscle contractile properties in two anatomically distinct hindlimb muscles that have well characterized differences in energetic efficiency (locomotory-extensor digitorum longus (EDL) and postural-soleus muscles) under conditions of reduced carbohydrate supply. 180 mins of acute ischemia resulted in complete energetic failure in all muscles tested, indicated by: loss of force production, substantial reductions in total adenosine nucleotide pool intermediates, and increased adenosine nucleotide degradation product - inosine monophosphate (IMP). These changes occurred in the absence of apparent myofiber structural damage assessed histologically by both transverse section and whole mount. Restriction of the available intracellular carbohydrate pool by fasting (~50% decrease in skeletal muscle) did not significantly alter the timing to muscle functional impairment or affect the overall force/work capacities of either muscle type. Fasting did cause rapid development of passive tension in both muscle types, which may have implications for optimal timing of reperfusion or administration of precision therapeutics.
Transcriptomic analysis of developing seeds in a wheat mutant RSD32 with reduced seed dormancy
Authors: Rikiishi Kazuhide , Sugimoto Manabu , Maekawa Masahiko
Published: November 2019

Seed dormancy, a major factor regulating pre-harvest sprouting, can severely hinder wheat cultivation. Abscisic acid biosynthesis and sensitivity play important roles in the regulation of seed dormancy. Reduced Seed Dormancy 32 (RSD32), a wheat mutant with reduced seed dormancy, is derived from the pre-harvest sprouting tolerant cultivar, Norin61. RSD32 is regulated by a single recessive gene and mutant phenotype expressed in a seed-specific manner. Results of this study show that Norin61 has a low germination index (GI) of whole seeds at 50 days after pollination (DAP) and earlier developmental stages. In RSD32, higher GI of whole seeds was found on DAP40. Dormancy was released by DAP50. Gene expressions in embryos of Norin61 and RSD32 were compared using RNA-seq analysis at the different developmental stages of DAP20, DAP30, and DAP40. Numbers of up-regulated gene in RSD32 are similar in all developmental stages. However, down-regulated genes in RSD32 are more numerous on DAP20 and DAP30 than on DAP40. Homologous genes related to circadian clock regulation and Ca2+ signaling pathway, which have fundamental functions for plant growth and development, are involved in down-regulated genes in RSD32 on DAP20. For central components affecting the circadian clock, genes homologous to CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY), which act as morning expressed genes, are expressed at lower levels in RSD32. However, higher expressions of TIMING OF CAB EXPRESSION 1 (TOC1) and PHYTOCLOCK 1 homologues, acting as evening expressed genes, are observed in RSD32. Homologues of Ca2+ signaling pathway related genes are found to be specifically expressed on DAP20 in Norin61. Lower expression is shown in RSD32. These results suggest that RSD32 mutation expresses on DAP20 and earlier seed developmental stages and suggest that circadian clock regulation and Ca2+ signaling pathway are involved in regulating wheat seed dormancy.
Syndecan-3 enhances anabolic bone formation through WNT signalling
Authors: Johnson de Sousa Brito Francesca Manuela , Butcher Andrew , Pisconti Addolorata , Poulet Blandine , Prior Amanda , Charlesworth Gemma , Sperinck Catherine , Scotto di Mase Michele , Bou-Gharios George , van ’t Hof Robert Jurgen , Daroszewska Anna
Published: November 2019

Osteoporosis is the most common age-related metabolic bone disorder, which is characterised by low bone mass and deterioration in bone architecture, with a propensity to fragility fractures. The best treatment for osteoporosis relies on stimulation of osteoblasts to form new bone and restore bone structure, however anabolic therapeutics are few and their use is time-restricted. Here we report that Syndecan-3 (SDC3) increases new bone formation through enhancement of WNT signalling. Young adultSdc3−/−mice have a low bone volume phenotype associated with reduced bone formation, increased bone marrow adipose tissue (BMAT), increased bone fragility and a blunted anabolic bone formation response to mechanical loading. The premature osteoporosis-like phenotype ofSdc3−/−mice is primarily explained by delayed osteoblast maturation and impaired osteoblast function, with contributing increased osteoclast-mediated bone resorption. Mechanistically, SDC3 enhances canonical WNT signalling in osteoblasts through stabilisation of Frizzled 1, making SDC3 an attractive target for novel anabolic drug development.
Identifying dynamic, partially occupied residues using anomalous scattering
Authors: Rocchio Serena , Duman Ramona , El Omari Kamel , Mykhaylyk Vitaliy , Orr Christian , Yan Zhen , Salmon Loïc , Wagner Armin , Bardwell James C. A. , Horowitz Scott
Published: November 2019

