bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upregulation of Human Endogenous Retrovirus-K (HML-2) mRNAs in hepatoblastoma: Identification of potential new immunotherapeutic targets and biomarkers
Authors: Grabski David F , Ratan Aakrosh , Gray Laurie R , Bekiranov Stefan , Rekosh David , Hammarskjold Marie-Louise , Rasmussen Sara K 
Published: March 2020

AbstractPurposeHepatoblastoma is the most common liver malignancy in children. In order to advance therapy against hepatoblastoma, novel immunologic targets and biomarkers are needed. Our purpose in this investigation is to examine hepatoblastoma transcriptomes for the expression of a class of genomic elements known as Human Endogenous Retrovirus (HERVs). HERVs are abundant in the human genome and are biologically active elements that have been associated with multiple malignancies and proposed as immunologic targets in a subset of tumors. A sub-family of HERVs, HERV-K (HML-2), have been shown to be tightly regulated in fetal development, making investigation of these elements in pediatric tumors paramount.MethodsWe first created a HERVK-FASTA file utilizing 91 previously described HML-2 proviruses. We then concatenated the file onto the GRCh38.95 cDNA library from Ensembl. We used this computational tool to evaluate existing RNA-seq data from 10 hepatoblastoma tumors and 3 normal liver controls (GEO accession ID: GSE89775). Quantification and differential proviral expression analysis between hepatoblastoma and normal liver controls was performed using the pseudo-alignment program Salmon and DESeq2, respectively.ResultsHERV-K mRNA was expressed in hepatoblastoma from multiple proviral loci. All HERV-K proviral loci were expressed at higher levels in hepatoblastoma compared to normal liver controls. Five HERV-K proviruses (1q21.3, 3q27.2, 7q22.2, 12q24.33 and 17p13.1) were significantly differentially expressed (p-adjusted value < 0.05, |log2 fold change| > 1.5) across conditions. The provirus at 17p13.1 had an approximately 300-fold increased expression in hepatoblastoma as compared to normal liver. This was in part due to the near absence of HERV-K mRNA at the 17p13.1 locus in fully differentiated liver samples.ConclusionsOur investigation demonstrates that HERV-K is expressed from multiple loci in hepatoblastoma and that the expression is increased from several proviruses as compared to normal liver controls. Our results suggest that HERV-K mRNA expression may find use as a biomarker in hepatoblastoma, given the large differential expression profiles in hepatoblastoma, with very low mRNA levels in liver control samples.
Within-patient evolution to piperacillin/tazobactam resistance in a clinical isolate ofEscherichia colidue to IS26-mediated amplification ofblaTEM-1B
Authors: Hubbard Alasdair T. M. , Mason Jenifer , Roberts Paul , Parry Christopher M. , Corless Caroline , van Aartsen Jon , Howard Alex , Fraser Alice J. , Adams Emily R. , Roberts Adam P. , Edwards Thomas 
Published: March 2020

AbstractA novel phenotype ofEscherichia coliand Klebsiella pneumoniae resistant to piperacillin/tazobactam (TZP), but susceptible to carbapenems and 3rdgeneration cephalosporins has recently emerged. The resistance mechanism of this phenotype has been identified as hyperproduction of the β-lactamaseblaTEM, however the mechanism of hyperproduction in isolates lacking promoter region mutations is not well understood. We sought to understand this mechanism by focussing on a pair of isolates obtained from an individual patient across two infection episodes and displaying within-patient evolution to TZP resistance. Following confirmation that the two isolates were clonal, we found that the TZP-resistant isolate hyperproduced a β-lactamase but lacked mutations within β-lactamase promoter regions. Hybrid assembly of long and short sequencing reads of the two isolates revealed both harboured a novel IS26-flanked composite transposon containing several antibiotic resistance genes, includingblaTEM-1B, which was designated Tn6762. These resistance genes are also found to be present on a translocatable unit which had excised from Tn6762in the TZP-resistant isolate. By replicating the evolutionary event leading to TZP resistance we were able to observe excision of the translocatable unit from Tn6762following exposure to TZP and capture the TU in a plasmid containing a copy of IS26. Subsequent amplification of the TU, and by extensionblaTEM-1B, leads to β-lactamase hyperproduction and TZP resistance. Despite a significant increase in gene copy number (P value = <0.0001), we found that the TZP-resistant isolate was as fit as the susceptible ancestor. This mechanism of gene amplification, and the subsequent hyperproduction, ofblaTEM-1Bis an important consideration when using genomic data to predict resistance/susceptibility to TZP.
Using high-throughput phenotypes to enable genomic selection by inferring genotypes
Authors: Whalen Andrew , Gaynor Chris , Hickey John M 
Published: March 2020

