bluuebunny/crossref_metadata_2025 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

Purpose

Hepatoblastoma 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.

Methods

We 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.

Results

HERV-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.

Conclusions

Our 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

A 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

In 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

The 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

Some 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

Oxygenic 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

The 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

Macrophage 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

Exercise 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

Background

Diploid 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.

Findings

We 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.

Conclusions

We 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

Dispersal 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

Resistant 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

Wrist 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.
Evaluation of neutralizing antibodies produced by papaya mosaic virus nanoparticles fused to the E2EP3 peptide epitope of Chikungunya envelope
Authors: Rothan Hussin A. , Yusof Rohana
Published: March 2020

Chikungunya virus (CHIKV) infection is the cause of acute symptoms and chronic symmetrical polyarthritis associated with long-term morbidity and mortality. Currently, there is no available licensed vaccine or particularly useful drug for human use against CHIKV infection. This study was conducted to evaluate the efficacy of antibodies produced by papaya mosaic virus (PapMV) nanoparticles fused to E2EP3 peptide of CHIKV envelope as a recombinant CHIKV vaccine. PapMV, PapMV E2EP3, and E2EP3 PapMV were produced in E. coli with an approximate size of 27 to 30 kDa. ICR mice (5 to 6 weeks of age) were injected subcutaneously with 25 micrograms of vaccine construct, and ELISA measured the titer of CHIKV specific IgG antibodies. The results showed that both recombinant proteins E2EP3 PapMV and PapMV E2EP3 were able to induce IgG antibodies production in immunized mice against CHIKV while immunization with recombinant PapMV showed no IgG antibodies induction. The neutralizing activity of the antibodies generated by either E2EP3 PapMV or PapMV E2EP3 exhibited similar inhibition to CHIKV replication in Vero cells using the cells based antibody neutralizing assay and analyzed by plaque formation assay. This study showed the effectiveness of nanoparticles vaccine generated by fusing epitope peptide of CHIKV envelope to papaya mosaic virus envelope in inducing a robust immune response in mice against CHIKV. The data showed that levels of neutralizing antibodies correlate with a protective immune response CHIKV replication.
A Novel Non-hypermucoviscous ST11 Hypervirulent Carbapenem-resistantKlebsiella pneumoniaeLacking Classical Virulence Factors
Authors: Zhang Min , Zhang Jinyong , Li Jia , Xu Shuye , Hu Chunxia , Deng Qiuyang , Wu Xianglin , Xiao Lihua , Liu Zhou , Yang Xiyao , Hu Xiaoqian , Zhang Wenhui , Wang Nan , Yang Liqi , Liu Shiyi , Cui Ruiqin , Hui Zhen , Zhong Yuxin , Luo Yutian , Chen Huaisheng , Wu Weiyuan , Wu Jinsong , Lu Yuemei , Liu Xueyan , Zou Quanming , Huang Wei
Published: March 2020

Background

HypervirulentKlebsiella pneumoniaelacking classical virulence factors is uncommon, and the virulence mechanisms of this organism are not understood.

Methods

Following a retrospective study of carbapenem-resistantK. pneumoniaebased on core genome multilocus sequence typing (cgMLST), isolates that caused high mortality were investigated with a genome-wide association study (GWAS), proteome analysis and an animal model.

Results

The sublineage of sequence type 11 (ST11)K. pneumoniae, which belongs to complex type 3176 (CT3176) and K-locus 47 (KL47), was highlighted due to the high mortality of infected patients. GWAS analysis showed thatampRwas associated with the CT3176 isolates. In a mouse model, the mortality ofampR-carrying isolates was comparable to that of the typical hypervirulent isolate GM2. Even during the first 24 hours of infection, the bacterial load and pathological changes of theampR-carrying isolates in the lungs were more severe than those of GM2. TheampRcomplement mutant was able to enhance the virulence of the KL47 isolate but not the virulence of KL1. Proteome analysis showed that the expression of WcaJ in theampR+isolates was significantly higher than that in theampR−isolates, and this result was also confirmed by transcription tests and capsule staining. It is suggested that the enhancement of the initial stage of capsule synthesis may be the cause of the high virulence of these non-hypermucoviscous ST11 carbapenem-resistantK. pneumoniaeisolates.