Although often presented as taking single `snapshots' of the conformation of a protein, X-ray crystallography provides an averaged structure over time and space within the crystal. The important but difficult task of characterizing structural ensembles in crystals is typically limited to small conformational changes, such as multiple side-chain conformations. A crystallographic method was recently introduced that utilizes residual electron and anomalous density (READ) to characterize structural ensembles encompassing large-scale structural changes. Key to this method is an ability to accurately measure anomalous signals and distinguish them from noise or other anomalous scatterers. This report presents an optimized data-collection and analysis strategy for partially occupied iodine anomalous signals. Using the long-wavelength-optimized beamline I23 at Diamond Light Source, the ability to accurately distinguish the positions of anomalous scatterers with occupancies as low as ∼12% is demonstrated. The number and positions of these anomalous scatterers are consistent with previous biophysical, kinetic and structural data that suggest that the protein Im7 binds to the chaperone Spy in multiple partially occupied conformations. Finally, READ selections demonstrate that re-measured data using the new protocols are consistent with the previously characterized structural ensemble of the chaperone Spy with its client Im7. This study shows that a long-wavelength beamline results in easily validated anomalous signals that are strong enough to be used to detect and characterize highly disordered sections of crystal structures.
X-ray crystallographic studies on the hydrogen isotope effects of green fluorescent protein at sub-ångström resolutions
Authors: Tai Yang , Takaba Kiyofumi , Hanazono Yuya , Dao Hoang-Anh , Miki Kunio , Takeda Kazuki
Published: November 2019

Hydrogen atoms are critical to the nature and properties of proteins, and thus deuteration has the potential to influence protein function. In fact, it has been reported that some deuterated proteins show different physical and chemical properties to their protiated counterparts. Consequently, it is important to investigate protonation states around the active site when using deuterated proteins. Here, hydrogen isotope effects on the S65T/F99S/M153T/V163A variant of green fluorescent protein (GFP), in which the deprotonated B form is dominant at pH 8.5, were investigated. The pH/pD dependence of the absorption and fluorescence spectra indicates that the protonation state of the chromophore is the same in protiated GFP in H2O and protiated GFP in D2O at pH/pD 8.5, while the pK
a of the chromophore became higher in D2O. Indeed, X-ray crystallographic analyses at sub-ångström resolution revealed no apparent changes in the protonation state of the chromophore between the two samples. However, detailed comparisons of the hydrogen OMIT maps revealed that the protonation state of His148 in the vicinity of the chromophore differed between the two samples. This indicates that protonation states around the active site should be carefully adjusted to be the same as those of the protiated protein when neutron crystallographic analyses of proteins are performed.
[Oxybis(ethane-1,2-diyl)]bis(dimethylammonium) octamolybdate dihydrate
Authors: Ermert David M. , Gembicky Milan , Rheingold Arnold L.
Published: November 2019

The title compound, (C8H22N2O)2[Mo8O26]·H2O, (cis-H2
L)2[β-Mo8O26]·H2O, where L = (bis[2-N,N-dimethylamino)ethyl] ether), was synthesized from bis[2-(dimethylamino)ethyl] ether and MoO3 under solvothermal conditions and characterized by multinuclear NMR and single-crystal X-ray diffraction techniques. The structure displays two [oxybis(ethane-1,2-diyl)]bis(dimethylammonium), or [cis-H2
L]2+, cations, a central [β-Mo8O26]4− anionic cluster consisting of eight distorted MoO6 octahedra, and two water molecules in their deuterated form. The central anion lies across an inversion center. The [cis-H2
L]2+ cations are hydrogen bonded to the central [β-Mo8O26]4− cluster via bridging water molecules. In the crystal, O—H...O hydrogen bonds link the components into chains along [010]. Weak C—H...O hydrogen bonds link these chains into a three-dimensional network.
Post internationalization strategies of born global service firms
Authors: Dhandapani Karthik , Upadhyayula Rajesh Srinivas , Basant Rakesh
Published: November 2019

Purpose

Extant literature suggests that post-entry internationalization strategies and performance implications of born globals are an under-researched area. This paper aims to examine the internationalization strategies of born global service firms (BGSFs) and performance implications thereof through strategic group analysis of hand-collected data from Indian information technology (IT) firms.

