bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel triple combination of pharmacological chaperones improves F508del-CFTR correction
Authors: Carlile Graeme W. , Yang Qi , Matthes Elizabeth , Liao Jie , Radinovic Stevo , Miyamoto Carol , Robert Renaud , Hanrahan John W. , Thomas David Y. 
Published: July 2018

AbstractPharmacological chaperones (e.g. VX-809, lumacaftor) that bind directly to F508del-CFTR and correct its mislocalization are promising therapeutics for Cystic Fibrosis (CF). However to date, individual correctors provide only ~4% improvement in lung function measured as FEV1, suggesting that multiple drugs will be needed to achieve substantial clinical benefit. Here we examine if multiple sites for pharmacological chaperones exist and can be targeted to enhance the rescue of F508del-CFTR with the premise that additive or synergistic rescue by multiple pharmacological chaperones compared to single correctors indicates that they have different sites of action. First, we found that a combination of the pharmacological chaperones VX-809 and RDR1 provide additive correction of F508del-CFTR. Then using cellular thermal stability assays (CETSA) we demonstrated the possibility of a third pharmacologically important site using the novel pharmacological chaperone tool compound 4-methyl-N-[3-(morpholin-4-yl) quinoxalin-2-yl] benzenesulfonamide (MCG1516A). All three pharmacological chaperones appear to interact with the first nucleotide-binding domain (NBD1). The triple combination of MCG1516A, RDR1, and VX-809 restored CFTR function to >20% that of non-CF cells in well differentiated HBE cells and to much higher levels in other cell types. Thus the results suggest the presence of at least three distinct sites for pharmacological chaperones on F508del-CFTR NBD1, encouraging the development of triple corrector combinations.
Rhythmicity of Mood Symptoms in Individuals at Risk for Psychiatric Disorders
Authors: Pilz Luísa K. , Carissimi Alicia , Oliveira Melissa A. B. , Francisco Ana Paula , Fabris Raul C. , Medeiros Madeleine S. , Scop Marina , Frey Benicio N. , Adan Ana , Hidalgo Maria Paz 
Published: July 2018

AbstractDespite emerging evidence that disruption in circadian rhythms may contribute to the pathophysiology of psychiatric disorders, there is a significant knowledge gap on the rhythmicity of psychological symptoms. Here, we aimed at investigating the rhythmicity of mood symptoms in individuals at risk for psychiatric disorders. 391 Brazilian and 317 Spanish participants completed the Self-Reporting Questionnaire-20 for non-psychotic mental disorders; the Mood Rhythm Instrument was used to assess rhythmicity of mood symptoms and the Munich ChronoType Questionnaire to assess sleep patterns. We found that the rhythmicity of specific mood-related symptoms and behaviors, particularly pessimism and motivation to exercise, were associated with being at risk for psychiatric disorders, even after controlling for sleep timing, sleep deficit, and season of data collection. We also found that the peak of some mood symptoms and behaviors were different between individuals at high vs. low risk for psychiatric disorders, with specific differences between countries. These results are consistent with previous research showing that circadian misalignment is associated with higher risk for mental health conditions. These findings also suggest that lifestyle changes preventing circadian misalignment might be useful to reduce the risk of psychiatric disorders, where cultural differences must be taken into account.
Fate and transport of radioactive gypsum stack water entering the Floridan aquifer due to a sinkhole collapse
Authors: Sandhu Daljit , Singh Arvind , Duranceau Steven J. , Nam Boo Hyun , Mayo Talea , Wang Dingbao 
Published: July 2018

