bluuebunny/crossref_metadata_2025_split huggingface dataset:
Erlotinib sensitivity of MAPK1p.D321N mutation in head and neck squamous cell carcinoma
Authors: Ngan Hoi-Lam , Poon Peony Hiu Yan , Su Yu-Xiong , Chan Jason Ying Kuen , Lo Kwok-Wai , Yeung Chun Kit , Liu Yuchen , Wong Eileen , Li Hui , Lau Chin Wang , Piao Wenying , Lui Vivian Wai Yan 
Published: April 2020

AbstractHead and neck squamous cell carcinoma (HNSCC) lacks predictive biomarkers for drug responses. By targeted sequencing, we identified two MAPK1 mutations in recurrent HNSCC, MAPK1p.D321N, and p.R135K. We previously reported an exceptional erlotinib responder with MAPK1p.E322K. Here, by in silico and drug studies, we determined functions of these two recurrence-associated MAPK1 mutations. Residues D321, R135, and E322 are in 3D proximity. MAPK1p.D321N drives marked in vivo erlotinib sensitivity, while p.R135K’s effect is moderate.
Language in schizophrenia: relation with diagnosis, symptomatology and white matter tracts
Authors: de Boer J. N. , van Hoogdalem M. , Mandl R. C. W. , Brummelman J. , Voppel A. E. , Begemann M. J. H. , van Dellen E. , Wijnen F. N. K. , Sommer I. E. C. 
Published: April 2020

AbstractLanguage deviations are a core symptom of schizophrenia. With the advances in computational linguistics, language can be easily assessed in exact and reproducible measures. This study investigated how language characteristics relate to schizophrenia diagnosis, symptom, severity and integrity of the white matter language tracts in patients with schizophrenia and healthy controls. Spontaneous speech was recorded and diffusion tensor imaging was performed in 26 schizophrenia patients and 22 controls. We were able to classify both groups with a sensitivity of 89% and a specificity of 82%, based on mean length of utterance and clauses per utterance. Language disturbances were associated with negative symptom severity. Computational language measures predicted language tract integrity in patients (adjustedR2 = 0.467) and controls (adjustedR2 = 0.483). Quantitative language analyses have both clinical and biological validity, offer a simple, helpful marker of both severity and underlying pathology, and provide a promising tool for schizophrenia research and clinical practice.
The FLAME-accelerated signalling tool (FaST) for facile parallelisation of flexible agent-based models of cell signalling
Authors: Fullstone Gavin , Guttà Cristiano , Beyer Amatus , Rehm Markus 
Published: April 2020

AbstractAgent-based modelling is particularly adept at modelling complex features of cell signalling pathways, where heterogeneity, stochastic and spatial effects are important, thus increasing our understanding of decision processes in biology in such scenarios. However, agent-based modelling often is computationally prohibitive to implement. Parallel computing, either on central processing units (CPUs) or graphical processing units (GPUs), can provide a means to improve computational feasibility of agent-based applications but generally requires specialist coding knowledge and extensive optimisation. In this paper, we address these challenges through the development and implementation of the FLAME-accelerated signalling tool (FaST), a software that permits easy creation and parallelisation of agent-based models of cell signalling, on CPUs or GPUs. FaST incorporates validated new agent-based methods, for accurate modelling of reaction kinetics and, as proof of concept, successfully converted an ordinary differential equation (ODE) model of apoptosis execution into an agent-based model. We finally parallelised this model through FaST on CPUs and GPUs resulting in an increase in performance of 5.8× (16 CPUs) and 53.9×, respectively. The FaST takes advantage of the communicating X-machine approach used by FLAME and FLAME GPU to allow easy alteration or addition of functionality to parallel applications, but still includes inherent parallelisation optimisation. The FaST, therefore, represents a new and innovative tool to easily create and parallelise bespoke, robust, agent-based models of cell signalling.
Genomic diversifications of five Gossypium allopolyploid species and their impact on cotton improvement
Authors: Chen Z. Jeffrey , Sreedasyam Avinash , Ando Atsumi , Song Qingxin , De Santiago Luis M. , Hulse-Kemp Amanda M. , Ding Mingquan , Ye Wenxue , Kirkbride Ryan C. , Jenkins Jerry , Plott Christopher , Lovell John , Lin Yu-Ming , Vaughn Robert , Liu Bo , Simpson Sheron , Scheffler Brian E. , Wen Li , Saski Christopher A. , Grover Corrinne E. , Hu Guanjing , Conover Justin L. , Carlson Joseph W. , Shu Shengqiang , Boston Lori B. , Williams Melissa , Peterson Daniel G. , McGee Keith , Jones Don C. , Wendel Jonathan F. , Stelly David M. , Grimwood Jane , Schmutz Jeremy 
Published: April 2020

