bluuebunny/crossref_metadata_2025 huggingface dataset:
Age-associated changes of cytochrome P450 and related phase-2 gene/proteins in livers of rats
Authors: Xu Shangfu , Hu Anling , Xie Lu , Liu Jiajia , Wu Qin , Liu Jie J
Published: April 2019

Cytochrome P450s (CYPs) are phase-I metabolic enzymes playing important roles in drug metabolism, dietary chemicals and endogenous molecules. Age is a key factor influencing P450s expression. Thus, age-related changes of CYP 1-4 families and bile acid homeostasis-related CYPs, the corresponding nuclear receptors and a few phase-II genes were examined. Livers from male Sprague-Dawley rats at fetus (-2 d), neonates (1, 7, and 14 d), weanling (21 d), puberty (28 and 35 d), adulthood (60 and 180 d), and aging (540 and 800 d) were collected and subjected to qPCR analysis. Liver proteins from 14, 28, 60, 180, 540 and 800 days of age were also extracted for selected protein analysis by Western-blot. In general, there were three patterns of their expression: Some of the drug-metabolizing enzymes and related nuclear receptors were low in fetal and neonatal stage, increased with liver maturation and decreased quickly at aging (AhR, Cyp1a1, Cyp2b1, Cyp2b2, Cyp3a1, Cyp3a2, Ugt1a2); the majority of P450s (Cyp1a2, Cyp2c6, Cyp2c11, Cyp2d2, Cyp2e1, CAR, PXR, FXR, Cyp7a1, Cyp7b1. Cyp8b1, Cyp27a1, Ugt1a1, Sult1a1, Sult1a2) maintained relatively high levels throughout the adulthood, and decreased at 800 days of age; and some had an early peak between 7 and 14 days (CAR, PXR, PPARα, Cyp4a1, Ugt1a2). The protein expression of CYP1A2, CYP2B1, CYP2E1, CYP3A1, CYP4A1, and CYP7A1 corresponded the trend of mRNA changes. In summary, this study characterized three expression patterns of 16 CYPs, 5 nuclear receptors, and 4 phase-II genes during development and aging in rat liver, adding to our understanding of age-related CYP expression changes and age-related disorders.
Analysis of virulence factors and emm typing of Streptococcus pyogenes clinical isolates.
Authors: Sambrano Gustavo Enck , Riboldi Gustavo P , Reiter Keli C , Paim Thiago Galvão da Silva , Tolfo Neidmar Correa , Soares Renata O , d'Azevedo Pedro A
Published: April 2019

Background: Streptococcus pyogenes, a Group A streptococci (GAS), is an important human pathogen that causes a wide range of infections. Methods: Twenty five clinical isolates of S. pyogenes were submitted to an emm typing and to a Real-time PCR analysis for 23 important virulence factors. Results: Fourteen emm types were found and the emm1 type was the most prevalent. The majority of the isolates were classified as emm pattern E, followed by A-C3. No pattern D was found. Among the virulence factors, the most prevalent were SpeG, Slo, C5a-peptidase and SPNA. Phage encoded virulence genes were also found among the strains, such as mf-2, SpeJ and SpeL. Discussion: The emm1 type was the most prevalent while the 13 others M types were distributed along the strains. No tissue tropism was found on the isolates. The virulence factors analysis demonstrated that chromosomally and phage-encoded genes were found, which confers a potential for high virulent micro-organisms.
Endoplasmic reticulum-associated SKN-1A/Nrf1 mediates a cytoplasmic unfolded protein response and promotes longevity
Authors: Lehrbach Nicolas J , Ruvkun Gary
Published: April 2019

Unfolded protein responses (UPRs) safeguard cellular function during proteotoxic stress and aging. In a previous paper (Lehrbach and Ruvkun, 2016) we showed that the ER-associated SKN-1A/Nrf1 transcription factor activates proteasome subunit expression in response to proteasome dysfunction, but it was not established whether SKN-1A/Nrf1 adjusts proteasome capacity in response to other proteotoxic insults. Here, we reveal that misfolded endogenous proteins and the human amyloid beta peptide trigger activation of proteasome subunit expression by SKN-1A/Nrf1. SKN-1A activation is protective against age-dependent defects caused by accumulation of misfolded and aggregation-prone proteins. In a C. elegans Alzheimer’s disease model, SKN-1A/Nrf1 slows accumulation of the amyloid beta peptide and delays adult-onset cellular dysfunction. Our results indicate that SKN-1A surveys cellular protein folding and adjusts proteasome capacity to meet the demands of protein quality control pathways, revealing a new arm of the cytosolic UPR. This regulatory axis is critical for healthy aging and may be a target for therapeutic modulation of human aging and age-related disease.
Yazılı Basında Mülteci Haberleri Üzerine Karşılaştırmalı Bir İnceleme: The Guardian ve Hürriyet Örneği / A Comparative Study on Refugee News in Press: Example of The Guardian and Hürriyet
Authors: Kasap Fevzi , Dolunay Ayhan , İneci Özcan
Published: April 2019

Abstract

With the invention of writing around BC 3000 and the invention of the printing in 1450s, developments occurred in culture, art, science and communication fields and the human beings started to communicate and interact with each other. The immigration phenomenon, which can date back as far as the human history also developed and continued to increase with the globalization and the developments in communication tools.  These two important facts developed and increased parallel with each other and they became the most important subjects of the world in recent times. The refugee and asylum-seeker movements form the world agenda nowadays and it continues to be in the agenda due to press and media organisations following the subject closely and creating a public opinion. The growing refugee crisis gained speed and continued to increase especially with the protests and civil wars called “The Arab Spring”, happening in the Arabic peninsula, and became the most emphasized topic by the media and the press agencies of many countries. In this study, six days’ news coverage on the topic of refugees in The Guardian in England and the Hürriyet newspaper in Turkey were analysed and compared. The study will try to explain and focus on the similarities and differences between these news contents, from what perspective the refugee problems are looked at and how they are reported in the news.

