bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and genetic diversity analysis of a male-sterile gene (MS1) in Japanese cedar (Cryptomeria japonicaD. Don)
Authors: Hasegawa Yoichi , Ueno Saneyoshi , Wei Fu-Jin , Matsumoto Asako , Uchiyama Kentaro , Ujino-Ihara Tokuko , Hakamata Tetsuji , Fujino Takeshi , Kasahara Masahiro , Bino Takahiro , Yamaguchi Katsushi , Shigenobu Shuji , Tsumura Yoshihiko , Moriguchi Yoshinari 
Published: May 2020

AbstractIdentifying causative genes for a target trait in conifer reproduction is challenging for species lacking whole-genome sequences. In this study, we searched for the male-sterility gene (MS1) inCryptomeria japonica, aiming to promote marker-assisted selection (MAS) of male-sterileC. japonicato reduce the pollinosis caused by pollen dispersal from artificialC. japonicaforests in Japan. We searched for mRNA sequences expressed in male strobili and found the gene CJt020762, coding for a lipid transfer protein containing a 4-bp deletion specific to male-sterile individuals. We also found a 30-bp deletion by sequencing the entire gene of another individual with thems1. All nine breeding materials with the allelems1had either a 4-bp or 30-bp deletion in gene CJt020762, both of which are expected to result in faulty gene transcription and function. Furthermore, the 30-bp deletion was detected from three of five individuals in the Ishinomaki natural forest. From our findings, CJt020762 was considered to be the causative gene ofMS1. Thus, by performing MAS using two deletion mutations as a DNA marker, it will be possible to find novel breeding materials ofC. japonicawith the allelems1adapted to the unique environment of each region of the Japanese archipelago.
Generating Artificial Sensations with Spinal Cord Stimulation in Primates and Rodents
Authors: Yadav Amol P. , Li Shuangyan , Krucoff Max O. , Lebedev Mikhail A. , Abd-El-Barr Muhammad M. , Nicolelis Miguel A.L. 
Published: May 2020

AbstractFor patients who have lost sensory function due to a neurological injury such as spinal cord injury (SCI), stroke, or amputation, spinal cord stimulation (SCS) may provide a mechanism for restoring somatic sensations via an intuitive, non-visual pathway. Inspired by this vision, here we trained rhesus monkeys and rats to detect and discriminate patterns of epidural SCS. Thereafter, we constructed psychometric curves describing the relationship between different SCS parameters and the animal’s ability to detect SCS and/or changes in its characteristics. We found that the stimulus detection threshold decreased with higher frequency, longer pulse-width, and increasing duration of SCS. Moreover, we found that monkeys were able to discriminate temporally- and spatially-varying patterns (i.e. variations in frequency and location) of SCS delivered through multiple electrodes. Additionally, sensory discrimination of SCS-induced sensations in rats obeyed Weber’s law of just noticeable differences. These findings suggest that by varying SCS intensity, temporal pattern, and location different sensory experiences can be evoked. As such, we posit that SCS can provide intuitive sensory feedback in neuroprosthetic devices.
Protein stability and functional activity during nebulization: A comparative study of three nebulizer!
Authors: Singh Niti , Yadav Preeti , Gaur Prekcha , Gaur Manish , Yadav Awadh Bihari 
Published: May 2020

AbstractDelivery of therapeutics protein to the lung offers effective treatments of lungs disease. Efficacy of delivered therapeutics molecules depends on integrity and stability of protein during nebulization. In this study, we compared three nebulizers: compressed air nebulizer (CAN), ultrasonic nebulizer (USN) and mesh nebulizer (MAN) to deliver aerosol dose, stability and functional activity of a model protein lysozyme. Lysozyme/BSA delivered dose assessed by indirect and direct method. It was shown CAN deliver 0.142±0.027 to 0.632± 0.09 ml of protein, USN deliver 0.511±0.119 to 1.688±0.173 ml and MAN deliver 0.238±0.006 to 0.731±0.013 ml of protein in the same time. Integrity of nebulized proteins were assessed by gel electrophoresis and circular diochorism. It was found integrity of lysozyme compromised in all three nebulizer maximum in CAN and minimum with MAN. The functional activity of protein was assessed after nebulization by turbidometry assay. The functional activity was compromised by all three nebulizer upto some extent. In conclusion, nebulization compromise protein stability: this impact depend on nebulization techniques as well as nature of protein. The CAN deliver protein more precisely in small amount in comparison to the other nebulizer.Abstract FigureGraphical Abstract
Isolation of full-length IgG antibodies from combinatorial libraries expressed in the cytoplasm ofEscherichia coli
Authors: Robinson Michael-Paul , Cox Emily C. , Li Mingji , Jaroentomeechai Thapakorn , Zheng Xiaolu , Chang Matthew , Berkmen Mehmet , DeLisa Matthew P. 
Published: May 2020

