bluuebunny/crossref_metadata_2025 huggingface dataset:
Screening Different Divalent and Trivalent Metals Containing Binary and Ternary Layered Double Hydroxides for Optimum Phosphate Uptake
Authors: Almojil Sattam Fahad , Othman Mohamed Abdelhalim
Published: October 2019

The elements constituting a layered double hydroxides material provide many alternatives for its optimization. Ten different layered double hydroxides materials with various combinations of Ni, Cu, Zn, Al, Cr, and Fe elements were studied as sorbent materials for phosphate ion. The type of element used in the layered double hydroxides affected the uptake capacity of phosphate. The influence of a specific element alone was not the primary role of enhancing the sorption performance of phosphate ion on the LDHs material. However, using specific two or three elements together is the key to achieve the best result due to synergistic effects. BET surface area of the sorbent showed no correlation with phosphate uptake. From the examined materials, Four layered double hydroxides of Cu-Zn-Cr, Zn-Cr, Ni-Al, and Cu-Ni-Cr showed high phosphate sorption capability. Sorption equilibrium isotherm, reaction kinetics, and desorption of phosphate from the sorbent materials were also investigated.
GPR40 activation initiates store-operated Ca2+ entry and potentiates insulin secretion via the IP3R1/STIM1/Orai1 pathway in pancreatic β-cells
Authors: Usui Ryota , Yabe Daisuke , Fauzi Muhammad , Goto Hisanori , Botagarova Ainur , Tokumoto Shinsuke , Tatsuoka Hisato , Tahara Yumiko , Kobayashi Shizuka , Manabe Toshiya , Baba Yoshihiro , Kurosaki Tomohiro , Herrera Pedro Luis , Ogura Masahito , Nagashima Kazuaki , Inagaki Nobuya
Published: October 2019

The long-chain fatty acid receptor GPR40 plays an important role in potentiation of glucose-induced insulin secretion (GIIS) from pancreatic β-cells. Previous studies demonstrated that GPR40 activation enhances Ca2+ release from the endoplasmic reticulum (ER) by activating inositol 1,4,5-triphosphate (IP3) receptors. However, it remains unknown how ER Ca2+ release via the IP3 receptor is linked to GIIS potentiation. Recently, stromal interaction molecule (STIM) 1 was identified as a key regulator of store-operated Ca2+ entry (SOCE), but little is known about its contribution in GPR40 signaling. We show that GPR40-mediated potentiation of GIIS is abolished by knockdown of IP3 receptor 1 (IP3R1), STIM1 or Ca2+-channel Orai1 in insulin-secreting MIN6 cells. STIM1 and Orai1 knockdown significantly impaired SOCE and the increase of intracellular Ca2+ by the GPR40 agonist, fasiglifam. Furthermore, β-cell-specific STIM1 knockout mice showed impaired fasiglifam-mediated GIIS potentiation not only in isolated islets but also in vivo. These results indicate that the IP3R1/STIM1/Orai1 pathway plays an important role in GPR40-mediated SOCE initiation and GIIS potentiation in pancreatic β-cells.
Genes A27L and F13L as Genetic Markers for the Isolation of Recombinant Vaccinia Virus
Authors: Lorenzo María M. , Sánchez-Puig Juana M. , Blasco Rafael
Published: October 2019

After assembly in the cytosol, some Vaccinia virus particles go through a complex process that leads to virus egress and eventually cell-to-cell transmission. Intracellular particles are fully infectious, and therefore virus mutants lacking essential functions in the exit pathway are unable to form plaques but can multiply intracellularly. We isolated virus mutants in which two of the genes required for virus spread (F13L and A27L) were deleted independently or concurrently. The phenotypes of the mutant viruses were consistent with the need of A27L and F13L for intercellular virus transmission, the effect of the ΔA27L mutation being more severe than that of ΔF13L. Despite their defect in spread, ΔA27L mutant viruses could be expanded by infecting cell cultures at high multiplicity of infection, followed by the release of virions from infected cells by physical means. We developed a novel system for the isolation of recombinant Vaccinia virus in which selection is efficiently achieved by recovering plaque formation capacity after re-introduction of A27L into a ΔA27L virus. This system allowed the insertion of foreign DNA into the viral genome without the use of additional genetic markers. Furthermore, starting with a double mutant (ΔA27L-ΔF13L) virus, A27L selection was used in conjunction with F13L selection to mediate simultaneous dual insertions in the viral genome. This selection system facilitates combined expression of multiple foreign proteins from a single recombinant virus.
Direct determination of phenolic secoiridoids in olive oil by ultra-high performance liquid chromatography-triple quadruple mass spectrometry analysis
Authors: Luque-Muñoz Antonio , Tapia Ruben , Haidour Ali , Justicia Jose , Cuerva Juan M.
Published: October 2019

In recent years, a large number of biological properties and an important role in the organoleptic characteristics of olive oil have been attributed to phenolic secoiridoids, such as oleacein, oleocanthal, oleuropein aglycone and ligstroside aglycone. Consequently, quantifying them is of great interest for the olive oil sector. Currently, there is no consensus in which analytical method must be use to accurately determine these compounds in olive oil, mainly owing to the lack of reference standards for calibration. In this work, analytical standards of phenolic secoiridoids have been used to develop a quantitative and rapid analytical method by UHPLC-MS/MS, in which sample extraction is not carried out. Simple dilutions of the sample with dry tetrahydrofuran and dry acetonitrile were performed before analysing them. It is worth noting that under these conditions the generation of artefacts such as acetals and hemiacetals of the aldehydic forms is highly reduced. The detection and quantification was performed with a Xevo TQS tandem quadrupole mass spectrometer. The method was validated at four concentration levels and finally applied to six samples of extra virgin olive oil.
A new perspective in understanding rainfall from satellites over a complex topographic region of India
Authors: Thakur Manoj Kumar , Kumar T. V. Lakshmi , Koteswara Rao K. , Barbosa Humberto , Rao V. Brahmananda
Published: October 2019