Design/methodology/approach

Strategic group analysis has been used to examine if there are any differences in the strategic decisions across firms and if there are any implications of these strategies on the performance of firms. The strategic group approach helps understand not only the antecedents but also the strategic trade-offs that different groups of BGSFs face after internationalization. The study uses Indian IT industry as the context for analysis of BGSFs, as studies have found that the Indian IT industry to have significant presence of born globals.

Findings

Four distinct strategic paths were found to be followed by BGSFs. In addition, the nature of services and ways of mobilization or deployment of resources explain the different internationalization paths and consequently performance. The performance differences primarily stem from the choice of degree of commitment and scope of internationalization.

Practical implications

This study provides distinct insights to practice by charting internationalization paths for an emerging born global.

Originality/value

This paper contributes to the theory on born globals by using strategic lens to explain the internationalization paths and their performance implications.
Business success factors of Muslim women entrepreneurs in Indonesia
Authors: Rafiki Ahmad , Nasution Fahmi Natigor
Published: November 2019

Purpose

This paper aims to identify important factors affecting the success of Muslim women entrepreneurs (WOE) in the Medan city, North Sumatera province in Indonesia. There are 19 factors that are derived from trait-based, social psychological-based and behavioral-based approaches.

Design/methodology/approach

A descriptive, exploratory factor and confirmatory factor analyses are used in this study. There are 110 respondents of members of Indonesian Woman Entrepreneur Association and Indonesian Muslim Women Entrepreneur Association in North Sumatera, Indonesia.

Findings

The profile of Muslim WOE is elaborated, and 19 important factors are rated, while the top three factors of each approach are analyzed and discussed. This paper prioritizes the important factors and develops a framework that acts as a reference for success factors of Muslim WOE.

Research limitations/implications

For the government, the rules and regulations must be created to support and facilitate the Muslim WOE and to conduct programs to enhance the development of their business. While for the researchers, they could see an increasing interest of Muslim WOE in business. With a combination of frameworks, the list of important success factors can be compared with the research studies by male counterparts and can be used for further studies.

Originality/value

The success in business is achievable regardless of gender difference. The Muslim WOE make everyone recognize the challenges that they were exposed to and the struggles that they have overcome in managing a business as what men may have already been through.
Does CSR influence firm performance? A longitudinal study of SME sectors of Pakistan
Authors: Ikram Muhammad , Sroufe Robert , Mohsin Muhammad , Solangi Yasir Ahmed , Shah Syed Zulfiqar Ali , Shahzad Farrukh
Published: November 2019

Purpose

This study aims to examine whether corporate social responsibility (CSR) activities influence firm performance based on a longitudinal survey for small and medium-sized enterprises (SMEs) in Pakistan. Empirical studies suggest that the SME sector plays an essential role in the economic development of Pakistan and can be considered the backbone of the economy.

Design/methodology/approach

The data for this study were collected from SMEs located in the cities of Karachi, Lahore and Faisalabad in Pakistan. A well-designed questionnaire was administrated over 240 entrepreneurs to analyze and measure the impact of CSR on financial performance for a 12-month period. The authors used econometric analysis of the data using structural equation modeling.

Findings

Results reveal significant relationships between CSR and two determinants of firm performance, namely, employee commitment and corporate reputation.

Research limitations/implications

Findings of the study are important for policymakers, entrepreneurs and other professionals in SMEs sectors both in under-developed and, with further application and exploration, in developing countries.