AbstractWe describe a facile and robust genetic selection for isolating full-length IgG antibodies from combinatorial libraries expressed in the cytoplasm of the genetically engineeredEscherichia colistrain, SHuffle. The method is based on the transport of a bifunctional substrate comprised of an antigen fused to chloramphenicol acetyltransferase, which allows positive selection of bacterial cells co-expressing cytoplasmic IgGs called ‘cyclonals’ that specifically capture the chimeric antigen and sequester the antibiotic resistance marker in the cytoplasm. The selective power of this approach was demonstrated by facile isolation of novel complementarity-determining regions for a cyclonal that specifically recognized the basic-region leucine zipper domain of the yeast transcriptional activator protein Gcn4.
Meta-Signer: Metagenomic Signature Identifier based on Rank Aggregation of Features
Authors: Reiman Derek , Metwally Ahmed A. , Sun Jun , Dai Yang 
Published: May 2020

AbstractBackgroundThe advance of metagenomic studies provides the opportunity to identify microbial taxa that are associated to human diseases. Multiple methods exist for the association analysis. However, the results could be inconsistent, presenting challenges in interpreting the host-microbiome interactions. To address this issue, we introduce Meta-Signer, a novelMetagenomicSignature Identifiertool based on rank aggregation of features identified from multiple machine learning models including Random Forest, Support Vector Machines, LASSO, Multi-Layer Perceptron Neural Networks, and our recently developed Convolutional Neural Network framework (PopPhy-CNN). Meta-Signer generates ranked taxa lists by training individual machine learning models over multiple training partitions and aggregates them into a single ranked list by an optimization procedure to represent the most informative and robust microbial features. Meta-Signer can rank taxa using two input forms of the data: the relative abundances of the original taxa and taxa from the populated taxonomic trees generated from the original taxa. The latter form allows the evaluation of the association of microbial features at different taxonomic levels to the disease, which is attributed to our novel model of PopPhy-CNN.ResultsWe evaluate Mega-Signer on five different human gut-microbiome datasets. We demonstrate that the features derived from Meta-Signer were more informative compared to those obtained from other available feature ranking methods. The highly ranked features are strongly supported by published literature.ConclusionMeta-Signer is capable of deriving a robust set of microbial features at multiple taxonomic levels for the prediction of host phenotype. Meta-Signer is user-friendly and customizable, allowing users to explore their datasets quickly and efficiently.
Evolutionary and Functional Lessons from Human-Specific Amino-Acid Substitution Matrices
Authors: Shauli Tair , Brandes Nadav , Linial Michal 
Published: May 2020

AbstractThe characterization of human genetic variation in coding regions is fundamental to our understanding of protein function, structure, and evolution. Amino-acid (AA) substitution matrices such as BLOSUM (BLOcks SUbstitution Matrix) and PAM (Point Accepted Mutations) encapsulate the stochastic nature of such proteomic variation and are used in studying protein families and evolutionary processes. However, these matrices were constructed from protein sequences spanning long evolutionary distances and are not designed to reflect polymorphism within species. To accurately represent proteomic variation within the human population, we constructed a set of human-centric substitution matrices derived from genetic variations by analyzing the frequencies of >4.8M single nucleotide variants (SNVs). These human-specific matrices expose short-term evolutionary trends at both codon and AA resolution and therefore present an evolutionary perspective that differs from that implicated in the traditional matrices. Specifically, our matrices consider the directionality of variants, and uncover a set of AA pairs that exhibit a strong tendency to substitute in a specific direction. We further demonstrate that the substitution rates of nucleotides only partially determine AA substitution rates. Finally, we investigate AA substitutions in post-translational modification (PTM) and ion-binding sites. We confirm a strong propensity towards conservation of the identity of the AA that participates in such functions. The empirically-derived human-specific substitution matrices expose purifying selection over a range of residue-based protein properties. The new substitution matrices provide a robust baseline for the analysis of protein variations in health and disease. The underlying methodology is available as an open-access to the biomedical community.
Universal MS/MS Visualization and Retrieval with the Metabolomics Spectrum Resolver Web Service
Authors: Bittremieux Wout , Chen Christopher , Dorrestein Pieter C. , Schymanski Emma L. , Schulze Tobias , Neumann Steffen , Meier Rene , Rogers Simon , Wang Mingxun 
Published: May 2020