AbstractIn this paper we develop and test a method which uses high-throughput phenotypes to infer the genotypes of an individual. The inferred genotypes can then be used to perform genomic selection. Previous methods which used high-throughput phenotype data to increase the accuracy of selection assumed that the high-throughput phenotypes correlate with selection targets. When this is not the case, we show that the high-throughput phenotypes can be used to determine which haplotypes an individual inherited from their parents, and thereby infer the individual’s genotypes. We tested this method in two simulations. In the first simulation, we explored, how the accuracy of the inferred genotypes depended on the high-throughput phenotypes used and the genome of the species analysed. In the second simulation we explored whether using this method could increase genetic gain a plant breeding program by enabling genomic selection on non-genotyped individuals. In the first simulation, we found that genotype accuracy was higher if more high-throughput phenotypes were used and if those phenotypes had higher heritability. We also found that genotype accuracy decreased with an increasing size of the species genome. In the second simulation, we found that the inferred genotypes could be used to enable genomic selection on non-genotyped individuals and increase genetic gain compared to random selection, or in some scenarios phenotypic selection. This method presents a novel way for using high-throughput phenotype data in breeding programs. As the quality of high-throughput phenotypes increases and the cost decreases, this method may enable the use of genomic selection on large numbers of non-genotyped individuals.
Vitamin D receptor and STAT3 cooperate to establish TET2-mediated tolerogenesis
Authors: Català-Moll Francesc , Li Tianlu , Ciudad Laura , Rodríguez-Ubreva Javier , Ballestar Esteban 
Published: March 2020

SUMMARYThe active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), induces stable tolerogenesis in dendritic cells (DCs). This process involves the vitamin D receptor (VDR), which translocates to the nucleus, binds its cognate genomic sites, and promotes epigenetic and transcriptional remodeling. In this study, we investigated the interplay between the VDR and other transcription factors to induce DNA methylation changes that might provide phenotypic stability to the tolerogenic phenotype of DCs. Our study reveals the occurrence of vitamin D-specific DNA demethylation and transcriptional activation at VDR binding sites associated with the acquisition of tolerogenesis. Tolerogenic properties in DCs are acquired together with activation of the IL6-JAK-STAT3 pathway. In fact, VDR directly binds theIL6gene, and JAK2-mediated STAT3 phosphorylation is specific to vitamin D stimulation. VDR and the phosphorylated form of STAT3 interact with each other and with methylcytosine dioxygenase TET2 following vitamin D treatment. Most importantly, pharmacological inhibition of STAT3 phosphorylation reverts the vitamin-induced tolerogenic properties of DCs. Our results reveal an interplay between VDR and STAT3 leading to the DNA demethylation-dependent induction of tolerogenesis by vitamin D.
Effects of emotion and semantic relatedness on recognition memory: Behavioral and electrophysiological evidence
Authors: Han Meng , Li Bingcan , Guo Chunyan , Tibon Roni 
Published: March 2020

AbstractSome aspects of our memory are enhanced by emotion, whereas other can be unaffected or even hindered. Previous studies report impaired associative memory of emotional content, an effect termed associative “emotional interference”. The current study used EEG and an associative recognition paradigm to investigate the cognitive and neural mechanisms associated with this effect. In two experiments, participants studied negative and neutral stimulus-pairs that were either semantically related or unrelated. In Experiment 1 emotions were relevant to the encoding task (valence judgment) whereas in Experiment 2 emotions were irrelevant (familiarity judgment). In a subsequent associative recognition test, EEG was recorded while participants discriminated between intact, rearranged, and new pairs. An associative emotional interference effect was observed in both experiments, but was attenuated for semantically related pairs in Experiment 1, where valence was relevant to the task. Moreover, a modulation of an early associative memory ERP component (300-550 ms) occurred for negative pairs when valence was task-relevant (Experiment 1), but for semantically related pairs when valence was irrelevant (Experiment 2). A later ERP component (550-800 ms) showed a more general pattern, and was observed in all experimental conditions. These results suggest that both valence and semantic relations can act as an organizing principle that promotes associative binding. Their ability to contribute to successful retrieval depends on specific task demands.
Time-resolved comparative molecular evolution of oxygenic photosynthesis
Authors: Oliver Thomas , Sánchez-Baracaldo Patricia , Larkum Anthony W. , Rutherford A. William , Cardona Tanai 
Published: March 2020

