bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery of Mcl-1 inhibitors from integrated high throughput and virtual screening
Authors: Mady Ahmed S. A. , Liao Chenzhong , Bajwa Naval , Kump Karson J. , Abulwerdi Fardokht A. , Lev Katherine L. , Miao Lei , Grigsby Sierrah M. , Perdih Andrej , Stuckey Jeanne A. , Du Yuhong , Fu Haian , Nikolovska-Coleska Zaneta 
Published: June 2018

AbstractProtein-protein interactions (PPIs) represent important and promising therapeutic targets that are associated with the regulation of various molecular pathways, particularly in cancer. Although they were once considered “undruggable,” the recent advances in screening strategies, structure-based design, and elucidating the nature of hot spots on PPI interfaces, have led to the discovery and development of successful small-molecule inhibitors. In this report, we are describing an integrated high-throughput and computational screening approach to enable the discovery of small-molecule PPI inhibitors of the anti-apoptotic protein, Mcl-1. Applying this strategy, followed by biochemical, biophysical, and biological characterization, nineteen new chemical scaffolds were discovered and validated as Mcl-1 inhibitors. A novel series of Mcl-1 inhibitors was designed and synthesized based on the identified difuryl-triazine core scaffold and structure-activity studies were undertaken to improve the binding affinity to Mcl-1. Compounds with improved in vitro binding potency demonstrated on-target activity in cell-based studies. The obtained results demonstrate that structure-based analysis complements the experimental high-throughput screening in identifying novel PPI inhibitor scaffolds and guides follow-up medicinal chemistry efforts. Furthermore, our work provides an example that can be applied to the analysis of available screening data against numerous targets in the PubChem BioAssay Database, leading to the identification of promising lead compounds, fuelling drug discovery pipelines.
Electron heating in rf capacitive discharges at atmospheric-to-subatmospheric pressures
Authors: Park Sanghoo , Choe Wonho , Kim Holak 
Published: June 2018

AbstractElectron heating is a fundamental and multidisciplinary phenomenon in partially ionized gases, from the planet’s ionosphere to laboratory-scale plasmas. Plasmas produced at ambient or reduced pressures have recently shown potential for scientific and industrial applications. However, electron heating, which is strongly coupled to the physicochemical properties of these plasmas, has been poorly understood. We experimentally found the rapid structural transition from non-local to local electron heating in collisional radio-frequency discharges at atmospheric-to-subatmospheric pressures. As the gas pressure decreased from 760 to 200 Torr, the time-averaged electron density increased from 1.3 × 1012 to 1.3 × 1013 cm−3, and the electron temperature decreased from 2.5 to 1.1 eV at the maximum allowable discharge current in the abnormal α-mode in the plasma bulk. The spatiotemporal evolution of the electron temperature clearly shows that the electron temperature increases uniformly throughout the bulk plasma region during sheath expansion and collapse at 760 Torr, but the electron heating weakens with sheath collapse as the gas pressure decreases.
Bio-based products control black rot (Xanthomonas campestris pv. campestris) and increase the nutraceutical and antioxidant components in kale
Authors: Nuñez Andrés M. P. , Rodríguez Gabriel A. A. , Monteiro Fernando P. , Faria Amanda F. , Silva Julio C. P. , Monteiro Ana C. A. , Carvalho Carolina V. , Gomes Luiz A. A. , Souza Ricardo M. , de Souza Jorge T. , Medeiros Flávio H. V. 
Published: June 2018

AbstractBlack rot of crucifers, (Xanthomonas campestris pv. campestris) is the principal yield-limiting and destructive pathogen of cruciferous crop worldwide. In order to validate a bio-based control alternative for this disease, whey, lime sulfur, biofertilizer, Bordeaux mixture or raw milk were applied to kale (Brassica oleracea var. acephala) plants. The disease control was achieved by most of the tested products. Milk-based products (raw milk and whey) and biofertilizer reduced the severity by 44 and 56% in the field. Antioxidants, crude fibber, crude protein and lipid contents and kale yield were verified in the five treatments on the leaves with and without X. campestris pv. campestris inoculation. In the absence of the pathogen (non-inoculated), lime sulfur and Bordeaux mixture improved plant nutritional value compared to organic treatments, nevertheless milk-based products and biofertilizer improved the evaluated variables more than the control. However, on leaves inoculated with X. campestris pv. campestris raw milk increased antioxidant activity, crude protein and fiber contents, whereas biofertilizer increased kale yield, lipid and antioxidant contents. Milk-based products and biofertilizer were further evaluated in greenhouse trials to determinate the activity of defense-related enzymes and lignin content. Biofertilizer treatment resulted in increased phenylalanine ammonia lyase, catalase, peroxidase activities and lignin content. Hence, the application of milk-based products and biofertilizer are promising to control black rot of crucifers and also improves food quality by boosting nutritional values and antioxidant activity.
Blue light excited retinal intercepts cellular signaling
Authors: Ratnayake Kasun , Payton John L. , Lakmal O. Harshana , Karunarathne Ajith 
Published: June 2018