Present study focuses on rainfall over Western Ghats (WG), a complex topographic region (elevation > 500 m) of India to evaluate and to better understand the satellite behavior in contrast with a flat region (FR) (elevation < 500 m) of central India from 1998 to 2016 using the combinatory data sets of TMPA and IMERG (satellite rainfall estimation). The categorical Intra Seasonal Oscillations (ISO) of Indian summer monsoon (ISM) namely, Madden Julian Oscillation (MJO) and Quasi Bi-Weekly Oscillation (QBWO) are tested in satellite and India Meteorological Department (IMD) gridded rainfall data sets to find out the satellite performance. As the accurate estimation of rainfall from satellites over higher elevation zones is challenging, here we propose a new perspective to select the rainfall products of satellite for better comparison with ground measurements. Considering the satellite’s best capability in detecting the cold clouds resulting from deep convection and its coupling with higher-level circulation, we show that the rainfall from satellites yield fruitful comparison with ground measurements when moist static stability, tropical easterly jet is above the climatological values.
Improved Characterisation of Vegetation and Land Surface Seasonal Dynamics in Central Japan with Himawari-8 Hypertemporal Data
Authors: Miura Tomoaki , Nagai Shin , Takeuchi Mika , Ichii Kazuhito , Yoshioka Hiroki
Published: October 2019

Spectral vegetation index time series data, such as the normalized difference vegetation index (NDVI), from moderate resolution, polar-orbiting satellite sensors have widely been used for analysis of vegetation seasonal dynamics from regional to global scales. The utility of these datasets is often limited as frequent/persistent cloud occurrences reduce their effective temporal resolution. In this study, we evaluated improvements in capturing vegetation seasonal changes with 10-min resolution NDVI data derived from Advanced Himawari Imager (AHI), one of new-generation geostationary satellite sensors. Our analysis was focused on continuous monitoring sites, representing three major ecosystems in Central Japan, wherein situtime-lapse digital images documenting sky and surface vegetation conditions were available. The very large number of observations available with AHI resulted in improved NDVI temporal signatures that were remarkably similar to those acquired within situspectrometers and captured seasonal changes in vegetation and snow cover conditions in finer detail with more certainty than those obtained from Visible Infrared Imaging Radiometer Suite (VIIRS), one of the latest polar-orbiting satellite sensors. With the ability to capturein situ-quality NDVI temporal signatures, AHI “hypertemporal” data have the potential to improve spring and autumn phenology characterisation as well as the classification of vegetation formations.
Caveolin-1 rs4730751 single-nucleotide polymorphism may not influence kidney transplant allograft survival
Authors: Maanaoui Mehdi , Lenain Rémi , Hamroun Aghilès , Van der Hauwaert Cynthia , Lopez Benjamin , Gibier Jean-Baptiste , Frimat Marie , Savary Grégoire , Hennart Benjamin , Larrue Romain , Pottier Nicolas , Broly Franck , Provôt François , Hazzan Marc , Glowacki François , Cauffiez Christelle
Published: October 2019

Caveolin-1 is a protein (encoded by the CAV1 gene) supposedly harboring a protective effect against fibrosis. CAV1 rs4730751 single nucleotide polymorphism (SNP) AA genotype was initially associated with lower graft survival compared to non-AA. However, subsequent studies could not find the same effect. CAV1 rs4730751 SNP was investigated on 918 kidney donors. Multivariate Cox-model analyses were performed to evaluate risk factors for graft loss. Longitudinal changes on long-term estimated glomerular filtration rate (eGFRs) were evaluated with a linear mixed model. Histopathological findings from protocolled biopsies after 3 months post transplantation were also analyzed. Donor CAV1 rs4730751 genotyping proportions were 7.1% for AA, 41.6% for AC and 51.3% for CC. The AA genotype, compared to non-AA, was not associated with lower graft survival censored or not for death (multivariate analysis: HR = 1.23 [0.74–2.05] and HR = 1.27 [0.84–1.92]). Linear mixed model on long-term eGFRs revealed also no significant difference according to the genotype, yet we observed a trend. AA genotype was also not associated with a higher degree of fibrosis index on protocolled kidney biopsies at 3 months. To conclude, donor CAV1 rs4730751 SNP may impact on kidney transplantation outcomes, but this study could not confirm this hypothesis.
Photosynthetical activity modelisation of olive trees growing under drought conditions
Authors: Sghaier Abderrahman , Perttunen Jari , Sievaènen Risto , Boujnah Dalenda , Ouessar Mohamed , Ben Ayed Rayda , Naggaz Kamel
Published: October 2019

Predicting photosynthetic production in olive trees is a key feature in managing the effect of climate change on arid areas. Functional-structural plant modelling is a promising tool for achieving this goal. We used a photosynthetic sub-model that accounted for water and temperature stress and implemented it into LIGNUM model. We then conducted an experiment to validate the model at the leaf level using olive trees (Olea europaea) grown under various climatic condition. Then, we simulated photosynthetic production of three static olive tree models aged 1, 2, and 3 years. Results revealed a good fit between observed and predicted photosynthesis, with coefficient of determination (R2) values of 0.94 and 0.93 for Chemlali and Zarrazi cultivars, respectively. These results showed that the impact of water stress on photosynthetic production was marginal.
Nanoparticles transported from aquatic to terrestrial ecosystems via emerging aquatic insects compromise subsidy quality
Authors: Bundschuh Mirco , Englert Dominic , Rosenfeldt Ricki R. , Bundschuh Rebecca , Feckler Alexander , Lüderwald Simon , Seitz Frank , Zubrod Jochen P. , Schulz Ralf
Published: October 2019

