bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monoclonal antibodies for the S2 subunit of spike of SARS-CoV cross-react with the newly-emerged SARS-CoV-2
Authors: Zheng Zhiqiang , Monteil Vanessa M. , Maurer-Stroh Sebastian , Yew Chow Wenn , Leong Carol , Mohd-Ismail Nur Khairiah , Arularasu Suganya Cheyyatraivendran , Chow Vincent Tak Kwong , Pin Raymond Lin Tzer , Mirazimi Ali , Hong Wanjin , Tan Yee-Joo 
Published: March 2020

AbstractThe emergence of a novel coronavirus, SARS-CoV-2, at the end of 2019 has resulted in widespread human infections across the globe. While genetically distinct from SARS-CoV, the etiological agent that caused an outbreak of severe acute respiratory syndrome (SARS) in 2003, both coronaviruses exhibit receptor binding domain (RBD) conservation and utilize the same host cell receptor, angiotensin-converting enzyme 2 (ACE2), for virus entry. Therefore, it will be important to test the cross-reactivity of antibodies that have been previously generated against the surface spike (S) glycoprotein of SARS-CoV in order to aid research on the newly emerged SARS-CoV-2. Here, we show that an immunogenic domain in the S2 subunit of SARS-CoV S is highly conserved in multiple strains of SARS-CoV-2. Consistently, four murine monoclonal antibodies (mAbs) raised against this immunogenic SARS-CoV fragment were able to recognise the S protein of SARS-CoV-2 expressed in a mammalian cell line. Importantly, one of them (mAb 1A9) was demonstrated to detect S in SARS-CoV-2-infected cells. To our knowledge, this is the first study showing that mAbs targeting the S2 domain of SARS-CoV can cross-react with SARS-CoV-2 and this observation is consistent with the high sequence conservation in the S2 subunit. These cross-reactive mAbs may serve as tools useful for SARS-CoV-2 research as well as for the development of diagnostic assays for its associated coronavirus disease COVID-19.
Transcriptome analysis of the NematodeCaenorhabditis elegansin acidic stress environments
Authors: Cong Yanyi , Yang Hanwen , Zhang Pengchi , Xie Yusu , Cao Xuwen , Zhang Liusuo 
Published: March 2020

AbstractOcean acidification and acid rain, caused by modern industrial fossil fuels burning, lead to decrease of living environmental pH, which results in a series of negative effects on many organisms. However, the underlying mechanisms of animals’response to acidic pH stress are largely unknown. In this study, we used the nematodeCaenorhabditis elegansas an animal model to explore the regulatory mechanisms of organisms’response to pH decline. Two major stress-responsive pathways were found through transcriptome analysis in acidic stress environments. Firstly, when the pH dropped from 6.33 to 4.33, the worms responded to the pH stress by up-regulation of thecol,nasanddpygenes, which are required for cuticle synthesis and structure integrity. Secondly, when the pH continued to decrease from 4.33, the metabolism of xenobiotics by cytochrome P450 pathway genes (cyp, gst, ugt,and ABC transporters) played a major role in protecting the nematodes from the toxic substances probably produced by the more acidic environment. At the same time, cuticle synthesis slowed down might due to its insufficient protective ability. Moreover, the systematic regulation pattern we found in nematodes, might also be applied to other invertebrate and vertebrate animals to survive in the changing pH environments. Thus, our data might lay the foundation to identify the master gene(s) responding and adaptation to acidic pH stress in further studies, and might also provide new solutions to improve assessment and monitoring of ecological restoration outcomes, or generate novel genotypes via genome editing for restoring in challenging environments especially in the context of acidic stress through global climate change.
Rcirc: an R package for circRNA analyses and visualization
Authors: Sun Peisen , Wang Haoming , Li Guanglin 
Published: March 2020

