bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-stimulated regions in early visual cortex encode the contents of conscious visual perception
Authors: van Kemenade Bianca M. , Wilbertz Gregor , Müller Annalena , Sterzer Philipp 
Published: November 2020

AbstractPredictions shape our perception. The theory of predictive processing poses that our brains make sense of incoming sensory input by generating predictions, which are sent back from higher to lower levels of the processing hierarchy. These predictions are based on our internal model of the world and enable inferences about the hidden causes of the sensory input data. It has been proposed that conscious perception corresponds to the currently most probable internal model of the world. Accordingly, predictions influencing conscious perception should be fed back from higher to lower levels of the processing hierarchy. Here, we used functional magnetic resonance imaging (fMRI) and multivoxel pattern analysis to show that non-stimulated regions of early visual areas contain information about the conscious perception of an ambiguous visual stimulus. These results indicate that early sensory cortices in the human brain receive predictive feedback signals that reflect the current contents of conscious perception.
Identification of novel Alzheimer’s disease genes co-expressed withTREM2
Authors: Reddy Joseph S. , Allen Mariet , Wang Xue , Biernacka Joanna M. , Coombes Brandon J. , Jenkins Gregory D. , Sinnwell Jason P. , Carrasquillo Minerva M. , Pottier Cyril P. , Ren Yingxue , Sarangi Vivekananda , Younkin Curtis S. , Asmann Yan W. , Ross Owen A. , Rademakers Rosa , Golde Todd E. , Ertekin-Taner Nilüfer , Younkin Steven G. 
Published: November 2020

AbstractBy analyzing whole-exome data from the Alzheimer’s disease sequencing project (ADSP), we identify a set of 4 genes that show highly significant association with Alzheimer’s disease (AD). These genes were identified within a humanTREM2co-expression network using a novel approach wherein prioritized polygenic score analyses were performed sequentially to identify significant polygenic components. Two of the 4 genes (TREM2,RIN3) have previously been linked to AD and two (ATP8B4,IL17RA) are novel. LikeTREM2, the 2 novel AD genes are selectively expressed in human microglial cells. The most significant variants inATP8B4andIL17RAare non-synonymous variants with strong effects comparable to the APOE ε4 and ε2 alleles. These protein-altering variants will provide unique opportunities to further explore the biological role of microglial cells in AD and help inform future immune modulatory therapeutic development for AD.
Pathway-extended gene expression signatures integrate novel biomarkers that improve predictions of patient responses to kinase inhibitors
Authors: Bagchee-Clark Ashis J. , Mucaki Eliseos J. , Whitehead Tyson , Rogan Peter K. 
Published: November 2020

AbstractCancer chemotherapy responses have been related to multiple pharmacogenetic biomarkers, often for the same drug. This study utilizes machine learning to derive multi-gene expression signatures that predict individual patient responses to specific tyrosine kinase inhibitors, including erlotinib, gefitinib, sorafenib, sunitinib, lapatinib and imatinib. Support Vector Machine learning was used to train mathematical models that distinguished sensitivity from resistance to these drugs using a novel systems biology-based approach. This began with expression of genes previously implicated in specific drug responses, then expanded to evaluate genes whose products were related through biochemical pathways and interactions. Optimal pathway-extended support vector machines predicted responses in patients at accuracies of 70% (imatinib), 71% (lapatinib), 83% (sunitinib), 83% (erlotinib), 88% (sorafenib) and 91% (gefitinib). These best performing pathway-extended models demonstrated improved balance predicting both sensitive and resistant patient categories, with many of these genes having a known role in cancer etiology. Ensemble machine learning-based averaging of multiple pathway-extended models derived for an individual drug increased accuracy to >70% for erlotinib, gefitinib, lapatinib, and sorafenib. Through incorporation of novel cancer biomarkers, machine learning-based pathway-extended signatures display strong efficacy predicting both sensitive and resistant patient responses to chemotherapy.
Real-time monitoring of subcellular H2O2distribution inChlamydomonas reinhardtii
Authors: Niemeyer Justus , Scheuring David , Oestreicher Julian , Morgan Bruce , Schroda Michael 
Published: November 2020