Nanoparticle contaminants enter aquatic ecosystems and are transported along the stream network. Here, we demonstrate a novel pathway for the return of nanoparticles from aquatic to terrestrial ecosystems via cross-boundary subsidies. During their emergence, trichopteran caddisflies carried titanium dioxide and gold nanoparticles into their terrestrial life stages. Moreover, their emergence was delayed by ≤30 days, and their energy reserves were depleted by ≤25%. Based on worst case estimates, it is suggested that terrestrial predators, such as bats feeding on aquatic prey, may ingest up to three orders of magnitude higher gold levels than anticipated for humans. Additionally, terrestrial predator species may suffer from alterations in the temporal availability and nutritional quality of their prey. Considering the substantial transfer of insect biomass to terrestrial ecosystems, nanoparticles may decouple aquatic and terrestrial food webs with important (meta-)ecosystem level consequences.
Kinematics of perceived dyadic coordination in dance
Authors: Hartmann Martin , Mavrolampados Anastasios , Allingham Emma , Carlson Emily , Burger Birgitta , Toiviainen Petri
Published: October 2019

We investigated the relationships between perceptions of similarity and interaction in spontaneously dancing dyads, and movement features extracted using novel computational methods. We hypothesized that dancers’ movements would be perceived as more similar when they exhibited spatially and temporally comparable movement patterns, and as more interactive when they spatially oriented more towards each other. Pairs of dancers were asked to move freely to two musical excerpts while their movements were recorded using optical motion capture. Subsequently, in two separate perceptual experiments we presented stick figure animations of the dyads to observers, who rated degree of interaction and similarity between dancers. Mean perceptual ratings were compared with three different approaches for quantifying coordination: torso orientation, temporal coupling, and spatial coupling. Correlations and partial correlations across dyads were computed between each estimate and the perceptual measures. A systematic exploration showed that torso orientation (dancers facing more towards each other) is a strong predictor of perceived interaction even after controlling for other features, whereas temporal and spatial coupling (dancers moving similarly in space and in time) are better predictors for perceived similarity. Further, our results suggest that similarity is a necessary but not sufficient condition for interaction.
Nanoscale structural defects in oblique Ar+ sputtered Si(111) surfaces
Authors: Gupta Divya , Chawla Mahak , Singhal Rahul , Aggarwal Sanjeev
Published: October 2019

The present endeavor investigates the controlled surface modifications and evolution of self-assembled nano-dimensional defects on oblique Ar+ sputtered Si(111) surfaces which are important substrates for surface reconstruction. The defect formation started at off-normal incidences of 50° and then deflates into defined defect zones with decrease in oblique incidence, depending strongly on angle of ion incidence. Interestingly, it is observed that mean size & height decreases while average density of these defects increases with decreasing oblique incidence. Non-linear response of roughness of irradiated Si(111) with respect to oblique incidence is observed. Crystalline (c-Si) to amorphous (a-Si) phase transition under oblique argon ion irradiation has been revealed by Raman spectroscopy. Our analysis, thus, shows that high dose argon ion irradiation generates of self-assembled nano-scale defects and surface vacancies & their possible clustering into extended defect zones. Explicitly, ion beam-stimulated mass transport inside the amorphous layers governs the observed defect evolution. This investigation of crystalline (c-Si) coupled with amorphous (a-Si) phases of nano-structured surfaces provides insight into the potential applications in the nano-electronic and optoelectronic devices thus, initiating a new era for fabricating multitude of novel structures.
Chronic kidney disease exacerbates ischemic limb myopathy in mice via altered mitochondrial energetics
Authors: Berru Fabian N. , Gray Sarah E. , Thome Trace , Kumar Ravi A. , Salyers Zachary R. , Coleman Madeline , Dennis Le  , O’Malley Kerri , Ferreira Leonardo F. , Berceli Scott A. , Scali Salvatore T. , Ryan Terence E.
Published: October 2019

Chronic kidney disease (CKD) substantially increases the severity of peripheral arterial disease (PAD) symptomology, however, the biological mechanisms remain unclear. The objective herein was to determine the impact of CKD on PAD pathology in mice. C57BL6/J mice were subjected to a diet-induced model of CKD by delivery of adenine for six weeks. CKD was confirmed by measurements of glomerular filtration rate, blood urea nitrogen, and kidney histopathology. Mice with CKD displayed lower muscle force production and greater ischemic lesions in the tibialis anterior muscle (78.1 ± 14.5% vs. 2.5 ± 0.5% in control mice, P < 0.0001, N = 5–10/group) and decreased myofiber size (1661 ± 134 μm2 vs. 2221 ± 100 μm2 in control mice, P < 0.01, N = 5–10/group). This skeletal myopathy occurred despite normal capillary density (516 ± 59 vs. 466 ± 45 capillaries/20x field of view) and limb perfusion. CKD mice displayed a ~50–65% reduction in muscle mitochondrial respiratory capacity in ischemic muscle, whereas control mice had normal mitochondrial function. Hydrogen peroxide emission was modestly higher in the ischemic muscle of CKD mice, which coincided with decreased oxidant buffering. Exposure of cultured myotubes to CKD serum resulted in myotube atrophy and elevated oxidative stress, which were attenuated by mitochondrial-targeted therapies. Taken together, these findings suggest that mitochondrial impairments caused by CKD contribute to the exacerbation of ischemic pathology.
Study of Periodontal Health in Almada-Seixal (SoPHiAS): a cross-sectional study in the Lisbon Metropolitan Area
Authors: Botelho João , Machado Vanessa , Proença Luís , Alves Ricardo , Cavacas Maria Alzira , Amaro Luís , Mendes José João
Published: October 2019

