bluuebunny/crossref_metadata_2025 huggingface dataset:
Online information on face masks in Italian and English websites: deficiencies and responsibilities of search engines
Authors: Meta Shaily , Ghezzi Daria , Catalani Alessia , Vanzolini Tania , Ghezzi Pietro
Published: October 2020

Countries have major differences in the acceptance of face mask use for the prevention of COVID-19. We analyzed 450 webpages returned by searching the string “are face masks dangerous” in Italy, the UK and the USA using three search engines (Bing, Duckduckgo and Google). The majority (64-79%) were pages from news outlets, with few (2-6%) pages from government and public health agencies. Webpages with a positive stance on masks were more frequent in English (50%) than in Italian (36%), and those with a negative stance were more frequent in Italian (28% vs. 19% in English). Google returned the highest number of mask-positive pages and Duckduckgo the lowest. Google also returned the lowest number of pages mentioning conspiracy theories and Duckduckgo the highest. Webpages in Italian scored lower than those in English in transparency (reporting authors, their credentials and backing the information with references). When issues about the use of face masks were analyzed, mask effectiveness was the most discussed followed by hypercapnia (accumulation of carbon dioxide), contraindication in respiratory disease, and hypoxia, with issues related to their contraindications in mental health conditions and disability mentioned by very few pages. This study suggests that: 1) public health agencies should increase their web presence in providing correct information on face masks; 2) search engines should improve the information quality criteria in their ranking; 3) the public should be more informed on issues related to the use of masks and disabilities, mental health and stigma arising for those people who cannot wear masks.
Neuronal and synaptic plasticity in the visual thalamus in mouse models of glaucoma
Authors: Van Hook Matthew J. , Monaco Corrine , Smith Jennie C.
Published: October 2020

Homeostatic plasticity plays important roles in regulating synaptic and intrinsic neuronal function to stabilize output following perturbations to circuit activity. In glaucoma, a neurodegenerative disease of the visual system commonly associated with elevated intraocular pressure (IOP), early disease is associated with altered synaptic inputs to retinal ganglion cells (RGCs), changes in RGC intrinsic excitability, and deficits in optic nerve transport and energy metabolism. These early functional changes can precede RGC degeneration and are likely to alter RGC outputs to their target structures in the brain and thereby trigger homeostatic changes in synaptic and neuronal properties in those brain regions. In this study, we sought to determine whether and how neuronal and synaptic function is altered in the dorsal lateral geniculate nucleus (dLGN), an important RGC projection target in the thalamus, and how functional changes relate to IOP. We accomplished this using patch-clamp recordings from thalamocortical (TC) relay neurons in the dLGN in two established mouse models of glaucoma – the DBA/2J (D2) genetic mouse model and an inducible glaucoma model with intracameral microbead injections to elevate IOP. We found that the intrinsic excitability of TC neurons was enhanced in D2 mice and these functional changes were mirrored in recordings of TC neurons from microbead-injected mice. Notably, many neuronal properties were correlated with IOP in older D2 mice, but not younger D2 mice or microbead-injected mice. The frequency of miniature excitatory synaptic currents (mEPSCs) was reduced in both ages of D2 mice, and vGlut2 staining of RGC synaptic terminals was reduced in an IOP-dependent manner in older D2 mice. Among D2 mice, functional changes observed in younger mice without elevated IOP were distinct from those observed in older mice with elevated IOP and RGC degeneration, suggesting that glaucoma-associated changes to neurons in the dLGN might represent a combination of stabilizing/homeostatic plasticity at earlier stages and pathological dysfunction at later stages.
Geometric and Topological Approaches to Shape Variation inGinkgoLeaves
Authors: Hang Haibin , Bauer Martin , Mio Washington , Mander Luke
Published: October 2020

Leaf shape is a key plant trait that varies enormously. The diversity of leaf shape, and the range of applications for data on this trait, requires frequent methodological developments so that researchers have an up-to-date toolkit with which to quantify leaf shape. We generated a dataset of 468 leaves produced byGinkgo biloba, and 24 fossil leaves produced by evolutionary relatives of extantGinkgo. We quantified the shape of each leaf by developing a geometric method based on elastic curves and a topological method based on persistent homology. Our geometric method indicates that shape variation in our modern sample is dominated by leaf size, furrow depth, and the angle of the two lobes at the base of the leaf that is also related to leaf width. Our topological method indicates that shape variation in our modern sample is dominated by leaf size and furrow depth. We have applied both methods to modern and fossil material: the methods are complementary, identifying similar primary patterns of variation, but also revealing some different aspects of morphological variation. Our topological approach distinguishes long-shoot leaves from short-shoot leaves and both methods indicate that leaf shape influences or is at least related to leaf area.
The anti-mycobacterial activity ofArtemisia annuaL is based on deoxyartemisinin and artemisinic acid
Authors: Bhowmick Sumana , Baptista Rafael , Fazakerley David , Whatley Kezia E. , Hoffmann Karl F. , Shen Jianying , Mur Luis A. J.
Published: October 2020