AbstractH2O2has been recognized as an important signaling molecule in plants. We sought to establish a genetically encoded, fluorescent H2O2sensor that allows H2O2monitoring in all major subcompartments of a Chlamydomonas cell. To this end we engineered the hypersensitive H2O2sensor, roGFP2-Tsa2ΔCR, as a genetic part for the Chlamydomonas Modular Cloning toolbox. Using previously generated parts, together with new ones, we constructed modules and devices that target the sensor to the cytosol, nucleus, mitochondrial matrix, chloroplast stroma, thylakoid lumen, and ER. The sensor was functional in all compartments, except for the ER where it was fully oxidized. Employing our novel sensors, we show that H2O2produced by photosynthetic linear electron transport (PET) in the stroma leaks into the cytosol but only reaches other subcellular compartments if produced under non-physiological conditions. Our results thus imply the establishment of steep intracellular H2O2gradients under normal physiological conditions and suggest that the cytosolic complement of H2O2scavenging enzymes effectively limits H2O2diffusion. Furthermore, in heat stressed cells, we show that cytosolic H2O2levels closely mirror temperature up- and downshifts and are independent from PET. We anticipate that these sensors will greatly facilitate future investigations into H2O2biology in algal and plant cells.
CRISPAltRations: a validated cloud-based approach for interrogation of double-strand break repair mediated by CRISPR genome editing
Authors: Kurgan Gavin , Turk Rolf , Li Heng , Roberts Nathan , Rettig Garrett R. , Jacobi Ashley M. , Tso Lauren , Mertens Massimo , Noten Roel , Florus Kurt , Behlke Mark A. , Wang Yu , McNeill Matthew S. 
Published: November 2020

AbstractCRISPR systems enable targeted genome editing in a wide variety of organisms by introducing single- or double-strand DNA breaks, which are repaired using endogenous molecular pathways. Characterization of on- and off-target editing events from CRISPR proteins can be evaluated using targeted genome resequencing. We characterized DNA repair footprints that result from non-homologous end joining (NHEJ) after double stranded breaks (DSBs) were introduced by Cas9 or Cas12a for >500 paired treatment/control experiments. We found that building our understanding into a novel analysis tool (CRISPAltRations) improved results’ quality. We validated our software using simulated rhAmpSeq™ amplicon sequencing data (11 gRNAs and 603 on- and off-target locations) and demonstrate that CRISPAltRations outperforms other publicly available software tools in accurately annotating CRISPR-associated indels and homology directed repair (HDR) events. We enable non-bioinformaticians to use CRISPAltRations by developing a web-accessible, cloud-hosted deployment, which allows rapid batch processing of samples in a graphical user-interface (GUI) and complies with HIPAA security standards. By ensuring that our software is thoroughly tested, version controlled, and supported with a UI we enable resequencing analysis of CRISPR genome editing experiments to researchers no matter their skill in bioinformatics.
Spontaneous thalamic activity modulates the cortical innervation of the primary visual nucleus of the thalamus
Authors: Moreno-Juan Verónica , Aníbal-Martínez Mar , Herrero-Navarro Álvaro , Valdeolmillos Miguel , Martini Francisco J. , López-Bendito Guillermina 
Published: November 2020

SummarySensory processing relies on the correct development of thalamocortical loops. Visual corticothalamic axons (CTAs) invade the dorsolateral geniculate nucleus (dLGN) of the thalamus in early postnatal mice according to a regulated program that includes activity-dependent mechanisms. Spontaneous retinal activity influences the thalamic incursion of CTAs, yet the perinatal thalamus also generates intrinsic patterns of spontaneous activity whose role in modulating afferent connectivity remains unknown. Here, we found that patterned spontaneous activity in the dLGN contributes to proper spatial and temporal innervation of CTAs. Disrupting patterned spontaneous activity in the dLGN delays corticogeniculate innervation under normal conditions and upon eye enucleation. The delayed innervation was evident throughout the first two postnatal weeks but resumes after eye-opening, suggesting that visual experience is necessary for the homeostatic recovery of corticogeniculate innervation.
High-resolution transcriptome atlas and improved genome assembly of common buckwheat,Fagopyrum esculentum
Authors: Penin Aleksey A. , Kasianov Artem S. , Klepikova Anna V. , Kirov Ilya V. , Gerasimov Evgeny S. , Fesenko Aleksey N. , Logacheva Maria D. 
Published: November 2020

