bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabotropic Glutamate Receptor Subtype 5 in Alcohol-Induced Negative Affect
Authors: Kasten Chelsea R. , Holmgren Eleanor B. , Wills Tiffany A.
Published: July 2019

Allosteric modulators of metabotropic glutamate 5 receptors (mGlu5 receptors) have been identified as a promising treatment to independently alleviate both negative affective states and ethanol-seeking and intake. However, these conditions are often comorbid and might precipitate one another. Acute and protracted ethanol withdrawal can lead to negative affective states. In turn, these states are primary drivers of alcohol relapse, particularly among women. The current review synthesizes preclinical studies that have observed the role of mGlu5 receptor modulation in negative affective states following ethanol exposure. The primary behavioral assays discussed are ethanol-seeking and intake, development and extinction of ethanol-associated cues and contexts, behavioral despair, and anxiety-like activity. The work done to-date supports mGlu5 receptor modulation as a promising target for mediating negative affective states to reduce ethanol intake or prevent relapse. Limitations in interpreting these data include the lack of models that use alcohol-dependent animals, limited use of adolescent and female subjects, and a lack of comprehensive evaluations of negative affective-like behavior.
New Insight into Therapies Targeting Angiogenesis in Hepatocellular Carcinoma
Authors: Mossenta Monica , Busato Davide , Baboci Lorena , Di Cintio Federica , Toffoli Giuseppe , Dal Bo Michele
Published: July 2019

Hepatocellular carcinoma (HCC) is a malignancy characterized by neoangiogenesis that is determined by an augmented production of proangiogenesis factors by tumor and adjacent cells. This unbalanced angiogenesis process is a key feature of HCC carcinogenesis and progression. Proangiogenic factors also have a relevant role in the generation and maintenance of an immunosuppressive tumor microenvironment. Several therapeutic options for HCC treatment are based on the inhibition of angiogenesis, both in the early/intermediate stages of the disease and in the late stages of the disease. Conventional treatment options employing antiangiogenic approaches provide for the starving of tumors of their blood supply to avoid the refueling of oxygen and nutrients. An emerging alternative point of view is the normalization of vasculature leading to enhance tumor perfusion and oxygenation, potentially capable, when proposed in combination with other treatments, to improve delivery and efficacy of other therapies, including immunotherapy with checkpoint inhibitors. The introduction of novel biomarkers can be useful for the definition of the most appropriate dose and scheduling for these combination treatment approaches. The present review provides a wide description of the pharmaceutical compounds with an antiangiogenic effect proposed for HCC treatment and investigated in clinical trials, including antibodies and small-molecule kinase inhibitors.
Assessment of Ag Nanoparticles Interaction over Low-Cost Mesoporous Silica in Deep Desulfurization of Diesel
Authors: V. Sales Rafael , Moura Heloise O. M. A. , Câmara Anne B. F. , Rodríguez-Castellón Enrique , Silva José A. B. , Pergher Sibele B. C. , Campos Leila M. A. , Urbina Maritza M. , Bicudo Tatiana C. , de Carvalho Luciene S.
Published: July 2019

Chemical interactions between metal particles (Ag or Ni) dispersed in a low-cost MCM-41M produced from beach sand amorphous silica and sulfur compounds were evaluated in the deep adsorptive desulfurization process of real diesel fuel. N2 adsorption-desorption isotherms, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), high-resolution transmission electron microscopy (HRTEM) and scanning transmission electron microscopy coupled to energy-dispersive X-ray spectroscopy (STEM-EDX) were used for characterizing the adsorbents. HRTEM and XPS confirmed the high dispersion of Ag nanoparticles on the MCM-41 surface, and its chemical interaction with support and sulfur compounds by diverse mechanisms such as π-complexation and oxidation. Thermodynamic tests indicated that the adsorption of sulfur compounds over Ag(I)/MCM-41M is an endothermic process under the studied conditions. The magnitude of ΔH° (42.1 kJ/mol) indicates that chemisorptive mechanisms govern the sulfur removal. The best fit of kinetic and equilibrium data to pseudo-second order (R2 > 0.99) and Langmuir models (R2 > 0.98), respectively, along with the results for intraparticle diffusion and Boyd’s film-diffusion kinetic models, suggest that the chemisorptive interaction between organosulfur compounds and Ag nanosites controls sulfur adsorption, as seen in the XPS results. Its adsorption capacity (qm = 31.25 mgS/g) was 10 times higher than that obtained for pure MCM-41M and double the qm for the Ag(I)/MCM-41C adsorbent from commercial silica. Saturated adsorbents presented a satisfactory regeneration rate after a total of five sulfur adsorption cycles.
Synthesis of Brominated Polyethylene by Copolymerization of Ethylene with ω–bromoalkene Catalyzed by a Metallocene and Methylaluminoxane System
Authors: Toda Tomoyuki , Miura Itaru , Miya Masamitsu , Takenaka Katsuhiko
Published: July 2019