The discovery of antimalarial artemisinin fromArtemisia annuaL. is an example of how Traditional Chinese Medicine (TCM) may be exploited to meet a recognized need. In this study, we systemically investigatedA. annuaL. for its antimicrobial activity and assessed it as a source of bioactive natural products for anti-mycobacterial activity.

We used a silica gel column to perform antimicrobial activity-guided purification of theA. annualeaf, whose identity was confirmed byrbcLDNA barcoding, and used UHPLC-HRMS and NMR to elucidate the structure of purified active compounds. The antimicrobial activity of crude extracts, isolated compounds and the control artemisinin (Apollo Scientific Ltd) was assessed againstEscherichia coli,Pseudomonas aeruginosa,Staphylococcus aureus, methicillin-resistantStaphylococcus aureus(MRSA),Mycobacterium smegmatisstrains by serial micro dilution method (31.25-1000 μg/mL). The isolated compounds were tested for synergistic effects against mycobacterium.

Bioactive compounds were purified and identified as deoxyartemisinin and artemisinic acid. Artemisinic acid (MIC 250 μg/mL) was more effective in comparison to deoxyartemisinin (MIC 500 μg/mL) and artemisinin (MIC 1000 μg/mL) againstM. smegmatis. We used a molecular docking approach to investigate the interactions between selected anti-mycobacterial compounds and proteins involved in vital physiological functions inM. tuberculosis, namelyMtPks13, MtPknB, MtPanK, MtKasA, MtInhA andMtDprE1 and found artemisinic acid showed docking scores superior to the control inhibiters forMtKasA, suggesting it to be a potential nick for furtherin vitrobiological evaluation and anti-TB drug design.
Latent Evolutionary Signatures: A General Framework for Analyzing Music and Cultural Evolution
Authors: Warrell Jonathan , Salichos Leonidas , Gancz Michael , Gerstein Mark B.
Published: October 2020

Cultural processes of change bear many resemblances to biological evolution. The underlying units of non-biological evolution have, however, remained elusive, especially in the domain of music. Here, we introduce a general framework to jointly identify underlying units and their associated evolutionary processes. We model musical styles and principles of organization in dimensions such as harmony and form as following an evolutionary process. Furthermore, we propose that such processes can be identified by extracting latent evolutionary signatures from musical corpora, analogous to identifying mutational signatures in genomics. These signatures provide a latent embedding for each song or musical piece. We develop a deep generative architecture for our model, which can be viewed as a type of Variational Autoencoder with an evolutionary prior constraining the latent space; specifically, the embeddings for each song are tied together via an energy-based prior, which encourages songs close in evolutionary space to share similar representations. As illustration, we analyze songs from the McGill Billboard dataset. We find frequent chord transitions and formal repetition schemes and identify latent evolutionary signatures related to these features. Finally, we show that the latent evolutionary representations learned by our model outperform non-evolutionary representations in such tasks as period and genre prediction.
Alignment-free methods for polyploid genomes: quick and reliable genetic distance estimation
Authors: VanWallendael Acer , Alvarez Mariano
Published: October 2020

Polyploid genomes pose several inherent challenges to population genetic analyses. While alignment-based methods are fundamentally limited in their applicability to polyploids, alignment-free methods bypass most of these limits. We investigated the use ofMash, a k-mer analysis tool that uses the MinHash method to reduce complexity in large genomic datasets, for basic population genetic analyses of polyploid sequences. We measured the degree to whichMashcorrectly estimated pairwise genetic distance in simulated diploid and polyploid short-read sequences with various levels of missing data.Mash-based estimates of genetic distance were comparable to alignment-based estimates, and were less impacted by missing data. We also usedMashto analyze publicly available short-read data for three polyploid and one diploid species, then comparedMashresults to published results. For both simulated and real data,Mashaccurately estimated pairwise genetic differences for polyploids as well as diploids as much as 476 times faster than alignment-based methods, though we found thatMashgenetic distance estimates could be biased by per-sample read depth.Mashmay be a particularly useful addition to the toolkit of polyploid geneticists for rapid confirmation of alignment-based results and for basic population genetics in reference-free systems with poor quality DNA.
MicroRNA840 accelerates leaf senescence by targeting the overlapping 3’UTRs ofPPRandWHIRLY3inArabidopsis thaliana
Authors: Yujun Ren , Wanzhen Wang , Wei Lan , Dirk Schenke , Daguang Cai , Ying Miao
Published: October 2020

