bluuebunny/crossref_metadata_2025 huggingface dataset:
An Empirical Mode-Spatial Model for Environmental Data Imputation
Authors: Nelsen Benjamin , Williams D. Alexandra , Williams Gustavious P. , Berrett Candace
Published: November 2018

Complete and accurate data are necessary for analyzing and understanding trends in time-series datasets; however, many of the available time-series datasets have gaps that affect the analysis, especially in the earth sciences. As most available data have missing values, researchers use various interpolation methods or ad hoc approaches to data imputation. Since the analysis based on inaccurate data can lead to inaccurate conclusions, more accurate data imputation methods can provide accurate analysis. We present a spatial-temporal data imputation method using Empirical Mode Decomposition (EMD) based on spatial correlations. We call this method EMD-spatial data imputation or EMD-SDI. Though this method is applicable to other time-series data sets, here we demonstrate the method using temperature data. The EMD algorithm decomposes data into periodic components called intrinsic mode functions (IMF) and exactly reconstructs the original signal by summing these IMFs. EMD-SDI initially decomposes the data from the target station and other stations in the region into IMFs. EMD-SDI evaluates each IMF from the target station in turn and selects the IMF from other stations in the region with periodic behavior most correlated to target IMF. EMD-SDI then replaces a section of missing data in the target station IMF with the section from the most closely correlated IMF from the regional stations. We found that EMD-SDI selects the IMFs used for reconstruction from different stations throughout the region, not necessarily the station closest in the geographic sense. EMD-SDI accurately filled data gaps from 3 months to 5 years in length in our tests and favorably compares to a simple temporal method. EMD-SDI leverages regional correlation and the fact that different stations can be subject to different periodic behaviors. In addition to data imputation, the EMD-SDI method provides IMFs that can be used to better understand regional correlations and processes.
The Efficacy of Inpatient vs. Home-Based Physiotherapy Following Coronary Artery Bypass Grafting
Authors: Szylińska Aleksandra , Listewnik Mariusz , Rotter Iwona , Rył Aleksandra , Kotfis Katarzyna , Mokrzycki Krzysztof , Kuligowska Ewelina , Walerowicz Paweł , Brykczyński Mirosław
Published: November 2018

Background: Intensive post-operative physiotherapy after cardiac surgery helps to reduce the number of complications, accelerating convalescence and decreasing peri-operative mortality. Cardiac rehabilitation is aimed at regaining lost function and sustaining the effect of cardiac surgery. The aim of this study was to compare the efficacy of inpatient and home-based phase II physiotherapy following coronary artery bypass grafting, and inpatient phase II post-operative physiotherapy based on the analysis of the spirometry results. Methods: A prospective observational study included 104 adult patients of both sexes undergoing planned coronary artery bypass grafting and were randomized to one of the two groups—inpatients (InPhysio) and home-based (HomePhysio) at a 1:1 ratio. All patients had undergone spirometry testing prior to surgery (S1) and on the fifth day after the operation (S2), i.e., on the day of completion of the first phase (PI) of physiotherapy. Both the study group (InPhysio) and the control group (HomePhysio) performed the same set of exercises in the second phase (PII) of cardiac physiotherapy, either in the hospital or at home, respectively, according to the program obtained in the hospital. Both groups have undergone spirometry testing (S3) at 30 days after the operation. Results: The demographic and peri-operative data for both groups were comparable and showed no statistically significant differences. An analysis of gradients between the results of spirometry tests before surgery and at 30 days after the surgery showed a smaller decrease in forced vital capacity (FVC) in the study group than in the control group (p < 0.001). The results at five and 30 days after the surgery showed a greater increase in FVC in the study group than in the control group (680 mL vs. 450 mL, p = 0.009). There were no statistically significant differences in other parameters studied. Conclusions: The advantage of inpatient over home-based physiotherapy was evidenced by much smaller decreases in FVC between the initial and final tests, and greater increases between the fifth day after surgery and the final test. Our analysis showed greater efficacy of inpatient physiotherapy as compared with home-based exercises and raises concerns about patient adherence.
Wind Turbine Noise and Sleep: Pilot Studies on the Influence of Noise Characteristics
Authors: Ageborg Morsing Julia , Smith Michael G. , Ögren Mikael , Thorsson Pontus , Pedersen Eja , Forssén Jens , Persson Waye Kerstin
Published: November 2018

The number of onshore wind turbines in Europe has greatly increased over recent years, a trend which can be expected to continue. However, the effects of wind turbine noise on long-term health outcomes for residents living near wind farms is largely unknown, although sleep disturbance may be a cause for particular concern. Presented here are two pilot studies with the aim of examining the acoustical properties of wind turbine noise that might be of special relevance regarding effects on sleep. In both pilots, six participants spent five consecutive nights in a sound environment laboratory. During three of the nights, participants were exposed to wind turbine noise with variations in sound pressure level, amplitude modulation strength and frequency, spectral content, turbine rotational frequency and beating behaviour. The impact of noise on sleep was measured using polysomnography and questionnaires. During nights with wind turbine noise there was more frequent awakening, less deep sleep, less continuous N2 sleep and increased subjective disturbance compared to control nights. The findings indicated that amplitude modulation strength, spectral frequency and the presence of strong beats might be of particular importance for adverse sleep effects. The findings will be used in the development of experimental exposures for use in future, larger studies.
Students’ Willingness to Intervene in Bullying: Direct and Indirect Associations with Classroom Cohesion and Self-Efficacy
Authors: Wachs Sebastian , Bilz Ludwig , Fischer Saskia M. , Schubarth Wilfried , Wright Michelle F.
Published: November 2018