The metallocene-catalyzed copolymerization of ethylene and 11–bromo–1–undecene was carried out to synthesize brominated polyethylene (PE). A modified methylaluminoxane (MMAO) solution was used as a cocatalyst and rac–Et(H4Ind)2ZrCl2 as a catalyst. The copolymerization showed a high activity and afforded the copolymer with a 11-bromo-1-undecene incorporation ranging from 1.0 to 4.3 mol%. When using a dried methylaluminoxane (dMAO) as a cocatalyst, the incorporation ratio of 11-bromo-1-undecene increased remarkably to 25.2 mol%. It was demonstrated that the type of MAO used as a cocatalyst affects the composition of the ethylene/11-bromo-1-undecene copolymer without changing the structure of the catalytic complex.
Wnt Receptor Frizzled-4 as a Marker for Isolation of Enteric Neural Progenitors in Human Children
Authors: Neckel Peter H. , Scharr Melanie , Seid Karin , Nothelfer Katharina , Fuchs Jörg , Obermayr Florian , Hirt Bernhard , Huber Stephan M. , Just Lothar
Published: July 2019

Identification and isolation of neural progenitor cells from the human enteric nervous system (ENS) is currently hampered by the lack of reliable, specific markers. Here, we define the Wnt-receptor frizzled-4 as a marker for the isolation of enteric neural progenitor cells derived from paediatric gut samples. We show that the Wnt-receptor frizzled-4 is expressed in the human colon and in Tunica muscularis-derived enterospheres. To obtain a purified culture, we carried out fluorescence-activated cell sorting (FACS) using PE-conjugated frizzled-4 antibodies. Frizzled-4positive cells gave rise to neurosphere-like bodies and ultimately differentiated into neurons as revealed by BrdU-proliferation assays and immunocytochemistry, whereas in frizzled-4negative cultures we did not detect any neuronal and glial cells. By using a patch-clamp approach, we also demonstrated the expression of functional sodium and potassium channels in frizzled-4positive cell cultures after differentiation in vitro.
Cholesterol Interaction Directly Enhances Intrinsic Activity of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)
Authors: Chin Stephanie , Ramjeesingh Mohabir , Hung Maurita , Ereño-Oreba June , Cui Hong , Laselva Onofrio , Julien Jean-Philippe , Bear Christine E.
Published: July 2019

The recent cryo-electron microscopy structures of zebrafish and the human cystic fibrosis transmembrane conductance regulator (CFTR) provided unprecedented insights into putative mechanisms underlying gating of its anion channel activity. Interestingly, despite predictions based on channel activity measurements in biological membranes, the structure of the detergent purified, phosphorylated, and ATP-bound human CFTR protein did not reveal a stably open conduction pathway. This study tested the hypothesis that the functional properties of the detergent solubilized CFTR protein used for structural determinations are different from those exhibited by CFTR purified under conditions that retain associated lipids native to the membrane. It was found that CFTR purified together with phospholipids and cholesterol using amphipol: A8-35, exhibited higher rates of catalytic activity, phosphorylation dependent channel activation and potentiation by the therapeutic compound, ivacaftor, than did CFTR purified in detergent. The catalytic activity of phosphorylated CFTR detergent micelles was rescued by the addition of phospholipids plus cholesterol, but not by phospholipids alone, arguing for a specific role for cholesterol in modulating this function. In summary, these studies highlight the importance of lipid interactions in the intrinsic activities and pharmacological potentiation of CFTR.
Importance and Applications of Robotic and Autonomous Systems (RAS) in Railway Maintenance Sector: A Review
Authors: Vithanage Randika K. W. , Harrison Colin S. , DeSilva Anjali K. M.
Published: July 2019

Maintenance, which is critical for safe, reliable, quality, and cost-effective service, plays a dominant role in the railway industry. Therefore, this paper examines the importance and applications of Robotic and Autonomous Systems (RAS) in railway maintenance. More than 70 research publications, which are either in practice or under investigation describing RAS developments in the railway maintenance, are analysed. It has been found that the majority of RAS developed are for rolling-stock maintenance, followed by railway track maintenance. Further, it has been found that there is growing interest and demand for robotics and autonomous systems in the railway maintenance sector, which is largely due to the increased competition, rapid expansion and ever-increasing expenses.
Thick Hydride Vapor Phase Heteroepitaxy: A Novel Approach to Growth of Nonlinear Optical Materials
Authors: Tassev Vladimir L. , Vangala Shivashankar R.
Published: July 2019

At the time when many nonlinear optical (NLO) materials for frequency conversion of laser sources in the mid and long-wave infrared have achieved their fundamental or technological limits, we propose heteroepitaxy as a solution to develop novel NLO materials. Heteroepitaxy, is the most applied method to combine two different materials—by growing one material on another. In this work we show that combining two binary materials in a ternary may significantly improve the NLO properties that are of great importance for the pursued applications. Plus, due to the closer lattice match to the related substrate, a ternary is always a more favorable heteroepitaxial case than the two completely different materials. We also discuss combining different growth methods—one close-to-equilibrium (e.g., hydride vapor phase epitaxy—HVPE) with one far-from-equilibrium (e.g., metal organic chemical vapor deposition (MOCVD) or molecular beam epitaxy (MBE)) growth processes—to explore new opportunities for the growth of novel heterostructures, including ternary layers with gradual change in composition. The combination of different materials by nature—organics with inorganics—in a hybrid quasi-phase matching (QPM) structure is another topic we briefly discuss, along with some innovative techniques for the fabrication of orientation-patterned (OP) templates, including such that are based on the most universal semiconductor material—Si. Still, the focus in this work is on a series of NLO materials—GaAs, GaP, ZnSe, GaSe, ZnTe, GaN… and some of their ternaries grown with high surface and crystalline quality on non-native substrates and on non-native OP templates using hydride vapor phase epitaxy (HVPE). The grown thick device quality QPM structures were used for further development of high power, compact, broadly tunable frequency conversion laser sources for the mid and longwave infrared with various applications in defense, security, industry, medicine and science.
HIV Viral Load Estimation Using Hematocrit Corrected Dried Blood Spot Results on a BioMerieux NucliSENS® Platform
Authors: Nyagupe Charles , Shewade Hemant Deepak , Ade Serge , Timire Collins , Tweya Hannock , Vere Norah , Chipuka Sandra , Sisya Lucia , Gumbo Hlanai , Ditima Ezekiel , Zinyowera Sekesai
Published: July 2019

