bluuebunny/crossref_metadata_2025 huggingface dataset:
De Novo Hepatic Transcriptome Assembly and Systems Level Analysis of Three Species of Dietary Fish, Sardinops sagax, Scomber japonicus, and Pleuronichthys verticalis
Authors: Richards Dylan J. , Renaud Ludivine , Agarwal Nisha , Starr Hazard E. , Hyde John , Hardiman Gary
Published: October 2018

The monitoring of marine species as sentinels for ecosystem health has long been a valuable tool worldwide, providing insight into how both anthropogenic pollution and naturally occurring phenomena (i.e., harmful algal blooms) may lead to human and animal dietary concerns. The marine environments contain many contaminants of anthropogenic origin that have sufficient similarities to steroid and thyroid hormones, to potentially disrupt normal endocrine physiology in humans, fish, and other animals. An appropriate understanding of the effects of these endocrine disrupting chemicals (EDCs) on forage fish (e.g., sardine, anchovy, mackerel) can lead to significant insight into how these contaminants may affect local ecosystems in addition to their potential impacts on human health. With advancements in molecular tools (e.g., high-throughput sequencing, HTS), a genomics approach offers a robust toolkit to discover putative genetic biomarkers in fish exposed to these chemicals. However, the lack of available sequence information for non-model species has limited the development of these genomic toolkits. Using HTS and de novo assembly technology, the present study aimed to establish, for the first time for Sardinops sagax (Pacific sardine), Scomber japonicas (Pacific chub mackerel) and Pleuronichthys verticalis (hornyhead turbot), a de novo global transcriptome database of the liver, the primary organ involved in detoxification. The assembled transcriptomes provide a foundation for further downstream validation, comparative genomic analysis and biomarker development for future applications in ecotoxicogenomic studies, as well as environmental evaluation (e.g., climate change) and public health safety (e.g., dietary screening).
Satellite DNAs Unveil Clues about the Ancestry and Composition of B Chromosomes in Three Grasshopper Species
Authors: Milani Diogo , Bardella Vanessa B. , Ferretti Ana B. S. M. , Palacios-Gimenez Octavio M. , Melo Adriana de S. , Moura Rita C. , Loreto Vilma , Song Hojun , Cabral-de-Mello Diogo C.
Published: October 2018

Supernumerary (B) chromosomes are dispensable genomic elements occurring frequently among grasshoppers. Most B chromosomes are enriched with repetitive DNAs, including satellite DNAs (satDNAs) that could be implicated in their evolution. Although studied in some species, the specific ancestry of B chromosomes is difficult to ascertain and it was determined in only a few examples. Here we used bioinformatics and cytogenetics to characterize the composition and putative ancestry of B chromosomes in three grasshopper species, Rhammatocerus brasiliensis, Schistocerca rubiginosa, and Xyleus discoideus angulatus. Using the RepeatExplorer pipeline we searched for the most abundant satDNAs in Illumina sequenced reads, and then we generated probes used in fluorescent in situ hybridization (FISH) to determine chromosomal position. We used this information to infer ancestry and the events that likely occurred at the origin of B chromosomes. We found twelve, nine, and eighteen satDNA families in the genomes of R. brasiliensis, S. rubiginosa, and X. d. angulatus, respectively. Some satDNAs revealed clustered organization on A and B chromosomes varying in number of sites and position along chromosomes. We did not find specific satDNA occurring in the B chromosome. The satDNAs shared among A and B chromosomes support the idea of putative intraspecific ancestry from small autosomes in the three species, i.e., pair S11 in R. brasiliensis, pair S9 in S. rubiginosa, and pair S10 in X. d. angulatus. The possibility of involvement of other chromosomal pairs in B chromosome origin is also hypothesized. Finally, we discussed particular aspects in composition, origin, and evolution of the B chromosome for each species.
Copy Number Variants Account for a Tiny Fraction of Undiagnosed Myopathic Patients
Authors: Giugliano Teresa , Savarese Marco , Garofalo Arcomaria , Picillo Esther , Fiorillo Chiara , D’Amico Adele , Maggi Lorenzo , Ruggiero Lucia , Vercelli Liliana , Magri Francesca , Fattori Fabiana , Torella Annalaura , Ergoli Manuela , Rubegni Anna , Fanin Marina , Musumeci Olimpia , Bleecker Jan , Peverelli Lorenzo , Moggio Maurizio , Mercuri Eugenio , Toscano Antonio , Mora Marina , Santoro Lucio , Mongini Tiziana , Bertini Enrico , Bruno Claudio , Minetti Carlo , Comi Giacomo , Santorelli Filippo , Angelini Corrado , Politano Luisa , Piluso Giulio , Nigro Vincenzo
Published: October 2018

Next-generation sequencing (NGS) technologies have led to an increase in the diagnosis of heterogeneous genetic conditions. However, over 50% of patients with a genetically inherited disease are still without a diagnosis. In these cases, different hypotheses are usually postulated, including variants in novel genes or elusive mutations. Although the impact of copy number variants (CNVs) in neuromuscular disorders has been largely ignored to date, missed CNVs are predicted to have a major role in disease causation as some very large genes, such as the dystrophin gene, have prone-to-deletion regions. Since muscle tissues express several large disease genes, the presence of elusive CNVs needs to be comprehensively assessed following an accurate and systematic approach. In this multicenter cohort study, we analyzed 234 undiagnosed myopathy patients using a custom array comparative genomic hybridization (CGH) that covers all muscle disease genes at high resolution. Twenty-two patients (9.4%) showed non-polymorphic CNVs. In 12 patients (5.1%), the identified CNVs were considered responsible for the observed phenotype. An additional ten patients (4.3%) presented candidate CNVs not yet proven to be causative. Our study indicates that deletions and duplications may account for 5–9% of genetically unsolved patients. This strongly suggests that other mechanisms of disease are yet to be discovered.
Special Issue “Laboratory Geosciences: Modelling Surface Processes” in Geosciences
Authors: Nones Michael
Published: October 2018