This study aimed to describe the prevalence and extent of periodontal diseases among adults in the southern region of the Lisbon Metropolitan Area. This population-based cross-sectional study included 1,064 randomized participants (aged 18 to 95 years, 617 females/447 males). Sociodemographic, behaviours and medical information were recorded. Periodontal conditions were assessed with a full-mouth circumferential periodontal examination. It was used the American Association of Periodontology/European Federation of Periodontology 2017 case definitions. A logistic regression analysis was applied to ascertain hypothetical risk factors towards periodontitis. The prevalence of periodontitis was 59.9%, with 24.0% and 22.2% of the participants exhibiting severe and moderate periodontitis, respectively. The risk of periodontitis significantly increased with age (OR = 1.05, 95% CI: 1.04–1.06), for active and former smokers (OR = 3.76 and OR = 2.11, respectively), with lower education levels (OR = 2.08, OR = 1.86, for middle and elementary education, respectively) and with diabetes mellitus (OR = 1.53). This study confirms a high burden of periodontitis in the target (Portuguese) sub-population. The findings provide a comprehensive understanding that will empower appropriate national public oral health programmes and population-based preventive actions.
An improved overlap extension PCR for simultaneous multiple sites large fragments insertion, deletion and substitution
Authors: Guo Wei , Xie Binhua , Jiang Min , Zhu Xiao-Jing , Qiu Mengsheng , Dai Zhong-Min
Published: October 2019

The existing molecular cloning methods are often limited by the availability of suitable restriction sites. It is still a challenge for simultaneous cloning of multiple fragments into different sites of a single vector. Here we developed a novel method named improved overlap extension PCR (IOEP) for restriction enzyme independent cloning of large fragments. The addition of primers enables IOEP to exponentially amplify the overlap extension product, thus greatly improves the amplification efficiency of large fragments. Moreover, coupled with the benefit of T4 DNA polymerase to improve cloning efficiency, our method can be used to simultaneously insert, delete and replace multiple DNA fragments at different sites.
Femtosecond Laser Pulse Ablation of Sub-Cellular Drusen-Like Deposits
Authors: Smith Katherine N. , Katchinskiy Nir , Elezzabi Abdulhakem Y.
Published: October 2019

Age-related macular degeneration (AMD) is a condition affecting the retina and is the leading cause of vision loss. Dry AMD is caused by the accumulation of lipid deposits called drusen, which form under the retina. This work demonstrates, for the first time, the removal of drusen-like deposits underneath ARPE-19 cell layers using femtosecond laser pulses. A novel cell culture model was created in response to the limited access to primary cell lines and the absence of animal models that recapitulate all aspects of AMD. In the cell culture model, deposits were identified with fluorescent stains specific to known deposit constituents. Trains of sub-10 femtosecond laser pulses from a Ti:Sapphire laser were used to successfully ablate the deposits without causing damage to surrounding cells. This drusen removal method can be used as a potential treatment for dry-stage AMD.
8-OxoG in GC-rich Sp1 binding sites enhances gene transcription in adipose tissue of juvenile mice
Authors: Park Jong Woo , Han Young In , Kim Sung Woo , Kim Tae Min , Yeom Su Cheong , Kang Jaeku , Park Joonghoon
Published: October 2019

The oxidation of guanine to 8-oxoguanine (8-oxoG) is the most common type of oxidative DNA lesion. There is a growing body of evidence indicating that 8-oxoG is not only pre-mutagenic, but also plays an essential role in modulating gene expression along with its cognate repair proteins. In this study, we investigated the relationship between 8-oxoG formed under intrinsic oxidative stress conditions and gene expression in adipose and lung tissues of juvenile mice. We observed that transcriptional activity and the number of active genes were significantly correlated with the distribution of 8-oxoG in gene promoter regions, as determined by reverse-phase liquid chromatography/mass spectrometry (RP-LC/MS), and 8-oxoG and RNA sequencing. Gene regulation by 8-oxoG was not associated with the degree of 8-oxoG formation. Instead, genes with GC-rich transcription factor binding sites in their promoters became more active with increasing 8-oxoG abundance as also demonstrated by specificity protein 1 (Sp1)- and estrogen response element (ERE)-luciferase assays in human embryonic kidney (HEK293T) cells. These results indicate that the occurrence of 8-oxoG in GC-rich Sp1 binding sites is important for gene regulation during adipose tissue development.
Effects of Microwave Energy on Fast Compressive Strength Development of Coal Bottom Ash-Based Geopolymers
Authors: Hong Sungil , Kim Hyo
Published: October 2019

Microwave energy has been shown to be effective for geopolymer synthesis due to its fast and penetrative heating characteristics; however, the changes in the physicochemical properties of the geopolymer, resulting from the microwave irradiation, have not been fully elucidated. Therefore, this study is aimed at investigating the effect of the microwaving on the properties of coal bottom ash(CBA) geopolymers. We prepared geopolymer samples by casting a mixture of ground CBA and 14 M NaOH solution against cubic molds with a hand press machine, followed by pre-curing in a dry oven at 75 °C for 24 h and microwaving under various powers and durations. The compressive strength strongly depended on the moisture content, i.e., the strength increased from 21 to 65 MPa or higher as the moisture content decreased to critical values, after which the strength began to decrease. The results showed that microwave energy stimulated an additional geopolymerization by evaporating the redundant free water. This led to the strength gain, although the over-irradiation generated a high internal stress and poor structural integrity, which resulted in the strength loss. Therefore, the appropriate application of microwave energy is a promising option for synthesizing high-strength geopolymers in a cost- and time-effective manner.
Evaluation of the dose-related concentration approach in therapeutic drug monitoring of diuretics and β-blockers – drug classes with low adherence in antihypertensive therapy
Authors: Ritscher Sabrina , Hoyer Milena , Wunder Cora , Obermüller Nicholas , Toennes Stefan W.
Published: October 2019