While reporting human immunodeficiency virus (HIV) viral load (VL) using dried blood spot (DBS) in the BioMerieux NucliSENS platform, application of the hematocrit correction factor has been suggested. In this cross-sectional study from the National Microbiology Reference Laboratory of Zimbabwe, we assessed whether hematocrit correction (individual and/or mean) in DBS results improved the correlation with plasma VL and prediction of VL non-suppression (≥1000 copies per ml in plasma). Of 517 specimens during August–December 2018, 65(12.6%) had non-suppressed plasma VL results. The hematocrit correction factor ranged from 1.3 to 2.0 with a mean of 1.6, standard deviation (SD: 1.5, 1.7). The intraclass correlation (ICC) for mean (0.859, 95% CI: 0.834, 0.880) and individual (0.809, 95% CI: 0.777, 0.837) hematocrit corrected DBS results were not significantly different. The uncorrected DBS results had a significantly lower ICC (0.640, 95% CI: 0.586, 0.688) when compared to corrected DBS results. There were no significant differences in validity, predictive values, and areas under the receiver operating characteristics curves for all three DBS results when predicting VL non-suppression. To conclude, hematocrit correction of DBS VL results improved agreement with the plasma results but did not improve prediction of VL non-suppression. The results were not significantly different for individual and mean corrected results.
Identification of Main Genetic Causes Responsible for Non-Syndromic Hearing Loss in a Peruvian Population
Authors: Figueroa-Ildefonso Erick , Bademci Guney , Rajabli Farid , Cornejo-Olivas Mario , Chacón Villanueva Ruy Diego , Badillo-Carrillo Rodolfo , Inca-Martinez Miguel , Milla Neyra Karina , Sineni Claire , Tekin Mustafa
Published: July 2019

Hearing loss (HL) is a common sensory disorder affecting over 5% of the global population. The etiology underlying HL includes congenital and acquired causes; genetic factors are the main cause in over 50% of congenital cases. Pathogenic variants in the GJB2 gene are a major cause of congenital non-syndromic hearing loss (NSHL), while their distribution is highly heterogeneous in different populations. To the best of our knowledge, there is no data regarding the genetic etiologies of HL in Peru. In this study, we screened 133 Peruvian families with NSHL living in Lima. We sequenced both exons of the GJB2 gene for all probands. Seven probands with familial NSHL that remained negative for GJB2 variants underwent whole genome sequencing (WGS). We identified biallelic pathogenic variants in GJB2 in 43 probands; seven were heterozygous for only one allele. The c.427C>T variant was the most common pathogenic variant followed by the c.35delG variant. WGS revealed three novel variants in MYO15A in two probands, one of them was predicted to affect splicing and the others produce a premature stop codon. The Peruvian population showed a complex profile for genetic variants in the GJB2 gene, this particular profile might be a consequence of the admixture history in Peru.
Untangling the Genetics of Human Longevity—A Challenging Quest
Authors: Dato Serena , Soerensen Mette , Rose Giuseppina
Published: July 2019

Human average life expectancy in developed countries has increased dramatically in the last century, a phenomenon which is potentially accompanied by a significant rise in multi-morbidity and frailty among older individuals [...]
Key Factors of Precipitation Stable Isotope Fractionation in Central-Eastern Africa and Central Mediterranean
Authors: Balagizi Charles M. , Liotta Marcello
Published: July 2019

The processes of isotope fractionation in the hydrological cycle naturally occur during vapor formation, vapor condensation, and moisture transportation. These processes are therefore dependent on local and regional surface and atmospheric physical features such as temperature, pressure, wind speed, and land morphology, and hence on the climate. Because of the strong influence of climate on the isotope fractionation, latitudinal and altitudinal effects on the δ18O and δ2H values of precipitation at a global scale are observed. In this study, we present and compare the processes governing precipitation isotope fractionation from two contrasting climatic regions: Virunga in Central-Eastern Africa and the Central Mediterranean (Stromboli and Sicily, Italy). While Virunga is a forested rainy tropical region located between Central and Eastern Africa, the Mediterranean region is characterized by a rainy mild winter and a dry hot summer. The reported δ18O and δ2H dataset are from precipitation collected on rain gauges sampled either on a monthly or an approximately bimonthly basis and published in previous papers. Both regions show clearly defined temporal and altitudinal variations of δ18O and δ2H, depending on precipitation amounts. The Central Mediterranean shows a clear contribution of local vapor forming at the sea–air interface, and Virunga shows a contribution from both local and regional vapor. The vapor of Virunga is from two competing sources: the first is the continental recycled moisture from soil/plant evaporation that dominates during the rainy season, and the second is from the East African Great Lakes evaporation that dominates during the dry season.
Are Opportunities Being Missed? Burden of HIV, STI and TB, and Unawareness of HIV among African Migrants
Authors: Dias Sónia , Gama Ana , Tavares Ana Maria , Reigado Vera , Simões Daniel , Carreiras Emília , Mora Cristina , Pinto Ferreira Andreia
Published: July 2019