AbstractGroundwater aquifers are an essential source of drinking water, and must be protected against contamination. Phosphogypsum stacks originating from the processing of phosphate rock contain small amounts of radionuclides, such as 226Ra. In September 2016, a sinkhole located beneath a phosphogypsum stack collapsed under central Florida’s carbonate karst terrain, where the aquifer is mostly confined, raising concern over water quality in the regions nearby. Monitoring and modeling the transport of the contaminated plume is vital to ensure drinking water criteria are met and to improve decision making regarding treatment. To achieve this, a geochemical modeling using PHREEQC software was employed to investigate the trajectory of the plume based on hydraulic and hydrologic conditions. Adsorption was simulated as a removal mechanism that could further reduce the intensity of the plume. The aquifer’s response to the release of contaminated water from the collapsed stack was quantified by simulating a number of scenarios, including variable radionuclide leakage quantities. Results suggest that it may take between 11–17 years and between 5.2 to 8.3 km from the sinkhole leak to reduce radionuclide concentrations to previous levels. Coupling the adsorption effect by minerals in Floridan aquifer (e.g. ferrihydrite, carbonate) can reduce radionuclide migration time to 9–16 years and distances between 4.3 to 7.8 km from the sinkhole leak. It can also reduce the distance needed to lower radionuclide concentrations, though not significantly. Additionally, due to the complexities of soil chemistry, the importance of groundwater remediation is emphasized.
Regulation of cytochrome c oxidase activity by modulation of the catalytic site
Authors: Schäfer Jacob , Dawitz Hannah , Ott Martin , Ädelroth Pia , Brzezinski Peter 
Published: July 2018

AbstractThe respiratory supercomplex factor 1 (Rcf 1) in Saccharomyces cerevisiae binds to intact cytochrome c oxidase (CytcO) and has also been suggested to be an assembly factor of the enzyme. Here, we isolated CytcO from rcf1Δ mitochondria using affinity chromatography and investigated reduction, inter-heme electron transfer and ligand binding to heme a3. The data show that removal of Rcf1 yields two CytcO sub-populations. One of these sub-populations exhibits the same functional behavior as CytcO isolated from the wild-type strain, which indicates that intact CytcO is assembled also without Rcf1. In the other sub-population, which was shown previously to display decreased activity and accelerated ligand-binding kinetics, the midpoint potential of the catalytic site was lowered. The lower midpoint potential allowed us to selectively reduce one of the two sub-populations of the rcf1Δ CytcO, which made it possible to investigate the functional behavior of the two CytcO forms separately. We speculate that these functional alterations reflect a mechanism that regulates O2 binding and trapping in CytcO, thereby altering energy conservation by the enzyme.
Deep-ultraviolet Raman scattering spectroscopy of monolayer WS2
Authors: Liu Hsiang-Lin , Yang Teng , Tatsumi Yuki , Zhang Ye , Dong Baojuan , Guo Huaihong , Zhang Zhidong , Kumamoto Yasuaki , Li Ming-Yang , Li Lain-Jong , Saito Riichiro , Kawata Satoshi 
Published: July 2018

AbstractRaman scattering measurements of monolayer WS2 are reported as a function of the laser excitation energies from the near-infrared (1.58 eV) to the deep-ultraviolet (4.82 eV). In particular, we observed several strong Raman peaks in the range of 700∼850 cm−1 with the deep-ultraviolet laser lights (4.66 eV and 4.82 eV). Using the first-principles calculations, these peaks and other weak peaks were appropriately assigned by the double resonance Raman scattering spectra of phonons around the M and K points in the hexagonal Brillouin zone. The relative intensity of the first-order $${{\boldsymbol{E}}}_{{\bf{2}}{\boldsymbol{g}}}^{{\bf{1}}}$$

E

2
g

1

to A1g peak changes dramatically with the 1.58 eV and 2.33 eV laser excitations, while the comparable relative intensity was observed for other laser energies. The disappearance of the $${{\boldsymbol{E}}}_{{\bf{2}}{\boldsymbol{g}}}^{{\bf{1}}}$$

E

2
g

1

peak with the 1.58 eV laser light comes from the fact that valley polarization of the laser light surpasses the $${{\boldsymbol{E}}}_{{\bf{2}}{\boldsymbol{g}}}^{{\bf{1}}}$$

E

2
g

1

mode since the $${{\boldsymbol{E}}}_{{\bf{2}}{\boldsymbol{g}}}^{{\bf{1}}}$$

E

2
g

1

mode is the helicity-exchange Raman mode. On the other hand, the disappearance of the A1g peak with the 2.33 eV laser light might be due to the strain effect on the electron-phonon matrix element.
Preparation, physicochemical characterization and antimicrobial activities of novel two phenolic chitosan Schiff base derivatives
Authors: Hassan Mohamed A. , Omer Ahmed M. , Abbas Eman , Baset Walid M. A. , Tamer Tamer M. 
Published: July 2018

