bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short and Long-read Sequencing Survey of the Dynamic Transcriptomes of African Swine Fever Virus and its Host
Authors: Olasz Ferenc , Tombácz Dóra , Torma Gábor , Csabai Zsolt , Moldován Norbert , Dörmő Ákos , Prazsák István , Mészáros István , Magyar Tibor , Tamás Vivien , Zádori Zoltán , Boldogkői Zsolt 
Published: February 2020

AbstractAfrican swine fever virus (ASFV) is an important animal pathogen causing substantial economic losses in the swine industry globally. At present, little is known about the molecular biology of ASFV, including its transcriptome organization. In this study, we applied cutting-edge sequencing approaches, namely the Illumina short-read sequencing (SRS) and the Oxford Nanopore Technologies long-read sequencing (LRS) techniques, together with several library preparation chemistries to analyze the ASFV dynamic transcriptome. SRS can generate a large amount of high-precision sequencing reads, but it is inefficient for identifying long RNA molecules, transcript isoforms and overlapping transcripts. LRS can overcome these limitations, but this approach also has shortcomings, such as its high error rate and the low coverage. Amplification-based LRS techniques produce relatively high read counts but also high levels of spurious transcripts, whereas the non-amplified cDNA and direct RNA sequencing techniques are more precise but achieve lower throughput. The drawbacks of the various technologies can be circumvented by the combined use of these approaches.
Dampened PI3K/AKT signaling contributes to cancer resistance of the naked mole rat
Authors: Zhao Jing , Tian Xiao , Zhu Yabing , Zhang Zhihui , Rydkina Elena , Yuan Yongxuan , Zhang Hongyun , Roy Bhaskar , Cornwell Adam , Nevo Eviatar , Shang Xiaoxiao , Huang Runyue , Kristiansen Karsten , Seluanov Andrei , Fang Xiaodong , Gorbunova Vera 
Published: February 2020

AbstractMammalian species have a dramatically different susceptibility to cancer. However, how cancer-resistant species resist oncogenic transformation is not fully understood. Here, we performed a comprehensive analysis of oncogene-induced transcriptional changes in the fibroblasts of a cancer-prone species, the mouse, and three cancer-resistant species, the human, the blind mole rat, and the naked mole rat. We report that multiple cellular processes are more refractory to oncogene-induced transcriptional changes in blind mole-rat, naked mole-rat, or human cells compared to mouse cells, such as cell division, cell adhesion, extracellular matrix organization, and metabolism. Strikingly, naked mole rat cells are more resistant to Ras-induced transcriptional changes compared to the other three species. As a mechanism, we found that critical genes in the PI3K pathway includingAkt1andPik3caare downregulated in naked mole rat cells. Activating the PI3K/AKT pathway in the naked mole rat cells renders them susceptible to tumorigenic transformation. This study provides multiple new insights into anti-cancer mechanisms in cancer-resistant species of mammals.Significance statementAnimal species differ greatly in their cancer susceptibility. Cancer rates in the mouse range from 50-90%, while two other rodent species, the naked mole rat and the blind mole rat have only a few cancer cases ever reported. Here we examined the mechanisms responsible these differences by comparing changes in transcription patters in response to oncoproteins in the mouse, naked mole rat, blind mole rat and human cells. The most striking finding was that the naked mole rat cells were resistant to transcriptional changes induced by oncogenic Ras. We found that pathways downstream of Ras were naturally attenuated in the naked mole rat. This finding identifies a novel mechanism that evolved to provide tumor resistance to the naked mole rat.
mTOR-driven widespread exon skipping renders multifaceted gene regulation and proteome complexity
Authors: Cheng Sze , Fahmi Naima Ahmed , Park Meeyeon , Chang Jae-Woong , Sun Jiao , Thao Kaitlyn , Yeh Hsin-Sung , Zhang Wei , Yong Jeongsik 
Published: February 2020

