bluuebunny/crossref_metadata_2025 huggingface dataset:
The Relationship between Perceived Coaching Behaviors, Competitive Trait Anxiety, and Athlete Burnout: A Cross-Sectional Study
Authors: Cho Seongkwan , Choi Hunhyuk , Kim Youngsook
Published: April 2019

Athletes possibly experience a great deal of stress which may cause anxiety and burnout. Athletes’ perceptions of their coaches’ behaviors influence their performance and psychological well-being. The purpose of this study is to investigate the relationship between athletes’ perception of their coaches’ coaching behaviors and burnout, and also to examine the medication effects of competitive trait anxiety on the relationship. A total of 368 collegiate athletes participated in the study, and their ages ranged from 20 to 26 years old (Mage = 21.21 years, SD = 1.07 years). A cross-sectional research design was employed to collect the data. Descriptive statistics and structural equation modeling are utilized to analyze the data. Trait anxiety in athletes had a significant correlation with athlete burnout as well as significant pathways. Controlling coaching behaviors were significantly related to athletes’ competitive trait anxiety, whereas autonomy-supportive coaching behaviors were not significantly related to trait anxiety. A significant positive pathway from controlling coaching to trait anxiety was observed. The bootstrapping results indicated a significant and indirect pathway from controlling coaching to athlete burnout via competitive trait anxiety. Given that controlling coaching behaviors affected trait anxiety and, in turn, burnout, it is concluded that coaches should provide less controlling coaching to reduce anxiety and burnout in athletes.
Physical Activity and Thyroid Cancer Risk: A Case-Control Study in Catania (South Italy)
Authors: Fiore Maria , Cristaldi Antonio , Okatyeva Valeriya , Lo Bianco Salvatore , Oliveri Conti Gea , Zuccarello Pietro , Copat Chiara , Caltabiano Rosario , Cannizzaro Matteo , Ferrante Margherita
Published: April 2019

Background: The health benefits of physical activity are well established, but the association between physical activity and thyroid cancer remains poorly understood. The aim of the study was to investigate the relationship between physical activity and thyroid cancer in order to determine type, frequency, and duration of exercise needed to maximize prevention. Method: Cases, diagnosed from January 2009 to July 2018, and controls were enrolled at the University Hospital “Policlinico-Vittorio Emanuele” of Catania (South Italy). Logistic regression models were used to estimate the crude and adjusted odds ratios (ORs) and their 95% confidence intervals. Results: A total of 106 cases (91.2% papillary type) and 217 controls were enrolled. Physical activity was rare in Catania (32.8%) and was not correlated to risk of total thyroid cancer (OR: 0.997; 95% CI: 0.515–1.929). Conversely, walking every day for at least 60 minutes reduced the risk of thyroid cancer (OR: 0.357; 95% CI: 0.157–0.673). Conclusions: Our study showed that daily walking duration was associated with lower risk of thyroid cancer using a case-control study. Unfortunately, the frequency of physical activity often declines with age, particularly among the elderly, thus more research on physical activity adherence is needed to determine which approaches are most effective in promoting sustained physical activity participation.
Experimental and Numerical Simulation of the Formation of Cold Seep Carbonates in Marine Sediments
Authors: Ye Tao , Jin Guangrong , Wu Daidai , Liu Lihua
Published: April 2019

Cold seep emissions of low temperature fluid from the marine sediment basins are mainly comprised of methane and other hydrocarbons. A series of biogeochemical processes related to methane lead to the formation of authigenic carbonate minerals. In this study, a self-built experimental device was used to study the formation process of carbonate minerals under cold seep conditions. The concentrations of pore water chemicals, HCO3− and Ca2+ at different heights of the reactor under flow conditions can be observed. According to the experimental results, the formation process of carbonate minerals under cold seep conditions was estimated, that 1 m carbonate growth needs 12,000 and 7000 years, respectively, under fast (5 mL·min−1) and slow emission (1 mL·min−1) conditions. Furthermore, TOUGHREACT was used to simulate the diagenesis process. A 1D unsteady react-transport model was developed, and the experimental data was used to constrain the simulation. The results of simulation show that the carbonates need 17,000 and 9700 years to grow 1 m under the condition of fast and slow flow scenarios, respectively. The results of this work will contribute to the study of foundation on the formation of authigenic minerals in cold seep areas, and for the physical properties of sedimentary media as well.
Dating Whole Genome Duplication in Ceratopteris thalictroides and Potential Adaptive Values of Retained Gene Duplicates
Authors: Zhang Rui , Wang Fa-Guo , Zhang Jiao , Shang Hui , Liu Li , Wang Hao , Zhao Guo-Hua , Shen Hui , Yan Yue-Hong
Published: April 2019