AbstractPhotoreceptor chromophore, 11-cis retinal (11CR) and the photoproduct, all-trans retinal (ATR), are present in the retina at higher concentrations and interact with the visual cells. Non-visual cells in the body are also exposed to retinal that enters the circulation. Although the cornea and the lens of the eye are transparent to the blue light region where retinal can absorb and undergo excitation, the reported phototoxicity in the eye has been assigned to lipophilic non-degradable materials known as lipofuscins, which also includes retinal condensation products. The possibility of blue light excited retinal interacting with cells; intercepting signaling in the presence or absence of light has not been explored. Using live cell imaging and optogenetic signaling control, we uncovered that blue light-excited ATR and 11CR irreversibly change/distort plasma membrane (PM) bound phospholipid; phosphatidylinositol 4,5 bisphosphate (PIP2) and disrupt its function. This distortion in PIP2 was independent of visual or non-visual G-protein coupled receptor activation. The change in PIP2 was followed by an increase in the cytosolic calcium, excessive cell shape change, and cell death. Blue light alone or retinal alone did not perturb PIP2 or elicit cytosolic calcium increase. Our data also suggest that photoexcited retinal-induced PIP2 distortion and subsequent oxidative damage incur in the core of the PM. These findings suggest that retinal exerts light sensitivity to both photoreceptor and non-photoreceptor cells, and intercepts crucial signaling events, altering the cellular fate.
A novel endoscopic classification for craniopharyngioma based on its origin
Authors: Tang Bin , Xie Shen Hao , Xiao Li Min , Huang Guan Lin , Wang Zhi Gang , Yang Le , Yang Xuan Yong , Xu Shan , Chen Ye Yuan , Ji Yu Qiang , Zeng Er Ming , Hong Tao 
Published: June 2018

AbstractEndoscopic endonasal approach for craniopharyngioma (CP) resection provides a wide view and direct observation of hypothalamus and origin of tumor. Under endoscopy, 92 CPs were classified into 2 types: Peripheral and Central, according to its relation to pituitary stalk. Peripheral type was further divided into 3 subtypes: Hypothalamic stalk, Suprasellar stalk and Intrasellar stalk CP, according to the different origin site along hypothalamus-pituitary axis. Peripheral type arisen from the stalk but expanded and grown laterally in an exophytic pattern, accounting for 71.7% of all CPs, preservation rate of stalk was higher (76.0%). Central type grew within and along pituitary stalk and located strictly in the midline. The pituitary stalk was hardly preserved (only15.4%). Hypothalamic stalk CPs (n = 36, 54.6%) developed from the junction of hypothalamus and stalk, hypothalamus damage was found in all of this subtype after surgery. Suprasellar stalk CPs (n = 14, 21.2%) originated from the lower portion of stalk and displaced hypothalamus upward rather than infiltrated it. Intrasellar stalk CPs (n = 16, 24.2%) arose from the subdiaphragma portion of the stalk, with less hypothalamus damage. Recoginzing the origin of CP is helpful to understand its growth pattern and relation to hypothalamus, which is critical in planning the most appropriate surgical approach and degree of excision.
DNA methylation landscape of the genes regulating D-serine and D-aspartate metabolism in post-mortem brain from controls and subjects with schizophrenia
Authors: Keller Simona , Punzo Daniela , Cuomo Mariella , Affinito Ornella , Coretti Lorena , Sacchi Silvia , Florio Ermanno , Lembo Francesca , Carella Massimo , Copetti Massimiliano , Cocozza Sergio , Balu Darrick T. , Errico Francesco , Usiello Alessandro , Chiariotti Lorenzo 
Published: June 2018