Öz

M.Ö 3000’li yıllarda yazının bulunması ve 1450’li yıllarda matbaanın bulunmasıyla kültür, sanat, bilim ve iletişim alanında gelişmeler meydana gelmiş, insanlar birbirleriyle iletişim ve etkileşime geçmeye başlamışlardır. İnsanlık tarihi kadar eski olan göç olgusu da aynı şekilde küreselleşme ve iletişim araçlarına koşut olarak gelişim göstermiştir. Bahse konu olgular, günümüz dünyasında, yüksek önemi haiz yapıdadır. Bu çeçervede, mülteci ve sığınmacı hareketleri, basın yayın kuruluşlarının konuyu yakından takip edip kamuoyu oluşturmalarıyla, dünya gündeminde yer bulmayı sürdürmektedir. Özellikle Arap yarımadasındaki “Arap Baharı” olarak adlandırılan, protesto ve iç savaşlarla hız kazanan ve artarak devam eden mülteci krizi birçok ülkenin basın yayın kuruluşları tarafından önemle üzerinde durulan bir konu haline gelmiştir. Bu çalışmada İngiltere’deki The Guardian ve Türkiye’deki Hürriyet gazetelerinin mülteci konusu hakkında yapmış oldukları altı günlük haberleri incelenip karşılaştırılmıştır. Bu haberler arasındaki benzerlik ve farklılıklar üzerinde durularak haberlerde mülteci sorunlarına hangi açıdan bakıldığı ve değinildiği, haberlerin içerikleri incelenerek açıklanmaya çalışılacaktır.
CopyrightX [Course Review]
Authors: Cirasella Jill
Published: April 2019

Review of the free online course CopyrightX.
Preparation of mitochondria to measure superoxide flashes in angiosperm flowers
Authors: Zhang Chulan , Sun Fengshuo , Xiong Biao , Zhang Zhixiang
Published: April 2019

Background

Mitochondria are the center of energy metabolism and the production of reactive oxygen species (ROS). ROS production results in a burst of “superoxide flashes”, which is always accompanied by depolarization of mitochondrial membrane potential. Superoxide flashes have only been studied in the model plant Arabidopsis thaliana using a complex method to isolate mitochondria. In this study, we present an efficient, easier method to isolate functional mitochondria from floral tissues to measure superoxide flashes.

Method

We used 0.5 g samples to isolate mitochondria within <1.5 h from flowers of two non-transgenic plants (Magnolia denudata and Nelumbo nucifera) to measure superoxide flashes. Superoxide flashes were visualized by the pH-insensitive indicator MitoSOX Red, while the mitochondrial membrane potential (ΔΨ m) was labelled with TMRM.

Results

Mitochondria isolated using our method showed a high respiration ratio. Our results indicate that the location of ROS and mitochondria was in a good coincidence. Increased ROS together with a higher frequency of superoxide flashes was found in mitochondria isolated from the flower pistil. Furthermore, a higher rate of depolarization of the ΔΨ m was observed in the pistil. Taken together, these results demonstrate that the frequency of superoxide flashes is closely related to depolarization of the ΔΨ m in petals and pistils of flowers.
Synopsis of the genusPonthieva(Orchidaceae) in Colombia
Authors: Szlachetko Dariusz L. , Kolanowska Marta , Olędrzyńska Natalia
Published: April 2019

The Neotropical orchid genusPonthievaR. Br. was established in 1813. The 70 representatives of this taxon are terrestrial, lithophytic, or epiphytic plants with basal, sessile, or petiolate leaves which are glabrous or pubescent. Their erect peduncle is pubescent and terminated by lax, few- to many-flowered raceme. Flowers are non-resupinate, with dissimilar sepals and asymmetrical petals which are adnate to the sides of the gynostemium. The lip is uppermost, fused to the lower part of the gynostemium. Here the synopsis of ColombianPonthievais presented. A list of national genus representatives includes 26 species, including one new species,P. vallecaucanaSzlach. Kolan. & Olędrzyńska, sp. nov., discovered during this study. We did not confirm occurrence of four species reported in previous research. To facilitate process of identification of genus representatives, we dividedPonthievainto six morphological complexes based on vegetative and floral characters. The highest number of species was found in Magdalena and Cauca Valley montane forests. Lectotypes forPonthieva inauditaandP. mandoniiare designated. Morphological characteristics and illustrations of perianth segments of Colombian representatives of the genus are provided as well as a key for their identification.
Genome-wide analysis of maize OSCA family members and their involvement in drought stress
Authors: Ding Shuangcheng , Feng Xin , Du Hewei , Wang Hongwei
Published: April 2019

Background

Worldwide cultivation of maize is often impacted negatively by drought stress. Hyperosmolality-gated calcium-permeable channels (OSCA) have been characterized as osmosensors in Arabidopsis. However, the involvement of members of the maize OSCA (ZmOSCA) gene family in response to drought stress is unknown. It is furthermore unclear which ZmOSCA gene plays a major role in genetic improvement of drought tolerance in Maize.

Methods

We predicted the protein domain structure and transmembrane regions by using the NCBI Conserved Domain Database database and TMHMM server separately. The phylogeny tree was built by Mega7. We used the mixed linear model in TASSEL to perform the family-based association analysis.

