bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional Variations of Fertility Control Behavior among Rural Reproductive Women in Bangladesh: A Hierarchical Analysis
Authors: Alam Muhammed Ashraful , Chamroonsawasdi Kanittha , Chansatitporn Natkamol , Munsawaengsub Chokchai , Islam Md Shafiqul
Published: August 2018

Women’s fertility decision is quite difficult in male-dominant rural culture due to their poor reproductive autonomy. A cross-sectional survey was conducted in rural community of Bangladesh between November 2017 and February 2018 among 1285 respondents selected by multi-stage stratified sampling to explore regional variations of rural women’s fertility control behavior and its determinants using hierarchical and other inferential statistics. Data collection was done by face-to-face interview using questionnaire. Average parity was 2.5 per woman and 41% respondents had three or more children. About 60% of them used modern contraceptives (MCs) and oral contraceptive pill (OCP) was their first choice. Male participation in contraceptive use was less than 5%. Regional variation, women’s empowerment, fertility control knowledge, family planning (FP) attitude, social influence, perceived behavioral control (PBC) and fertility intention were significant predictors of fertility control behavior (p < 0.05). Significant regional variations were determined in fertility control behavior of rural women (p < 0.05). Almost all of its predictors explained by Theory of Planned Behavior (TPB) also showed significant regional variations (p < 0.05). Current fertility control policy should be strengthened more not only to improve fertility behavior of rural women but also to establish regional equity in fertility control by improving their reproductive decision-making in a rational way.
Antithrombotic Agents and Cancer
Authors: Bruno Annalisa , Dovizio Melania , Tacconelli Stefania , Contursi Annalisa , Ballerini Patrizia , Patrignani Paola
Published: August 2018

Platelet activation is the first response to tissue damage and, if unrestrained, may promote chronic inflammation-related cancer, mainly through the release of soluble factors and vesicles that are rich in genetic materials and proteins. Platelets also sustain cancer cell invasion and metastasis formation by fostering the development of the epithelial-mesenchymal transition phenotype, cancer cell survival in the bloodstream and arrest/extravasation at the endothelium. Furthermore, platelets contribute to tumor escape from immune elimination. These findings provide the rationale for the use of antithrombotic agents in the prevention of cancer development and the reduction of metastatic spread and mortality. Among them, low-dose aspirin has been extensively evaluated in both preclinical and clinical studies. The lines of evidence have been considered appropriate to recommend the use of low-dose aspirin for primary prevention of cardiovascular disease and colorectal cancer by the USA. Preventive Services Task Force. However, two questions are still open: (i) the efficacy of aspirin as an anticancer agent shared by other antiplatelet agents, such as clopidogrel; (ii) the beneficial effect of aspirin improved at higher doses or by the co-administration of clopidogrel. This review discusses the latest updates regarding the mechanisms by which platelets promote cancer and the efficacy of antiplatelet agents.
TGF-βRII Knock-down in Pancreatic Cancer Cells Promotes Tumor Growth and Gemcitabine Resistance. Importance of STAT3 Phosphorylation on S727
Authors: Drubay Vincent , Skrypek Nicolas , Cordiez Lucie , Vasseur Romain , Schulz Céline , Boukrout Nihad , Duchêne Belinda , Coppin Lucie , Van Seuningen Isabelle , Jonckheere Nicolas
Published: August 2018

Pancreatic adenocarcinoma (PDAC) is one of the most deadly cancers in the Western world because of a lack of early diagnostic markers and efficient therapeutics. At the time of diagnosis, more than 80% of patients have metastasis or locally advanced cancer and are therefore not eligible for surgical resection. Pancreatic cancer cells also harbour a high resistance to chemotherapeutic drugs such as gemcitabine that is one of the main palliative treatments for PDAC. Proteins involved in TGF-β signaling pathway (SMAD4 or TGF-βRII) are frequently mutated in PDAC (50–80%). TGF-β signalling pathway plays antagonistic roles during carcinogenesis by initially inhibiting epithelial growth and later promoting the progression of advanced tumors and thus emerged as both tumor suppressor and oncogenic pathways. In order to decipher the role of TGF-β in pancreatic carcinogenesis and chemoresistance, we generated CAPAN-1 and CAPAN-2 cell lines knocked down for TGF-βRII (first actor of TGF-β signaling). The impact on biological properties of these TGF-βRII-KD cells was studied both in vitro and in vivo. We show that TGF-βRII silencing alters tumor growth and migration as well as resistance to gemcitabine. TGF-βRII silencing also leads to S727 STAT3 and S63 c-Jun phosphorylation, decrease of MRP3 and increase of MRP4 ABC transporter expression and induction of a partial EMT phenotype. These markers associated with TGF-β signaling pathways may thus appear as potent therapeutic tools to better treat/manage pancreatic cancer.
Catalytic Transfer Hydrogenolysis as an Effective Tool for the Reductive Upgrading of Cellulose, Hemicellulose, Lignin, and Their Derived Molecules
Authors: Espro Claudia , Gumina Bianca , Szumelda Tomasz , Paone Emilia , Mauriello Francesco
Published: August 2018