AbstractCircular RNA (circRNA), which has a closed-loop structure, is a kind of special endogenous RNA and plays important roles in many biological processes. With the improvement of next-generation sequencing technology and bioinformatics methods, some tools have been published for circRNA detection based on RNA-seq. However, only a few tools focus on downstream analyses, and they have poor visualization ability. Here, we developed the R package ‘Rcirc’ for further analyses of circRNA after its detection. Rcirc identifies the coding ability of circRNA and visualize various aspects of this feature. It also provides general visualization for both single circRNAs and meta-features of thousands of circRNAs. Rcirc was designed as a user-friendly tool that covers many highly automatic functions without running many complicated processes by users. It is available on GitHub (https://github.com/PSSUN/Rcirc) under the license GPL 3.0.
Deep learning-based adaptive detection of fetal nucleated red blood cells
Authors: Sun Chao , Wang Ruijie , Zhao Lanbo , Han Lu , Ma Sijia , Liang Dongxin , Wang Lei , Tuo Xiaoqian , Zhong Dexing , Li Qiling 
Published: March 2020

AbstractAimthis study, we established an artificial intelligence system for rapid identification of fetal nucleated red blood cells (fNRBCs).MethodDensity gradient centrifugation and magnetic-activated cell sorting were used for the separation of fNRBCs from umbilical cord blood. The cell block technique was used for fixation. We proposed a novel preprocessing method based on imaging characteristics of fNRBCs for region of interest (ROI) extraction, which automatically segmented individual cells in peripheral blood cell smears. The discriminant information from ROIs was encoded into a feature vector and pathological diagnosis were provided by the prediction network.ResultsFour umbilical cord blood samples were collected and validated based on a large dataset containing 260 samples. Finally, the dataset was classified into 3,720 and 1,040 slides for training and testing, respectively. In the test set, classifier obtained 98.5% accuracy and 96.5% sensitivity.ConclusionTherefore, this study offers an effective and accurate method for fNRBCs preservation and identification.
Unsupervised cell interaction profiling reveals major architectural differences between small intestinal and colonic epithelial crypts
Authors: Serviss Jason T. , Andrews Nathanael , Andersson Agneta B. , Dzwonkowska Ewa , Heijboer Rosan , Geyer Natalie , Gerling Marco , Enge Martin 
Published: March 2020

AbstractCellular identity in complex multicellular organisms is strictly maintained over the course of life. This control is achieved in part by the organ structure itself, such that neighboring cells influence each other’s identity. However, large-scale investigation of the cellular interactome has been technically challenging. Here, we develop CIM-seq, an unsupervised and high-throughput method to analyze direct physical cell-cell interactions between every cell type in a given tissue. CIM-seq is based on RNA sequencing of incompletely dissociated cells, followed by computational deconvolution of these into their constituent cell types using machine learning. We use CIM-seq to define the cell interaction landscape of the mouse small intestinal and colonic epithelium, uncovering both known and novel interactions. Specifically, we find that the general architecture of the stem cell niche is radically different between the two tissues. In small intestine, the stem-Paneth cell interaction forms an exceptionally strong and exclusive niche, in which Paneth cells provide Wnt ligands1. In colonic epithelium, no similar compartment exists to support stem cells, and Wnt signaling is provided by a mesenchymal cell layer2,3. However, colonic stem cells are supported by an adjacent, previously unrecognized goblet cell subtype expressing the wound-healing marker Plet1, which is also highly upregulated during regeneration of colon epithelium. These results identify novel cellular interactions specific for the colonic stem cell niche and suggest an additional level of structural control in the colon. CIM-seq is broadly applicable to studies that aim to simultaneously investigate the constituent cell types and the global interaction profile in a specific tissue.
Metabolic labeling of RNA using multiple ribonucleoside analogs enables simultaneous evaluation of transcription and degradation rates
Authors: Kawata Kentaro , Wakida Hiroyasu , Yamada Toshimichi , Taniue Kenzui , Han Han , Seki Masahide , Suzuki Yutaka , Akimitsu Nobuyoshi 
Published: March 2020

SummaryGene expression is one of the factors determining cellular conditions, and its level is determined by the balance between transcription and RNA degradation. However, it has been not well elucidated how transcription and degradation are related to each other. To elucidate the relationship of them, methods enabling simultaneous measurement of transcription and degradation are required. Here, we report the development of “Dyrec-seq” to evaluate transcription and RNA degradation rates simultaneously, by using 4-thiouridine and 5-bromouridine. Using Dyrec-seq, we quantified the transcription and degradation rates of 4,702 genes in HeLa cells. Functional enrichment analysis showed that the transcription and degradation rates of genes are actually determined by the genes’ biological functions. Comparison of theoretical and experimental analysis results revealed that the amount of RNA was determined by the ratio of transcription to degradation rates, while the rapidity of responses to external stimuli was determined only by the degradation rate. This study emphasizes that degradation as well as transcription is important in determining the behavior of RNA.
Photo-excited Toluidine Blue disaggregates the Repeat Tau and modulates cytoskeletal structure in neuronal cells
Authors: Dubey Tushar , Gorantla Nalini Vijay , Chinnathambi Subashchandrabose 
Published: March 2020

