bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Expression of Japanese Encephalitis Virus Envelope Gene in Green Cos
Authors: Tangkananond Wipa , Lomonossoff George 
Published: December 2019

The expression of Japanese encephalitis virus (JEV) envelope gene in green cos leaf was a project undertaken at the John Innes Centre during 6 September to 20 October 2018 and is one of the projects of the research training program at the John Innes Centre during long vacation every year since 2010 until now.
The summary of this research is as follows. The production of the envelope protein of the JEV in green cos by using the envelope gene expression by 8 epitopes (MEP: multiepitope) of Japanese encephalitis virus vaccine strain SA14-14-2 that provides the highest immune response against JEV. After incorporated the envelope gene into pEAQ-HT and pEAQ-HT-HBcAg-tEL vectors, we cloned genes in Escherichia coli and Agrobacterium tumefaciens, respectively, then expressed the envelope protein of JEV in green cos leaves. The result can be seen in photographs of green cos leaves by both visible light camera and ultraviolet light camera.
Further research should include the analysis and identification by chemiluminescence immunoassay and by the Matrix-assisted Laser Desorption/Ionization Time of Flight (MALDI-TOF). Further purification of the envelope protein expression of JEV in green cos that will be benefited for the production of the envelope protein of the JEV plant-based vaccine.
Key words: Japanese encephalitis virus, plant-based vaccine, chemiluminescence immunoassay, MALDI-TOF
Stage specific transcriptome profiling of castor bean tick Ixodes ricinus
Authors: Vechtova Pavlina , Füssy Zoltan , Sterba Jan , Cegan Radim , Benes Vladimir , Grubhoffer Libor 
Published: December 2019

Arthropod borne diseases are ubiquitously discussed topic whose relevance increases with ongoing changing climate, which extends the area of their incidence and affects profoundly the size of vector population, as well as its reproductive capacity, the abundance and spread of reservoir hosts and other variables that are generally tightly correlated with the spread of zoonoses.
The life cycle of arthropod borne pathogens are tightly bound to the life cycle of their host as well as to their vector organism. Therefore, the description of the vector life cycle should elucidate some questions related to the vector-pathogen dynamics including the factors important for successful disease transmission.
Tick has complex life cycle and for its completion it requires feeding on several host organisms, which is abused by the pathogen for its spreading within reservoir and host organisms.
Thus, more thorough description of factors driving tick developmental processes controlling its life cycle will be instrumental in understanding the nature of I. ricinus and its pathogens interactions and may also shed light on the process of blood feeding as an integral event in tick development as well as in potential pathogen transmission.
In our study we perform transcriptional profiling of all life stages of I. ricinus and provide a list of genes associated with particular life stages of I. ricinus and hence extend our knowledge in pursuit of potential acaricidal strategies.
Lumpy skin disease virus: transmission to dipteran vectors using animal and ex-vivo models
Authors: Bernardo Beatriz Sanz , Suckoo Rey , Darpel Karin , Hawes Pippa , Basu Sanjay , Langlands Zoe , Gubbins Simon , Beard Pip 
Published: December 2019

Lumpy skin disease (LSD) is a tropical neglected viral disease of cattle, characterised by numerous cutaneous lesions disseminated throughout the body. Historically endemic to the African continent, it has become a threat to Europe following the outbreaks of LSD in the Middle East and Eastern Europe.
LSD virus (LSDV) is a Capripoxvirus transmitted by insect vectors. Experimental and epidemiological studies have indicated a role for the stable fly (Stomoxys calcintrans) and the mosquito Aedes aegypti. Nevertheless the relative importance of these vector species and others is unclear. A study was designed to explore the risk of transmission of LSDV from cattle to different vector species including Aedes aegypti, Culex quinquefasciatus, Stomoxys calcitrans and Culicoides nubeculosus. Cattle was challenged with LSDV to produce a bovine experimental model used as a natural source of LSDV to the potential vectors. Cattle samples were taken to quantify LSDV in different tissues and characterise the disease. All insect species were allowed to feed on LSDV-challenged cattle at regular intervals and incubated for up to eight days. This data was then used to model the dynamics of LSDV infection and transmission. All four species were able to acquire and maintain LSDV for up to eight days post feeding, and the risk of transmission from bovine donor to insect was dependent on the severity of the disease. A model was then generated using ex-vivo skin lesions and infectious blood that will allow further studies of the role of these vectors.
ARIPOR2in-frame deletion is a frequent and highly penetrant cause of adult-onset hearing loss
Authors: de Bruijn Suzanne E. , Smits Jeroen J. , Liu Chang , Lanting Cornelis P. , Beynon Andy J. , Blankevoort Joëlle , Oostrik Jaap , Koole Wouter , de Vrieze Erik ,   DOOFNL Consortium, Cremers Cor W.R.J. , Cremers Frans P. M. , Roosing Susanne , Yntema Helger G. , Kunst Henricus P.M. , Zhao Bo , Pennings Ronald J.E. , Kremer Hannie 
Published: December 2019