Sub-Saharan African migrants (SSAMs) have been disproportionately affected by infectious disease burden. We aimed to identify correlates of HIV, past sexually transmitted infection (STI) and past Tuberculosis infection (TB), as well as examine HIV seropositivity unawareness and testing history among SSAMs. A venue-based sample of 790 SSAMs completed a cross-sectional biobehavioral survey on sexual practices, HIV testing and self-reported infectious diseases; an HIV rapid test was offered. Overall, 5.4% of participants were HIV-positive and 16.7% reported a past STI. Odds of being HIV positive or having a past STI were higher among participants with low socioeconomic status and who experienced violence from a partner. Increased odds of having a past STI were also found among long-term migrants and those who reported sexual risk behaviors. In total, 4.1% of participants had TB in the past; these were more likely male and HIV positive. Unawareness of HIV-positive status was notably high (35%). Half of the participants had never been tested for HIV before, including over a third of those who had STI or TB in the past. Efforts are needed to reduce missed opportunities for HIV/STIs prevention and uptake of HIV testing among SSAMs through more integrated care, while addressing social determinants of infectious diseases.
A Systematic Review of Physiological Measures of Mental Workload
Authors: Tao Da , Tan Haibo , Wang Hailiang , Zhang Xu , Qu Xingda , Zhang Tingru
Published: July 2019

Mental workload (MWL) can affect human performance and is considered critical in the design and evaluation of complex human-machine systems. While numerous physiological measures are used to assess MWL, there appears no consensus on their validity as effective agents of MWL. This study was conducted to provide a comprehensive understanding of the use of physiological measures of MWL and to synthesize empirical evidence on the validity of the measures to discriminate changes in MWL. A systematical literature search was conducted with four electronic databases for empirical studies measuring MWL with physiological measures. Ninety-one studies were included for analysis. We identified 78 physiological measures, which were distributed in cardiovascular, eye movement, electroencephalogram (EEG), respiration, electromyogram (EMG) and skin categories. Cardiovascular, eye movement and EEG measures were the most widely used across varied research domains, with 76%, 66%, and 71% of times reported a significant association with MWL, respectively. While most physiological measures were found to be able to discriminate changes in MWL, they were not universally valid in all task scenarios. The use of physiological measures and their validity for MWL assessment also varied across different research domains. Our study offers insights into the understanding and selection of appropriate physiological measures for MWL assessment in varied human-machine systems.
Multi-Scale Flow Field Mapping Method Based on Real-Time Feature Streamlines
Authors: Fang Yu , Ai Bo , Fang Jing , Xin Wenpeng , Zhao Xiangwei , Lv Guannan
Published: July 2019

Traditional static flow field visualization methods suffer from many problems, such as a lack of continuity expression in the vector field, uneven distribution of seed points, messy visualization, and time-consuming calculations. In response to these problems, this paper proposes a multi-scale mapping method based on real-time feature streamlines. The method uses feature streamlines to solve the problem of continuity expression in flow fields and introduces a streamline tracking algorithm which combines adaptive step length with velocity matching to render feature streamlines in a real-time and multi-scale way. In order to improve the stability and uniformity of the seed point layout, this method uses two different point placement methods which utilize a global regular grid distribution algorithm and feature area random distribution algorithm. In addition, this method uses a collision detection algorithm to detect and deal with the unreasonable covering between streamlines, which alleviates visual confusion in the resulting drawing. This method also uses HTML5 Canvas to render streamlines, which greatly improves the drawing speed. Therefore, use of this method can not only improve the uniformity of the seed point layout and the speed of drawing but also solve the problems of continuity expression in the vector field and messy visualization.
Improving the Positional Accuracy of Traditional Cadastral Index Maps with Membrane Adjustment in Slovenia
Authors: Čeh Marjan , Gielsdorf Frank , Trobec Barbara , Krivic Mateja , Lisec Anka
Published: July 2019

The main purpose of this research is to evaluate the improvement in positional accuracy (PAI) of cadastral boundary points’ coordinates through the adjustment of a large set of digital cadastral index maps of rural regions based on traditional Franciscan-origin maps of heterogeneous geometric quality. The distribution of residuals of local coordinates of reference points onto the as yet unconnected neighboring points is researched. In this article, we use the adjustment method based on neighborhood transformation with a mechanical membrane model deriving from Hooke’s Law and consider a general case study of a Slovenian traditional cadastral graphic database of various historical origins. The number of geometric errors in fieldbook information from outdated measurement technologies and inappropriate implementations of cadastral index map geometric maintenance reduces the number of complying datasets of relative geometry by 50%. Previous experiments in traditional cadastral index maps of rural regions, with triangle-based piecewise affine plane transformation (RMSE = 2.4 m), have been improved by the membrane method (RMSE = 1.0 m), based on tests at 623 control points. Positional accuracy improvement of cadastral geospatial data and the integration of geometric subsystems provided recognizable benefits for the future maintenance of a unique, integrated, centralized graphical cadastral subsystem, which is in the testing phase in Slovenia.
A Novel Adenosine Kinase from Bombyx mori: Enzymatic Activity, Structure, and Biological Function
Authors: Song Kai , Li Yu , He Huawei , Liu Lina , Zhao Ping , Xia Qingyou , Wang Yejing
Published: July 2019