AbstractOxygenic photosynthesis starts with the oxidation of water to O2, a light-driven reaction catalysed by photosystem II. Cyanobacteria are the only prokaryotes capable of water oxidation and therefore, it is assumed that relative to the origin of life and bioenergetics, the origin of oxygenic photosynthesis is a late innovation. However, when exactly water oxidation originated remains an unanswered question. Here we use relaxed molecular clocks to compare one of the two ancestral core duplications that are unique to water-oxidizing photosystem II, that leading to CP43 and CP47, with some of the oldest well-described events in the history of life. Namely, the duplication leading to the Alpha and Beta subunits of the catalytic head of ATP synthase, and the divergence of archaeal and bacterial RNA polymerases and ribosomes. We also compare it with more recent events such as the duplication of cyanobacteria-specific FtsH metalloprotease subunits, of CP43 variants used in a variety of photoacclimation responses, and the speciation events leading to Margulisbacteria, Sericytochromatia, Vampirovibrionia, and other clades containing anoxygenic phototrophs. We demonstrate that the ancestral core duplication of photosystem II exhibits patterns in the rates of protein evolution through geological time that are nearly identical to those of the ATP synthase, RNA polymerase, or the ribosome. Furthermore, we use ancestral sequence reconstruction in combination with comparative structural biology of photosystem subunits, to provide additional evidence supporting the premise that water oxidation had originated before the ancestral core duplications. Our work suggests that photosynthetic water oxidation originated closer to the origin of life and bioenergetics than can be documented based on species trees alone.
Structural attributes and principles of the neocortical connectome in the marmoset monkey
Authors: Theodoni Panagiota , Majka Piotr , Reser David H. , Wójcik Daniel K. , Rosa Marcello G.P. , Wang Xiao-Jing 
Published: March 2020

AbstractThe marmoset monkey has become an important primate model in Neuroscience. Here we characterize salient statistical properties of inter-areal connections of the marmoset cerebral cortex, using data from retrograde tracer injections. We found that the connectivity weights are highly heterogeneous, spanning five orders of magnitude, and are log-normally distributed. The cortico-cortical network is dense, heterogeneous and has high specificity. The reciprocal connections are the most prominent and the probability of connection between two areas decays with their functional dissimilarity. The laminar dependence of connections defines a hierarchical network correlated with microstructural properties of each area. The marmoset connectome reveals parallel streams associated with different sensory systems. Finally, the connectome is spatially embedded with a characteristic length that obeys a power law as a function of brain volume across species. These findings provide a connectomic basis for investigations of multiple interacting areas in a complex large-scale cortical system underlying cognitive processes.
Macrophage scavenger receptor 1 controls Chikungunya virus infection through autophagy
Authors: Yang Long , Geng Tingting , Yang Guang , Ma Jinzhu , Wang Leilei , Ketkhar Harshada , Yang Duomeng , Lin Tao , Hwang Jesse , Zhu Shu , Wang Yanlin , Dai Jianfeng , You Fuping , Cheng Gong , Vella Antony , Flavell Richard. A , Fikrig Erol , Wang Penghua 
Published: March 2020

