bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of processing on the biochemical contents of Acanthus montanus (Nees) T. Anderson (Acanthaceae) leaves
Authors: Igwe Andrew , Eleazu Chinedum
Published: December 2017

The effect of processing on the biochemical contents of Acanthus montanus leaves was investigated. The moisture, crude protein, lipid, fiber, ash, and total carbohydrate contents of the raw vegetable were 59.15, 1.85, 2.32, 3.76, 2.04, and 34.65 g/100 g, respectively. The saponin, alkaloid, tannin, flavonoid, phenol, and anthocyanin contents of the raw vegetable were 5.35, 4.04, 1.10, 3.53, 2.87, and 1.27 g/100 g, respectively, while it contained 2.65 mg/100 g calcium, 1.14 mg/100 g magnesium, 7.66 mg/100 g potassium, 350.75 μg/g vitamin A, 50.87 mg/100 g vitamin C, and 0.25% titratable acidity. There were significant reductions (p < .05) in the protein, lipid, fiber, ash, saponin, alkaloid, tannin, phenol, anthocyanin, calcium, magnesium, potassium, vitamin A, vitamin C, and titratable acidity of the boiled or boiled + sun‐dried A. montanus leaves; significant elevation of the moisture contents but significant reduction of the total carbohydrate contents of the boiled; and significant reduction of the moisture contents of the boiled + sun‐dried vegetable compared with the raw. There were significant increases (p < .05) in the total carbohydrate contents of the boiled + sun‐dried leaves; significant reductions (p < .05) in the moisture, saponin, alkaloid, and vitamins A and C contents of the sun‐dried vegetable; and no significant differences (p > .05) in the lipid, calcium, potassium, and ash, but significant increases (p < .05) in the protein, crude fiber, total carbohydrates, tannins, flavonoids, phenols, anthocyanin, magnesium, and titratable acidity of the sun‐dried vegetable when compared with the raw. Sun drying alone either retained or enhanced the release of some important bioactive compounds in A. montanus leaves. Furthermore, the reduced moisture content of the sun‐dried vegetable together with its increased titratable acidity will make the sun‐dried vegetable uninhabitable for microorganisms, thereby increasing its shelf life.
A suggested framework and guidelines for learning GIS in interdisciplinary research
Authors: Rickles Patrick , Ellul Claire , Haklay Muki
Published: December 2017

Interdisciplinary research with geographic information systems (GIS) can be rewarding as researchers from different disciplines have the opportunity to create something novel. GIS, though, is known to be difficult to use and learn. It is imperative for its successful use in projects that those who need to use GIS are able to learn it quickly and easily. To better support interdisciplinary research with GIS, it is necessary to understand what researchers with interdisciplinary experience wanted to use it for and how they learned it. The aim would be to advise geography educators on creating learning resources that could compliment or supplement existing learning approaches used by interdisciplinary researchers to improve the learning experience and uptake of GIS. This article explores the results from an online survey and interviews conducted between July 2014 and August 2015 with participants from the UK, the US and Europe on how interdisciplinary researchers learned GIS and which resources and platforms were utilised. Guidelines and a framework are presented, modifying the Technological Pedagogical and Content Knowledge framework, incorporating informal and context‐based learning and GIS concepts from the Geographic Information Science and Technology Body of Knowledge. Findings show that interdisciplinary researchers want to use GIS to capture, analyse and visualise information; they largely use informal learning approaches (e.g. internet searches, watching a video, ask a more experienced person); and they predominantly use ArcGIS, QGIS and web GIS platforms. Future work suggests resources use contextually relevant learning activities and bear in mind nuances of disciplinary language.
A robust and powerful two‐step testing procedure for local ancestry adjusted allelic association analysis in admixed populations
Authors: Duan Qing , Xu Zheng , Raffield Laura M. , Chang Suhua , Wu Di , Lange Ethan M. , Reiner Alex P. , Li Yun
Published: December 2017

Genetic association studies in admixed populations allow us to gain deeper understanding of the genetic architecture of human diseases and traits. However, population stratification, complicated linkage disequilibrium (LD) patterns, and the complex interplay of allelic and ancestry effects on phenotypic traits pose challenges in such analyses. These issues may lead to detecting spurious associations and/or result in reduced statistical power. Fortunately, if handled appropriately, these same challenges provide unique opportunities for gene mapping. To address these challenges and to take these opportunities, we propose a robust and powerful two‐step testing procedure Local Ancestry Adjusted Allelic (LAAA) association. In the first step, LAAA robustly captures associations due to allelic effect, ancestry effect, and interaction effect, allowing detection of effect heterogeneity across ancestral populations. In the second step, LAAA identifies the source of association, namely allelic, ancestry, or the combination. By jointly modeling allele, local ancestry, and ancestry‐specific allelic effects, LAAA is highly powerful in capturing the presence of interaction between ancestry and allele effect. We evaluated the validity and statistical power of LAAA through simulations over a broad spectrum of scenarios. We further illustrated its usefulness by application to the Candidate Gene Association Resource (CARe) African American participants for association with hemoglobin levels. We were able to replicate independent groups’ previously identified loci that would have been missed in CARe without joint testing. Moreover, the loci, for which LAAA detected potential effect heterogeneity, were replicated among African Americans from the Women's Health Initiative study. LAAA is freely available at https://yunliweb.its.unc.edu/LAAA.
Methods for meta‐analysis of multiple traits using GWAS summary statistics
Authors: Ray Debashree , Boehnke Michael
Published: December 2017