AbstractThe spatio-temporal regulation of genes involved in the synthesis and degradation of D-serine and D-aspartate such as serine racemase (SR), D-amino acid oxidase (DAO), G72 and D-aspartate oxidase (DDO), play pivotal roles in determining the correct levels of these D-amino acids in the human brain. Here we provide a comprehensive analysis of mRNA expression and DNA methylation status of these genes in post-mortem samples from hippocampus, dorsolateral prefrontal cortex, and cerebellum from patients with schizophrenia and non-psychiatric controls. DNA methylation analysis was performed at an ultradeep level, measuring individual epialleles frequency by single molecule approach. Differential CpG methylation and expression was detected across different brain regions, although no significant correlations were found with diagnosis. G72 showed the highest CpG and non-CpG methylation degree, which may explain the repression of G72 transcription in the brain regions considered here. Conversely, in line with the sustained SR mRNA expression in the analyzed areas, very low methylation levels were detected at this gene’s regulatory regions. Furthermore, for DAO and DDO, our single-molecule methylation approach demonstrated that analysis of epiallele distribution was able to detect differences in DNA methylation representing area-specific methylation signatures, which are likely not detectable with targeted or genome-wide classic methylation analyses.
Contactless Fluid Manipulation in Air: Droplet Coalescence and Active Mixing by Acoustic Levitation
Authors: Watanabe Ayumu , Hasegawa Koji , Abe Yutaka 
Published: June 2018

AbstractAcoustic manipulation by an ultrasonic phased array provides an entirely new approach to processes such as coalescence, mixing, separation, and evaporation occurring in the generation of new materials, physical property measurement, the biomedical industry, etc. However, to date, ultrasonic phased arrays have not been fully investigated for applications in fluid manipulation. This paper provides contactless coalescence and mixing techniques for droplets in air by controlling the acoustic potential by using an ultrasonic phased array. We focused on mode oscillation to propose an efficient mixing technique for liquid without contact. A comparison of mixing performance between cases with mode oscillation and without mode oscillation showed that the flow induced by mode oscillation promotes droplet mixing. Our paper demonstrates the feasibility of contactless coalescence and mixing as a first step in fluid manipulation with a phased array.
Genome Sequencing and analyses of Two Marine Fungi from the North Sea Unraveled a Plethora of Novel Biosynthetic Gene Clusters
Authors: Kumar Abhishek , Sørensen Jens Laurids , Hansen Frederik Teilfeldt , Arvas Mikko , Syed Muhammad Fahad , Hassan Lara , Benz J. Philipp , Record Eric , Henrissat Bernard , Pöggeler Stefanie , Kempken Frank 
Published: June 2018

AbstractMarine Fungi are potent secondary metabolite producers. However, limited genetic information are available their biosynthetic gene clusters (BGCs) and their biotechnological applications. To overcome this lack of information, herein, we used next-generation sequencing methods for genome sequencing of two marine fungi, isolated from the German Wadden Sea, namely Calcarisporium sp. KF525 and Pestalotiopsis sp. KF079. The assembled genome size of the marine isolate Calcarisporium sp. KF525 is about 36.8 Mb with 60 BGCs, while Pestalotiopsis sp. KF079 has a genome size of 47.5 Mb harboring 67 BGCs. Of all BGCs, 98% and 97% are novel clusters of Calcarisporium sp. and Pestalotiopsis sp., respectively. Only few of the BGCs were found to be expressed under laboratory conditions by RNA-seq analysis. The vast majority of all BGCs were found to be novel and unique for these two marine fungi. Along with a description of the identified gene clusters, we furthermore present important genomic features and life-style properties of these two fungi. The two novel fungal genomes provide a plethora of new BGCs, which may have biotechnological applications in the future, for example as novel drugs. The genomic characterizations will provide assistance in future genetics and genomic analyses of marine fungi.
Potential invasion of exotic ambrosia beetles Xyleborus glabratus and Euwallacea sp. in Mexico: A major threat for native and cultivated forest ecosystems
Authors: Lira-Noriega Andrés , Soberón Jorge , Equihua Julián 
Published: June 2018