AbstractPolyploidy is an evolutionary innovation for many animals and all flowering plants, but its impact on selection and domestication remains elusive. Here we analyze genome evolution and diversification for all five allopolyploid cotton species, including economically important Upland and Pima cottons. Although these polyploid genomes are conserved in gene content and synteny, they have diversified by subgenomic transposon exchanges that equilibrate genome size, evolutionary rate heterogeneities and positive selection between homoeologs within and among lineages. These differential evolutionary trajectories are accompanied by gene-family diversification and homoeolog expression divergence among polyploid lineages. Selection and domestication drive parallel gene expression similarities in fibers of two cultivated cottons, involving coexpression networks andN6-methyladenosine RNA modifications. Furthermore, polyploidy induces recombination suppression, which correlates with altered epigenetic landscapes and can be overcome by wild introgression. These genomic insights will empower efforts to manipulate genetic recombination and modify epigenetic landscapes and target genes for crop improvement.
Database of pharmacokinetic time-series data and parameters for 144 environmental chemicals
Authors: Sayre Risa R. , Wambaugh John F. , Grulke Christopher M. 
Published: April 2020

AbstractTime courses of compound concentrations in plasma are used in chemical safety analysis to evaluate the relationship between external administered doses and internal tissue exposures. This type of experimental data is rarely available for the thousands of non-pharmaceutical chemicals to which people may potentially be unknowingly exposed but is necessary to properly assess the risk of such exposures. In vitro assays and in silico models are often used to craft an understanding of a chemical’s pharmacokinetics; however, the certainty of the quantitative application of these estimates for chemical safety evaluations cannot be determined without in vivo data for external validation. To address this need, we present a public database of chemical time-series concentration data from 567 studies in humans or test animals for 144 environmentally-relevant chemicals and their metabolites (187 analytes total). All major administration routes are incorporated, with concentrations measured in blood/plasma, tissues, and excreta. We also include calculated pharmacokinetic parameters for some studies, and a bibliography of additional source documents to support future extraction of time-series. In addition to pharmacokinetic model calibration and validation, these data may be used for analyses of differential chemical distribution across chemicals, species, doses, or routes, and for meta-analyses on pharmacokinetic studies.
Asymmetric participation of defenders and critics of vaccines to debates on French-speaking Twitter
Authors: Gargiulo Floriana , Cafiero Florian , Guille-Escuret Paul , Seror Valérie , Ward Jeremy K. 
Published: April 2020

AbstractFor more than a decade, doubt about vaccines has become an increasingly important global issue. Polarization of opinions on this matter, especially through social media, has been repeatedly observed, but details about the balance of forces are left unclear. In this paper, we analyse the flow of information on vaccines on the French-speaking realm of Twitter between 2016 and 2017. Two major asymmetries appear. Rather than opposing themselves on each vaccine, defenders and critics focus on different vaccines and vaccine-related topics. Pro-vaccine accounts focus on hopes for new groundbreaking vaccines and on ongoing outbreaks of vaccine-preventable illnesses. Vaccine critics concentrate their posts on a limited number of “controversial” vaccines and adjuvants. Furthermore, vaccine-critical accounts display greater craft and energy, using a wider variety of sources, and a more coordinated set of hashtags. This double asymmetry can have serious consequences. Despite the presence of a large number of pro-vaccine accounts, some arguments raised by efficiently organized and very active vaccine-critical activists are left unanswered.
Improved fidelity of orientation perception: a learning effect dissociable from enhanced discriminability
Authors: Zhang En , Li Wu 
Published: April 2020