ABSTRACTHearing loss is one of the most prevalent disabilities worldwide, and has a significant impact on quality of life. The adult-onset type of the condition is highly heritable but the genetic causes are largely unknown, which is in contrast to childhood-onset hearing loss. We identified an in-frame deletion of 12 nucleotides inRIPOR2as a highly penetrant cause of adult-onset progressive hearing loss that segregated as an autosomal dominant trait in 12 families from the Netherlands. Hearing loss associated with the deletion in 63 subjects displayed variable audiometric characteristics and an average age of onset of 30.6 years (SD 14.9 years, range 0-70 years). A functional effect of theRIPOR2variant was demonstrated by aberrant localization of the mutant RIPOR2 in the stereocilia of cochlear hair cells and failure to rescue morphological defects in RIPOR2-deficient hair cells, in contrast to the wildtype protein. Strikingly, theRIPOR2variant is present in 18 of 22,952 individuals not selected for hearing loss in the Southeast Netherlands. Collectively, these data demonstrate that an inherited form of adult-onset hearing loss is relatively common, with potentially thousands of individuals at risk in the Netherlands and beyond, which makes it an attractive target for developing a (genetic) therapy.
Loss ofprdm1aaccelerates melanoma onset and progression
Authors: Iwanaga Ritsuko , Truong Brittany T. , Hsu Jessica Y. , Lambert Karoline A. , Vyas Rajesh , Orlicky David , Shellman Yiqun G. , Tan Aik-Choon , Ceol Craig , Artinger Kristin Bruk 
Published: December 2019

ABSTRACTMelanoma is an aggressive, deadly skin cancer derived from melanocytes, a neural crest cell derivative. Melanoma cells mirror the developmental program of neural crest cells in that they exhibit the same gene expression patterns and utilize similar cellular mechanisms, including increased cell proliferation, EMT and migration. Here we studied the role of neural crest regulator PRDM1 in melanoma onset and progression. In development, Prdm1a functions to promote neural crest progenitor fate, and in melanoma, we found thatPRDM1has reduced copy number and is recurrently deleted in both zebrafish and humans. When examining expression of neural crest and melanocyte development genes, we show thatsox10progenitor expression is high inprdm1a-/-mutants, while more differentiated melanocyte markers are reduced, suggesting that normally Prdm1a is required for differentiation. Data mining of human melanoma datasets indicate that highPRDM1expression in human melanoma is correlated with better patient survival and decreasedPRDM1expression is common in metastatic tumors. When one copy ofprdm1ais lost in the zebrafish melanoma model (Tg[mitfa:BRAFV600E];p53-/-;prdm1a+ /-), melanoma onset occurs more quickly, and the tumors that form have a larger area with increased expression ofsox10.These data demonstrate a novel role for PRDM1 as a tumor suppressor in melanoma.
Contrast-enhanced ultrasound with sub-micron sized contrast agents detects insulitis and β-cell mass decline in mouse models of type 1 diabetes
Authors: Ramirez David G. , Abenojar Eric , Hernandez Christopher , Papazian Lucine A. , Passman Samantha , Pham Vinh , Exner Agata A. , Benninger Richard K.P. 
Published: December 2019