Conclusions

Non-hypermucoviscous ST11 hypervirulent carbapenem-resistantK. pneumoniaewarrants continued surveillance and investigation.
Vicarious traumatization in the general public, members, and non-members of medical teams aiding in COVID-19 control
Authors: Li Zhenyu , Ge Jingwu , Yang Meiling , Feng Jianping , Qiao Mei , Jiang Riyue , Bi Jiangjiang , Zhan Gaofeng , Xu Xiaolin , Wang Long , Zhou Qin , Zhou Chenliang , Pan Yinbing , Liu Shijiang , Zhang Haiwei , Yang Jianjun , Zhu Bin , Hu Yimin , Hashimoto Kenji , Jia Yan , Wang Haofei , Wang Rong , Liu Cunming , Yang Chun
Published: March 2020

Since December 2019, more than 79,000 people have been diagnosed with infection of the Corona Virus Disease 2019 (COVID-19). A large number of medical staff were dispersed for Wuhan city and Hubei province to aid COVID-19 control. Psychological stress, especially vicarious traumatization (VT) caused by the COVID-19 pandemic, should not be ignored. To address this concern, the study employed a total of 214 general public (GP) and 526 nurses to evaluate VT scores via a mobile app-based questionnaire. Results showed that the VT scores slightly increased across periods of aiding COVID-19 control, although no statistical difference was noted (P = 0.083). However, the study found lower scores for VT in nurses [median = 69; interquartile range (IQR) = 56–85] than those of the GP (median = 75.5; IQR = 62–88.3) (P = 0.017). In addition, the VT scores for front-line nurses (FLNs; median = 64; IQR = 52–75), including scores for physiological and psychological responses, were significantly lower than those of non-front-line nurses (nFLNs; median = 75.5; IQR = 63–92) (P < 0.001). Interestingly, the VT scores of the GP were significantly higher than those of the FLNs (P < 0.001). However, no statistical difference was observed compared with those of nFLNs (P > 0.05). Importantly, nFLNs are more likely to suffer from VT, which might be related to two factors, namely, gender [odds ratio (OR) = 3.1717; 95% confidence interval (CI) = 4.247–18.808; P = 0.002] and fertility [OR = 2.072; 95%CI = 0.626–24.533; P = 0.039]. Therefore, increased attention should be paid to the psychological problems of the medical staff, especially nFLNs, and GP under the situation of the spread and control of COVID-19. Early strategies that aim to prevent and treat VT in medical staff and GP are extremely necessary.
Machine learning-based CT radiomics model for predicting hospital stay in patients with pneumonia associated with SARS-CoV-2 infection: A multicenter study
Authors: Qi Xiaolong , Jiang Zicheng , Yu Qian , Shao Chuxiao , Zhang Hongguang , Yue Hongmei , Ma Baoyi , Wang Yuancheng , Liu Chuan , Meng Xiangpan , Huang Shan , Wang Jitao , Xu Dan , Lei Junqiang , Xie Guanghang , Huang Huihong , Yang Jie , Ji Jiansong , Pan Hongqiu , Zou Shengqiang , Ju Shenghong
Published: March 2020

Objectives

To develop and test machine learning-based CT radiomics models for predicting hospital stay in patients with pneumonia associated with SARS-CoV-2 infection.

Design

Cross-sectional

Setting

Multicenter

Participants

A total of 52 patients with laboratory-confirmed SARS-CoV-2 infection and their initial CT images were enrolled from 5 designated hospitals in Ankang, Lishui, Zhenjiang, Lanzhou, and Linxia between January 23, 2020 and February 8, 2020. As of February 20, patients remained in hospital or with non-findings in CT were excluded. Therefore, 31 patients with 72 lesion segments were included in the final analysis.

Intervention

CT radiomics models based on logistic regression (LR) and random forest (RF) were developed on features extracted from pneumonia lesions in training and inter-validation datasets. The predictive performance was further evaluated in test dataset on lung lobe- and patients-level.

Main outcomes

Short-term hospital stay (≤10 days) and long-term hospital stay (>10 days).

Results

The CT radiomics models based on 6 second-order features were effective in discriminating short- and long-term hospital stay in patients with pneumonia associated with SARS-CoV-2 infection, with areas under the curves of 0.97 (95%CI 0.83-1.0) and 0.92 (95%CI 0.67-1.0) by LR and RF, respectively, in the test dataset. The LR model showed a sensitivity and specificity of 1.0 and 0.89, and the RF model showed similar performance with sensitivity and specificity of 0.75 and 1.0 in test dataset.

