bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultra-accurate Duplex Sequencing for the assessment of pretreatment ABL1 kinase domain mutations in Ph+ ALL
Authors: Short Nicholas J. , Kantarjian Hagop , Kanagal-Shamanna Rashmi , Sasaki Koji , Ravandi Farhad , Cortes Jorge , Konopleva Marina , Issa Ghayas C. , Kornblau Steven M. , Garcia-Manero Guillermo , Garris Rebecca , Higgins Jake , Pratt Gabriel , Williams Lindsey N. , Valentine Charles C. , Rivera Victor M. , Pritchard Justin , Salk Jesse J. , Radich Jerald , Jabbour Elias 
Published: May 2020

AbstractMutations of ABL1 are the dominant mechanism of relapse in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). We performed highly accurate Duplex Sequencing of exons 4–10 of ABL1 on bone marrow or peripheral blood samples from 63 adult patients with previously untreated Ph + ALL who received induction with intensive chemotherapy plus a BCR-ABL1 TKI. We identified ABL1 mutations prior to BCR-ABL1 TKI exposure in 78% of patients. However, these mutations were generally present at extremely low levels (median variant allelic frequency 0.008% [range, 0.004%–3.71%] and did not clonally expand and lead to relapse in any patient, even when the pretreatment mutation was known to confer resistance to the TKI received. In relapse samples harboring a TKI-resistant ABL1 mutation, the corresponding mutation could not be detected pretreatment, despite validated sequencing sensitivity of Duplex Sequencing down to 0.005%. In samples under the selective pressure of ongoing TKI therapy, we detected low-level, emerging resistance mutations up to 5 months prior to relapse. These findings suggest that pretreatment ABL1 mutation assessment should not guide upfront TKI selection in Ph + ALL, although serial testing while on TKI therapy may allow for early detection of clinically actionable resistant clones.
Regorafenib is effective against neuroblastoma in vitro and in vivo and inhibits the RAS/MAPK, PI3K/Akt/mTOR and Fos/Jun pathways
Authors: Subramonian Divya , Phanhthilath Nikki , Rinehardt Hannah , Flynn Sean , Huo Yuchen , Zhang Jing , Messer Karen , Mo Qianxing , Huang Shixia , Lesperance Jacqueline , Zage Peter E. 
Published: May 2020

AbstractBackgroundRegorafenib is an inhibitor of multiple kinases with aberrant expression and activity in neuroblastoma tumours that have potential roles in neuroblastoma pathogenesis.MethodsWe evaluated neuroblastoma cells treated with regorafenib for cell viability and confluence, and analysed treated cells for apoptosis and cell cycle progression. We evaluated the efficacy of regorafenib in vivo using an orthotopic xenograft model. We evaluated regorafenib-mediated inhibition of kinase targets and performed reverse-phase protein array (RPPA) analysis of neuroblastoma cells treated with regorafenib. Lastly, we evaluated the efficacy and effects of the combination of regorafenib and 13-cis-retinoic acid on intracellular signalling.ResultsRegorafenib treatment resulted in reduced neuroblastoma cell viability and confluence, with both induction of apoptosis and of cell cycle arrest. Regorafenib treatment inhibits known receptor tyrosine kinase targets RET and PDGFRβ and intracellular signalling through the RAS/MAPK, PI3K/Akt/mTOR and Fos/Jun pathways. Regorafenib is effective against neuroblastoma tumours in vivo, and the combination of regorafenib and 13-cis-retinoic acid demonstrates enhanced efficacy compared with regorafenib alone.ConclusionsThe effects of regorafenib on multiple intracellular signalling pathways and the potential additional efficacy when combined with 13-cis-retinoic acid represent opportunities to develop treatment regimens incorporating regorafenib for children with neuroblastoma.
Circular RNA circNRIP1 promotes migration and invasion in cervical cancer by sponging miR-629-3p and regulating the PTP4A1/ERK1/2 pathway
Authors: Li Xinhui , Ma Ningye , Zhang Yao , Wei Heng , Zhang Huijie , Pang Xiaoao , Li Xiang , Wu Dan , Wang Dian , Yang Zhuo , Zhang Shulan 
Published: May 2020