Results

In this report, 12 ZmOSCA genes were uncovered in the maize genome by a genome-wide survey and analyzed systematically to reveal their synteny and phylogenetic relationship with the genomes of rice, maize, and sorghum. These analyses indicated a relatively conserved evolutionary history of the ZmOSCA gene family. Protein domain and transmembrane analysis indicated that most of the 12 ZmOSCAs shared similar structures with their homologs. The result of differential expression analysis under drought at various stages, as well as the expression profiles in 15 tissues, revealed a functional divergence of ZmOSCA genes. Notably, the expression level of ZmOSCA4.1 being up-regulated in both seedlings and adult leaves. Notably, the association analysis between genetic variations in these genes and drought tolerance was detected. Significant associations between genetic variation in ZmOSCA4.1 and drought tolerance were found at the seedling stage. Our report provides a detailed analysis of the ZmOSCAs in the maize genome. These findings will contribute to future studies on the functional characterization of ZmOSCA proteins in response to water deficit stress, as well as understanding the mechanism of genetic variation in drought tolerance in maize.
PROVÁVEIS INFLUÊNCIAS DO PRIMEIRO ANO DO CURSO DE SECRETARIADO EXECUTIVO BILÍNGUE NO COTIDIANO DOS ESTUDANTES
Authors: Martins Cibele Barsalini , Genghini Luiz Antônio , Vicente Ismar , Terra Penha Maria Mendes
Published: April 2019

Neste artigo os autores têm como objetivo identificar as influências do primeiro ano do curso de Secretariado Executivo Bilíngüe no cotidiano dos alunos. Para tanto, aborda-se as questões relacionadas à evolução nos aspectos profissional, social e individual, segundo os parâmetros das diretrizes curriculares das Instituições de Ensino Superior, emitida pelo Ministério de Educação e Cultura - MEC. Utilizou-se para tanto o método de pesquisa exploratório, não probabilístico de conveniência, julgamento e cotas. Como principais pressupostos teóricos foram abordados os conceitos sobre a escolha do curso superior e as possibilidades de entrar no mercado de trabalho. Os resultados do estudo apontam que os alunos em Secretariado Executivo, vêm participando efetivamente do mercado de trabalho e possuem consciência da necessidade de constante aperfeiçoamento educacional objetivando melhorar, cada vez mais, sua qualificação profissional.
Diversity, Ethnobotanical Potential and Sustainability Assessment of Plants Used by Traditional Healers to Treat Cancer in Boyo Division, North-West Region, Cameroon
Authors: Avana-Tientcheu Marie-Louise , Sime Christian Herve , Tsobou Roger , Tchoundjeu Zacharie
Published: April 2019

Aims: Cancer is the second leading cause of death globally. Therefore, the knowledge on medicinal plants used to cure human cancer could be of great importance for their widespread use and scientific validation. The present study records information on anticancer plants in Boyo Division, in the western highland of Cameroon.

Methods: Thirty traditional healers, were interviewed to document their know-how on the type of human cancer allegedly cured, the plant species used as well as their use pattern. Guided field walks were made to the collection sites for plant and its habitat characterization as well as herbarium voucher collection. Ethnobotanical quantitative tools were used to analyze and summarize collected data. Sustainability of harvest was assessed using a vulnerability index based on seven parameters. 

Results: A total of 25 medicinal plants cited were identified as belonging to 13 families and 23 genera. The most represented families were Asteraceae (28%), Lamiaceae (16%), Fabaceae (12%) and Acanthaceae (8%). Out of the seven categories of cancer diseases reported, the highest number of plants species were reported to treat stomach, pancreas, liver, skin and breast cancers, with informant consensus factor (ICF) ranging from 0.79 to 0.82. Leaves (60%) and bark (20%) were the major plant parts used mostly in form of decoction (45.45%) and concoction (38.18%). The result of Relative frequency citations (RFCs) revealed that 9 of the 25 plants species cited were the most frequently used with fidelity levels ranging from 92% (Geniosporum rotundifolium and Ocimum tenuiflorum Aframomum melegueta and Entada abyssinica) to 100% (Coleus blumei, Ocimum gratissimum, Eremomastax speciosa, and Dichrocephala integrifolia). Six species were assessed as vulnerable (Vi ≥ 2), while two species were rated as highly vulnerable namely G. rotundifolium (Vi = 2.71) and E. abyssinica (Vi = 2.85).

Conclusion: New traditionally effective anticancer plants were identified in the present study, some of which were already vulnerable for exploitation in their actual habitat. Plants with high ICF, RFCs and FL values should be subjected to further phytochemical and pharmacological investigations for scientific validation while those with high Vulnerability index should be recommended for participatory domestication by the main users.
Genetic and clonal structures of the tree species Tilia cordata mill. in remnants of ancient forests in Denmark
Authors: Erichsen Eva Ortvald , Wolff Kirsten , Hansen Ole K.
Published: April 2019

The insect‐pollinated forest tree Tilia cordata Mill. grows today in small fragmented populations in Denmark and other western European countries but was, in prehistoric times, a dominating species and is considered an indicator species for ancient forest. The species is known to propagate both sexually and vegetatively, forming clonal groups. Few studies have been made on the species' population genetics and on how clonality affects the population structure. The aim of this study is to evaluate the Danish gene pool by estimating genetic diversity and differentiation, as well as through exhaustive sampling describe clonal structures in some of the populations. Genetic analysis was carried out using nine nuclear microsatellite markers in nine populations, of which four were exhaustively or partly exhaustively sampled. The markers showed a high degree of genetic diversity but low differentiation between populations, with no geographic‐related structure. Clonal structures were found in eight out of the nine populations. In the exhaustively sampled populations, recruitment strategies included both sexual and clonal reproduction with indications that clonality may be enhanced by management and other disturbances.
Domain structure of HelD, an interaction partner of Bacillus subtilis RNA polymerase
Authors: Kovaľ Tomáš , Sudzinová Petra , Perháčová Terézia , Trundová Mária , Skálová Tereza , Fejfarová Karla , Šanderová Hana , Krásný Libor , Dušková Jarmila , Dohnálek Jan
Published: April 2019

