bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell-Derived Vesicles as TRPC1 Channel Delivery Systems for the Recovery of Cellular Respiratory and Proliferative Capacities
Authors: Kurth Felix , Tai Yee Kit , Parate Dinesh , van Oostrum Marc , Schmid Yannick R. F. , Toh Shi Jie , Yee Yap Jasmine Lye , Wollscheid Bernd , Othman Alaa , Dittrich Petra S. , Franco-Obregón Alfredo
Published: May 2020

Pulsed electromagnetic fields (PEMFs) are capable of specifically activating a TRPC1-mitochondrial axis underlying cell expansion and mitohormetic survival adaptations. This study characterizes cell-derived vesicles (CDVs) generated from C2C12 murine myoblasts and shows that they are equipped with the sufficient molecular machinery to confer mitochondrial respiratory capacity and associated proliferative responses upon their fusion with recipient cells. CDVs derived from wild type C2C12 myoblasts include the cation-permeable transient receptor potential (TRP) channels, TRPC1 and TRPA1, and directly respond to PEMF exposure with TRPC1-mediated calcium entry. By contrast, CDVs derived from C2C12 muscle cells in which TRPC1 had been genetically knocked-down using CRISPR/Cas9 genome editing, do not. Wild type C2C12-derived CDVs are also capable of restoring PEMF-induced proliferative and mitochondrial activation in two C2C12-derived TRPC1 knockdown clonal cell lines in accordance to their endogenous degree of TRPC1 suppression. C2C12 wild type CDVs respond to menthol with calcium entry and accumulation, likewise verifying TRPA1 functional gating and further corroborating compartmental integrity. Proteomic and lipidomic analyses confirm the surface membrane origin of the CDVs providing an initial indication of the minimal cellular machinery required to recover mitochondrial function. CDVs hence possess the potential of restoring respiratory and proliferative capacities to senescent cells and tissues.
CATA: a comprehensive chromatin accessibility database for cancer
Authors: Zhou Jianyuan , Li Xuecang , Chen Jiaxin , Li Taisong , Zhan Weijie , Zhao Jianmei , Li Meng , Yu Zhengmin , Yu Rui , Zou Haiying , Fang Wangkai , Wang Qiuyu , Xie Jianjun
Published: May 2020

Chromatin accessibility is a crucial epigenetic concept that plays a biological role in oncology. As humans become more involved in cancer research, a comprehensive database is required to identify and annotate tumor chromatin accessible regions (CARs). Here, CATA was developed to provide cancer-related CAR annotation. Currently, CATA possesses 2,991,163 CARs, relevant clinical data, and transcription factor binding predictions for cancer CARs from 410 tumor samples of 24 cancer types. Furthermore, CARs were annotated by SNPs, risk SNPs, eQTLs, linkage disequilibrium SNPs, transcription factors, CNV, SNV, enhancer, and 450K methylation sites in our database. By combining all these resources, we believe that CATA will provide better service for researchers on oncology. Our database is accessible athttp://bio.licpathway.net/cata/
Higher prevalence ofBacteroides fragilisin Crohn’s disease exacerbations and strain-dependent increase of epithelial resistance
Authors: Becker Heike E. F. , Jamin Casper , Bervoets Liene , Xu Pan , Pierik Marie J. , Stassen Frank R. M. , Savelkoul Paul H. M. , Penders John , Jonkers Daisy M. A. E.
Published: May 2020

Bacteroides fragilishas previously been linked to Crohn’s disease (CD) exacerbations, but results are inconsistent and underlying mechanisms unknown. This study investigates the epidemiology ofB. fragilisand its virulence factorsbft (enterotoxin) andubiquitinamong 181 CD patients and the impact on the intestinal epithelial barrierin vitro.

The prevalence ofB. fragiliswas significantly higher in active (n=69/88, 78.4%) as compared to remissive (n=58/93, 62.4%, p=0.018) CD patients. Moreover,B. fragiliswas associated with intestinal strictures. Interestingly, the intestinal barrier function, as examined by transepithelial electrical resistance (TEER) measurements of Caco-2 monolayers, improved when exposed to secretomes ofbft-positive (increased TEER ∼160%,p<0.001) but not when exposed tobft-negative strains. Whole metagenome sequencing and metabolomics, respectively, identified 19 coding sequences and two metabolites that discriminated TEER-increasing from non-TEER-increasing strains.

This study revealed a higherB. fragilisprevalence during exacerbation. Surprisingly,bft-positive secretomes improved epithelial resistance.
Multifocal imaging for precise, label-free tracking of fast biological processes in 3D
Authors: Hansen Jan N. , Gong An , Wachten Dagmar , Pascal René , Turpin Alex , Jikeli Jan F. , Kaupp U. Benjamin , Alvarez Luis
Published: May 2020