SummaryCommon buckwheat (Fagopyrum esculentum) is an important non-cereal grain crop and a prospective component of functional food. Despite this, the genomic resources for this species and for the whole family Polygonaceae, to which it belongs, are scarce. Here, we report the assembly of the buckwheat genome using long-read technology and a high-resolution expression atlas including 46 organs and developmental stages. We found that the buckwheat genome has an extremely high content of transposable elements, including several classes of recently (0.5-1 Mya) multiplied TEs (“transposon burst”) and gradually accumulated TEs. The difference in TE content is a major factor contributing to the 3-fold increase in the genome size ofF. esculentumcompared with its sister speciesF. tataricum. Moreover, we detected the differences in TE content between the wild ancestral subspeciesF. esculentumssp.ancestraleand buckwheat cultivars, suggesting that TE activity accompanied buckwheat domestication. Expression profiling allowed us to test a hypothesis about the genetic control of petaloidy in buckwheat. We showed that it is not mediated by B-class gene activity, in contrast to the prediction from the ABC model. Based on a survey of expression profiles and phylogenetic analysis, we identified the MYB family transcription factor gene tr_18111 as a potential candidate for the determination of conical cells in buckwheat petaloid tepals. The information on expression patterns has been integrated into the publicly available database TraVA:http://travadb.org/browse/Species=Fesc/. The improved genome assembly and transcriptomic resources will enable research on buckwheat, including practical applications.
Anatomic position determines oncogenic specificity in melanoma
Authors: Weiss Joshua M. , Hunter Miranda V. , Cruz Nelly M. , Baggiolini Arianna , Tagore Mohita , Ma Yilun , Misale Sandra , Marasco Michelangelo , Simon-Vermot Theresa , Campbell Nathaniel R. , Newell Felicity , Wilmott James S. , Johansson Peter A. , Thompson John F. , Long Georgina V. , Pearson John V. , Mann Graham J. , Scolyer Richard A. , Waddell Nicola , Montal Emily D. , Huang Ting-Hsiang , Jonsson Philip , Donoghue Mark T.A. , Harris Christopher C. , Taylor Barry S. , Xu Tianhao , Chaligné Ronan , Shliaha Pavel V. , Hendrickson Ronald , Jungbluth Achim A. , Lezcano Cecilia , Koche Richard , Studer Lorenz , Ariyan Charlotte E. , Solit David B. , Wolchok Jedd D. , Merghoub Taha , Rosen Neal , Hayward Nicholas K. , White Richard M. 
Published: November 2020

SummaryOncogenic alterations to DNA are not transforming in all cellular contexts1,2. This may be due to pre-existing transcriptional programs in the cell of origin. Here, we define anatomic position as a major determinant of why cells respond to specific oncogenes. Cutaneous melanoma arises throughout the body, whereas the acral subtype arises on the palms of the hands, soles of the feet, or under the nails3. We sequenced the DNA of cutaneous and acral melanomas from a large cohort of human patients and found a specific enrichment for BRAF mutations in cutaneous melanoma but CRKL amplifications in acral melanoma. We modeled these changes in transgenic zebrafish models and found that CRKL-driven tumors predominantly formed in the fins of the fish. The fins are the evolutionary precursors to tetrapod limbs, indicating that melanocytes in these acral locations may be uniquely susceptible to CRKL. RNA profiling of these fin/limb melanocytes, compared to body melanocytes, revealed a positional identity gene program typified by posterior HOX13 genes. This positional gene program synergized with CRKL to drive tumors at acral sites. Abrogation of this CRKL-driven program eliminated the anatomic specificity of acral melanoma. These data suggest that the anatomic position of the cell of origin endows it with a unique transcriptional state that makes it susceptible to only certain oncogenic insults.
Sodium-Calcium Exchanger Mediates Sensory-Evoked Glial Calcium Transients in the Developing Retinotectal System
Authors: Benfey Nicholas J. , Li Vanessa J. , Schohl Anne , Ruthazer Edward S. 
Published: November 2020