The HelD is a helicase‐like protein binding to Bacillus subtilis RNA polymerase (RNAP), stimulating transcription in an ATP‐dependent manner. Here, our small angle X‐ray scattering data bring the first insights into the HelD structure: HelD is compact in shape and undergoes a conformational change upon substrate analog binding. Furthermore, the HelD domain structure is delineated, and a partial model of HelD is presented. In addition, the unique N‐terminal domain of HelD is characterized as essential for its transcription‐related function but not for ATPase activity, DNA binding, or binding to RNAP. The study provides a topological basis for further studies of the role of HelD in transcription.
Zinc cooperates with p53 to inhibit the activity of mitochondrial aconitase through reactive oxygen species accumulation
Authors: Xue Ya‐Nan , Liu Ya‐Nan , Su Jing , Li Jiu‐Ling , Wu Yao , Guo Rui , Yu Bing‐Bing , Yan Xiao‐Yu , Zhang Li‐Chao , Sun Lian‐Kun , Li Yang
Published: April 2019

Metabolic reprogramming is a central hallmark of cancer. Therefore, targeting metabolism may provide an effective strategy for identifying promising drug targets for cancer treatment. In prostate cancer, cells undergo metabolic transformation from zinc‐accumulating, citrate‐producing cells to citrate‐oxidizing malignant cells with lower zinc levels and higher mitochondrial aconitase (ACO2) activity. ACO2 is a Krebs cycle enzyme that converts citrate to isocitrate and is sensitive to reactive oxygen species (ROS)‐mediated damage. In this study, we found that the expression of ACO2 is positively correlated with the malignancy of prostate cancer. Both zinc and p53 can lead to an increase in ROS. ACO2 can be a target for remodeling metabolism by sensing changes in the ROS levels of prostate cancer. Our results indicate that targeting ACO2 through zinc and p53 can change prostate cancer metabolism, and thus provides a potential new therapeutic strategy for prostate cancer.
The crime, mental health, and economic impacts of prearrest diversion of people with mental health problems: A systematic review
Authors: Schucan Bird Karen , Shemilt Ian
Published: April 2019

Background

Prearrest diversion strategies are being adopted across the Western world, enabling the police to identify and divert people suspected of having mental disorder towards health and community services rather than the criminal justice system.

Aims

To quantify longer‐term criminal justice and mental health outcomes after prearrest diversion of people with suspected mental disorder and consider economic correlates.

Methods

A systematic review of published literature on longer term outcomes after prearrest diversion.

Results

Only two quasi‐experimental studies, with four independent samples, could be included. Findings for criminal and mental health outcomes were inconclusive, but potential for adverse outcomes was identified. Ten studies with cost data suggested that prearrest diversion can lead to overall cost savings.

Conclusions

There is still inadequate evidence on which to base prearrest diversion programmes. Although some benefits have been identified by the review, so have possible harms. Future research and funding strategies must build in high‐quality, systematic evaluation of outcomes before implementing a theoretically attractive strategy more widely.
Tailoring the Porosity in Iron Phosphosulfide Nanosheets to Improve the Performance of Photocatalytic Hydrogen Evolution
Authors: Zhang Jian , Feng Fang , Pu Yong , Li Xing'ao , Lau Cher Hon , Huang Wei
Published: April 2019

Metal sulfide photocatalysts are typically required during water splitting to produce hydrogen. However, the rapid recombination of photogenerated electron–hole pairs in these highly unstable photocatalysts has restricted hydrogen production to small‐scale batch reactions. In this work, porous transition‐metal thiophosphites were used to enable continuous long‐term hydrogen production through photocatalysis. A wide bandgap (2.04 eV) was essential for generating hydrogen at a rate of 305.6 μmol h−1 g−1, 180 % faster than nonporous FePS3 nanosheets. More importantly, the high in‐plane stiffness of these approximately 7 nm thick porous FePS3 nanosheets ensured structural stability during 56 h of continuous photocatalysis reactions. The reaction results with D2O instead of H2O indicated that hydrogen mainly came from H2O. Furthermore, a sacrificial reagent (triethylamine) was photodegraded into diethylamine and acetaldehyde through a monoelectronic oxidation process, as indicated by HPLC and LC–MS. This synthesis strategy reported for FePS3 porous nanosheets paves a new pathway for designing other dianion‐based inorganic nanocrystals for hydrogen energy applications.
Real‐world treatment patterns of sacubitril/valsartan: a longitudinal cohort study in Germany
Authors: Wachter Rolf , Fonseca Ana F. , Balas Bogdan , Kap Elisabeth , Engelhard Johanna , Schlienger Raymond , Klebs Sven , Wirta Sara Bruce , Kostev Karel
Published: April 2019

Aims

To analyse real‐world treatment patterns of sacubitril/valsartan (sac/val) using data from a pharmacy database in Germany.