AbstractAlzheimer’s disease is a progressive neurological disorder characterized by the intracellular accumulation of Tau protein aggregates. Inhibition of protein aggregation by photo-excited dyes is emerging as novel strategy for the treatment of certain diseases. Toluidine Blue is a basic phenothiazine dye having potency of photo-excitation by irradiation with red light at 630±20 nm. In present work, we studied the effect of Toluidine Blue and photo-excited TB on aggregation of repeat Tau in-vitrousing Thioflavin S fluorescence assay, SDS-PAGE and electron microscopy. Results show that TB efficiently inhabited the formation of higher order aggregates. Moreover, the photo-excited TB led to disaggregation of the mature repeat Tau fibrils. Further, studies on the effect of Toluidine blue on cell viability and cytoskeleton network of Neuro2acells show that TB was not toxic to neuronal cells at lower concentrations but at high concentrations (> 5 μM) both TB and photo-excited TB induced significant toxicity. Immunofluorescence studies on the cytoskeleton of Neuro2a cells show that Toluidine Blue and photo-excited Toluidine Blue treatment at non-toxic concentration of 0.5 μM stimulated formation of actin rich lamellipodia and filopodia structures. Tubulin networks were also differentially modulated after the treatment of Toluidine Blue and photo-excited Toluidine Blue. End Binding protein 1 (EB1) levels were observed to increase after Toluidine Blue and photo-excited Toluidine Blue treatment indicating the accelerated microtubule polymerization. The overall study suggested that Toluidine Blue inhibited the aggregation of soluble Tau and photo-excited Toluidine Blue disaggregated the pre-formed Tau filaments.
Unprecedentedly efficient CUG initiation of an overlapping reading frame inPOLGmRNA yields novel protein POLGARF
Authors: Loughran G , Zhdanov AV , Mikhaylova MS , Rozov FN , Datskevich PN , Kovalchuk SI , Serebryakova MV , Kiniry S , Michel AM , O’Connor PBF , Papkovsky DB , Atkins JF , Baranov PV , Shatsky IN , Andreev DE 
Published: March 2020

AbstractWhile near cognate codons are frequently used for translation initiation in eukaryotes, their efficiencies are usually low (<10% compared to an AUG in optimal context). Here we describe a rare case of highly efficient near cognate initiation. A CUG triplet located in the 5’ leader ofPOLGmRNA initiates almost as efficiently (~60-70%) as an AUG in optimal context. This CUG directs translation of a conserved 260 triplet-long overlapping ORF, which we callPOLGARF(POLGAlternativeReadingFrame). Translation of a short upstream ORF 5’ of this CUG governs the ratio between DNA polymerase and POLGARF produced from a singlePOLGmRNA. Functional investigation of POLGARF points to extracellular signalling. While unprocessed POLGARF resides in the nucleoli together with its interacting partner C1QBP, serum stimulation results in rapid secretion of POLGARF C-terminal fragment. Phylogenetic analysis shows thatPOLGARFevolved ~160 million years ago due to an MIR transposition into the 5’ leader sequence of the mammalianPOLGgene which became fixed in placental mammals. The discovery ofPOLGARFunveils a previously undescribed mechanism ofde novoprotein-coding gene evolution.Significance StatementIn this study, we describe previously unknown mechanism ofde novoprotein-coding gene evolution. We show that thePOLGgene, which encodes the catalytic subunit of mitochondrial DNA polymerase, is in fact a dual coding gene. Ribosome profiling, phylogenetic conservation, and reporter construct analyses all demonstrate thatPOLGmRNA possesses a conserved CUG codon which serves as a start of translation for an exceptionally long overlapping open reading frame (260 codons in human) present in all placental mammals. We called the protein encoded in this alternative reading frame POLGARF. We provide evidence that the evolution ofPOLGARFwas incepted upon insertion of an MIR transposable element of the SINE family.
Irgm2 and Gate-16 cooperatively dampen targeting of caspase-11 to Gram-negative bacterial products
Authors: Eren Elif , Planès Rémi , Bagayoko Salimata , Bordignon Pierre-Jean , Chaoui Karima , Hessel Audrey , Santoni Karin , Pinilla Miriam , Burlet-Schiltz Odile , Howard Jonathan C. , Yamamoto Masahiro , Meunier Etienne 
Published: March 2020