Lignocellulosic biomasses have a tremendous potential to cover the future demand of bio-based chemicals and materials, breaking down our historical dependence on petroleum resources. The development of green chemical technologies, together with the appropriate eco-politics, can make a decisive contribution to a cheap and effective conversion of lignocellulosic feedstocks into sustainable and renewable chemical building blocks. In this regard, the use of an indirect H-source for reducing the oxygen content in lignocellulosic biomasses and in their derived platform molecules is receiving increasing attention. In this contribution we highlight recent advances in the transfer hydrogenolysis of cellulose, hemicellulose, lignin, and of their derived model molecules promoted by heterogeneous catalysts for the sustainable production of biofuels and biochemicals.
Photocatalytic Water Disinfection under Solar Irradiation by d-Glucose-Modified Titania
Authors: Markowska-Szczupak Agata , Rokicka Paulina , Wang Kunlei , Endo Maya , Morawski Antoni Waldemar , Kowalska Ewa
Published: August 2018

Modified titania photocatalysts were synthesized by the pressure method using titanium(IV) oxide from Grupa Azoty Zakłady Chemiczne “Police” S.A., Police, Poland, and d-glucose solution. Characterization of obtained composites was performed by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), elemental analysis, and measurements of zeta potential and specific surface area (SSA). The possibility of using glucose-titania composites as photocatalysts for simulated solar-assisted disinfection against gram-negative Escherichia coli and gram-positive Stapchyloccocus epidermidis bacteria were examined in two reaction systems, i.e., for suspended and immobilized photocatalysts (on the concrete). It was found that an increase in the d-glucose concentration, i.e., higher carbon content, led to a decrease in antibacterial properties. The sample obtained from 1% of d-glucose solution at 100 °C (TiO2-1%-G-100) showed superior photocatalytic activity under UV-Vis irradiation toward both bacteria species. Water disinfection was more efficient for suspended photocatalyst than that for supported one, where complete disinfection was reached during 55–70 min and 120 min of irradiation, respectively. For the first time, it has been shown that titania modified with monosaccharides can be efficiently used for water disinfection, and the immobilization of photocatalyst on the concrete might be a prospective method for public water supplies.
The Effect of Neurotoxin MPTP and Neuroprotector Isatin on the Profile of Ubiquitinated Brain Mitochondrial Proteins
Authors: Buneeva Olga , Kopylov Arthur , Kapitsa Inga , Ivanova Elena , Zgoda Victor , Medvedev Alexei
Published: August 2018

Mitochondria are a crucial target for the actions of neurotoxins, causing symptoms of Parkinson’s disease in various experimental animal models, and also neuroprotectors. There is evidence that mitochondrial dysfunction induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) influences functioning of the ubiquitin-proteasomal system (UPS) responsible for selective proteolytic degradation of proteins from various intracellular compartments (including mitochondria) and neuroprotective effects of certain anti-Parkisonian agents (monoamine oxidase inhibitors) may be associated with their effects on the UPS. In this study, we have investigated the effect of the neurotoxin MPTP and neuroprotector isatin, and their combination on the profile of ubiquitinated brain mitochondrial proteins. The development of movement disorders induced by MPTP administration caused dramatic changes in the profile of ubiquitinated proteins associated with mitochondria. Pretreatment with the neuroprotector isatin decreased manifestations of MPTP-induced Parkinsonism, and had a significant impact on the profile of ubiquitinated mitochondrial proteins (including oxidative modified proteins). Administration of isatin alone to intact mice also influenced the profile of ubiquitinated mitochondrial proteins, and increased the proportion of oxidized proteins carrying the ubiquitination signature. These alterations in the ubiquitination of mitochondrial proteins observed within 2 h after administration of MPTP and isatin obviously reflect immediate short-term biological responses to these treatments.
A Review on Ionic Substitutions in Hydroxyapatite Thin Films: Towards Complete Biomimetism
Authors: Graziani Gabriela , Boi Marco , Bianchi Michele
Published: August 2018

Plasma sprayed coatings composed of stoichiometric hydroxyapatite have been extensively used to improve integration of metallic implants in the host bone, as hydroxyapatite (HA) is normally regarded as similar to the mineralized phase of bone. However, these coatings exhibited several drawbacks that limited their success. On the one hand biological apatite is a carbonated-HA, containing significant amounts of foreign ions, having low crystallinity and a small crystals size. This means that it differs from stoichiometric HA in terms of composition, stoichiometry, crystallinity degree, crystal size/morphology and, as a direct consequence, solubility, and ions release in the peri-implant environment. On the other hand, thick plasma sprayed coatings can undergo cracking and delamination and are scarcely uniform. For these reasons, research is pushing into two directions: (i) Increasing the similarity of apatite coatings to real bone, and (ii) exploring deposition by alternative plasma assisted techniques, allowing to achieve thin films, and having superior adhesion and a better control over the coating composition. In this article, we review the latest advances in the field of plasma-assisted deposition of ion-substituted hydroxyapatite thin films, highlighting the state of the art, the limitations, potentialities, open challenges, and the future scenarios for their application.
Series Active Filter Design Based on Asymmetric Hybrid Modular Multilevel Converter for Traction System
Authors: Ali Muhammad , Khan Muhammad Mansoor , Xu Jianming , Faiz Muhammad Talib , Ali Yaqoob , Hashmi Khurram , Tang Houjun
Published: August 2018