AbstractEmerging evidence indicates that circRNAs play essential roles in tumorigenesis and development. However, the role of circRNAs in cervical cancer (CC) remains unclear. CircRNA microarrays performed on the immortal cervical cell line H8 and the cervical cancer cell line SiHa were used to identify a circRNA, termed circNRIP1 (hsa_circ_0004771), which was upregulated in SiHa. QRT-PCR confirmed that circNRIP1 was upregulated in CC tissues, where its expression was correlated with lymphovascular space invasion. Besides, both in vitro and in vivo experiments demonstrated that circNRIP1 promotes cell proliferation, migration, and invasion. Additionally, we found that miR-629-3p induced tumor suppression by regulating PTP4A1 and the ERK1/2 pathway. Finally, we confirmed that circNRIP1 exerts its effect, at least partially, by sponging miR-629-3p and thereby regulating the PTP4A1/ERK1/2 pathway. Therefore, circNRIP1 may be useful as a potential prognostic biomarker and therapeutic target in CC patients.
Phenology and related traits for wheat adaptation
Authors: Hyles Jessica , Bloomfield Maxwell T. , Hunt James R. , Trethowan Richard M. , Trevaskis Ben 
Published: May 2020

AbstractWheat is a major food crop, with around 765 million tonnes produced globally. The largest wheat producers include the European Union, China, India, Russia, United States, Canada, Pakistan, Australia, Ukraine and Argentina. Cultivation of wheat across such diverse global environments with variation in climate, biotic and abiotic stresses, requires cultivars adapted to a range of growing conditions. One intrinsic way that wheat achieves adaptation is through variation in phenology (seasonal timing of the lifecycle) and related traits (e.g., those affecting plant architecture). It is important to understand the genes that underlie this variation, and how they interact with each other, other traits and the growing environment. This review summarises the current understanding of phenology and developmental traits that adapt wheat to different environments. Examples are provided to illustrate how different combinations of alleles can facilitate breeding of wheat varieties with optimal crop performance for different growing regions or farming systems.
Hurricane-induced disturbance increases genetic diversity and population admixture of the direct-brooding isopod, Gnathia marleyi
Authors: Pagán J. Andrés , Veríssimo Ana , Sikkel Paul C. , Xavier Raquel 
Published: May 2020

AbstractSevere disturbances can substantially alter eco-evolutionary processes and dynamics. While the impacts of catastrophic events on the biophysical attributes of communities are sometimes assessed, their effects on the genetic patterns of species remain poorly understood. To characterize how severe disturbances impact species at the molecular level, we examined the effects of the most energetic North Atlantic hurricane season in 50 years on the genetic diversity and structure of a dispersal-limited isopod, Gnathia marleyi. We sequenced a portion of the cytochrome oxidase I gene for 432 gnathiids, collected from six localities, ranging from western Puerto Rico to St John, US Virgin Islands. Importantly, multiple years of pre-hurricane sample collection allowed us to characterize temporal genetic patterns under undisturbed conditions and detect the changes subsequent to the 2017 hurricanes. Our results revealed no change to genetic diversity or structure for the years prior to the 2017 hurricanes, with genetic structure occurring at the local and regional levels, with three main clusters corresponding to Southwest Puerto Rico, East Puerto Rico, and the US Virgin Islands. However, directly following the 2017 hurricanes, genetic diversity increased at five of the six sampled localities. Additionally, we found a clear homogenizing effect prompted by increased shared genetic diversity among geographically distant regions and sites that resulted in substantially decreased among-region and among-site differentiation. Our work shows that severe disturbances caused by major tropical hurricanes facilitate gene-flow and increase overall genetic diversity and population admixture of dispersal limited coral reef species, potentially impacting the ecology and evolution of a key regional endemic.
Microfluidic Enrichment Barcoding (MEBarcoding): a new method for high throughput plant DNA barcoding
Authors: Gostel Morgan R. , Zúñiga Jose D. , Kress W. John , Funk Vicki A. , Puente-Lelievre Caroline 
Published: May 2020

AbstractDNA barcoding is a valuable tool to support species identification with broad applications from traditional taxonomy, ecology, forensics, food analysis, and environmental science. We introduce Microfluidic Enrichment Barcoding (MEBarcoding) for plant DNA Barcoding, a cost-effective method for high-throughput DNA barcoding. MEBarcoding uses the Fluidigm Access Array to simultaneously amplify targeted regions for 48 DNA samples and hundreds of PCR primer pairs (producing up to 23,040 PCR products) during a single thermal cycling protocol. As a proof of concept, we developed a microfluidic PCR workflow using the Fluidigm Access Array and Illumina MiSeq. We tested 96 samples for each of the four primary DNA barcode loci in plants: rbcL, matK, trnH-psbA, and ITS. This workflow was used to build a reference library for 78 families and 96 genera from all major plant lineages – many currently lacking in public databases. Our results show that this technique is an efficient alternative to traditional PCR and Sanger sequencing to generate large amounts of plant DNA barcodes and build more comprehensive barcode databases.
Temporal rate is not a distinct perceptual metric
Authors: Motala Aysha , Heron James , McGraw Paul V. , Roach Neil W. , Whitaker David 
Published: May 2020