Genome‐wide association studies (GWAS) for complex diseases have focused primarily on single‐trait analyses for disease status and disease‐related quantitative traits. For example, GWAS on risk factors for coronary artery disease analyze genetic associations of plasma lipids such as total cholesterol, LDL‐cholesterol, HDL‐cholesterol, and triglycerides (TGs) separately. However, traits are often correlated and a joint analysis may yield increased statistical power for association over multiple univariate analyses. Recently several multivariate methods have been proposed that require individual‐level data. Here, we develop metaUSAT (where USAT is unified score‐based association test), a novel unified association test of a single genetic variant with multiple traits that uses only summary statistics from existing GWAS. Although the existing methods either perform well when most correlated traits are affected by the genetic variant in the same direction or are powerful when only a few of the correlated traits are associated, metaUSAT is designed to be robust to the association structure of correlated traits. metaUSAT does not require individual‐level data and can test genetic associations of categorical and/or continuous traits. One can also use metaUSAT to analyze a single trait over multiple studies, appropriately accounting for overlapping samples, if any. metaUSAT provides an approximate asymptoticP‐value for association and is computationally efficient for implementation at a genome‐wide level. Simulation experiments show that metaUSAT maintains proper type‐I error at low error levels. It has similar and sometimes greater power to detect association across a wide array of scenarios compared to existing methods, which are usually powerful for some specific association scenarios only. When applied to plasma lipids summary data from the METSIM and the T2D‐GENES studies, metaUSAT detected genome‐wide significant loci beyond the ones identified by univariate analyses. Evidence from larger studies suggest that the variants additionally detected by our test are, indeed, associated with lipid levels in humans. In summary, metaUSAT can provide novel insights into the genetic architecture of a common disease or traits.
COPS5 and LASP1 synergistically interact to downregulate 14‐3‐3σ expression and promote colorectal cancer progression via activating PI3K/AKT pathway
Authors: Zhou Rui , Shao Ziyun , Liu Jian , Zhan Wanqi , Gao Qingzu , Pan Zhihua , Wu Ling , Xu Lijun , Ding Yanqing , Zhao Liang
Published: December 2017

Overexpression of LIM and SH3 protein 1 (LASP1) is required for colorectal cancer (CRC) development and progression. Here, C‐Jun activation domain‐binding protein‐1 (Jab1), also known as COP9 signalosome subunit 5 (COPS5), was verified as a new LASP1‐interacting protein through yeast two‐hybrid assay. The role of COPS5 in LASP1‐mediated CRC progression remains unknown. GST pull‐down assay indicated that the SH3 domain of LASP1 could directly bind to MPN domain of COPS5. In vitro gain‐ and loss‐of‐function analyses revealed the stimulatory role of COPS5 on CRC cell proliferation, migration and invasion. Endogenous overexpression of COPS5 could also enhance the homing capacity of CRC cells in vivo. Further analysis showed that COPS5 and LASP1 synergistically interact to stimulate the ubiquitination and degradation of 14‐3‐3σ and promote colorectal cancer progression via PI3K/Akt dependent signaling pathway. Clinically, the expression of COPS5 was studied in CRC tissues and it is associated with CRC differentiation, metastasis and poor prognosis. The colocalization of LASP1 and COPS5 was demonstrated in both nonmetastatic and metastatic CRC tissues. A positive correlation was found between the expression of LASP1 and COPS5 while a negative correlation existed between 14‐3‐3σ and COPS5/LASP1 in most CRC samples. A combination of COPS5 and LASP1 tends to be an independent prognostic indicator for CRC patients, and this is also suitable for CRC without lymph node metastasis. The current research has further advanced our understanding on the complicated molecular mechanism underlying LASP1‐mediated CRC progression, which hopefully will contribute to the development of novel diagnostic and therapeutic strategies in CRC.
Breast cancer‐associated mitochondrial DNA haplogroup promotes neoplastic growth via ROS‐mediated AKT activation
Authors: Ma Lin , Fu Qingzi , Xu Bing , Zhou Huaibin , Gao Jing , Shao Xiaoli , Xiong Jingting , Gu Qianru , Wen Shumeng , Li Fengjie , Shen Lijun , Chen Guorong , Fang Hezhi , Lyu Jianxin
Published: December 2017

In the last decade, mitochondrial DNA (mtDNA) haplogroups have been associated with the occurrence of breast cancer. However, the underlying mechanism is not known. Combining a case‐control study with a large cohort of women from Southern China with breast cancer and functional analyses with trans‐mitochondrial technology, we demonstrate that the D5 haplogroup is associated with an increased risk of breast cancer [odds ratio (OR) = 2.789; 95% confidence interval (CI) [1.318, 5.901]; p = 0.007]. Furthermore, mitochondrial respiration, mitochondrial ATP content and membrane potential, were lower in both bone osteosarcoma and breast cancer cell models of cytoplasmic hybrids (cybrids) containing the mtDNA D5 haplogroup than in those with non‐D5 haplogroups. Using in vitro and in vivo tumorigenicity assays, we found that cells with the D5 haplogroup were more susceptible to tumorigenesis compared to cells with non‐D5 haplogroups. Mechanistically, the D5 haplogroup may promote tumorigenesis at least partially through activation of the v‐AKT murine thymoma viral oncogene (AKT) via phosphorylation of threonine 308, which is mediated by increased reactive oxygen species generation in D5 cybrids. Our findings demonstrate that there is decreased mitochondrial function in cells with the D5 haplogroup compared to cells with non‐D5 haplogroups, which may be associated with increased neoplastic growth in breast cancer.
Estimating Soil Hydraulic and Solute Transport Parameters in Subsurface Drainage Systems Using an Inverse Modelling Approach
Authors: Sedaghatdoost Amir , Ebrahimian Hamed , Liaghat Abdolmajid
Published: December 2017

