bluuebunny/crossref_metadata_2025_split huggingface dataset:
Digital imaging outperforms traditional scoring methods of spittlebug tolerance inUrochloa humidicolahybrids
Authors: Hernandez Luis M. , Espitia Paula , Castiblanco Valheria , Cardoso Juan A 
Published: October 2020

AbstractAmerican spittlebug complex (Hemiptera: Cercopidae) is a critical pest for existingUrochloa humidicolacultivars in the neotropical savannas. TheU. humidicolabreeding program of the International Center for Tropical Agriculture aims to increase tolerance to spittlebugs. To developU. humidicolagenotypes with superior tolerance to spittlebugs than existing cultivars, adequate screening methods ought to be deployed. Currently, visual scores of plant damage by spittlebugs is the standard method to screen for variation in plant tolerance. However, visual scoring is prone to human bias, is of medium throughput and relies of the expertise of well-trained personnel. In this study, we compared estimations of plant damage from two alternative methods (SPAD measurements and digital images) and visual scoring from an inexpert evaluator with the plant damage estimated from an expert. This information should instruct if different methods could be implemented in theU. humidicolabreeding program. Time needed to evaluate damage was recorded for each method. Lin’s correlation coefficient, Pearson’s correlation coefficient and broad sense heritability values were also calculated. Overall, damage estimated from digital images showed the highest throughput (twice as fast as visual scoring from an expert); high correlations with visual scoring (r> 0.80, p < 0.0001); and heritability values for plant damage as good or better (> 0.7) than those obtained by visual scoring from an expert. Our results indicate that digital imaging is a phenotyping method that might improve the efficiency of breeding for increased tolerance to spittlebugs inU. humidicola.HighlightDigital imaging outperformed standard scoring method of spittlebug tolerance inUrochloa humidicola,suggesting that this method might improve the efficiency of breeding for such stress.
An absence of temporal filling-in at the physiological blind-spot
Authors: Dhupia Neha , Schwarzkopf D. Samuel , Arnold Derek H. 
Published: October 2020

AbstractVisual objects that extend across physiological blind spots seem to encapsulate the extent of blindness, due to a process commonly referred to as a perceptual filling-in of spatial vision. It is unclear if temporal perception is similar, so we examined temporal relationships governing causality perception across the blind spot. We found the human brain does not allow for the time an object should take to traverse the blind-spot when engaging in a causal interaction. We also used electroencephalogram (EEG), to examine temporal signatures of elements flickering on and off in tandem, or in counter-phase. At a control site, we found more brain activity was entrained at the duty cycle by flicker relative to counter-phase changes, whereas these conditions were indistinguishable about blind spots. Our data suggest a common pool of neurons might encode temporal properties on either side of physiological blind-spots. This would explain the absence of any allowance for the extent of blindness in causality perception, and the weakened differences between temporal representations of flicker and counter-phased changes about the blind spot. Overall, our data suggest that, unlike spatial vision, there is no temporal filling-in for perceptual representations about physiological blind spots.
Assessing cerebellar-cortical connectivity using concurrent TMS-EEG: A Feasibility Study
Authors: Fernandez Lara , Biabani Mana , Do Michael , Opie George M. , Hill Aron T. , Barham Michael P. , Teo Wei-Peng , Byrne Linda K. , Rogasch Nigel C. , Enticott Peter G. 
Published: October 2020

AbstractBackgroundCombined single-pulse transcranial magnetic stimulation (TMS) and electroencephalography (EEG) has been used to probe the features of local networks in the cerebral cortex. Here we investigate whether we can use this approach to explore long-range connections between the cerebellum and cerebral cortex.ObjectiveTo assess the feasibility of using cerebellar TMS-EEG for the exploration of cerebellar-cerebral network dynamics.MethodsTen healthy adults received single-pulse suprathreshold TMS to the cerebellum and an occipital/parietal control site with double-cone and figure-of-eight coils while cerebral activity was recorded. A multisensory electrical control condition was used to simulate the sensation of the double-cone coil at the cerebellar site. Two cleaning pipelines were compared, and the spatiotemporal relationships of the EEG output between conditions were examined at sensor and source levels.ResultsCerebellar stimulation with the double-cone coil resulted in large artefacts in the EEG trace. The addition of SOUND filtering to the cleaning pipeline improved the signal such that further analyses could be undertaken. The cortical potentials evoked by the active TMS conditions showed strong relationships with the responses to the multisensory control condition after ~50 ms. A distinct parietal component at ~42 ms was found following cerebellar double-cone stimulation.ConclusionsCerebellar double-cone stimulation produces large artefacts in the EEG. Cerebellar-specific responses could not be reliably differentiated from sensory evoked potentials after ~50 ms. While evoked potentials differed across conditions at early latencies, it is unclear as to whether these represented TMS-related network activation of the cerebellarthalamocortical tract, or whether components were dominated by sensory contamination and/or coil-driven artefacts. Further work will be required to clarify the specific contribution of cerebellar-cortical connectivity to the observed early latency signals.
Effects ofNT5C2germline variants on 6-mecaptopurine metabolism in children with acute lymphoblastic leukemia
Authors: Jiang Chuang , Yang Wenjian , Moriyama Takaya , Liu Chengcheng , Smith Colton , Yang Wentao , Qian Maoxiang , Li Ziping , Tulstrup Morten , Schmieglow Kjeld , Crews Kristine R. , Zhang Hui , Pui Ching-Hon , Evans William , Relling Mary , Bhatia Smita , Yang Jun J. 
Published: October 2020