AbstractMacrophage scavenger receptor 1 (MSR1) mediates the endocytosis of modified low-density lipoproteins and plays an important antiviral role. However, the molecular mechanism underlying MSR1 antiviral actions remains elusive. Herein, we report that MSR1 activates autophagy to restrict infection of Chikungunya virus (CHIKV), an arthritogenic alphavirus that causes acute and chronic crippling arthralgia. Msr1 expression was rapidly upregulated after CHIKV infection in mice.Msr1knockout mice had elevated viral loads and increased susceptibility to CHIKV arthritis along with a normal type I IFN response. Induction of LC3 lipidation by CHIKV, a marker of autophagy, was reduced inMsr1-/-cells. Mechanistically, MSR1 interacted with ATG12 through its cytoplasmic tail and this interaction was enhanced by CHIKV nsP1 protein. MSR1 repressed CHIKV replication through ATG5-ATG12-ATG16L1 and this was dependent on the FIP200-and-WIPI2-binding domain, but not the WD40 domain of ATG16L1. Our results elucidate an antiviral role for MSR1 involving the autophagic function of ATG5-ATG12-ATG16L1.
Voluntary running does not increase capillary blood flow but promotes neurogenesis and short-term memory in the APP/PS1 mouse model of Alzheimer’s disease
Authors: Falkenhain Kaja , Ruiz-Uribe Nancy E. , Haft-Javaherian Mohammad , Ali Muhammad ,   Stall Catchers contributors, Michelucci Pietro E. , Schaffer Chris B. , Bracko Oliver 
Published: March 2020

ABSTRACTExercise exerts a beneficial effect on the major pathological and clinical symptoms associated with Alzheimer’ s disease in humans and mouse models of the disease. While numerous mechanisms for such benefits from exercise have been proposed, a clear understanding of the causal links remains elusive. Recent studies also suggest that cerebral blood flow in the brain of both Alzheimer’ s patients and mouse models of the disease is decreased and that the cognitive symptoms can be improved when blood flow is restored. We therefore hypothesized that the mitigating effect of exercise on the development and progression of Alzheimer’ s disease may be mediated through an increase in the otherwise reduced brain blood flow. To test this idea, we examined the impact of three months of voluntary wheel running in ∼1-year-old APP/PS1 mice on short-term memory function, brain inflammation, amyloid deposition, and cerebral blood flow. Our findings that exercise led to improved memory function, a trend toward reduced brain inflammation, markedly increased neurogenesis in the dentate gyrus, and no changes in amyloid-beta deposits are consistent with other reports on the impact of exercise on the progression of Alzheimer’ s related symptoms in mouse models. Notably, we did not observe any impact of wheel running on overall cortical blood flow nor on the incidence of non-flowing capillaries, a mechanism we recently identified as one contributing factor to cerebral blood flow deficits in mouse models of Alzheimer’ s disease. Overall, our results replicate previous findings that exercise is able to ameliorate certain aspects of Alzheimer’ s disease pathology, but show that this benefit does not appear to act through increases in cerebral blood flow.
A haplotype-resolved,de novogenome assembly for the wood tiger moth (Arctia plantaginis) through trio binning
Authors: Yen Eugenie C. , McCarthy Shane A. , Galarza Juan A. , Generalovic Tomas N. , Pelan Sarah , Nguyen Petr , Meier Joana I. , Warren Ian A. , Mappes Johanna , Durbin Richard , Jiggins Chris D. 
Published: March 2020

ABSTRACTBackgroundDiploid genome assembly is typically impeded by heterozygosity, as it introduces errors when haplotypes are collapsed into a consensus sequence. Trio binning offers an innovative solution which exploits heterozygosity for assembly. Short, parental reads are used to assign parental origin to long reads from their F1 offspring before assembly, enabling complete haplotype resolution. Trio binning could therefore provide an effective strategy for assembling highly heterozygous genomes which are traditionally problematic, such as insect genomes. This includes the wood tiger moth (Arctia plantaginis), which is an evolutionary study system for warning colour polymorphism.FindingsWe produced a high-quality, haplotype-resolved assembly forArctia plantaginisthrough trio binning. We sequenced a same-species family (F1 heterozygosity ∼1.9%) and used parental Illumina reads to bin 99.98% of offspring Pacific Biosciences reads by parental origin, before assembling each haplotype separately and scaffolding with 10X linked-reads. Both assemblies are highly contiguous (mean scaffold N50: 8.2Mb) and complete (mean BUSCO completeness: 97.3%), with complete annotations and 31 chromosomes identified through karyotyping. We employed the assembly to analyse genome-wide population structure and relationships between 40 wild resequenced individuals from five populations across Europe, revealing the Georgian population as the most genetically differentiated with the lowest genetic diversity.ConclusionsWe present the first invertebrate genome to be assembled via trio binning. This assembly is one of the highest quality genomes available for Lepidoptera, supporting trio binning as a potent strategy for assembling highly heterozygous genomes. Using this assembly, we provide genomic insights into geographic population structure ofArctia plantaginis.
Increased population density depresses activity but does not influence emigration in the snailPomatias elegans
Authors: Dahirel Maxime , Menut Loïc , Ansart Armelle 
Published: March 2020