Originality/value

There is no single longitudinal study prior to this has been carried out on the relationships of CSR and firm performance in the SME sector in the context of the Pakistani economy. Hence, this study significantly fills an important gap in the research.
Identifying key actors in an international crisis using dynamic network analysis
Authors: Tawadros Amira S.N. , Soliman Sally
Published: November 2019

Purpose

The purpose of this study is to examine the extent to which dynamic network analysis (DNA), text mining and natural language processing (NLP) are helpful research tools in identifying the key actors in a complex international crisis. The study uses these tools to identify the key actors in the Syrian crisis as a case study to validate the proposed algorithm.

Design/methodology/approach

To achieve its main purpose, the study uses a collection of three methodologies, namely, DNA, text mining and NLP.

Findings

The results of the analysis show four key actors in the Syrian crisis, namely, Russia, the USA, Turkey and China. The results also reveal changes in their powerful positions from 2012 to 2016, which matches the changes that occurred in the real world. The matching between the findings of the proposed algorithm and the real world events that happened in Syria validate our proposed algorithm and proves that the algorithm can be used in identifying the key actors in complex international crises.

Originality/value

The importance of the study lies in two main points. It proposes a new algorithm that mixes NLP, network extraction from textual unstructured data and DNA to understand and monitor changes occurring in a complex international crisis. It applies the proposed algorithm on the Syrian crisis as a case study to identify the key actors and hence validate the proposed algorithm.
Case of chickenpox in which varicella zoster virus genotype E was identified for the first time in Japan
Authors: Egawa Gyohei , Egawa Kiyofumi , Kabashima Kenji
Published: November 2019

Varicella zoster virus (VZV) is now classified into seven genotypes, and type J (clade 2) is known as an exclusively prevalent genotype in Japan. Here, we describe an adult Japanese patient who was suffering from chickenpox caused by VZV type E, the most prevalent genotype in Western Europe. Because the eruptions were distributed over the trunk and limbs and the patient had a high titer of immunoglobulin G against VZV, we diagnosed this case as secondary VZV infection. To investigate the current prevalence of VZV genotypes in Japan, we examined the genotype of VZV in an additional 49 Japanese varicella/zoster patients who visited our hospital during 2018–2019. We found that VZV type E was still an exceptionally rare genotype (1/50) in Japan. Because foreign nationals living in Japan who carry VZV genotypes other than type J are increasing in number, secondary chickenpox may increase in Japan in the near future, as well as in the USA where multiple VZV genotypes are distributed.
A directly GP130‐targeting small molecule ameliorates collagen‐induced arthritis (CIA) by inhibiting IL‐6/GP130 signalling and Th17 differentiation
Authors: Park Yeon‐Hwa , Kim Hee Jung , Heo Tae‐Hwe
Published: November 2019

Rheumatoid arthritis is a chronic inflammatory disease associated with joint inflammation and destruction driven by T helper 17 (Th17) cells. Interleukin‐6 (IL‐6) is secreted by many cell types, including macrophages and synovial fibroblasts. It induces the differentiation and function of Th17 cells that can increase lymphocytic infiltration in the joint. LMT‐28 can suppress IL‐6 signalling through direct binding to glycoprotein‐130 and alleviate inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease. The purpose of this study was to assess whether LMT‐28 could potently inhibit Th17 differentiation and to determine the mechanism involved in the attenuating effect of LMT‐28 on rheumatoid arthritis through the IL‐6 signalling pathway. LMT‐28 reduced the arthritis score and showed protective effects against bone and cartilage destruction in collagen‐induced arthritis (CIA) mice. In mice with CIA, LMT‐28 markedly decreased serum levels of IL‐6, TNF and IL‐1β compared to vehicle control. Moreover, LMT‐28 attenuated Th17 cell activation in lymph nodes of CIA mice. We demonstrated that LMT‐28 suppressed differentiation of Th17 in mouse splenocytes and human peripheral blood mononuclear cells (PBMCs). Additionally, LMT‐28 inhibited phosphorylation of GP130, STAT3 and ERK induced by Hyper‐IL‐6 in human fibroblast‐like synoviocytes (FLS). Collectively, these results suggest that LMT‐28 can inhibit differentiated/activated‐Th17 cells in rheumatoid arthritis by blocking activation of the STAT3 pathway. LMT‐28 can attenuate rheumatoid arthritis by inhibiting differentiation/activation of Th17 cells and suppressing the proliferation and signalling activation of the IL‐6/solubleIL‐6 receptor complex stimulated FLS.
Geographical patterns and environmental drivers of functional diversity and trait space of amphibians of Europe
Authors: Tsianou Mariana A. , Kallimanis Athanasios S.
Published: November 2019