Although school climate and self-efficacy have received some attention in the literature, as correlates of students’ willingness to intervene in bullying, to date, very little is known about the potential mediating role of self-efficacy in the relationship between classroom climate and students’ willingness to intervene in bullying. To this end, the present study analyzes whether the relationship between classroom cohesion (as one facet of classroom climate) and students’ willingness to intervene in bullying situations is mediated by self-efficacy in social conflicts. This study is based on a representative stratified random sample of two thousand and seventy-one students (51.3% male), between the ages of twelve and seventeen, from twenty-four schools in Germany. Results showed that between 43% and 48% of students reported that they would not intervene in bullying. A mediation test using the structural equation modeling framework revealed that classroom cohesion and self-efficacy in social conflicts were directly associated with students’ willingness to intervene in bullying situations. Furthermore, classroom cohesion was indirectly associated with higher levels of students’ willingness to intervene in bullying situations, due to self-efficacy in social conflicts. We thus conclude that: (1) It is crucial to increase students’ willingness to intervene in bullying; (2) efforts to increase students’ willingness to intervene in bullying should promote students’ confidence in dealing with social conflicts and interpersonal relationships; and (3) self-efficacy plays an important role in understanding the relationship between classroom cohesion and students’ willingness to intervene in bullying. Recommendations are provided to help increase adolescents’ willingness to intervene in bullying and for future research.
Health Risk in Urbanizing Regions: Examining the Nexus of Infrastructure, Hygiene and Health in Tashkent Province, Uzbekistan
Authors: Veluswami Subramanian Saravanan , Cho Min Jung , Mukhitdinova Fotima
Published: November 2018

Worldwide, development agencies have increased their investments in water supply and sanitation as a “powerful preventive medicine” to address infectious diseases. These interventions have focused on on-site technical interventions or social engineering approaches, emulating the result-based targets of the development goals. Against this backdrop, the study examines the following research question: What is the role of socio-cultural backgrounds, housing characteristics, and environmental hygiene practices in addressing water-transmitted diseases in the Tashkent province of Uzbekistan. In a country where public statistics and official maps are rarely accessible, and research is restrictive, the study carried out a household survey using open data kit (ODK) between July and October 2015 in Olmalik, an industrial district, and the Kibray urbanizing district in the province. The findings reveal that demographic factors, poor sanitation practices, housing characteristics, and social behaviors are key predictors of water-transmitted diseases in the two districts. In the industrial township, poor housing, larger household size, and poor excreta disposal habits increased the occurrence of diseases, while in urbanizing districts, higher household size, frequently eating out, and access to public taps significantly increased the occurrence of water-transmitted diseases. The study, which was carried out in a challenging institutional environment, highlights the need for Uzbekistan to focus their policies on environmental hygiene, demographic factors and social behavior as key interventions rather than merely on on-site drinking water and sanitation interventions.
Released Volatile Organic Compounds in Southern Yellow Pine before and after Heat Treatment
Authors: Wang Chen , Wang Zhiping , Qin Ye , Yin Xiaoqian , Huang Anmin
Published: November 2018

As the main material in indoor furniture, southern yellow pine (Pinus spp.) releases volatile organic compounds (VOCs) into the environment during use. To better understand variations in the contents of VOCs in southern yellow pine before and after heat treatment, this study conducts dry heat treatment on southern yellow pine at 140 °C and 220 °C. Headspace solid phase micro-extraction was used to extract VOCs from southern yellow pine. The VOCs of southern yellow pine before and after heat treatment were identified via gas chromatography-mass spectrometry, and chemical component differences were characterized via Fourier transform infrared spectroscopy. Results reveal 86 VOCs in pure southern yellow pine, including alcohols, aromatics, acids, aldehydes, alkanes, alkenes, and some trace compounds (e.g., furans, ketones, phenols, and esters). With an increase in heat-treatment temperature, the contents of alkanes increased, whereas those of alcohols and alkenes decreased. The contents of aromatics, acids, and aldehydes were highest when heat treated at 140 °C. At 220 °C, the total contents of key VOCs in southern yellow pine were lowest.
Corporate Social Responsibility and Rule 144A Debt Offerings: Empirical Evidence
Authors: Dbouk Wassim , Jin Dawei , Wang Haizhi , Wang Jianrong
Published: November 2018

Rule 144A allows a firm to issue securities without a public registration statement with the Securities and Exchange Commission, and only qualified institutional investors can purchase such securities. In this study, focusing on corporate bonds issued under Rule 144A, we empirically investigate the relationship between the corporate social responsibility (CSR) of issuing firms and the bond yield spread at issuance. We document a significant and positive relation between CSR concerns, whereas CSR strengths seem to play an insignificant role in determining bond yield spread. Our main findings are robust to the instrumental variable approach and simultaneous equation estimation to address the potential endogeneity issues. We further explore the time-series changes in issuing firms’ CSR profiles, and report that institutional investors demand a higher bond yield spread when issuing firms’ exposure to higher social, environmental, and stakeholder concerns. Our analyses reveal that the main sources of such risk exposure are stakeholder conflict and concerns from primary stakeholder groups.
Direct Impacts of Climate Change and Indirect Impacts of Non-Climate Change on Land Surface Phenology Variation across Northern China
Authors: Luo Zhaohui , Song Qingmei , Wang Tao , Zeng Huanmu , He Tao , Zhang Hengjun , Wu Wenchen
Published: November 2018