Many biological processes happen on a nano-to millimeter scale and within milliseconds. Established methods such as confocal microscopy are suitable for precise 3D recordings but lack the temporal or spatial resolution to resolve fast 3D processes and require labeled samples. Multifocal imaging (MFI) allows high-speed 3D imaging but is limited by the compromise between high spatial resolution and large field-of-view (FOV), and the requirement for bright fluorescent labels. Here, we provide a new open-source 3D reconstruction algorithm for multifocal images that allows using MFI for fast, precise, label-free tracking spherical and filamentous structures in a large FOV and across a high depth. We characterize fluid flow and flagellar beating of human and sea urchin sperm with a high z-precision of 0.15 μm, in a large volume of 240 x 260 x 21 μm, and at high speed (500 Hz). The large sampling volume allowed to follow sperm trajectories while simultaneously recording their flagellar beat. Our MFI concept is cost-effective, can be easily implemented, and does not rely on object labeling, which renders it broadly applicable.
CRYPTOCHROME suppresses the circadian proteome and promotes protein homeostasis
Authors: Wong David C.S. , Seinkmane Estere , Stangherlin Alessandra , Zeng Aiwei , Rzechorzek Nina M. , Beale Andrew D. , Day Jason , Reed Martin , Chew Sew Peak , Styles Christine T. , Edgar Rachel S. , Putker Marrit , O’Neill John S.
Published: May 2020

The daily organisation of most mammalian cellular functions is attributed to circadian regulation of clock-controlled protein expression, driven by daily cycles of CRYPTOCHROME-dependent transcriptional feedback repression. To test this, we compared the circadian proteome and phosphoproteome of wild type and CRY-deficient fibroblast cells. Strikingly, CRY-deficient cells showed a two-fold increase in circadian-regulated proteins, phosphopeptides, and K+transport. This was accompanied by extensive remodelling of the cellular proteome overall, including reduced phosphatase and proteasome subunit expression. These adaptations rendered CRY-deficient cells more sensitive to stress, which may account for their reduced circadian robustness and contribute to the wide-ranging phenotypes of CRY-deficient mice. We suggest that CRY ultimately functions to suppress, rather than generate, daily rhythms in cellular protein abundance, thereby maintaining protein and osmotic homeostasis.
The structural variation landscape in 492 Atlantic salmon genomes
Authors: Bertolotti Alicia C. , Layer Ryan M. , Gundappa Manu Kumar , Gallagher Michael D. , Pehlivanoglu Ege , Nome Torfinn , Robledo Diego , Kent Matthew P. , Røsæg Line L. , Holen Matilde M. , Mulugeta Teshome D. , Ashton Thomas J. , Hindar Kjetil , Sægrov Harald , Florø-Larsen Bjørn , Erkinaro Jaakko , Primmer Craig R. , Bernatchez Louis , Martin Samuel A.M. , Johnston Ian A. , Sandve Simen R. , Lien Sigbjørn , Macqueen Daniel J.
Published: May 2020

Structural variants (SVs) are a major source of genetic and phenotypic variation, but remain challenging to accurately type and are hence poorly characterized in most species. We present an approach for reliable SV discovery in non-model species using whole genome sequencing and report 15,483 high-confidence SVs in 492 Atlantic salmon (Salmo salar L.) sampled from a broad phylogeographic distribution. These SVs recover population genetic structure with high resolution, include an active DNA transposon, widely affect functional features, and overlap more duplicated genes retained from an ancestral salmonid autotetraploidization event than expected. Changes in SV allele frequency between wild and farmed fish indicate polygenic selection on behavioural traits during domestication, targeting brain-expressed synaptic networks linked to neurological disorders in humans. This study offers novel insights into the role of SVs in genome evolution and the genetic architecture of domestication traits, along with resources supporting reliable SV discovery in non-model species.
Identification of deleterious single nucleotide polymorphism (SNP)s on the humanTBX5gene & prediction of their structural & functional consequences: Anin silicoapproach
Authors: Mahfuz A M U B , Khan Md. Arif
Published: May 2020

T-box transcription factor 5 (TBX5) gene encodes the transcription factor TBX5, which plays a crucial role in developing the heart and upper limbs. Damaging single nucleotide variants in this gene alters the protein structure, disturbs the functions of TBX5, and ultimately causes Holt-Oram Syndrome (HOS). By analyzing available single nucleotide polymorphism information in the dbSNP database, this study was designed to identify the most deleteriousTBX5SNPs throughsilicoapproaches and predict their structural and functional consequences.

Fifty-eight missense substitutions were found damaging by sequences homology-based tools like SIFT and PROVEAN and structure homology-based tools like PolyPhen-2. These SNPs were further scrutinized by various disease association meta-predictor tools. Additionally, the conservation profile of amino acid residues, their surface accessibility, stability, and structural integrity of the native protein upon mutations was assessed. From these analyses, finally 5 SNPs were detected as the most damaging ones [rs1565941579 (P85S), rs1269970792 (W121R), rs772248871 (V153D), rs769113870 (E208D), and rs1318021626 (I222N)]. Analyses of stop-loss, nonsense, UTR, and splice site SNPs were also conducted.