Detection of antihypertensive drugs in biological samples is an important tool to assess the adherence of hypertensive patients. Urine and serum/plasma screenings based on qualitative results may lead to misinterpretations regarding drugs with a prolonged detectability. The aim of the present study was to develop a method that can be used for therapeutic drug monitoring (TDM) of antihypertensive drugs with focus on adherence assessment. Therefore, a method for quantification of four diuretics and four β-blockers using high-performance liquid chromatography-mass spectrometric analysis (LC-MS/MS) of combined acidic and basic serum extracts was developed and validated. The method was applied to 40 serum samples from 20 patients in a supervised medication setting (trough and peak serum samples). Literature data on therapeutic concentration ranges, as well as dose-related drug concentrations (calculated from data of pharmacokinetic studies) were used to evaluate adherence assessment criteria. Concentrations were measured for bisoprolol (n = 9 patients), metoprolol (n = 7), nebivolol (n = 1), canrenone (n = 2, metabolite of spironolactone), hydrochlorothiazide (n = 10) and torasemide (n = 8). The measured concentrations were within the therapeutic reference ranges, except for 24% of the samples (mainly β-blockers). In contrast, all measured concentrations were above the lower dose-related concentration (DRC), which appears superior in evaluating adherence. In conclusion, the quantitative analysis of antihypertensive drugs in serum samples and its evaluation on the basis of the individually calculated lower DRC is a promising tool to differentially assess adherence. This method could possibly detect a lack of adherence or other causes of insufficient therapy more reliably than qualitative methods.
Caffeoyl-β-d-glucopyranoside and 1,3-dihydroxy-2-tetracosanoylamino-4-(E)-nonadecene isolated from Ranunculus muricatus exhibit antioxidant activity
Authors: Azam Farooq , Chaudhry Bashir Ahmad , Ijaz Hira , Qadir Muhammad Imran
Published: October 2019

This study evaluates the antioxidant activity of Ranunculus muricatus and isolation and structure elucidation of the active constituents. The aerial parts of the plants were shade dried at room temperature and powdered and extracted with methanol. The free radical scavenging activity was evaluated by 1,1-diphenyl-2-picryl-hydrazyl (DPPH) assay. The percentage scavenging activity was determined based on the percentage of DPPH radical scavenged. Column chromatography was used in order to isolate the active compounds. Spectral techniques UV, IR, 1H NMR, 13CNMR and HREI-MS were used for the structure elucidation of the isolated compounds. Two isolated compounds, A (caffeoyl-β-d-glucopyranoside) and B (1,3-dihydroxy-2-tetracosanoylamino-4-(E)-nonadecene), exibited a significant antioxidant activity as showed by DPPH radical scavenging method. Percentage inhibition for compound A (at 0.5 mM) was 82.67 ± 0.19 with IC50 of 93.25 ± 0.12 (μM), and for compound B (at 0.5 mM) was 69.23 ± 0.19 with IC50 of 183.34 ± 0.13 (μM). Quercetin was used as standard control. It was conclued from the present study that caffeoyl-β-d-glucopyranoside and 1,3-dihydroxy-2-tetracosanoylamino-4-(E)-nonadecene isolated from methanol extract of aerial parts of Ranunculus muricatus posses antioxidant activity.
Neoadjuvant therapy versus upfront surgery in resectable pancreatic cancer according to intention-to-treat and per-protocol analysis: A systematic review and meta-analysis
Authors: Lee Yoon Suk , Lee Jong-Chan , Yang Se Yeol , Kim Jaihwan , Hwang Jin-Hyeok
Published: October 2019

The effectiveness of neoadjuvant therapy (NAT) remains unclear in resectable pancreatic cancer (PC) as compared with upfront surgery (US). The aim of this study was to investigate the survival gain of NAT over US in resectable PC. PubMed and EMBASE were searched for studies comparing survival outcomes between NAT and US for resectable PC until June 2018. Overall survival (OS) was analyzed according to treatment strategy (NAT versus US) and analytic methods (intention-to-treat analysis (ITT) and per-protocol analysis (PP)). In 14 studies, 2,699 and 6,992 patients were treated with NAT and US, respectively. Although PP analysis showed the survival gain of NAT (HR 0.72, 95% CI 0.68–0.76), ITT analysis did not show the statistical significance (HR 0.96, 95% CI 0.82–1.12). However, NAT completed with subsequent surgery showed better survival over US completed with adjuvant therapy (HR 0.82, 95% CI 0.71–0.93). In conclusion, the supporting evidence for NAT in resectable PC was insufficient because the benefit was not demonstrated in ITT analysis. However, among the patients who completed both surgery and chemotherapy, NAT showed survival benefit over adjuvant therapy. Therefore, NAT could have a role of triaging the patients for surgery even in resectable PC.
UGCG influences glutamine metabolism of breast cancer cells
Authors: Schömel Nina , Hancock Sarah E. , Gruber Lisa , Olzomer Ellen M. , Byrne Frances L. , Shah Divya , Hoehn Kyle L. , Turner Nigel , Grösch Sabine , Geisslinger Gerd , Wegner Marthe-Susanna
Published: October 2019