The aim of this study is to present an inverse modelling approach with a genetic algorithm for estimating soil hydraulic and solute transport parameters in two subsurface drainage systems in Iran. In this study, measured data were obtained from Amirkabir and Shoaybiyeh sugarcane fields equipped with subsurface drainage systems. The SWAP model was used for simulating the outputs of subsurface drainage systems. The accuracy of different objective functions which were based on the discrepancies between measured and simulated values of drainage discharge, groundwater depth and drainage water salinity was evaluated in the inverse modelling approach. Based on sensitivity analysis of the SWAP model in studied areas, n shape parameter, lateral hydraulic conductivity, depth to impermeable layer, saturated water content and α shape parameter were selected in the inverse modelling approach. By applying the objective function which is based on drainage discharge and salinity in the Amirkabir study area, the Nash–Sutcliffe Efficiency (NSE) values for predicting drainage discharge and salinity were 0.63 and 0.79, respectively. In the Shoaybiyeh study area, the objective function which includes drainage discharge, groundwater depth and drainage water salinity resulted in NSE values of 0.83, 0.95 and 0.89 for predicting drainage discharge, groundwater depth and drainage water salinity, respectively. Copyright © 2017 John Wiley & Sons, Ltd.
Effect of Lateral Flushing on Emitter Clogging under Drip Irrigation with Yellow River Water and a Suitable Method
Authors: Han Siqi , Li Yunkai , Xu Feipeng , Sun Dongxuan , Feng Ji , Liu Zeyuan , Wu Ruonan , Wang Zhenhua
Published: December 2017

Lateral flushing is expected to become an important means of controlling emitter clogging in drip irrigation systems. This research investigated the effect of different flushing frequencies (once every 32, 64, 96 and 128 h) and flushing velocities (0.2, 0.4 and 0. m s−1) on emitter clogging. The experimental results showed that the substances that clogged the emitters mainly come from the cast of internal laterals, and could be effectively controlled by lateral flushing. And emitter clogging was most effectively relieved for the frequency of once per 64 h, and the velocity of 0.4 m s−1. The discharge ratio variation (Dra) and the coefficient of uniformity (CU) of the drip irrigation system, increased from 7.7 to 21.9% and 11.6 to 67.4%, respectively, compared with non‐flushed laterals. Also, as the frequency increased, Dra and CU first decreased and then increased. Similarly, with the increase of flushing velocity, Dra and CU also decreased then increased. In conclusion, for the drip irrigation system with YRW, the suitable lateral flushing velocity was found to be 0.4 m s−1 at a frequency of once per 64 h. Copyright © 2017 John Wiley & Sons, Ltd.
A multicomponent approach to thinning reinforcer delivery during noncontingent reinforcement schedules
Authors: Slocum Sarah K. , Grauerholz‐Fisher Emma , Peters Kerri P. , Vollmer Timothy R.
Published: December 2017

We evaluated a noncontingent reinforcement procedure that involved initially providing three subjects with signaled, continuous access to the functional reinforcer for aggression and slowly increasing the amount of time subjects were exposed to the signaled unavailability of the reinforcer. Additionally, alternative potential reinforcers were available throughout the sessions. Results showed immediate and substantial reductions in aggression for all three subjects. The clinical utility of this intervention is discussed, and future research directions are recommended.
Development of an artificial neural network model for risk assessment of skin sensitization using human cell line activation test, direct peptide reactivity assay, KeratinoSens™ and in silico structure alert parameter
Authors: Hirota Morihiko , Ashikaga Takao , Kouzuki Hirokazu
Published: December 2017

It is important to predict the potential of cosmetic ingredients to cause skin sensitization, and in accordance with the European Union cosmetic directive for the replacement of animal tests, several in vitro tests based on the adverse outcome pathway have been developed for hazard identification, such as the direct peptide reactivity assay, KeratinoSens™ and the human cell line activation test. Here, we describe the development of an artificial neural network (ANN) prediction model for skin sensitization risk assessment based on the integrated testing strategy concept, using direct peptide reactivity assay, KeratinoSens™, human cell line activation test and an in silico or structure alert parameter. We first investigated the relationship between published murine local lymph node assay EC3 values, which represent skin sensitization potency, and in vitro test results using a panel of about 134 chemicals for which all the required data were available. Predictions based on ANN analysis using combinations of parameters from all three in vitro tests showed a good correlation with local lymph node assay EC3 values. However, when the ANN model was applied to a testing set of 28 chemicals that had not been included in the training set, predicted EC3s were overestimated for some chemicals. Incorporation of an additional in silico or structure alert descriptor (obtained with TIMES‐M or Toxtree software) in the ANN model improved the results. Our findings suggest that the ANN model based on the integrated testing strategy concept could be useful for evaluating the skin sensitization potential.
Ex vivo confocal microscopy features of cutaneous squamous cell carcinoma
Authors: Hartmann Daniela , Krammer Sebastian , Bachmann Mario R. , Mathemeier Leonie , Ruzicka Thomas , Bagci Isin S. , von Braunmühl Tanja
Published: December 2017

Background

Rapid microscopic evaluation of cutaneous squamous cell carcinoma (SCC), its grade of differentiation and level of invasiveness would enable better management of patients’ therapy.