AbstractInflammatory caspase-11 (rodent) and caspases-4 and -5 (human) detect gram-negative bacterial component LPS in the host cell cytosol, which promotes activation of the non-canonical inflammasome. Although non-canonical inflammasome-induced pyroptosis and IL-1 related cytokine release is of importance to mount an efficient immune response against various bacteria, its unrestrained activation drives sepsis. This suggests that cellular components might tightly control the threshold level of the non-canonical inflammasome in order to ensure efficient but not deleterious inflammatory response. Here we show that the IFN-inducible protein Irgm2 and the ATG8 family member Gate-16 cooperatively slow down non-canonical inflammasome activation both in macrophages andin vivo. Specifically, the Irgm2/Gate-16 axis dampens caspase-11 targeting to intracellular bacteria, which lower caspase-11-mediated pyroptosis and cytokine release. Specifically, deficiency inIrgm2orGate16opens an alternative road for caspase-11 targeting to intracellular bacteria, independently of the classical pathway driven by the Guanylate Binding Proteins (GBPs). Thus, our findings provide new molecular effectors involved at fine-tuning the optimal non-canonical inflammasome response and add novel insights in the understanding of the immune pathways they control.
DMLDA-LocLIFT: Identification of multi-label protein subcellular localization using DMLDA dimensionality reduction and LIFT classifier
Authors: Zhang Qi , Li Shan , Yu Bin , Zhang Qingmei , Zhang Yan , Ma Qin 
Published: March 2020

ABSTRACTBackgroundMulti-label proteins occur in two or more subcellular locations, which play a vital part in cell development and metabolism. Prediction and analysis of multi-label subcellular localization (SCL) can present new angle with drug target identification and new drug design. However, the prediction of multi-label protein SCL using biological experiments is expensive and labor-intensive. Therefore, predicting large-scale SCL with machine learning methods has turned into a hot study topic in bioinformatics.MethodsIn this study, a novel multi-label learning means for protein SCL prediction, called DMLDA-LocLIFT, is proposed. Firstly, the dipeptide composition, encoding based on grouped weight, pseudo amino acid composition, gene ontology and pseudo position specific scoring matrix are employed to encode subcellular protein sequences. Then, direct multi-label linear discriminant analysis (DMLDA) is used to reduce the dimension of the fused feature vector. Lastly, the optimal feature vectors are input into the multi-label learning with Label-specIfic FeaTures (LIFT) classifier to predict the location of multi-label proteins.ResultsThe jackknife test showed that the overall actual accuracy on Gram-negative bacteria, Gram-positive bacteria, and plant datasets are 98.60%, 99.60%, and 97.90% respectively, which are obviously better than other state-of-the-art prediction methods.ConclusionThe proposed model can effectively predict SCL of multi-label proteins and provide references for experimental identification of SCL. The source codes and data are publicly available athttps://github.com/QUST-AIBBDRC/DMLDA-LocLIFT/.
Conjugative dissemination of plasmids in rapid sand filters: a trojan horse strategy to enhance pesticide degradation in groundwater treatment
Authors: Pinilla-Redondo Rafael , Olesen Asmus Kalckar , Russel Jakob , de Vries Lisbeth Elvira , Christensen Lisbeth Damkjær , Musovic Sanin , Nesme Joseph , Sørensen Søren Johannes 
Published: March 2020