This paper presents a comparative analysis of a new topology based on an asymmetric hybrid modular multilevel converter (AHMMC) with recently proposed multilevel converter topologies. The analysis is based on various parameters for medium voltage-high power electric traction system. Among recently proposed topologies, few converters have been analysed through simulation results. In addition, the study investigates AHMMC converter which is a cascade arrangement of H-bridge with five-level cascaded converter module (FCCM) in more detail. The key features of the proposed AHMMC includes: reduced switch losses by minimizing the switching frequency as well as the components count, and improved power factor with minimum harmonic distortion. Extensive simulation results and low voltage laboratory prototype validates the working principle of the proposed converter topology. Furthermore, the paper concludes with the comparison factors evaluation of the discussed converter topologies for medium voltage traction applications.
Experimental Investigation of the Physical and Mechanical Properties of Sisal Fiber-Reinforced Concrete
Authors: Okeola Abass Abayomi , Abuodha Silvester Ochieng , Mwero John
Published: August 2018

Concrete is a very popular material in the construction industry—it is, however, susceptible to quasi-brittle failure and restricted energy absorption after yielding. The incorporation of short discrete fibers has shown great promise in addressing these shortfalls. A natural fiber such as sisal is renewable, cheap, and easily available. It has also exhibited good tensile strength and can significantly improve the performance of concrete. In this study, the physical and mechanical properties of sisal fiber-reinforced concrete were reported. Sisal fibers were added in the mix at percentages of 0.5%, 1.0%, 1.5%, and 2.0% by weight of cement. Physical properties measured are workability, water absorption, and density while mechanical properties reported are compression strength, split tensile strength, and static modulus of elasticity. The computed modulus of elasticity of sisal fiber-reinforced concrete was compared with predicted values in some common design codes. From the study, it was concluded that sisal fiber can enhance the split tensile strength and Young’s modulus of concrete but cannot improve its workability, water absorption, and compressive strength.
Effect of Traditional Household Processes on Iron, Zinc and Copper Bioaccessibility in Black Bean (Phaseolus vulgaris L.)
Authors: Feitosa Sabrina , Greiner Ralf , Meinhardt Ann-Katrin , Müller Alexandra , Almeida Deusdélia T. , Posten Clemens
Published: August 2018

Micronutrient deficiencies are a major public health problem. Beans are an important plant-based source of iron, zinc and copper, but their absorption is reduced in the presence of anti-nutrients such as phytates, polyphenols and tannins. Soaking and discarding the soaking water before cooking is unanimously recommended, but this can result in mineral loss. Data on the consequences for mineral bioaccessibility is still limited. This study aimed to evaluate iron, zinc and copper bioaccessibility in black beans cooked (regular pan, pressure cooker) with and without the soaking water. For that, three batches of black beans were investigated in triplicate, each split in nine parts (raw grains and four different household processes in duplicate) and analyzed by applying the quarter technique, resulting in a grand total of 164 samples. Minerals were quantified by ICP-MS (inductively coupled plasma mass spectrometry), myo-inositol phosphates (InsP5, InsP6) by HPLC (high-performance liquid chromatography) ion-pair chromatography, total polyphenols using Folin-Denis reagent and condensed tannins using Vanillin assay. Mineral bioaccessibility was determined by in vitro digestion and dialysis. All treatments resulted in a statistically significant reduction of total polyphenols (30%) and condensed tannins (20%). Only when discarding the soaking water a loss of iron (6%) and copper (30%) was observed, and InsP6 was slightly decreased (7%) in one treatment. The bioaccessibility of iron and zinc were low (about 0.2% iron and 35% zinc), but copper presented high bioaccessibility (about 70%). Cooking beans under pressure without discarding the soaking water resulted in the highest bioaccessibility levels among all household procedures. Discarding the soaking water before cooking did not improve the nutritional quality of the beans.
PRDM Histone Methyltransferase mRNA Levels Increase in Response to Curative Hormone Treatment for Cryptorchidism-Dependent Male Infertility
Authors: Hadziselimovic Faruk , Cathomas Gieri , Verkauskas Gilvydas , Dasevicius Darius , Stadler Michael B.
Published: August 2018

There is a correlation between cryptorchidism and an increased risk of testicular cancer and infertility. During orchidopexy, testicular biopsies are performed to confirm the presence of type A dark (Ad) spermatogonia, which are a marker for low infertility risk (LIR). The Ad spermatogonia are absent in high infertility risk (HIR) patients, who are treated with a gonadotropin-releasing hormone agonist (GnRHa) to significantly lower the risk of infertility. Despite its prevalence, little is known about the molecular events involved in cryptorchidism. Previously, we compared the transcriptomes of LIR versus HIR patients treated with and without hormones. Here, we interpreted data regarding members of the positive regulatory domain-containing (PRDM) family; some of which encoded histone methyltransferases that are important for reproduction. We found there were lower levels of PRDM1, PRDM6, PRDM9, PRDM13, and PRDM14 mRNA in the testes of HIR patients compared with LIR patients, and that PRDM7, PRDM9, PRDM12, and PRDM16 were significantly induced after GnRHa treatment. Furthermore, we observed PRDM9 protein staining in the cytoplasm of germ cells in the testes from LIR and HIR patients, indicating that the mRNA and protein levels corresponded. This result indicated that the curative hormonal therapy for cryptorchidism involved conserved chromatin modification enzymes.
RNA Structure Elements Conserved between Mouse and 59 Other Vertebrates
Authors: Thiel Bernhard C. , Ochsenreiter Roman , Gadekar Veerendra P. , Tanzer Andrea , Hofacker Ivo L.
Published: August 2018