Amphibians are among the most endangered group of vertebrates. To conserve their diversity we need to comprehend how functional diversity and species traits vary across environmental gradients. We investigate the distribution of functional diversity (functional richness–functional dispersion–functional evenness) and the environmental drivers (climate, energy availability, landscape and anthropogenic attributes) of these patterns for the 68 amphibian species of Europe using generalized least squares models and hierarchical partitioning. Based on eight functional traits, species were arranged in a multidimensional functional trait space and principal coordinates analysis (PCoA) was applied to investigate the occupancy of this space by amphibians. Functional richness mirrored species richness pattern and decreased towards higher latitudes; while, functional dispersion showed an even stronger negative correlation with latitude. Functional evenness did not display a clear latitudinal trend. Areas with higher functional richness and functional dispersion are associated with lower temperature seasonality and increased land cover diversity, in contrast areas with higher functional evenness are characterized by lower mean annual temperature. Climate seasonality mostly influenced the traits related to the first two PCoA axes (i.e., foraging location, mobility mode) which could have been considered as functional response traits and could be used as indicators to examine how communities respond to environmental change. Our work describes the macroecological patterns and discusses the relative importance of alternative underlying mechanisms driving functional diversity of this high‐risk taxonomical group and highlight that species richness presents only part of the biodiversity patterns, while other facets like functional evenness behave distinctively differently.
LncRNA TUG1 contributes to ESCC progression via regulating miR‐148a‐3p/MCL‐1/Wnt/β‐catenin axis in vitro
Authors: Tang Yin , Yang Ping , Zhu Yunfeng , Su Yong
Published: November 2019

Background

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies. Latest studies report that long noncoding RNAs (LncRNAs) play an essential role in diversified pathological processes of ESCC, although the mechanism by which they do so remains unknown. This study aimed to explore the parts of lncRNA taurine upregulated gene 1 (TUG1) in ESCC tissues and cells, its biofunctional effect and its underlying regulatory mechanism in ESCC.

Methods

The levels of TUG1 and miR‐148a‐3p were detected by quantitative real‐time polymerase chain reaction (qRT‐PCR) in ESCC cells and tissues. The biofunctional effects were examined by MTT, flow cytometry, and transwell assay. The protein expression levels of epithelial‐mesenchymal transition (EMT)‐related proteins and MCL‐1 were determined by western blot analysis. The binding sites between miR‐148a‐3p and TUG1 or MCL‐1 were predicted by online software starBase and confirmed by dual luciferase reporter assay.

Results

The mRNA expression of TUG1 was significantly upregulated in ESCC tissues or cells, and was negatively correlated to miR‐148a‐3p expression in tissues. Knockdown of TUG1 inhibited the proliferation, migration, and invasion, promoted apoptosis, and relieved the EMT progression in EC9706 and OE19 cells. Besides, knockdown of miR‐148a‐3p inverted positive effects from TUG1 deletion on ESCC cells. Besides, MCL‐1 reversed the inhibitive effects from TUG1 deletion on expression of EMT‐associated proteins (Wnt1, C‐myc, CyclinD1, and β‐catenin) above subsequently.

Conclusion

TUG1 regulated the biofunction and EMT progression of ESCC by mediating miR‐148a‐3p/MCL‐1/Wnt/β‐catenin axis in vitro.
Development of a Scale Based on Nursing Outcome Classification “Dignified Life Closure” (1307) to Assess End‐of‐Life Dignity of Patients in Care Homes for the Elderly
Authors: Puente‐Fernández Daniel , Palma‐Ayllón Elena , Sánchez‐García María Remedios , Hueso‐Montoro César , Esteban‐Burgos Ana Alejandra , Montoya‐Juárez Rafael
Published: November 2019

PURPOSE

To develop and pilot the DD‐14 scale, a 14‐indicator scale based on the Nursing Outcome Classification “Dignified life closure” (1307).

