bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tau interactome analyses in CRISPR-Cas9 engineered neuronal cells reveal ATPase-dependent binding of wild-type but not P301L Tau to non-muscle myosins
Authors: Wang Xinzhu , Williams Declan , Müller Iris , Lemieux Mackenzie , Dukart Ramona , Maia Isabella B. L. , Wang Hansen , Woerman Amanda L. , Schmitt-Ulms Gerold 
Published: November 2019

AbstractProtein interactions of Tau are of interest in efforts to decipher pathogenesis in Alzheimer’s disease, a subset of frontotemporal dementias, and other tauopathies. We CRISPR-Cas9 edited two human cell lines to generate broadly adaptable models for neurodegeneration research. We applied the system to inducibly express balanced levels of 3-repeat and 4-repeat wild-type or P301L mutant Tau. Following 12-h induction, quantitative mass spectrometry revealed the Parkinson’s disease-causing protein DJ-1 and non-muscle myosins as Tau interactors whose binding to Tau was profoundly influenced by the presence or absence of the P301L mutation. The presence of wild-type Tau stabilized non-muscle myosins at higher steady-state levels. Strikingly, in human differentiated co-cultures of neuronal and glial cells, the preferential interaction of non-muscle myosins to wild-type Tau depended on myosin ATPase activity. Consistently, transgenic P301L Tau mice exhibited reduced phosphorylation of regulatory myosin light chains known to activate this ATPase. The direct link of Tau to non-muscle myosins corroborates independently proposed roles of Tau in maintaining dendritic spines and mitochondrial fission biology, two subcellular niches affected early in tauopathies.
Rapid deacetylation of yeast Hsp70 mediates the cellular response to heat stress
Authors: Xu Linan , Nitika  , Hasin Naushaba , Cuskelly Daragh D. , Wolfgeher Donald , Doyle Sean , Moynagh Paul , Perrett Sarah , Jones Gary W. , Truman Andrew W. 
Published: November 2019

AbstractHsp70 is a highly conserved molecular chaperone critical for the folding of new and denatured proteins. While traditional models state that cells respond to stress by upregulating inducible HSPs, this response is relatively slow and is limited by transcriptional and translational machinery. Recent studies have identified a number of post-translational modifications (PTMs) on Hsp70 that act to fine-tune its function. We utilized mass spectrometry to determine whether yeast Hsp70 (Ssa1) is differentially modified upon heat shock. We uncovered four lysine residues on Ssa1, K86, K185, K354 and K562 that are deacetylated in response to heat shock. Mutation of these sites cause a substantial remodeling of the Hsp70 interaction network of co-chaperone partners and client proteins while preserving essential chaperone function. Acetylation/deacetylation at these residues alter expression of other heat-shock induced chaperones as well as directly influencing Hsf1 activity. Taken together our data suggest that cells may have the ability to respond to heat stress quickly though Hsp70 deacetylation, followed by a slower, more traditional transcriptional response.
Preferential Paths of Air-water Two-phase Flow in Porous Structures with Special Consideration of Channel Thickness Effects
Authors: Liu Jinhui , Ju Yang , Zhang Yingqi , Gong Wenbo 
Published: November 2019

AbstractAccurate understanding and predicting the flow paths of immiscible two-phase flow in rocky porous structures are of critical importance for the evaluation of oil or gas recovery and prediction of rock slides caused by gas-liquid flow. A 2D phase field model was established for compressible air-water two-phase flow in heterogenous porous structures. The dynamic characteristics of air-water two-phase interface and preferential paths in porous structures were simulated. The factors affecting the path selection of two-phase flow in porous structures were analyzed. Transparent physical models of complex porous structures were prepared using 3D printing technology. Tracer dye was used to visually observe the flow characteristics and path selection in air-water two-phase displacement experiments. The experimental observations agree with the numerical results used to validate the accuracy of phase field model. The effects of channel thickness on the air-water two-phase flow behavior and paths in porous structures were also analyzed. The results indicate that thick channels can induce secondary air flow paths due to the increase in flow resistance; consequently, the flow distribution is different from that in narrow channels. This study provides a new reference for quantitatively analyzing multi-phase flow and predicting the preferential paths of immiscible fluids in porous structures.
Developmental transcriptomes of the sea star, Patiria miniata, illuminate how gene expression changes with evolutionary distance
Authors: Gildor Tsvia , Cary Gregory A. , Lalzar Maya , Hinman Veronica F. , Ben-Tabou de-Leon Smadar 
Published: November 2019