ABSTRACTType 1 diabetes (T1D) is characterized by the infiltration of autoreactive T-cells into the islet of Langerhans, and depletion of insulin-secreting β-cells. This immune cell infiltration (insulitis) first occurs during an asymptomatic phase of T1D that can take place many years prior to clinical diagnosis. Methods to diagnose insulitis and changes in β-cell mass during this asymptomatic phase are limited, thus precluding early therapeutic intervention. While therapeutic treatments can delay T1D progression, treatment efficacy is limited and widely varying, and a method to track this efficacy is also lacking. During T1D progression, the islet microvasculature increases permeability as a result of insulitis, in both mouse models of T1D and humans with T1D. This increased permeability can allow nanoparticles, such as contrast agents for diagnostic imaging, to access the islet microenvironment. Contrast enhanced ultrasound (CEUS) uses shell-stabilized gas bubbles to provide high acoustic backscatter in vasculature and tissue and is clinically approved. A novel, sub-micron sized ‘nanobubble’ (NB) ultrasound contrast agent has been developed and shown to extravasate and accumulate in tumors, where microvascular permeability is high. To test whether CEUS can be used to measure increased islet microvasculature permeability and indicate the asymptomatic phase of T1D, we applied CEUS measurements with NBs in pre-clinical T1D models. NOD mice and mice receiving an adoptive-transfer of diabetogenic splenocytes showed accumulation of NBs specifically within the pancreatic islets, and only in the presence of insulitis. This accumulation was measured by both ultrasound contrast and histological analysis, and accumulation only occurred for sub-micron sized bubbles. Importantly, accumulation was detected as early as 4w in NOD mice. Thus, CEUS with sub-micron sized NB contrast agent may provide a predicative marker for disease progression early in asymptomatic T1D, as well as monitoring of disease prevention or reversal.
A switch in cilia-mediated Hedgehog signaling controls muscle stem cell quiescence and cell cycle progression
Authors: Cruz-Migoni Sara Betania , Imran Kamalliawati Mohd , Wahid Aysha , Rahman Oisharja , Briscoe James , Borycki Anne-Gaëlle 
Published: December 2019

SummaryTissue homeostasis requires a tight control of stem cells to maintain quiescence in normal conditions, and ensure a balance between progenitor cell production and the need to preserve a stem cell pool in repair conditions. Using ex-vivo and in-vivo genetic approaches, we provide evidence that primary cilium-mediated repressive Hedgehog (Hh) signalling is required to maintain skeletal muscle stem cells (MuSCs) in a quiescent state. De-repression and further activation of Hh signalling initiates MuSC entry and progression through the cell cycle, and controls self-renewal to ensure efficient repair of injured muscles. We propose a model whereby disassembly of primary cilia upon MuSC activation induces a switch in Hh signalling from a repressive to active state that controls exit from quiescence. Positive Hh response in bi-potential muscle progenitor cells regulates also cell cycle progression and drives MuSC self-renewal. These findings identify Hh signalling as a major regulator of MuSC activity.HighlightsCilia-containing quiescent MuSCs are Hh signalling suppressedMuSC activation coincides with a switch to active Hh signallingSmomutation delays cell cycle entry and progression, and causes impaired self-renewalPtch1mutation promotes exit from quiescence, rapid cell cycle and increased self-renewalGraphical abstract
The DNA Methylation Landscape of Giant Viruses
Authors: Jeudy Sandra , Rigou Sofia , Alempic Jean-Marie , Claverie Jean-Michel , Abergel Chantal , Legendre Matthieu 
Published: December 2019

AbstractDNA methylation is an important epigenetic mark that contributes to various regulations in all domains of life. Prokaryotes use it through Restriction-Modification (R-M) systems as a host-defense mechanism against viruses. The recently discovered giant viruses are widespread dsDNA viruses infecting eukaryotes with gene contents overlapping the cellular world. While they are predicted to encode DNA methyltransferases (MTases), virtually nothing is known about the DNA methylation status of their genomes. Using single-molecule real-time sequencing we studied the complete methylome of a large spectrum of families: the Marseilleviridae, the Pandoraviruses, the Molliviruses, the Mimiviridae along with their associated virophages and transpoviron, the Pithoviruses and the Cedratviruses (of which we report a new strain). Here we show that DNA methylation is widespread in giant viruses although unevenly distributed. We then identified the corresponding viral MTases, all of which are of bacterial origins and subject to intricate gene transfers between bacteria, viruses and their eukaryotic host. If some viral MTases undergo pseudogenization, most are conserved, functional and under purifying selection, suggesting that they increase the viruses’ fitness. While the Marseilleviridae, Pithoviruses and Cedratviruses DNA MTases catalyze N6-methyl-adenine modifications, some MTases of Molliviruses and Pandoraviruses unexpectedly catalyze the formation of N4-methyl-cytosine modifications. In Marseilleviridae, encoded MTases are paired with cognate restriction endonucleases (REases) forming complete R-M systems. Our data suggest that giant viruses MTases could be involved in different kind of virus-virus interactions during coinfections.
Cross-species analysis of melanoma enhancer logic using deep learning
Authors: Minnoye Liesbeth , Taskiran Ibrahim Ihsan , Mauduit David , Fazio Maurizio , Van Aerschot Linde , Hulsemans Gert , Christiaens Valerie , Makhzami Samira , Seltenhammer Monika , Karras Panagiotis , Primot Aline , Cadieu Edouard , van Rooijen Ellen , Marine Jean-Christophe , Maskos Giorgia Egidy , Ghanem Ghanem-Elias , Zon Leonard , Wouters Jasper , Aerts Stein 
Published: December 2019