AbstractVisual perception can be influenced by stimulus context, selective attention, and prior experience. Many previous studies have shown complex interactions among these influencing factors, but it remains unclear whether context-induced illusions could be reduced by perceptual training and whether such a change in perceptual fidelity is linked to improved perceptual discriminability. To address this question, we introduced a context-induced tilt illusion into an orientation discrimination training paradigm. This resulted in parallel and long-term improvements in the discriminability and fidelity of orientation perception. The improved discriminability was specific to the task-relevant target stimulus but nonspecific to the task-irrelevant context. By contrast, the improved perceptual fidelity was specific to the task-irrelevant contextual stimulus that induced the illusion, but not specific to the task-relevant target stimulus or task performed on one of its features. These results indicate two dissociable learning effects associated with the same training procedure. Such a dissociation was further supported by the observation that the sizes of the two learning effects were uncorrelated across the subjects. Our findings suggest two parallel learning processes: a task-dependent process giving rise to enhanced discriminability for the task-relevant stimulus attribute, and a context-dependent process leading to improved perceptual fidelity for the attended stimuli.
Effect of excessive gestational weight on daughters’ breast density at the end of puberty onset
Authors: López Ana , Garmendia María Luisa , Shepherd John , Michels Karin , Corvalán Camila , Pereira Ana 
Published: April 2020

AbstractThe effect of excessive gestational weight gain (EGWG) is related to adverse health outcomes in the offspring; however, its effect on the daughters’ breast density is unclear. We aimed to assess the association between EGWG and daughters’ breast composition (% of fibroglandular volume (%FGV) and absolute fibroglandular volume (AFGV)) at Tanner stage 4 (Tanner B4)). We included 341 girls and their mothers from an ongoing cohort of low-income Chilean girls born from 2002–2003. Maternal gestational weight gain was self-reported in 2007, and breast density by digital mammography was measured in 2010. Weight, height and breast composition by dual X-ray absorptiometry (DXA) were measured in daughters at Tanner B4. Logistic regression models were run to assess the association between EGWG and the 80th percentile of %FGV and AFGV. Mean gestational weight gain was 13.7 kg (SD = 6.9 kg). Women with pregestational overweight or obesity exceeded the recommended gestational weight gain (58.8% vs. 31.8%, respectively). Daughters of women who had EGWG had higher levels of AFGV (OR: 2.02; 95%CI 1.16–3.53) at Tanner B4, which could be explained by metabolic and hormonal exposure in utero. However, we did not observe an association with %FGV.
Extensive transcriptome changes during seasonal leaf senescence in field-grown black cottonwood (Populus trichocarpa Nisqually-1)
Authors: Lu Haiwei , Gordon Michael I. , Amarasinghe Vindhya , Strauss Steven H. 
Published: April 2020

AbstractTo better understand the molecular control of leaf senescence, we examined transcriptome changes during seasonal leaf senescence in Populus trichocarpa Nisqually-1, the Populus reference genome, growing in its natural habitat. Using monthly (from May to October) transcriptomes for three years (2009, 2015, and 2016), we identified 17,974 differentially expressed genes (DEGs; false discovery rate <0.05; log-fold change cutoff = 0) from 36,007 expressed Populus gene models. A total of 14,415 DEGs were directly related to transitions between four major developmental phases – growth, senescence initiation, reorganization, and senescence termination. These DEGs were significantly (p < 0.05) enriched in 279 gene ontology (GO) terms, including those related to photosynthesis, metabolic process, catalytic activity, protein phosphorylation, kinase activity, pollination, and transport. Also, there were 881 differentially expressed transcription factor (TF) genes from 54 TF families, notably bHLH, MYB, ERF, MYB-related, NAC, and WRKY. We also examined 28 DEGs known as alternative splicing (AS) factors that regulate AS process, and found evidence for a reduced level of AS activity during leaf senescence. Furthermore, we were able to identify a number of promoter sequence motifs associated with leaf senescence. This work provides a comprehensive resource for identification of genes involved in seasonal leaf senescence in trees, and informs efforts to explore the conservation and divergence of molecular mechanisms underlying leaf senescence between annual and perennial species.
Design and efficient synthesis of pyrazoline and isoxazole bridged indole C-glycoside hybrids as potential anticancer agents
Authors: Kumari Priti , Mishra Vishnu S. , Narayana Chintam , Khanna Ashish , Chakrabarty Anindita , Sagar Ram 
Published: April 2020