In this work, we present a computational screen conducted for functional RNA structures, resulting in over 100,000 conserved RNA structure elements found in alignments of mouse (mm10) against 59 other vertebrates. We explicitly included masked repeat regions to explore the potential of transposable elements and low-complexity regions to give rise to regulatory RNA elements. In our analysis pipeline, we implemented a four-step procedure: (i) we screened genome-wide alignments for potential structure elements using RNAz-2, (ii) realigned and refined candidate loci with LocARNA-P, (iii) scored candidates again with RNAz-2 in structure alignment mode, and (iv) searched for additional homologous loci in mouse genome that were not covered by genome alignments. The 3’-untranslated regions (3’-UTRs) of protein-coding genes and small noncoding RNAs are enriched for structures, while coding sequences are depleted. Repeat-associated loci make up about 95% of the homologous loci identified and are, as expected, predominantly found in intronic and intergenic regions. Nevertheless, we report the structure elements enriched in specific genome elements, such as 3’-UTRs and long noncoding RNAs (lncRNAs). We provide full access to our results via a custom UCSC genome browser trackhub freely available on our website (http://rna.tbi.univie.ac.at/trackhubs/#RNAz).
Mitochondrial DNA Haplogroups and Breast Cancer Risk Factors in the Avon Longitudinal Study of Parents and Children (ALSPAC)
Authors: Riley Vivienne , Erzurumluoglu A Mesut , Rodriguez Santiago , Bonilla Carolina
Published: August 2018

The relationship between mitochondrial DNA (mtDNA) and breast cancer has been frequently examined, particularly in European populations. However, studies reporting associations between mtDNA haplogroups and breast cancer risk have had a few shortcomings including small sample sizes, failure to account for population stratification and performing inadequate statistical tests. In this study we investigated the association of mtDNA haplogroups of European origin with several breast cancer risk factors in mothers and children of the Avon Longitudinal Study of Parents and Children (ALSPAC), a birth cohort that enrolled over 14,000 pregnant women in the Southwest region of the UK. Risk factor data were obtained from questionnaires, clinic visits and blood measurements. Information on over 40 independent breast cancer risk factor-related variables was available for up to 7781 mothers and children with mtDNA haplogroup data in ALSPAC. Linear and logistic regression models adjusted for age, sex and population stratification principal components were evaluated. After correction for multiple testing we found no evidence of association of European mtDNA haplogroups with any of the breast cancer risk factors analysed. Mitochondrial DNA haplogroups are unlikely to underlie susceptibility to breast cancer that occurs via the risk factors examined in this study of a population of European ancestry.
Prioritizing Abandoned Mine Lands Rehabilitation: Combining Landscape Connectivity and Pattern Indices with Scenario Analysis Using Land-Use Modeling
Authors: Zhang Liping , Zhang Shiwen , Huang Yajie , Xing An , Zhuo Zhiqing , Sun Zhongxiang , Li Zhen , Cao Meng , Huang Yuanfang
Published: August 2018

Connectivity modeling approaches for abandoned mine lands (AML) patches are limited in post-mining landscape restoration, especially where great land use changes might be expected due to large-scale land reclamation. This study presents a novel approach combining AML patch sizes with a proximity index to characterize patch-scaled connectivity for determining the spatial positions of patches with huge sizes and high connectivity. Then this study propose a scenario-based method coupled with landscape-scale metrics for quantifying landscape-scaled connectivity, which aims at exploring the optimal reclamation scheme with the highest connectivity. Using the Mentougou District in Beijing, China, as a case study, this paper confirmed which patches should be reclaimed first to meet the predetermined reclamation numbers; then this paper tested three different reclamation scenarios (i.e., cultivated land-oriented, forest-oriented, and construction land-oriented scenarios) to describe the impact of the different development strategies on landscape connectivity. The research found that the forest-oriented scenario increased connectivity quantitatively, showing an increase in the integral index of connectivity (IIC) and other landscape-scale metrics. Therefore, this paper suggests that future land-use policies should emphasize converting AML into more forest to blend in with the surrounding land-use categories. The findings presented here can contribute to better understanding the quantitative analysis of the connectivity of AML patches at both the patch scale and the landscape scale, thus providing scientific support for AML management in mine-site rehabilitation.
Mapping Rural Road Networks from Global Positioning System (GPS) Trajectories of Motorcycle Taxis in Sigomre Area, Siaya County, Kenya
Authors: Oloo Francis
Published: August 2018

Effective transport infrastructure is an essential component of economic integration, accessibility to vital social services and a means of mitigation in times of emergency. Rural areas in Africa are largely characterized by poor transport infrastructure. This poor state of rural road networks contributes to the vulnerability of communities in developing countries by hampering access to vital social services and opportunities. In addition, maps of road networks are incomplete, and not up-to-date. Lack of accurate maps of village-level road networks hinders determination of access to social services and timely response to emergencies in remote locations. In some countries in sub-Saharan Africa, communities in rural areas and some in urban areas have devised an alternative mode of public transport system that is reliant on motorcycle taxis. This new mode of transport has improved local mobility and has created a vibrant economy that depends on the motorcycle taxi business. The taxi system also offers an opportunity for understanding local-level mobility and the characterization of the underlying transport infrastructure. By capturing the spatial and temporal characteristics of the taxis, we could design detailed maps of rural infrastructure and reveal the human mobility patterns that are associated with the motorcycle taxi system. In this study, we tracked motorcycle taxis in a rural area in Kenya by tagging volunteer riders with Global Positioning System (GPS) data loggers. A semi-automatic method was applied on the resulting trajectories to map rural-level road networks. The results showed that GPS trajectories from motorcycle taxis could potentially improve the maps of rural roads and augment other mapping initiatives like OpenStreetMap.
Cloning and Functional Characterisation of the Duplicated RDL Subunits from the Pea Aphid, Acyrthosiphon pisum
Authors: Del Villar Silvia G. , Jones Andrew K.
Published: August 2018