AbstractGenomic enhancers form the central nodes of gene regulatory networks by harbouring combinations of transcription factor binding sites. Deciphering the combinatorial code by which these binding sites are assembled within enhancers is indispensable to understand their regulatory involvement in establishing a cell’s phenotype, especially within biological systems with dysregulated gene regulatory networks, such as melanoma. In order to unravel the enhancer logic of the two most common melanoma cell states, namely the melanocytic and mesenchymal-like state, we combined comparative epigenomics with machine learning. By profiling chromatin accessibility using ATAC-seq on a cohort of 27 melanoma cell lines across six different species, we demonstrate the conservation of the two main melanoma states and their underlying master regulators. To perform an in-depth analysis of the enhancer architecture, we trained a deep neural network, called DeepMEL, to classify melanoma enhancers not only in the human genome, but also in other species. DeepMEL revealed the presence, organisation and positional specificity of important transcription factor binding sites. Together, this extensive analysis of the melanoma enhancer code allowed us to propose the concept of a core regulatory complex binding to melanocytic enhancers, consisting of SOX10, TFAP2A, MITF and RUNX, and to disentangle their individual roles in regulating enhancer accessibility and activity.
Learning immune cell differentiation
Authors: Maslova Alexandra , Ramirez Ricardo N. , Ma Ke , Schmutz Hugo , Wang Chendi , Fox Curtis , Ng Bernard , Benoist Christophe , Mostafavi Sara ,   the Immunological Genome Project
Published: December 2019

SUMMARYThe mammalian genome contains several million cis-regulatory elements, whose differential activity marked by open chromatin determines organogenesis and differentiation. This activity is itself embedded in the DNA sequence, decoded by sequence-specific transcription factors. Leveraging a granular ATAC-seq atlas of chromatin activity across 81 immune cell-types we show that a convolutional neural network (“AI-TAC”) can learn to infer cell-type-specific chromatin activity solely from the DNA sequence. AI-TAC does so by rediscovering, with astonishing precision, binding motifs for known regulators, and some unknown ones, mapping them with high concordance to positions validated by ChIP-seq data. AI-TAC also uncovers combinatorial influences, establishing a hierarchy of transcription factors (TFs) and their interactions involved in immunocyte specification, with intriguingly different strategies between lineages. Mouse-trained AI-TAC can parse human DNA, revealing a strikingly similar ranking of influential TFs. Thus, Deep Learning can reveal the regulatory syntax that drives the full differentiative complexity of the immune system.
NADPH diaphorase neuronal dystrophy in gracile nucleus, cuneatus nucleus and spinal trigeminal nucleus in aged rat
Authors: Hou Wei , Jia Yunge , Li Yinhua , Wei Zichun , Wen Xiaoxin , Rao Chenxu , Xu Ximeng , Li Fuhong , Wu Xianhui , Sun Haoran , Li Hang , Huang Yizhe , Sun Jingjing , Shu Gege , Wang Xinghang , Zhang Tianyi , Shi Geming , Guo Anchen , Xu Shengfei , Du Guanghui , Tan Huibing 
Published: December 2019

AbstractNADPH-diaphorase (N-d) activity is commonly used to identify NOS-ergic neurons. In our previous study, N-d positive neuritic dystrophy and spheroid termed aging-related N-d Body is discovered in the lumbosacral spinal cord in the normal aging rats. Histological studies also reveal that N-d positive neurodegenerative changes occur in the gracile nucleus. We re-examined N-d activity in gracile nucleus in aged rat. We found N-d positive neuritic dystrophy and spheroid also occurred in the cuneatus nucleus and spinal trigeminal nucleus. Besides regular coronal section, longitudinal oriented dystrophic neurites were detected in the sagittal and horizontal section in gracile nucleus and dorsal column. We fziurther examined the medullary oblongata with regular classical histology including Golgi staining, immunocytochemistry of NOS and phosphorylated tau protein, neuronal tracing method with wheat germ agglutinin conjugated alexa-fluor-488 through sciatic nerve, and spinal cord transection at thoracic level. Most of N-d positive neuritic dystrophy and spheroid did not showed colocalization with NOS or phosphorylated tau protein. Neuronal tracing and spinal cord transection revealed that N-d dystrophic neurites in gracile nucleus originated from terminal of sensory projection from spinal cord and peripheral somatic input. The results suggested that aging-related N-d dystrophy in the gracile nucleus was unique morphological feature. In conclusion, it was postulated that the N-d dystrophy as a morphological marker of aging degenerative damage in normal aged organisms.
Pattern regulation in a regenerating jellyfish
Authors: Sinigaglia Chiara , Peron Sophie , Eichelbrenner Jeanne , Chevalier Sandra , Steger Julia , Barreau Carine , Houliston Evelyn , Leclère Lucas 
Published: December 2019