In the last decades, new and advanced measurement techniques have been developed to track the dynamics of surface processes and the formation of river bedforms, bars and island as well as complex fluvial networks, gullies and rills by means of small-scale laboratory experiments, aiming to integrate and support mathematical models [...]
Analysis of Different Statistical Models in Probabilistic Joint Estimation of Porosity and Litho-Fluid Facies from Acoustic Impedance Values
Authors: Aleardi Mattia
Published: October 2018

We discuss the influence of different statistical models in the prediction of porosity and litho-fluid facies from logged and inverted acoustic impedance (Ip) values. We compare the inversion and classification results that were obtained under three different statistical a-priori assumptions: an analytical Gaussian distribution, an analytical Gaussian-mixture model, and a non-parametric mixtu re distribution. The first model assumes Gaussian distributed porosity and Ip values, thus neglecting their facies-dependent behaviour related to different lithologic and saturation conditions. Differently, the other two statistical models relate each component of the mixture to a specific litho-fluid facies, so that the facies-dependency of porosity and Ip values is taken into account. Blind well tests are used to validate the final predictions, whereas the analysis of the maximum-a-posteriori (MAP) solutions, the coverage ratio, and the contingency analysis tools are used to quantitatively compare the inversion outcomes. This work points out that the correct choice of the statistical petrophysical model could be crucial in reservoir characterization studies. Indeed, for the investigated zone, it turns out that the simple Gaussian model constitutes an oversimplified assumption, while the two mixture models provide more accurate estimates, although the non-parametric one yields slightly superior predictions with respect to the Gaussian-mixture assumption.
Tectono-Thermal Evolution and Morphodynamics of the Central Dronning Maud Land Mountains, East Antarctica, Based on New Thermochronological Data
Authors: Sirevaag Hallgeir , Ksienzyk Anna K. , Jacobs Joachim , Dunkl István , Läufer Andreas
Published: October 2018

The lack of preserved Mesozoic–Cenozoic sediments and structures in central Dronning Maud Land has so far limited our understanding of the post-Pan-African evolution of this important part of East Antarctica. In order to investigate the thermal evolution of the basement rocks and place constraints on landscape evolution, we present new low-temperature thermochronological data from 34 samples. Apatite fission track ages range from 280–85 Ma, while single-grain (U-Th)/He ages from apatite and zircon range from 305–15 and 420–340 Ma, respectively. Our preferred thermal history models suggest late Paleozoic–early Mesozoic peneplanation and subsequent burial by 3–6 km of Beacon sediments. The samples experienced no additional burial in the Jurassic, thus the once voluminous continental flood basalts of western Dronning Maud Land did not reach central Dronning Maud Land. Mesozoic–early Cenozoic cooling of the samples was slow. Contrary to western Dronning Maud Land, central Dronning Maud Land lacks a mid-Cretaceous cooling phase. We therefore suggest that the mid-Cretaceous cooling of western Dronning Maud Land should be attributed to the proximity to the collapse of the orogenic plateau at the Panthalassic margin of Gondwana. Cooling rates accelerated considerably with the onset of glaciation at 34 Ma, due to climate deterioration and glacial denudation of up to 2 km.
Short Communication: Health Interventions in Volcanic Eruptions—Community Wearability Assessment of Respiratory Protection against Volcanic Ash from Mt Sinabung, Indonesia
Authors: Galea Karen S. , Covey Judith , Mutia Timur Sari , Horwell Claire J. , Nugroho Fentiny , Mueller William
Published: October 2018

Inhalation of ash can be of great concern for affected communities, during and after volcanic eruptions. Governmental and humanitarian agencies recommend and distribute a variety of respiratory protection (RP), commonly surgical masks but, also, industry-certified N95-style masks. However, there is currently no evidence on how wearable they are within affected populations or how protective wearers perceive them being against volcanic ash (which will influence the likelihood of uptake of recommended interventions). Volunteers living near Mt. Sinabung, Sumatra, Indonesia, participated in a field wearability study, which included a high-efficiency mask certified to industry standards (N95-equiv.); a standard, pleated surgical mask (Surgical); a Basic flat-fold mask (Flat-fold), and the surgical mask plus a scarf tied over the top (Surgical Plus) to improve fit. These types of RP had all performed well during earlier laboratory filtration efficiency tests. The N95-equiv. mask had performed significantly better than the other RP in the subsequent total inward leakage volunteer trials, whilst the Flat-fold and Surgical masks performed poorly, letting in a third of PM2.5 particles (data published elsewhere). Thirty volunteers wore each mask for a 15-min walk before being asked to rate the comfort, breathability and perceived protection and fit of each. After wearing all of the masks, volunteers compared and identified their preferred type of protection. The feedback received from the volunteers suggested that the Surgical Plus and N95-equiv. masks were rated as being significantly hotter and more humid than other masks. The Flat-fold was rated to have better breathability than the other masks. The N95-equiv. mask was ranked as providing the best level of effectiveness of the four masks tested. Ultimately, when asked which type of mask they would choose to wear during ashfall, 33% selected the Flat-fold mask due to its comfort and simplicity, with the Surgical Plus being the least likely to be chosen of the four tested. The study findings are of benefit to agencies who need to make informed decisions on the procurement and distribution of RP for use by those affected in future eruptions and the provision of advice to communities on their usage.
Adolescents’ Aided Recall of Targeted and Non-Targeted Tobacco Communication Campaigns in the United States
Authors: Kowitt Sarah D. , Lazard Allison J. , Queen Tara L. , Noar Seth M. , Goldstein Adam O.
Published: October 2018