The insect GABA receptor, RDL (resistance to dieldrin), is a cys-loop ligand-gated ion channel (cysLGIC) that plays a central role in neuronal signaling, and is the target of several classes of insecticides. Many insects studied to date possess one Rdl gene; however, there is evidence of two Rdls in aphids. To characterise further this insecticide target from pests that cause millions of dollars’ worth of crop damage each year, we identified the complete cysLGIC gene superfamily of the pea aphid, Acyrthosiphon pisum, using BLAST analysis. This confirmed the presence of two Rdl-like genes (RDL1 and RDL2) that likely arose from a recent gene duplication. When expressed individually in Xenopus laevis oocytes, both subunits formed functional ion channels gated by GABA. Alternative splicing of RDL1 influenced the potency of GABA, and the potency of fipronil was different on the RDL1bd splice variant and RDL2. Imidacloprid and clothianidin showed no antagonistic activity on RDL1, whilst 100 μM thiacloprid reduced the GABA responses of RDL1 and RDL2 to 55% and 62%, respectively. It was concluded that gene duplication of Rdl may have conferred increased tolerance to natural insecticides, and played a role in the evolution of insect cysLGICs.
Calcitriol and Calcidiol Can Sensitize Melanoma Cells to Low–LET Proton Beam Irradiation
Authors: Podgorska Ewa , Drzal Agnieszka , Matuszak Zenon , Swakon Jan , Slominski Andrzej , Elas Martyna , Urbanska Krystyna
Published: August 2018

Proton beam irradiation promises therapeutic utility in the management of uveal melanoma. Calcitriol (1,25(OH)2D3)—the biologically active metabolite of vitamin D3—and its precursor, calcidiol (25(OH)D3), exert pleiotropic effects on melanoma cells. The aim of the study was to evaluate the effect of both calcitriol and calcidiol on melanoma cell proliferation and their response to proton beam irradiation. Three melanoma cell lines (human SKMEL-188 and hamster BHM Ma and BHM Ab), pre-treated with 1,25(OH)2D3 or 25(OH)D3 at graded concentrations (0, 10, 100 nM), were irradiated with 0–5 Gy and then cultured in vitro. Growth curves were determined by counting the cell number every 24 h up to 120 h, which was used to calculate surviving fractions. The obtained survival curves were analysed using two standard models: linear-quadratic and multi-target single hit. Calcitriol inhibited human melanoma proliferation at 10 nM, while only calcidiol inhibited proliferation of hamster lines at 10 and 100 nM doses. Treatment with either 1,25(OH)2D3 or 25(OH)D3 radio sensitized melanoma cells to low doses of proton beam radiation. The strength of the effect increased with the concentration of vitamin D3. Our data suggest that vitamin D3 may be an adjuvant that modifies proton beam efficiency during melanoma therapy.
Bisphenol-A and Nonylphenol Induce Apoptosis in Reproductive Tract Cancer Cell Lines by the Activation of ADAM17
Authors: Urriola-Muñoz Paulina , Lagos-Cabré Raúl , Patiño-García Daniel , Reyes Juan G. , Moreno Ricardo D.
Published: August 2018

Endocrine-disruptor chemicals (EDCs), such as bisphenol A (BPA) and nonylphenol (NP), have been widely studied due to their negative effects on human and wildlife reproduction. Exposure to BPA or NP is related to cell death, hormonal deregulation, and cancer onset. Our previous studies showed that both compounds induce A Disintegrin And Metalloprotease 17 (ADAM17) activation. Here, we show that BPA and NP induce apoptosis in prostate and ovary cancer cell lines, in a process dependent on ADAM17 activation. ADAM17 knockdown completely prevented apoptosis as well as the shedding of ADAM17 substrates. Both compounds were found to induce an increase in intracellular calcium (Ca2+) only in Ca2+-containing medium, with the NP-treated cells response being more robust than those treated with BPA. Additionally, using a phosphorylated protein microarray, we found that both compounds stimulate common intracellular pathways related to cell growth, differentiation, survival, and apoptosis. These results suggest that BPA and NP could induce apoptosis through ADAM17 by activating different intracellular signaling pathways that may converge in different cellular responses, one of which is apoptosis. These results confirm the capacity of these compounds to induce cell apoptosis in cancer cell lines and uncover ADAM17 as a key regulator of this process in response to EDCs.
Tubeimoside I Protects Dopaminergic Neurons Against Inflammation-Mediated Damage in Lipopolysaccharide (LPS)-Evoked Model of Parkinson’s Disease in Rats
Authors: He Dewei , Huang Bingxu , Fu Shoupeng , Li Yuhang , Ran Xin , Liu Yandan , Chen Guangxin , Liu Juxiong , Liu Dianfeng
Published: August 2018