UDP-glucose ceramide glucosyltransferase (UGCG) is the key enzyme in glycosphingolipid (GSL) metabolism by being the only enzyme that generates glucosylceramide (GlcCer) de novo. Increased UGCG synthesis is associated with pro-cancerous processes such as increased proliferation and multidrug resistance in several cancer types. We investigated the influence of UGCG overexpression on glutamine metabolism in breast cancer cells. We observed adapted glucose and glutamine uptake in a limited energy supply environment following UGCG overexpression. Glutamine is used for reinforced oxidative stress response shown by increased mRNA expression of glutamine metabolizing proteins such as glutathione-disulfide reductase (GSR) resulting in increased reduced glutathione (GSH) level. Augmented glutamine uptake is also used for fueling the tricarboxylic acid (TCA) cycle to maintain the proliferative advantage of UGCG overexpressing cells. Our data reveal a link between GSL and glutamine metabolism in breast cancer cells, which is to our knowledge a novel correlation in the field of sphingolipid research.
Herbal components of Japanese Kampo medicines exert laxative actions in colonic epithelium cells via activation of BK and CFTR channels
Authors: Numata Tomohiro , Sato-Numata Kaori , Okada Yasunobu
Published: October 2019

Japanese Kampo medicines Junchoto and Mashiningan are mixtures of numerous herbal plant extracts and empirically known to exert laxative actions by stimulating fluid secretion in the colonic epithelium. However, it is unknown which and how the herbal components of these crude Kampo drugs are effective to stimulate ion effluxes causing fluid secretion. Here, we selected four herbal components of Junchoto and Mashiningan, Mashinin (MSN), Kyonin (KYN), Tonin (TON), and Daio (DIO), which are putatively laxatives, and examined their effects on the ion channel activity of human colonic epithelial Caco-2 cells. Patch clamp analyses revealed that MSN activated whole-cell current characteristics of the cystic fibrosis transmembrane conductance regulator (CFTR) channel, whereas KYN, TON, and DIO activated the large-conductance and voltage-activated K+ (BK) channel. Furthermore, electronic cell sizing showed that MSN induced secretory volume decrease (SVD) sensitivity to a CFTR blocker, whereas TON, KYN, and DIO induced SVD sensitivity to a K+ channel blocker. In conclusion, MSN and TON, KYN, and DIO promote fluid secretion from colonic epithelial cells by activating CFTR and BK channels. Thus, Japanese Kampo medicines, Junchoto and Mashiningan, exert anti-constipation actions by inducing KCl efflux through the combined actions of CFTR- and BK-stimulating herbal components.
The effects of intravitreal sodium iodate injection on retinal degeneration following vitrectomy in rabbits
Authors: Ahn So Min , Ahn Jungryul , Cha Seongkwang , Yun Cheolmin , Park Tae Kwann , Kim Young-Jin , Goo Yong Sook , Kim Seong-Woo
Published: October 2019

We sought to develop and characterize outer retinal degeneration induced by intravitreal injection of sodium iodate (SI) after vitrectomy in rabbits. To determine the effective dose of SI, the right eyes of 19 male New Zealand white rabbits received an intravitreal injection of SI or sham. Based on the dose-dependence results, 0.4 mg of SI in 0.05 mL of total volume was injected into the right eyes of 10 rabbits at two weeks after vitrectomy. In the dose-dependence study, localized retinal atrophy was observed with 0.3- and 0.4-mg SI injections without vitrectomy. Severe and diffuse retinal atrophy was identified by spectral-domain optical coherence tomography (SD-OCT) at one month after a 0.5-mg SI injection following vitrectomy. In the second experiment, 0.4 mg of SI in 0.05 mL was injected, and the severity of outer retinal degeneration was graded as one of two types according to electroretinography (ERG) response change. There was no response on ERG in complete retinal degeneration, 30% of all 10 rabbits. Intravitreal injection of 0.4 mg of SI into vitrectomized rabbit eyes induces diffuse outer retinal degeneration, and the degree of retinal degeneration can be evaluated through in vivo ophthalmic examination.
Cigarette smoke affects the onco-suppressor DAB2IP expression in bronchial epithelial cells of COPD patients
Authors: Anzalone Giulia , Arcoleo Giuseppe , Bucchieri Fabio , Montalbano Angela M. , Marchese Roberto , Albano Giusy D. , Di Sano Caterina , Moscato Monica , Gagliardo Rosalia , Ricciardolo Fabio L. M. , Profita Mirella
Published: October 2019

Cigarette smoke is a risk factor for COPD and lung cancer. In cancer, epigenetic modifications affect the expression of Enhancer of Zester Homolog 2 (EZH2), and silenced disabled homolog 2 interacting protein gene (DAB2IP) (onco-suppressor gene) by Histone H3 tri-methylation in lysine 27 (H3K27me3). In“ex vivo”studies, we assessed EZH2, H3K27me3 and DAB2IP immunoreactivity in bronchial epithelial cells from COPD patients (smokers, ex-smokers), Smoker and control subjects. In“in vitro” experiments we studied the effect of cigarette smoke extract (CSE) on EZH2/H3K27me3/DAB2IP expression, apoptosis, invasiveness, and vimentin expression in 16HBE, primary cells, and lung cancer cell lines (A549) long-term exposed to CSE. Finally, in “in vitro”studies, we tested the effect of GSK343 (selective inhibitor of EZH2). EZH2 and H3K27me3 expression was higher, while DAB2IP was lower levels, in bronchial epithelium from COPD and Smokers than in Controls. CSE increased EZH2, H3K27me3 expression and decreased DAB2IP, cell apoptosis and invasiveness in epithelial cells. GSK343 restored the effects of CSE. Cigarette smoke affects EZH2 expression, and reduced DAB2IP via H3K27me3 in COPD patients. The molecular mechanisms associated with EZH2 expression, generate a dysregulation of cell apoptosis, mesenchymal transition, and cell invasiveness in bronchial epithelial cells, encouraging the progression of airway inflammation toward lung cancer in COPD patients.
A novel phospho-modulatory mechanism contributes to the calcium-dependent regulation of T-type Ca2+ channels
Authors: Chemin Jean , Stamenic Tamara Timic , Cazade Magalie , Llinares Jodie , Blesneac Iulia , Todorovic Slobodan M. , Lory Philippe
Published: October 2019