We examined whether advertisements from two national tobacco control campaigns targeting adolescents (i.e., The Real Cost, Fresh Empire) and one campaign targeting adults (i.e., Tips from Former Smokers) were reaching adolescents. Data came from a national sample of adolescents aged 13 to 17 years (n = 975) surveyed by phone from August 2016 to May 2017. We assessed recall and attitudes toward five specific advertisements and three campaign slogans and examined differences by sub-groups. Almost all (95%) adolescents recalled seeing at least one campaign advertisement. Aided recall of The Real Cost and Tips from Former Smokers slogans was high (65.5% and 71.6%, respectively), while aided recall of Fresh Empire slogan was lower (15.3%) (χ2 p-value: p < 0.001); however, Black adolescents had higher odds of recalling the Fresh Empire ad (aOR: 2.28, 95% CI: 1.39, 3.73) and slogan (aOR: 2.64, 95% CI: 1.06, 6.54) compared to White adolescents. Increased exposure to the advertisements (i.e., recalling more advertisements) was significantly associated with higher odds of reporting negative feelings toward tobacco products in 4/5 models (aORs from 1.34 to 1.61). Large-scale national campaigns can have wide reach among both targeted and non-targeted audiences with added benefits for cumulative cross-campaign exposure to advertisements.
Evaluation of Caffeine Consumption among Pregnant Women from Southern Poland
Authors: Błaszczyk-Bębenek Ewa , Piórecka Beata , Kopytko Monika , Chadzińska Zuzanna , Jagielski Paweł , Schlegel-Zawadzka Małgorzata
Published: October 2018

Caffeine is the most widely consumed stimulant worldwide, including by pregnant women. Products containing caffeine should be limited in accordance with the recommendations for pregnancy. The purpose of this study was to evaluate consumption of caffeinated products and daily caffeine intake from food by pregnant women. The study was conducted on a group of healthy pregnant women: attendees of antenatal classes (n = 70) and patients of an outpatient gynecological clinic (n = 70) from Krakow (Southern Poland). A questionnaire about the frequency of consumption of selected foods and drinks containing caffeine was used. The average caffeine content in food products obtained from other Polish studies was used to estimate average daily caffeine intake in our study group. Mean daily caffeine intake was 49.60 ± 59.15 mg/day and the maximum was 498.0 mg/day. The main sources of caffeine were as follows: black tea (bags, leaf), instant coffee and ground coffee. No statistically significant differences in caffeine intake between the groups were found. A weak negative correlation (rs) = −0.28 (p = 0.0208) between month of pregnancy and caffeine intake was observed among attendees of antenatal classes. Mean daily caffeine intake did not exceed the maximum recommended dose in our study group.
Evaluation of User Performance in Interactive and Static 3D Maps
Authors: Herman Lukáš , Juřík Vojtěch , Stachoň Zdeněk , Vrbík Daniel , Russnák Jan , Řezník Tomáš
Published: October 2018

Interactive 3D visualizations of geospatial data are currently available and popular through various applications such as Google EarthTM and others. Several studies have focused on user performance with 3D maps, but static 3D maps were mostly used as stimuli. The main objective of this paper was to identify differences between interactive and static 3D maps. We also explored the role of different tasks and inter-individual differences of map users. In the experimental study, we analyzed effectiveness, efficiency, and subjective preferences, when working with static and interactive 3D maps. The study included 76 participants and used a within-subjects design. Experimental testing was performed using our own testing tool 3DmoveR 2.0, which was based on a user logging method and open web technologies. We demonstrated statistically significant differences between interactive and static 3D maps in effectiveness, efficiency, and subjective preferences. Interactivity influenced the results mainly in ‘spatial understanding’ and ‘combined’ tasks. From the identified differences, we concluded that the results of the user studies with static 3D maps as stimuli could not be transferred to interactive 3D visualizations or virtual reality.
Genome-wide Identification, Classification, Molecular Evolution and Expression Analysis of Malate Dehydrogenases in Apple
Authors: Ma Baiquan , Yuan Yangyang , Gao Meng , Xing Libo , Li Cuiying , Li Mingjun , Ma Fengwang
Published: October 2018