Adenosine kinase (ADK) is the first enzyme in the adenosine remediation pathway that catalyzes adenosine phosphorylation into adenosine monophosphate, thus regulating adenosine homeostasis in cells. To obtain new insights into ADK from Bombyx mori (BmADK), we obtained recombinant BmADK, and analyzed its activity, structure, and function. Gel-filtration showed BmADK was a monomer with molecular weight of approximately 38 kDa. Circular dichroism spectra indicated BmADK had 36.8% α-helix and 29.9% β-strand structures, respectively. The structure of BmADK was stable in pH 5.0–11.0, and not affected under 30 °C. The melting temperature and the enthalpy and entropy changes in the thermal transition of BmADK were 46.51 ± 0.50 °C, 253.43 ± 0.20 KJ/mol, and 0.79 ± 0.01 KJ/(mol·K), respectively. Site-directed mutagenesis demonstrated G68, S201, E229, and D303 were key amino acids for BmADK structure and activity. In particular, S201A mutation significantly increased the α-helix content of BmADK and its activity. BmADK was located in the cytoplasm and highly expressed in the silk gland during the pre-pupal stage. RNA interference revealed the downregulation of BmADK decreased ATG-8, Caspase-9, Ec-R, E74A, and Br-C expression, indicating it was likely involved in 20E signaling, apoptosis, and autophagy to regulate silk gland degeneration and silkworm metamorphosis. Our study greatly expanded the knowledge on the activity, structure, and role of ADK.
Contact Lenses Delivering Nitric Oxide under Daylight for Reduction of Bacterial Contamination
Authors: Seggio Mimimorena , Nostro Antonia , Ginestra Giovanna , Quaglia Fabiana , Sortino Salvatore
Published: July 2019

Ocular infection due to microbial contamination is one of the main risks associated with the wearing of contact lens, which demands novel straightforward strategies to find reliable solutions. This contribution reports the preparation, characterization and biological evaluation of soft contact lenses (CL) releasing nitric oxide (NO), as an unconventional antibacterial agent, under daylight exposure. A tailored NO photodonor (NOPD) was embedded into commercial CL leading to doped CL with an excellent optical transparency (transmittance = 100%) at λ ≥ 450 nm. The NOPD results homogeneously distributed in the CL matrix where it fully preserves the photobehavior exhibited in solution. In particular, NO release from the CL and its diffusion in the supernatant physiological solution is observed upon visible light illumination. The presence of a blue fluorescent reporting functionality into the molecular skeleton of the NOPD, which activates concomitantly to the NO photorelease, allows the easy monitoring of the NO delivery in real-time and confirms that the doped CL work under daylight exposure. The NO photoreleasing CL are well-tolerated in both dark and light conditions by corneal cells while being able to induce good growth inhibition of Staphylococcus aureus under visible light irradiation. These results may pave the way to further engineering of the CL with NOPD as innovative ocular devices activatable by sunlight.
Endothelium-Dependent Hyperpolarization (EDH) in Diabetes: Mechanistic Insights and Therapeutic Implications
Authors: Goto Kenichi , Kitazono Takanari
Published: July 2019

Diabetes mellitus is one of the major risk factors for cardiovascular disease and is an important health issue worldwide. Long-term diabetes causes endothelial dysfunction, which in turn leads to diabetic vascular complications. Endothelium-derived nitric oxide is a major vasodilator in large-size vessels, and the hyperpolarization of vascular smooth muscle cells mediated by the endothelium plays a central role in agonist-mediated and flow-mediated vasodilation in resistance-size vessels. Although the mechanisms underlying diabetic vascular complications are multifactorial and complex, impairment of endothelium-dependent hyperpolarization (EDH) of vascular smooth muscle cells would contribute at least partly to the initiation and progression of microvascular complications of diabetes. In this review, we present the current knowledge about the pathophysiology and underlying mechanisms of impaired EDH in diabetes in animals and humans. We also discuss potential therapeutic approaches aimed at the prevention and restoration of EDH in diabetes.
Effects of Aging on Hair Color, Melanosome Morphology, and Melanin Composition in Japanese Females
Authors: Itou Takashi , Ito Shosuke , Wakamatsu Kazumasa
Published: July 2019

In a previous study, we showed that the size of melanosomes isolated from Japanese female hairs enlarges with age, and this affects the hair color. In this study, we analyzed the age-dependent changes in hair melanin in order to further explore the factors related to hair color changing by aging. A significant positive correlation with age was found in the total melanin amount (TM) and the mol% of 5,6-dihydroxyindole (DHI) units, while no correlation was found in pheomelanin mol%. TM showed significant correlations with hair color parameters and the melanosome volume, suggesting that hair color darkening by aging is caused by the increase in TM due to the enlargement of the size of melanosome. From the measurement of absorbance spectra on synthetic eumelanins with different ratios of DHI and 5,6-dihydroxyindole-2-carboxylic acid (DHICA), we found that the increase in DHI mol% also contributes to the darkening of hair color by aging. In addition, the level of pyrrole-2,3-dicarboxylic acid (PDCA), a marker of DHI melanin, showed a significant negative correlation with the aspect ratio of melanosome, suggesting a contribution of DHI melanin to the change in melanosome morphology by aging.
Endometrial Stromal Cells Circulate in the Bloodstream of Women with Endometriosis: A Pilot Study
Authors: Vallvé-Juanico Júlia , López-Gil Carlos , Ballesteros Agustín , Santamaria Xavier
Published: July 2019