Land surface phenology (LSP) is a sensitive indicator of climate change. Understanding the variation in LSP under various impacts can improve our knowledge on ecosystem dynamics and biosphere-atmosphere interactions. Over recent decades, LSP derived from remote sensing data and climate change-related variation of LSP have been widely reported at the regional and global scales. However, the smoothing methods of the vegetation index (i.e., NDVI) are diverse, and discrepancies among methods may result in different results. Additionally, LSP is affected by climate change and non-climate change simultaneously. However, few studies have focused on the isolated impacts of climate change and the impacts of non-climate change on LSP variation. In this study, four methods were applied to reconstruct the MODIS enhanced vegetation index (EVI) dataset to choose the best smoothing result to estimate LSP. Subsequently, the variation in the start of season (SOS) and end of season (EOS) under isolated impacts of climate change were analyzed. Furthermore, the indirect effects of isolated impacts of non-climate change were conducted based on the differences between the combined impact (the impacts of both climate change and non-climate change) and isolated impacts of climate change. Our results indicated that the Savitzky-Golay method is the best method of the four for smoothing EVI in Northern China. Additionally, SOS displayed an advanced trend under the impacts of both climate change and non-climate change (hereafter called the combined impact), isolated impacts of climate change, and isolated impacts of non-climate change, with mean values of −0.26, −0.07, and −0.17 days per year, respectively. Moreover, the trend of SOS continued after 2000, but the magnitudes of changes in SOS after 2000 were lower than those that were estimated over the last two decades of the twentieth century (previous studies). EOS showed a delayed trend under the combined impact and isolated impacts of non-climate change, with mean values of 0.41 and 0.43 days per year, respectively. However, EOS advanced with a mean value of −0.16 days per year under the isolated impacts of climate change. Furthermore, the absolute mean values of SOS and EOS trends under the isolated impacts of non-climate change were larger than that of the isolated impacts of climate change, indicating that the effect of non-climate change on LSP variation was larger than that of climate change. With regard to the relative contribution of climatic factors to the variation in SOS and EOS, the proportion of solar radiation was the largest for both SOS and EOS, followed by precipitation and temperature.
Place versus Space: From Points, Lines and Polygons in GIS to Place-Based Representations Reflecting Language and Culture
Authors: Blaschke Thomas , Merschdorf Helena , Cabrera-Barona Pablo , Gao Song , Papadakis Emmanuel , Kovacs-Györi Anna
Published: November 2018

Around the globe, Geographic Information Systems (GISs) are well established in the daily workflow of authorities, businesses and non-profit organisations. GIS can effectively handle spatial entities and offer sophisticated analysis and modelling functions to deal with space. Only a small fraction of the literature in Geographic Information Science—or GIScience in short—has advanced the development of place, addressing entities with an ambiguous boundary and relying more on the human or social attributes of a location rather than on crisp geographic boundaries. While the GIScience developments support the establishment of the digital humanities, GISs were never designed to handle subjective or vague data. We, an international group of authors, juxtapose place and space in English language and in several other languages and discuss potential consequences for Geoinformatics and GIScience. In particular, we address the question of whether linguistic and cultural settings play a role in the perception of place. We report on some facts revealed by this multi-language and multi-cultural dialogue, and what particular aspects of place we were able to discern regarding the few languages addressed.
The Protective and Restorative Effects of Growth Hormone and Insulin-Like Growth Factor-1 on Methadone-Induced Toxicity In Vitro
Authors: Nylander Erik , Zelleroth Sofia , Nyberg Fred , Grönbladh Alfhild , Hallberg Mathias
Published: November 2018

Evidence to date suggests that opioids such as methadone may be associated with cognitive impairment. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) are suggested to be neuroprotective and procognitive in the brain and may therefore counteract these effects. This study aims to explore the protective and restorative effects of GH and IGF-1 in methadone-treated cell cultures. Primary cortical cell cultures were harvested from rat fetuses and grown for seven days in vitro. To examine the protective effects, methadone was co-treated with or without GH or IGF-1 for three consecutive days. To examine the restorative effects, methadone was added for the first 24 h, washed, and later treated with GH or IGF-1 for 48 h. At the end of each experiment, mitochondrial function and membrane integrity were evaluated. The results revealed that GH had protective effects in the membrane integrity assay and that both GH and IGF-1 effectively recovered mitochondrial function and membrane integrity in cells pretreated with methadone. The overall conclusion of the present study is that GH, but not IGF-1, protects primary cortical cells against methadone-induced toxicity, and that both GH and IGF-1 have a restorative effect on cells pretreated with methadone.
Nuclear Receptor Metabolism of Bile Acids and Xenobiotics: A Coordinated Detoxification System with Impact on Health and Diseases
Authors: Garcia Manon , Thirouard Laura , Sedès Lauriane , Monrose Mélusine , Holota Hélène , Caira Françoise , Volle David H. , Beaudoin Claude
Published: November 2018