MicroRNAs (miRNAs) negatively regulate gene expression by cleaving the target mRNA and/or impairing its translation, thereby playing a crucial role in plant development and environmental stress responses. In Arabidopsis,MIR840is located within the overlapping 3’UTR ofPPRandWHIRLY3 (WHY3),both being predicted targets of miR840. Gain- and loss-of-function of miR840 in Arabidopsis resulted in opposite senescent phenotypes. Highest expression ofpri-miR840is observed at senescence initiation, and is negatively correlated with a significant reduction ofPPRtranscripts but not ofWHY3.AlthoughWHY3transcript levels were not significantly affected by miR840 overexpression, its protein synthesis was strongly reduced. Mutating the cleavage sites or replacing the target sequences abolishes the miR840-mediated degradation ofPPRtranscripts and inhibition ofWHY3translation. In support for this, concurrent knock-down of bothPPRandWHY3in the WT resulted in the senescent phenotype resembling that of the miR840-overexpressing mutant. This indicates that both PRR and WHY3 are targets in the miR840-regulated senescent pathway. Moreover, single knockout mutant ofPPRorWHY3shows a convergent up-regulated subset of senescence-associated genes, which are also found among those induced by miR840 overexpression. Our data provide evidences for a regulatory role of miR840 in plant senescence.

Highlight

MicroRNA840 (miR840) has a unique miRNA-target configuration regulatingPPRandWHIRLY3genes in Arabidopsis. MiR840 is highly expressed at the onset of plant senescent stage. BothPPRandWHIRLY3transcripts are specifically targetedin vivowithin their 3’UTR region by mature miR840 or its star strandin vivo.Interestingly,PPRexpression is mainly repressed on mRNA transcript level by cleavage, while WHIRLY3 is predominantly translationally inhibited. We conclude that miR840 enhances plant senescenceviapost transcriptional gene silencing ofPPRandWHIRLY3, which appear to be novel negative joint regulators of plant senescence.

Footnote: The author(s) responsible for distribution of materials integral to the findings presented in this article in accordance with the policy described in the intructions for Authors is: Ying Miao (ymiao@fafu.edu.cn)
Bayesian inference: The comprehensive approach to analyzing single-molecule experiments
Authors: Kinz-Thompson Colin D. , Ray Korak Kumar , Gonzalez Ruben L.
Published: October 2020

Biophysics experiments performed at single-molecule resolution contain exceptional insight into the structural details and dynamic behavior of biological systems. However, extracting this information from the corresponding experimental data unequivocally requires applying a biophysical model. Here, we discuss how to use probability theory to apply these models to single-molecule data. Many current single-molecule data analysis methods apply parts of probability theory, sometimes unknowingly, and thus miss out on the full set of benefits provided by this self-consistent framework. The full application of probability theory involves a process called Bayesian inference that fully accounts for the uncertainties inherent to single-molecule experiments. Additionally, using Bayesian inference provides a scientifically rigorous manner to incorporate information from multiple experiments into a single analysis and to find the best biophysical model for an experiment without the risk of overfitting the data. These benefits make the Bayesian approach ideal for analyzing any type of single-molecule experiment.
Mice hypomorphic forPitx3define a minimal dopamine neuron population sufficient for entraining behavior and metabolism to scheduled feeding
Authors: Scarpa Lori L. , Wanken Brad , Smidt Marten , Mistlberger Ralph E. , Steele Andrew D.
Published: October 2020