Objectives

Analyzing specific ex vivo confocal microscopy criteria whether they can predict diagnosis of invasive SCC vs carcinoma in situ and poorly differentiated or undifferentiated vs well and moderately differentiated SCC.

Methods

Ex vivo confocal images of 102 SCCs in 57 patients were evaluated immediately after excision for the presence of predefined criteria based on confocal and histological knowledge.

Results

In histopathological examination, 30 SCCs were in situ and 72 invasive. Of these, 29 invasive SCC tumors were well, 19 moderately, 15 poorly differentiated and 9 undifferentiated. χ2 analysis demonstrated that presence of erosion/ulceration, plump bright or speckled cells in dermis, keratin pearls and peritumoral inflammatory infiltrate correlated with diagnosis of invasive SCC. Erosion/ulceration and peritumoral inflammatory infiltrate were observed more frequently in poorly differentiated or undifferentiated tumors. Plump bright or speckled cells in the dermis were observed less often in well‐differentiated tumors. The presence of keratin pearls was associated with well or moderately differentiated tumors.

Conclusion

Ex vivo CLSM allowed rapid examination of SCC and provided useful information on invasiveness and grading of the tumor.
Intestinal organoids containing poly(lactic‐co‐glycolic acid) nanoparticles for the treatment of inflammatory bowel diseases
Authors: Davoudi Zahra , Peroutka‐Bigus Nathan , Bellaire Bryan , Wannemuehler Michael , Barrett Terrence A , Narasimhan Balaji , Wang Qun
Published: December 2017

Inflammatory bowel disease (IBD) causes inflammation to the gastrointestinal tract. Local administration of anti‐inflammatory drugs such as 5‐aminosalicylic acid (5‐ASA) can alleviate the symptoms of IBD. The application of nanoparticles for IBD treatment in direct rectal administration showed high drug availability and treatment efficacy. However, relying on size‐dependent adsorption of smaller particles is not sufficient for making the formulation capable of targeting. Intestinal organoids can improve the functionality of the nanoparticles due to their ability to adsorb small nanoparticle inside the lumen and attach to the damaged area. In this study, intestinal organoids were used as carriers of 5‐ASA‐loaded poly(lactic‐co‐glycolic acid) nanoparticles. The nanoparticle sizes, confirmed by scanning electron microscopy, were 200–300 nm and the zeta potential were negative. The nanoparticles did not have any noticeable pernicious effect on organoid growth and viability. After mixing the nanoparticles with Matrigel and organoids, Rhodamine B loaded inside the nanoparticles was highly detected inside the organoid's lumen after 3 days by confocal fluorescent microscopy and no longer detected in the lumen after day 4. It may be attributed to the ability of the lumen to digest particles. Thus, the organoid Trojan horse system is a possible approach for delivering drugs to inflamed areas. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 876–886, 2018.
Solvent or thermal extraction of ethylene oxide from polymeric materials: Medical device considerations
Authors: Lucas Anne D. , Forrey Christopher , Saylor David M. , Vorvolakos Katherine
Published: December 2017

Ethylene oxide (EO) gas is commonly used to sterilize medical devices. Bioavailable residual EO, however, presents a significant toxicity risk to patients. Residual EO is assessed using international standards describing extraction conditions for different medical device applications. We examine a series of polymers and explore different extraction conditions to determine residual EO. Materials were sterilized with EO and exhaustively extracted in water, in one of three organic solvents, or in air using thermal desorption. The EO exhaustively extracted varies significantly and is dictated by two factors: the EO that permeates the material during sterilization; and the effectiveness of the extraction protocol in flushing residual EO from the material. Extracted EO is maximized by a close matches between Hildebrand solubility parameters δpolymer, δEO, and δsolvent. There remain complexities to resolve, however, because maximized EO uptake and detection are accompanied by great variability. These observations may inform protocols for material selection, sterilization, and EO extraction. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2455–2463, 2018.
Proof of concept testing of a positive reference material for in vivo and in vitro skin irritation testing
Authors: Nomura Yusuke , Lee Michelle , Fukui Chie , Watanabe Kayo , Olsen Daniel , Turley Audrey , Morishita Yuki , Kawakami Tsuyoshi , Yuba Toshiyasu , Fujimaki Hideo , Inoue Kaoru , Yoshida Midori , Ogawa Kumiko , Haishima Yuji
Published: December 2017

In vivo and in vitro irritation testing is important for evaluating the biological safety of medical devices. Here, the performance of positive reference materials for skin irritation testing was evaluated. Four reference standards, referred to as Y‐series materials, were analyzed: a polyvinyl chloride (PVC) sheet spiked with 0 (Y‐1), 1.0 (Y‐2), 1.5 (Y‐3), or 10 (Y‐4) parts of Genapol X‐080 per 100 parts of PVC by weight. Y‐1, Y‐2, and Y‐3 did not induce skin irritation responses in an in vitro reconstructed human epidermis (RhE) tissue model, as measured by tissue viability or interleukin‐1α release, or in an in vivo intracutaneous response test using rabbits. In contrast, Y‐4 extracts prepared with saline or sesame oil at 37°C and 50°C clearly elicited positive irritation responses, including reduced viability (< 50%) and significantly higher interleukin‐1α release compared with the solvent alone group, in the RhE tissue model and an intracutaneous response test, where substantial necrosis was observed by histopathology. The positive skin irritation responses induced in vitro under various extraction conditions, as well as those elicited in vivo, indicate that Y‐4 is an effective extractable positive control material for in vivo and in vitro skin irritation tests of medical devices. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2807–2814, 2018.
Amino group of salicylic acid exhibits enhanced inhibitory potential against insulin amyloid fibrillation with protective aptitude toward amyloid induced cytotoxicity
Authors: Zaman Masihuz , Khan Mohsin Vahid , Zakariya Syed Mohammad , Nusrat Saima , Meeran Syed Mustapha , Alam Parvez , Ajmal Mohammad Rehan , Wahiduzzaman Wahiduzzaman , Shahein Yasser E. , Abouelella Amira M. , Khan Rizwan Hasan
Published: December 2017