AbstractDispersal is a key trait linking ecological and evolutionary dynamics, allowing organisms to optimize fitness expectations in spatially and temporally heterogeneous environments. Some organisms can either actively disperse or reduce activity in response to challenging conditions, and both responses may be under a trade-off. To understand how such organisms respond to changes in environmental conditions, we studied emigration (the first step of dispersal) and activity behaviour in the gonochoric land snailPomatias elegans, a litter decomposer that can reach very high local densities, over most of the range of ecologically relevant densities. We found that crowding had no detectable effect on emigration tendency in this species, contrary to previous results in many hermaphroditic snails.Pomatias elegansis nonetheless able to detect population density; we show they reduce activity rather than increase dispersal in response to crowding. We propose that limiting activity may be more advantageous than moving away in species with especially poor movement abilities, even by land mollusc standards, likeP. elegans. Interestingly, emigration and activity were positively correlated independently of density; this dispersal syndrome may reflect an underlying pace-of-life syndrome, and is compatible with a dispersal-dormancy trade-off, which would require further investigation. Additionally, we found snails with heavier shells relative to their size tended to be less mobile, which may reflect physical and metabolic constraints on movement and/or survival during inactivity. We finally discuss how the absence of density-dependent dispersal may explain whyP. elegansis often found at very high local densities, and the possible consequences of this behaviour for ecosystem functioning and litter decomposition.
Metaproteomic responses ofin vitrogut microbiomes to resistant starches: the role of resistant starch type and inter-individual variations
Authors: Li Leyuan , Ryan James , Ning Zhibin , Zhang Xu , Mayne Janice , Lavallée-Adam Mathieu , Stintzi Alain , Figeys Daniel 
Published: March 2020

AbstractResistant starches (RS) are dietary compounds processed by the gut microbiota into metabolites, such as butyrate, that are beneficial to the host. The production of butyrate by the microbiome appears to be affected by the plant source and type of RS as well as the individual’s microbiota. In this study, we usedin vitroculture and metaproteomic methods to explore the consistency and variations in individual microbiome’s functional responses to three types of RS - RS2(Hi Maize 260), RS3(Novelose 330) and RS4(Fibersym RW). Results showed that RS2 and RS3 significantly altered the levels of protein expression in the individual gut microbiomes, while RS4 did not result in significant protein changes. Significantly elevated protein groups were enriched in carbohydrate metabolism and transport functions of families Eubacteriaceae, Lachnospiraceae and Ruminococcaceae. In addition, Bifidobacteriaceae was significantly increased in response to RS3. We also observed taxon-specific enrichments of starch metabolism and pentose phosphate pathways corresponding to this family. Functions related to starch utilization, ABC transporters and pyruvate metabolism pathways were consistently increased in the individual microbiomes in response to RS2 and RS3; in contrast, the downstream butyrate producing pathway response varied. Our study confirm that different types of RS have markedly variable functional effects on the human gut microbiome, and also found considerable inter-individual differences in microbiome pathway responses.
A machine learning approach for Colles’ fracture treatment diagnosis
Authors: Ngan Kwun Ho , d’Avila Garcez Artur , Knapp Karen M. , Appelboam Andy , Reyes-Aldasoro Constantino Carlos 
Published: March 2020

AbstractWrist fractures (e.g. Colles’ fracture) are the most common injuries in the upper extremity treated in Emergency Departments. Most patients are treated with a procedure called Manipulation under Anaesthesia. Surgical treatment may still be needed in complex fractures or if the wrist stability is not restored. This can lead to inefficiency in constrained medical resources and patients’ inconvenience. Previous geometric measurements in X-ray images were found to provide statistical differences between healthy controls and fractured cases as well as pre- and post-intervention images. The most discriminating measurements were associated with the texture analysis of the radial bone.This work presents further analysis of these measurements and applying them as features to identify the best machine learning model for Colles’ fracture treatment diagnosis. Random forest was evaluated to be the best model based on validation accuracy. The non-linearity of the measurement features has attributed to the superior performance of an ensembled tree-based model. It is also interesting that the most important features (i.e. texture and swelling) required in the optimised random forest model are consistent with previous findings.