AbstractThe growth of online mass spectrometry metabolomics resources, including data repositories, spectral library databases, and online analysis platforms has created an environment of online/web accessibility. Here, we introduce the Metabolomics Spectrum Resolver (https://metabolomics-usi.ucsd.edu/), a tool that builds upon these exciting developments to allow for consistent data export (in human and machine-readable forms) and publication-ready visualisations of tandem mass spectrometry spectra. This tool supports the Human Proteome Organization – Proteomics Standards Initiative’s Universal Spectrum Identifier (USI) specification, which has been extended to deal with the metabolomics use cases. To date, this resource already supports data formats from GNPS, MassBank, MS2LDA, MassIVE, MetaboLights, and Metabolomics Workbench and is integrated into several of these resources.
Mitogen-activated protein kinases are carbon dioxide receptors in plants
Authors: Gałgańska Hanna , Gałgański Łukasz 
Published: May 2020

AbstractThe amount of CO2in the atmosphere is increasing continuously in the industrial era, posing a threat to the ecological balance on Earth. There are two ways to reduce elevated CO2concentrations ([CO2]high): reducing human emissions or increasing their absorption by oceans and plants. However, in response to [CO2]high, plants diminish gas exchange and CO2uptake by closing stomata. Surprisingly, we do not know how plants sense CO2in their environment, and the basic mechanisms of the plant response to [CO2]highare very poorly understood. Here, we show that mitogen-activated protein kinases (MAPKs) are plant CO2receptors. We demonstrate that MPK4, a prominent MAPK that is known to be involved in the stomatal response to [CO2]high1–3, is capable of binding CO2and is directly activated by a very low increase in [CO2]in vivoandin vitro. Unlike MPK4 activation by infections4, stress and hormones within known MAPK signalling cascades, [CO2]high-induced MPK4 activation is independent of the upstream regulators MKK1 and MKK2. Moreover, once activated, MPK4 is prone to inactivation by bicarbonate. The identification of stress-responsive MPK4 as a CO2receptor sheds new light on the integration of various environmental signals in guard cells, setting up MPK4 as the main hub regulating CO2availability for photosynthesis. This result could help to find new ways to increase CO2uptake by plants.
Multiple introductions, regional spread and local differentiation during the first week of COVID-19 epidemic in Montevideo, Uruguay
Authors: Salazar Cecilia , Díaz-Viraqué Florencia , Pereira-Gómez Marianoel , Ferrés Ignacio , Moreno Pilar , Moratorio Gonzalo , Iraola Gregorio 
Published: May 2020

BackgroundAfter its emergence in China in December 2019, the new coronavirus disease (COVID-19) caused by SARS-CoV-2, has rapidly spread infecting more than 3 million people worldwide. South America is among the last regions hit by COVID-19 pandemic. In Uruguay, first cases were detected on March 13th2020 presumably imported by travelers returning from Europe.MethodsWe performed whole-genome sequencing of 10 SARS-CoV-2 from patients diagnosed during the first week (March 16thto 19th) of COVID-19 outbreak in Uruguay. Then, we applied genomic epidemiology using a global dataset to reconstruct the local spatio-temporal dynamics of SARS-CoV-2.ResultsOur phylogeographic analysis showed three independent introductions of SARS-CoV-2 from different continents. Also, we evidenced regional circulation of viral strains originally detected in Spain. Introduction of SARS-CoV-2 in Uruguay could date back as early as Feb 20th. Identification of specific mutations showed rapid local genetic differentiation.ConclusionsWe evidenced early independent introductions of SARS-CoV-2 that likely occurred before first cases were detected. Our analysis set the bases for future genomic epidemiology studies to understand the dynamics of SARS-CoV-2 in Uruguay and the Latin America and the Caribbean region.
Neuropathic Pain Linked to Defective Dopaminergic Inhibition in Anterior Cingulate Cortex
Authors: Lançon Kevin , Navratilova Edita , Porreca Frank , Séguéla Philippe 
Published: May 2020