AbstractUnderstanding how changes in developmental gene expression alter morphogenesis is a fundamental problem in development and evolution. A promising approach to address this problem is to compare the developmental transcriptomes between related species. The echinoderm phylum consists of several model species that have significantly contributed to the understanding of gene regulation and evolution. Particularly, the regulatory networks of the sea star, Patiria miniata (P. miniata), have been extensively studied, however developmental transcriptomes for this species were lacking. Here we generated developmental transcriptomes of P. miniata and compared these with those of two sea urchins species. We demonstrate that the conservation of gene expression depends on gene function, cell type and evolutionary distance. With increasing evolutionary distance the interspecies correlations in gene expression decreases. The reduction is more severe in the correlations between morphologically equivalent stages (diagonal elements) than in the correlation between morphologically distinct stages (off-diagonal elements). This could reflect a decrease in the morphological constraints compared to other constraints that shape gene expression at large evolutionary divergence. Within this trend, the interspecies correlations of developmental control genes maintain their diagonality at large evolutionary distance, and peak at the onset of gastrulation, supporting the hourglass model of phylotypic stage conservation.
An assessment of energy storage options for large-scale PV-RO desalination in the extended Mediterranean region
Authors: Ganora D. , Dorati C. , Huld T. A. , Udias A. , Pistocchi A. 
Published: November 2019

AbstractSeawater desalination is already a largely adopted option to cope with the scarcity of natural water resources, but the increasing concerns about water availability in the future make it even more attractive. Because desalination is a highly energy-demanding process, its coupling with renewable energy sources is an essential step for the sustainable production of desalinated water at large scales. In this work we analyze the potential to deploy large-scale seawater desalination using reverse osmosis (RO) under the hypothesis that all the required energy is provided by photovoltaic (PV) production. A simulation over the extended Mediterranean area shows that securing desalinated water for up to about 200 million people in the region is technically possible using PV only, and the benefits of energy storage in batteries and/or water reservoirs are usually higher than its costs. This suggests that water management policies could consider desalination more broadly and encourage PV-based RO, as a possible win-win and cost-effective strategy to improve water and energy resources security.
Luminescence reveals variations in local structural order of calcium carbonate polymorphs formed by different mechanisms
Authors: Toffolo Michael B. , Ricci Giulia , Caneve Luisa , Kaplan-Ashiri Ifat 
Published: November 2019

AbstractIn nature, calcium carbonate (CaCO3) in the form of calcite and aragonite nucleates through different pathways including geogenic and biogenic processes. It may also occur as pyrogenic lime plaster and laboratory-precipitated crystals. All of these formation processes are conducive to different degrees of local structural order in CaCO3 crystals, with the pyrogenic and precipitated forms being the least ordered. These variations affect the manner in which crystals interact with electromagnetic radiation, and thus formation processes may be tracked using methods such as X-ray diffraction and infrared spectroscopy. Here we show that defects in the crystal structure of CaCO3 may be detected by looking at the luminescence of crystals. Using cathodoluminescence by scanning electron microscopy (SEM-CL) and laser-induced fluorescence (LIF), it is possible to discern different polymorphs and their mechanism of formation. We were thus able to determine that pyrogenic calcite and aragonite exhibit blue luminescence due to the incorporation of distortions in the crystal lattice caused by heat and rapid precipitation, in agreement with infrared spectroscopy assessments of local structural order. These results provide the first detailed reference database of SEM-CL and LIF spectra of CaCO3 standards, and find application in the characterization of optical, archaeological and construction materials.
Measuring Electric Charge and Molecular Coverage on Electrode Surface from Transient Induced Molecular Electronic Signal (TIMES)
Authors: Chen Ping-Wei , Tseng Chi-Yang , Shi Fumin , Bi Bo , Lo Yu-Hwa 
Published: November 2019