Through integrative bioinformatics analyses, this study has identified SNPs that are deleterious to the TBX5 protein structure and have the potential to cause HOS. Further wet-lab experiments can validate these findings.
Vasculature-staining with lipophilic dyes in tissue-cleared brains assessed by deep learning
Authors: Henriksen Beatriche L. E. , Jensen Kristian H. R. , Berg Rune W.
Published: May 2020

Visualization of the vasculature in three dimensions (3D) has become attractive, particularly in stroke models. 3D-reconstruction is aided by tissue-clearing, where the transparency allows imaging of fluorescent probes in deeper structures. The vasculature is commonly stained by fluorescent lipophilic dyes that are incorporated into the wall during transcardial perfusion. Nevertheless, tissue clearing involves extracting the light-scattering lipids, and hence also the lipid-appended dyes. The wash-out likely depends on dye and its aldehyde-fixability. Fixation secures cross-linking to proteins and hence retainment in the tissue. However, the compatibility of various types of dyes is largely unknown. We tested and compared 9 different dyes for vasculature staining and tolerance to lipid clearing, which was quantified using deep learning image segmentation. Among the dyes, we found a subset that is both cost-effective and compatible with tissue lipid clearing. We suggest these dyes will provide a valuable tool for future investigations.

Highlights

Size, alkyl-chains and aldehyde-fixable groups improve dye retention and performance.

Cost-effective dyes in specific liposomes result in optimal vessel staining.

SP-DiIC18 is compatible with CLARITY and BrainFilm and advantageous for most studies.

We recommend, SP-DiI and R18, cost-effective dyes, for vessel-painting with CLARITY.

Abstract Figure
Assessing the predation function via quantitative and qualitative interaction components
Authors: Martínez-Núñez Carlos , Rey Pedro J
Published: May 2020

Interactions among organisms can be defined by two main features: a quantitative component (i.e. frequency of occurrence) and a qualitative component (i.e. success of the interaction). Measuring properly these two components at the community level, can provide a good estimate of the ecosystem functions mediated by biotic interactions. Although this approach has been frequently applied to evaluate the eco-evolutionary consequences of mutualistic relationships, it has never been extended to the predation function and the associated pest control ecosystem service. Here, we introduce a simple measure that accounts for the quantitative and the qualitative components of predation interactions, and facilitates a precise characterization of this ecosystem function at the community level, while accounting for variations at species and individual levels. This measure arises as a fine indicator of predation pressure, and provides great opportunities to better understand how different components of predation and pest control potential vary across environmental gradients.
Sex differences and effects of estrous stage on hippocampal-prefrontal theta communications
Authors: Schoepfer Kristin J. , Xu Yiqi , Wilber Aaron A. , Wu Wei , Kabbaj Mohamed
Published: May 2020

Effective communication between the mammalian hippocampus and neocortex is essential to certain cognitive-behavioral tasks critical to survival in a changing environment. Notably, functional synchrony between local field potentials (LFPs) of the ventral hippocampus (vHPC) and the medial prefrontal cortex (mPFC) within the theta band (4-12 Hz) underlies innate avoidance behavior during approach-avoidance conflict tasks in male rodents. However, the physiology of vHPC-mPFC communications in females remains unestablished. Furthermore, little is known about how mPFC subdivisions functionally interact in the theta band with hippocampal subdivisions in both sexes in the absence of task demands. Given the established roles of biological sex and gonadal hormone status on innate avoidance behaviors and neuronal excitability, here, we characterize the effects of biological sex and female estrous stage on hippocampal-prefrontal theta signaling in freely-moving female and male rats. LFPs from vHPC, dorsal hippocampus (dHPC), mPFC-prelimbic (PrL), and mPFC-infralimbic (IL) were simultaneously recorded during spontaneous exploration of a familiar arena. Data suggest that theta phase and power in vHPC preferentially synchronize with PrL; conversely, dHPC and IL preferentially synchronize. Males displayed greater vHPC-PrL theta synchrony than females, despite similar regional frequency band power and inter-regional coherence. Additionally, several significant estrous-linked changes in hippocampal-prefrontal theta dynamics were observed. These findings support the hypothesis that biological sex and female estrous stage can both affect hippocampal-prefrontal theta signaling in a familiar environment. These findings establish novel research avenues concerning sexual dimorphisms and effects of gonadal hormone status in HPC-mPFC network activity pertaining to threat evaluation biomarkers.

SIGNIFICANCE STATEMENT

Effective signaling between subregions of the hippocampus and the prefrontal cortex underlies several cognitive-behavioral processes necessary for survival. Theta-frequency synchrony between the local fields of the ventral hippocampus and the prefrontal cortex regulates innate avoidance behavior in male rodents. However, this circuit remains understudied in females, despite its potential utility in research modeling the neurobiology of anxiety disorders (and sex differences therein). Here, we demonstrate that both biological sex and female hormone status have multifaceted effects on hippocampal-prefrontal theta-frequency signaling in freely-moving rats during exploration of a familiar arena. These findings provide insight into how biological sex and female estrous stage shape the way in which these circuits may represent the potential for threat.
Towards a unifying diversity-area relationship (DAR) of species- and gene-diversity
Authors: Ma Zhanshan (Sam) , Ellison Aaron M.
Published: May 2020

Aim

The microbiome as a biogeographic entity can be investigated, to the minimum, from two perspectives: one is the spatial/temporal distribution of species (or any level of the operational taxonomic unit or OTU) diversity, and another is the spatial/temporal distribution of metagenomic gene diversity. Both are necessary for comprehensive understanding of the taxonomical, ecological, evolutionary and functional aspects of the microbiome biogeography. Here we propose to investigate the metagenomic diversity-area relationship (m-DAR), which is a transformation of the species-DAR (s-DAR) that extended the classic SAR (species-area relationship) by replacing the species richness with general species diversity measured in Hill numbers.