Parkinson’s disease (PD), a frequent degenerative disease in the elderly, is characterized by dopaminergic neurodegeneration in the substantia nigra pars compacta (SNpc). Neuroinflammation caused by over-activated microglia plays a crucial role in the pathogenesis of PD. Tubeimoside I (TBMS1) has a broad anti-inflammatory effect in peripheral tissues, but the effect on neuroinflammation has not been reported. Therefore, we explored whether TBMS1 could protect dopaminergic neurons by inhibiting the activation of microglia in lipopolysaccharide (LPS)-induced PD rat model. In addition, then, the effect and mechanism of TBMS1 on neuroinflammation were assessed in LPS-exposed murine microglial BV-2 cells. The results in vivo showed that TBMS1 suppressed microglial activation and dopaminergic neurons’ reduction in LPS-injected PD rat model. In vitro study found that TBMS1 could inhibit LPS-induced inflammatory responses in BV-2 cells, and this effect was mediated by suppressing the phosphorylation of protein kinase B (AKT), nuclear factor-kappa B (NF-κB p65), p38 and extracellular regulated protein kinases (ERK1/2). Taken together, these results demonstrated for the first time that TBMS1 played a role in protecting dopaminergic neurons by inhibiting neuroinflammation mediated by microglia.
Agrobiotechnology Goes Wild: Ancient Local Varieties as Sources of Bioactives
Authors: Berni Roberto , Cantini Claudio , Romi Marco , Hausman Jean-Francois , Guerriero Gea , Cai Giampiero
Published: August 2018

The identification and use of species that have best adapted to their growth territory is of paramount importance to preserve biodiversity while promoting sustainable agricultural practices. Parameters including resistance to natural conditions (biotic and abiotic risk factors), biomass and fruit productivity, and phytochemical content with nutraceutical potential, could be used as quantitative markers of the adaptability of plants to wild environments characterized by minimal human impact. Ancient varieties, which are plant varieties growing in regional territories and not destined for market distribution, are a source of unique genetic characters derived from many years of adaptation to the original territory. These plants are often more resistant to biotic and abiotic stresses. In addition, these varieties have a high phytochemical (also known as bioactives) content considered health-beneficial. Notably, the content of these compounds is often lower in commercial cultivars. The use of selected territorial varieties according to the cultivation area represents an opportunity in the agricultural sector in terms of biodiversity preservation, environmental sustainability, and valorization of the final products. Our survey highlights the nutraceutical potential of ancient local varieties and stresses the importance of holistic studies (-omics) to investigate their physiology and secondary metabolism.
Facilitating the Cellular Accumulation of Pt-Based Chemotherapeutic Drugs
Authors: Lambert Ian Henry , Sørensen Belinda Halling
Published: August 2018

Cisplatin, carboplatin, and oxaliplatin are Pt-based drugs used in the chemotherapeutic eradication of cancer cells. Although most cancer patient cells initially respond well to the treatment, the clinical effectiveness declines over time as the cancer cells develop resistance to the drugs. The Pt-based drugs are accumulated via membrane-bound transporters, translocated to the nucleus, where they trigger various intracellular cell death programs through DNA interaction. Here we illustrate how resistance to Pt-based drugs, acquired through limitation in the activity/subcellular localization of canonical drug transporters, might be circumvented by the facilitated uptake of Pt-based drug complexes via nanocarriers/endocytosis or lipophilic drugs by diffusion.
Fernblock Prevents Dermal Cell Damage Induced by Visible and Infrared A Radiation
Authors: Zamarrón Alicia , Lorrio Silvia , González Salvador , Juarranz Ángeles
Published: August 2018

Sun overexposure leads to higher risk of photoaging and skin cancer. The contribution of infrared (IR) and visible light (VIS) radiation is currently being taken into account in their pathogenesis. Erythema, hyperpigmentation, genotoxicity or the increase of matrix metalloproteinases (MMPs) expression are some of the effects induced by these types of radiation. Extracts of various botanicals endowed with antioxidant activity are emerging as new photoprotective compounds. A natural extract from Polypodium leucotomos (Fernblock®, FB) has antioxidant and photoprotective properties and exhibits a strong anti-aging effect. In this study, we evaluated the protective capacity of FB against the detrimental effects of infrared A (IRA) and VIS radiation in human dermal fibroblasts. We analyzed the effects of FB on the morphology, viability, cell cycle and expression of extracellular matrix components of fibroblasts subjected to VIS and IRA. Our results indicate that FB prevents cell damage caused by VIS and IRA. Moreover, it reduces the increase in MMP-1 and cathepsin K expression induced by both VIS and IRA radiation, and curbs alterations in fibrillin 1, fibrillin 2 and elastin expression. All these findings support FB as a feasible approach to prevent or treat skin damage caused by IRA or VIS exposure.
Autophagy in Human Skin Fibroblasts: Impact of Age
Authors: Kim Hei Sung , Park Seo-Yeon , Moon Seok Hoon , Lee Jeong Deuk , Kim Sungjoo
Published: August 2018