Structural and functional studies have provided numerous insights over the past years on how members of the nuclear hormone receptor superfamily tightly regulate the expression of drug-metabolizing enzymes and transporters. Besides the role of the farnesoid X receptor (FXR) in the transcriptional control of bile acid transport and metabolism, this review provides an overview on how this metabolic sensor prevents the accumulation of toxic byproducts derived from endogenous metabolites, as well as of exogenous chemicals, in coordination with the pregnane X receptor (PXR) and the constitutive androstane receptor (CAR). Decrypting this network should provide cues to better understand how these metabolic nuclear receptors participate in physiologic and pathologic processes with potential validation as therapeutic targets in human disabilities and cancers.
Is the Response of Tumours Dependent on the Dietary Input of Some Amino Acids or Ratios among Essential and Non-Essential Amino Acids? All That Glitters Is Not Gold
Authors: Dioguardi Francesco S. , Flati Vincenzo , Corsetti Giovanni , Pasini Evasio , Romano Claudia
Published: November 2018

Energy production is the main task of the cancer cell metabolism because the costs of duplicating are enormous. Although energy is derived in cells by dismantling the carbon-to-carbon bonds of any macronutrient, cancer nutritional needs for energetic purposes have been studied primarily as being dependent on glycolysis. Since the end of the last century, the awareness of the dependence of cancer metabolism on amino acids not only for protein synthesis but also to match energy needs has grown. The roles of specific amino acids such as glutamine, glycine and serine have been explored in different experimental conditions and reviewed. Moreover, epidemiological evidence has revealed that some amino acids used as a supplement for therapeutic reasons, particularly the branched-chain ones, may reduce the incidence of liver cancer and a specific molecular mechanism has been proposed as functional to their protective action. By contrast and puzzling clinicians, the metabolomic signature of some pathologies connected to an increased risk of cancer, such as prolonged hyperinsulinemia in insulin-resistant patients, is identified by elevated plasma levels of the same branched-chain amino acids. Most recently, certain formulations of amino acids, deeply different from the amino acid compositions normally present in foods, have shown the power to master cancer cells epigenetically, slowing growth or driving cancer cells to apoptotic death, while being both beneficial for normal cell function and the animal’s health and lifespan. In this review, we will analyze and try to disentangle some of the many knots dealing with the complexities of amino acid biology and links to cancer metabolism.
Genome-Wide Identification of Flowering-Time Genes in Brassica Species and Reveals a Correlation between Selective Pressure and Expression Patterns of Vernalization-Pathway Genes in Brassica napus
Authors: Li Haojie , Fan Yonghai , Yu Jingyin , Chai Liang , Zhang Jingfang , Jiang Jun , Cui Cheng , Zheng Benchuan , Jiang Liangcai , Lu Kun
Published: November 2018

Flowering time is a key agronomic trait, directly influencing crop yield and quality. Many flowering-time genes have been identified and characterized in the model plant Arabidopsis thaliana; however, these genes remain uncharacterized in many agronomically important Brassica crops. In this study, we identified 1064, 510, and 524 putative orthologs of A. thaliana flowering-time genes from Brassica napus, Brassica rapa, and Brassica oleracea, respectively, and found that genes involved in the aging and ambient temperature pathways were fewer than those in other flowering pathways. Flowering-time genes were distributed mostly on chromosome C03 in B. napus and B. oleracea, and on chromosome A09 in B. rapa. Calculation of non-synonymous (Ka)/synonymous substitution (Ks) ratios suggested that flowering-time genes in vernalization pathways experienced higher selection pressure than those in other pathways. Expression analysis showed that most vernalization-pathway genes were expressed in flowering organs. Approximately 40% of these genes were highly expressed in the anther, whereas flowering-time integrator genes were expressed in a highly organ-specific manner. Evolutionary selection pressures were negatively correlated with the breadth and expression levels of vernalization-pathway genes. These findings provide an integrated framework of flowering-time genes in these three Brassica crops and provide a foundation for deciphering the relationship between gene expression patterns and their evolutionary selection pressures in Brassica napus.
Protein Structural Dynamics of Wild-Type and Mutant Homodimeric Hemoglobin Studied by Time-Resolved X-Ray Solution Scattering
Authors: Yang Cheolhee , Choi Minseo , Kim Jong Goo , Kim Hanui , Muniyappan Srinivasan , Nozawa Shunsuke , Adachi Shin-ichi , Henning Robert , Kosheleva Irina , Ihee Hyotcherl
Published: November 2018

The quaternary transition between the relaxed (R) and tense (T) states of heme-binding proteins is a textbook example for the allosteric structural transition. Homodimeric hemoglobin (HbI) from Scapharca inaequivalvis is a useful model system for investigating the allosteric behavior because of the relatively simple quaternary structure. To understand the cooperative transition of HbI, wild-type and mutants of HbI have been studied by using time-resolved X-ray solution scattering (TRXSS), which is sensitive to the conformational changes. Herein, we review the structural dynamics of HbI investigated by TRXSS and compare the results of TRXSS with those of other techniques.
A Proteomic Approach for Understanding the Mechanisms of Delayed Corneal Wound Healing in Diabetic Keratopathy Using Diabetic Model Rat
Authors: Yamamoto Tetsushi , Otake Hiroko , Hiramatsu Noriko , Yamamoto Naoki , Taga Atsushi , Nagai Noriaki
Published: November 2018