METHODS

Sixteen experts selected 14 indicators for Spanish populations. Six care home nurses piloted the scale in 50 terminal patients without cognitive impairment. Factorial and reliability analyses were performed and correlations were determined with dependency, symptomatology, and palliative care quality.

FINDINGS

DD‐14 demonstrated high reliability (α = 0.916) and a stable factorial structure. It was not influenced by sex, age, or disease and correlated positively with the Barthel index (r = .622; p = .00) and negatively with the Palliative Outcome Scale (r = −.542;p = .00).

CONCLUSIONS

DD‐14 is a useful scale for evaluating end‐of‐life dignity.

IMPLICATIONS FOR NURSING PRACTICE

This instrument could be useful in planning nursing interventions.
Effects of post‐operative furosemide in adult surgical patients: A systematic review and meta‐analysis of randomised clinical trials
Authors: Winther‐Olesen Marie , Møller Morten Hylander , Johansen Karina K. , Aasvang Eske K.
Published: November 2019

Background

Acute kidney injury (AKI) is associated with increased morbidity and mortality and may present as oliguria in the post‐operative phase. Diuretics, including furosemide, are commonly used in post‐operative patients. Accordingly, we aimed to assess the balance between benefits and harms of furosemide post‐operatively in adult surgical patients.

Methods

We conducted a systematic review with meta‐analysis according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statements, the Cochrane Handbook and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. We included randomised clinical trials (RCTs) comparing post‐operative treatment with furosemide vs no furosemide in adult surgical patients. Risk ratios (RR) with 95% confidence intervals (CI) were estimated by conventional meta‐analysis and trial sequential analysis (TSA).

Results

Two thousand five hundred and sixty seven records were identified and four trials with 325 patients in total were included. All were adjudicated as having overall high risk of bias. We observed no statistically significant difference between furosemide‐ vs no furosemide‐treated patients in any of the predefined outcome measures, including AKI (RR 1.07, 95% CI 0.43‐2.65), all‐cause mortality (RR 1.73, 95% CI 0.62‐4.80, use of vasopressors post‐operatively (RR 1.04, 95% CI 0.74‐1.44) or need for renal replacement therapy (RR 3.87, 95% CI 0.44‐33.99). TSA highlighted sparse data, and the overall quality of evidence was very low.

Conclusion

In this systematic review, we found that the quantity and quality of evidence for using furosemide post‐operatively in adult surgical patients were very low with no firm evidence for benefit or harm.
Decreased pericellular matrix production and selection for enhanced cell membrane repair may impair osteocyte responses to mechanical loading in the aging skeleton
Authors: Hagan Mackenzie L. , Yu Kanglun , Zhu Jiali , Vinson Brooke N. , Roberts Rachel L. , Montesinos Cartagena Marlian , Johnson Maribeth H. , Wang Liyun , Isales Carlos M. , Hamrick Mark W. , McNeil Paul L. , McGee‐Lawrence Meghan E.
Published: November 2019

Transient plasma membrane disruptions (PMD) occur in osteocytes with in vitro and in vivo loading, initiating mechanotransduction. The goal here was to determine whether osteocyte PMD formation or repair is affected by aging. Osteocytes from old (24 months) mice developed fewer PMD (−76% females, −54% males) from fluid shear than young (3 months) mice, and old mice developed fewer osteocyte PMD (−51%) during treadmill running. This was due at least in part to decreased pericellular matrix production, as studies revealed that pericellular matrix is integral to formation of osteocyte PMD, and aged osteocytes produced less pericellular matrix (−55%). Surprisingly, osteocyte PMD repair rate was faster (+25% females, +26% males) in osteocytes from old mice, and calcium wave propagation to adjacent nonwounded osteocytes was blunted, consistent with impaired mechanotransduction downstream of PMD in osteocytes with fast PMD repair in previous studies. Inducing PMD via fluid flow in young osteocytes in the presence of oxidative stress decreased postwounding cell survival and promoted accelerated PMD repair in surviving cells, suggesting selective loss of slower‐repairing osteocytes. Therefore, as oxidative stress increases during aging, slower‐repairing osteocytes may be unable to successfully repair PMD, leading to slower‐repairing osteocyte death in favor of faster‐repairing osteocyte survival. Since PMD are an important initiator of mechanotransduction, age‐related decreases in pericellular matrix and loss of slower‐repairing osteocytes may impair the ability of bone to properly respond to mechanical loading with bone formation. These data suggest that PMD formation and repair mechanisms represent new targets for improving bone mechanosensitivity with aging.
Video Discharge Instructions for Acute Otitis Media in Children: A Randomized Controlled Open‐label Trial
Authors: Belisle Sheena , Dobrin Andrei , Elsie Sharlene , Ali Samina , Brahmbhatt Shaily , Kumar Kriti , Jasani Hardika , Miller Michael , Ferlisi Frank , Poonai Naveen
Published: November 2019