AbstractCharge density and molecular coverage on the surface of electrode play major roles in the science and technology of surface chemistry and biochemical sensing. However, there has been no easy and direct method to characterize these quantities. By extending the method of Transient Induced Molecular Electronic Signal (TIMES) which we have used to measure molecular interactions, we are able to quantify the amount of charge in the double layers at the solution/electrode interface for different buffer strengths, buffer types, and pH values. Most uniquely, such capabilities can be applied to study surface coverage of immobilized molecules. As an example, we have measured the surface coverage for thiol-modified single-strand deoxyribonucleic acid (ssDNA) as anchored probe and 6-Mercapto-1-hexanol (MCH) as blocking agent on the platinum surface. Through these experiments, we demonstrate that TIMES offers a simple and accurate method to quantify surface charge and coverage of molecules on a metal surface, as an enabling tool for studies of surface properties and surface functionalization for biochemical sensing and reactions.
Identification of HLA-A*02:06:01 as the primary disease susceptibility HLA allele in cold medicine-related Stevens-Johnson syndrome with severe ocular complications by high-resolution NGS-based HLA typing
Authors: Nakatani Ken , Ueta Mayumi , Khor Seik-Soon , Hitomi Yuki , Okudaira Yuko , Masuya Anri , Wada Yuki , Sotozono Chie , Kinoshita Shigeru , Inoko Hidetoshi , Tokunaga Katsushi 
Published: November 2019

AbstractStevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening acute inflammatory vesiculobullous reactions of the skin and mucous membranes. These severe cutaneous drug reactions are known to be caused by inciting drugs and infectious agents. Previously, we have reported the association of HLA-A*02:06 and HLA-B*44:03 with cold medicine (CM)-related SJS/TEN with severe ocular complications (SOCs) in the Japanese population. However, the conventional HLA typing method (PCR-SSOP) sometimes has ambiguity in the final HLA allele determination. In this study, we performed HLA-disease association studies in CM-SJS/TEN with SOCs at 3- or 4-field level. 120 CM-SJS/TEN patients with SOCs and 817 Japanese healthy controls are HLA genotyped using the high-resolution next-generation sequencing (NGS)-based HLA typing of HLA class I genes, including HLA-A, HLA-B, and HLA-C. Among the alleles of HLA class I genes, HLA-A*02:06:01 was strongly associated with susceptibility to CM-SJS/TEN (p = 1.15 × 10−18, odds ratio = 5.46). Four other alleles (HLA-A*24:02:01, HLA-B*52:01:01, HLA-B*46:01:01, and HLA-C*12:02:02) also demonstrated significant associations. HLA haplotype analyses indicated that HLA-A*02:06:01 is primarily associated with susceptibility to CM-SJS/TEN with SOCs. Notably, there were no specific disease-causing rare variants among the high-risk HLA alleles. This study highlights the importance of higher resolution HLA typing in the study of disease susceptibility, which may help to elucidate the pathogenesis of CM-SJS/TEN with SOCs.
Gut Microbiota-Mediated Drug-Drug Interaction between Amoxicillin and Aspirin
Authors: Zhang Juanhong , Sun Yuemei , Wang Rong , Zhang Junmin 
Published: November 2019

AbstractThe effects of antibiotics on the intestinal flora can create potential drug-drug interactions. The combination of amoxicillin and aspirin is high and there is a high probability of interaction. We used 16S rRNA, incubation experiments and liquid chromatography-tandem mass spectrometry to analyze rat biological samples to characterize the effect of amoxicillin on the pharmacokinetics of aspirin metabolites. We first discovered that amoxicillin reduced the species and number of intestinal flora in rats, such as reducing the abundance of Helicobacter pylori and Prevotella_copri. After 12, 24, and 36 hours of incubation, the remaining amount of aspirin in the aspirin and amoxicillin treatment groups decreased, and salicylic acid production increased, suggesting that aspirin is metabolized by the intestinal flora, and the main metabolite is salicylic acid. As the incubation time prolonged, the reduction of aspirin and the production of salicylic acid in the amoxicillin treatment group were slower. It is indicated that the metabolic activity of aspirin through the intestinal flora is slowed down after administration of amoxicillin. The pharmacokinetic experiments showed that after administration of amoxicillin, the area under the salicylic acid curve increased by 91.38%, the peak concentration increased by 60.43%, and the clearance rate decreased by 43.55%.The results demonstrated that amoxicillin affected the pharmacokinetics of aspirin active metabolite salicylic acid by slowing down the metabolic activity of intestinal flora on aspirin. The interaction between amoxicillin and aspirin mediated by the intestinal flora may affect the efficacy of aspirin and cause more significant adverse effects.
Cumulative impact of anti-sea lice treatment (azamethiphos) on health status of Rainbow trout (Oncorhynchus mykiss, Walbaum 1792) in aquaculture
Authors: Barisic Josip , Cannon Stuart , Quinn Brian 
Published: November 2019