AbstractPyramidal neurons in the anterior cingulate cortex (ACC), a prefrontal region involved in processing the affective components of pain, display hyperexcitability in chronic neuropathic conditions and their silencing abolishes hyperalgesia in rodents. We show here that dopamine, through D1-like receptor signaling, inhibits layer 2/3 pyramidal neurons of mouse ACC. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels control the firing activity of these pyramidal neurons. Through Gs-coupled D1-like receptors, dopamine induces the opening of HCN channels at physiological membrane potentials, driving a significant decrease in input resistance and excitability. Systemic L-DOPA rescues HCN channel activity, pyramidal excitability in ACC as well as sensory phenotype in neuropathic mice while microinjection of a selective D1-like agonist in ACC induces relief of ongoing pain in neuropathic animals. We conclude that decreased dopaminergic inhibition in ACC plays a critical role in an abnormal top-down modulation leading to neuropathic pain.
Transcriptome analysis reveals the genetic basis underlying the development of skin appendages and immunity in hedgehog (Atelerix albiventris)
Authors: Li Hui-Ming , Yang Bi-Ze , Zhang Xiu-Juan , Jiang Hai-Ying , Li Lin-Miao , Ahmad Hafiz Ishfaq , Chen Jin-Ping 
Published: May 2020

AbstractThe expression of hair features is an evolutionary adaptation resulting from interactions between many organisms and their environment. Elucidation of the mechanisms that underlie the expression of such traits is a topic in evolutionary biology research. Therefore, we assessed thede novotranscriptome ofAtelerix albiventrisat three developmental stages and compared gene expression profiles between abdomen hair and dorsal spine tissues. We identified 328,576 unigenes in our transcriptome, among which 3,598 were differentially expressed between hair- and spine-type tissues. Dorsal and abdomen skin tissues 5 days after birth were compared and the resulting differentially expressed genes were mainly enriched in keratin filament, epithelium cell differentiation, and epidermis development based on GO enrichment analysis, and tight junction, p53, and cell cycle signaling pathways based on KEGG enrichment analysis. Expression variations ofMBP8, SFN, Wnt10, KRT1,andKRT2may be the main factors regulating hair and spine differentiation for the hedgehog. Strikingly, DEGs in hair-type tissues were also significantly enriched in immune-related terms and pathways with hair-type tissues exhibiting more upregulated immune genes than spine-type tissues. Thus, we propose that spine development was an adaptation that provided protection against injuries or stress and reduced hedgehog vulnerability to infection.
Notch1 switches progenitor competence in inducing medulloblastoma
Authors: Ballabio Claudio , Gianesello Matteo , Lago Chiara , Okonechnikov Konstantin , Anderle Marica , Aiello Giuseppe , Antonica Francesco , Zhang Tingting , Gianno Francesca , Giangaspero Felice , Hassan Bassem A. , Pfister Stefan M. , Tiberi Luca 
Published: May 2020

SummaryThe identity of the cell of origin is a key determinant of cancer subtype, progression and prognosis. Group 3 Medulloblastoma (MB) is a malignant childhood brain cancer with poor prognosis and unknown cell of origin. We overexpressed the Group 3 MB genetic drivers MYC and Gfi1 in different candidate cells of origin in the postnatal mouse cerebellum. We found that S100b+cells are competent to initiate Group 3 MB, while Math1+, Sox2+or Ascl1+cells are not. We noted that S100b+cells have higher levels of Notch1 pathway activity compared to Math1+cells. Interestingly, we found that additional activation of Notch1 in Math1+cells was sufficient to induce Group 3 MB upon MYC/Gfi1 expression. Taken together, our data suggest that the MB cell of origin competence depends on the cellular identity, which relies on Notch1 activity.Graphical Abstract
Fronto-parietal, cingulo-opercular and striatal contributions to learning and implementing control policies
Authors: Bhandari Apoorva , Badre David 
Published: May 2020