Abstract6-mercaptopurine (6-MP) is widely used in the treatment of acute lymphoblastic leukemia (ALL), and its cytotoxicity is primarily mediated by thioguanine nucleotide metabolites (TGN). Recent genome-wide association study has identified germline polymorphisms (e.g., rs72846714) in theNT5C2gene associated with 6-MP metabolism in patients with ALL. However, the full spectrum of genetic variation inNT5C2is unclear and its impact on 6-MP drug activation has not been comprehensively examined. To this end, we performed targeted sequencing ofNT5C2in 588 children with ALL and identified 121 single nucleotide polymorphisms (SNPs) nominally associated with erythrocyte TGN during 6-MP treatment (P< 0.05). Of these, 61 variants were validated in a replication cohort of 372 children with ALL. After considering linkage disequilibrium and multivariate analysis, we confirmed two clusters of variants, represented by rs72846714 and rs58700372, that independently affected 6-MP metabolism. Functional studies showed that rs58700372 directly altered the activity of an intronic enhancer, with the variant allele linked to higher transcription activity and reduced 6-MP metabolism (lower TGN). By contrast, rs72846714 was not located in a regulatory element and instead its association signal was explained by linkage disequilibrium with a proximal functional variant rs12256506 that activatedNT5C2transcription in-cis. Our results indicated thatNT5C2germline variation significantly contributes to inter-patient variability in thiopurine drug disposition.
Spike development inhibition in theftinmutant is associated with multiple phenotypes and regulated by multiple biological pathways
Authors: Zheng Yongsheng , Zhang Jinpeng , Liu Cheng , Zhang Han , Ji Xiajie , Wang Mumu , wang Hui , Zhang Rongzhi , Li Ruyu , Liu Weihua 
Published: October 2020

SummarySpike development of wheat line 3558M was strongly inhibited by low temperature stress in spring. Thefertile tiller inhibition(ftin) gene in the wheat line 3558M is associated with multiple phenotypes, including the production of fewer tillers, delayed floral transition, and death of the shoot apical meristem. We systematically investigated the genes and pathways underlying the differences using ITRAQ proteomics and RNA-sequencing technologies and found multiple biological pathways including to the cold acclimation pathway and multiple defence responses (e.g. reactive oxygen species-mediated hypersensitive response, salicylic acid-mediated systemic acquired resistance) are activated and led to tillers death of the wheat line 3558M under cold stress. Meanwhile, the cold acclimation pathway inhibited the SVP-SCO1-LFY flowering pathway and led to delayed floral transition. Particularly, two TaPIN proteins were significantly downregulated, and multiple auxin signalling genes were also differentially expressed. Knocking down the twoTaPINgenes using RNAi technology significantly reduced the tiller number. The cold stress inhibited the auxin transport to reduce the tillers of 3558M. Taken together, theftingene might be a cold-sensitive mutation and that is the cause of multiple biological pathways and phenotypic changes.
Social contact patterns among employees in 3 U.S. companies during early phases of the COVID-19 pandemic, April to June 2020
Authors: Kiti Moses C. , Aguolu Obianuju G. , Liu Carol Y. , Mesa Ana R. , Regina Rachel , Willebrand Kathryn , Couzens Chandra , Bartelsmeyer Tilman , Nelson Kristin , Jenness Samuel , Riley Steven , Melegaro Alessia , Ahmed Faruque , Malik Fauzia , Lopman Ben , Omer Saad B. 
Published: October 2020