Malate dehydrogenase plays crucial roles in energy homeostasis, plant development and cold and salt tolerance, as it mediates the reversible conversion of malate to oxaloacetate. However, the evolutionary pattern of MDH genes in apple remains elusive. In this study, a total of 20 MDH genes were identified from the “Golden Delicious” apple draft genome. We revealed the physiological and biochemical properties, gene structure, and conserved motifs of MdMDH genes. Chromosomal localization and Ka/Ks ratio analysis of MdMDH genes revealed different selective pressures acted on duplicated MdMDH genes. Exploration of the phylogenetic relationships revealed six clades and similar frequencies between old and recent duplications, and significant differences in the evolutionary rates of the MDH gene family were observed. One MdMDH gene, MDP0000807458, which was highly expressed during apple fruit development and flower bud differentiation, was under positive selection. Thus, we speculated that MDP0000807458 is a likely candidate gene involved in regulation of flower bud differentiation and organic acid metabolism in apple fruits. This study provides a foundation for improved understanding of the molecular evolution of MdMDH genes and further facilitates the functional analysis of MDP0000807458 to unravel its exact role in flower bud differentiation and organic acid metabolism.
Inwardly Rectifying Potassium Channel Kir4.1 as a Novel Modulator of BDNF Expression in Astrocytes
Authors: Ohno Yukihiro , Kinboshi Masato , Shimizu Saki
Published: October 2018

Brain-derived neurotrophic factor (BDNF) is a key molecule essential for neural plasticity and development, and is implicated in the pathophysiology of various central nervous system (CNS) disorders. It is now documented that BDNF is synthesized not only in neurons, but also in astrocytes which actively regulate neuronal activities by forming tripartite synapses. Inwardly rectifying potassium (Kir) channel subunit Kir4.1, which is specifically expressed in astrocytes, constructs Kir4.1 and Kir4.1/5.1 channels, and mediates the spatial potassium (K+) buffering action of astrocytes. Recent evidence illustrates that Kir4.1 channels play important roles in bringing about the actions of antidepressant drugs and modulating BDNF expression in astrocytes. Although the precise mechanisms remain to be clarified, it seems likely that inhibition (down-regulation or blockade) of astrocytic Kir4.1 channels attenuates K+ buffering, increases neuronal excitability by elevating extracellular K+ and glutamate, and facilitates BDNF expression. Conversely, activation (up-regulation or opening) of Kir4.1 channels reduces neuronal excitability by lowering extracellular K+ and glutamate, and attenuates BDNF expression. Particularly, the former pathophysiological alterations seem to be important in epileptogenesis and pain sensitization, and the latter in the pathogenesis of depressive disorders. In this article, we review the functions of Kir4.1 channels, with a focus on their regulation of spatial K+ buffering and BDNF expression in astrocytes, and discuss the role of the astrocytic Kir4.1-BDNF system in modulating CNS disorders.
The 2β Splice Variation Alters the Structure and Function of the Stromal Interaction Molecule Coiled-Coil Domains
Authors: Chung Steve , Zhang MengQi , Stathopulos Peter B.
Published: October 2018

Stromal interaction molecule (STIM)-1 and -2 regulate agonist-induced and basal cytosolic calcium (Ca2+) levels after oligomerization and translocation to endoplasmic reticulum (ER)-plasma membrane (PM) junctions. At these junctions, the STIM cytosolic coiled-coil (CC) domains couple to PM Orai1 proteins and gate these Ca2+ release-activated Ca2+ (CRAC) channels, which facilitate store-operated Ca2+ entry (SOCE). Unlike STIM1 and STIM2, which are SOCE activators, the STIM2β splice variant contains an 8-residue insert located within the conserved CCs which inhibits SOCE. It remains unclear if the 2β insert further depotentiates weak STIM2 coupling to Orai1 or independently causes structural perturbations which prevent SOCE. Here, we use far-UV circular dichroism, light scattering, exposed hydrophobicity analysis, solution small angle X-ray scattering, and a chimeric STIM1/STIM2β functional assessment to provide insights into the molecular mechanism by which the 2β insert precludes SOCE activation. We find that the 2β insert reduces the overall α-helicity and enhances the exposed hydrophobicity of the STIM2 CC domains in the absence of a global conformational change. Remarkably, incorporation of the 2β insert into the STIM1 context not only affects the secondary structure and hydrophobicity as observed for STIM2, but also eliminates the more robust SOCE response mediated by STIM1. Collectively, our data show that the 2β insert directly precludes Orai1 channel activation by inducing structural perturbations in the STIM CC region.
Quercitrin Nanocoated Implant Surfaces Reduce Osteoclast Activity In Vitro and In Vivo
Authors: Córdoba Alba , Manzanaro-Moreno Nahuel , Colom Carme , Rønold Hans J. , Lyngstadaas Staale P. , Monjo Marta , Ramis Joana M.
Published: October 2018

In this study, the effect on osteoclast activity in vitro and in vivo of titanium implants that were coated with quercitrin was evaluated. Titanium surfaces were covalently coated with the flavonoid quercitrin. The effect of the surfaces on osteoclastogenesis was first tested in vitro on RAW264.7 cells that were supplemented with receptor activator of nuclear factor kappa-B ligand (RANKL) to generate osteoclast-like cells by tartrate-resistant acid phosphatase (TRAP) inmunostaining after five days of culture, and by analysis of the mRNA expression levels of markers related to bone resorption after seven days of culture. A rabbit tibial model was used to evaluate the in vivo biological response to the implant surfaces after eight weeks of healing, analyzing the lactate dehydrogenase (LDH) and the alkaline phosphatase (ALP) activities in the wound fluid that were present at the implant interface and the peri-implant bone mRNA expression levels of several markers related to inflammation, bone resorption and osteoblast-osteoclast interaction. No differences between groups and control surfaces were found in the wound fluid analyses. Moreover, quercitrin implant surfaces significantly decreased the expression of osteoclast related genes in vitro (Trap, CalcR, Ctsk, H+ATPase, Mmp9) and in vivo (Ctsk, H+ATPase, Mmp9) as well as the expression of RankL in vivo. Moreover, quercitrin surfaces were not cytotoxic for the cells. Thus, quercitrin implant surfaces were biocompatible and decreased osteoclastogenesis in vitro and in vivo. This could be used to improve the performance of dental implants.
Antagonism of Transient Receptor Potential Ankyrin Type-1 Channels as a Potential Target for the Treatment of Trigeminal Neuropathic Pain: Study in an Animal Model
Authors: Demartini Chiara , Greco Rosaria , Zanaboni Anna Maria , Francesconi Oscar , Nativi Cristina , Tassorelli Cristina , Deseure Kristof
Published: October 2018