Protein misfolding and aggregation lead to amyloid generation that in turn may induce cell membrane disruption and leads to cell apoptosis. In an effort to prevent or treat amyloidogenesis, large number of studies has been paying attention on breakthrough of amyloid inhibitors. In the present work, we aim to access the effect of two drugs, that is, acetylsalicylic acid and 5‐amino salicylic acid on insulin amyloids by using various biophysical, imaging, cell viability assay, and computational approaches. We established that both drugs reduce the turbidity, light scattering and fluorescence intensity of amyloid indicator dye thioflavin T. Premixing of drugs with insulin inhibited the nucleation phase and inhibitory potential was boosted by increasing the concentration of the drug. Moreover, addition of drugs at the studied concentrations attenuated the insulin fibril induced cytotoxicity in breast cancer cell line MDA‐MB‐231. Our results highlight the amino group of salicylic acid exhibited enhanced inhibitory effects on insulin fibrillation in comparison to acetyl group. It may be due to presence of amino group that helps it to prolong the nucleation phase with strong binding as well as disruption of aromatic and hydrophobic stacking that plays a key role in amyloid progression.
Resistance of oral cancer cells to 5‐ALA‐mediated photodynamic therapy
Authors: Rosin Flávia Cristina P. , Teixeira Marina Gabriela , Pelissari Cibele , Corrêa Luciana
Published: December 2017

Photodynamic therapy (PDT) has been indicated for oral squamous cell carcinoma (OSCC) at early stages. Chemo and radio‐resistance are frequently observed in OSCC, but it is unknown whether this tumor can develop resistance to PDT. It was investigated the process of acquiring resistance to multiple cycles of PDT by using OSCC cells. We also analyzed the expression of anti‐apoptotic proteins and those related to Akt/mTOR pathway. Sub‐lethal doses of PDT were applied, consisting of a constant concentration of 5‐aminolevulinic acid (5‐ALA) (1 mM, 4‐h incubation) and increasing irradiation dose with LED (from 5.86 to 10.54 J/cm2). Cell viability, migration capacity, intracellular expression of protoporphyrin IX (PpIX), mitochondrial density, and pro‐survival proteins were investigated in PDT‐resistant cells. Six OSCC cell generations resistant to PDT were isolated. The resistant cells exhibited a survival phenotype characterized by a reduction in the expression of endogenous PpIX, increase in mitochondrial density, increase in migration capacity, and up‐regulation of p‐NFκB, p‐survivin, iNOS, p‐Akt Ser473, cyclin D1, p‐mTOR Ser2481, and p‐mTOR Ser2448. OSCC cells are able to survive doses of 5‐ALA‐PDT by reducing PpIX synthesis and activating signaling pathways related to the inhibition of apoptosis and improvement of cell proliferation. Further studies are necessary to confirm whether this PDT‐resistance phenotype can be clinically present, mainly in OSCC showing clinical recurrences after exposure to different PDT protocols.
Identification of potential crucial genes associated with carcinogenesis of clear cell renal cell carcinoma
Authors: Song Erlin , Song Wenting , Ren Minghua , Xing Li , Ni Wenjun , Li Yongxiang , Gong Mancheng , Zhao Mingbo , Ma Xin , Zhang Xu , An Ruihua
Published: December 2017

Clear cell renal cell carcinoma (ccRCC) is a common genitourinary malignancy with high mortality. However, the molecular pathogenesis of ccRCC remains unclear and effective biomarkers for daily practice are still limited. Thus, we aimed to identify the potential crucial genes and pathways associated with carcinogenesis of ccRCC and further analyze the molecular mechanisms implicated in tumorigenesis. In the present study, expression profiles GSE 66270, GSE 53757, GSE 36895, and GSE 76351 were downloaded from GEO database, including 244 matched primary and adjacent normal tissues, furthermore, the level 3 RNAseq dataset (RNAseqV2 RSEM) of KIRC was also downloaded from The Cancer Genome Atlas (TCGA), which consist of 529 ccRCC tumors and 72 normal tissues. Then, differentially expressed genes (DEGs) and pathway enrichment were analyzed by using R software. A total of 129 up‐ and 123 down‐regulated genes were identified, which were aberrantly expressed both in GEO and TCGA data. Second, Gene ontology (GO) analyses revealed that most of the DEGs were significantly enriched in integral component of membrane, extracellular exosome, plasma membrane, cell adhesion, and receptor binding. Signaling pathway analyses indicated that DEGs had common pathways in signal transduction, metabolism, and immune system. Third, hub genes were identified with protein‐protein interaction (PPI) network, including PTPRC, TGFB1, EGF, MYC, ITGB2, CTSS, FN1, CCL5, KNG1, and CD86. Additionally, sub‐networks analyse was also performed by using MCODE plugin. In conclusion, the novel DEGs and pathways in ccRCC identified in this study may provide new insight into the underlying molecular mechanisms that facilitates RCC carcinogenesis.
Do surfaces of positive electrostatic potential on different halogen derivatives in molecules attract? like attracting like!
Authors: Varadwaj Arpita , Varadwaj Pradeep R. , Yamashita Koichi
Published: December 2017