Whole-genome duplications (WGDs) are widespread in plants and frequently coincide with global climatic change events, such as the Cretaceous–Tertiary (KT) extinction event approximately 65 million years ago (mya). Ferns have larger genomes and higher chromosome numbers than seed plants, which likely resulted from multiple rounds of polyploidy. Here, we use diploid and triploid material from a model fern species, Ceratopteris thalictroides, for the detection of WGDs. High-quality RNA-seq data was used to infer the number of synonymous substitutions per synonymous site (Ks) between paralogs; Ks age distribution and absolute dating approach were used to determine the age of WGD events. Evidence of an ancient WGD event with a Ks peak value of approximately 1.2 was obtained for both samples; however, the Ks frequency distributions varied significantly. Importantly, we dated the WGD event at 51–53 mya, which coincides with the Paleocene-Eocene Thermal Maximum (PETM), when the Earth became warmer and wetter than any other period during the Cenozoic. Duplicate genes were preferentially retained for specific functions, such as environment response, further support that the duplicates may have promoted quick adaption to environmental changes and potentially resulted in evolutionary success, especially for pantropical species, such as C. thalictroides, which exhibits higher temperature tolerance.
The Impact of O-Glycosylation on Cyanidin Interaction with RBCs and HMEC-1 Cells—Structure–Activity Relationships
Authors: Cyboran-Mikołajczyk Sylwia , Solarska-Ściuk Katarzyna , Mieszała Katarzyna , Glatzel-Plucińska Natalia , Matczak Karolina , Kleszczyńska Halina
Published: April 2019

With the aim of contributing to the knowledge about their potential therapeutic activity, we determined the biological activities of cyanidin and its selected O-glycosides in relation to erythrocytes (RBCs) and human dermal vascular endothelial cells (HMEC-1). Furthermore, on the basis of changes in the physical/functional properties of the cells, the structure–activity relationships of the compounds were determined. Concerning erythrocytes, we analyzed the antioxidant activity of the compounds and their impact on the RBCs’ shape and transmembrane potential. The compounds’ cytotoxic activity, ability to modulate apoptosis, cell cycle, and intracellular ROS generation, as well as inhibitory activity against AAPH-inducted oxidative stress, were determined in relation to HMEC-1 cells. We demonstrated that biological activity of cyanidin and its O-glycosides strongly depends on the number and type of sugar substituents, and varies depending on the extracellular environment and type of cells. The compounds are practically non-cytotoxic, and do not induce apoptosis or disturb the progression of the cell cycle. Additionally, the compounds alter the shape of RBCs, but they do not affect their transmembrane potential. They effectively protect erythrocytes against free radicals and affect intracellular reactive oxygen spices (ROS) generation under physiological and AAPH-induced oxidative stress conditions. Our results suggest a potential beneficial effect of cyanidin on the cardiovascular system.
Aminoacyl-tRNA Synthetases and tRNAs for an Expanded Genetic Code: What Makes them Orthogonal?
Authors: Melnikov Sergey V. , Söll Dieter
Published: April 2019

In the past two decades, tRNA molecules and their corresponding aminoacyl-tRNA synthetases (aaRS) have been extensively used in synthetic biology to genetically encode post-translationally modified and unnatural amino acids. In this review, we briefly examine one fundamental requirement for the successful application of tRNA/aaRS pairs for expanding the genetic code. This requirement is known as “orthogonality”—the ability of a tRNA and its corresponding aaRS to interact exclusively with each other and avoid cross-reactions with additional types of tRNAs and aaRSs in a given organism.
Moringin from Moringa Oleifera Seeds Inhibits Growth, Arrests Cell-Cycle, and Induces Apoptosis of SH-SY5Y Human Neuroblastoma Cells through the Modulation of NF-κB and Apoptotic Related Factors
Authors: Cirmi Santa , Ferlazzo Nadia , Gugliandolo Agnese , Musumeci Laura , Mazzon Emanuela , Bramanti Alessia , Navarra Michele
Published: April 2019

In the last decades, glucosinolates (GLs), precursors of isothiocyanates (ITCs), have been studied mostly for their chemopreventive and chemotherapeutic properties. The aim of our research was to study the antiproliferative effect of 4-(α-L-rhamnopyranosyloxy) benzyl glucosinolate (glucomoringin; GMG) bioactivated by myrosinase enzyme to form the corresponding isothiocyanate 4-(α-L-rhamnopyranosyloxy) benzyl C (moringin) in SH-SY5Y human neuroblastoma cells. We found that moringin significantly reduced SH-SY5Y cell growth in a time and concentration-dependent (p < 0.05, 0.01, and 0.001 vs. ctrl, after treatment with 16.4 µM moringin for 24, 48, and 72 h, respectively) manner through a mechanism involving the activation of apoptotic machinery. In addition, it altered the normal progression of cells through the cell cycle, increasing the cell population in both G2 and S phases, as well as decreasing that in the G1 phase. Studying the drug mechanism of action, we found that moringin was able to increase the expression of p53, p21, and Bax at both the protein and transcriptional level. Moreover, exposure of SH-SY5Y cells to moringin significantly increased the gene expression of both caspase 3 and 9 and enhanced their cleavage, thereby initiating an intrinsic apoptotic cascade. Finally, moringin inhibited nuclear translocation of NF-κB. Our study demonstrates the ability of moringin to reduce the growth of SH-SY5Y cells and reveals its mechanism of action, suggesting its promising role as an anticancer drug.
The Crosstalk Between Cell Adhesion and Cancer Metabolism
Authors: Sousa Bárbara , Pereira Joana , Paredes Joana
Published: April 2019