AbstractThe supply of clean water for human consumption is being challenged by the appearance of pesticide pollutants in groundwater ecosystems. Biological rapid sand filtration is a commonly employed method for the removal of organic and inorganic impurities in water which relies on the degradative properties of microorganisms for the removal of diverse contaminants, including pesticides. Although sustainable and relatively inexpensive, the bioremediation capabilities of rapid sand filters vary greatly across waterworks. Bioaugmentation efforts with degradation-proficient bacteria have proven difficult due to the inability of the exogenous microbes to stably colonize the sand filters. Pesticide degrading genes, however, are often encoded naturally by plasmids—extrachromosomal DNA elements that can transfer between bacteria—yet their ability to spread within rapid sand filters have remained unknown. To evaluate the potential use of plasmids for the dissemination of pesticide degrading genes, we examined the permissiveness of rapid sand filter communities towards four environmental transmissible plasmids; RP4, RSF1010, pKJK5 and TOL (pWWO), using a dual-fluorescent bioreporter platform combined with FACS and 16S rRNA gene amplicon sequencing. Our results reveal that plasmids can transfer at high frequencies and across distantly related taxa from rapid sand filter communities, emphasizing their suitability for introducing pesticide degrading determinants in the microbiomes of underperforming water purification plants.
Altered Sensorimotor-to-Transmodal Hierarchical Organization in Schizophrenia
Authors: Dong Debo , Yao Dezhong , Wang Yulin , Hong Seok-Jun , Genon Sarah , Xin Fei , Jung Kyesam , He Hui , Chang Xuebin , Duan Mingjun , Bernhardt Boris , Margulies Daniel S. , Sepulcre Jorge , Eickhoff Simon B. , Luo Cheng 
Published: March 2020

AbstractFor decades, schizophrenia has been primarily conceptualized as a disorder of high-order cognitive functions with deficits in executive brain regions. Yet due to the increasing reports of early sensory processing deficit, recent models focus more on the developmental effects of impaired sensory process on high-order functions. The present study examined whether this pathological interaction relates to an overarching system-level imbalance, specifically a disruption in macroscale hierarchy affecting integration and segregation of unimodal and transmodal networks. We applied a novel combination of connectome gradient and stepwise connectivity analysis to resting-state functional magnetic resonance imaging (rsfMRI) to characterize the sensorimotor-to-transmodal cortical hierarchy organization (96 patients vs. 122 controls). Using these techniques, we demonstrated compression of the cortical hierarchy organization in schizophrenia, with a prominent compression from the sensorimotor region and a less prominent compression from the frontal-parietal region, resulting in a diminished separation between sensory and fronto-parietal cognitive systems. Further analyses suggested reduced differentiation related to atypical functional connectome transition from unimodal to transmodal brain areas. Specifically, we found hypo-connectivity within unimodal regions and hyper-connectivity between unimodal regions and frontoparietal and ventral attention regions along the classical sensation-to-cognition continuum established in prior neuroanatomical work. The compression of cortical hierarchy organization represents a novel and integrative system-level substrate underlying the pathological interaction of early sensory and cognitive function in schizophrenia. This abnormal cortical hierarchy organization suggests cascaded impairments stemming from the disrupted somatosensory-motor system and inefficient integration of bottom-up sensory information with attentional demands and executive control processes partially account for high-level cognitive deficits characteristic of schizophrenia.
Rapid mechanoenzymatic saccharification of lignocellulosic biomass without bulk water or chemical pre-treatment
Authors: Hammerer Fabien , Ostadjoo Shaghayegh , Dietrich Karolin , Dumont Marie-Josée , Del Rio Luis F. , Friščić Tomislav , Auclair Karine 
Published: March 2020

AbstractLignocellulosic material is an abundant renewable resource with the potential to replace petroleum as a feedstock for the production of fuels and chemicals. The large scale deployment of biomass saccharification is, however, hampered by the necessity to use aggressive reagents and conditions, formation of side-products, and the difficulty to reach elevated monosaccharide concentrations in the crude product. Herein we report the high efficacy of Reactive Aging (or Raging, a technique where enzymatic reaction mixtures, without any bulk aqueous or organic solvent, are treated to multiple cycles of milling and aging) for gram-scale saccharification of raw lignocellulosic biomass samples from different agricultural sources (corn stover, wheat straw, and sugarcane bagasse). The solvent-free enzymatic conversion of lignocellulosic biomass was found to proceed in excellent yields (ca. 90%) at protein loadings as low as 2% w/w, without the need for any prior chemical pre-treatment or high temperatures, to produce highly concentrated (molar) monosaccharides. This crude product of mechanoenzymatic depolymerization is non-toxic to bacteria and can be used as a carbon source for bacterial growth.