AbstractC-glycosides are important class of molecules exhibit diverse biological activities and present as structural motif in many natural products. Two series of new pyrazoline and isoxazole bridged indoleC-glycoside molecular hybrids (n = 36) were efficiently synthesized starting from diverse indole 3-carboxaldehydes derived α, β-unsaturated ketone derivatives of β-D-glucosyl-propan-2-one, β-D-galactosyl-propan-2-one and β-D-mannosyl-propan-2-one, reacting with hydrazine hydrate and hydroxyl amine hydrochloride in shorter reaction time (15 min) under microwave assisted condition. Anticancer activity of these newly synthesized pyrazoline and isoxazole bridged indolesC-glycoside hybrids were determined in details through cellular assays against MCF-7, MDA-MB-453 and MDA-MB-231 cancer cell lines. The selected library members displayed low micromolar (IC50 = 0.67–4.67 µM) and selective toxicity against breast cancer cell line (MCF-7). Whereas these compounds were nontoxic towards normal cell line (MCF-10A). Mechanistic studies showed that, active compounds inhibit COX-2 enzyme, which was also supported by molecular docking studies. These findings are expected to provide new leads towards anticancer drug discovery.
Hers and his: Silk glands used in egg sac construction by female spiders potentially repurposed by a ‘modern’ male spider
Authors: Townley Mark A. , Harms Danilo 
Published: April 2020

AbstractCylindrical silk gland (CY) spigots distinguish a large clade of modern spiders, the CY spigot clade, which includes all entelegyne spiders and their closest relatives. Following a widespread paradigm, CYs and their spigots are only known to occur in female spiders and they produce silk used in the construction of egg sacs. Here we report the occurrence of a CY spigot or CY nubbin on each posterior median spinneret (PMS) in males (5th stadium and later) of the spider Australomimetus maculosus. Late juvenile males had a CY spigot on each PMS, whereas adult males either had a CY spigot or, more often, a non-functional CY nubbin. This indicates that potential CY use by males is at least largely limited to late juvenile instars and is not involved with egg sac construction. Despite the presence of CY spigots in both sexes, sexual dimorphism with respect to CYs was still evident since males lacked the CY spigot on each posterior lateral spinneret present in late juvenile and adult females, and CY spigots of males never had the wide shaft and opening of adult females. This study adds to our knowledge of spinning apparatus variability in modern spiders and demonstrates an exception to the paradigm that, in the CY spigot clade, such spigots are restricted to female spiders.
NusA directly interacts with antitermination factor Q from phage λ
Authors: Dudenhoeffer Benjamin R. , Borggraefe Jan , Schweimer Kristian , Knauer Stefan H. 
Published: April 2020

AbstractAntitermination (AT) is a ubiquitous principle in the regulation of bacterial transcription to suppress termination signals. In phage λ antiterminator protein Q controls the expression of the phage’s late genes with loading of λQ onto the transcription elongation complex halted at a σ-dependent pause requiring a specific DNA element. The molecular basis of λQ-dependent AT and its dependence on N-utilization substance (Nus) A is so far only poorly understood. Here we used solution-state nuclear magnetic resonance spectroscopy to show that the solution structure of λQ is in agreement with the crystal structure of an N-terminally truncated variant and that the 60 residues at the N-terminus are unstructured. We also provide evidence that multidomain protein NusA interacts directly with λQ via its N-terminal domain (NTD) and the acidic repeat (AR) 2 domain, with the λQ:NusA-AR2 interaction being able to release NusA autoinhibition. The binding sites for NusA-NTD and NusA-AR2 on λQ overlap and the interactions are mutually exclusive with similar affinities, suggesting distinct roles during λQ-dependent AT, e.g. the λQ:NusA-NTD interaction might position NusA-NTD in a way to suppress termination, making NusA-NTD repositioning a general scheme in AT mechanisms.
Synchrotron-based high-resolution photoemission spectroscopy study of ZIRLO cladding with H2O adsorption: Coverage and temperature dependence
Authors: Park Sangjune , Kim Ki-jeong , Lee Jeongmook , Kim Jong-Yun , Lee Dong Woo , Lim Sang Ho , Youn Young-Sang 
Published: April 2020