Background

Thirty percent of children with acute otitis media (AOM) experience symptoms < 7 days after initiating treatment, highlighting the importance of comprehensive discharge instructions.

Methods

We randomized caregivers of children 6 months to 17 years presenting to the emergency department (ED) with AOM to discharge instructions using a video on management of pain and fever to a paper handout. The primary outcome was the AOM Severity of Symptom (AOM‐SOS) score at 72 hours postdischarge. Secondary outcomes included caregiver knowledge (10‐item survey), absenteeism, recidivism, and satisfaction (5‐item Likert scale).

Results

A total of 219 caregivers were randomized and 149 completed the 72‐hour follow‐up (72 paper and 77 video). The median (IQR) AOM‐SOS score for the video was significantly lower than paper, even after adjusting for preintervention AOM‐SOS score and medication at home (8 [7–11] vs. 10 [7–13], respectively; p = 0.004). There were no significant differences between video and paper in mean (±SD) knowledge score (9.2 [±1.3] vs. 8.8 [±1.8], respectively; p = 0.07), mean (±SD) number of children that returned to a health care provider (8/77 vs. 10/72, respectively; p = 0.49), mean (±SD) number of daycare/school days missed by child (1.2 [±1.5] vs. 1.1 [±2.1], respectively; p = 0.62), mean (±SD) number of workdays missed by caregiver (0.5 [±1] vs. 0.8 [±2], respectively; p = 0.05), or median (IQR) satisfaction score (5 [4–5] vs. 5 [4–5], respectively; p = 0.3).

Conclusions

Video discharge instructions in the ED are associated with less perceived AOM symptomatology compared to a paper handout.
Novel Ethanol‐Sensitive Mutants Identified in an F3 Forward Genetic Screen
Authors: Swartz Mary E. , Lovely Charles Ben , McCarthy Neil , Kuka Tim , Eberhart Johann K.
Published: November 2019

Background

Fetal alcohol spectrum disorders (FASD) collectively refer to all deleterious outcomes due to prenatal alcohol exposures. Alterations to the face are common phenotypes in FASD. While alcohol exposure is the underlying cause of FASD, many variables modify the outcomes of such exposures. Genetic risk is one such variable, yet we still have a limited understanding of the nature of the genetic loci mediating susceptibility to FASD.

Methods

We employed ENU‐based random mutagenesis in zebrafish to identify mutations that enhanced the teratogenicity of ethanol (EtOH). F3 embryos obtained from 126 inbred F2 families were exposed to 1% EtOH in the medium (approximately 41 mM tissue levels). Zebrafish stained with Alcian Blue and Alizarin Red were screened for qualitative alterations to the craniofacial skeleton between 4 and 7 days postfertilization (dpf).

Results

In all, we recovered 6 EtOH‐sensitive mutants, 5 from the genetic screen itself and one as a background mutation in one of our wild‐type lines. Each mutant has a unique EtOH‐induced phenotype relative to the other mutant lines. All but 1 mutation appears to be recessive in nature, and only 1 mutant, au29, has apparent craniofacial defects in the absence of EtOH. To validate the genetic screen, we genetically mapped au29 and found that it carries a mutation in a previously uncharacterized gene, si:dkey‐88l16.3.