Innovation

Them-DAR ands-DAR, using the same mathematical models, offer a unifying tool for investigating the biogeography of microbiome from ecological, metagenomic and functional perspectives. Specifically, we investigatem-DAR of the human gut metagenome in terms of the MG (metagenomic gene) and MFGC (metagenome functional gene cluster) respectively, by sketching out the DAR-profile, PDO (pair-wise diversity overlap) profile, MAD (maximal accrual diversity) profile, and RIP (ratio of individual- to population-diversity) profile at each scale. These profiles constitute our unifying DAR toolset and can be applied to any microbiomes beyond the human gut microbiome.

Main conclusions

We demonstrate the construction and applications of them-DAR and its associated four profiles with six large datasets of the human gut metagenomes including three microbiome-associated diseases (obesity, diabetes, IBD) and their healthy controls, supported with randomization tests to determine the differences between healthy and diseased treatments in theirm-DAT parameters. Theoretically, our study presents a successful case to demonstrate the feasibility of unifying systematic biogeographyvs. evolutionary biogeography, of an inclusive biogeography of plants, animal and microbes. Practically, our approach offers an important tool for investigating the spatial scaling of human metagenome diversity in a population (cohort) and its relationship with individual-level diversity.
Advancing Divide-and-Conquer Phylogeny Estimation using Robinson-Foulds Supertrees
Authors: Yu Xilin , Le Thien , Christensen Sarah A. , Molloy Erin K. , Warnow Tandy
Published: May 2020

One of the Grand Challenges in Science is the construction of theTree of Life, an evolutionary tree containing several million species, spanning all life on earth. However, the construction of the Tree of Life is enormously computationally challenging, as all the current most accurate methods are either heuristics forNP-hard optimization problems or Bayesian MCMC methods that sample from tree space. One of the most promising approaches for improving scalability and accuracy for phylogeny estimation uses divide-and-conquer: a set of species is divided into overlapping subsets, trees are constructed on the subsets, and then merged together using a “supertree method”. Here, we present Exact-RFS-2, the first polynomial-time algorithm to find an optimal supertree of two trees, using the Robinson-Foulds Supertree (RFS) criterion (a major approach in supertree estimation that is related to maximum likelihood supertrees), and we prove that finding the RFS of three input trees isNP-hard. We also present GreedyRFS (a greedy heuristic that operates by repeatedly using Exact-RFS-2 on pairs of trees, until all the trees are merged into a single supertree). We evaluate Exact-RFS-2 and GreedyRFS, and show that they have better accuracy than the current leading heuristic for RFS. Exact-RFS-2 and GreedyRFS are available in open source form on Github atgithub.com/yuxilin51/GreedyRFS.
INSCT: Integrating millions of single cells using batch-aware triplet neural networks
Authors: Simon Lukas M. , Wang Yin-Ying , Zhao Zhongming
Published: May 2020

Efficient integration of heterogeneous and increasingly large single cell RNA sequencing (scRNA-seq) data poses a major challenge for analysis and in particular, comprehensive atlasing efforts. Here, we developed a novel deep learning algorithm to overcome batch effects using batch-aware triplet neural networks, called INSCT (“Insight”). Using simulated and real data, we demonstrate that INSCT generates an embedding space which accurately integrates cells across experiments, platforms and species. Our benchmark comparisons with current state-of-the-art scRNA-seq integration methods revealed that INSCT outperforms competing methods in scalability while achieving comparable accuracies. Moreover, using INSCT in semi-supervised mode enables users to classify unlabeled cells by projecting them into a reference collection of annotated cells. To demonstrate scalability, we applied INSCT to integrate more than 2.6 million transcriptomes from four independent studies of mouse brains in less than 1.5 hours using less than 25 gigabytes of memory. This feature empowers researchers to perform atlasing scale data integration in a typical desktop computer environment. INSCT is freely available athttps://github.com/lkmklsmn/insct.

Highlights

INSCT accurately integrates multiple scRNA-seq datasets

INSCT accurately predicts cell types for an independent scRNA-seq dataset

Efficient deep learning framework enables integration of millions of cells on a personal computer
Back to feedback: aberrant sensorimotor control in music performance under pressure
Authors: Furuya Shinichi , Ishimaru Reiko , Oku Takanori , Nagata Noriko
Published: May 2020

Precisely timed production of dexterous actions is often destabilized in anxiogenic situations. Previous studies demonstrated that cognitive functions such as attention and working memory as well as autonomic nervous functions are susceptible to induced anxiety in skillful performance while playing sports or musical instruments. However, it is not known whether the degradation of motor functions, sensory perception, or sensorimotor control underlies such a compromise of skillful performance due to psychophysiological distress. Here, we addressed this issue through a series of behavioral experiments, which provided no evidence supporting for detrimental effects of the stress on the perceptual accuracy and precision of the finger movements in pianists. By contrast, after transiently delaying the timing of tone production while playing the piano, the local tempo was abnormally disrupted only under pressure. The results suggest that psychological stress degraded the temporal stability of movement control due to an abnormal increase in sensory feedback gain but not temporal perception or motor precision. A learning experiment further demonstrated that the temporal instability of auditory-motor control under pressure was alleviated after practicing piano while ignoring delayed auditory feedback but not after practicing while compensating for the delayed feedback. Together, these findings suggest an abnormal transition from feedforward to feedback control in expert piano performance in anxiogenic situations, which can be mitigated through specialized sensorimotor training that involves piano practice while volitionally ignoring the artificially delayed provision of auditory feedback.
BrainGNN: Interpretable Brain Graph Neural Network for fMRI Analysis
Authors: Li Xiaoxiao , Zhou Yuan , Dvornek Nicha , Zhang Muhan , Gao Siyuan , Zhuang Juntang , Scheinost Dustin , Staib Lawrence , Ventola Pamela , Duncan James
Published: May 2020