Methods and results

A retrospective cohort study of 26 191 adult patients (aged ≥ 18 years) in the IMS® longitudinal prescriptions database in Germany who were dispensed sac/val from January 2016 to June 2017 was conducted. The analysis included sac/val dose titration assessed in the 6 months from first sac/val prescription; prescriptions of concomitant cardiovascular medications in the 6 months pre‐ and post‐index and compliance and persistence during 12 months post‐index. Two‐thirds of patients were prescribed the lowest sac/val dose of 50 mg twice daily (b.i.d.) at index and up‐titration during the first 6 months was attempted in 41% of these patients. Ten percent of patients prescribed 200 mg b.i.d. at index had to be stably down‐titrated; among patients prescribed 50 or 100 mg b.i.d. at index that were up‐titrated, > 80% remained on the higher dose. Overall, the mean daily diuretic dose decreased by 25% after initiation of sac/val. High compliance and persistence rates were observed across sac/val doses, increasing with higher sac/val dose at index. Prior dose of angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker had only minor impact on first sac/val dose, compliance and persistence.

Conclusions

Most patients prescribed sac/val are not initiated on the recommended dose nor up‐titrated as recommended by the EU Summary of Product Characteristics. Initiation of sac/val was associated with high persistence and compliance and a dose reduction of diuretics. Barriers to up‐titration must be explored.
Research and application of Boolean operation for triangular mesh model of underground space engineering—Boolean operation for triangular mesh model
Authors: Qin Yaguang , Luo Zhouquan , Wen Lei , Feng Chundi , Zhang Xuyang , Lan Ming , Liu Bing
Published: April 2019

This study is aiming at the problems of slow collision detection speed of bounding box, low efficiency of triangle intersection detection, and triangulation in regions where complex intersecting lines are segmented that exist in Boolean operation of triangular mesh model in underground space engineering. The orientation calculation method of underground space engineering is put forward, and the precise definition of bounding box is realized. A simple method to realize the fast intersection detection algorithm between triangles is presented, the process of transforming the projection of intersecting lines into scalar and then judging is eliminated, and the efficiency of triangle intersection detection is improved. On the basis of Delaunay triangulation robust algorithm, numbering method of intersection position is improved. Central axis region division method and hierarchical subdivision triangulation method are proposed, which can divide all the regions of mixed complex intersections in one traversal. A subdivision triangulation method by comparing the cosine value of internal tension angle is proposed, and the subdivision triangulation of polygon is optimized. The feasibility of the algorithm is verified by practical engineering application.
Causes of hOCT1‐Dependent Cholangiocarcinoma Resistance to Sorafenib and Sensitization by Tumor‐Selective Gene Therapy
Authors: Lozano Elisa , Macias Rocio I.R. , Monte Maria J. , Asensio Maitane , del Carmen Sofia , Sanchez‐Vicente Laura , Alonso‐Peña Marta , Al‐Abdulla Ruba , Munoz‐Garrido Patricia , Satriano Letizia , O'Rourke Colm J. , Banales Jesus M. , Avila Matias A. , Martinez‐Chantar Maria L. , Andersen Jesper B. , Briz Oscar , Marin Jose J.G.
Published: April 2019

Although the multi‐tyrosine kinase inhibitor sorafenib is useful in the treatment of several cancers, cholangiocarcinoma (CCA) is refractory to this drug. Among other mechanisms of chemoresistance, impaired uptake through human organic cation transporter type 1 (hOCT1) (gene SLC22A1) has been suggested. Here we have investigated the events accounting for this phenotypic characteristic and have evaluated the interest of selective gene therapy strategies to overcome this limitation. Gene expression and DNA methylation of SLC22A1 were analyzed using intrahepatic (iCCA) and extrahepatic (eCCA) biopsies (Copenhagen and Salamanca cohorts; n = 132) and The Cancer Genome Atlas (TCGA)‐CHOL (n = 36). Decreased hOCT1 mRNA correlated with hypermethylation status of the SLC22A1 promoter. Treatment of CCA cells with decitabine (demethylating agent) or butyrate (histone deacetylase inhibitor) restored hOCT1 expression and increased sorafenib uptake. MicroRNAs able to induce hOCT1 mRNA decay were analyzed in paired samples of TCGA‐CHOL (n = 9) and Copenhagen (n = 57) cohorts. Consistent up‐regulation in tumor tissue was found for miR‐141 and miR‐330. High proportion of aberrant hOCT1 mRNA splicing in CCA was also seen. Lentiviral‐mediated transduction of eCCA (EGI‐1 and TFK‐1) and iCCA (HuCCT1) cells with hOCT1 enhanced sorafenib uptake and cytotoxic effects. In chemically induced CCA in rats, reduced rOct1 expression was accompanied by impaired sorafenib uptake. In xenograft models of eCCA cells implanted in mouse liver, poor response to sorafenib was observed. However, tumor growth was markedly reduced by cotreatment with sorafenib and adenoviral vectors encoding hOCT1 under the control of the BIRC5 promoter, a gene highly up‐regulated in CCA. Conclusion: The reason for impaired hOCT1‐mediated sorafenib uptake by CCA is multifactorial. Gene therapy capable of selectively inducing hOCT1 in tumor cells can be considered a potentially useful chemosensitization strategy to improve the response of CCA to sorafenib.
Effects of exercise preconditioning and HSP72 on diaphragm muscle function during mechanical ventilation
Authors: Smuder Ashley J. , Morton Aaron B. , Hall Stephanie E. , Wiggs Michael P. , Ahn Bumsoo , Wawrzyniak Nicholas R. , Sollanek Kurt J. , Min Kisuk , Kwon Oh Sung , Nelson W. Bradley , Powers Scott K.
Published: April 2019