AbstractWe analyze the invasive potential of two Asian ambrosia beetles, Xyleborus glabratus and Euwallacea sp., into Mexico and the southern United States. The fungal symbionts of these beetles have been responsible for damage to trees of the family Lauraceae, including Persea americana and other non-cultivated tree species on both coasts of the United States. We estimate their potential threat using ecological niche modeling and spatial multi-criteria evaluation protocols to incorporate plant and beetle suitabilities as well as forest stress factors across Mexico. Mexico contains higher climatic and habitat suitability for X. glabratus than for Euwallacea sp. Within this country, the neotropical region is most vulnerable to invasion by both of these species. We also identify a corridor of potential invasion for X. glabratus along the Gulf of Mexico coast where most Lauraceae and native Xyleborus species are present; dispersal of either X. glabratus or Euwallacea sp. into this region would likely lead to major disease spread. However, the overall potential damage that these beetles can cause may be a function of how many reproductive hosts and how many other ambrosia beetles are present, as well as of their capacity to disperse. This work can also alert relevant managers and authorities regarding this threat.
Physiological and genetic characterization of calcium phosphate precipitation by Pseudomonas species
Authors: Fishman Maxwell R. , Giglio Krista , Fay David , Filiatrault Melanie J. 
Published: June 2018

AbstractMicrobial biomineralization is a widespread phenomenon. The ability to induce calcium precipitation around bacterial cells has been reported in severalPseudomonasspecies but has not been thoroughly tested. We assayed 14Pseudomonasstrains representing five different species for the ability to precipitate calcium. Calcium phosphate precipitated adjacent to the colonies of all thePseudomonasstrains tested and also precipitated on the surface of colonies for several of thePseudomonasstrains assayed. The precipitate was commonly precipitated as amorphous calcium phosphate, however seven of the 14Pseudomonasstrains tested precipitated amorphous apatite in agar adjacent to the colonies. Out of the sevenPseudomonasstrains that precipitated amorphous apatite, six are plant pathogenic. The formation of amorphous apatite was commonly observed in the area of the agar where amorphous calcium phosphate had previously formed. A transposon mutagenesis screen inPseudomonas syringaepv. tomato DC3000 revealed genes involved in general metabolism, lipopolysaccharide and cell wall biogenesis, and in regulation of virulence play a role in calcium precipitation. These results shed light on the common ability ofPseudomonasspecies to perform calcium precipitation and the underlying genetic regulation involved in biomineralization.
Association of meteorological factors and air NO2 and O3 concentrations with acute exacerbation of elderly chronic obstructive pulmonary disease
Authors: Lin Ming-Tai , Kor Chew-Teng , Chang Chun-Chi , Chai Woei-Horng , Soon Maw-Soan , Ciou Yi-Siang , Bin Lian Ie , Chang Chia-Chu 
Published: June 2018

AbstractWe studied the combined effect of air pollutant concentrations and meteorological factors [e.g., temperature and atmospheric pressure (AP)] on the acute exacerbation of coronary obstructive pulmonary disease (COPD) in 277 older patients with COPD (240 men and 37 women; average age, 75.3 ± 9.3 years). Average air pollutant concentrations, AP, temperature, and relative humidity corresponding to each of the 7 days before the date of hospitalisation were identified as the case and the two other weekly averages, 4 and 8 weeks prior to admission, were considered the controls. During the warming-up season, COPD exacerbation more likely occurred on days of temperature increase or AP decrease than on other days. Increments in CO, NO2 and O3 concentrations were significantly associated with 5%, 11% and 4% increases in COPD exacerbation risks, respectively. During the cooling-down season, increments in PM10 concentrations were significant risk factors; the exacerbation likely occurred on days of temperature decreases than on other days. Air pollution with increased NO2, CO, O3 and PM10 concentrations and continual temperature changes (colder during cooling-down seasons or hotter during warning-up seasons) were associated with acute exacerbation of COPD in older patients.
Reuse of malaria rapid diagnostic tests for amplicon deep sequencing to estimate Plasmodium falciparum transmission intensity in western Uganda
Authors: Boyce Ross M. , Hathaway Nick , Fulton Travis , Reyes Raquel , Matte Michael , Ntaro Moses , Mulogo Edgar , Waltmann Andreea , Bailey Jeffrey A. , Siedner Mark J. , Juliano Jonathan J. 
Published: June 2018