AbstractThe coverage and temperature dependence of ZIRLO cladding with H2O adsorption are studied using synchrotron-based high-resolution photoemission spectroscopy (HRPES). Based on the analytical results of the Zr 3d, O 1 s, C 1 s, and Sn 3d HRPES profiles prior to H2O adsorption, we determine the surface compositions of O2−, hydroxyl OH−, chemisorbed H2O, zirconium carbide, adventitious carbon, Sn metal, and SnO2 in ZIRLO. When ZIRLO is exposed to H2O molecules, the relative proportion of zirconium metal decreases, whereas that of the total zirconium oxides increases, suggesting the reaction between H2O and the zirconium metal in ZIRLO. On annealing a sample with 1000 L H2O on ZIRLO at 300 °C, Zr2O3 and ZrO2 decompose, and oxygen diffuses into the bulk, thereby reducing the oxidation states of zirconium on the surface. Moreover, at this temperature, the excess H2O molecules on ZIRLO are thoroughly desorbed and tin element is diffused into the bulk in ZIRLO.
Development of a quantitative, portable, and automated fluorescent blue-ray device-based malaria diagnostic equipment with an on-disc SiO2 nanofiber filter
Authors: Yamamoto Takeki , Hashimoto Muneaki , Nagatomi Kenji , Nogami Takahiro , Sofue Yasuyuki , Hayashi Takuya , Ido Yusuke , Yatsushiro Shouki , Abe Kaori , Kajimoto Kazuaki , Tamari Noriko , Awuor Beatrice , Sonye George , Kongere James , Munga Stephen , Ohashi Jun , Oka Hiroaki , Minakawa Noboru , Kataoka Masatoshi , Mita Toshihiro 
Published: April 2020

AbstractThere is an urgent need to develop an automated malaria diagnostic system that can easily and rapidly detect malaria parasites and determine the proportion of malaria-infected erythrocytes in the clinical blood samples. In this study, we developed a quantitative, mobile, and fully automated malaria diagnostic system equipped with an on-disc SiO2 nanofiber filter and blue-ray devices. The filter removes the leukocytes and platelets from the blood samples, which interfere with the accurate detection of malaria by the blue-ray devices. We confirmed that the filter, which can be operated automatically by centrifugal force due to the rotation of the disc, achieved a high removal rate of leukocytes (99.7%) and platelets (90.2%) in just 30 s. The automated system exhibited a higher sensitivity (100%) and specificity (92.8%) for detecting Plasmodium falciparum from the blood of 274 asymptomatic individuals in Kenya when compared to the common rapid diagnosis test (sensitivity = 98.1% and specificity = 54.8%). This indicated that this system can be a potential alternative to conventional methods used at local health facilities, which lack basic infrastructure.
Hemocyte phagosomal proteome is dynamically shaped by cytoskeleton remodeling and interorganellar communication with endoplasmic reticulum during phagocytosis in a marine invertebrate, Crassostrea gigas
Authors: Mao Fan , Mu Huawei , Wong Nai-Kei , Liu Kunna , Song Jingchen , Qiu Jianwen , Lin Yue , Zhang Xiangyu , Xu Duo , Xiang Zhiming , Li Jun , Zhang Yang , Yu Ziniu 
Published: April 2020

AbstractPhagosomes are task-force organelles of innate immune systems, and evolutionary diversity and continuity abound in the protein machinery executing this coordinately regulated process. In order to clarify molecular mechanisms underlying phagocytosis, we studied phagocyte response to beads and Vibrio species, using hemocytes of the Pacific oysters (Crassostrea gigas) as a marine invertebrate model. Phagosomes from different stages of phagocytosis were isolated by density-gradient centrifugation, and more than 400 phagosome-associated proteins were subsequently identified via high-throughput quantitative proteomics. In modeling key networks of phagosomal proteins, our results support the essential roles of several processes driving phagosome formation and maturation, including cytoskeleton remodeling and signal transduction by Rab proteins. Several endoplasmic reticulum (ER)-associated proteins were identified, while live cell imaging confirms an apparent intimate interaction between the ER and phagosomes. In further quantitative proteomic analysis, the signal transducers CgRhoGDI and CgPI4K were implicated. Through experimental validation, CgRhoGDI was shown to negatively regulate actin cytoskeleton remodeling in the formation of oyster phagosomes, while CgPI4K signaling drives phagosome maturation and bacterial killing. Our current work illustrates the diversity and dynamic interplay of phagosomal proteins, providing a framework for better understanding host-microbe interactions during phagosome activities in under-examined invertebrate species.