Background

Mechanical ventilation (MV) is a life‐saving measure for patients in respiratory failure. However, prolonged MV results in significant diaphragm atrophy and contractile dysfunction, a condition referred to as ventilator‐induced diaphragm dysfunction (VIDD). While there are currently no clinically approved countermeasures to prevent VIDD, increased expression of heat shock protein 72 (HSP72) has been demonstrated to attenuate inactivity‐induced muscle wasting. HSP72 elicits cytoprotection via inhibition of NF‐κB and FoxO transcriptional activity, which contribute to VIDD. In addition, exercise‐induced prevention of VIDD is characterized by an increase in the concentration of HSP72 in the diaphragm. Therefore, we tested the hypothesis that increased HSP72 expression is required for the exercise‐induced prevention of VIDD. We also determined whether increasing the abundance of HSP72 in the diaphragm, independent of exercise, is sufficient to prevent VIDD.

Methods

Cause and effect was determined by inhibiting the endurance exercise‐induced increase in HSP72 in the diaphragm of exercise trained animals exposed to prolonged MV via administration of an antisense oligonucleotide targeting HSP72. Additional experiments were performed to determine if increasing HSP72 in the diaphragm via genetic (rAAV‐HSP72) or pharmacological (BGP‐15) overexpression is sufficient to prevent VIDD.

Results

Our results demonstrate that the exercise‐induced increase in HSP72 protein abundance is required for the protective effects of exercise against VIDD. Moreover, both rAAV‐HSP72 and BGP‐15‐induced overexpression of HSP72 were sufficient to prevent VIDD. In addition, modification of HSP72 in the diaphragm is inversely related to the expression of NF‐κB and FoxO target genes.

Conclusions

HSP72 overexpression in the diaphragm is an effective intervention to prevent MV‐induced oxidative stress and the transcriptional activity of NF‐κB and FoxO. Therefore, overexpression of HSP72 in the diaphragm is a potential therapeutic target to protect against VIDD.
Comprehensive analysis of serum tumor markers and BRCA1/2 germline mutations in Chinese ovarian cancer patients
Authors: Deng Hongyu , Chen Ming , Guo Xinwu , Heng Jianfu , Xu Xunxun , Peng Limin , Jiang Hui , Li Guoli , Day Julia X. , Li Jinliang , Shan Dongyong , Li Yinghua , Zhou Yanjie , Liu Bin , Dai Lizhong , Wang Xiaochun , Wang Jun
Published: April 2019

Background

The serum tumor markers has been widely used in ovarian cancer diagnosis. BRCA1/2 germline mutations are the most common predisposing factors for ovarian cancer development. This study aimed to comprehensively investigate serum tumor markers and BRCA1/2 germline mutations and analyze their associations with ovarian cancer.

Methods

Levels of 11 serum tumor markers were examined in ovarian cancer patients and controls with benign gynecologic diseases. By integrating multiplex PCR and next‐generation sequencing technologies, BRCA1/2 germline mutations were analyzed and confirmed by Sanger sequencing. The discriminative models with serum tumor markers and BRCA1/2 mutation status were constructed for ovarian cancer detection and patient stratification.

Results

Among 11 markers, six of them were significantly elevated and only beta‐human chorionic gonadotropin (β‐HCG) was significantly reduced in ovarian cancer patients. A total of 54 (23.3%) ovarian cancer patients were found to harbor BRCA1/2 deleterious mutations, and BRCA1/2 mutations were significantly associated with Hereditary Breast and Ovarian Cancer‐related tumors and family history of cancer. Carbohydrate antigen 125 showed a good performance in ovarian cancer detection as a single marker (AUC = 0.799), while a panel of eight markers showed a good performance in BRCA1 mutation detection with an AUC value of 0.974. In addition, a panel of five serum tumor markers combined with BRCA1/2 mutation status showed a good performance in lymph node metastasis prediction (AUC = 0.843).

Conclusions

We found the association between BRCA1/2 germline mutation status and serum tumor marker levels, and identified discriminative models that combined serum tumor markers with BRCA1/2 mutation status for ovarian cancer detection and patient stratification.
Take two: Utility of the repeat skeletal muscle biopsy
Authors: Aburahma Samah K. , Wicklund Matthew P. , Quan Dianna
Published: April 2019

Introduction: The utility of repeat muscle biopsy has not been adequately evaluated. Methods: A retrospective review was undertaken of 144 repeat muscle biopsies performed from 1980 to 2017. Repeat biopsy was considered clinically relevant if it provided a new diagnosis, changed the existing diagnosis, or led to treatment changes or further investigations. Results: Repeat biopsy was abnormal in 118 cases, different from the initial biopsy in 67 cases, and specific in 40 cases. Factors with a significant effect on clinical relevance of the repeat biopsy (P < 0.05) were an abnormal, specific, or inflammatory initial biopsy, proximal muscle weakness, absence of myalgia, and a repeat biopsy that is different, specific, or consistent with polymyositis or inclusion body myositis. Conclusions: Utility of repeat biopsy was limited to weak patients whose initial biopsy showed inflammatory myositis. Ongoing advances in the diagnosis of immune inflammatory myopathies have led to evolution of the role of repeat biopsy. Muscle Nerve, 2019
Structure‐activity relationship studies on naphthoquinone analogs. The search for new herbicides based on natural products
Authors: Durán Alexandra G , Chinchilla Nuria , Molinillo José MG , Macías Francisco A
Published: April 2019

BACKGROUND

Allelopathy and bioassays constitute fundamental tools in the search for new herbicide templates. The work described here is a continuation of a previous study focused on the structure–activity relationships between transport phenomena and phytotoxic activity. Different modifications were made to the naphthoquinone backbone and two key factors were identified as being responsible for changes in activity: lipophilicity and the nature of the functional group. The study of other naturally occurring and semi‐synthetic naphthoquinones was also proposed.