Cancer cells preferentially use aerobic glycolysis over mitochondria oxidative phosphorylation for energy production, and this metabolic reprogramming is currently recognized as a hallmark of cancer. Oncogenic signaling frequently converges with this metabolic shift, increasing cancer cells’ ability to produce building blocks and energy, as well as to maintain redox homeostasis. Alterations in cell–cell and cell–extracellular matrix (ECM) adhesion promote cancer cell invasion, intravasation, anchorage-independent survival in circulation, and extravasation, as well as homing in a distant organ. Importantly, during this multi-step metastatic process, cells need to induce metabolic rewiring, in order to produce the energy needed, as well as to impair oxidative stress. Although the individual implications of adhesion molecules and metabolic reprogramming in cancer have been widely explored over the years, the crosstalk between cell adhesion molecular machinery and metabolic pathways is far from being clearly understood, in both normal and cancer contexts. This review summarizes our understanding about the influence of cell–cell and cell–matrix adhesion in the metabolic behavior of cancer cells, with a special focus concerning the role of classical cadherins, such as Epithelial (E)-cadherin and Placental (P)-cadherin.
Optimizing PCR Detection of West Nile Virus from Body Fluid Specimens to Delineate Natural History in an Infected Human Cohort
Authors: Gorchakov Rodion , Gulas-Wroblewski Bonnie E. , Ronca Shannon E. , Ruff Jeanne C. , Nolan Melissa S. , Berry Rebecca , Alvarado R. Elias , Gunter Sarah M. , Murray Kristy O.
Published: April 2019

West Nile virus (WNV), a mosquito-borne arbovirus, remains a major global health concern. In this study, we optimized PCR methods then assessed serially-collected whole blood (WB), urine (UR), saliva, and semen specimens from a large cohort of WNV-positive participants to evaluate the natural history of infection and persistent shedding of WNV RNA. Viral RNA extraction protocols for frozen WB and UR specimens were optimized and validated through spiking experiments to maximize recovery of viral RNA from archived specimens and to assess the degradation of WNV RNA in stored UR specimens. The resultant procedures were used in conjunction with PCR detection to identify WNV-positive specimens and to quantify their viral loads. A total of 59 of 352 WB, 10 of 38 UR, and 2 of 34 saliva specimens tested positive for WNV RNA. Although a single semen specimen was positive 22 days post onset, we could not definitively confirm the presence of WNV RNA in the remaining specimens. WNV RNA-positive UR specimens exhibited profound loss of viral RNA during storage, highlighting the need for optimal preservation pre-storage. This study provides optimized methods for WNV RNA detection among different fluid types and offers alternative options for diagnostic testing during the acute stages of WNV.
The Antioxidant from Ethanolic Extract of Rosa cymosa Fruits Activates Phosphatase and Tensin Homolog In Vitro and In Vivo: A New Insight on Its Antileukemic Effect
Authors: Wang Kuan-Chih , Liu Yi-Chang , El-Shazly Mohamed , Shih Shou-Ping , Du Ying-Chi , Hsu Yu-Ming , Lin Hung-Yu , Chen Yu-Cheng , Wu Yang-Chang , Yang Shyh-Chyun , Lu Mei-Chin
Published: April 2019

Rosa cymosa Tratt is a Chinese herbal remedy that is used in the treatment of diarrhea, burns, rheumatoid arthritis, and hemorrhage. Despite its use in Asian folk medicine, there are limited reports on the biological activity of R. cymosa fruits. This study focused on the investigation of the antitumor effect of the antioxidative ethanolic extract of R. cymosa fruits (RCE) along with its underlying mechanism of action. RCE showed a potent cytotoxic effect against Sup-T1 and Molt-4 lymphoblastic leukemia cells. In the xenograft animal model, the tumor size was significantly reduced to about 59.42% in the RCE-treated group in comparison with the control group. The use of RCE (37.5, 75, or 150 μg/mL) triggered apoptosis by 26.52–83.49%, disrupted mitochondrial membrane potential (MMP) by 10.44–58.60%, and promoted calcium release by 1.29-, 1.44-, and 1.71-fold compared with the control group. The extract induced redox oxygen species (ROS) generation through the elimination of Nrf2/Keap1/P62-mediated oxidative stress response. The loss of phosphatase and tensin homolog (PTEN) activation by RCE impaired PI3K/Akt/Foxo and Jak/Stat activation pathways, which contributed to tumorigenesis. These multiple targets of R. cymosa against hematologic cancer cells suggested its potential application as an antileukemic dietary supplement.
Nonsteroidal Anti-Inflammatory Drugs Prevent Vincristine-Dependent Cancer-Associated Fibroblasts Formation
Authors: Wawro Marta Ewelina , Sobierajska Katarzyna , Ciszewski Wojciech Michał , Niewiarowska Jolanta
Published: April 2019