AbstractThe mammalian target of rapamycin (mTOR) pathway is crucial in cell proliferation. Previously, we reported transcriptome-wide 3’-untranslated region (UTR) shortening by alternative polyadenylation upon mTOR activation and its impact on the proteome. Here, we further interrogated the mTOR-activated transcriptome and found that hyperactivation of mTOR promotes transcriptome-wide exon-skipping/exclusion, producing short isoform transcripts from genes. This widespread exon skipping confers multifarious regulations in the mTOR-controlled functional proteomics: alternative splicing (AS) in the 5’-UTR controls translation efficiency while AS in coding regions widely affects the protein length and functional domains. They also alter the half-life of proteins and affect the regulatory post-translational modifications. Among the RNA processing factors differentially regulated by mTOR signaling, we found that SRSF3 mechanistically facilitates exon skipping in the mTOR-activated transcriptome. This study reveals a role of mTOR in AS regulation and demonstrates that widespread AS is a multifaceted modulator of the mTOR-regulated functional proteome.
Gradient of Tactile Properties in the Rat Whisker Pad
Authors: Gugig Erez , Sharma Hariom , Azouz Rony 
Published: February 2020

AbstractThe array of vibrissae on a rat’s face is the first stage in a high-resolution tactile sensing system. Progressing from rostral to caudal in any vibrissae row results in an increase in whisker length and thickness. This in turn may provide a systematic map of separate tactile channels governed by the mechanical properties of the whiskers. To examine whether this map is expressed in a location-dependent transformation of tactile signals into whisker vibrations and neuronal responses, we monitored whiskers’ movements across various surfaces and edges. We found a robust rostral-caudal gradient of tactile information transmission in which rostral shorter vibrissae displayed a higher sensitivity and a bigger differences in response to the different textures, whereas longer caudal vibrissae were less sensitive to the different textures. Nonetheless, we found that texture identity is not represented spatially across the whisker pad. Based on the responses of first-order sensory neurons, we found that neurons innervating rostral whiskers were better suited for textures discrimination, whereas neurons innervating caudal whiskers were more suited for edge detection. To examine the functional role of this organization, we monitored the whisking activity of awake rats foraging for food. We found a caudal-rostral gradient of whisking angle movements in which the longer caudal vibrissae spanned a larger space making them more suitable for object localization, whereas the rostral shorter vibrissae hardly moved. These results suggest that the whisker array in rodents forms a sensory structure in which different facets of tactile information are transmitted through location-dependent gradient of vibrissae on the rat’s face.
LC-Based Metabolomics and Multivariate Analyses Reveal Metabolite Variations in Different Propagation Methods ofEurycoma longifoliaRoots Harvested at Different Ages and Locations
Authors: Alias Nur Nabilah , Azizan Kamalrul Azlan , Basherudin Norlia , Hassan Nor Hasnida , Abdullah Nazirah 
Published: February 2020

AbstractEurycoma longifoliais a well-known medicinal plant with pharmacological effects and important bioactive compounds such as alkaloids and quassinoids. The suitable age of harvestingE. longifoliaroot for commercial use is relatively unknown and could influence the overall bioactive compounds present in the plant. In this study, non-targeted liquid chromatography mass spectrometer (LC-MS) and multivariate analyses (MVA) were performed to determine the chemical constituent of aqueous extract of 3-month-oldE. longifoliahairy root (HR) culture, 1-, 4- and 11-year-old harvestedE. longifoliaroots. Unsupervised principle component analysis (PCA) and supervised partial least square discriminant analysis (PLSDA) were applied to evaluate metabolic similarities and differences inE. longifoliaroots and hairy root in response to different harvesting age, locations and propagation methods. A total of 34 significant buckets with variable importance in projection (VIP) exceeding 1 were selected and identified. It was found that putatively identified quassinoids were significantly higher in 1-, 4- and 11-year-oldE. longifoliaroots whereas putative canthin-6-one alkaloids were abundantly present in 3-month-oldE. longifoliahairy root (HR). These findings may be applicable to improve the harvesting age and increase the content of bioactive compounds inE. longifoliaroots.
Cerebral organoid model reveals excessive proliferation of human caudal late interneuron progenitors in Tuberous Sclerosis Complex
Authors: Eichmüller Oliver L. , Corsini Nina S. , Vértesy Ábel , Scholl Theresa , Gruber Victoria-Elisabeth , Peer Angela M. , Chu Julia , Novatchkova Maria , Paredes Mercedes F. , Feucht Martha , Knoblich Jürgen A. 
Published: February 2020