AbstractVarious types of sensory stimuli have been shown to induce calcium elevations in glia. However, a mechanistic understanding of the signalling pathways mediating sensory-evoked activity in glia in intact animals is still emerging. Here we demonstrate that during early development of the Xenopus laevis visual system, radial astrocytes in the optic tectum are highly responsive to sensory stimulation. Calcium transients occur spontaneously in radial astrocytes at rest and are abolished by silencing neuronal activity with tetrodotoxin. Visual stimulation drives temporally correlated increases in the activity patterns of neighbouring radial astrocytes. Following blockade of all glutamate receptors, visually-evoked calcium activity in radial astrocytes is enhanced, rather than suppressed, while the additional blockade of either glutamate transporters or sodium-calcium exchangers (NCX) fully prevents visually-evoked responses. Additionally, we demonstrate that blockade of NCX alone is sufficient to prevent visually-evoked responses in radial astrocytes, highlighting a pivotal role for NCX in glia during development.
TCRβ Sequencing Reveals Spatial and Temporal Evolution of Clonal CD4 T cell Responses in a Breach of Tolerance Model of Inflammatory Arthritis
Authors: Al-Khabouri Shaima , Benson Robert A. , Prendergast Catriona T. , Gray Joshua I. , Otto Thomas D , Brewer James M , Garside Paul 
Published: November 2020

ABSTRACTEffective tolerogenic intervention in Rheumatoid Arthritis (RA) will rely upon understanding the evolution of articular antigen specific CD4 T cell responses. TCR clonality of endogenous CD4 T cell infiltrates in early inflammatory arthritis was assessed to monitor evolution of the TCR repertoire in the inflamed joint and associated lymph node (LN). Mouse models of antigen-induced breach of self-tolerance and chronic polyarthritis were used to recapitulate early and late phases of RA. The infiltrating endogenous, antigen experienced CD4 T cells in inflamed joints and LNs were analysed using flow cytometry and TCRβ sequencing. TCR repertoires from inflamed late phase LNs displayed increased clonality and diversity compared to early phase LNs, while inflamed joints remained similar with time. Repertoires from late phase LNs accumulated clones with a diverse range of TRBV genes, while inflamed joints at both phases contained clones expressing similar TRBV genes. Repertoires from LNs and joints at the late phase displayed reduced CDR3β sequence overlap compared to the early disease phase, however the most abundant clones in LNs accumulate in the joint at the later phase. The results indicate CD4 T cell repertoire clonality and diversity broadens with progression of inflammatory arthritis and is first reflected in LNs before mirroring in the joint. These observations imply that antigen specific tolerogenic therapies could be more effective if targeted at earlier phases of disease when CD4 T cell clonality is least diverse.
Mayaro Virus Infection Elicits an Innate Immune Response inAnopheles stephensi
Authors: Henderson Cory , Brustolin Marco , Hegde Shivanand , Dayama Gargi , Lau Nelson , Hughes Grant L. , Bergey Christina , Rasgon Jason L. 
Published: November 2020

ABSTRACTMayaro virus (MAYV) is an arboviral pathogen in the genusAlphavirusthat is circulating in South America with potential to spread to naïve regions. MAYV is also one of the few viruses with the ability to be transmitted by mosquitoes in the genusAnopheles, as well as the typical arboviral transmitting mosquitoes in the genusAedes. Few studies have investigated the infection response ofAnophelesmosquitoes. In this study we detail the transcriptomic and small RNA responses ofAn. stephensito infection with MAYV via infectious bloodmeal at 2, 7, and 14 days post infection (dpi). 487 unique transcripts were significantly regulated, 78 putative novel miRNAs were identified, and an siRNA response is observed targeting the MAYV genome. Gene ontology analysis of transcripts regulated at each timepoint suggested activation of the Toll pathway at 7 dpi and repression of pathways related to autophagy and apoptosis at 14 dpi. These findings provide a basic understanding of the infection response ofAn. stephensito MAYV and help to identify host factors which might be useful to target to inhibit viral replication inAnophelesmosquitoes.AUTHOR SUMMARYMayaro virus (MAYV) is a mosquito-borne Alphavirus responsible for outbreaks in South America and the Caribbean. In this study we infectedAnopheles stephensiwith MAYV and sequenced mRNA and small RNA to understand how MAYV infection impacts gene transcription and the expression of small RNAs in the mosquito vector. Genes involved with innate immunity and signaling pathways related to cell death are regulated in response to MAYV infection ofAn. stephensi, we also discover novel miRNAs and describe the expression patterns of miRNAs, siRNAs, and piRNAs following bloodmeal ingestion. These results suggest that MAYV does induce a molecular response to infection in its mosquito vector species.
Loss of ASH1L in developing brains causes autistic-like behaviors in a mouse model
Authors: Gao Yuen , Duque-Wilckens Natalia , Aljazi Mohammad B , Wu Yan , Moeser Adam J , Mias George I , Robison Alfred J , He Jin 
Published: November 2020