Understanding which brain regions are related to a specific neurological disorder or cognitive stimuli has been an important area of neuroimaging research. We propose BrainGNN, a graph neural network (GNN) framework to analyze functional magnetic resonance images (fMRI) and discover neurological biomarkers. Considering the special property of brain graphs, we design novel ROI-aware graph convolutional (Ra-GConv) layers that leverage the topological and functional information of fMRI. Motivated by the need for transparency in medical image analysis, our BrainGNN contains ROI-selection pooling layers (R-pool) that highlight salient ROIs (nodes in the graph), so that we can infer which ROIs are important for prediction. Furthermore, we propose regularization terms—unit loss, topK pooling (TPK) loss and group-level consistency (GLC) loss—on pooling results to encourage reasonable ROI-selection and provide flexibility to encourage either fully individual- or patterns that agree with group-level data. We apply the BrainGNN framework on two independent fMRI datasets: an Autism Spectrum Disorder (ASD) fMRI dataset and data from the Human Connectome Project (HCP) 900 Subject Release. We investigate different choices of the hyper-parameters and show that BrainGNN outperforms the alternative fMRI image analysis methods in terms of four different evaluation metrics. The obtained community clustering and salient ROI detection results show a high correspondence with the previous neuroimaging-derived evidence of biomarkers for ASD and specific task states decoded for HCP. We will make BrainGNN codes public available after acceptance.
Metagenomic identification of diverse animal hepaciviruses and pegiviruses
Authors: Porter Ashleigh F. , Pettersson John H.-O. , Chang Wei-Shan , Harvey Erin , Rose Karrie , Shi Mang , Eden John-Sebastian , Buchmann Jan , Moritz Craig , Holmes Edward C.
Published: May 2020

The RNA virus familyFlaviviridaeharbours several important pathogens of humans and other animals, including Zika virus, dengue virus and hepatitis C virus. TheFlaviviridaeare currently divided into four genera -Hepacivirus,Pegivirus,PestivirusandFlavivirus– each of which have a diverse host range. Members of the genusHepacivirusare associated with a diverse array of animal species, including humans and non-human primates, other mammalian species, as well as birds and fish, while the closely related pegiviruses have been identified in a variety of mammalian taxa including humans. Using a combination of meta-transcriptomic and whole genome sequencing we identified four novel hepaciviruses and one novel variant of a known virus, in five species of native Australian wildlife, expanding our knowledge of the diversity in this important group of RNA viruses. The infected hosts comprised native Australian marsupials and birds, as well as a native gecko (Gehyra lauta). The addition of these novel viruses led to the identification of a distinct marsupial clade within the hepacivirus phylogeny that also included an engorgedIxodes holocyclustick collected while feeding on Australian long-nosed bandicoots (Perameles nasuta). Gecko and avian associated hepacivirus lineages were also identified. In addition, by mining the short-read archive (SRA) database we identified another five novel members ofFlaviviridae, comprising three new hepaciviruses from avian and primate hosts, as well as two primate-associated pegiviruses. The large-scale phylogenetic analysis of these novel hepacivirus and pegivirus genomes provides additional support for virus-host co-divergence over evolutionary time-scales.
Transcriptome analysis reveals infection strategies employed byFusarium graminearumas a root pathogen
Authors: Ding Yi , Gardiner Donald M , Kazan Kemal
Published: May 2020

The fungal pathogenFusarium graminearuminfect both heads and roots of cereal crops causing several economically important diseases such as head blight, seedling blight, crown rot and root rot. Trichothecene mycotoxins such as deoxynivalenol (DON), a well-known virulence factor, produced byF. graminearum(Fg) during disease development is also an important health concern. Although howF. graminearuminfects above-ground tissues is relatively well studied, very little is known about molecular processes employed by the pathogen during below-ground infection. Also unknown is the role of DON during root infection. In the present study, we analyzed the transcriptome ofF. graminearumduring root infection of the model cerealBrachypodium distachyon.We also compared ourFgtranscriptome data during root infection with those reported during wheat head infection. These analyses suggested that both shared and unique infection strategies employed by the pathogen during colonization of different host tissues. Several metabolite biosynthesis genes induced inF. graminearumduring root infection could be linked to phytohormone production, implying that the pathogen likely interferes root specific defenses. In addition, to understand the role of DON inFgroot infection, we analyzed the transcriptome of the DON deficientTri5mutant. These analyses showed that the absence of DON had a significant effect on fungal transcriptional responses. Although DON was produced in infected roots, this mycotoxin did not act as a virulence factor during root infection. Our results reveal new mechanistic insights into the below-ground strategies employed byF. graminearumthat may benefit the development of new genetic tools to combat this important cereal pathogen.
Lipoic acid biosynthesis is essential forPlasmodium falciparumtransmission and influences redox response and carbon metabolism of parasite asexual blood stages
Authors: Biddau Marco , Kumar T.R. Santha , Henrich Philipp , Laine Larissa M. , Blackburn Gavin J. , Chokkathukalam Achuthanunni , Li Tao B , Sim Kim Lee , Hoffman Stephen L , Barrett Michael P. , Coombs Graham H. , McFadden Geoffrey I. , Fidock David A. , Müller Sylke , Sheiner Lilach
Published: May 2020