Endometriosis is characterized by the presence of endometrial tissue outside the uterus. While endometriotic tissue is commonly localized in the pelvic cavity, it can also be found in distant sites, including the brain. The origin and pathophysiology of tissue migration is poorly understood; retrograde menstruation is thought to be the cause, although the presence of endometrium at distant sites is not explained by this hypothesis. To determine whether dissemination occurs via the bloodstream in women with endometriosis, we analyzed circulating blood for the presence of endometrial cells. Circulating endometrial stromal cells were identified only in women with endometriosis but not in controls, while endometrial epithelial cells were not identified in the circulation of either group. Our results support the hypothesis that endometrial stromal cells may migrate through circulation and promote the pathophysiology of endometriosis. The detection of these cells in circulation creates avenues for the development of less invasive diagnostic tools for the disease, and opens possibilities for further study of the origin of endometriosis.
Synergistic Reaction of SO2 with NO2 in Presence of H2O and NH3: A Potential Source of Sulfate Aerosol
Authors: Wang Zehua , Zhang Chenxi , Lv Guochun , Sun Xiaomin , Wang Ning , Li Zhiqiang
Published: July 2019

Effect of H2O and NH3 on the synergistic oxidation reaction of SO2 and NO2 is investigated by theoretical calculation using the molecule system SO2-2NO2-nH2O (n = 0, 1, 2, 3) and SO2-2NO2-nH2O-mNH3 (n = 0, 1, 2; m = 1, 2). Calculated results show that SO2 is oxidized to SO3 by N2O4 intermediate. The additional H2O in the systems can reduce the energy barrier of oxidation step. The increasing number of H2O molecules in the systems enhances the effect and promotes the production of HONO. When the proportion of H2O to NH3 is 1:1, with NH3 included in the system, the energy barrier is lower than two pure H2O molecules in the oxidation step. The present study indicates that the H2O and NH3 have thermodynamic effects on promoting the oxidation reaction of SO2 and NO2, and NH3 has a more significant role in stabilizing product complexes. In these hydrolysis reactions, nethermost barrier energy (0.29 kcal/mol) can be found in the system SO2-2NO2-H2O. It is obvious that the production of HONO is energetically favorable. A new reaction mechanism about SO2 oxidation in the atmosphere is proposed, which can provide guidance for the further study of aerosol surface reactions.
Gadolinium Chloride Restores the Function of the Gap Junctional Intercellular Communication between Hepatocytes in a Liver Injury
Authors: Yang Le , Dong Chengbin , Tian Lei , Ji Xiaofang , Yang Lin , Li Liying
Published: July 2019

Background: Gadolinium chloride (GdCl3) has been reported to attenuate liver injury caused by a variety of toxicants. Gap junctional intercellular communication (GJIC) is thought to be essential in controlling liver homeostasis and pathology. Here we evaluate the effects of GdCl3 on functional GJIC and connexin expression in mouse models and primary hepatocytes. Methods: Mice were administered GdCl3 intraperitoneally the day before a carbon tetrachloride (CCl4) injection or bile duct ligation (BDL) operation. Primary hepatocytes were treated with CCl4 or lipopolysaccharides (LPS), with or without GdCl3. A scrape loading/dye transfer assay was performed to assess the GJIC function. The expression of connexins was examined by real-time reverse transcription polymerase chain reaction (RT-PCR), western blot and immunofluorescent staining. Results: CCl4 treatment or the BDL operation led to the dysfunction of GJIC and a down-regulation of Cx32 and Cx26 in injured liver. GdCl3 administration restored GJIC function between hepatocytes by facilitating the transfer of fluorescent dye from one cell into adjacent cells via GJIC, and markedly prevented the decrease of Cx32 and Cx26 in injured liver. In primary hepatocytes, CCl4 or LPS treatment induced an obvious decline of Cx32 and Cx26, whereas GdCl3 pretreatment prevented the down-regulation of connexins. In vivo GdCl3 protected hepatocytes and attenuated the liver inflammation and fibrosis in liver injury mouse models. Conclusion: GdCl3 administration protects functional GJIC between hepatocytes, and prevents the decrease of connexin proteins at mRNA and protein levels during liver injury, leading to the alleviation of chronic liver injury.
New Insights about the Wnt/β-Catenin Signaling Pathway in Primary Bone Tumors and Their Microenvironment: A Promising Target to Develop Therapeutic Strategies?
Authors: Danieau Geoffroy , Morice Sarah , Rédini Françoise , Verrecchia Franck , Brounais-Le Royer Bénédicte
Published: July 2019