AbstractAutism spectrum disorder (ASD) is a neurodevelopmental disease associated with various gene mutations. Recent genetic and clinical studies report that mutations of the epigenetic geneASH1Lare highly associated with human ASD and intellectual disability (ID). However, the causal link betweenASH1Lmutations and ASD/ID remains undetermined. Here we show loss of ASH1L in developing mouse brains is sufficient to cause multiple developmental defects, core autistic-like behaviors, and impaired cognitive memory. Gene expression analyses uncover critical roles of ASH1L in regulating gene expression during neural cell development. Thus, our study establishes a new ASD/ID mouse model revealing the critical function of ASH1L in normal brain development, a causality betweenAsh1Lmutations and ASD/ID-like behaviors in mice, and potential molecular mechanisms linkingAsh1Lmutations to brain functional abnormalities.
Greek chemical engineers. Are they static or mobile? Evidence from the national archive of PhD theses
Authors: Sachini Evi , Sioumalas-Christodoulou Konstantinos , Chrysomallidis Charalampos , Siganos Galatios , Karampekios Nikolaos 
Published: November 2020

Purpose
The purpose of this paper is to identify the geographical location of researchers.

Design/methodology/approach
Combine standard bibliometric databases with social media data.

Findings
The majority of the population of the sample (71.8%) – Greek chemical engineers – are static. A significant portion of the mobile researchers (28.2%) returned to their country of origin (25.6%). Performing network analysis, the cluster of countries corresponding to the mobile category of researchers is identified and depicted.

Originality/value
Herein, this study introduce a new, national data set on doctorate holders that will allow multiple bibliometric analyses in the future. Also, this study is among the few (Gendronneau et al., 2019) that combines standard bibliometric databases with social media data. In cases where multiple affiliations per year pose a difficulty in understanding the geographical location of each individual, LinkedIn data were used. The analysis sheds light on a field of science that is not extensively examined in terms of brain circulation. While similar publications focus on physicians (i.e. cardiologists – Dyachenko and Mironenko, 2018), this paper focus on a subset of doctorate holders in engineering.
Measuring the supply chain competitiveness of e-commerce industry in Indonesia
Authors: Febransyah Ade , Camelia Goni Joklan Imelda 
Published: November 2020

Purpose
The purpose of this study is to measure the supply chain competitiveness of the e-commerce industry in Indonesia.

Design/methodology/approach
The study used a multi-criteria decision-making model based on the analytic hierarchy process. Four main criteria are used to measure the supply chain competitiveness, i.e. cost, differentiation, sustainability and infrastructure.

Findings
The findings of this study show that cost is the most important criterion with a degree of importance of 33.19%, followed by infrastructure of 29.40%, differentiation of 27.96% and sustainability of 9.45%. It shows that the internally controlled strategy contributes about 70% of supply chain competitiveness. The internal infrastructure criterion that consists of software and hardware contributes 65.92% to the whole infrastructure criterion. The internal infrastructure then contributes 19.38% to supply chain competitiveness. Therefore, the internally controlled strategies and internal infrastructure contribute up to 90.08% to the supply chain competitiveness of e-commerce in Indonesia. This result implies that to attain the supply chain competitiveness, the company must carry out strategies focusing on the performance such as cost, differentiation, sustainability as well as on the internal infrastructure such as software and hardware.

Research limitations/implications
In this paper, the authors limited their study to the business to business (B2B) and business to consumer (B2C) players because these two platforms have been experiencing a very rapid growth. While e-commerce business can take many platforms besides B2B and B2C, the future research should include other platform such as consumer to consumer as well. Because the focus in this study is more the information and material flows, it will be of great interest if the future research covers the platform of mobile payment as well that guarantee the ease of cashflows within supply chains. Also, with the occurrence of the Covid-19 pandemic when this paper was written, in the near future, it is then of great interest to incorporate the pandemic context into the proposed model used in this study. The further study should analyze long-term changes happened as the result of pandemic such as behavioral changes of online shopping from customer side or shift in e-commerce supply chain infrastructure and inventory practice.

Practical implications
With this study, it is expected that it can be determined which criteria contribute the most to the supply chain competitiveness of the e-commerce industry in Indonesia that will be useful for industry player.

Originality/value
E-commerce development in Indonesia is still facing serious challenges. The multi-criteria decision making approach used in this research lays a foundation of how supply chain competitiveness is determined based on the judgment of experts coming from major companies within the supply chain.