Vincristine is used in the clinical treatment of colon cancer, especially in patients diagnosed in the advanced phase of cancer development. Unfortunately, similar to other agents used during antitumor therapy, vincristine might induce chemoresistance. Studies of this process focus mainly on the analysis of the molecular mechanisms within cancer, usually ignoring the role of stromal cells. Our present findings confirm that vincristine stimulates the secretion of tumor growth factors class beta and interleukin-6 from cancer-associated fibroblasts as a result of paracrine stimulation by cancer cells. Based on alterations in morphology, modulation of capillary formation, and changes in endothelial and mesenchymal marker profile, our findings demonstrate that higher levels of tumor growth factor-βs and interleukin-6 enhance cancer-associated fibroblast-like cell formation through endothelial–mesenchymal transition and that nonsteroidal anti-inflammatory drug treatment (aspirin and ibuprofen) is able to inhibit this phenomenon. The process appears to be regulated by the rate of microtubule polymerization, depending on β-tubulin composition. While higher levels of tubulin-β2 and tubulin-β4 caused slowed polymerization and reduced the level of factors secreted to the extracellular matrix, tubulin-β3 induced the opposite effect. We conclude that nonsteroidal anti-inflammatory drugs should be considered for use during vincristine monotherapy in the treatment of patients diagnosed with colorectal cancer.
Non-Cryogenic Structure and Dynamics of HIV-1 Integrase Catalytic Core Domain by X-ray Free-Electron Lasers
Authors: Park Jae-Hyun , Yun Ji-Hye , Shi Yingchen , Han Jeongmin , Li Xuanxuan , Jin Zeyu , Kim Taehee , Park Jaehyun , Park Sehan , Liu Haiguang , Lee Weontae
Published: April 2019

HIV-1 integrase (HIV-1 IN) is an enzyme produced by the HIV-1 virus that integrates genetic material of the virus into the DNA of infected human cells. HIV-1 IN acts as a key component of the Retroviral Pre-Integration Complex (PIC). Protein dynamics could play an important role during the catalysis of HIV-1 IN; however, this process has not yet been fully elucidated. X-ray free electron laser (XFEL) together with nuclear magnetic resonance (NMR) could provide information regarding the dynamics during this catalysis reaction. Here, we report the non-cryogenic crystal structure of HIV-1 IN catalytic core domain at 2.5 Å using microcrystals in XFELs. Compared to the cryogenic structure at 2.1 Å using conventional synchrotron crystallography, there was a good agreement between the two structures, except for a catalytic triad formed by Asp64, Asp116, and Glu152 (DDE) and the lens epithelium-derived growth factor binding sites. The helix III region of the 140–153 residues near the active site and the DDE triad show a higher dynamic profile in the non-cryogenic structure, which is comparable to dynamics data obtained from NMR spectroscopy in solution state.
Evolution Analysis of the Fasciclin-Like Arabinogalactan Proteins in Plants Shows Variable Fasciclin-AGP Domain Constitutions
Authors: He Jiadai , Zhao Hua , Cheng Zhilu , Ke Yuwei , Liu Jiaxi , Ma Haoli
Published: April 2019

The fasciclin-like arabinogalactan proteins (FLAs) play important roles in plant development and adaptation to the environment. FLAs contain both fasciclin domains and arabinogalactan protein (AGP) regions, which have been identified in several plants. The evolutionary history of this gene family in plants is still undiscovered. In this study, we identified the FLA gene family in 13 plant species covering major lineages of plants using bioinformatics methods. A total of 246 FLA genes are identified with gene copy numbers ranging from one (Chondrus crispus) to 49 (Populus trichocarpa). These FLAs are classified into seven groups, mainly based on the phylogenetic analysis of plant FLAs. All FLAs in land plants contain one or two fasciclin domains, while in algae, several FLAs contain four or six fasciclin domains. It has been proposed that there was a divergence event, represented by the reduced number of fasciclin domains from algae to land plants in evolutionary history. Furthermore, introns in FLA genes are lost during plant evolution, especially from green algae to land plants. Moreover, it is found that gene duplication events, including segmental and tandem duplications are essential for the expansion of FLA gene families. The duplicated gene pairs in FLA gene family mainly evolve under purifying selection. Our findings give insight into the origin and expansion of the FLA gene family and help us understand their functions during the process of evolution.
Pathophysiological, Molecular and Therapeutic Issues of Nonalcoholic Fatty Liver Disease: An Overview
Authors: Marchisello Simona , Di Pino Antonino , Scicali Roberto , Urbano Francesca , Piro Salvatore , Purrello Francesco , Rabuazzo Agata
Published: April 2019

Nonalcoholic Fatty Liver Disease (NAFLD) represents the leading cause of liver disease in developed countries but its diffusion is currently also emerging in Asian countries, in South America and in other developing countries. It is progressively becoming one of the main diseases responsible for hepatic insufficiency, hepatocarcinoma and the need for orthotopic liver transplantation. NAFLD is linked with metabolic syndrome in a close and bidirectional relationship. To date, NAFLD is a diagnosis of exclusion, and liver biopsy is the gold standard for diagnosis. NAFLD pathogenesis is complex and multifactorial, mainly involving genetic, metabolic and environmental factors. New concepts are constantly arising in the literature promising new diagnostic and therapeutic tools. One of the challenges will be to better characterize not only NAFLD development but overall NAFLD progression, in order to better identify NAFLD patients at higher risk of metabolic, cardiovascular and neoplastic complications. This review analyses NAFLD epidemiology and the different prevalence of the disease in distinct groups, particularly according to sex, age, body mass index, type 2 diabetes and dyslipidemia. Furthermore, the work expands on the pathophysiology of NAFLD, examining multiple-hit pathogenesis and the role of different factors in hepatic steatosis development and progression: genetics, metabolic factors and insulin resistance, diet, adipose tissue, gut microbiota, iron deposits, bile acids and circadian clock. In conclusion, the current available therapies for NAFLD will be discussed.
Dose-Dependent Effect of Hyperbaric Oxygen Treatment on Burn-Induced Neuropathic Pain in Rats
Authors: Wu Zong-Sheng , Wu Sheng-Hua , Lee Su-Shin , Lin Cen-Hung , Chang Chih-Hau , Lo Jing-Jou , Chai Chee-Yin , Wu Ching-Shuang , Huang Shu-Hung
Published: April 2019