Osteosarcoma and Ewing sarcoma are the most common malignant primary bone tumors mainly occurring in children, adolescents and young adults. Current standard therapy includes multidrug chemotherapy and/or radiation specifically for Ewing sarcoma, associated with tumor resection. However, patient survival has not evolved for the past decade and remains closely related to the response of tumor cells to chemotherapy, reaching around 75% at 5 years for patients with localized forms of osteosarcoma or Ewing sarcoma but less than 30% in metastatic diseases and patients resistant to initial chemotherapy. Despite Ewing sarcoma being characterized by specific EWSR1-ETS gene fusions resulting in oncogenic transcription factors, currently, no targeted therapy could be implemented. It seems even more difficult to develop a targeted therapeutic strategy in osteosarcoma which is characterized by high complexity and heterogeneity in genomic alterations. Nevertheless, the common point between these different bone tumors is their ability to deregulate bone homeostasis and remodeling and divert them to their benefit. Therefore, targeting different actors of the bone tumor microenvironment has been hypothesized to develop new therapeutic strategies. In this context, it is well known that the Wnt/β-catenin signaling pathway plays a key role in cancer development, including osteosarcoma and Ewing sarcoma as well as in bone remodeling. Moreover, recent studies highlight the implication of the Wnt/β-catenin pathway in angiogenesis and immuno-surveillance, two key mechanisms involved in metastatic dissemination. This review focuses on the role played by this signaling pathway in the development of primary bone tumors and the modulation of their specific microenvironment.
Association of Polymorphisms in Genes Involved in One-Carbon Metabolism with MTHFR Methylation Levels
Authors: Coppedè Fabio , Stoccoro Andrea , Tannorella Pierpaola , Gallo Roberta , Nicolì Vanessa , Migliore Lucia
Published: July 2019

Methylenetetrahydrofolate reductase (MTHFR) is a pivotal enzyme in the one-carbon metabolism, a metabolic pathway required for DNA synthesis and methylation reactions. MTHFR hypermethylation, resulting in reduced gene expression, can contribute to several human disorders, but little is still known about the factors that regulate MTHFR methylation levels. We performed the present study to investigate if common polymorphisms in one-carbon metabolism genes contribute to MTHFR methylation levels. MTHFR methylation was assessed in peripheral blood DNA samples from 206 healthy subjects with methylation-sensitive high-resolution melting (MS-HRM); genotyping was performed for MTHFR 677C>T (rs1801133) and 1298A>C (rs1801131), MTRR 66A>G (rs1801394), MTR 2756A>G (rs1805087), SLC19A1 (RFC1) 80G>A (rs1051266), TYMS 28-bp tandem repeats (rs34743033) and 1494 6-bp ins/del (rs34489327), DNMT3A -448A>G (rs1550117), and DNMT3B -149C>T (rs2424913) polymorphisms. We observed a statistically significant effect of the DNMT3B -149C>T polymorphism on mean MTHFR methylation levels, and particularly CT and TT carriers showed increased methylation levels than CC carriers. The present study revealed an association between a functional polymorphism of DNMT3B and MTHFR methylation levels that could be of relevance in those disorders, such as inborn defects, metabolic disorders and cancer, that have been linked to impaired DNA methylation.
Decision-Making Deficits in Elderly Can Be Alleviated by Attention Training
Authors: Schmicker Marlen , Menze Inga , Koch David , Rumpf Ulrike , Müller Patrick , Pelzer Lasse , Müller Notger G.
Published: July 2019

Decision-making is an important everyday function that deteriorates during normal aging. Here, we asked whether value-based decision-making can be improved in the elderly by cognitive training. We compared the effects of two training regimens on the performance in the Iowa Gambling Task (IGT), a real-life decision-making simulation task. Elderly participants (age 62–75 years) were randomized into three matched groups. The filter training (FT) group performed a selective attention task and the memory training (MT) group performed a memory storage task on five consecutive days. The control group (CG) did not perform another task besides the IGT. Only the FT group showed an improvement in IGT performance over the five days—the overall gain rose and the prominent deck B phenomenon decreased. The latter refers to the selection of cards associated with high gains and rare losses, which are nevertheless a disadvantageous choice as the frequent losses lead to a negative net outcome. As the deck B phenomenon has been associated with impaired cognitive abilities in aging, the positive effect of FT here is of special importance. In sum, attention training seems superior in improving decision-making in the elderly.
Periodontitis: A Multifaceted Disease of Tooth-Supporting Tissues
Authors: Könönen Eija , Gursoy Mervi , Gursoy Ulvi
Published: July 2019

Periodontitis is an infection-driven inflammatory disease in which the composition of biofilms plays a significant role. Dental plaque accumulation at the gingival margin initiates an inflammatory response that, in turn, causes microbial alterations and may lead to drastic consequences in the periodontium of susceptible individuals. Chronic inflammation affects the gingiva and can proceed to periodontitis, which characteristically results in irreversible loss of attachment and alveolar bone. Periodontitis appears typically in adult-aged populations, but young individuals can also experience it and its harmful outcome. Advanced disease is the major cause of tooth loss in adults. In addition, periodontitis is associated with many chronic diseases and conditions affecting general health.
Reliability of Instantaneous Wave-Free Ratio (iFR) for the Evaluation of Left Main Coronary Artery Lesions
Authors: De Rosa Salvatore , Polimeni Alberto , De Velli Giovanni , Conte Micaela , Sorrentino Sabato , Spaccarotella Carmen , Mongiardo Annalisa , Sabatino Jolanda , Contarini Marco , Todaro Daniel , Indolfi Ciro
Published: July 2019