Cav3 / T-type Ca2+ channels are dynamically regulated by intracellular Ca2+ ions, which inhibit Cav3 availability. Here, we demonstrate that this inhibition becomes irreversible in the presence of non-hydrolysable ATP analogs, resulting in a strong hyperpolarizing shift in the steady-state inactivation of the residual Cav3 current. Importantly, the effect of these ATP analogs was prevented in the presence of intracellular BAPTA. Additional findings obtained using intracellular dialysis of inorganic phosphate and alkaline phosphatase or NaN3 treatment further support the involvement of a phosphorylation mechanism. Contrasting with Cav1 and Cav2 Ca2+ channels, the Ca2+-dependent modulation of Cav3 channels appears to be independent of calmodulin, calcineurin and endocytic pathways. Similar findings were obtained for the native T-type Ca2+ current recorded in rat thalamic neurons of the central medial nucleus. Overall, our data reveal a new Ca2+ sensitive phosphorylation-dependent mechanism regulating Cav3 channels, with potentially important physiological implications for the multiple cell functions controlled by T-type Ca2+ channels.
Hurricane María’s Precipitation Signature in Puerto Rico: A Conceivable Presage of Rains to Come
Authors: Ramos-Scharrón Carlos E. , Arima Eugenio
Published: October 2019

The effects of global climate change on the intensity of tropical cyclones are yet to be fully understood due to the variety of factors that affect storm intensity, the limited time spans of existing records, and the diversity of metrics by which intensity is characterized. The 2017 North Atlantic hurricane season induced record-breaking economic losses and caused hundreds of fatalities, and for many represents a presage of what the future holds under warmer tropical sea surface temperatures. This article focuses on one such major hurricane, María, and answers the question of how this event compares to the historical record of tropical storms that have assailed the island of Puerto Rico since 1898. Comparisons relied on interpolated weather station total rainfall and maximum 24-h rainfall intensities. María proved to have the greatest 24-h rain intensities among all storms recorded in Puerto Rico, yielding maximum 24-h recurrence intervals greater than 250 years for about 8% of the island.
Generation of complex human organoid models including vascular networks by incorporation of mesodermal progenitor cells
Authors: Wörsdörfer Philipp , Dalda Nahide , Kern Anna , Krüger Sarah , Wagner Nicole , Kwok Chee Keong , Henke Erik , Ergün Süleyman
Published: October 2019

Organoids derived from human pluripotent stem cells are interesting models to study mechanisms of morphogenesis and promising platforms for disease modeling and drug screening. However, they mostly remain incomplete as they lack stroma, tissue resident immune cells and in particular vasculature, which create important niches during development and disease. We propose, that the directed incorporation of mesodermal progenitor cells (MPCs) into organoids will overcome the aforementioned limitations. In order to demonstrate the feasibility of the method, we generated complex human tumor as well as neural organoids. We show that the formed blood vessels display a hierarchic organization and mural cells are assembled into the vessel wall. Moreover, we demonstrate a typical blood vessel ultrastructure including endothelial cell-cell junctions, a basement membrane as well as luminal caveolae and microvesicles. We observe a high plasticity in the endothelial network, which expands, while the organoids grow and is responsive to anti-angiogenic compounds and pro-angiogenic conditions such as hypoxia. We show that vessels within tumor organoids connect to host vessels following transplantation. Remarkably, MPCs also deliver Iba1+ cells that infiltrate the neural tissue in a microglia-like manner.
Theoretical Insights on the High Pressure Behavior of Pentazolate Anion Complex [Co(H2O)4(N5)2]·4H2O
Authors: Zhao Guozheng , Li Huili , Jia Jianfeng , Wu Haishun , Lu Ming
Published: October 2019

Periodic dispersion corrected density functional theory (DFT) calculations were carried out to examine the Hirshfeld surface, two dimensional (2D) fingerprint plots, crystal structure, molecular structure and density of state of all-nitrogen pentazolate anion complex [Co(H2O)4(N5)2]·4H2O under hydrostatic pressure from 0 to 20 GPa. The GGA/PW91-OBS method was applied in the present study. The intercontacts in [Co(H2O)4(N5)2]·4H2O were analyzed by Hirshfeld surfaces and 2D fingerprint plots. With ascending pressure, the lattice constants, compression rates, bond lengths, bond angles, and density of states change irregularly. Under 11.5, 13.0 and 15.8 GPa, covalent interaction competition is obvious between Co−N and Co−O bonds. It is possible to achieve orderly modification and regulation of the internal structure of [Co(H2O)4(N5)2]·4H2O by applied pressure. This is in accordance with the results from density of states analysis. The external compression causes the nonuniformity of electron density and the differential covalent interaction between pentazolate anion, coordinated water and atom Co. It is of great significance to interpret inter/intramolecular interaction and structural stability of [Co(H2O)4(N5)2]·4H2O and provide theoretical guidance for the design of metal complexes of all-nitrogen pentazolate anion.
Berberine decreases plasma triglyceride levels and upregulates hepatic TRIB1 in LDLR wild type mice and in LDLR deficient mice
Authors: Singh Amar Bahadur , Liu Jingwen
Published: October 2019