AbstractClytia hemisphaericajellyfish, with their tetraradial symmetry, offer a novel paradigm for addressing patterning mechanisms during regeneration. Here we show that an interplay between mechanical forces, cell migration and proliferation allows jellyfish fragments to regain shape and functionality rapidly, notably by efficient restoration of the central feeding organ (manubrium). Fragmentation first triggers actomyosin-powered remodeling that restores body umbrella shape, causing radial smooth muscle fibers to converge around “hubs” which serve as positional landmarks. Stabilization of these hubs, and associated expression ofWnt6, depends on the configuration of the adjoining muscle fiber “spokes”. Stabilized hubs presage the site of the manubrium blastema, whose growth is Wnt/β-catenin dependent and fueled by both cell proliferation and long-range cell recruitment. Manubrium morphogenesis is modulated by its connections with the gastrovascular canal system. We conclude that body patterning in regenerating jellyfish emerges mainly from local interactions, triggered and directed by the remodeling process.
Modeling acute kidney injury in kidney organoids with cisplatin
Authors: Digby Jenny L. M. , Przepiorski Aneta , Davidson Alan J. , Sander Veronika 
Published: December 2019

ABSTRACTAcute kidney injury (AKI) remains a major global healthcare problem and there is a need to develop human-based models to study AKIin vitro. Towards this goal, we have characterized induced pluripotent stem cell-derived human kidney organoids and their response to cisplatin, a chemotherapeutic drug that induces AKI and preferentially damages the proximal tubule. We found that a single treatment with 50 µM cisplatin inducesHAVCR1andCXCL8expression, DNA damage (γH2AX) and cell death in the organoids in a dose-dependent manner but greatly impairs organoid viability. DNA damage was not specific to the proximal tubule but also affected the distal tubule and interstitial populations. This lack of specificity correlated with low expression of the proximal tubule-specificSLC22A2/OCT2transporter for cisplatin. To improve viability, we developed a repeated low-dose regimen of 4x 5 µM cisplatin over 7 days and found this causing less toxicity while still inducing a robust AKI response that included secretion of known AKI biomarkers and inflammatory cytokines. This work validates the use of human kidney organoids to model aspects of AKIin vitro, with the potential to identify new AKI biomarkers and develop better therapies.
Skip segment Hirschsprung disease: modelling the trans-mesenteric origin of the enteric nervous system in the human colon
Authors: Newgreen Donald F , Osborne James M , Zhang Dongcheng 
Published: December 2019

ABSTRACTSkip segment Hirschsprung disease is a difficult to explain human enteric neuropathy where a ganglionated region lies within a region of total colonic aganglionosis.. Recently, trans-mesenteric migration was described in the mouse intestine whereby neural crest cells migrate via the mesentery across a U-shape gut loop from the midgut to the hindgut: this could explain skip segment Hirschsprung disease. To investigate this, human intestinal growth parameters were derived from published sources and correlated with enteric neural crest cell migration. These processes were then simulated using agent based mathematical models scaled to human intestinal growth. A Hirschsprung-associated slowing of migration was imposed and trans-mesenteric migration was allowed. From the developmental anatomy we conclude that trans-mesenteric migration is unlikely in normal human embryogenesis, but with a Hirschsprung-associated slowing of enteric neural crest cell migration it could occur at Carnegie stages 17 and 18. By varying the division rate of enteric neural crest agents we could reproduce full colonisation, short segment, long segment and skip segment Hirschsprung and hypoganglionic segments.Summary StatementSkip segment Hirschsprung disease in humans challenges current explanations. Mathematical modelling shows how this birth defect could develop.