AbstractSensory adaptation experiments have revealed the existence of ‘rate after-effects’ - adapting to a relatively fast rate makes an intermediate test rate feel slow, and adapting to a slow rate makes the same moderate test rate feel fast. The present work aims to deconstruct the concept of rate and clarify how exactly the brain processes a regular sequence of sensory signals. We ask whether rate forms a distinct perceptual metric, or whether it is simply the perceptual aggregate of the intervals between its component signals. Subjects were exposed to auditory or visual temporal rates (a ‘slow’ rate of 1.5 Hz and a ‘fast’ rate of 6 Hz), before being tested with single unfilled intervals of varying durations. Results show adapting to a given rate strongly influences the perceived duration of a single empty interval. This effect is robust across both interval reproduction and duration discrimination judgments. These findings challenge our understanding of rate perception. Specifically, they suggest that contrary to some previous assertions, the perception of sequence rate is strongly influenced by the perception of the sequence’s component duration intervals.
Aspartate/asparagine-β-hydroxylase: a high-throughput mass spectrometric assay for discovery of small molecule inhibitors
Authors: Brewitz Lennart , Tumber Anthony , Pfeffer Inga , McDonough Michael A. , Schofield Christopher J. 
Published: May 2020

AbstractThe human 2-oxoglutarate dependent oxygenase aspartate/asparagine-β-hydroxylase (AspH) catalyses the hydroxylation of Asp/Asn-residues in epidermal growth factor-like domains (EGFDs). AspH is upregulated on the surface of malign cancer cells; increased AspH levels correlate with tumour invasiveness. Due to a lack of efficient assays to monitor the activity of isolated AspH, there are few reports of studies aimed at identifying small-molecule AspH inhibitors. Recently, it was reported that AspH substrates have a non-canonical EGFD disulfide pattern. Here we report that a stable synthetic thioether mimic of AspH substrates can be employed in solid phase extraction mass spectrometry based high-throughput AspH inhibition assays which are of excellent robustness, as indicated by high Z’-factors and good signal-to-noise/background ratios. The AspH inhibition assay was applied to screen approximately 1500 bioactive small-molecules, including natural products and active pharmaceutical ingredients of approved human therapeutics. Potent AspH inhibitors were identified from both compound classes. Our AspH inhibition assay should enable the development of potent and selective small-molecule AspH inhibitors and contribute towards the development of safer inhibitors for other 2OG oxygenases, e.g. screens of the hypoxia-inducible factor prolyl-hydroxylase inhibitors revealed that vadadustat inhibits AspH with moderate potency.
Temporal variation in daily temperature minima in coral reefs of Nanwan Bay, Southern Taiwan
Authors: Lee I-Huan , Fan Tung-Yung , Fu Ke-Hsien , Ko Dong Shan 
Published: May 2020

AbstractTemporal variation in seawater temperature plays a crucial role in coral reef ecology. Nanwan Bay, Southern Taiwan is home to well-developed coral reefs, which frequently experience cold-water intrusions caused by internal wave-induced upwelling, that manifest in distinct daily temperature minima. These temperature minima and their associated sources were studied by recording in situ bottom temperatures and sea levels observed at depths of 5 and 30 m from May 2007 to September 2008. These data were then compared to the East Asian Seas Nowcast/Forecast System, and it was found that daily temperature minima presented large variations with magnitudes of 2–3 °C over periods from days to months. It was further demonstrated that the cold-water intrusions may have originated from depths of ~100 m and were strongly affected by westward propagating mesoscale eddies from the Pacific basin. An impinging warm anticyclonic eddy in July 2007 may have combined with the El Niño, resulting in temperatures surpassing 29 °C and degree heating days >4.0 °C-days at both depths, which were coincidental with a mass coral bleaching event. This eddy’s impact was additionally evident in high correlations between daily temperature minima and residual sea levels, suggesting that mesoscale eddies alter stratification, substantially influence temperature variation, and play important roles in understanding ecological processes on coral reefs.
Evidence of Biorealistic Synaptic Behavior in Diffusive Li-based Two-terminal Resistive Switching Devices
Authors: Ioannou Panagiotis S. , Kyriakides Evripides , Schneegans Olivier , Giapintzakis John 
Published: May 2020