Transient receptor potential ankyrin type-1 (TRPA1) channels are known to actively participate in different pain conditions, including trigeminal neuropathic pain, whose clinical treatment is still unsatisfactory. The aim of this study was to evaluate the involvement of TRPA1 channels by means of the antagonist ADM_12 in trigeminal neuropathic pain, in order to identify possible therapeutic targets. A single treatment of ADM_12 in rats 4 weeks after the chronic constriction injury of the infraorbital nerve (IoN-CCI) significantly reduced the mechanical allodynia induced in the IoN-CCI rats. Additionally, ADM_12 was able to abolish the increased levels of TRPA1, calcitonin gene-related peptide (CGRP), substance P (SP), and cytokines gene expression in trigeminal ganglia, cervical spinal cord, and medulla induced in the IoN-CCI rats. By contrast, no significant differences between groups were seen as regards CGRP and SP protein expression in the pars caudalis of the spinal nucleus of the trigeminal nerve. ADM_12 also reduced TRP vanilloid type-1 (TRPV1) gene expression in the same areas after IoN-CCI. Our findings show the involvement of both TRPA1 and TRPV1 channels in trigeminal neuropathic pain, and in particular, in trigeminal mechanical allodynia. Furthermore, they provide grounds for the use of ADM_12 in the treatment of trigeminal neuropathic pain.
In Vitro Screening of Molecularly Engineered Polyethylene Glycol Hydrogels for Cartilage Tissue Engineering using Periosteum-Derived and ATDC5 Cells
Authors: Kudva Abhijith K. , Luyten Frank P. , Patterson Jennifer
Published: October 2018

The rapidly growing field of tissue engineering and regenerative medicine has brought about an increase in demand for biomaterials that mimic closely the form and function of biological tissues. Therefore, understanding the cellular response to the changes in material composition moves research one step closer to a successful tissue-engineered product. With this in mind, polyethylene glycol (PEG) hydrogels comprised of different concentrations of polymer (2.5%, 4%, 6.5%, or 8% (w/v)); different protease sensitive, peptide cross-linkers (VPMSMRGG or GPQGIWGQ); and the incorporation or lack of a peptide cell adhesion ligand (RGD) were screened for their ability to support in vitro chondrogenesis. Human periosteum-derived cells (hPDCs), a mesenchymal stem cell (MSC)-like primary cell source, and ATDC5 cells, a murine carcinoma-derived chondrogenic cell line, were encapsulated within the various hydrogels to assess the effects of the different formulations on cellular viability, proliferation, and chondrogenic differentiation while receiving exogenous growth factor stimulation via the medium. Through the results of this screening process, the 6.5% (w/v) PEG constructs, cross-linked with the GPQGIWGQ peptide and containing the RGD cell binding molecule, demonstrated an environment that consistently supported cellular viability and proliferation as well as chondrogenic differentiation.
Exogenous Cripto-1 Suppresses Self-Renewal of Cancer Stem Cell Model
Authors: Alam Md Jahangir , Takahashi Ryota , Afify Said M. , Oo Aung Ko Ko , Kumon Kazuki , Nawara Hend M. , Khayrani Aprilliana Cahya , Du Juan , Zahra Maram H. , Seno Akimasa , Salomon David S. , Seno Masaharu
Published: October 2018

Cripto-1 is a glycophosphatidylinositol (GPI) anchored signaling protein of epidermal growth factor (EGF)-Cripto-1-FRL1-Cryptic (CFC) family and plays a significant role in the early developmental stages and in the different types of cancer cells, epithelial to mesenchymal transition and tumor angiogenesis. Previously, we have developed cancer stem cells (miPS-LLCcm) from mouse iPSCs by culturing them in the presence of conditioned medium of Lewis Lung Carcinoma (LLC) cells for four weeks. Nodal and Cripto-1 were confirmed to be expressed in miPS-LLCcm cells by quantitative reverse transcription PCR (rt-qPCR) implying that Cr-1 was required in maintaining stemness. To investigate the biological effect of adding exogenous soluble CR-1 to the cancer stem cells, we have prepared a C-terminally truncated soluble form of recombinant human CR-1 protein (rhsfCR-1), in which the GPI anchored moiety was removed by substitution of a stop codon through site-directed mutagenesis. rhsfCR-1 effectively suppressed the proliferation and sphere forming ability of miPS-LLCcm cells in a dose-dependent manner in the range of 0 to 5 µg/mL, due to the suppression of Nodal-Cripto-1/ALK4/Smad2 signaling pathway. Frequency of sphere-forming cells was dropped from 1/40 to 1/69 by rhsfCR-1 at 1 µg/mL. Moreover, rhsfCR-1 in the range of 0 to 1 µg/mL also limited the differentiation of miPS-LLCcm cells into vascular endothelial cells probably due to the suppression of self-renewal, which should reduce the number of cells with stemness property. As demonstrated by a soluble form of exogenous Cripto-1 in this study, the efficient blockade would be an attractive way to study Cripto-1 dependent cancer stem cell properties for therapeutic application.
Assessment of Human Skin Gene Expression by Different Blends of Plant Extracts with Implications to Periorbital Skin Aging
Authors: Namkoong Jin , Kern Dale , Knaggs Helen E.
Published: October 2018