TRIB1 is a GWAS locus associated with plasma cholesterol and triglycerides (TG) levels. In mice, liver-specific overexpression of TRIB1 lowers plasma lipid levels. Berberine (BBR) is a natural lipid lowering drug that reduces plasma LDL-cholesterol (LDL-C), total cholesterol (TC) and TG in hyperlipidemic patients and in mice by mechanisms involving upregulation of hepatic LDL receptor (LDLR). Here, we demonstrated that BBR treatment reduced plasma LDL-C, TC and TG in LDLR wildtype (WT) mice fed a high fat and high cholesterol diet and it only lowered TG in LDLR WT mice fed a normal chow diet. In hypercholesterolemic LDLR deficient mice (Ldlr−/−), BBR treatment reduced plasma TG levels by 51% compared to the vehicle control without affecting plasma cholesterol levels. Hepatic gene expression analysis revealed that Trib1 mRNA levels were significantly elevated by BBR treatment in all three mouse models and increases of Trib1 mRNA expression were associated with reduced expression of lipogenic genes including Cebpa, Acc1 and Scd1. In vitro studies further demonstrate that BBR induces TRIB1 mRNA expression by a transcriptional mechanism via ERK signaling pathway. These new findings warrant future in vivo studies to determine the causal role of Trib1 in BBR-mediated TG lowering independent of LDLR regulation.
Gene expression profile of Aedes aegypti females in courtship and mating
Authors: Alonso Diego Peres , Campos Melina , Troca Heitor , Kunii Rafael , Tripet Frédéric , Ribolla Paulo Eduardo Martins
Published: October 2019

Aedes aegypti is the most synanthropic and anthropophilic mosquito of Culicidae. This species always cohabits with humans and is extremely opportunistic. Vector dispersal is directly related to the ability of the females on successfully finding a mate in a generally patchy urban scenario. In the present work, we investigate transcriptional changes in Ae. aegypti females during the courtship process and after mating. We observe a substantial alteration in gene expression triggered just upon contact with Ae. aegypti males, which in turn was not fully correlated to the changes triggered by the contact. After analysing shared significant differentially regulated genes between conspecific contact and insemination, the major part of the observed transcriptomic change triggered by contact is reversed after mating, indicating an intermediary situation between naive and mating conditions that we hypothesize to be crucial for mating success. Upon contact, several chemosensory related genes are repressed, especially odorant binding proteins. Most of these genes return to higher expression rates after mating. None of these genes are significantly regulated by the encounter of a different species, Aedes albopictus. The results presented here might be applied to an innovative control approach focusing on the semiochemical systems of mosquitoes in an effort to disrupt undesirable host–insect interaction to reduce the risk of pathogen transmission to humans.
11C-methionine-PET for differentiating recurrent brain tumor from radiation necrosis: radiomics approach with random forest classifier
Authors: Hotta Masatoshi , Minamimoto Ryogo , Miwa Kenta
Published: October 2019

Differentiating recurrent brain tumor from radiation necrosis is often difficult. This study aims to investigate the efficacy of 11C-methionine (MET)-PET radiomics for distinguishing recurrent brain tumor from radiation necrosis, as compared with conventional tumor-to-normal cortex (T/N) ratio evaluation. We enrolled 41 patients with metastatic brain tumor or glioma treated using radiation therapy who underwent MET-PET. The area with a standardized uptake value > 1.3 times that of the normal brain cortex was contoured. Forty-two PET features were extracted and used in a random forest classifier and the diagnostic performance was evaluated using a 10-fold cross-validation scheme. Gini index was measured to identify relevant PET parameters for classification. The reference standard was surgical histopathological analysis or more than 6 months of follow-up with MRI. Forty-four lesions were used for the analysis. Thirty-three and 11 lesions were confirmed as recurrent brain tumor and radiation necrosis, respectively. Radiomics and T/N ratio evaluation showed sensitivities of 90.1% and 60.6%, and specificities of 93.9% and 72.7% with areas under the curve of 0.98 and 0.73, respectively. Gray level co-occurrence matrix dissimilarity was the most pertinent feature for diagnosis. MET-PET radiomics yielded excellent outcome for differentiating recurrent brain tumor from radiation necrosis, which outperformed T/N ratio evaluation.
Prevalence and correlates of suicide attempt among Chinese individuals receiving methadone maintenance treatment for heroin dependence
Authors: Zhong Bao-Liang , Xie Wu-Xiang , Zhu Jun-Hong , Lu Jin , Chen Hongxian
Published: October 2019

To date, there have been very limited studies regarding the clinical epidemiology of attempted suicide in Chinese individuals with heroin-dependence. The objective of this study was to examine the prevalence and correlates of suicide attempt in Chinese individuals receiving methadone maintenance treatment for heroin dependence. Demographic, clinical, and psychosocial data of 603 methadone-maintained patients with heroin dependence were collected with a standardized self-administered questionnaire. The presence of suicide attempt and antisocial personality disorder was assessed by using a single question and the Mini-International Neuropsychiatric Interview 5.0. The one-month and lifetime prevalence rates of suicide attempt were 9.5% and 34.2%, respectively. In multivariable logistic regression, lifetime suicide attempt was significantly associated with female gender (OR = 2.81), being 20–39 years old (OR = 2.73), an education level of primary school or lower (OR = 2.07), poor economic status (OR = 3.06), injecting heroin before methadone maintenance treatment (OR = 2.92), depressive symptoms (OR = 3.46), anxiety symptoms (OR = 1.88), and antisocial personality disorder (OR = 2.85). Suicide attempt is very prevalent among Chinese individuals receiving methadone maintenance treatment for heroin dependence. Services for patients with heroin dependence in methadone maintenance treatment clinics in China should include psychosocial supports, periodic screening for suicide attempt and other suicidal behaviors and, when needed, psychiatric treatment and crisis intervention.