AbstractFollowing the recent advances in artificial synaptic devices and the renewed interest regarding artificial intelligence and neuromorphic computing, a new two-terminal resistive switching device, based on mobile Li+ ions is hereby explored. Emulation of neural functionalities in a biorealistic manner has been recently implemented through the use of synaptic devices with diffusive dynamics. Mimicking of the spontaneous synaptic weight relaxation of neuron cells, which is regulated by the concentration kinetics of positively charged ions like Ca2+, is facilitated through the conductance relaxation of such diffusive devices. Adopting a battery-like architecture, using LiCoO2 as a resistive switching cathode layer, SiOx as an electrolyte and TiO2 as an anode, Au/LiCoO2/SiOx/TiO2/p++-Si two-terminal devices have been fabricated. Analog conductance modulation, via voltage-driven regulation of Li+ ion concentration in the cathode and anode layers, along with current rectification and nanobattery effects are reported. Furthermore, evidence is provided for biorealistic synaptic behavior, manifested as paired pulse facilitation based on the summation of excitatory post-synaptic currents and spike-timing-dependent plasticity, which are governed by the Li+ ion concentration and its relaxation dynamics.
The false cleanerfish relies on aggressive mimicry to bite fish fins when benthic foods are scarce in their local habitat
Authors: Fujisawa Misaki , Sakai Yoichi , Kuwamura Tetsuo 
Published: May 2020

AbstractThe false cleanerfish, Aspidontus taeniatus (Blenniidae), is known for its morphological resemblance to the bluestreak cleaner wrasse Labroides dimidiatus (Labridae). It has been suggested that A. taeniatus, which acts as a mimic, can easily bite the fins of other fishes that are deceived into requesting cleaning from it or allowing it to approach them. In fact, A. taeniatus frequently utilises benthic food items, such as damselfish eggs, the Christmas tree worm Spirobranchus giganteus, and the boring clam Tridacna crocea. Although geographical variation in the reliance on aggressive mimicry (fin biting) has been reported, the factors have not been determined. We hypothesised that one of the factors is the abundance of benthic food items. To examine our hypothesis, we compared the feeding behaviour of A. taeniatus at two locations showing contrasting abundances of benthic food items in Okinawa, southern Japan. The frequency of fin biting by the small A. taeniatus in Ishigaki Island, where S. giganteus and T. crocea were very rare, was significantly higher than that in Sesoko Island, where the two food items were abundant. We conclude that the importance of aggressive mimicry in A. taeniatus varies depending on local food conditions.
SIRT3 and GCN5L regulation of NADP+- and NADPH-driven reactions of mitochondrial isocitrate dehydrogenase IDH2
Authors: Smolková Katarína , Špačková Jitka , Gotvaldová Klára , Dvořák Aleš , Křenková Alena , Hubálek Martin , Holendová Blanka , Vítek Libor , Ježek Petr 
Published: May 2020

AbstractWild type mitochondrial isocitrate dehydrogenase (IDH2) was previously reported to produce oncometabolite 2-hydroxyglutarate (2HG). Besides, mitochondrial deacetylase SIRT3 has been shown to regulate the oxidative function of IDH2. However, regulation of 2HG formation by SIRT3-mediated deacetylation was not investigated yet. We aimed to study mitochondrial IDH2 function in response to acetylation and deacetylation, and focus specifically on 2HG production by IDH2. We used acetylation surrogate mutant of IDH2 K413Q and assayed enzyme kinetics of oxidative decarboxylation of isocitrate, 2HG production by the enzyme, and 2HG production in cells. The purified IDH2 K413Q exhibited lower oxidative reaction rates than IDH2 WT. 2HG production by IDH2 K413Q was largely diminished at the enzymatic and cellular level, and knockdown of SIRT3 also inhibited 2HG production by IDH2. Contrary, the expression of putative mitochondrial acetylase GCN5L likely does not target IDH2. Using mass spectroscopy, we further identified lysine residues within IDH2, which are the substrates of SIRT3. In summary, we demonstrate that 2HG levels arise from non-mutant IDH2 reductive function and decrease with increasing acetylation level. The newly identified lysine residues might apply in regulation of IDH2 function in response to metabolic perturbations occurring in cancer cells, such as glucose-free conditions.
Use of synergistic mixture of chelating agents for in situ LDH growth on the surface of PEO-treated AZ91
Authors: Petrova E. , Serdechnova M. , Shulha T. , Lamaka S. V. , Wieland D. C. F. , Karlova P. , Blawert C. , Starykevich M. , Zheludkevich M. L. 
Published: May 2020