Conclusions

The machine learning-based CT radiomics models showed feasibility and accuracy for predicting hospital stay in patients with pneumonia associated with SARS-CoV-2 infection.
Infected macrophages engage alveolar epithelium to metabolically reprogram myeloid cells and promote antibacterial inflammation
Authors: Liu Xin , Boyer Mark A. , Holmgren Alicia M. , Shin Sunny
Published: March 2020

Alveolar macrophages are the primary immune cells that first detect lung infection. However, only one macrophage patrols every three alveoli. How this limited number of macrophages provides protection is unclear, as numerous pathogens block cell-intrinsic immune responses. The intracellular pathogenLegionella pneumophilainhibits host translation, thereby impairing the ability of infected macrophages to produce critical cytokines. Nevertheless, infected macrophages induce an IL-1-dependent inflammatory response by recruited myeloid cells that controls infection. Here, we show that collaboration with the alveolar epithelium is critical, in that IL-1 instructs the alveolar epithelium to produce GM-CSF. Intriguingly, GM-CSF drives maximal cytokine production in bystander myeloid cells by enhancing PRR-induced glycolysis. Our findings reveal that alveolar macrophages engage alveolar epithelial signals to metabolically reprogram myeloid cells and amplify antibacterial inflammation.

One Sentence Summary

The alveolar epithelium is a central signal relay between infected and bystander myeloid cells that orchestrates antibacterial defense.
Differential tissue stiffness of body column facilitates locomotion ofHydraon solid substrates
Authors: Naik Suyash , Unni Manu , Sinha Devanshu , Rajput Shatruhan Singh , Reddy P. Chandramouli , Kartvelishvily Elena , Solomonov Inna , Sagi Irit , Chatterji Apratim , Patil Shivprasad , Galande Sanjeev
Published: March 2020

The bell-shaped members of Cnidaria typically move around by swimming, whereas theHydrapolyp can perform locomotion on solid substrates in aquatic environment. To address the biomechanics of locomotion on rigid substrates, we studied the ‘somersaulting’ locomotion inHydra. We applied atomic force microscopy to measure the local mechanical properties ofHydra’sbody column and identified the existence of differential Young’s modulus between the shoulder region versus rest of the body column at 3:1 ratio. We show that somersault primarily depends on differential tissue stiffness of the body column and is explained by computational models that accurately recapitulate the mechanics involved in this process. We demonstrate that perturbation of the observed stiffness variation in the body column by modulating the extracellular matrix (ECM) polymerization impairs the ‘somersault’ movement. These results provide mechanistic basis for the evolutionary significance of differential extracellular matrix properties and tissue stiffness.
Validity of dynamical analysis to characterize heart rate and oxygen consumption during effort tests
Authors: Mongin D. , Chabert C. , Caparros A. Uribe , Collado A. , Hermand E. , Hue O. , Alvero Cruz J. R. , Courvoisier D. S.
Published: March 2020

Performance is usually assessed by simple indices stemming from cardiac and respiratory data measured during graded exercise test. The goal of this study is to test the interest of using a dynamical analysis of these data. Therefore, two groups of 32 and 14 athletes from two different cohorts performed two different graded exercise testing before and after a period of training or deconditioning. Heart rate (HR) and oxygen consumption (VO2) were measured. The new dynamical indices were the value without effort, the characteristic time and the amplitude (gain) of the HR and VO2response to the effort. The gain of HR was moderately to strongly associated with other performance indices, while the gain for VO2increased with training and decreased with deconditioning with an effect size slightly higher than VO2max. Dynamical analysis performed on the first 2/3 of the effort tests showed similar patterns than the analysis of the entire effort tests, which could be useful to assess individuals who cannot perform full effort tests. In conclusion, the dynamical analysis of HR and VO2obtained during effort test, especially through the estimation of the gain, provides a good characterization of physical performance, robust to less stringent effort test conditions.
TipQAD: an automated tool for quantifying apical fluorescence dynamics in tip-growing cells
Authors: Tambo Asongu L. , Bhanu Bir , Luo Nan , Rong Duoyan , Wang Fei , Craddock Christian , Lavagi Irene , Yang Zhenbiao
Published: March 2020