AbstractThis study intends to develop novel two antimicrobial phenolic chitosan Schiff bases (I) and (II) via coupling of chitosan with Indole-3-carboxaldehyde and 4-dimethylaminobenzaldehyde, respectively, for boosting the antimicrobial activity of native chitosan. The alterations in the chemical structure and morphology of the Schiff bases were verified using FT-IR, electronic spectrum analysis, and SEM, whereas the thermal properties were investigated by TGA and DSC instruments. The results obtained from the potentiometric analysis referred that the degrees of substitution were 1.15 and 12.05% for Schiff bases (I) and (II), respectively. The antimicrobial activities of Schiff base (I) were significantly augmented more than Schiff base (II) and chitosan. Minimum inhibitory concentration (MIC) of Schiff base (I) was perceived at 50 µg/ml against tested microorganisms except forB.cereusandC.albicans. The highest concentration of Schiff base (I) could inhibit the growth of Gram-positive up to 99%. However, Schiff base (II) recorded the maximum inhibition rate versus Gram-positive approximately 82%. The cytotoxicity of the developed materials was estimated by MTT assay that substantiated their safety to fibroblast cells. The findings emphasized that the developed Schiff bases might be implemented as antimicrobial contenders to pure chitosan for treatments of wound infections.
A Gustatory Receptor Used for Rapid Detection of Tyrophagus putrescentiae in Fungi Hosts
Authors: Qu Shao-Xuan , Wang Xiao-Fei , Li Hui-Ping , Luo Xin , Ma Lin 
Published: July 2018

AbstractThe storage mite,Tyrophagus putrescentiae, found worldwide in many habitats, is an important pest of edible fungi in China. Storage mites are tiny and difficult to observe, especially when they occur in fungi composts. In this study, one gustatory receptor protein (TputGR1) was identified from the transcriptome ofT. putrescentiae. Phylogenetic analysis of GRs families from 10 arthropod species revealed that TputGR1 had high homology with the SccaGR1 of Sarcoptes scabiei and TurtGR1-2 ofTetranychus urticae, but low homology with other insect species,Drosophila melanogaster,Anopheles gambiae,Bombyx mori,Aedes aegypti,Culex quinquefasciatus, andPediculus humanus. We developed a detection system for the mite on fungi hosts using the GR protein and the loop-mediated isothermal amplification (LAMP). This procedure was rapid (60 min from sampling to result) and had high sensitivity (0.5 ng/mL). LAMP provided rapid and reliable detection ofT. putrescentiae. It has good specificity for single samples and for large-scale surveys.
In vivo neutralization of the protagonist role of macrophages during the chronic inflammatory stage of Huntington’s disease
Authors: Pido-Lopez Jeffrey , Andre Ralph , Benjamin Agnesska C. , Ali Nadira , Farag Sahar , Tabrizi Sarah J. , Bates Gillian P. 
Published: July 2018

AbstractNeurodegenerative diseases, characterised by the progressive and selective neuronal death in the central nervous system, are frequently accompanied by an activated immune system. In Huntington’s disease (HD), clinical and animal studies show evidence of immune activity, along with hyper-reactive monocyte/macrophage responses, while application of immunosuppressive regimens have imparted beneficial effects to HD mice. These findings suggest a contributory role of the immune system in HD pathology, with immune-based interventions offering a potential therapeutic strategy. Herein, we show that peripheral and CNS immune system activity increased with disease progression in HD mouse models and defined the phenotype of the immune response. Additionally, the depletion of monocytes and macrophagesin vivo, via clodronate liposome treatment, revealed a major contributory role of these innate immune cells to the chronic inflammatory milieu observed during the course of the disease. This suggests that peripheral immunomodulatory strategies targeting monocytes and macrophages could be relevant for HD.
In vivo targeted single-nucleotide editing in zebrafish
Authors: Tanaka Shingo , Yoshioka Shin , Nishida Keiji , Hosokawa Hiroshi , Kakizuka Akira , Maegawa Shingo 
Published: July 2018