Conclusions

The phenotypes of these EtOH‐sensitive mutants differ from those in previous characterizations of gene–EtOH interactions. Thus, each mutant is likely to provide novel insights into EtOH teratogenesis. Given that most of these mutants only have craniofacial defects in the presence of EtOH and our mapping of au29, it is also likely that many of the mutants will be previously uncharacterized. Collectively, our findings point to the importance of unbiased genetic screens in the identification, and eventual characterization, of risk alleles for FASD.
Comparing rates and characteristics of ambulance attendances related to extramedical use of pharmaceutical opioids in Victoria, Australia from 2013 to 2018
Authors: Nielsen Suzanne , Crossin Rose , Middleton Melissa , Lam Tina , Wilson James , Scott Debbie , Martin Catherine , Smith Karen , Lubman Dan
Published: November 2019

Background and aims

Despite increases in opioid prescribing and related morbidity and mortality, few studies have comprehensively documented harms across opioid types. We examined a population‐wide indicator of extramedical pharmaceutical opioid‐related harm to determine if the supply‐adjusted rates of ambulance presentations, the severity of presentations or other attendance characteristics differed by opioid type.

Design

Retrospective observational study of coded ambulance patient care records related to extramedical pharmaceutical opioid use, January 2013 to September 2018.

Setting

Australia

Cases

Primary analyses used Victorian data (n = 9823), with available data from other Australian jurisdictions (n = 4338) used to determine generalizability.

Measurements

We calculated supply‐adjusted rates of attendances using Poisson regression, and used multinomial logistic regression to compare demographic, presentation severity, mental health, substance use and other characteristics of attendances associated with seven pharmaceutical opioids.

Findings

In Victoria, the highest rates of attendance [per 100 000 oral morphine equivalent mg (OME)] were for codeine (0.273/100 000) and oxycodone (0.113/100 000). The lowest rates were for fentanyl (0.019/100 000) and tapentadol (0.005/100 000). Oxycodone–naloxone rates (0.031/100 000) were lower than for oxycodone as a single ingredient (0.113/100 000). Fentanyl‐related attendances were associated with the most severe characteristics, most likely to be an accidental overdose, most likely to have naloxone administered and least likely to be transferred to hospital. In contrast, codeine‐related attendances were more likely to involve suicidal thoughts/behaviours, younger females and be transported to hospital. Supply‐adjusted attendance rates for individual opioids were stable over time. Victorian states were broadly consistent with non‐Victorian states.

Conclusions

In Australia, rates and characteristics of opioid‐related harm vary by opioid type. Supply‐adjusted ambulance attendance rates appear to be both stable over time and unaffected by large changes in supply.
Moral hazard and subsidized crop insurance
Authors: Wu Shenan , Goodwin Barry K. , Coble Keith
Published: November 2019

Along with adverse selection, moral hazard is one of the major hurdles that private and public insurance plans must contend with. Moral hazard occurs if risks are endogenous to a producer's behavior and if the insurer is unable to properly monitor the insured. We review the role of moral hazard in the US crop insurance program. We conduct an empirical analysis of one important aspect of the US crop insurance program—prevented planting. This provision provides indemnity payments if conditions are not suitable for planting. The program has been the subject of considerable controversy, especially during 2019, when the rate of claims is expected to be especially high. Because loss adjustors may encounter difficulties in assessing the weather conditions associated with prevented planting claims, the program is susceptible to moral hazard. We consider the extent to which prevented planting claims may be endogenous to prices. We find significant evidence of moral hazard. The likelihood of prevented planting claims increases as the expected market price decreases or as fertilizer costs increase for corn and soybeans in the Prairie Pothole Region and for grain sorghum and cotton in all states.
The Corporate Production of Nationalism
Authors: Koch Natalie
Published: November 2019

States, government officials, cultural elites, and ordinary citizens are typically the leading characters in academic treatises on nationalism—cast as the primary producers and consumers of nationalist ideology. Yet this conventional focus obscures the manycorporateaspects of nationalism. Drawing from the literature on “commercial nationalism”, this article examines the corporate production of nationalism surrounding National Day holiday celebrations in Qatar and the United Arab Emirates (UAE). Pairing participant observation and textual analysis of advertising landscapes, I illustrate how domestic and foreign corporations are key actors in (re)producing nationalist discourse—and state power—in the Gulf states. By situating this comparative case study in the broader literature on commercial nationalism, I argue that Qatar and the UAE are in fact typical of how corporate actors around the world routinely reinforce scripts that essentialise the “nation” by drawing upon and, in effect,producingnationalism—and their own commercial interests.