Cell polarity is a fundamental property essential for the function and development of all cellular organisms. Tip growth is an extreme form of polar growth requiring spatiotemporally dynamic but highly coordinated cellular activities. Quantification of these dynamic activities is important for the systematic study of the mechanisms controlling cell polarity, but an automated and unbiased method for analyzing and quantification of tip-growing cells has been missing. In this paper, we developed a computational model and an associated tool called TipQAD for quantifying the spatiotemporal dynamics of fluorescence protein (FP) labeled molecules or structures in tip-growing cells. This tool robustly and accurately measured the spatial distribution and temporal dynamics of FP-labeled proteins in the cytoplasm or the plasma membrane at the tip region of several types of tip-growing cells. We also demonstrated its ability to analyze data from FRAP experiments. In conclusion, this tool showed great potential for automated measurements of the spatiotemporal dynamics of fluorescent-labeled cellular molecules and structures.
Environmental DNA sampling in a terrestrial environment: methods to detect a critically endangered frog and a global pathogen
Authors: Burns Thomas J. , Clemann Nick , van Rooyen Anthony R. , Scheele Ben C. , Weeks Andrew R. , Driscoll Don A.
Published: March 2020

Environmental DNA techniques have become established as a useful tool for biological monitoring and are used extensively to determine species presence in aquatic systems. However, their application in terrestrial systems has been more limited, likely in part due to difficulties in choosing where to sample and ensuring that collected DNA reflects current species presence. We developed methods to sample eDNA in the terrestrial environment and trialled them under controlled and field conditions. We targeted three species, an elusive critically endangered frog, an abundant non-threatened frog, and the globally distributed amphibian skin pathogen chytrid fungus, which has been implicated in the decline of over 500 amphibian species. We used a sandpaper-sampling surface to ‘trap’ DNA. After sampling, we washed the surface and filtered the wash water to gather material for DNA extraction and subsequent qPCR. Our controlled condition experiments demonstrated that frog and chytrid fungus DNA was detectable after as few as five contacts between a frog and the sampling surface. Furthermore, this DNA remained detectable after two weeks in cool, shaded, outdoor conditions. Our field experiments demonstrated that these techniques were transferable to natural habitats, where we detected both the common and rare amphibian target species, as well as chytrid fungus. Field sampling eDNA results were broadly consistent with those derived from conventional survey methods. Our methods have potential application in non-invasive sampling of amphibians and other species in terrestrial systems, broadening the applicability of eDNA techniques for species detection and monitoring.
Fourier shell correlation criteria for local resolution estimation
Authors: Rohou Alexis
Published: March 2020

The resolution of three-dimensional (3D) maps obtained by electron microscopy and reconstruction is rarely constant, owing to the flexibility or compositional variability of the macromolecules of interest. Accurately estimating the local resolution within 3D reconstruction volumes is desirable for analytical purposes, and may help improve the reconstruction process itself. One approach to estimating the local resolution is to compute Fourier shell correlations (FSC) between equivalent local regions of maps computed from half datasets: the estimated local resolution is that of the Fourier shell where the FSC drops below a pre-established threshold value. Existing thresholds can lead to significant over-estimates of the local resolution because they do not take into account the low number of independent voxels in low-resolution Fourier shells typically encountered when dealing with small sub-volumes. We derive a modified FSC threshold criterion, and a simple statistical test of whether the FSC significantly exceeds it, which aims to remedy this by taking into account the bias and variance of the FSC as an estimator of signal-to-noise ratio.
Defining Strawberry Uniformity using 3D Imaging and Genetic Mapping
Authors: Li Bo , Cockerton Helen M. , Johnson Abigail W. , Karlström Amanda , Stavridou Eleftheria , Deakin Greg , Harrison Richard J.
Published: March 2020