2.AbstractImportanceDevising control strategies against diseases such as COVID-19 require understanding of contextual social mixing and contact patterns. There has been no standardized multi-site social contact study conducted in workplace settings in the United States that can be used to broadly inform pandemic preparedness policy in these settings.ObjectiveThe study aimed to characterize the patterns of social contacts and mixing across workplace environments, including on-site or when teleworking.DesignThis was a cross-sectional non-probability survey that used standardized social contact diaries to collect data. Employees were requested to record their physical and non-physical contacts in a diary over two consecutive days, documented at the end of each day. Employees from each company were enrolled through email and electronic diaries sent as individual links. Data were collected from April to June 2020.SettingTwo multinational consulting companies and one university administrative department, all located in Georgia, USA.ParticipantsEmployees opted into the study by accepting the invitation on a link sent via email.Main OutcomeThe outcome was median number of contacts per person per day. This was stratified by day of data collection, age, sex, race and ethnicity.ResultsOf 3,835 employees approached, 357 (9.3%) completed the first day of contact diary of which 304 completed both days of contact diary. There was a median of 2 contacts (IQR: 1-4, range: 0-21) per respondent on both day one and two. The majority (55%) of contacts involved conversation only, occurred at home (64%), and cumulatively lasted more than 4 hours (38%). Most contacts were repeated, and within same age groups, though participants aged 30-59 years reported substantial inter-generational mixing with children.ConclusionParticipating employees in 3 surveyed workplaces reported few contacts, similar to studies from the UK and China when shelter-in-place orders were in effect during the pandemic. Many contacts were repeated which may limit the spread of infection. Future rounds are planned to assess changes in contact patterns when employees resume work in the office after the lockdown due to COVID-19 pandemic.
The global burden of yellow fever
Authors: Gaythorpe Katy A. M. , Hamlet Arran T. P. , Jean Kevin , Ramos Daniel Garkauskas , Cibrelus Laurence , Garske Tini , Ferguson Neil M. 
Published: October 2020

AbstractBackgroundYellow fever (YF) is a viral haemorrhagic fever endemic in tropical regions of Africa and South America. Current intervention policies, namely the Eliminate Yellow fever Epidemics (EYE) strategy are actioned through vaccination. However, the stockpiles and production mean that vaccination can be in short supply. As such, intervention strategies need to be optimised; one of the tools for doing this is mathematical modelling.MethodsWe fit a generalised linear model of YF reports to occurrence data available from 1987 to 2019 in Africa and South America and available serology survey data to estimate the force of infection across the continents. Then, using demographic and vaccination data, we examine the impact of interventions.FindingsWe estimate that in 2018 there were approximately 51,000 (95%CrI [31,000 - 82,000]) deaths due to YF in Africa and South America. When we examine the impact of mass vaccination campaigns in Africa, these amount to approximately 10,000 (95%CrI [6,000 - 17,000]) deaths averted in 2018 due to mass vaccination activities in Africa; this corresponds to a 47% reduction (95%CrI [10% - 77%]).InterpretationWe find that the majority, 92% (95%CrI [89% - 95%]), of global burden occurs in Africa and that mass vaccination activities have significantly reduced the current deaths per year due to YF. This methodology allows us to evaluate the effectiveness of vaccination campaigns past, present and future and illustrates the need for continued vigilance and surveillance of YF.FundingBMGF and MRC
Novel age-dependent cortico-subcortical morphologic interactions predict fluid intelligence: A multi-cohort geometric deep learning study
Authors: Wu Yunan , Besson Pierre , Azcona Emanuel A. , Bandt S. Kathleen , Parrish Todd B , Breiter Hans C , Katsaggelos Aggelos K. 
Published: October 2020

AbstractBrain structure is tightly coupled with brain functions, but it remains unclear how cognition is related to brain morphology, and what is consistent across neurodevelopment. In this work, we developed graph convolutional neural networks (gCNNs) to predict Fluid Intelligence (Gf) from shapes of cortical ribbons and subcortical structures. T1-weighted MRIs from two independent cohorts, the Human Connectome Project (HCP; age: 28.81±3.70) and the Adolescent Brain Cognitive Development Study (ABCD; age: 9.93±0.62) were independently analyzed. Cortical and subcortical surfaces were extracted and modeled as surface meshes. Three gCNNs were trained and evaluated using six-fold nested cross-validation. Overall, combining cortical and subcortical surfaces yielded the best predictions on both HCP (R=0.454) and ABCD datasets (R=0.314), and outperformed the current literature. Across both datasets, the morphometry of the amygdala and hippocampus, along with temporal, parietal and cingulate cortex consistently drove the prediction of Gf, suggesting a novel reframing of the morphometry underlying Gf.
Structural characterisation of KKT4, an unconventional microtubule-binding kinetochore protein
Authors: Ludzia Patryk , Lowe Edward D. , Marcianò Gabriele , Mohammed Shabaz , Redfield Christina , Akiyoshi Bungo 
Published: October 2020