Diabetes mellitus is a widespread metabolic disorder, and long-term hyperglycemia in diabetics leads to diabetic keratopathy. In the present study, we used a shotgun liquid chromatography/mass spectrometry-based global proteomic approach using the cornea of streptozotocin-induced diabetic (STZ) rats to examine the mechanisms of delayed corneal wound healing in diabetic keratopathy. Applying a label-free quantitation method based on spectral counting, we identified 188 proteins that showed expression changes of >2.0-fold in the cornea of STZ rats. In particular, the level of lumican expression in the cornea of STZ rats was higher than that of the normal rats. In the cornea of the normal rat, the expression level of lumican was elevated during the wound healing process, and it returned to the same expression level as before cornea injury after the wound was healed completely. On the other hand, a high expression level of lumican in the cornea of STZ rats was still maintained even after the wound was healed completely. In addition, adhesion deficiency in corneal basal cells and Bowman’s membrane was observed in the STZ rat. Thus, abnormally overexpressed lumican may lead to adhesion deficiency in the cornea of STZ rats.
Dissemination of Genetic Acquisition/Loss Provides a Variety of Quorum Sensing Regulatory Properties in Pseudoalteromonas
Authors: Yu Zhiliang , Ding Yajuan , Yin Jianhua , Yu Dongliang , Zhang Jiadi , Zhang Mengting , Ding Mengdan , Zhong Weihong , Qiu Juanping , Li Jun
Published: November 2018

Quorum sensing (QS) enables single-celled bacteria to communicate with chemical signals in order to synchronize group-level bacterial behavior. Pseudoalteromonas are marine bacteria found in versatile environments, of which QS regulation for their habitat adaptation is extremely fragmentary. To distinguish genes required for QS regulation in Pseudoalteromonas, comparative genomics was deployed to define the pan-genomics for twelve isolates and previously-sequenced genomes, of which acyl-homoserine lactone (AHL)-based QS traits were characterized. Additionally, transposon mutagenesis was used to identify the essential QS regulatory genes in the selected Pseudoalteromonas isolate. A remarkable feature showed that AHL-based colorization intensity of biosensors induced by Pseudoalteromonas most likely correlates with QS regulators genetic heterogeneity within the genus. This is supported by the relative expression levels of two of the main QS regulatory genes (luxO and rpoN) analyzed in representative Pseudoalteromonas isolates. Notably, comprehensive QS regulatory schema and the working model proposed in Pseudoalteromonas seem to phylogenetically include the network architectures derived from Escherichia coli, Pseudomonas, and Vibrio. Several associated genes were mapped by transposon mutagenesis. Among them, a right origin-binding protein-encoding gene (robp) was functionally identified as a positive QS regulatory gene. This gene lies on a genomic instable region and exists in the aforementioned bioinformatically recruited QS regulatory schema. The obtained data emphasize that the distinctly- and hierarchically-organized mechanisms probably target QS association in Pseudoalteromonas dynamic genomes, thus leading to bacterial ability to accommodate their adaption fitness and survival advantages.
Identification, Classification, and Functional Analysis of AP2/ERF Family Genes in the Desert Moss Bryum argenteum
Authors: Li Xiaoshuang , Gao Bei , Zhang Daoyuan , Liang Yuqing , Liu Xiaojie , Zhao Jinyi , Zhang Jianhua , Wood Andrew J.
Published: November 2018

Bryum argenteum is a desert moss which shows tolerance to the desert environment and is emerging as a good plant material for identification of stress-related genes. AP2/ERF transcription factor family plays important roles in plant responses to biotic and abiotic stresses. AP2/ERF genes have been identified and extensively studied in many plants, while they are rarely studied in moss. In the present study, we identified 83 AP2/ERF genes based on the comprehensive dehydrationrehydration transcriptomic atlas of B. argenteum. BaAP2/ERF genes can be classified into five families, including 11 AP2s, 43 DREBs, 26 ERFs, 1 RAV, and 2 Soloists. RNA-seq data showed that 83 BaAP2/ERFs exhibited elevated transcript abundances during dehydration–rehydration process. We used RT-qPCR to validate the expression profiles of 12 representative BaAP2/ERFs and confirmed the expression trends using RNA-seq data. Eight out of 12 BaAP2/ERFs demonstrated transactivation activities. Seven BaAP2/ERFs enhanced salt and osmotic stress tolerances of yeast. This is the first study to provide detailed information on the identification, classification, and functional analysis of the AP2/ERFs in B. argenteum. This study will lay the foundation for the further functional analysis of these genes in plants, as well as provide greater insights into the molecular mechanisms of abiotic stress tolerance of B. argenteum.
Structure–Activity Relationship Study of Newly Synthesized Iridium-III Complexes as Potential Series for Treating Thrombotic Diseases
Authors: Yang Chih-Hao , Hsia Chih-Wei , Jayakumar Thanasekaran , Sheu Joen-Rong , Hsia Chih-Hsuan , Khamrang Themmila , Chen Yen-Jen , Manubolu Manjunath , Chang Yi
Published: November 2018