AbstractThe principal possibility to grow layered double hydroxide (LDH) at ambient pressure on plasma electrolytic oxidation (PEO) treated magnesium alloy AZ91 in the presence of chelating agents is demonstrated for the first time. It avoids hydrothermal autoclave conditions, which strongly limit wide industrial application of such coating systems, and the presence of carbonate ions in the electrolyte, which lead to the formation of “passive” non-functionalizable LDH. A combination of chelating agents (sodium diethylenetriamine-pentaacetate (DTPA) and salicylate) were introduced to the treatment solution. The role of each additive and the influence of treatment bath composition on the LDH formation processes are discussed. A synergistic effect of DTPA and salicylate during LDH formation is discovered and its possible explanation is proposed.
Phase estimation algorithm for the multibeam optical metrology
Authors: Zemlyanov V. V. , Kirsanov N. S. , Perelshtein M. R. , Lykov D. I. , Misochko O. V. , Lebedev M. V. , Vinokur V. M. , Lesovik G. B. 
Published: May 2020

AbstractUnitary Fourier transform lies at the core of the multitudinous computational and metrological algorithms. Here we show experimentally how the unitary Fourier transform-based phase estimation protocol, used namely in quantum metrology, can be translated into the classical linear optical framework. The developed setup made of beam splitters, mirrors and phase shifters demonstrates how the classical coherence, similarly to the quantum coherence, poses a resource for obtaining information about the measurable physical quantities. Our study opens route to the reliable implementation of the small-scale unitary algorithms on path-encoded qudits, thus establishing an easily accessible platform for unitary computation.
A Gilbert syndrome-associated haplotype protects against fatty liver disease in humanized transgenic mice
Authors: Landerer Steffen , Kalthoff Sandra , Paulusch Stefan , Strassburg Christian P. 
Published: May 2020

AbstractUDP-glucuronosyltransferases 1 A (UGT1A) enzymes are capable of detoxifying a broad range of endo- and xenobiotic compounds, which contributes to antioxidative effects, modulation of inflammation and cytoprotection. In the presence of low-function genetic UGT1A variants fibrosis development is increased in various diseases. This study aimed to examine the role of common UGT1A polymorphisms in NASH. Therefore, htgUGT1A-WT mice and htgUGT1A-SNP mice (carrying a common human haplotype present in 10% of the white population) were fed a high-fat Paigen diet for 24 weeks. Serum aminotransferase activities, hepatic triglycerides, fibrosis development and UGT1A expression were assessed. Microscopic examination revealed higher hepatic fat deposition and a significant induction of UGT1A gene expression in htgUGT1A-WT mice. In agreement with these observations, lower serum aminotransferase activities and lower expression levels of fibrosis-related genes were measured in htgUGT1A-SNP mice. This was accompanied by reduced PPARα protein levels in htgUGT1A-WT but not in SNP mice. Our data demonstrate a protective effect of a UGT1A SNP haplotype, leading to milder hepatic steatosis and NASH. Higher PPARα protein levels in animals with impaired UGT1A activity are the likely result of reduced glucuronidation of ligands involved in PPARα-mediated fatty acid oxidation and may lead to the observed protection in htgUGT1A-SNP mice.
Poor neural and perceptual phoneme discrimination during acoustic variation in dyslexia
Authors: Virtala P. , Talola S. , Partanen E. , Kujala T. 
Published: May 2020

AbstractWhereas natural acoustic variation in speech does not compromise phoneme discrimination in healthy adults, it was hypothesized to be a challenge for developmental dyslexics. We investigated dyslexics’ neural and perceptual discrimination of native language phonemes during acoustic variation. Dyslexics and non-dyslexics heard /æ/ and /i/ phonemes in a context with fo variation and then in a context without it. Mismatch negativity (MMN) and P3a responses to phoneme changes were recorded with electroencephalogram to compare groups during ignore and attentive listening. Perceptual phoneme discrimination in the variable context was evaluated with hit-ratios and reaction times. MMN/N2bs were diminished in dyslexics in the variable context. Hit-ratios were smaller in dyslexics than controls. MMNs did not differ between groups in the context without variation. These results suggest that even distinctive vowels are challenging to discriminate for dyslexics when the context resembles natural variability of speech. This most likely reflects poor categorical perception of phonemes in dyslexics. Difficulties to detect linguistically relevant invariant information during acoustic variation in speech may contribute to dyslexics’ deficits in forming native language phoneme representations during infancy. Future studies should acknowledge that simple experimental paradigms with repetitive stimuli can be insensitive to dyslexics’ speech processing deficits.