Autophagy is an intracellular stress response that is enhanced under starvation conditions, and also when the cellular components are damaged. Aging accompanies an increase in intracellular stress and has significant impact on the skin. Since dermal fibroblasts are a powerful indicator of skin aging, we compared the autophagic activity of human skin fibroblasts between the young and old. According to TEM analyses, the number of autophagosomes per 1 μm2 cytoplasmic area was similar between young and aged fibroblasts. The amount of LC3 (microtubule-associated protein 1 light chain 3)-II, a form associated with autophagic vacuolar membranes, was also similar between the groups from Western blot analysis. Although residual bodies were more common in aged dermal fibroblasts, LC3 turnover and p62 assay showed little difference in the rate of lysosomal proteolysis between the young and old. RNA-seq analysis revealed that the major autophagy-modulating genes (BECN1, MAP1LC3B, ATG5, ATG7, ULK1, PIK3C3, mTOR) were not differentially expressed with age. Our results suggest that the basal autophagic flux in aged dermal fibroblasts is largely comparable to that of young fibroblasts. However, with a higher speed and amount of waste production in aged cells, we postulate that such autophagic flux may not be sufficient in keeping the old cells “clean”, resulting in skin aging. Aging is a complex process and, as such, the relationship between autophagy and aging is not straightforward. That is to say, autophagy does not simply decline with age. Regardless of the controversies on autophagic activity with age, autophagy plays a crucial role in counteracting aging, and strategies aimed at its modulation should hold promise for the prevention of skin aging.
Green Tea Polyphenols Coupled with a Bioactive Titanium Alloy Surface: In Vitro Characterization of Osteoinductive Behavior through a KUSA A1 Cell Study
Authors: Cazzola Martina , Ferraris Sara , Boschetto Francesco , Rondinella Alfredo , Marin Elia , Zhu Wenliang , Pezzotti Giuseppe , Vernè Enrica , Spriano Silvia
Published: August 2018

A chemically-treated titanium alloy (Ti6Al4V) surface, able to induce hydroxyapatite precipitation from body fluids (inorganic mineralization activity), was functionalized with a polyphenolic extract from green tea (tea polyphenols, TPH). Considering that green tea polyphenols have stimulating effects on bone forming cells (biological mineralization), the aim was to test their osteoinductive behavior due to co-operation of inorganic and biological mineralization on mesenchymal stem cells KUSA A1. The functionalized surfaces were characterized by using the Folin–Ciocalteu method and X-ray photoelectron spectroscopy to confirm the successful outcome of the functionalization process. Two cell cultures of mesenchymal stem cells, KUSA A1 were performed, with or without osteoinductive factors. The cells and surfaces were characterized for monitoring cell viability and hydroxyapatite production: Fourier Transform Infrared Spectroscopy and Raman spectroscopy analyses showed deposition of hydroxyapatite and collagen due to the cell activity, highlighting differentiation of KUSA A1 into osteoblasts. A higher production of extracellular matrix was highlighted on the functionalized samples by laser microscope and the fluorescence images showed higher viability of cells and greater presence of osteocalcin in these samples. These results highlight the ability of polyphenols to improve cell differentiation and to stimulate biological mineralization, showing that surface functionalization of metal implants could be a promising way to improve osteointegrability.
Typical and Atypical Inducers of Lysosomal Cell Death: A Promising Anticancer Strategy
Authors: Domagala Antoni , Fidyt Klaudyna , Bobrowicz Malgorzata , Stachura Joanna , Szczygiel Kacper , Firczuk Malgorzata
Published: August 2018

Lysosomes are conservative organelles with an indispensable role in cellular degradation and the recycling of macromolecules. However, in light of recent findings, it has emerged that the role of lysosomes in cancer cells extends far beyond cellular catabolism and includes a variety of cellular pathways, such as proliferation, metastatic potential, and drug resistance. It has been well described that malignant transformation leads to alterations in lysosomal structure and function, which, paradoxically, renders cancer cells more sensitive to lysosomal destabilization. Furthermore, lysosomes are implicated in the regulation and execution of cell death in response to diverse stimuli and it has been shown that lysosome-dependent cell death can be utilized to overcome apoptosis and drug resistance. Thus, the purpose of this review is to characterize the role of lysosome in cancer therapy and to describe how these organelles impact treatment resistance. We summarized the characteristics of typical inducers of lysosomal cell death, which exert its function primarily via alterations in the lysosomal compartment. The review also presents other anticancer agents with the predominant mechanism of action different from lysosomal destabilization, the activity of which is influenced by lysosomal signaling, including classical chemotherapeutics, kinase inhibitors, monoclonal antibodies, as well as photodynamic therapy.
Semantic Analysis of Posttranslational Modification of Proteins Accumulated in Thyroid Cancer Cells Exposed to Simulated Microgravity
Authors: Bauer Johann , Wehland Markus , Infanger Manfred , Grimm Daniela , Gombocz Erich
Published: August 2018

When monolayers of tissue cancer cells of various origins are exposed to real or simulated microgravity, many cells leave the monolayer and assemble to three-dimensional (3D) aggregates (spheroids). In order to define the cellular machinery leading to this change in growth behavior of FTC-133 human thyroid cancer cells and MCF-7 breast cancer cells, we recently performed proteome analyses on these cell lines and determined the proteins’ accumulation in monolayer cells grown under 1g-conditions as well as in the cells of spheroids assembled under simulated microgravity during three and 14 days, respectively. At that time, an influence of the increment or decrement of some of the more than 5000 proteins detected in each cell line was investigated. In this study, we focused on posttranslational modifications (PTMs) of proteins. For this purpose, we selected candidates from the list of the proteins detected in the two preceding proteome analyses, which showed significant accumulation in spheroid cells as compared to 1g monolayer cells. Then we searched for those PTMs of the selected proteins, which according to the literature have already been determined experimentally. Using the Semantic Protocol and RDF Query Language (SPARQL), various databases were examined. Most efficient was the search in the latest version of the dbPTM database. In total, we found 72 different classes of PTMs comprising mainly phosphorylation, glycosylation, ubiquitination and acetylation. Most interestingly, in 35 of the 69 proteins, N6 residues of lysine are modifiable.
A Novel Splice-Site Mutation in VEGFC Is Associated with Congenital Primary Lymphoedema of Gordon
Authors: Nadarajah Noeline , Schulte Dörte , McConnell Vivienne , Martin-Almedina Silvia , Karapouliou Christina , Mortimer Peter S. , Jeffery Steve , Schulte-Merker Stefan , Gordon Kristiana , Mansour Sahar , Ostergaard Pia
Published: August 2018