SummaryAlthough the intricate and prolonged development of the human brain critically distinguishes it from other mammals1, our current understanding of neurodevelopmental diseases is largely based on work using animal models. Recent studies revealed that neural progenitors in the human brain are profoundly different from those found in rodent animal models2–5. Moreover, post-mortem studies revealed extensive migration of interneurons into the late-gestational and post-natal human prefrontal cortex that does not occur in rodents6. Here, we use cerebral organoids to show that overproduction of mid-gestational human interneurons causes Tuberous Sclerosis Complex (TSC), a severe neuro-developmental disorder associated with mutations inTSC1andTSC2. We identify a previously uncharacterized population of caudal late interneuron progenitors, the CLIP-cells. In organoids derived from patients carrying heterozygousTSC2mutations, dysregulation of mTOR signaling leads to CLIP-cell over-proliferation and formation of cortical tubers and subependymal tumors. Surprisingly, second-hit events resulting from copy-neutral loss-of-heterozygosity (cnLOH) are not causative for but occur during the progression of tumor lesions. Instead, EGFR signaling is required for tumor proliferation, opening up a promising approach to treat TSC lesions. Our study demonstrates that the analysis of developmental disorders in organoid models can lead to fundamental insights into human brain development and neuropsychiatric disorders.
Prediction of the receptorome for the human-infecting virome
Authors: Zhang Zheng , Ye Sifan , Wu Aiping , Jiang Taijiao , Peng Yousong 
Published: February 2020

AbstractThe virus receptors are key for the viral infection of host cells. Identification of the virus receptors is still challenging at present. Our previous study has shown that human virus receptor proteins have some unique features including high N-glycosylation level, high number of interaction partners and high expression level. Here, a random-forest model was built to identify human virus receptorome from human cell membrane proteins with an accepted accuracy based on the combination of the unique features of human virus receptors and protein sequences. A total of 1380 human cell membrane proteins were predicted to constitute the receptorome of the human-infecting virome. In addition, the combination of the random-forest model with protein-protein interactions between human and viruses predicted in previous studies enabled further prediction of the receptors for 693 human-infecting viruses, such as the Enterovirus, Norovirus and West Nile virus. As far as we know, this study is the first attempt to predict the receptorome for the human-infecting virome and would greatly facilitate the identification of the receptors for viruses.
ULK1 and ULK2 are less redundant than previously thought: Computational analysis uncovers distinct regulation and functions of these autophagy induction proteins
Authors: Demeter Amanda , Romero-Mulero Mari Carmen , Csabai Luca , Ölbei Márton , Sudhakar Padhmanand , Haerty Wilfried , Korcsmáros Tamás 
Published: February 2020

AbstractMacroautophagy, the degradation of cytoplasmic content by lysosomal fusion, is an evolutionary conserved process promoting homeostasis and intracellular defence. Macroautophagy is initiated primarily by a complex containing ULK1 or ULK2 (two paralogs of the yeast Atg1 protein). Deletion of ULK1 is sufficient to interrupt autophagy, while ULK2 seems expendable. To understand the differences between ULK1 and ULK2, we compared the human ULK1 and ULK2 proteins and their regulation. Despite the high similarity in their enzymatic domain, we found that ULK1 and ULK2 have major differences in their post-translational and transcriptional regulators. We identified 18 ULK1-specific and 7 ULK2-specific protein motifs serving as different interaction interfaces. We identified threeULK1-specific and oneULK2-specific transcription factor binding sites, and eight sites shared by the regulatory region of both genes. Importantly, we found that both their post-translational and transcriptional regulators are involved in distinct biological processes - suggesting separate functions for ULK1 and ULK2. For example, we found a condition-specific, opposite effect on apoptosis regulation for the two ULK proteins. Given the importance of autophagy in diseases such as inflammatory bowel disease and cancer, unravelling differences between ULK1 and ULK2 could lead to a better understanding of how autophagy is dysregulated in diseased conditions.
Sensory input drives rapid homeostatic scaling of the axon initial segment in mouse barrel cortex
Authors: Jamann Nora , Dannehl Dominik , Wagener Robin , Corcelli Corinna , Schultz Christian , Staiger Jochen , Kole Maarten H.P. , Engelhardt Maren 
Published: February 2020