Malaria is still one of the most important global infectious diseases. Emergence of drug resistance and a shortage of new efficient anti-malarials continue to hamper a malaria eradication agenda. Malaria parasites are highly sensitive to changes in redox environment. Understanding the mechanisms regulating parasite redox could contribute to the design of new drugs. Malaria parasites have a complex network of redox regulatory systems housed in their cytosol, in their mitochondrion and in their plastid (apicoplast). While the roles of enzymes of the thioredoxin and glutathione pathways in parasite survival have been explored, the antioxidant role of α-lipoic acid (LA) produced in the apicoplast has not been tested. We analysed the effects of LA depletion on mutantPlasmodium falciparumlacking the apicoplast lipoic acid protein ligase B (lipB). Our results showed a change in expression of redox regulators in the apicoplast and the cytosol. We further detected a change in parasite central carbon metabolism, with LA depletion influencing glycolysis and tricarboxylic acid cycle activity. Importantly, abrogation of LipB impactedP. falciparummosquito development, preventing oocyst maturation and production of infectious sporozoite stages, thus flagging LA biosynthesis as a potential target for the development of new transmission drugs.
Morphological and genetic confirmation of the millipedeChordeuma sylvestreC. L. Koch, 1847 new to Ireland
Authors: Gaul Willson , Tighe Andrew J
Published: May 2020

We report the millipedeChordeuma sylvestreC. L. Koch, 1847 for the first time from Ireland. We used morphology of male gonopods and DNA barcoding of the COI gene from two individuals to confirm the identification of one male and one female collected from the campus of University College Dublin. DNA barcoding revealed two mitochondrial haplotypes, implying that colonization was from multiple females or eggs from multiple females. To evaluate how likely it is thatC. sylvestrearrived relatively recently in Ireland, we used species richness estimates and species accumulation curves to evaluate the completeness of the species list compiled during two previous periods of intensive millipede recording going back to 1971. Millipede recording in Ireland was far from complete during the period 1971 – 1984, with multiple species present but undetected. Recording was more complete during the period 1986 – 2005. The area within 20 km of the newC. sylvestrerecords was poorly recorded during the period 1986 – 2005, so we cannot rule out the possibility thatC. sylvestrehas been in Dublin for at least a few decades. However, the disjunct location of the current records compared to the species’s known native range in northern France, the urban location of the current site, and the lack of records from the relatively intensive millipede recording in Ireland between 1986 and 2005 suggest thatC. sylvestreis a recent anthropogenic introduction in Ireland.
Kmer2SNP: reference-free SNP calling from raw reads based on matching
Authors: Li Yanbo , Lin Yu
Published: May 2020

The development of DNA sequencing technologies provides the opportunity to call heterozygous SNPs for each individual. SNP calling is a fundamental problem of genetic analysis and has many applications, such as gene-disease diagnosis, drug design, and ancestry inference. Reference-based SNP calling approaches generate highly accurate results, but they face serious limitations especially when high-quality reference genomes are not available for many species. Although reference-free approaches have the potential to call SNPs without using the reference genome, they have not been widely applied on large and complex genomes because existing approaches suffer from low recall/precision or high runtime.

We develop a reference-free algorithm Kmer2SNP to call SNP directly from raw reads. Kmer2SNP first computes the k-mer frequency distribution from reads and identifies potential heterozygous k-mers which only appear in one haplotype. Kmer2SNP then constructs a graph by choosing these heterozygous k-mers as vertices and connecting edges between pairs of heterozygous k-mers that might correspond to SNPs. Kmer2SNP further assigns a weight to each edge using overlapping information between heterozygous k-mers, computes a maximum weight matching and finally outputs SNPs as edges between k-mer pairs in the matching.

We benchmark Kmer2SNP against reference-free methods including hybrid (assembly-based) and assembly-free methods on both simulated and real datasets. Experimental results show that Kmer2SNP achieves better SNP calling quality while being an order of magnitude faster than the state-of-the-art methods. Kmer2SNP shows the potential of calling SNPs only using k-mers from raw reads without assembly. The source code is freely available athttps://github.com/yanboANU/Kmer2SNP.
Impairment of a distinct cancer-associated fibroblast population limits tumour growth and metastasis
Authors: Jungwirth Ute , van Weverwijk Antoinette , Jenkins Liam , Alexander John , Vicente David , Gao Qiong , Haider Syed , Iravani Marjan , Isacke Clare M.
Published: May 2020