Platelets play a major role in hemostatic events and are associated with various pathological events, such as arterial thrombosis and atherosclerosis. Iridium (Ir) compounds are potential alternatives to platinum compounds, since they exert promising anticancer effects without cellular toxicity. Our recent studies found that Ir compounds show potent antiplatelet properties. In this study, we evaluated the in vitro antiplatelet, in vivo antithrombotic and structure–activity relationship (SAR) of newly synthesized Ir complexes, Ir-1, Ir-2 and Ir-4, in agonists-induced human platelets. Among the tested compounds, Ir-1 was active in inhibiting platelet aggregation induced by collagen; however, Ir-2 and Ir-4 had no effects even at their maximum concentrations of 50 μM against collagen and 500 μM against U46619-induced aggregation. Similarly, Ir-1 was potently inhibiting of adenosine triphosphate (ATP) release, calcium mobilization ([Ca2+]i) and P-selectin expression induced by collagen-induced without cytotoxicity. Likewise, Ir-1 expressively suppressed collagen-induced Akt, PKC, p38MAPKs and JNK phosphorylation. Interestingly, Ir-2 and Ir-4 had no effect on platelet function analyzer (PFA-100) collagen-adenosine diphosphate (C-ADP) and collagen-epinephrine (C-EPI) induced closure times in mice, but Ir-1 caused a significant increase when using C-ADP stimulation. Other in vivo studies revealed that Ir-1 significantly prolonged the platelet plug formation, increased tail bleeding times and reduced the mortality of adenosine diphosphate (ADP)-induced acute pulmonary thromboembolism in mice. Ir-1 has no substitution on its phenyl group, a water molecule (like cisplatin) can replace its chloride ion and, hence, the rate of hydrolysis might be tuned by the substituent on the ligand system. These features might have played a role for the observed effects of Ir-1. These results indicate that Ir-1 may be a lead compound to design new antiplatelet drugs for the treatment of thromboembolic diseases.
Visfatin Promotes Wound Healing through the Activation of ERK1/2 and JNK1/2 Pathway
Authors: Lee Byung-Cheol , Song Jisun , Lee Arim , Cho Daeho , Kim Tae Sung
Published: November 2018

Visfatin, a member of the adipokine family, plays an important role in many metabolic and stress responses. The mechanisms underlying the direct therapeutic effects of visfatin on wound healing have not been reported yet. In this study, we examined the effects of visfatin on wound healing in vitro and in vivo. Visfatin enhanced the proliferation and migration of human dermal fibroblasts (HDFs) and keratinocytes the expression of wound healing-related vascular endothelial growth factor (VEGF) in vitro and in vivo. Treatment of HDFs with visfatin induced activation of both extracellular signal-regulated kinases 1 and 2 (ERK1/2) and c-Jun N-terminal kinases 1 and 2 (JNK1/2) in a time-dependent manner. Inhibition of ERK1/2 and JNK1/2 led to a significant decrease in visfatin-induced proliferation and migration of HDFs. Importantly, blocking VEGF with its neutralizing antibodies suppressed the visfatin-induced proliferation and migration of HDFs and human keratinocytes, indicating that visfatin induces the proliferation and migration of HDFs and human keratinocytes via increased VEGF expression. Moreover, visfatin effectively improved wound repair in vivo, which was comparable to the wound healing activity of epidermal growth factor (EGF). Taken together, we demonstrate that visfatin promotes the proliferation and migration of HDFs and human keratinocytes by inducing VEGF expression and can be used as a potential novel therapeutic agent for wound healing.
Identification, Characterization, and Expression Patterns of TCP Genes and microRNA319 in Cotton
Authors: Yin Zujun , Li Yan , Zhu Weidong , Fu Xiaoqiong , Han Xiulan , Wang Junjuan , Lin Huan , Ye Wuwei
Published: November 2018

The TEOSINTE BRANCHED 1, CYCLOIDEA, and PROLIFERATING CELL FACTORS (TCP) gene family is a group of plant-specific transcription factors that have versatile functions in developmental processes and stress responses. In this study, a total of 73 TCP genes in upland cotton were identified and characterizated. Phylogenetic analysis classified them into three subgroups: 50 belonged to PCF, 16 to CIN, and 7 to CYC/TB1. GhTCP genes are randomly distributed in 22 of the 26 chromosomes in cotton. Expression patterns of GhTCPs were analyzed in 10 tissues, including different developmental stages of ovule and fiber, as well as under heat, salt, and drought stresses. Transcriptome analysis showed that 44 GhTCP genes exhibited varied transcript accumulation patterns in the tested tissues and 41 GhTCP genes were differentially expressed in response to heat, salt, and drought stresses. Furthermore, three GhTCP genes of the CIN clade were found to contain miR319-binding sites. An anti-correlation expression of GhTCP21 and GhTCP54 was analyzed with miR319 under salt and drought stress. Our results lay the foundation for understanding the complex mechanisms of GhTCP-mediated developmental processes and abiotic stress-signaling transduction pathways in cotton.
Auxin Controlled by Ethylene Steers Root Development
Authors: Qin Hua , Huang Rongfeng
Published: November 2018

Roots are important plant ground organs, which absorb water and nutrients to control plant growth and development. Phytohormones have been known to play a crucial role in the regulation of root growth, such as auxin and ethylene, which are central regulators of this process. Recent findings have revealed that root development and elongation regulated by ethylene are auxin dependent through alterations of auxin biosynthesis, transport and signaling. In this review, we focus on the recent advances in the study of auxin and auxin–ethylene crosstalk in plant root development, demonstrating that auxin and ethylene act synergistically to control primary root and root hair growth, but function antagonistically in lateral root formation. Moreover, ethylene modulates auxin biosynthesis, transport and signaling to fine-tune root growth and development. Thus, this review steps up the understanding of the regulation of auxin and ethylene in root growth.
Beneficial Effects of Deoxyshikonin on Delayed Wound Healing in Diabetic Mice
Authors: Park Jun Yeon , Shin Myoung-Sook , Hwang Gwi Seo , Yamabe Noriko , Yoo Jeong-Eun , Kang Ki Sung , Kim Jin-Chul , Lee Jeong Gun , Ham Jungyeob , Lee Hye Lim
Published: November 2018