AbstractTo date, several genome editing technologies have been developed and are widely utilized in many fields of biology. Most of these technologies, if not all, use nucleases to create DNA double-strand breaks (DSBs), raising the potential risk of cell death and/or oncogenic transformation. The risks hinder their therapeutic applications in humans. Here, we show that in vivo targeted single-nucleotide editing in zebrafish, a vertebrate model organism, can be successfully accomplished with the Target-AID system, which involves deamination of a targeted cytidine to create a nucleotide substitution from cytosine to thymine after replication. Application of the system to two zebrafish genes, chordin (chd) and one-eyed pinhead (oep), successfully introduced premature stop codons (TAG or TAA) in the targeted genomic loci. The modifications were heritable and faithfully produced phenocopies of well-known homozygous mutants of each gene. These results demonstrate for the first time that the Target-AID system can create heritable nucleotide substitutions in vivo in a programmable manner, in vertebrates, namely zebrafish.
Protective role of vitamin B6 (PLP) against DNA damage in Drosophila models of type 2 diabetes
Authors: Merigliano Chiara , Mascolo Elisa , La Torre Mattia , Saggio Isabella , Vernì Fiammetta 
Published: July 2018

AbstractGrowing evidence shows that improper intake of vitamin B6 increases cancer risk and several studies indicate that diabetic patients have a higher risk of developing tumors. We previously demonstrated that in Drosophila the deficiency of Pyridoxal 5′ phosphate (PLP), the active form of vitamin B6, causes chromosome aberrations (CABs), one of cancer prerequisites, and increases hemolymph glucose content. Starting from these data we asked if it was possible to provide a link between the aforementioned studies. Thus, we tested the effect of low PLP levels on DNA integrity in diabetic cells. To this aim we generated two Drosophila models of type 2 diabetes, the first by impairing insulin signaling and the second by rearing flies in high sugar diet. We showed that glucose treatment induced CABs in diabetic individuals but not in controls. More interestingly, PLP deficiency caused high frequencies of CABs in both diabetic models demonstrating that hyperglycemia, combined to reduced PLP level, impairs DNA integrity. PLP-depleted diabetic cells accumulated Advanced Glycation End products (AGEs) that largely contribute to CABs as α-lipoic acid, an AGE inhibitor, rescued not only AGEs but also CABs. These data, extrapolated to humans, indicate that low PLP levels, impacting on DNA integrity, may be considered one of the possible links between diabetes and cancer.
Fouling Development in A/O-MBR under Low Organic Loading Condition and Identification of Key Bacteria for Biofilm Formations
Authors: Takimoto Yuya , Hatamoto Masashi , Ishida Takaya , Watari Takahiro , Yamaguchi Takashi 
Published: July 2018

AbstractMembrane fouling in membrane bioreactors (MBR) remains a major issue and knowledge of microbes associated with biofilm formation might facilitate the control of this phenomenon, Thus, an anoxic/oxic membrane bioreactor (A/O-MBR) was operated under an extremely low organic loading rate (0.002 kg-COD·m−3·day−1) to induce membrane fouling and the major biofilm-forming bacteria were identified. After operation under extremely low organic loading condition, the reactor showed accumulation of total nitrogen and phosphorus along with biofilm development on the membrane surface. Thus, membrane fouling induced by microbial cell lysis was considered to have occurred. Although no major changes were observed in the microbial community structure of the activated sludge in the MBR before and after membrane fouling, uncultured bacteria were specifically increased in the biofilm. Therefore, bacteria belonging to candidate phyla including TM6, OD1 and Gammaproteobacteria could be important biofilm-forming bacteria.
Scalable Generation of Multi-mode NOON States for Quantum Multiple-phase Estimation
Authors: Zhang Lu , Chan Kam Wai Clifford 
Published: July 2018

AbstractMulti-mode NOON states have been attracting increasing attentions recently for their abilities of obtaining supersensitive and superresolved measurements for simultaneous multiple-phase estimation. In this paper, four different methods of generating multi-mode NOON states with a high photon number were proposed. The first method is a linear optical approach that makes use of the Fock state filtration to reduce lower-order Fock state terms from the coherent state inputs, which are jointly combined to produce a multi-mode NOON state with the triggering of multi-fold single-photon coincidence detections (SPCD) and appropriate postselection. The other three methods (two linear and one nonlinear) use N-photon Fock states as the inputs and require SPCD triggering only. All of the four methods can theoretically create a multi-mode NOON state with an arbitrary photon number. Comparisons among these four methods were made with respect to their feasibility and efficiency. The first method is experimentally most feasible since it takes considerably fewer photonic operations and, more importantly, requires neither the use of high-N Fock states nor high-degree of nonlinearity.
The coffee bean transcriptome explains the accumulation of the major bean components through ripening
Authors: Cheng Bing , Furtado Agnelo , Henry Robert J. 
Published: July 2018