Hyperbaric oxygen treatment (HBOT) has been used to reduce neuropathic pain. Melatonin and opioid receptors are involved in neuropathic pain, but it is not known if HBOT works through these pathways to achieve its antinociceptive effect. We divided anesthetized rats into two treatment and three sham groups. The two treatment groups received third-degree burns on their right hind paws, one treated in a hyperbaric chamber for a week and the other for two weeks. We evaluated the mechanical paw-withdrawal threshold (MWT) and expression of melatonin receptor 1 (MT1), melatonin receptor 2 (MT2), μ (MOR) and κ (KOR) opioid receptor, brain-derived neurotrophic factor (BDNF), Substance P, and calcitonin gene-related peptide (CGRP) in cuneate nucleus, dorsal horn, and hind paw skin by immunohistochemical, immunofluorescence assays and real-time quantitative polymerase chain reaction (RT-PCR). The group receiving one-week HBOT had increased expressions of MT1, MT2, MOR and KOR and decreased expressions of BDNF, Substance P, and CGRP. Their mechanically measured pain levels returned to normal within a week and lasted three weeks. This anti-allodynia effect lasted twice as long in those treated for two weeks. Our findings suggest that increasing the duration of HBOT can reduce burn-induced mechanical allodynia for an extended period of time in rats. The upregulation of melatonin and opioid receptors observed after one week of HBOT suggests they may be partly involved in attenuation of the mechanical allodynia. Downregulation of BDNF, substance P and CGRP may have also contributed to the overall beneficial effect of HBOT.
Role of Neuron–Glia Signaling in Regulation of Retinal Vascular Tone in Rats
Authors: Someya Eriko , Akagawa Mari , Mori Asami , Morita Akane , Yui Natsuko , Asano Daiki , Sakamoto Kenji , Nakahara Tsutomu
Published: April 2019

The interactions between neuronal, glial, and vascular cells play a key role in regulating blood flow in the retina. In the present study, we examined the role of the interactions between neuronal and glial cells in regulating the retinal vascular tone in rats upon stimulation of retinal neuronal cells by intravitreal injection of N-methyl-d-aspartic acid (NMDA). The retinal vascular response was assessed by measuring the diameter of the retinal arterioles in the in vivo fundus images. Intravitreal injection of NMDA produced retinal vasodilation that was significantly diminished following the pharmacological inhibition of nitric oxide (NO) synthase (nNOS), loss of inner retinal neurons, or intravitreal injection of glial toxins. Immunohistochemistry revealed the expression of nNOS in ganglion and calretinin-positive amacrine cells. Moreover, glial toxins significantly prevented the retinal vasodilator response induced by intravitreal injection of NOR3, an NO donor. Mechanistic analysis revealed that NO enhanced the production of vasodilatory prostanoids and epoxyeicosatrienoic acids in glial cells in a ryanodine receptor type 1-dependent manner, subsequently inducing the retinal vasodilator response. These results suggest that the NO released from stimulated neuronal cells acts as a key messenger in neuron–glia signaling, thereby causing neuronal activity-dependent and glial cell-mediated vasodilation in the retina.
ChimeraMiner: An Improved Chimeric Read Detection Pipeline and Its Application in Single Cell Sequencing
Authors: Lu Na , Li Junji , Bi Changwei , Guo Jing , Tao Yuhan , Luan Kaihao , Tu Jing , Lu Zuhong
Published: April 2019

As the most widely-used single cell whole genome amplification (WGA) approach, multiple displacement amplification (MDA) has a superior performance, due to the high-fidelity and processivity of phi29 DNA polymerase. However, chimeric reads, generated in MDA, cause severe disruption in many single-cell studies. Herein, we constructed ChimeraMiner, an improved chimeric read detection pipeline for analyzing the sequencing data of MDA and classified the chimeric sequences. Two datasets (MDA1 and MDA2) were used for evaluating and comparing the efficiency of ChimeraMiner and previous pipeline. Under the same hardware condition, ChimeraMiner spent only 43.4% (43.8% for MDA1 and 43.0% for MDA2) processing time. Respectively, 24.4 million (6.31%) read pairs out of 773 million reads, and 17.5 million (6.62%) read pairs out of 528 million reads were accurately classified as chimeras by ChimeraMiner. In addition to finding 83.60% (17,639,371) chimeras, which were detected by previous pipelines, ChimeraMiner screened 6,736,168 novel chimeras, most of which were missed by the previous pipeline. Applying in single-cell datasets, all three types of chimera were discovered in each dataset, which introduced plenty of false positives in structural variation (SV) detection. The identification and filtration of chimeras by ChimeraMiner removed most of the false positive SVs (83.8%). ChimeraMiner revealed improved efficiency in discovering chimeric reads, and is promising to be widely used in single-cell sequencing.
Identification of ADAM12 as a Novel Basigin Sheddase
Authors: Albrechtsen Reidar , Wewer Albrechtsen Nicolai , Gnosa Sebastian , Schwarz Jeanette , Dyrskjøt Lars , Kveiborg Marie
Published: April 2019