AbstractThe kinetochore is the macromolecular protein machinery that drives chromosome segregation by interacting with spindle microtubules. Unlike most other eukaryotes that have canonical kinetochore proteins, a group of evolutionarily divergent eukaryotes called kinetoplastids (such asTrypanosoma brucei) have a unique set of kinetochore proteins. To date, KKT4 is the only kinetoplastid kinetochore protein that is known to bind microtubules. Here we use X-ray crystallography, NMR spectroscopy, and crosslinking mass spectrometry to characterise the structure and dynamics of KKT4. We show that its microtubule-binding domain consists of a coiled-coil structure followed by a positively charged disordered tail. The crystal structure of the C-terminal BRCT domain of KKT4 reveals that it is likely a phosphorylation-dependent protein-protein interaction domain. The BRCT domain interacts with the N-terminal region of the KKT4 microtubule-binding domain and with a phosphopeptide derived from KKT8. Finally, we show that KKT4 binds DNA with high affinity. Taken together, these results provide the first structural insights into the unconventional kinetoplastid kinetochore protein KKT4.
Rapidemic, a versatile and label-free DNAzyme-based platform for visual nucleic acid detection
Authors: van den Brink Marijn , Tandar Sebastian T. , van den Akker Tim A. P. , Jovikj Sinisha , Defourt Violette , Langelaar Tom G. B. , Delzenne Tijn O. , van Strien Kelly , Schonk Amber W. , Beers Aukje J. A. M. , Golov Eugene , Chong Lucy J. , Bergman Güniz Özer , Meijdam Joey J. W. D. , Crooijmans Marjolein E. , Claessen Dennis , de Winde Johannes H. 
Published: October 2020

AbstractIn the last three decades, there have been recurring outbreaks of infectious diseases, brought to light with the recent outbreak of coronavirus disease 2019 (COVID-19). Attempts to effectively contain the spread of infectious diseases have been hampered by the lack of rapidly adaptable, accurate, and accessible point-of-care diagnostic testing. In this study, we present a novel design of a label-free DNAzyme-based detection method called Rapidemic. This assay combines recombinase polymerase amplification (RPA) with linear strand-displacement amplification (LSDA) and guanine-quadruplex (GQ) DNAzyme-catalysed colour-changing reaction. The colorimetry basis of the signal readout omits the need for extensive instrumentation. Moreover, the primer-based sequence detection of RPA gives Rapidemic a potential to be rapidly adapted to target a new sequence. As a proof of concept, we developed the assay to detect isolated genomic DNA ofSaccharomyces cerevisiae. The use of low-pH buffers and the optimization of the dilution rates from each preceding reaction to the next showed to be successful strategies to enable visible detection with this method. These findings demonstrate for the first time that a label-free DNAzyme-based detection method can be coupled to RPA and LSDA for nucleic acid detection.
Nucleolin is expressed in human fetal brain development and reactivated in human glial brain tumors regulating angiogenesis and vascular metabolism
Authors: Schwab Marc , de Trizio Ignazio , Shiu Jau-Ye , Ghobrial Moheb , Sürücü Oguzkan , Girolamo Francesco , Errede Mariella , Yilmaz Murat , Haybaeck Johannes , Moiraghi Alessandro , Monnier Philippe P. , Lawler Sean E. , Greenfield Jeffrey , Radovanovic Ivan , Frei Karl , Schlapbach Ralph , Vogel Viola , Virgintino Daniela , De Bock Katrien , Wälchli Thomas 
Published: October 2020