Pitx3akmice lack a functioning retina and nearly all dopamine neurons of the substantia nigra (SN). del Rio-Marten et al (2019) reported that entrainment of circadian rhythms to daily light-dark and feeding schedules is absent in these mice. With food limited to 12h/day, food anticipatory circadian rhythms failed to emerge, and metabolic rhythms failed to synchronize with locomotor and feeding rhythms. The authors propose that retinal innervation of the suprachiasmatic nucleus clock is required for development of cyclic metabolic homeostasis, but methodological issues limit interpretation of the results. Using standardized feeding schedules and procedures for distinguishing free-running from entrained circadian rhythms, we confirm that behavioral and metabolic rhythms inPitx3akmice do not entrain to LD cycles, but we find no desynchrony between these rhythms nor a deficit in entrainment to daily feeding schedules. SN dopamine neurons surviving inPitx3akmice may define a mininum population sufficient for food entrainment.
Ultrasound activates mechanosensitive TRAAK K+channels directly through the lipid membrane
Authors: Sorum Ben , Rietmeijer Robert A. , Gopakumar Karthika , Adesnik Hillel , Brohawn Stephen G.
Published: October 2020

Ultrasound modulates the electrical activity of excitable cells and offers advantages over other neuromodulatory techniques; for example, it can be non-invasively transmitted through skull and focused to deep brain regions. However, the fundamental cellular, molecular, and mechanistic bases of ultrasonic neuromodulation are largely unknown. Here, we demonstrate ultrasound activation of the mechanosensitive K+channel TRAAK with sub-millisecond kinetics to an extent comparable to canonical mechanical activation. Single channel recordings reveal a common basis for ultrasonic and mechanical activation with stimulus-graded destabilization of long-duration closures and promotion of full conductance openings. Ultrasonic energy is transduced to TRAAK directly through the membrane in the absence of other cellular components, likely increasing membrane tension to promote channel opening. We further demonstrate ultrasonic modulation of neuronally expressed TRAAK. These results suggest mechanosensitive channels underlie physiological responses to ultrasound and provides a framework for developing channel-based sonogentic actuators for acoustic neuromodulation of genetically targeted cells.
Connectome Gradient Dysfunction in Major Depression and Its Association with Gene Expression Profiles
Authors: Xia Mingrui , Liu Jin , Mechelli Andrea , Sun Xiaoyi , Ma Qing , Wang Xiaoqin , Wei Dongtao , Chen Yuan , Liu Bangshan , Huang Chu-Chung , Zheng Yanting , Wu Yankun , Chen Taolin , Cheng Yuqi , Xu Xiufeng , Gong Qiyong , Si Tianmei , Qiu Shijun , Lin Ching-Po , Cheng Jingliang , Tang Yanqing , Wang Fei , Qiu Jiang , Xie Peng , Li Lingjiang , He Yong ,   DIDA-Major Depressive Disorder Working Group
Published: October 2020

Background

Patients with major depressive disorder (MDD) exhibit concurrent deficits in sensory processing and high-order cognitive functions such as self-awareness and rumination. Connectome mapping studies have suggested a principal primary-to-transmodal gradient in functional brain networks, supporting the spectrum from sensation to cognition. However, whether this principal connectome gradient is disrupted in patients with MDD and how this disruption is associated with gene expression profiles remain unclear.

Methods

Using a large cohort of resting-state functional magnetic resonance imaging data from 2,234 participants (1,150 patients with MDD and 1,084 healthy controls) recruited at 10 sites, we investigated MDD-related alterations in the principal connectome gradient. We further used Neurosynth and postmortem gene expression data to assess the cognitive functions and transcriptional profiles related to the gradient alterations in MDD, respectively.

Results

Relative to controls, patients with MDD exhibited abnormal global topography of the principal primary-to-transmodal gradient, as indicated by reduced explanation ratio, gradient range, and gradient variation (Cohen’sd= −0.16∼-0.21). Focal alterations of gradient scores were mostly in the primary systems involved in sensory processing and in the transmodal systems implicated in high-order cognition. The transcriptional profiles explained 53.9% of the spatial variance in the altered gradient patterns, with the most correlated genes enriched in transsynaptic signaling and calcium ion binding.

Conclusions

These results highlight the dysfunction of the core connectome hierarchy in MDD and its linkage with gene expression profiles, providing insights into the neurobiological and molecular genetic underpinnings of sensory-cognitive deficits in this disorder.
Attribution of Cancer Origins to Endogenous, Exogenous, and Actionable Mutational Processes
Authors: Cannataro Vincent L. , Mandell Jeffrey D. , Townsend Jeffrey P.
Published: October 2020