SummaryThe axon initial segment (AIS) is an important axonal microdomain for action potential initiation and implicated in the regulation of neuronal excitability during activity-dependent cortical plasticity. While structural AIS plasticity has been suggested to fine-tune neuronal activity when network states change, whether it acts as a homeostatic regulatory mechanism in behaviorally relevant contexts remains poorly understood. Using anin vivomodel of the mouse whisker-to-barrel pathway in combination with immunofluorescence, confocal analysis and patch-clamp electrophysiological recordings, we observed bidirectional AIS plasticity. Furthermore, we find that structural and functional AIS remodeling occurs in distinct temporal domains: long-term sensory deprivation elicits an AIS length increase, accompanied with an increase in neuronal excitability, while sensory enrichment results in a rapid AIS shortening, accompanied by a decrease in action potential generation. Our findings highlight a central role of the AIS in the homeostatic regulation of neuronal input-output relations.
Elevated soluble Galectin-3 as a marker of chemotherapy efficacy in Breast cancer patients; a prospective study
Authors: Shafiq Arooj , Moore January , Suleman Aliya , Faiz Sabeen , Farooq Omar , Arshad Adnan , Tehseen Mohammad , Zafar Ammarah , Ali Syed Haider , Din Nasir Ud , Loya Asif , Siddiqui Neelam , Rehman Fatima K. 
Published: February 2020

ABSTRACTPurposeGalectin-3 (Gal-3) is a glycan-binding lectin with a debated role in cancer progression due to its various functions and patterns of expression. The current study investigates the relationship between breast cancer prognosis and secreted Gal-3.MethodsBreast cancer patients with first time cancer diagnosis and no prior treatment (n=88) were placed in either adjuvant or neoadjuvant setting based on their treatment modality. Stromal and plasma Gal-3 levels were measured in each patient at the time of diagnosis and then throughout treatment using immunohistochemistry (IHC) and ELISA respectively. Healthy women (>18 years of age,n=63) were used to establish baseline levels of plasma Gal-3. Patients were followed for 84 months for disease free survival analysis.ResultsEnhanced levels of plasma (adjuvant) and stromal (neo-adjuvant) Gal-3 were found to be markers of chemotherapy efficacy. The patients with chemotherapy induced increase in extracellular Gal-3 had longer disease-free interval and significantly lower rate of recurrence during 84-month follow-up compared to patients with unchanged or decreased secretion.ConclusionThe findings support the use of plasma Gal-3 as a marker for chemotherapy efficacy when no residual tumor is visible through imaging. Furthermore, stromal levels in any remaining tumors post chemotherapy can also be used to predict long term prognosis in patients.Key pointsIncreased Gal-3 secretion due to chemotherapy leads to better prognosis and longer disease-free survival.The analysis of soluble Gal-3 expression could be useful as a support tool in predicting treatment efficacy in patients with no visible tumor remaining for follow up through imaging.
Alteration of brain dynamics during natural dual-task walking
Authors: Nenna Federica , Do Cao-Tri , Protzak Janna , Gramann Klaus 
Published: February 2020

ABSTRACTWhile walking in our natural environment, we continuously solve additional cognitive tasks. This increases the demand of resources needed for both the cognitive and motor systems, resulting in Cognitive-Motor Interference (CMI). While it is well known that a performance decrease in one or both tasks can be observed, little is known about human brain dynamics underlying CMI during dual-task walking. Moreover, a large portion of previous investigations on CMI took place in static settings, emphasizing the experimental rigor but overshadowing the ecological validity. To address these problems, we developed a dual-task walking scenario in virtual reality (VR) combined with Mobile Brain/Body Imaging (MoBI). We aimed at investigating how brain dynamics are modulated during natural overground walking while simultaneously performing a visual discrimination task in an ecologically valid scenario. Even though the visual task did not affect performance while walking, a P3 amplitude reduction along with changes in power spectral densities (PSDs) during dual-task walking were observed. Replicating previous results, this reflects the impact of walking on the parallel processing of visual stimuli, even when the cognitive task is particularly easy. This standardized and easy to modify VR-paradigm helps to systematically study CMI, allowing researchers to control the complexity of different tasks and sensory modalities. Future investigations implementing an improved virtual design with more challenging cognitive and motor tasks will have to investigate the roles of both cognition and motion, allowing for a better understanding of the functional architecture of attention reallocation between cognitive and motor systems during active behavior.
AnnotatorJ: an ImageJ plugin to ease hand-annotation of cellular compartments
Authors: Hollandi Réka , Diósdi Ákos , Hollandi Gábor , Moshkov Nikita , Horváth Péter 
Published: February 2020