Lymphedema is characterized by chronic swelling of any body part caused by malfunctioning or obstruction in the lymphatic system. Primary lymphedema is often considered genetic in origin. VEGFC, which is a gene encoding the ligand for the vascular endothelial growth factor receptor 3 (VEGFR3/FLT4) and important for lymph vessel development during lymphangiogenesis, has been associated with a specific subtype of primary lymphedema. Through Sanger sequencing of a proband with bilateral congenital pedal edema resembling Milroy disease, we identified a novel mutation (NM_005429.2; c.361+5G>A) in VEGFC. The mutation induced skipping of exon 2 of VEGFC resulting in a frameshift and the introduction of a premature stop codon (p.Ala50ValfsTer18). The mutation leads to a loss of the entire VEGF-homology domain and the C-terminus. Expression of this Vegfc variant in the zebrafish floorplate showed that the splice-site variant significantly reduces the biological activity of the protein. Our findings confirm that the splice-site variant, c.361+5G>A, causes the primary lymphedema phenotype in the proband. We examine the mutations and clinical phenotypes of the previously reported cases to review the current knowledge in this area.
Reevaluation of Pluripotent Cytokine TGF-β3 in Immunity
Authors: Komai Toshihiko , Okamura Tomohisa , Inoue Mariko , Yamamoto Kazuhiko , Fujio Keishi
Published: August 2018

Transforming growth factor (TGF)-βs are pluripotent cytokines with stimulatory and inhibitory properties for multiple types of immune cells. Analyses of genetic knockouts of each isoform of TGF-β have revealed differing expression patterns and distinct roles for the three mammalian isoforms of TGF-β. Considerable effort has been focused on understanding the molecular mechanisms of TGF-β1-mediated immune regulation, given its pivotal role in prohibiting systemic autoimmune disease. In recent years, functional similarities and differences between the TGF-β isoforms have delineated their distinct roles in the development of immunopathology and immune tolerance, with increased recent attention being focused on TGF-β3. In addition to the characteristic properties of each TGF-β isoform, recent progress has identified determinants of context-dependent functionality, including various cellular targets, cytokine concentrations, tissue microenvironments, and cytokine synergy, which combine to shape the physiological and pathophysiological roles of the TGF-βs in immunity. Controlling TGF-β production and signaling is being tested as a novel therapeutic strategy in multiple clinical trials for several human diseases. This review highlights advances in the understanding of the cellular sources, activation processes, contextual determinants, and immunological roles of TGF-β3 with comparisons to other TGF-β isoforms.
The Enriching Interplay between Openness and Interest: A Theoretical Elaboration of the OFCI Model and a First Empirical Test
Authors: Ziegler Matthias , Schroeter Titus A. , Lüdtke Oliver , Roemer Lena
Published: August 2018

The Openness-Fluid-Crystallized-Intelligence (OFCI) model posits long-term relations between Openness and cognitive abilities and has been successfully tested with longitudinal data. However, research on the developmental interplay between cognitive abilities and personality exists only sparsely. The current paper focuses on a theoretical development of the OFCI model which suggests micro-level mechanisms underlying the long-term development. Specifically, within-situation relations between Openness, interests, situational perception, cognitive abilities, and emotions are proposed to explain longitudinal relations between Openness and cognitive abilities. Using experience sampling, selected parts of this elaboration were empirically scrutinized in a first test of the proposed ideas. Openness and specific interest both varied substantially across situations and covaried systematically. In interaction with an indicator of fluid intelligence, this covariation was related to an indicator of crystallized intelligence. The paper contributes to theorizing the intertwined development of personality and cognitive abilities, and highlights the importance of within-situation research for explaining long-term development.
CMIP5-Derived Single-Forcing, Single-Model, and Single-Scenario Wind-Wave Climate Ensemble: Configuration and Performance Evaluation
Authors: Semedo Alvaro , Dobrynin Mikhail , Lemos Gil , Behrens Arno , Staneva Joanna , De Vries Hylke , Sterl Andreas , Bidlot Jean-Raymond , Miranda Pedro M. A. , Murawski Jens
Published: August 2018

A Coupled Model Intercomparison Project Phase 5 (CMIP5)-derived single-forcing, single-model, and single-scenario dynamic wind-wave climate ensemble is presented, and its historic period (1979–2005) performance in representing the present wave climate is evaluated. A single global climate model (GCM)-forcing wave climate ensemble was produced with the goal of reducing the inter GCM variability inherent in using a multi-forcing approach for the same wave model. Seven CMIP5 EC-Earth ensemble runs were used to force seven WAM wave model realizations, while future wave climate simulations, not analyzed here, were produced using a high-emission representative concentration pathway 8.5 (RCP8.5) set-up. The wave climate ensemble’s historic period was extensively compared against a set of 72 in situ wave-height observations, as well as to ERA-Interim reanalysis and Climate Forecast System Reanalysis (CFSR) hindcast. The agreement between the wave climate ensemble and the in situ measurements and reanalysis of mean and extreme wave heights, mean wave periods, and mean wave directions was good, in line with previous studies or even better in some areas of the global ocean, namely in the extratropical latitudes. These results give a good degree of confidence in the ability of the ensemble to simulate a realistic climate change signal.