Mutational processes in tumors leave tell-tale genomic signatures composed of “passenger” mutations and mutations that have quantifiable effects on the proliferation and survival of cancer cell lineages. We identify the contributions of mutational processes to each oncogenic variant, quantifying responsibility for origination of changes at oncogenic variant sites contributing to tumorigenesis in 23 cancer types. We demonstrate that the variants driving melanomas and lung cancers are predominantly attributable to the actionable, preventable, exogenous mutational processes of ultraviolet light and tobacco exposure, whereas gliomas and prostate adenocarcinomas are largely attributable to endogenous processes associated with aging. Preventable mutations associated with pathogen exposure and APOBEC activity account for a large proportion of the cancer effect within head and neck, bladder, cervical, and breast cancers. These attributions complement epidemiological approaches—revealing the burden of cancer driven by single-nucleotide variants caused by either endogenous or exogenous, non-actionable or actionable processes, and crucially inform cancer prevention.
EGF-Activated Grb7 Confers to STAT3-Mediated EPHA4 Gene Expression in Regulating Lung Cancer Progression
Authors: Chu Pei-Yu , Tai Yu-Ling , Wang Ming-Yang , Lee Hsinyu , Kuo Wen Hung , Shen Tang-Long
Published: October 2020

Growth factor receptor bound protein-7 (Grb7) is a multi-domain signaling adaptor protein that regulates various cellular functions acting as an adaptor protein in relaying signal transduction. Although several studies indicated that Grb7 amplifies EGFR-mediated signaling in cancers, the detailed regulatory mechanism of whether and how Grb7 is involved in EGFR-mediated lung cancer progression remains unclear. Here, we demonstrate that EGF-regulated Grb7 phosphorylation promotes lung cancer progression through phosphorylation of STAT3. Intrinsically, EGF/EGFR signal is required for the formation of Grb7/STAT3 complex as well as its nuclear accumulation. Once in the nucleus, STAT3 interacts withEPHA4promoter, which in turn affects the gene expression level ofEPHA4through transcriptional regulation. Functionally, EphA4 together with EGFR promotes cancer migration, proliferation, and anchorage-independent growth. Our study reveals a novel mechanism in which Grb7 contribute to lung cancer malignancies through its interaction with STAT3 that leads to sequential regulation ofEPHA4gene expression in an EGF/EGFR signal-dependent manner.
A role of DAO1 in oxidation of IAA amino acid conjugates revealed through metabolite, high throughput transcript and protein level analysis
Authors: Karel Müller , Petre Dobrev I. , Aleš Pěnčík , Petr Hošek , Zuzana Vondráková , Roberta Filepová , Kateřina Malínská , Lenka Helusová , Tomáš Moravec , Retzer Katarzyna , Karel Harant , Ondřej Novák , Klára Hoyerová , Jan Petrášek
Published: October 2020

Auxin metabolism is, together with auxin transport, a key determinant of auxin signalling output in plant cells, yet details on the underlying mechanisms and factors involved are still largely unknown. Processes involved in the auxin metabolism are subject to regulation based on numerous signals, including auxin concentration itself. Altered auxin availability and the subsequent changes of auxin metabolite profiles can therefore elucidate the function and regulatory role of individual elements in the auxin metabolic machinery.

After analysing auxin metabolism in auxin dependent tobacco BY-2 cell line grown in presence or absence of synthetic auxin 2,4-D we found that both conditions were similarly characterized by very low levels of endogenous indole-3-acetic acid (IAA) and its metabolites. However, metabolic profiling after exogenous application of IAA uncovered that the concentration of N-(2-oxindole-3-acetyl)-L-aspartic acid (oxIAA-Asp), the most abundantly formed auxin metabolite in the control culture, dramatically decreased in auxin-starved conditions. To describe the molecular mechanism behind this regulation, we analysed transcriptome and proteome changes caused by auxin starvation. While no changes in the expression of auxin biosynthetic machinery were observed, many genes related to auxin conjugation and degradation showed differential expression. Selected putative auxin glycosylating enzymes as well as members of the Gretchen Hagen 3 gene family involved in auxin amino acid conjugation showed both up- and down-regulation. Contrarily to that, all tobacco homologs ofArabidopsis thalianaDIOXYGENASE FOR AUXIN OXIDATION 1 (DAO1), known to be responsible for the formation of oxIAA from IAA, showed significant downregulation at both transcript and protein levels. To validate the role of DAO1 in auxin metabolism, we performed auxin metabolite profiling in BY-2 mutants carrying either siRNA-silenced or CRISPR-Cas9-mutatedNtDAO1, as well as indao1-1 Arabidopsis thalianaplants. Both mutants showed not only expectedly lower levels of oxIAA, but also significantly lower abundance of oxidated amino acid conjugates of IAA (oxIAA-Asp). Our results thus represent the first direct evidence on DAO1 activity on IAA amino acid conjugates.