Coulomb's law states that like charges repel, and unlike charges attract. However, it has recently been theoretically revealed that two similarly charged conducting spheres will almost always attract each other when both are in close proximity. Using multiscale first principles calculations, we illustrate practical examples of several intermolecular complexes that are formed by the consequences of attraction between positive atomic sites of similar or dissimilar electrostatic surface potential on interacting molecules. The results of the quantum theory of atoms in molecules and symmetry adapted perturbation theory support the attraction between the positive sites, characterizing the F•••X (X = F, Cl, Br) intermolecular interactions in a series of 20 binary complexes as closed‐shell type, although the molecular electrostatic surface potential approach does not (a failure!). Dispersion that has anr−6dependence, whereris the equilibrium distance of separation, is found to be the sole driving force pushing the two positive sites to attract. © 2017 Wiley Periodicals, Inc.
Single‐pass incremental force updates for adaptively restrained molecular dynamics
Authors: Singh Krishna Kant , Redon Stephane
Published: December 2017

Adaptively restrained molecular dynamics (ARMD) allows users to perform more integration steps in wall‐clock time by switching on and off positional degrees of freedoms. This article presents new, single‐pass incremental force updates algorithms to efficiently simulate a system using ARMD. We assessed different algorithms for speedup measurements and implemented them in the LAMMPS MD package. We validated the single‐pass incremental force update algorithm on four different benchmarks using diverse pair potentials. The proposed algorithm allows us to perform simulation of a system faster than traditional MD in both NVE and NVT ensembles. Moreover, ARMD using the new single‐pass algorithm speeds up the convergence of observables in wall‐clock time. © 2017 Wiley Periodicals, Inc.
Genetic polymorphisms of microRNA machinery genes predict overall survival of esophageal squamous carcinoma
Authors: Wang Cuiju , Dong Hailing , Fan Haiyan , Wu Jianhua , Wang Guiying
Published: December 2017

Background

MicroRNA (miRNA)‐related single nucleotide polymorphisms (miR‐SNPs) in miRNA processing machinery genes are implicated in carcinogenesis, as they change the expression profiles of miRNA. Six miR‐SNPs in miRNA processing machinery genes, including Dicer (rs3742330), RAN (rs14035), XPO5 (rs11077), TNRC6B (rs9623117), GEMIN3 (rs197412), and GEMIN4 (rs2740348), were evaluated for their association with esophageal squamous cell carcinoma (ESCC).

Methods

The miR‐SNP of the miRNA processing genes were genotyped using the polymerase chain reaction‐ligase detection reaction (PCR‐LDR) assay, while the XPO5 expression levels in ESCC tissues were measured by immunochemistry methods.

Results

Patients carrying the rs11077 AA allele exhibited a significantly increased lifespan than AC+CC carriers, as determined by univariate and multivariate analyses (relative risk: 2.490; 95% confidence interval [CI]: 1.225‐5.058; P=.012). Furthermore, the rs11077 AA genotype displayed a trend for high XPO5 expression in ESCC tissues by immunochemistry analysis, and these high XPO5 expression levels were also associated with high survival rates among ESCC patients.

Conclusion

Our results suggested that the miRNA machinery gene expression‐associated miR‐SNPs would modify cancer outcomes; in this light, XPO5 may be an important new target for ESCC therapy.
Role of IL‐6‐mediated expression of NS5ATP9 in autophagy of liver cancer cells
Authors: Lu Hongping , Han Ming , Yuan Xiaoxue , Tursun Kelbinur , Zhang Yu , Li Yaru , Li Zhongshu , Feng Shenghu , Zhou Li , Pan Zhipeng , Wang Qi , Han Kai , Liu Shunai , Cheng Jun
Published: December 2017

This study aimed to investigate the relationship between interleukin‐6 (IL‐6) and NS5ATP9 in autophagy of liver cancer cells. Autophagy is one of the important regulators of the replication of hepatitis C virus and the survival of tumors. IL‐6 is a multifunctional cytokine that plays an important role in autophagy and development of many kinds of tumors. However, the role of IL‐6 in autophagy has not been fully explored. A previous study had shown that a novel gene, NS5ATP9, could modulate autophagy. The present study demonstrated that human IL‐6 recombinant protein induced autophagy of HepG2 cells. Conversely, autophagy decreased after IL‐6 was silenced or neutralized with monoclonal antibody against human IL‐6. In addition, NS5ATP9 was upregulated by IL‐6 via nuclear factor–kappaB activation, as detected by Western blot. Further studies indicated that the induction of autophagy by IL‐6 could be attenuated by silencing NS5ATP9. Interestingly, the expression of NS5ATP9, in turn, resulted in the upregulation of IL‐6. In conclusion, IL‐6 could induce autophagy by expressing NS5ATP9, while NS5ATP9 upregulated IL‐6 levels in turn, which further induced autophagy.
RETREG1 (FAM134B): A new player in human diseases: 15 years after the discovery in cancer
Authors: Islam Farhadul , Gopalan Vinod , Lam Alfred King‐yin
Published: December 2017