AbstractMolecular techniques are not routinely employed for malaria surveillance, while cross-sectional, community-based parasite surveys require significant resources. Here, we describe a novel use of malaria rapid diagnostic tests (RDTs) collected at a single facility as source material for sequencing to esimtate malaria transmission intensity across a relatively large catchment area. We extracted Plasmodium falciparum DNA from RDTs, then amplified and sequenced a region of the apical membrane antigen 1 (pfama1) using targeted amplicon deep sequencing. We determined the multiplicity of infection (MOI) for each sample and examined associations with demographic, clinical, and spatial factors. We successfully genotyped 223 of 287 (77.7%) of the samples. We demonstrated an inverse relationship between the MOI and elevation with individuals presenting from the highest elevation villages harboring infections approximately half as complex as those from the lowest (MOI 1.85 vs. 3.51, AOR 0.25, 95% CI 0.09–0.65, p = 0.004). This study demonstrates the feasibility and validity of using routinely-collected RDTs for molecular surveillance of malaria and has real-world utility, especially as the cost of high-throughpout sequencing continues to decline.
A Mouse Model of Schnyder Corneal Dystrophy with the N100S Point Mutation
Authors: Dong Fei , Jin Xueting , Boettler Michelle A. , Sciulli Harrison , Abu-Asab Mones , Del Greco Christina , Wang Shurong , Hu Yueh-Chiang , Campos Maria M. , Jackson Shelley N. , Muller Ludovic , Woods Amina S. , Combs Christian A. , Zhang Jianhua , Nickerson Michael L. , Kruth Howard S. , Weiss Jayne S. , Kao Winston W. 
Published: June 2018

AbstractSchnyder corneal dystrophy (SCD) is a rare autosomal dominant disease in humans, characterized by abnormal deposition of cholesterol and phospholipids in cornea caused by mutations in the UbiA prenyltransferase domain containing 1 (UBIAD1) gene. In this study, we generated a mouse line carrying Ubiad1 N100S point mutation using the CRISPR/Cas9 technique to investigate the pathogenesis of SCD. In vivo confocal microscopy revealed hyper-reflective dot-like deposits in the anterior cornea in heterozygotes and homozygotes. No significant change was found in corneal epithelial barrier function or wound healing. Electron microscopy revealed abnormal mitochondrial morphology in corneal epithelial, stromal, and endothelial cells. Mitochondrial DNA copy number assay showed 1.27 ± 0.07 fold change in homozygotes versus 0.98 ± 0.05 variation in wild type mice (P < 0.05). Lipidomic analysis indicated abnormal metabolism of glycerophosphoglycerols, a lipid class found in mitochondria. Four (34:1, 34:2, 36:2, and 44:8) of the 11 glycerophosphoglycerols species identified by mass spectrometry showed a significant increase in homozygous corneas compared with heterozygous and wild-type mouse corneas. Unexpectedly, we did not find a difference in the corneal cholesterol level between different genotypes by filipin staining or lipidomic analysis. The Ubiad1N100S mouse provides a promising animal model of SCD revealing that mitochondrial dysfunction is a prominent component of the disease. The different phenotype in human and mouse may due to difference in cholesterol metabolism between species.
Melatonin alleviates low-sulfur stress by promoting sulfur homeostasis in tomato plants
Authors: Hasan Md. Kamrul , Liu Chen-Xu , Pan Yan-Ting , Ahammed Golam Jalal , Qi Zhen-Yu , Zhou Jie 
Published: June 2018

AbstractDespite involvement of melatonin (MT) in plant growth and stress tolerance, its role in sulfur (S) acquisition and assimilation remains unclear. Here we report that low-S conditions cause serious growth inhibition by reducing chlorophyll content, photosynthesis and biomass accumulation. S deficiency evoked oxidative stress leading to the cell structural alterations and DNA damage. In contrast, MT supplementation to the S-deprived plants resulted in a significant diminution in reactive oxygen species (ROS) accumulation, thereby mitigating S deficiency-induced damages to cellular macromolecules and ultrastructures. Moreover, MT promoted S uptake and assimilation by regulating the expression of genes encoding enzymes involved in S transport and metabolism. MT also protected cells from ROS-induced damage by regulating 2-cysteine peroxiredoxin and biosynthesis of S-compounds. These results provide strong evidence that MT can enhance plant tolerance to low-S-induced stress by improving S uptake, metabolism and redox homeostasis, and thus advocating beneficial effects of MT on increasing the sulfur utilization efficiency.