Since the skin is the major protective barrier of the body, it is affected by intrinsic and extrinsic factors. Environmental influences such as ultraviolet (UV) irradiation, pollution or dry/cold air are involved in the generation of radical oxygen species (ROS) and impact skin aging and dermal health. Assessment of human skin gene expression and other biomarkers including epigenetic factors are used to evaluate the biological/molecular activities of key compounds in cosmetic formulas. The objective of this study was to quantify human gene expression when epidermal full-thickness skin equivalents were exposed to: (a) a mixture of betaine, pentylene glycol, Saccharomyces cerevisiae and Rhodiola rosea root extract (BlendE) for antioxidant, skin barrier function and oxidative stress (with hydrogen peroxide challenge); and (b) a mixture of Narcissus tazetta bulb extract and Schisandra chinensis fruit extract (BlendIP) for various biomarkers and microRNA analysis. For BlendE, several antioxidants, protective oxidative stress biomarkers and many skin barrier function parameters were significantly increased. When BlendE was evaluated, the negative impact of the hydrogen peroxide was significantly reduced for the matrix metalloproteinases (MMP 3 and MMP 12), the skin aging and oxidative stress biomarkers, namely FBN2, ANXA1 and HGF. When BlendIP was tested for cell proliferation and dermal structural components to enhance the integrity of the skin around the eyes: 8 growth factors, 7 signaling, 7 structural/barrier function and 7 oxidative stress biomarkers were significantly increased. Finally, when BlendIP was tested via real-time RT-PCR for microRNA expression: miR-146a, miR-22, miR155, miR16 and miR21 were all significantly increased over control levels. Therefore, human skin gene expression studies are important tools to assess active ingredient compounds such as plant extract blends to advance dermal hypotheses toward validating cosmetic formulations with botanical molecules.
Proteolipid Protein 2 Overexpression Indicates Aggressive Tumor Behavior and Adverse Prognosis in Human Gliomas
Authors: Chen Yi-Hsuan , Hueng Dueng-Yuan , Tsai Wen-Chiuan
Published: October 2018

Proteolipid protein 2 (PLP2), a membrane protein of the endoplasmic reticulum, is related to tumor proliferation and metastasis in some human cancers, but not in gliomas. First, we performed western-blot analysis, real-time quantitative PCR and immunohistochemical stains to detect PLP2 expression in 4 glioma cell lines and human glioma tissues. In addition, we used small interfering RNA (SiPLP2) and short hairpin RNA (shPLP2) to knockdown PLP2 expression in GBM8401 and LN229 glioma cell lines. After then, the alteration of PLP2 suppressed glioma cells behavior were examined by cell proliferation, wound healing, cell invasion, and colonies formation assays. Finally, the possible mechanism of PLP2 was analyzed by detecting the expression of the proteins related to cell-cycle checkpoints, cell-proliferative signaling factors, and cell-matrix interaction. Compared with normal brain cell lysates and mRNA, all glioma cell lines displayed PLP2 protein and mRNA overexpression. Besides, higher PLP2 IHC staining significantly correlated with more advanced tumor grades and poorer prognosis in human gliomas. Both siPLP2 transfected gliomas showed a clear inhibition of glioma cell proliferation, migration, and invasion as well as down-regulating p-p38, p-ERK, MMP-2, and MMP-9 expression. In conclusion, we successfully demonstrated that PLP2 overexpression played an oncogenic role in glioma development and aggressive tumor behavior.
Using a Consensus Docking Approach to Predict Adverse Drug Reactions in Combination Drug Therapies for Gulf War Illness
Authors: Jaundoo Rajeev , Bohmann Jonathan , Gutierrez Gloria E. , Klimas Nancy , Broderick Gordon , Craddock Travis J. A.
Published: October 2018

Gulf War Illness (GWI) is a chronic multisymptom illness characterized by fatigue, musculoskeletal pain, and gastrointestinal and cognitive dysfunction believed to stem from chemical exposures during the 1990–1991 Persian Gulf War. There are currently no treatments; however, previous studies have predicted a putative multi-intervention treatment composed of inhibiting Th1 immune cytokines followed by inhibition of the glucocorticoid receptor (GCR) to treat GWI. These predictions suggest the use of specific monoclonal antibodies or suramin to target interleukin-2 and tumor necrosis factor α , followed by mifepristone to inhibit the GCR. In addition to this putative treatment strategy, there exist a variety of medications that target GWI symptomatology. As pharmaceuticals are promiscuous molecules, binding to multiple sites beyond their intended targets, leading to off-target interactions, it is key to ensure that none of these medications interfere with the proposed treatment avenue. Here, we used the drug docking programs AutoDock 4.2, AutoDock Vina, and Schrödinger’s Glide to assess the potential off-target immune and hormone interactions of 43 FDA-approved drugs commonly used to treat GWI symptoms in order to determine their putative polypharmacology and minimize adverse drug effects in a combined pharmaceutical treatment. Several of these FDA-approved drugs were predicted to be novel binders of immune and hormonal targets, suggesting caution for their use in the proposed GWI treatment strategy symptoms.
Circulating Cell-Free DNA and Colorectal Cancer: A Systematic Review
Authors: Vymetalkova Veronika , Cervena Klara , Bartu Linda , Vodicka Pavel
Published: October 2018