Strawberry uniformity is a complex trait, influenced by multiple genetic and environmental components. To complicate matters further, the phenotypic assessment of strawberry uniformity is confounded by the difficulty of quantifying geometric parameters ‘by eye’ and variation between assessors. An in-depth genetic analysis of strawberry uniformity has not been undertaken to date, due to the lack of accurate and objective data. Nonetheless, uniformity remains one of the most important fruit quality selection criteria for the development of a new variety. In this study, a 3D-imaging approach was developed to characterise berry uniformity. We show that circularity of the maximum circumference had the closest predictive relationship with the manual uniformity score. Combining five or six automated metrics provided the best predictive model, indicating that human assessment of uniformity is highly complex. Furthermore, visual assessment of strawberry fruit quality in a multi-parental QTL mapping population has allowed the identification of genetic components controlling uniformity. A “regular shape” QTL was identified and found to be associated with three uniformity metrics. The QTL was present across a wide array of germplasm, indicating a strong candidate for marker-assisted breeding. A greater understanding of berry uniformity has been achieved through the study of the relative impact of automated metrics on human perceived uniformity. Furthermore, the comprehensive definition of strawberry uniformity using 3D imaging tools has allowed precision phenotyping, which has improved the accuracy of trait quantification. This tool has allowed us to illustrate the use of advanced image analysis towards the breeding of greater uniformity in strawberry.
Structural basis of transcription-translation coupling
Authors: Wang Chengyuan , Molodtsov Vadim , Firlar Emre , Kaelber Jason T. , Blaha Gregor , Su Min , Ebright Richard H.
Published: March 2020

In bacteria, transcription and translation are coupled processes, in which movement of RNA polymerase (RNAP) synthesizing mRNA is coordinated with movement of the first ribosome translating mRNA. Coupling is modulated by the transcription factors NusG--which is thought to bridge RNAP and ribosome--and NusA. Here, we report cryo-EM structures ofEscherichia colitranscription-translation complexes (TTCs) containing different-length mRNA spacers between RNAP and the ribosome active-center P-site. Structures of TTCs containing short spacers show a state incompatible with NusG bridging and NusA binding (TTC-A; previously termed “expressome”). Structures of TTCs containing longer spacers reveal a new state compatible with NusG bridging and NusA binding (TTC-B) and reveal how NusG bridges and NusA binds. We propose that TTC-B mediates NusG- and NusA-dependent transcription-translation coupling.

One Sentence Summary

Cryo-EM defines states that mediate NusG- and NusA-dependent transcription-translation coupling in bacteria
The Effect of Obesity on Pain Severity and Pain Interference
Authors: Basem Jade , White Robert S. , Chen Stephanie A. , Mauer Elizabeth , Steinkamp Michele L. , Inturrisi Charles E. , Witkin Lisa
Published: March 2020

Background and objectives

Obesity is one of the most prevalent comorbidities associated with chronic pain, the experience of which can severely interfere with activities of daily living and increase the utilization of clinical resources. Obesity is also a risk factor for increased pain severity (pain intensity) and pain interference (pain related disability). We hypothesize that a higher level of obesity, as measured by body mass index (BMI), would be associated with increased levels of pain severity and interference in a population of chronic pain clinic patients.

Methods

Participant data was pulled from a multi-site chronic pain outpatient database from 7/8/2011 to 10/17/2016. The Brief Pain Inventory (BPI), opioid prescriptions, and basic demographic information were queried and we categorized participants into three different ordinal categories based on recorded BMI levels (underweight, normal and overweight, obese). Bivariate analyses were performed to compare pain outcomes by BMI and by other demographic/clinical patient characteristics. Multivariable linear regressions were constructed to model each of four pain severity scores in addition to total pain interference score. All models examined BMI as the primary predictor, controlling for age, receipt of a pain procedure within 45 days prior to the pain clinic encounter, opioid prescription within 45 days prior to the encounter, and diagnosis. The total pain interference model additionally included pain severity (as measured by worst pain in the past 24 hours) as a covariate.

Results

2509 patients were included in the study. The median BMI was 27 and the median age was 59 years. 77% of patients were diagnosed with musculoskeletal pain conditions. Bivariate tests revealed significant differences between BMI groups for all pain severity scores and for total pain interference score. On multivariable modelling controlling for age, pain procedure within 45 days prior to pain clinic encounter, opioid prescription with 45 days prior, and diagnosis, obese patients had significantly higher pain severity (as measured by worst, least, average, and current pain in the past 24 hours) as well as higher pain interference (as measured by the overall pain interference score) than normal weight and overweight patients.

Conclusion

In our study of pain clinic patients, obesity was found to be associated with increased pain severity and pain interference. We believe that this relationship is multifactorial and bidirectional. Pain phyisicans should consider the impact of obesity when addressing pain management for patients.