Shiunko ointment is composed of five ingredients including Lithospermi Radix (LR), Angelicae Gigantis Radix, sesame seed oil, beeswax, and swine oil. It is externally applied as a treatment for a wide range of skin conditions such as eczema, psoriasis, hair loss, burns, topical wounds, and atopic dermatitis. Deoxyshikonin is the major angiogenic compound extracted from LR. In this study, we investigated the efficacy of LR extract and deoxyshikonin on impaired wound healing in streptozotocin (STZ)-induced diabetic mice. Treatment with LR extract elevated tube formation in human umbilical vein endothelial cells (HUVECs) and exerted antioxidant activity. An open skin wound was produced on the backs of diabetic mice and was then topically treated with deoxyshikonin or vehicle. In addition, deoxyshikonin promoted tube formation in high glucose conditions exposed to HUVECs, and which may be regulated by increased VEGFR2 expression and phosphorylation of Akt and p38. Our results demonstrate that deoxyshikonin application promoted wound repair in STZ-induced diabetic mice. Collectively, these data suggest that deoxyshikonin is an active ingredient of LR, thereby contributing to wound healing in patients with diabetes.
Interplay of Glycemic Index, Glycemic Load, and Dietary Antioxidant Capacity with Insulin Resistance in Subjects with a Cardiometabolic Risk Profile
Authors: Galarregui Cristina , Zulet María Ángeles , Cantero Irene , Marín-Alejandre Bertha Araceli , Monreal José Ignacio , Elorz Mariana , Benito-Boillos Alberto , Herrero José Ignacio , Tur Josep Antoni , Abete Itziar , Martínez José Alfredo
Published: November 2018

Background: Dietary total antioxidant capacity (TAC), glycemic index (GI), and glycemic load (GL) are accepted indicators of diet quality, which have an effect on diet–disease relationships. The aim of this study was to evaluate potential associations of dietary TAC, GI, and GL with variables related to nutritive status and insulin resistance (IR) risk in cardiometabolic subjects. Methods: A total of 112 overweight or obese adults (age: 50.8 ± 9 years old) were included in the trial. Dietary intake was assessed by a validated 137-item food frequency questionnaire (FFQ), which was also used to calculate the dietary TAC, GI, and GL. Anthropometrics, blood pressure, body composition by dual-energy X-ray absorptiometry (DXA), glycemic and lipid profiles, C-reactive protein (CRP), as well as fatty liver quantification by magnetic resonance imaging (MRI) were assessed. Results: Subjects with higher values of TAC had significantly lower circulating insulin concentration and homeostatic model assessment of insulin resistance (HOMA-IR). Participants with higher values of HOMA-IR showed significantly higher GI and GL. Correlation analyses showed relevant inverse associations of GI and GL with TAC. A regression model evidenced a relationship of HOMA-IR with TAC, GI, and GL. Conclusion: This data reinforces the concept that dietary TAC, GI, and GL are potential markers of diet quality, which have an impact on the susceptible population with a cardiometabolic risk profile.
Discovery of Novel Druggable Sites on Zika Virus NS3 Helicase Using X-ray Crystallography-Based Fragment Screening
Authors: Munawar Ali , Beelen Steven , Munawar Ahmad , Lescrinier Eveline , Strelkov Sergei V.
Published: November 2018

The flavivirus family contains several important human pathogens, such as Zika virus (ZIKV), dengue, West Nile, and Yellow Fever viruses, that collectively lead to a large, global disease burden. Currently, there are no approved medicines that can target these viruses. The sudden outbreak of ZIKV infections in 2015–2016 posed a serious threat to global public health. While the epidemic has receded, persistent reservoirs of ZIKV infection can cause reemergence. Here, we have used X-ray crystallography-based screening to discover two novel sites on ZIKV NS3 helicase that can bind drug-like fragments. Both sites are structurally conserved in other flaviviruses, and mechanistically significant. The binding poses of four fragments, two for each of the binding sites, were characterized at atomic precision. Site A is a surface pocket on the NS3 helicase that is vital to its interaction with NS5 polymerase and formation of the flaviviral replication complex. Site B corresponds to a flexible, yet highly conserved, allosteric site at the intersection of the three NS3 helicase domains. Saturation transfer difference nuclear magnetic resonance (NMR) experiments were additionally used to evaluate the binding strength of the fragments, revealing dissociation constants (KD) in the lower mM range. We conclude that the NS3 helicase of flaviviruses is a viable drug target. The data obtained open opportunities towards structure-based design of first-in-class anti-ZIKV compounds, as well as pan-flaviviral therapeutics.
Central Nervous System Responses to Simulated Galactic Cosmic Rays
Authors: Cekanaviciute Egle , Rosi Susanna , Costes Sylvain V.
Published: November 2018