There is a strong demand for the identification of new biomarkers in colorectal cancer (CRC) diagnosis. Among all liquid biopsy analysts, cell-free circulating DNA (cfDNA) is probably the most promising tool with respect to the identification of minimal residual diseases, assessment of treatment response and prognosis, and identification of resistance mechanisms. Circulating cell-free tumor DNA (ctDNA) maintains the same genomic signatures that are present in the matching tumor tissue allowing for the quantitative and qualitative evaluation of mutation burdens in body fluids. Thus, ctDNA-based research represents a non-invasive method for cancer detection. Among the numerous possible applications, the diagnostic, predictive, and/or prognostic utility of ctDNA in CRC has attracted intense research during the last few years. In the present review, we will describe the different aspects related to cfDNA research and evidence from studies supporting its potential use in CRC diagnoses and the improvement of therapy efficacy. We believe that ctDNA-based research should be considered as key towards the introduction of personalized medicine and patient benefits.
Motivation Perspectives on Opening up Municipality Data: Does Municipality Size Matter?
Authors: Zuiderwijk Anneke , Volten Cécile , Kroesen Maarten , Gill Mark
Published: October 2018

National governments often expect municipalities to develop toward open cities and be equally motivated to open up municipal data, yet municipalities have different characteristics influencing their motivations. This paper aims to reveal how municipality size influences municipalities’ motivation perspectives on opening up municipality data. To this end, Q-methodology is used, which is a method that is suited to objectify people’s frames of mind on a particular topic. By applying this method to 37 municipalities in the Netherlands, we elicited the motivation perspectives of three main groups of municipalities: (1) advocating municipalities, (2) careful municipalities, and (3) conservative municipalities. We found that advocating municipalities are mainly large-sized municipalities (>65,000 inhabitants) and a few small-sized municipalities (<35,000 inhabitants). Careful municipalities concern municipalities of all sizes (small, medium, and large). The conservative municipality perspective is more common among smaller-sized municipalities. Our findings do not support the statement “the smaller the municipality, the less motivated it is to open up its data”. However, the type and amount of municipality resources do influence motivations to share data or not. We provide recommendations for how open data policy makers on the national level need to support the three groups of municipalities and municipalities of different sizes in different ways to stimulate the provision of municipal data to the public as much as possible. Moreover, if national governments can identify which municipalities adhere to which motivation perspective, they can then develop more targeted open data policies that meet the requirements of the municipalities that adhere to each perspective. This should result in more open data value creation.
Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE-MTDPS1)
Authors: Filosto Massimiliano , Cotti Piccinelli Stefano , Caria Filomena , Gallo Cassarino Serena , Baldelli Enrico , Galvagni Anna , Volonghi Irene , Scarpelli Mauro , Padovani Alessandro
Published: October 2018

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE-MTDPS1) is a devastating autosomal recessive disorder due to mutations in TYMP, which cause a loss of function of thymidine phosphorylase (TP), nucleoside accumulation in plasma and tissues, and mitochondrial dysfunction. The clinical picture includes progressive gastrointestinal dysmotility, cachexia, ptosis and ophthalmoparesis, peripheral neuropathy, and diffuse leukoencephalopathy, which usually lead to death in early adulthood. Other two MNGIE-type phenotypes have been described so far, which are linked to mutations in POLG and RRM2B genes. Therapeutic options are currently available in clinical practice (allogeneic hematopoietic stem cell transplantation and carrier erythrocyte entrapped thymidine phosphorylase therapy) and newer, promising therapies are expected in the near future. Since successful treatment is strictly related to early diagnosis, it is essential that clinicians be warned about the clinical features and diagnostic procedures useful to suspect diagnosis of MNGIE-MTDPS1. The aim of this review is to promote the knowledge of the disease as well as the involved mechanisms and the diagnostic processes in order to reach an early diagnosis.
Which Cognitive Abilities Make the Difference? Predicting Academic Achievements in Advanced STEM Studies
Authors: Berkowitz Michal , Stern Elsbeth
Published: October 2018