AbstractDespite its widespread use in aquaculture, the impact of chemical anti-sea lice treatment on salmonids following application in a commercial farm has not been previously reported. This work reports the cumulative effect of three consecutive anti-sea lice treatments using azamethiphos on the health status of aquaculture reared rainbow trout through the investigation of clinical chemistry, histopathology and proteome expression. The serum biomarkers showed decreasing trends in total protein, albumin and potassium concentrations and an average increase of total bilirubin and phosphate concentration towards the end of the treatment period. Principal component analysis clearly distinguished correlated pairs of biomarkers and also demonstrates a shift from acute to chronic effects as treatment progresses. Proteomic analysis confirmed alterations of proteins involved in clot formation, immune reaction and free heme binding. Tissue damage after the series of delousing treatments, exhibited increased deposits of hemosiderin. Results from this study suggest an impact of azamethiphos on trout health through intravascular haemolysis and consequently from pathophysiologic process of haemoglobin metabolism and its products, causing chronic kidney injury from iron deposits. This is the first report to demonstrate in fish the impact of active iron accumulation in different organs from physiological processes that can seriously impair normal function.
Impact of BMI on peak growth hormone responses to provocative tests and therapeutic outcome in children with growth hormone deficiency
Authors: Yang Aram , Cho Sung Yoon , Kwak Min Jung , Kim Su Jin , Park Sung Won , Jin Dong-Kyu , Lee Ji-Eun 
Published: November 2019

AbstractThis study investigated the relationship between peak stimulated growth hormone (GH) and body mass index (BMI), as well as the impact of BMI on therapeutic response in patients with GH deficiency (GHD). A total of 460 patients were enrolled in the study. The patients were divided into four groups as per the etiology and peak GH values: idiopathic (n = 439), organic (n = 21), complete (n = 114), and partial (n = 325) GHD groups. Subsequently, they were classified as normal, overweight, or obese based on their BMI. There was no difference in BMI between complete and partial GHD. A significant negative relationship between peak GH and BMI were found. Moreover, obese GHD children had a considerably better therapeutic response in height increase and BMI decrease during 2 years of GH treatment compared to non-obese children with GHD. There was no difference between peak GH and type of GH stimulation test (GHST), except the clonidine test, which showed a much lower peak GH in obese GHD children. In conclusion, BMI had a negative impact on peak GH response, and therapeutic outcome was more favorable in the obese group. Despite no difference in GH response by type of GHST, the degree of obesity differentially affected the results.
Synergistic activity of Hsp90 inhibitors and anticancer agents in pancreatic cancer cell cultures
Authors: Daunys Simonas , Matulis Daumantas , Petrikaitė Vilma 
Published: November 2019