The transmembrane glycoprotein basigin, a member of the immunoglobulin superfamily, stimulates matrix metalloproteinase (MMP)-mediated extracellular matrix (ECM) degradation and thereby drives cancer cell invasion. Basigin is proteolytically shed from the cell surface and high concentrations of soluble basigin in the blood dictates poor prognosis in cancer patients. A positive correlation between basigin and a disintegrin and metalloproteinase (ADAM)-12 in serum from prostate cancer patients has been reported. Yet, the functional relevance of this correlation is unknown. Here, we show that ADAM12 interacts with basigin and cleaves it in the juxtamembrane region. Specifically, overexpression of ADAM12 increases ectodomain shedding of an alkaline phosphatase-tagged basigin reporter protein from the cell surface. Moreover, CRISPR/Cas9-mediated knockout of ADAM12 in human HeLa carcinoma cells results in reduced shedding of the basigin reporter, which can be rescued by ADAM12 re-expression. We detected endogenous basigin fragments, corresponding to the expected size of the ADAM12-generated ectodomain, in conditioned media from ADAM12 expressing cancer cell-lines, as well as serum samples from a healthy pregnant donor and five bladder cancer patients, known to contain high ADAM12 levels. Supporting the cancer relevance of our findings, we identified several cancer-associated mutations in the basigin membrane proximal region. Subsequent in vitro expression showed that some of these mutants are more prone to ADAM12-mediated shedding and that the shed ectodomain can enhance gelatin degradation by cancer cells. In conclusion, we identified ADAM12 as a novel basigin sheddase with a potential implication in cancer.
Glycosaminoglycans and Glycosaminoglycan Mimetics in Cancer and Inflammation
Authors: Morla Shravan
Published: April 2019

Glycosaminoglycans (GAGs) are a class of biomolecules expressed virtually on all mammalian cells and usually covalently attached to proteins, forming proteoglycans. They are present not only on the cell surface, but also in the intracellular milieu and extracellular matrix. GAGs interact with multiple ligands, both soluble and insoluble, and modulate an important role in various physiological and pathological processes including cancer, bacterial and viral infections, inflammation, Alzheimer’s disease, and many more. Considering their involvement in multiple diseases, their use in the development of drugs has been of significant interest in both academia and industry. Many GAG-based drugs are being developed with encouraging results in animal models and clinical trials, showcasing their potential for development as therapeutics. In this review, the role GAGs play in both the development and inhibition of cancer and inflammation is presented. Further, advancements in the development of GAGs and their mimetics as anti-cancer and anti-inflammatory agents are discussed.
mACPpred: A Support Vector Machine-Based Meta-Predictor for Identification of Anticancer Peptides
Authors: Boopathi Vinothini , Subramaniyam Sathiyamoorthy , Malik Adeel , Lee Gwang , Manavalan Balachandran , Yang Deok-Chun
Published: April 2019

Anticancer peptides (ACPs) are promising therapeutic agents for targeting and killing cancer cells. The accurate prediction of ACPs from given peptide sequences remains as an open problem in the field of immunoinformatics. Recently, machine learning algorithms have emerged as a promising tool for helping experimental scientists predict ACPs. However, the performance of existing methods still needs to be improved. In this study, we present a novel approach for the accurate prediction of ACPs, which involves the following two steps: (i) We applied a two-step feature selection protocol on seven feature encodings that cover various aspects of sequence information (composition-based, physicochemical properties and profiles) and obtained their corresponding optimal feature-based models. The resultant predicted probabilities of ACPs were further utilized as feature vectors. (ii) The predicted probability feature vectors were in turn used as an input to support vector machine to develop the final prediction model called mACPpred. Cross-validation analysis showed that the proposed predictor performs significantly better than individual feature encodings. Furthermore, mACPpred significantly outperformed the existing methods compared in this study when objectively evaluated on an independent dataset.
Inhibitory Effect of Berberine on Broiler P-glycoprotein Expression and Function: In Situ and In Vitro Studies
Authors: Zhang Yujuan , Guo Li , Huang Jinhu , Sun Yong , He Fang , Zloh Mire , Wang Liping
Published: April 2019

Overcoming P-glycoprotein (P-gp) efflux is a strategy to improve the absorption and pharmacokinetics of its substrate drugs. Berberine inhibits P-gp and thereby increases the bioavailability of the P-gp substrate digoxin in rodents. However, the effects of berberine on P-gp in chickens are still unclear. Here, we studied the role of berberine in modulating broilers P-gp expression and function through both in situ and in vitro models. In addition, molecular docking was applied to analyze the interactions of berberine with P-gp as well as with chicken xenobiotic receptor (CXR). The results showed that the mRNA expression levels of chicken P-gp and CXR decreased in the ileum following exposure to berberine. The absorption rate constant of rhodamine 123 increased after berberine treatment, as detected using an in situ single-pass intestinal perfusion model. Efflux ratios of P-gp substrates (tilmicosin, ciprofloxacin, clindamycin, ampicillin, and enrofloxacin) decreased and the apparent permeability coefficients increased after co-incubation with berberine in MDCK-chAbcb1 cell models. Bidirectional assay results showed that berberine could be transported by chicken P-gp with a transport ratio of 4.20, and this was attenuated by verapamil (an inhibitor of P-gp), which resulted in a ratio of 1.13. Molecular docking revealed that berberine could form favorable interactions with the binding pockets of both CXR and P-gp, with docking scores of −7.8 and −9.5 kcal/mol, respectively. These results indicate that berberine is a substrate of chicken P-gp and down-regulates P-gp expression in chicken tissues, thereby increasing the absorption of P-gp substrates. Our findings suggest that berberine increases the bioavailability of other drugs and that drug-drug interactions should be considered when it is co-administered with other P-gp substrates with narrow therapeutic windows.
The Addition of High Doses of Hyaluronic Acid to a Biphasic Bone Substitute Decreases the Proinflammatory Tissue Response
Authors: Sieger Dominik , Korzinskas Tadas , Jung Ole , Stojanovic Sanja , Wenisch Sabine , Smeets Ralf , Gosau Martin , Schnettler Reinhard , Najman Stevo , Barbeck Mike
Published: April 2019