FAM134B (family with sequence similarity 134, member B)/RETREG1 and its functional roles are relatively new in human diseases. This review aimed to summarize various functions of FAM134B since our first discovery of the gene in 2001. The protein encoded by FAM134B is a reticulophagy receptor that regulates turnover of the endoplasmic reticulum (ER) by selective phagocytosis. Absence or non‐functional expression of FAM134B protein impairs ER‐turnover and thereby is involved in the pathogenesis of some human diseases. FAM134B inhibition contributes to impair proteostasis in the ER due to the accumulation of misfolded or aggregated proteins, which in turn leads to compromised neuronal survival and progressive neuronal degenerative diseases. Mutations in FAM134B associated with hereditary sensory and autonomic neuropathy type IIB (HSAN IIB). Selective cleavage of FAM134B by Dengue, Zika, and West Nile virus encoded protease NS2B3 leads to the increased production of infection units, whereas upregulation of FAM134B inhibits viral replication. In cancer, FAM134B acts as a tumor suppressor and inhibit cancer growth both in‐vitro and in‐vivo. Pharmacological upregulation of FAM134B resulted in reduced cancer cell growth and proliferation. In addition, FAM134B mutations are common in patients with colorectal adenocarcinoma, and oesophageal squamous cell carcinoma. These mutations and expression changes of FAM134B were associated with the biological aggressiveness of these cancers. FAM134B also plays a role in allergic rhinitis, vascular dementia, and identification of stem cells. Taken together, information available in the literature suggests that FAM134B plays critical roles in human diseases, by interacting with different biological and chemical mediators, which are primarily regulated by ER turnover.
Retracted: Protective effects of microRNA‐431 against cerebral ischemia‐reperfusion injury in rats by targeting the Rho/Rho‐kinase signaling pathway
Authors: Han Xin‐Rui , Wen Xin , Wang Yong‐Jian , Wang Shan , Shen Min , Zhang Zi‐Feng , Fan Shao‐Hua , Shan Qun , Wang Liang , Li Meng‐Qiu , Hu Bin , Sun Chun‐Hui , Wu Dong‐Mei , Lu Jun , Zheng Yuan‐Lin
Published: December 2017

This study investigates the protective effects of miR‐431 against cerebral ischemia‐reperfusion injury through the Rho/Rho‐kinase signaling pathway. SD rats were randomly classified into normal, sham, and model (middle cerebral artery occluded) groups. Rho expression and cerebral infarction were visualized by immunohischemistry and TTC staining, respectively. qRT‐PCR and western blotting were used to measure mRNA and protein expression of miR‐431 and Rho/Rho‐kinase signaling pathway‐related genes. Hippocampal neurons were extracted and assigned into normal, blank, negative control (NC), miR‐431 mimics, miR‐431 inhibitors, siRNA‐Rho, and miR‐431 inhibitors + siRNA‐Rho groups. Proliferation and apoptosis were detected by MTT and flow cytometry, respectively. Compared with the normal group, the model group showed elevated Rho expression, area of cerebral infarction, and expressions of Rho/Rho‐kinase related genes but reduced miR‐431 expression. Compared with the blank group, expression of Rho, Rho‐kinase α, and Rho‐kinase β decreased and miR‐431 expression increased in the miR‐431 mimics and siRNA‐Rho groups, and the tendency reversed in the miR‐431 inhibitors group. Enhanced proliferation and inhibited apoptosis were exhibited in the miR‐431 mimics and siRNA‐Rho groups while results in the miR‐431 inhibitors group reversed. Findings obtained from this study indicated that miR‐431 confers protection against cerebral ischemia‐reperfusion injury through negatively regulating the Rho/Rho‐kinase signaling pathway.
MicroRNAs in cutaneous melanoma: Role as diagnostic and prognostic biomarkers
Authors: Ross Casey L. , Kaushik Shivani , Valdes‐Rodriguez Rodrigo , Anvekar Rina
Published: December 2017

Melanoma is the leading cause of skin cancer deaths in the United States, and its incidence has been rising steadily for the past 30 years (Aftab, Dinger, & Perera, 2014). A more complete understanding of the molecular mechanisms that drive melanomagenesis is crucial to improve diagnosis, prognostication, and treatment of this disease. Given that melanoma survival rates are better when the disease is detected early, precise diagnostic tests for early melanoma detection would be extremely useful. In addition, as survival rates decrease drastically when the disease becomes metastatic, improved tools to more precisely identify high‐risk patients as well as to predict treatment response are necessary. The role of microRNAs (miRNAs) in melanoma biology could be the key. miRNA expression profiling has identified several miRNAs that play a crucial role in melanoma cell proliferation, migration, and invasion, as well as miRNAs involved in apoptosis and in the immune response. Here we review the most current data on the miRNAs involved in melanoma as well as their potential roles as diagnostic and prognostic biomarkers of this disease.
Synthesis of a New Imidazo[4′,5′:3,4]pyrazolo[5,1‐c][1,2,4]triazine‐4,8‐dione Heterocyclic System
Authors: Ivanov Sergey M. , Mironovich Lyudmila M. , Solyev Pavel N. , Rodinovskaya Lyudmila A. , Shestopalov Anatoliy M.
Published: December 2017