Profiling studies have revealed considerable phenotypic heterogeneity in cancer-associated fibroblasts (CAFs) present within the tumour microenvironment, however, functional characterisation of different CAF subsets is hampered by the lack of specific markers defining these populations. Here we show that genetic deletion of the Endo180 (MRC2) receptor, predominantly expressed by a population of matrix-remodelling CAFs, profoundly limits tumour growth and metastasis; effects that can be recapitulated in 3D co-culture assays. This impairment results from a CAF-intrinsic contractility defect and reduced CAF viability which, coupled with the lack of phenotype in the normal mouse, demonstrates that upregulated Endo180 expression by a specific, potentially targetable CAF subset is required to generate a supportive tumour microenvironment. Further, characterisation of a tumour subline selected via serialin vivopassage for its ability to overcome these stromal defects provides important insight into how tumour cells adapt to a non-activated stroma in the early stages of metastatic colonisation.
A High Accurate Machine Learning Meta-Strategy for the Prediction of Intrinsically Disorder Proteins
Authors: Hu Chengbin , Qin Yiru , Ye Chuan , jin Jiao , Zhou Ting , He Zhixu , Shu Liping
Published: May 2020

Background: Many proteins or partial regions of proteins do not have stable and well-defined three-dimensional structures in vitro. Understanding intrinsically disorder proteins (IDPs) is significant for interpreting biological function as well as studying many diseases. Although more than 70 disorder predictors have been invented, many existing predictors are limited on the characteristics of proteins and do not have very high accuracy. Therefore, it is critical to formulate new strategies on disorder protein prediction. Results: Here, we propose a machine learning meta-strategy to improve the accuracy of disordered proteins and disordered regions prediction. We first use logistic forward parameter selection to select eight most significant predictors from the current available IDP predictors. Then we design a novel meta-strategy using several machine learning models, including Decision-tree based algorithm, Naive Bayes, Random forest, and Convolutional Neural Network (CNN). By applying different strategies, the results suggest Random forest can improve the predicted single amino acid accuracy significantly to 93.35%. Using the combination vector data of eight most significant predictors as input, the Convolution Neural Network can improve the whole protein prediction to 95.62%. Conclusion: According to the performance of our machine learning meta-strategy, the Random forest and CNN models can improve the accuracy to predict intrinsically disorder proteins.
Industrial districts and the fourth industrial revolution
Authors: Bettiol Marco , Capestro Mauro , De Marchi Valentina , Di Maria Eleonora , Sedita Silvia Rita
Published: May 2020

Purpose

This paper aims to explore if firms located in industrial districts (IDs) have different adoption paths concerning Industry 4.0 technologies and get different results with respect to other similar firms located outside IDs.

Design/methodology/approach

The study is based on a quantitative analysis related to an original data set of 206 Italian manufacturing firms specializing in made in Italy industries and adopting Industry 4.0 technologies. A case study of a district firm is also presented to explain the rationale of investment strategies and results obtained.

Findings

The analysis shows that there are differences between district and non-district firms when Industry 4.0 technology investments are concerned (higher investment rate in big data/cloud and augmented reality for district firms than non-district ones). In contrast to a breakthrough view of the fourth industrial revolution, the study suggests that 4.0 technologies emphasize the peculiarities and competitiveness factors typical of the district model in terms of customization and flexibility. There are differences in the motivations of adoption (product diversification for district firms vs productivity enhancement for non-district firms) and in the results achieved.

Originality/value

The paper is one of the first attempts to empirically explore the technological innovation paths related to Industry 4.0 within IDs, therefore, contributing to the debate on the possible evolution of the district model
Obstetric haemorrhage and risk of cardiovascular disease after three decades: a population‐based cohort study
Authors: Ukah UV , Platt RW , Potter BJ , Paradis G , Dayan N , He S , Auger N
Published: May 2020

Objective

To investigate the association between obstetric haemorrhage and cardiovascular disease up to three decades after pregnancy.

Design

Population‐based cohort study.

Setting and population

All women who delivered between 1989 and 2016 in Quebec, Canada.

Methods

Using hospital admissions data, 1 224 975 women were followed from their first delivery until March 2018. The main exposure measures were antenatal (placenta praevia, placental abruption, peripartum haemorrhage) or postpartum haemorrhage, with or without transfusion. Adjusted Cox regression models were used to assess the association between obstetric haemorrhage and future cardiovascular disease.

Main outcome measure

Cardiovascular hospitalisation.

Results

Among 104 291 (8.5%) women with haemorrhage, 4612 (4.4%) required transfusion. Women with haemorrhage had a higher incidence of cardiovascular hospitalisation than women without haemorrhage (15.5 versus 14.1 per 10 000 person‐years; 2437 versus 28 432 events). Risk of cardiovascular hospitalisation was higher for obstetric haemorrhage, with or without transfusion, compared with no haemorrhage (adjusted hazard ratio [aHR] 1.06, 95% CI 1.02–1.10). Women with haemorrhage and transfusion had a substantially greater risk of cardiovascular hospitalisation (aHR 1.47, 95% CI 1.23–1.76). Among transfused women, placental abruption (aHR 1.79, 95% CI 1.06–3.00) and postpartum haemorrhage (aHR 1.38, 95% CI 1.13–1.68) were both associated with risk of cardiovascular hospitalisation. Antenatal haemorrhage with transfusion was associated with 2.46 times the risk of cardiovascular hospitalisation at 5 years (95% CI 1.59–3.80) and 2.14 times the risk at 10 years (95% CI 1.47–3.12).