Previous research has shown that psychometrically assessed cognitive abilities are predictive of achievements in science, technology, engineering and mathematics (STEM) even in highly selected samples. Spatial ability, in particular, has been found to be crucial for success in STEM, though its role relative to other abilities has been shown mostly when assessed years before entering higher STEM education. Furthermore, the role of spatial ability for mathematics in higher STEM education has been markedly understudied, although math is central across STEM domains. We investigated whether ability differences among students who entered higher STEM education were predictive of achievements during the first undergraduate year. We assessed 317 undergraduate students in Switzerland (150 from mechanical engineering and 167 from math-physics) on multiple measures of spatial, verbal and numerical abilities. In a structural equation model, we estimated the effects of latent ability factors on students’ achievements on a range of first year courses. Although ability-test scores were mostly at the upper scale range, differential effects on achievements were found: spatial ability accounted for achievements in an engineering design course beyond numerical, verbal and general reasoning abilities, but not for math and physics achievements. Math and physics achievements were best predicted by numerical, verbal and general reasoning abilities. Broadly, the results provide evidence for the predictive power of individual differences in cognitive abilities even within highly competent groups. More specifically, the results suggest that spatial ability’s role in advanced STEM learning, at least in math-intensive subjects, is less critical than numerical and verbal reasoning abilities.
Risk Assessment of Housing Market Segments: The Lender’s Perspective
Authors: Wilhelmsson Mats , Zhao Jianyu
Published: October 2018

It is well known that risk factors influence how investment portfolios perform from a lender’s perspective; therefore, a thorough risk assessment of the housing market is vital. The aim of this paper was to analyze the risks from housing apartments in different housing market segments by using the Stockholm, Sweden, owner-occupied apartment market as a case study. By applying quantitative and systems engineering methods, we (1) established the relationship between the overall housing market and several housing market segments, (2) analyzed the results from the quantitative model, and (3) finally provided a feasible portfolio regarding risk control based on the given data. The goal was to determine how different housing segment factors could reveal risk towards the overall market and offer better outlooks for risk management when it comes to housing apartments. The results indicated that the risk could be reduced at the same time as the return increased. From a lender’s perspective, this could reduce the overall risk.
Ultraviolet Irradiation on a Pyrite Surface Improves Triglycine Adsorption
Authors: Galvez-Martinez Santos , Mateo-Marti Eva
Published: October 2018

We characterized the adsorption of triglycine molecules on a pyrite surface under several simulated environmental conditions by X-ray photoemission spectroscopy. The triglycine molecular adsorption on a pyrite surface under vacuum conditions (absence of oxygen) shows the presence of two different states for the amine functional group (NH2 and NH3+), therefore two chemical species (anionic and zwitterionic). On the other hand, molecular adsorption from a solution discriminates the NH2 as a unique molecular adsorption form, however, the amount adsorbed in this case is higher than under vacuum conditions. Furthermore, molecular adsorption on the mineral surface is even favored if the pyrite surface has been irradiated before the molecular adsorption occurs. Pyrite surface chemistry is highly sensitive to the chemical changes induced by UV irradiation, as XPS analysis shows the presence of Fe2O3 and Fe2SO4—like environments on the surface. Surface chemical changes induced by UV help to increase the probability of adsorption of molecular species and their subsequent concentration on the pyrite surface.
In-Situ Synthesis and Characterization of Biodegradable Estolides via Epoxidation from Canola Biodiesel
Authors: Borugadda Venu Babu , Dalai Ajay K.
Published: October 2018

Research on the formulation of estolides from plant seed oils has attracted substantial attention due to their favorable low-temperature properties and environmentally friendly nature. The present research investigates the formulation of canola biodiesel derived estolides for low-temperature applications. The dual-step research method includes ring opening of epoxidized canola biodiesel in the presence of oleic acid, followed by esterification with oleic acid to produce estolides using a mesoporous aluminosilicates possessing Modernite Framework Inverted (MFI) type pentasil structure as a heterogeneous acidic catalyst. Prepared catalyst was characterized to measure the properties essential for the effective catalysis. The catalyst demonstrated promising activity for the estolides formation, >95% conversion was achieved at 110 °C for 6 h using 15 wt % of catalyst loading. 1H NMR technique and oxirane oxygen titrimetric analysis were employed to determine product purity. Physicochemical properties of the reaction products were determined by standard methods and characterization results revealed that the formulated estolides had improved low-temperature, lubricity and rheological properties, and thermo-oxidative stability. Also, biodegradability of the estolides was found to be 92% within 28 days as per the bio-kinetic model. Wear scar diameter of 106 µm was noticed for 10% of alkoxide blend with standard diesel fuel. Overall, outcomes of the physicochemical characterization data indicated that the prepared estolides can act as possible alternative bio-lubricant basestock for various low-temperature applications.
Electromagnetic Analysis, Characterization and Discussion of Inductive Transmission Parameters for Titanium Based Housing Materials in Active Medical Implantable Devices
Authors: Gruenwald Waldemar , Bhattacharrya Mayukh , Jansen Dirk , Reindl Leonhard
Published: October 2018

The growing demand for active medical implantable devices requires data and or power links between the implant and the outside world. Every implant has to be encapsulated from the body by a specific housing and one of the most common materials used is titanium or titanium alloy. Titanium thas the necessary properties in terms of mechanical and chemical stability and biocompatibility. However, its electrical conductivity presents a challenge for the electromagnetic transmission of data and power. The proposed paper presents a fast and practical method to determine the necessary transmission parameters for titanium encapsulated implants. Therefore, the basic transformer-transmission-model is used with measured or calculated key values for the inductances. Those are then expanded with correction factors to determine the behavior with the encapsulation. The correction factors are extracted from finite element method simulations. These also enable the analysis of the magnetic field distribution inside of the housing. The simulated transmission properties are very close to the measured values. Additionally, based on lumped elements and magnetic field distribution, the influential parameters are discussed in the paper. The parameter discussion describes how to enhance the transmitted power, data-rate or distance, or to reduce the size of the necessary coils. Finally, an example application demonstrates the usage of the methods.