Biphasic bone substitutes (BBS) are currently well-established biomaterials. Through their constant development, even natural components like hyaluronic acid (HY) have been added to improve both their handling and also their regenerative properties. However, little knowledge exists regarding the consequences of the addition of HY to their biocompatibility and the inflammatory tissue reactions. Thus, the present study was conducted, aiming to analyze the influence of two different amounts of high molecular weight HY (HMWHY), combined with a BBS, on in vitro biocompatibility and in vivo tissue reaction. Established in vitro procedures, using L929 cells, were used for cytocompatibility analyses under the test conditions of DIN EN:ISO 10993-5. For the in vivo part of the study, calvarial defects were created in 20 Wistar rats and subsequently filled with BBS, and BBS combined with two different HMWHY amounts, i.e., BBS + HY(L) and BBS + HY(H). As controls, empty defects were used. Established histological, immunohistochemical, and histomorphometrical methods were applied to analyze the tissue reactions to the three different materials, including the induction of pro- and anti-inflammatory macrophages and multinucleated giant cells (BMGCs). The in vitro results showed that none of the materials or compositions caused biological damage to the L929 cells and can be considered to be non-toxic. The in vivo results showed that only the addition of high doses of HY to a biphasic bone substitute significantly decreases the occurrence of pro-inflammatory macrophages (* p < 0.05), comparable to the numbers found in the control group, while no significant differences within the three study groups for M2-macrophages nor BMGCs were detected. In conclusion, the addition of different amounts of HMWHY does not seem to affect the inflammation response to BBS, while improving the material handling properties.
A Metadynamics-Based Protocol for the Determination of GPCR-Ligand Binding Modes
Authors: Söldner Christian A. , Horn Anselm H. C. , Sticht Heinrich
Published: April 2019

G protein-coupled receptors (GPCRs) are a main drug target and therefore a hot topic in pharmaceutical research. One important prerequisite to understand how a certain ligand affects a GPCR is precise knowledge about its binding mode and the specific underlying interactions. If no crystal structure of the respective complex is available, computational methods can be used to deduce the binding site. One of them are metadynamics simulations which have the advantage of an enhanced sampling compared to conventional molecular dynamics simulations. However, the enhanced sampling of higher-energy states hampers identification of the preferred binding mode. Here, we present a novel protocol based on clustering of multiple walker metadynamics simulations which allows identifying the preferential binding mode from such conformational ensembles. We tested this strategy for three different model systems namely the histamine H1 receptor in combination with its physiological ligand histamine, as well as the β 2 adrenoceptor with its agonist adrenaline and its antagonist alprenolol. For all three systems, the proposed protocol was able to reproduce the correct binding mode known from the literature suggesting that the approach can more generally be applied to the prediction of GPCR ligand binding in future.
Local and Landscape Drivers of Carabid Activity, Species Richness, and Traits in Urban Gardens in Coastal California
Authors: Philpott Stacy M. , Albuquerque Simone , Bichier Peter , Cohen Hamutahl , Egerer Monika H. , Kirk Claire , Will Kipling W.
Published: April 2019

Urban ecosystems, as mosaics of residential, industrial, commercial, and agricultural land, present challenges for species survival due to impervious surface, degradation, fragmentation, and modification of natural habitat, pollution, and introduced species. Some urban habitats, such as community gardens, support biodiversity and promote ecosystem services. In gardens, local factors (e.g., vegetation, groundcover) and landscape surroundings (e.g., agriculture, built or impervious cover) may influence species abundance, richness, and functional traits that are present. We examined which local and landscape factors within 19 community gardens in the California central coast influence ground beetle (Carabidae) activity density, species richness, functional group richness, and functional traits—body size, wing morphology, and dispersal ability. Gardens with higher crop richness and that are surrounded by agricultural land had greater carabid activity density, while species and functional group richness did not respond to any local or landscape factor. Gardens with more leaf litter had lower carabid activity, and gardens with more leaf litter tended to have more larger carabids. Changes in local (floral abundance, ground cover) and landscape (urban land cover) factors also influenced the distribution of individuals with certain wing morphology and body size traits. Thus, both local and landscape factors influence the taxonomic and functional traits of carabid communities, with potential implications for pest control services that are provided by carabids.
Does Herpes Zoster Increase the Risk of Stroke and Myocardial Infarction? A Comprehensive Review
Authors: Wu Ping-Hsun , Chuang Yun-Shiuan , Lin Yi-Ting
Published: April 2019