ABSTRACTGlioblastoma (GBM) is amongst the deadliest human cancers and is characterized by high levels of vascularisation. Angiogenesis is highly dynamic during brain development and almost quiescent in the adult brain, but is reactivated in vascular-dependent CNS pathologies such as brain tumors. Nucleolin (NCL) is a known regulator of cell proliferation and angiogenesis, but its roles on physiological and pathological brain vasculature remain unknown. Here, we studied the expression of Nucleolin in the neurovascular unit (NVU) in human fetal brains and human gliomasin vivoas well as its effects on sprouting angiogenesis and endothelial metabolismin vitro. Nucleolin is highly expressed in endothelial- and perivascular cells during brain development, downregulated in the adult brain, and upregulated in glioma. Moreover, Nucleolin expression in tumor- and blood vessel cells correlated with glioma malignancyin vivo. In culture, siRNA-mediated NCL knockdown reduced human umbilical vein endothelial cell (HUVEC) sprouting angiogenesis, proliferation and filopodia extension, and reduced glucose metabolism. Mechanistically, RNA sequencing of Nucleolin knockdown in HUVECs revealed a putative p53-TIGAR-HK2 regulation of endothelial glycolysis. These findings identify Nucleolin as a neurodevelopmental factor reactivated in glioma that positively regulates sprouting angiogenesis and endothelial metabolism. Our findings have important implications in therapeutic targeting of glioma.
Augmentation of Antibacterial Activity in Mesenchymal Stromal Cells Through Systems-Level Analysis and CRISPR-mediated Activation of CD14
Authors: Hirakawa Matthew P. , Tjahjono Nikki , Light Yooli K. , Chintalapudi Prem , Butler Kimberly S. , Branda Steven S. , Krishnakumar Raga 
Published: October 2020

ABSTRACTMesenchymal stromal cells (MSCs) have broad-ranging therapeutic capabilities, however MSC use is confounded by cell-to-cell heterogeneity, and source-to-source phenotypic inconsistencies. We utilized a systems-based approach to compare MSCs which displayed different capacity for antibacterial activity. Although MSCs from both sources satisfied traditional MSC-defining criteria, comparative transcriptomics and quantitative membrane proteomics demonstrated two unique molecular profiles. The antibacterial MSCs respond rapidly to bacterial lipopolysaccharide (LPS) and have elevated levels of the LPS co-receptor CD14. CRISPR-mediated overexpression of endogenous CD14 in non-antibacterial MSCs resulted in faster LPS response and enhanced antimicrobial activity. Single-cell transcriptome profiling of CD14-activated MSCs revealed uniform enhancement of LPS response kinetics, and a shift in the ground state of these MSCs. Our results demonstrate that systems-level analysis can reveal critical molecular targets to optimize desirable properties in MSCs, and that overexpression of CD14 in these cells can shift their state to be more responsive to future bacterial challenge.
HDAC3 regulates senescence and lineage specificity in non-small cell lung cancer
Authors: Eichner Lillian J. , Curtis Stephanie D. , Brun Sonja N. , Baumgart Joshua T. , Ross Debbie S. , Rymoff Tammy J. , Shaw Reuben J. 
Published: October 2020

SummaryTranscriptional deregulation is a common feature of many cancers, which is often accompanied by changes in epigenetic controls. These findings have led to the development of therapeutic agents aimed at broad modulation and reprogramming of transcription in a variety of cancers. Histone Deacetylase 3, HDAC3, is one of the main targets of HDAC inhibitors currently in clinical development as cancer therapies, yet thein vivorole of HDAC3 in solid tumors is unknown. Here, we define the role of HDAC3 in two genetic engineered models of the most common subtypes of Kras-driven Non-Small Cell Lung Cancer (NSCLC), KrasG12D, STK11−/−(KL) and KrasG12D, p53−/−(KP), where we found that HDAC3 is strongly required for tumor growth of both genotypesin vivo. Transcriptional profiling and mechanistic studies revealed that HDAC3 represses p65 NF-κB-mediated induction of the Senescence Associated Secretory Program (SASP) and HDAC3 binds directly at the promoters of SASP CXC chemokines. Additionally, HDAC3 was found to cooperate with the lung cancer lineage transcription factor NKX2-1 to mediate expression of a common set of target genes. Leveraging observations about one HDAC3/NKX2-1 common target, FGFR1, we identified that an HDAC3-dependent transcriptional cassette becomes hyperactivated as Kras mutant cancer cells develop resistance to the MEK inhibitor Trametinib, and this can be rescued by treatment with the Class I HDAC inhibitor Entinostat. These unexpected findings reveal new roles for HDAC3 in proliferation control in tumorsin vivoand identify specific therapeutic contexts for the utilization of HDAC3 inhibitors, whose ability to mechanistically induce SASP may be harnessed therapeutically.