Conclusions

Obstetric haemorrhage requiring transfusion is associated with maternal cardiovascular disease. The benefit of cardiovascular risk prevention in pregnant women with obstetric haemorrhage requires further investigation.

Tweetable abstract

Risk of future cardiovascular disease is increased for women with obstetric haemorrhage who require transfusion.
Evolution and risk factors of anal incontinence during the first 6 years after first delivery: a prospective cohort study
Authors: Johannessen HH , Mørkved S , Stordahl A , Wibe A , Falk RS
Published: May 2020

Objective

To explore changes in prevalence of anal incontinence (AI) from late first pregnancy to 6 years postpartum, and to evaluate possible risk factors for changes in AI during the 6‐year period.

Design

Prospective longitudinal cohort study.

Setting

Two Norwegian health regions.

Population or sample

Women with first deliveries between May 2009 and December 2010.

Methods

Participants reported AI in late pregnancy, 6 months, 1 and 6 years after first delivery using postal or digital questionnaires. AI prevalence was calculated, and mixed effects Poisson regression analyses with robust variance were applied.

Main outcome measures

AI from late pregnancy to 6 years postpartum.

Results

Among 1571 participants, 65% had normal vaginal first deliveries, 20% had vaginal deliveries complicated by instrumental intervention and/or obstetric anal sphincter injury (IVD ± OASIS). Nearly 1 in 10 women reported persistent incontinence during the 6 years. The overall AI prevalence was reduced from late pregnancy to 1 year postpartum for all modes of delivery. At 6 years postpartum, women with IVD ± OASIS had a higher AI prevalence (23%; 95% CI 16–30%) compared with women with caesarean section (8%; 95% CI 2–13%) or normal vaginal delivery (12%; 95% CI 9–16%). Moreover, women who were <23 years, ≥34 years, unemployed during first pregnancy, who had active bowel disease (PR: 2.4; 95% CI 2.0–2.7), or bowel evacuation problems during the 6‐year period had higher AI prevalence.

Conclusions

Mode of first delivery modified AI prevalence during the 6‐year period, whereas age, bowel disease and bowel evacuation problems were associated with higher prevalence of AI from late first pregnancy to 6 years postpartum.

Tweetable abstract

Complicated vaginal delivery, age and bowel emptying problems increase the risk of long‐term anal incontinence.
Can weekly discussions in a sensory science course influence student's perception and confidence in their professional success skills?
Authors: Albiol Tapia Marta , Lee Soo‐Yeun
Published: May 2020

The Institute of Food Technologists’ (IFT) success skills highlight the importance of developing professional skills in the food science curriculum. On the other hand, many students in higher education report that the public school system feels disconnected and unrelated to their future. In this context, this study aimed to evaluate student's perceived importance of professional skills, as well as to enhance their awareness and confidence in them. Students in a sensory science class at the University of Illinois completed a questionnaire at the beginning, middle, and end of the semester to assess their opinion of and self‐assurance in professional skills, such as writing technical reports, providing leadership, making formal presentations, and applying critical thinking. During the semester, students received basic training and guidelines on each skill and were given assignments and activities to practice them as part of their coursework. Results showed increased knowledge about the existence of IFT core competencies, as well as an increased motivation to practice success skills regularly. They also showed an increased perceived importance of presentation skills, leadership, dealing with group conflict, researching scientific information, and library resources. Confidence in 80% of the skills increased significantly by the end of the semester, after students had been presented with opportunities to practice and discuss the skills in groups. Students were also able to relate their learning of specific success skills to different course assignments. This study concluded that a general exposure to the importance of practicing professional skills in a college setting enhanced student's experiences and awareness by connecting them to their future professional careers.
A highly sensitive monoclonal antibody−based paper sensor for simultaneously detecting valnemulin and tiamulin in porcine liver
Authors: Na Guanqiong , Hu Xiaofei , Sun Yaning , Kwee Sharon , Xing Guangxu , Xing Yunrui , Zhang Gaiping
Published: May 2020

Valnemulin (VAL) and tiamulin (TIA) are pleuromutilin antibiotics used primarily for treating bacterial infections in swine or other food animals. Furthermore, VAL and TIA are also employed as feed additives to promote animal growth. However, the illegal use of VAL and TIA could cause a series of hazards to consumers. Here, VAL was designed to be conjugated with bovine serum protein to prepare immunogen. A highly sensitive monoclonal antibody that recognized both VAL and TIA has been successfully produced. Moreover, an immunochromatographic strip assay for rapidly screening VAL and TIA in porcine liver was established with visual detection limits (cutoff values) of 50 and 25 ng/g, respectively. The IC50 values calculated from the equation of the standard curve were 6.06 and 3.45 ng/g and the limits of detection were 0.96 and 0.29 ng/g for VAL and TIA. According to the recovery experiment results, the test strip exhibited acceptable accuracy and precision. Generally, the proposed strip provided a practical tool for the detection of VAL and TIA.

Practical Application

We produced a highly sensitive monoclonal antibody and developed an immunoassay strip for simultaneously monitoring TIA and VAL. Additionally it was preliminarily confirmed that the rapid detection tool was suitable for screening TIA and VAL in porcine liver.