A novel imidazo[4′,5′:3,4]pyrazolo[5,1‐c][1,2,4]triazine‐4,8‐dione heterocyclic system was synthesized starting from available 4‐amino‐6‐tert‐butyl‐3‐methylthio‐1,2,4‐triazin‐5(4H)‐one in four steps with 28% overall yield.
Bombesin‐functionalized water‐soluble gold nanoparticles for targeting prostate cancer
Authors: Simpson Emily J. , Gobbo Pierangelo , Bononi Fernanda C. , Murrell Emily , Workentin Mark S. , Luyt Leonard G.
Published: December 2017

Cancer targeting can be used for both tumor diagnosis and therapy. Recently, gold nanoparticles (AuNPs) have found utility in this field as they are very small in size, and thus display an enhanced permeability and retention effect, allowing them to be taken up by tumor cells through “passive targeting.” However, this accumulation is non‐specific. Conversely, AuNPs functionalized with targeting entities such as peptides, antibodies, or small molecules can specifically target tumors through interaction with cancer‐specific protein receptors. In this study, targeted AuNPs were developed using an azide‐modified peptide that was able to react with alkyne‐functionalized AuNPs through an interfacial strain‐promoted azide‐alkyne cycloaddition. Small (3 nm) AuNPs were made water‐soluble through PEGylation and functionalized with dibenzocyclooctyne to add the alkyne functionality. For the targeting entity, a pan‐bombesin peptide ([D‐Phe6,β‐Ala11,Phe13,Nle14]bombesin(6–14)) was chosen as it binds to all four receptor subtypes of the gastrin releasing peptide receptor, which is highly expressed in prostate cancer. Prostate cancer (PC‐3) cells were incubated with the targeted AuNPs and studied via transmission electron microscopy. AuNPs conjugated with bombesin showed higher accumulation in PC‐3 cells than either the blocking or control studies. These results suggest that these small, water‐soluble, bombesin‐functionalized AuNPs have potential applications in targeting prostate cancer as diagnostic or therapeutic entities.
Origin and transformation of the in‐flight wing‐coupling structure in Psocodea (Insecta: Paraneoptera)
Authors: Ogawa Naoki , Yoshizawa Kazunori
Published: December 2017

Many four‐winged insects have mechanisms that unite the forewings and hindwings in a single plane. Such an in‐flight wing coupling apparatus may improve flight performance in four‐winged insects, but its structure is variable among different insect groups. The wings of bark lice (Insecta: Psocodea: “Psocoptera”) also have an in‐flight wing coupling apparatus, but to date, its morphology has not been studied in detail. In this study, we examined the wing‐coupling structure in representative species of the three suborders of bark lice (Trogiomorpha, Troctomorpha, and Psocomorpha) and inferred its origin and transformation. We conclude that the main component of the psocodean wing coupling apparatus evolved once in the common ancestor via modification of cuticular structures at the apex of the forewing CuP vein. Morphological differences in components of the coupling structures are phylogenetically informative at the intraorder level and include an autapomorphy that characterizes Troctomorpha and a synapomorphy that supports a sister relationship between Troctomorpha and Psocomorpha.
The ontogeny of the female reproductive system in the parasitic castrator pea crab Calyptraeotheres garthi: Implications for its mating system
Authors: Ocampo Emiliano H. , Luppi Tomás A. , Spivak Eduardo D. , Klaus Sebastian
Published: December 2017

The knowledge of the mating system of pea crabs is still fragmentary as it remains dubious whether females copulate in the juvenile and free‐living ‘hard’ or in the obligatory symbiotic stages (adult stage ‘V’ or intermediate stages II to IV). To discriminate between these two possibilities, we analysed the female seminal receptacles, vagina and opercula, and the sperm content in different stages of the pea crab Calyptraeotheres garthi. Our histology and scanning electron microscopy results revealed that in the hard stage the seminal receptacle is simple without secretory epithelia, and vagina and opercula are not controlled by musculature. In stages II to IV, the seminal receptacles, vagina, and opercula are under development and these structures reach maturity in stage V. These results suggest that females become receptive in stage V and not during predating stages. We found no spermatozoa in SR of ‘hard’ and stage II to IV females while these structures were loaded of sperm in most stage V, indicating that females start to mate in stage V. Our results support the notion that males of C. garthi roam among hosts in search for sedentary stage V females, as predicted by Baeza and Thiel's () model of mating systems for symbiotic crustaceans. Nevertheless, we failed to reveal whether females mate repeatedly: the accumulation of sperm in larger females might indicate occurrence of multiple copula or a high variability in male sperm transfer.
Elaborate ultrastructure of the Hirudo (Annelida: Hirudinae) cocoon surface
Authors: Saidel William M. , Saglam Naim , Salas‐de la Cruz David , Saunders Ralph , Shain Daniel H.
Published: December 2017

Species of medicinal leeches (Hirudo medicinalis, H. verbana, and H. sulukii) secrete hard‐shelled cocoons. When initially deposited, a cocoon is surrounded by a foam. Over a short time, the foam is transformed into a three‐dimensional structure. We show here that this peripheral structure likely forms by the solidification and dehydration of a moderately viscous, proteinaceous substance that surrounds bubbles of various sizes. The resulting matrix‐like structure comprises a network of curved branches juxtaposed at ∼120° and taper in width as a function of distance from the outer cocoon wall. The material is proteinaceous, and traps environmental material in its composition, especially silicon. The geometry of compartments and abundance of silicon on branch surfaces suggest a mechanism for trapping water to prevent desiccation in a terrestrial environment.