AbstractThe composition of the maturing coffee bean determines the processing performance and ultimate quality of the coffee produced from the bean. Analysis of differences in gene expression during bean maturation may explain the basis of genetic and environmental variation in coffee quality. The transcriptome of the coffee bean was analyzed at three stages of development, immature (green), intermediate (yellow) and mature (red). A total of more than 120 million 150 bp paired-end reads were collected by sequencing of transcripts of triplicate samples at each developmental stage. A greater number of transcripts were expressed at the yellow stage. As the beans matured the types of highly expressed transcripts changed from transcripts predominantly associated with galactomannan, triacylglycerol (TAG), TAG lipase, 11 S and 7S-like storage protein and Fasciclin-like arabinogalactan protein 17 (FLA17) in green beans to transcripts related to FLA1 at the yellow stage and TAG storage lipase SDP1, and SDP1-like in red beans. This study provides a genomic resource that can be used to investigate the impact of environment and genotype on the bean transcriptome and develop coffee varieties and production systems that are better adapted to deliver quality coffee despite climate variations.
Prognostic role of carotid intima-media thickness in off-pump coronary artery bypass surgery
Authors: Ham Sung-Yeon , Song Jong-Wook , Shim Jae-Kwang , Soh Sarah , Kim Hee-Jung , Kwak Young-Lan 
Published: July 2018

AbstractCarotid intima-media thickness (IMT) is a well-known predictor of adverse outcomes in the ischemic heart disease patients; however, evidence is lacking in patients undergoing off-pump coronary artery bypass surgery (OPCAB). Data from 407 patients who underwent OPCAB between April 2013 and August 2016 were retrospectively reviewed. A composite of cardiovascular morbidity endpoints was defined as the presence of stroke, acute myocardial infarction, new cardiac arrhythmia (newly developed atrial fibrillation, atrial flutter, or atrioventricular block), cardiovascular death, or cerebrovascular death within 30 days after surgery. Increased carotid IMT was defined as ≥0.9 mm on one or both sides. The incidence of a composite of cardiovascular morbidity endpoints was 24.0% in the normal IMT group (n = 221) and 34.4% in the increased IMT group (n = 186) (p = 0.021). Multivariable analysis revealed increased IMT (odds ratio 1.719, 95% confidence interval 1.108 to 2.666, p = 0.016) and preoperative renal replacement therapy (odds ratio 4.264, 95% confidence interval 1.679 to 10.829, p = 0.002) as independent predictors of a composite of cardiovascular morbidity endpoints. In patients undergoing OPCAB, preoperative assessment of carotid IMT may help predicting the development of a postoperative composite of cardiovascular morbidity endpoints.
Binding modes of CYP106A2 redox partners determine differences in progesterone hydroxylation product patterns
Authors: Sagadin Tanja , Riehm Jan L. , Milhim Mohammed , Hutter Michael C. , Bernhardt Rita 
Published: July 2018

AbstractNatural redox partners of bacterial cytochrome P450s (P450s) are mostly unknown. Therefore, substrate conversions are performed with heterologous redox partners; in the case of CYP106A2 from Bacillus megaterium ATCC 13368, bovine adrenodoxin (Adx) and adrenodoxin reductase (AdR). Our aim was to optimize the redox system for CYP106A2 for improved product formation by testing 11 different combinations of redox partners. We found that electron transfer protein 1(516–618) showed the highest yield of the main product, 15β-hydroxyprogesterone, and, furthermore, produced a reduced amount of unwanted polyhydroxylated side products. Molecular protein–protein docking indicated that this is caused by subtle structural changes leading to alternative binding modes of both redox enzymes. Stopped-flow measurements analyzing the CYP106A2 reduction and showing substantial differences in the apparent rate constants supported this conclusion. The study provides for the first time to our knowledge rational explanations for differences in product patterns of a cytochrome P450 caused by difference in the binding mode of the redox partners.