AbstractEfficient task performance requires co-ordination of internal cognitive processes by implementing control policies adapted to the dynamic structure of task demands. The cognitive and neural basis of control policy implementation remains poorly characterized, in part because it is typically confounded with implementing new stimulus-response rules. To disambiguate these processes, we asked participants to perform multiple novel variants of a working memory control task. Each variant had a unique, novel sequential trial structure, but all shared common stimulusresponse rules, enabling us to test control policy implementation separate from rule learning. Behaviorally, we found evidence for two adaptive processes tied to control policy implementation. One process was reflected in slower responses on the first trial with a novel sequential trial structure, followed by rapid speeding on subsequent trials. A second process was reflected in the diminishing size of the first trial cost as participants accommodated different variants of the task over many blocks. Using fMRI, we observed that the striatum and a cingulo-opercular cortical network increased activity to the first trial, tracking the fast adjustment. This pattern of activity dissociated these regions from a fronto-parietal network including dorsolateral PFC, inferior frontal junction, inferior parietal sulcus, and rostrolateral PFC, which showed a slower decline in activity across trials, mirroring findings in rule implementation studies, but in the absence of rule implementation demands. Our results reveal two adaptive processes underlying the implementation of efficient, generalizable control policies, and suggest a broader account of the role of a cortico-striatal network in control policy implementation.Significance statementRapid adaptation to novel tasks is a hallmark of human behavior. Understanding how human brains achieve this is of critical importance in neuroscience. Here we broaden the scope of this problem, going beyond task rules to more broadly consider the cognitive control demands produced by novel task dynamics. We propose that humans rely on two adaptive processes to rapidly implement efficient, generalizable control policies as task dynamics change, even when task rules remain unchanged. One process unfolds rapidly and underlies efficient adaptation. A second process unfolds slowly with experience across task conditions and underlies generalization of control policies. Using fMRI, we identify cingulo-opercular cortex, fronto-parietal cortex and striatum as dissociable components of a cortico-striatal network that contribute to control implementation.
Aging markers in human urine: A comprehensive, non-targeted LC-MS study
Authors: Teruya Takayuki , Goga Haruhisa , Yanagida Mitsuhiro 
Published: May 2020

SummaryMetabolites in human biofluids document individual physiological status. We conducted comprehensive, non-targeted, non-invasive metabolomic analysis of urine from 27 healthy human subjects, comprising 13 youths (30±3 yr) and 14 seniors (76±4 yr). Quantitative analysis of 99 metabolites revealed 55 that were linked to aging, displaying significant differences in abundance between the two groups. These include 13 standard amino acids, 5 methylated, 4 acetylated, and 9 other amino acids, 6 nucleosides, nucleobases, and derivatives, 4 sugar derivatives, 5 sugar phosphates, 4 carnitines, 2 hydroxybutyrates, 1 choline, and 1 ethanolamine derivative, and glutathione disulfide. Abundances of 53 compounds decreased, while 2 increased in elderly people. Many age-linked markers were highly correlated; 42 of 55 compounds, showed Pearson’s correlation coefficients larger than 0.70. As metabolite profiles of urine and blood are quite different, age-related information in urine components offer yet more valuable insights into aging mechanisms of endocrine system and related organ systems.
Heparan sulfate proteoglycans as attachment factor for SARS-CoV-2
Authors: Liu Lin , Chopra Pradeep , Li Xiuru , Bouwman Kim M. , Tompkins S. Mark , Wolfert Margreet A. , de Vries Robert P. , Boons Geert-Jan 
Published: May 2020

ABSTRACTSevere acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) is causing an unprecedented global pandemic demanding the urgent development of therapeutic strategies. Microarray binding experiments using an extensive heparan sulfate (HS) oligosaccharide library showed that the receptor binding domain (RBD) of the spike of SARS-CoV-2 can bind HS in a length-and sequence-dependent manner. Hexa- and octa-saccharides composed of IdoA2S-GlcNS6S repeating units were identified as optimal ligands. Surface plasma resonance (SPR) showed the SARS-CoV-2 spike protein binds with much higher affinity to heparin (KD = 55 nM) compared to the RBD (KD = 1 μM) alone. We also found that heparin does not interfere in angiotensin-converting enzyme 2 (ACE2) binding or proteolytic processing of the spike. Our data supports a model in which HS functions as the point of initial attachment for SARS-CoV-2 infection. Tissue staining studies using biologically relevant tissues indicate that heparan sulfate proteoglycan (HSPG) is a critical attachment factor for the virus. Collectively, our results highlight the potential of using HS oligosaccharides as a therapeutic agent by inhibiting SARS-CoV-2 binding to target cells.