In preparation for lunar and Mars missions it is essential to consider the challenges to human health that are posed by long-duration deep space habitation via multiple stressors, including ionizing radiation, gravitational changes during flight and in orbit, other aspects of the space environment such as high level of carbon dioxide, and psychological stress from confined environment and social isolation. It remains unclear how these stressors individually or in combination impact the central nervous system (CNS), presenting potential obstacles for astronauts engaged in deep space travel. Although human spaceflight research only within the last decade has started to include the effects of radiation transmitted by galactic cosmic rays to the CNS, radiation is currently considered to be one of the main stressors for prolonged spaceflight and deep space exploration. Here we will review the current knowledge of CNS damage caused by simulated space radiation with an emphasis on neuronal and glial responses along with cognitive functions. Furthermore, we will present novel experimental approaches to integrate the knowledge into more comprehensive studies, including multiple stressors at once and potential translation to human functions. Finally, we will discuss the need for developing biomarkers as predictors for cognitive decline and therapeutic countermeasures to prevent CNS damage and the loss of cognitive abilities.
Functionalized Keratin as Nanotechnology-Based Drug Delivery System for the Pharmacological Treatment of Osteosarcoma
Authors: Martella Elisa , Ferroni Claudia , Guerrini Andrea , Ballestri Marco , Columbaro Marta , Santi Spartaco , Sotgiu Giovanna , Serra Massimo , Donati Davide Maria , Lucarelli Enrico , Varchi Greta , Duchi Serena
Published: November 2018

Osteosarcoma therapy might be moving toward nanotechnology-based drug delivery systems to reduce the cytotoxicity of antineoplastic drugs and improve their pharmacokinetics. In this paper, we present, for the first time, an extensive chemical and in vitro characterization of dual-loaded photo- and chemo-active keratin nanoparticles as a novel drug delivery system to treat osteosarcoma. The nanoparticles are prepared from high molecular weight and hydrosoluble keratin, suitably functionalized with the photosensitizer Chlorin-e6 (Ce6) and then loaded with the chemotherapeutic drug Paclitaxel (PTX). This multi-modal PTX-Ce6@Ker nanoformulation is prepared by both drug-induced aggregation and desolvation methods, and a comprehensive physicochemical characterization is performed. PTX-Ce6@Ker efficacy is tested on osteosarcoma tumor cell lines, including chemo-resistant cells, using 2D and 3D model systems. The single and combined contributions of PTX and Ce6 is evaluated, and results show that PTX retains its activity while being vehiculated through keratin. Moreover, PTX and Ce6 act in an additive manner, demonstrating that the combination of the cytostatic blockage of PTX and the oxidative damage of ROS upon light irradiation have a far superior effect compared to singularly administered PTX or Ce6. Our findings provide the proof of principle for the development of a novel, nanotechnology-based drug delivery system for the treatment of osteosarcoma.
Sedoheptulose-1,7-Bisphosphatase is Involved in Methyl Jasmonate- and Dark-Induced Leaf Senescence in Tomato Plants
Authors: Ding Fei , Wang Meiling , Zhang Shuoxin
Published: November 2018

Leaf senescence represents the final stage of leaf development and is regulated by diverse internal and environmental factors. Jasmonates (JAs) have been demonstrated to induce leaf senescence in several species; however, the mechanisms of JA-induced leaf senescence remain largely unknown in tomato plants (Solanum lycopersicum). In the present study, we tested the hypothesis that sedoheptulose-1,7-bisphosphatase (SBPase), an enzyme functioning in the photosynthetic carbon fixation in the Calvin–Benson cycle, was involved in methyl jasmonate (MeJA)- and dark-induced leaf senescence in tomato plants. We found that MeJA and dark induced senescence in detached tomato leaves and concomitantly downregulated the expression of SlSBPASE and reduced SBPase activity. Furthermore, CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9)-mediated mutagenesis of SlSBPASE led to senescence-associated characteristics in slsbpase mutant plants, including loss of chlorophyll, repressed photosynthesis, increased membrane ion leakage, and enhanced transcript abundance of senescence-associated genes. Collectively, our data suggest that repression of SBPase by MeJA and dark treatment plays a role in JA- and dark-induced leaf senescence.
Correction: Serwotka-Suszczak, A. M. et al. A Conjugate Based on Anti-HER2 Diaffibody and Auristatin E Targets HER2-Positive Cancer Cells. Int. J. Mol. Sci. 2017, 18, 401
Authors: Serwotka-Suszczak Anna , Sochaj-Gregorczyk Alicja , Pieczykolan Jerzy , Krowarsch Daniel , Jelen Filip , Otlewski Jacek
Published: November 2018

It has been brought to our attention that the affiliation of Dr. Jerzy Pieczykolan at the time when he was responsible for the work described in the paper [...]
Quantifying Bicycle Network Connectivity in Lisbon Using Open Data
Authors: Abad Lorena , Van der Meer Lucas
Published: November 2018

Stimulating non-motorized transport has been a key point on sustainable mobility agendas for cities around the world. Lisbon is no exception, as it invests in the implementation of new bike infrastructure. Quantifying the connectivity of such a bicycle network can help evaluate its current state and highlight specific challenges that should be addressed. Therefore, the aim of this study is to develop an exploratory score that allows a quantification of the bicycle network connectivity in Lisbon based on open data. For each part of the city, a score was computed based on how many common destinations (e.g., schools, universities, supermarkets, hospitals) were located within an acceptable biking distance when using only bicycle lanes and roads with low traffic stress for cyclists. Taking a weighted average of these scores resulted in an overall score for the city of Lisbon of only 8.6 out of 100 points. This shows, at a glance, that the city still has a long way to go before achieving their objectives regarding bicycle use in the city.