The assessment of the left main coronary artery (LMCA) by coronary angiography has several limitations. The fractional flow reserve (FFR) is useful for the functional evaluation of LMCA stenoses. The instantaneous wave-free ratio (iFR), a resting index, was developed to simplify functional coronary assessment. However, its performance for LMCA stenoses has yet to be explored. The iFR was measured at rest, and the FFR was measured under maximal hyperemia. We calculated that a sample size of 90 lesions would have provided 90% power at a 5% significance level to detect an Area Under the Curve (AUC) < 0.7 for the iFR to identify FFR-positive stenoses. A total of 91 measurements were performed on angiographically intermediate LMCA stenoses at three centers. The comparison between the iFR and the FFR showed a significant correlation (r = 0.67, p < 0.001). At receiver operating characteristic (ROC) analysis, the iFR revealed a good diagnostic performance when compared to the FFR (AUC = 0.84; p < 0.001). A classification agreement between the iFR and the FFR was recorded in 81% of cases. The left ventricular ejection fraction (LVEF) was an independent predictor of the discrepancy between the FFR and iFR values (p = 0.040). The present study is the first demonstrating that the assessment of LMCA stenoses with the instantaneous wave-free ratio is a reliable adenosine-free alternative to classic fractional flow reserve. If confirmed in larger populations, these findings could be of relevance for real world daily practice.
Effect of MgO Addition on the Mechanical and Dynamic Properties of Zirconia Toughened Alumina (ZTA) Ceramics
Authors: Arab Ali , Sktani Zhwan , Zhou Qiang , Ahmad Zainal , Chen Pengwan
Published: July 2019

Zirconia toughened alumina (ZTA) is a promising advanced ceramic material for a wide range of applications that are subjected to dynamic loading. Therefore, the investigation of dynamic compressive strength, fracture toughness and hardness is essential for ZTA ceramics. However, the relationship between these mechanical properties in ZTA has not yet been established. An example of this relationship is demonstrated using ZTA samples added with MgO prepared through conventional sintering. The microstructure and mechanical properties of ZTA composites were characterized. The hardness of ZTA composites increased for ≤0.7 wt.% MgO due to the pinning effect of MgO and decrease of the porosity in the microstructure. Oppositely, the fracture toughness of ZTA composites continuously decreased due to the size reduction of Al2O3 grains. This is the main reason of deteriorate of dynamic compressive strength more than 0.2 wt.% of MgO addition. Therefore, the SHPB test shows the improvement of the dynamic compressive strength only up to a tiny amount (0.2 wt.% of MgO addition) into ZTA ceramics.
A Terahertz (THz) Single-Polarization-Single-Mode (SPSM) Photonic Crystal Fiber (PCF)
Authors: Yang Tianyu , Ding Can , Ziolkowski Richard W. , Guo Y. Jay
Published: July 2019

This paper presents a novel approach to attain a single-polarization-single-mode (SPSM) photonic crystal fiber (PCF) in the terahertz (THz) regime. An initial circular hole PCF design is modified by introducing asymmetry in the first ring of six air holes in the cladding, i.e., epsilon-near-zero (ENZ) material is introduced into only four of those air holes and the other two remain air-filled but have different diameters. The resulting fundamental X-polarized (XP) and Y-polarized (YP) modes have distinctly different electric field distributions. The asymmetry is arranged so that the YP mode has a much larger amount of the field distributed in the ENZ material than the XP mode. Since the ENZ material is very lossy, the YP mode suffers a much higher loss than the XP mode. Consequently, after a short propagation distance, the loss difference (LD) between the XP and YP modes will be large enough that only the XP mode still realistically exists in the PCF. To further enhance the outcome, gain material is introduced into the core area to increase the LDs between the wanted XP mode and any unwanted higher order (HO) modes, as well as to compensate for the XP mode loss without affecting the LD between the XP and YP modes. The optimized PCF exhibits LDs between the desired XP mode and all other modes greater than 8.0 dB/cm across a wide frequency range of 0.312 THz. Consequently, the reported PCF only needs a length of 2.5 cm to attain an SPSM result, with the unwanted modes being more than 20 dB smaller than the wanted mode over the entire operational band.
Monitoring the Environmental Aging of Nanomaterials: An Opportunity for Mesocosm Testing?
Authors: Masion Armand , Auffan Mélanie , Rose Jérôme
Published: July 2019

Traditional aging protocols typically examine only the effects of a limited number of stresses, and relatively harsh conditions may trigger degradation mechanisms that are not observed in actual situations. Environmental aging is, in essence, the complex interaction of multiple mechanical, physicochemical and biological stresses. As yet, there is no (pre)standardized procedure that addresses this issue in a satisfactory manner. Mesocosm experiments can be designed to specifically cover the aging of nanomaterials while characterizing the associated exposure and hazard. The scenario of exposure and the life time of the nanomaterial appear as the predominant factors in the design of the experiment, and appropriate precautions need to be taken. This should the subject of guidance that may be divided into product/application categories.
Appell-Type Functions and Chebyshev Polynomials
Authors: Natalini Pierpaolo , Ricci Paolo Emilio
Published: July 2019

In a recent article we noted that the first and second kind Cebyshev polynomials can be used to separate the real from the imaginary part of the Appell polynomials. The purpose of this article is to show that the same classic polynomials can also be used to separate the even part from the odd part of the Appell polynomials and of the Appell–Bessel functions.