RESULTS

A total of 12 5‐O‐acyl plumbagins and 18 analogs with unsaturated and aromatic substituents at positions 2 and 5 were synthesized. These compounds were evaluated in the wheat coleoptile bioassay and against Standard Target Species (STS) and three weeds, namely Echinochloa crus‐galli L., Lolium rigidum Gaud. and Lolium perenne L. A strong structure–function relationship was observed for the different naphthoquinones and root and shoot length were the parameters that were most affected.

CONCLUSION

Strong inhibitory effects were observed for the isomeric forms 23 and 33 and the derivatives with a free hydroxyl group, i.e. 24 and 30, gave values higher than 70% inhibition for root length in barnyardgrass and perennial ryegrass. These results highlight the potential of these compounds as models in the development of herbicides based on natural products. © 2019 Society of Chemical Industry
Testing the ability of unmanned aerial systems and machine learning to map weeds at subfield scales: a test with the weed Alopecurus myosuroides (Huds)
Authors: Lambert James PT , Childs Dylan Z , Freckleton Rob P
Published: April 2019

BACKGROUND

It is important to map agricultural weed populations to improve management and maintain future food security. Advances in data collection and statistical methodology have created new opportunities to aid in the mapping of weed populations. We set out to apply these new methodologies (unmanned aerial systems; UAS) and statistical techniques (convolutional neural networks; CNN) to the mapping of black‐grass, a highly impactful weed in wheat fields in the UK. We tested this by undertaking extensive UAS and field‐based mapping over the course of 2 years, in total collecting multispectral image data from 102 fields, with 76 providing informative data. We used these data to construct a vegetation index (VI), which we used to train a custom CNN model from scratch. We undertook a suite of data engineering techniques, such as balancing and cleaning to optimize performance of our metrics. We also investigate the transferability of the models from one field to another.

RESULTS

The results show that our data collection methodology and implementation of CNN outperform pervious approaches in the literature. We show that data engineering to account for ‘artefacts’ in the image data increases our metrics significantly. We are not able to identify any traits that are shared between fields that result in high scores from our novel leave one field our cross validation (LOFO‐CV) tests.

CONCLUSION

We conclude that this evaluation procedure is a better estimation of real‐world predictive value when compared with past studies. We conclude that by engineering the image data set into discrete classes of data quality we increase the prediction accuracy from the baseline model by 5% to an area under the curve (AUC) of 0.825. We find that the temporal effects studied here have no effect on our ability to model weed densities. © 2019 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Network‐based integral sliding mode control for descriptor systems with event‐triggered sampling scheme
Authors: Wang Yuzhong , Zhang Tie , Ren Junchao , Li Jinna
Published: April 2019

This paper investigates event‐triggered sliding mode control for descriptor systems subject to networked‐induced delay. For handling disturbance and saving data transmission in networks for descriptor systems, sliding model control and event‐triggered control are combined, whereas how to combine them to design a stable controller is challenging due to the complexity of descriptor systems. Firstly, a new discrete event‐triggered scheme is introduced for deciding whether sampled data is sent out or not for networked‐based descriptor systems. Secondly, integral‐type switching surface and event‐triggered scheme are integrated resulting in a novel time‐delay system. The existence condition of integral‐type switching surface and the stability condition of the sliding mode dynamic are presented. An event‐triggered sliding mode controller is derived for driving the closed‐loop system trajectories to the practical switching surface in finite time. Finally, two examples are employed to show the effectiveness and advantages of the proposed method.
Psychopathological Consequences Related to Problematic Instagram Use Among Adolescents: The Mediating Role of Body Image Dissatisfaction and Moderating Role of Gender
Authors: Yurdagül Cemil , Kircaburun Kagan , Emirtekin Emrah , Wang Pengcheng , Griffiths Mark D.
Published: April 2019

In a minority of cases, problematic use of technology can negatively impact on adolescents and impair some aspects of their social, emotional, and psychological development. The purpose of the present study was to examine the direct and indirect effects of problematic Instagram use (PIU) on different psychopathological outcomes including loneliness, depression, anxiety, and social anxiety via body image dissatisfaction (BID). Additionally, moderating role of gender on the relationships among variables was investigated. A total of 491 adolescents (Mage = 15.92 years, SDage = 1.07; range = 14 to 19 years) were recruited for the study to complete a questionnaire that included the relevant assessment tools for the aforementioned variables. Mediation and moderation analyses showed that among male adolescents, PIU was directly associated with loneliness, depression, general anxiety, and social anxiety and BID partially mediated these associations. Among females, PIU was directly associated with depression and indirectly with general anxiety and social anxiety via BID. Gender significantly moderated the direct relationships of PIU with loneliness, general anxiety, and social anxiety. PIU was directly associated with loneliness, general anxiety, and social anxiety among males only, whereas among females, PIU was indirectly associated with general and social anxiety via BID but was not related to loneliness. Results of this study indicate that PIU has different negative psychological effects on male and female adolescents and that BID appears to be one explanatory factor for these impairments especially among females.
Timing of Cleavage Development in Relation to Folding and its Implications: An Example from the Deformed Mesoproterozoic Sedimentary Cover of Kaladgi Basin, Southwestern India
Authors: Mukherjee Mrinal Kanti , Modak Kunal
Published: April 2019

Detailed analysis of cleavage-fold relationships in the Mesoproterozoic cover sediments of Kaladgi basin, south western India, revealed three types of timing relationships between cleavage and folds: (1) cleavage developed earlier than folds. (2) Cleavage developed later at some stage of folding and (3) non-development of cleavages in folds.