AbstractHeat shock protein 90 (Hsp90) is a widely investigated target for anticancer therapy. The experimental Hsp90 inhibitors ICPD47 and ICPD62 demonstrated anticancer activity against colorectal, osteosarcoma and cervical cancer cell lines. However, their anticancer activity has not been investigated against pancreatic cancer cell lines yet, and there are no data about synergistic activity of these compounds in combination with clinically used anticancer agents. Pancreatic cancer cell lines, MIA PaCa-2 and PANC-1 were exposed to ICPD47 and ICPD62 alone and in combinations with antimetabolites gemcitabine (GEM), 5-fluorouracil (5-FU) and topoisomerase inhibitor doxorubicin (DOX). Effects on cell viability were determined by MTT assay. The synergistic activity was evaluated using Chou-Talalay method. Also, 3D cell cultures were formed using 3D Bioprinting method and the activity of each compound and their combinations was examined by measuring the size change of spheroids. The strongest synergistic activities were determined in combinations using all ratios of ICPD47 with GEM and ICPD62 with GEM in MIA PaCa-2 cell line (combination index <0.5). The combinations of ICPD47 with 5-FU and ICPD47 with GEM in a ratio of 1:5 showed the greatest effect on tumour spheroid growth in both cell lines. The ICPD47 in combination with mild hyperthermia showed significant results, where the EC50 value in PANC-1 cell line dropped from 4.04 ± 0.046 to 1.68 ± 0.004 µM. The ICPD47 and ICPD62 under the same conditions could act synergistically with GEM, 5-FU and DOX and is worth of further investigations, and studies of synergistic effect is a promising path for more efficient anticancer therapies.
Correlations between the metabolic profile and 18F-FDG-Positron Emission Tomography-Computed Tomography parameters reveal the complexity of the metabolic reprogramming within lung cancer patients
Authors: Vanhove Karolien , Thomeer Michiel , Derveaux Elien , Shkedy Ziv , Owokotomo Olajumoke Evangelina , Adriaensens Peter , Mesotten Liesbet 
Published: November 2019

AbstractSeveral studies have demonstrated that the metabolite composition of plasma may indicate the presence of lung cancer. The metabolism of cancer is characterized by an enhanced glucose uptake and glycolysis which is exploited by 18F-FDG positron emission tomography (PET) in the work-up and management of cancer. This study aims to explore relationships between 1H-NMR spectroscopy derived plasma metabolite concentrations and the uptake of labeled glucose (18F-FDG) in lung cancer tissue. PET parameters of interest are standard maximal uptake values (SUVmax), total body metabolic active tumor volumes (MATVWTB) and total body total lesion glycolysis (TLGWTB) values. Patients with high values of these parameters have higher plasma concentrations of N-acetylated glycoproteins which suggest an upregulation of the hexosamines biosynthesis. High MATVWTB and TLGWTB values are associated with higher concentrations of glucose, glycerol, N-acetylated glycoproteins, threonine, aspartate and valine and lower levels of sphingomyelins and phosphatidylcholines appearing at the surface of lipoproteins. These higher concentrations of glucose and non-carbohydrate glucose precursors such as amino acids and glycerol suggests involvement of the gluconeogenesis pathway. The lower plasma concentration of those phospholipids points to a higher need for membrane synthesis. Our results indicate that the metabolic reprogramming in cancer is more complex than the initially described Warburg effect.
Three-dimensional descriptive study of the pterygomaxillary region related to pterygoid implants: A retrospective study
Authors: Salinas-Goodier Carmen , Rojo Rosa , Murillo-González Jorge , Prados-Frutos Juan Carlos 
Published: November 2019

AbstractThe objective of this study was to analyze three-dimensionally the morphological characteristics of the pterygomaxillary region related to pterygoid implants. Volume, height, width and bone density were studied in relation to age, sex and dental status. This retrospective observational study analyzed the CBCT of 52 hemi-maxillas three-dimensionally (females n = 28, males n = 24; dentate = 31, edentulous = 21). Patients were exposed between September 2009 and October 2014, and data collection was performed between November 2015 and May 2016. Bone density, volume, height and width were analyzed in various locations of the maxilla and pterygoid process, and the variables age, gender and dental status patients were compared. The results show that the mean width of the pterygomaxillary joint was 7.5 mm (SD 1.00 mm), mean height was 12.51 mm (SD 1,82 mm) and mean volume was 321.7 mm3 (SD 142.02 mm3). Statistically significant differences between dentate and edentulous patients were found, showing a higher osseous density in dentate patients in the pterygoid process (758.2, SD 106.8, 95% CI 729.2 to 787.3 GSD - Gray Scale Density - compared to 689.9, SD 107.3, 95% CI 660.8 to 719.1 GSD; P = 0.022). In the maxilla, density was statistically significant lower in female subjects (571.0, SD 74.1, 95% CI 594.9 to 645.4 GSD) than in male subjects (620.2, SD 93.8, 95% CI 594.4 to 645.4 GSD, P = 0.047). In conclusion, due to the significant variation in the morphological characteristics of the pterygomaxillary region among subjects, personalized pre-surgical radiological assessment should always be performed. Gender, age and dental status are critical factors as they significantly affect bone density in this region.