Herpes zoster (HZ) caused by varicella zoster virus (VZV) reactivation is characterized as a vesicular rash of unilateral distribution that can also cause multiple complications; such as post-herpetic neuralgia; ophthalmic zoster; and other neurological issues. VZV can also increase incident hemorrhagic or ischemic complications by causing inflammatory vasculopathy. Thus; emerging epidemiological and clinical data recognizes an association between HZ and subsequent acute strokes or myocardial infarction (MI). This study reviewed published articles to elucidate the association between HZ and cerebrovascular and cardiac events. Individuals exposed to HZ or herpes zoster ophthalmicus had 1.3 to 4-fold increased risks of cerebrovascular events. Higher risks were noted among younger patients (age < 40 years) within one year after an HZ episode. The elevated risk of CV events diminished gradually according to age and length of time after an HZ episode. The putative mechanisms of VZV vasculopathy were also discussed. Several studies showed that the development of herpes zoster and herpes zoster ophthalmicus increased the risks of stroke; transient ischemic attack; and acute cardiac events. The association between VZV infection and cardiovascular events requires further studies to establish the optimal antiviral treatment and zoster vaccination to reduce zoster-associated vascular risk
A Quality Control Method for Broad-Beam HF Radar Current Velocity Measurements
Authors: Lipa Belinda , Barrick Donald , Whelan Chad
Published: April 2019

This paper describes a method to provide quality control for radial velocity maps derived from radar echo voltage cross spectra measured by broad-beam high frequency radars. The method involves the comparison of voltage cross spectra measured at Doppler frequencies in the Bragg region with values predicted from basic equations defining the complex voltage cross spectra in terms of the measured antenna patterns and the radar cross section. Poor agreement at a given Doppler frequency indicates contamination of the spectra, usually due to interference; velocity results from that Doppler frequency are then eliminated. Examples are given of its application to broad-beam radars operating at four sites.
Evaluation of the Potential of Sasobit REDUX Additive to Lower Warm-Mix Asphalt Production Temperature
Authors: Almeida Arminda , Sergio Michela
Published: April 2019

Environmental and health concerns have been increasing in the road construction industry. This industry has provided several techniques and a wide range of additives to lower the production temperatures of asphalt mixtures, generating, among others, a new mix type called warm-mix asphalt (WMA). This paper aims to evaluate the potential of the Sasobit REDUX additive to lower the production temperatures of WMA. This additive, which is an alternative to the well-known Sasobit, is completely soluble in bitumen at temperatures above 85 °C while the same temperature for the Sasobit is 115 °C. For that reason, three target compaction temperatures were considered (90, 100 and 110 °C) and both Marshall and compactability tests were carried out. A hot-mix asphalt (HMA) was tested in parallel for comparison. It was concluded that the volumetric properties (air voids content about 4%) and the Marshall properties (stability about 11 kN, flow about 4 mm and Marshall quotient higher than 2 kN/km) of the Sasobit REDUX-WMA were globally satisfactory. In relation to the compactability test, the Sasobit REDUX-WMA mixtures were relatively easier to be compacted compared to the HMA mixture. The three Sasobit REDUX-WMA mixtures (90, 100 and 110 °C) exhibited a very similar compactability (differences lower than 0.4%). Therefore, it seems reasonable to conclude that the Sasobit REDUX has potential to lower WMA production temperatures by 20 °C. A reduction of that magnitude would lead to significant environmental gains.
Docosane-Organosilica Microcapsules for Structural Composites with Thermal Energy Storage/Release Capability
Authors: Fredi Giulia , Dirè Sandra , Callone Emanuela , Ceccato Riccardo , Mondadori Francesco , Pegoretti Alessandro
Published: April 2019

Organic phase change materials (PCMs) represent an effective solution to manage intermittent energy sources as the solar thermal energy. This work aims at encapsulating docosane in organosilica shells and at dispersing the produced capsules in epoxy/carbon laminates to manufacture multifunctional structural composites for thermal energy storage (TES). Microcapsules of different sizes were prepared by hydrolysis-condensation of methyltriethoxysilane (MTES) in an oil-in-water emulsion. X-ray diffraction (XRD) highlighted the difference in the crystalline structure of pristine and microencapsulated docosane, and 13C solid-state nuclear magnetic resonance (NMR) evidenced the influence of microcapsules size on the shifts of the representative docosane signals, as a consequence of confinement effects, i.e., reduced chain mobility and interaction with the inner shell walls. A phase change enthalpy up to 143 J/g was determined via differential scanning calorimetry (DSC) on microcapsules, and tests at low scanning speed emphasized the differences in the crystallization behavior and allowed the calculation of the phase change activation energy of docosane, which increased upon encapsulation. Then, the possibility of embedding the microcapsules in an epoxy resin and in an epoxy/carbon laminate to produce a structural TES composite was investigated. The presence of microcapsules agglomerates and the poor capsule-epoxy adhesion, both evidenced by scanning electron microscopy (SEM), led to a decrease in the mechanical properties, as confirmed by three-point bending tests. Dynamic mechanical analysis (DMA) highlighted that the storage modulus decreased by 15% after docosane melting and that the glass transition temperature of the epoxy resin was not influenced by the PCM. The heat storage/release properties of the obtained laminates were proved through DSC and thermal camera imaging tests.