In the first case cleavage developed earlier than the folding. Evidences that support such an interpretation include high cleavage-bedding angle throughout the fold, asymmetric fanning of cleavage in the folds with large fan angles and rotation of cleavage more in the steep and short limbs of asymmetric fold. In the second case, cleavage initiated later at some stage during folding which is evident from low cleavage fan angles, relatively low cleavage–bedding angles in the limbs of folds and the offset of bedding trace against cleavage trace due to pressure solution. Even though pressure solution is ubiquitous throughout the fold the effects of offset are more pronounced in the limbs compared to that in the hinge due to changing angular relationship of bedding and cleavage throughout the fold. In the third case, cleavage is absent in the folds resulting in its sporadic occurrences and reflects its diachronous nature.

The final geometry of cleavage in relation to folds at any location is a combined effect of relative timing of cleavage development and mechanism of folding involving layer parallel shortening, flexural slip, tangential longitudinal strain, syn- to postfold flattening and hinge migration.
Ichnological Significance of Upper Disang Formation and Lower Barail Formation (Late Eocene to Early Oligocene) of Nagaland, Northeast India, in the Indo-Myanmar Ranges
Authors: Rajkumar H. S. , Soibam I. , Khaidem K. S. , Sanasam S. S. , Khuman Ch. M.
Published: April 2019

The Upper Disang-Lower Barail Transition Sequences of Nagaland in northeast India, Indo-Myanmar Ranges (IMR) are found to preserve reasonably diverse biological sedimentary structures. Three ichnofacies were observed, Skolithos ichnofacies consisting of Bergaueria hemispherica, Gyrochorte comosa, Ophiomorpha nodosa, Skolithos linearis and Thalassinoides paradoxicus; Cruziana ichnofacies – Curvolithus simplex, Scolicia plana, Scolicia strozzii, Scolicia vertebralis, Treptichnus pedum, Taenidium diesingi and Palaeophycus tubularis; and Nereites ichnofacies – Chondrites targionii and Paleomeandron elegans. Presence of Skolithos and Cruziana ichnofacies suggest well oxidising, substrate rich depositional environment in the foreshoreface to offshore setting in general; and an overall possible fluctuation in the depositional bathymetry which is supported by the presence of Nereites ichnofacies in horizons alternating with Skolithos and Cruziana ichnofacies. The depositional system is proposed to be proximal to distal hyperpycnal-delta-fed turbidite system. Observation of sand spherules also suggests possibility of shoreline as one of the depositional environments.
Uranium Mineralization in Leucogranite of Mastipuram Area, Wanaparti District, Telangana – A New Find
Authors: Rajaraman H. S. , Bisht B. S. , Jeyagopal A. V. , Verma M. B.
Published: April 2019

The NNW-SSE trending leucogranites in and around Mastipuram, Wanaparthi district, Telangana are intrusive into Peninsular Gneissic complex. The leucogranite is metaluminous to mildly peraluminous, alkali-feldspar granite with I-type signatures, probably formed from a fractionated melt involving crustal component. Magmatic and hydrothermal contributions are supported by wide range of U/Th ratios in mineralized samples, which also show Na-enrichment as compared to non-mineralized leucogranites. Average U and Th contents and U/Th ratio in mineralized leucogranite is 541ppm, 147 ppm and 2.85, respectively. Main ore mineral is uraninite and its altered form - gummite, while secondary uranium minerals such as schoepite, uranophane and haiweeite are also identified in leucogranite by XRD. Reconnoitory drilling of ten boreholes have confirmed sub-surface continuation of uranium mineralization with varying width of 1m to 31m at vertical depth of about 50m. Thus, the leucogranites bordering Gadwal schist belt around Mastipuram forms a very potential target.
Eye-tracking for assessing medical image interpretation: A pilot feasibility study comparing novice vs expert cardiologists
Authors: Brunyé Tad T. , Nallamothu Brahmajee K. , Elmore Joann G.
Published: April 2019

Introduction As specialized medical professionals such as radiologists, pathologists, and cardiologists gain education and experience, their diagnostic efficiency and accuracy change, and they show altered eye movement patterns during medical image interpretation. Existing research in this area is limited to interpretation of static medical images, such as digitized whole slide biopsies, making it difficult to understand how expertise development might manifest during dynamic image interpretation, such as with angiograms or volumetric scans.

Methods A two-group (novice, expert) comparative pilot study examined the feasibility and utility of tracking and interpreting eye movement patterns while cardiologists viewed video-based coronary angiograms. A non-invasive eye tracking system recorded cardiologists’ (n = 8) visual behaviour while they viewed and diagnosed a series of eight angiogram videos. Analyses assessed frame-by-frame video navigation behaviour, eye fixation behaviour, and resulting diagnostic decision making.

Results Relative to novices, expert cardiologists demonstrated shorter and less variable video review times, fewer eye fixations and saccadic eye movements, and less time spent paused on individual video frames. Novices showed repeated eye fixations on critical image frames and regions, though these were not predictive of accurate diagnostic decisions.

Discussion These preliminary results demonstrate interpretive decision errors among novices, suggesting they identify and process critical diagnostic features, but sometimes fail to accurately interpret those features. Results also showcase the feasibility of tracking and understanding eye movements during video-based coronary angiogram interpretation and suggest that eye tracking may be valuable for informing assessments of competency progression during medical education and training.