AbstractAnnotatorJ combines single-cell identification with deep learning and manual annotation. Cellular analysis quality depends on accurate and reliable detection and segmentation of cells so that the subsequent steps of analyses e.g. expression measurements may be carried out precisely and without bias. Deep learning has recently become a popular way of segmenting cells, performing unimaginably better than conventional methods. However, such deep learning applications may be trained on a large amount of annotated data to be able to match the highest expectations. High-quality annotations are unfortunately expensive as they require field experts to create them, and often cannot be shared outside the lab due to medical regulations.We propose AnnotatorJ, an ImageJ plugin for the semi-automatic annotation of cells (or generally, objects of interest) on (not only) microscopy images in 2D that helps find the true contour of individual objects by applying U-Net-based pre-segmentation. The manual labour of hand-annotating cells can be significantly accelerated by using our tool. Thus, it enables users to create such datasets that could potentially increase the accuracy of state-of-the-art solutions, deep learning or otherwise, when used as training data.
Fluorophore-labelled RNA aptamers to common protein tags as super-resolution imaging reagents
Authors: Wang Juan , Singh Avtar , Ozer Abdullah , Zipfel Warren R. 
Published: February 2020

ABSTRACTDeveloping labelling methods that densely and specifically label targeted cellular structures is critically important for centroid localization-based super-resolution microscopy. Being easy and inexpensive to produce in the laboratory and of relatively small size, RNA aptamers have potential as a substitute for conventional antibody labelling. By using aptamers selected against common protein tags - GFP (green fluorescent protein) in this case - we demonstrate labelling methods using dSTORM-compatible fluorophores for STORM and hybridizable imager strands for DNA-PAINT super-resolution optical imaging of any cellular proteins fused to the aptamer binding target. We show that we can label both extracellular and intracellular proteins for super-resolution imaging, and that the method in particular, offers some interesting advantages for live cell super-resolution imaging of plasma membrane proteins.KEY POINTSA simple to use RNA aptamer method for super-resolution STORM and PAINT imaging in cells expressing common protein tags.The method has a number of unique advantages for live cell imaging at the nanometer scale.Provides a means to quantify the number of proteins being trafficked on the plasma membrane.
New environment, new invaders - repeated horizontal transfer of LINEs to sea snakes
Authors: Galbraith James D. , Ludington Alastair J. , Suh Alexander , Sanders Kate L. , Adelson David L. 
Published: February 2020

AbstractWhile numerous studies have found horizontal transposon transfer (HTT) to be widespread across metazoans, few have focused on HTT in marine ecosystems. To investigate potential recent HTTs into marine species we searched for novel repetitive elements in sea snakes, a group of elapids which transitioned to a marine habitat at most 18 Mya. Our analysis uncovered repeated HTTs into sea snakes following their marine transition. Such major shifts in habitat should require significant genomic changes.The seven subfamilies of horizontally transferred LINE retrotransposons we identified in the olive sea snake (Aipysurus laevis) are transcribed, and hence are likely still active and expanding across the genome. A search of 600 metazoan genomes found all seven were absent from other amniotes, including terrestrial elapids, with the most similar transposons present in fish and marine invertebrates. The one exception was a similar transposon found in sea kraits, a lineage of amphibious elapids which independently transitioned to a marine environment following their divergence from terrestrial species 25 Mya. Our finding of repeated horizontal transfer events into separate lineages of marine snakes greatly expands past findings of frequent horizontal transfer in the marine environment, suggesting it is ideal for the transfer of transposons.Transposons are drivers of evolution as sources of genomic sequence and hence genomic novelty. This provides evidence of the environment influencing evolution of metazoans not only through specific selection pressures, but also by contributing novel genomic material.