Statement of significance

Here we present an analysis of auxin metabolism on metabolite, transcript and protein levels in tobacco BY-2 cell line, collectively identifying oxidation of IAA amino acid conjugates as a new role of DIOXYGENASE FOR AUXIN OXIDATION 1 within an auxin-level-responsive metabolic system.
Actin-based protrusions lead microtubules during stereotyped axon initiation in spinal neuronsin vivo
Authors: Moore Rachel E. , Pop Sînziana , Alleyne Caché , Clarke Jonathan DW
Published: October 2020

In vitro, developing neurons progress through well-defined stages to form an axon and multiple dendrites.In vivo, neurons are derived from progenitors within a polarised neuroepithelium and it is not clear how axon initiation observedin vitrorelates to what occurs in a complex, three-dimensionalin vivoenvironment. Here we show that the position of axon initiation in embryonic zebrafish spinal neurons is extremely consistent across neuronal sub-types. We investigated what mechanisms may regulate axon positioningin vivoand found that microtubule organising centres are located distant from the site of axon initiation in contrast to that observedin vitro, and that microtubule plus-ends are not enriched in the axon during axon initiation. F-actin accumulation precedes axon formation and nascent axons form but are not stabilised in the absence of microtubules. Laminin depletion removes a spatial cue for axon initiation but axon initiation remains robust.
Immunoglobulins, MHC and T Cell receptors genes in Cetaceans
Authors: Gambón-Deza Francisco
Published: October 2020

Cetaceans correspond to mammals that have returned to the marine environment. Adaptive changes are very significant with the conversion of the limbs into flippers. It is studied the changes that have occurred in immunoglobulins, MHC class I and II and T cell receptors genes. Constant regions of immunoglobulins are similar to those of the rest of mammals. An exception is the IgD gene, which is composed of three CH domains but CH1 similar to CH1 of immunoglobulin M. In the IGHV locus, it exist a decrease in the number of VH genes with the absence of genes within Clan I. The number of Vλgenes is greater than that of Vκ. In the genes for T lymphocyte receptors, it exists a decrease in the number of Vαgenes with loss of significant clades and subclades. In Vβand Vγ, there is also the loss of clades. These declines of Vα, Vβand Vγare not present Artiodactyla, and they are specific to Cetaceans. In MHC present tree evolutive lines of class I genes. These species have DQ, DR, DO and DM genes, but they are no present DP genes.
Identification of a new orthonairovirus associated with human febrile illness in China
Authors: Ma Jun , Lv Xiao-Long , Zhang Xu , Han Shu-Zheng , Wang Ze-Dong , Li Liang , Sun He-Ting , Ma Li-Xin , Cheng Zheng-Lei , Shao Jian-Wei , Chen Chen , Zhao Ying-Hua , Sui Liyan , Liu Lin-Na , Qian Jun , Wang Wei , Liu Quan
Published: October 2020

The genusOrthonairovirusof the familyNairoviridaeincludes the important tick-transmitted pathogens, Crimean-Congo hemorrhagic fever virus (CCHFV) and Nairobi sheep disease virus (NSDV), as well as many other poorly characterized viruses isolated from ticks, birds, and mammals1,2. Here we identified a novel orthonairovirus, designated Sōnglǐng virus (SGLV), from patients who reported being bitten by a tick in China. The genome of SGLV shared similar structural features with orthonairoviruses, with 46.5–65.7% sequence identify. Phylogenetic analysis showed that SGLV belonged to theTamdy orthonairovirusand formed a unique clade in theNairoviridaefamily. Electron microscopy revealed typical morphological characteristics of orthonairoviruses. The isolated SGLVs from the blood samples of patients could induce cytopathic effects in human hepatoma cells. SGLV infection was confirmed in 42 patients in 2017-2018, with the main clinical manifestations of headache, fever, depression, fatigue and dizziness. Serological assays showed that 69% patients generated virus-specific antibody responses in the acute phase. In contrast, neither SGLV viral RNA nor specific antibodies against SGLV were detected in healthy individuals. SGLV was also detected inIxodes crenulatus, Haemaphysalis longicornis, Haemaphysalis concinna, andIxodes persulcatusin northeastern China. Collectively, a newly discovered orthonairovirus was shown to be associated with human febrile illness in northeastern China.
Serotonin neurons modulate learning rate through uncertainty
Authors: Grossman Cooper D. , Bari Bilal A. , Cohen Jeremiah Y.
Published: October 2020

Regulating how fast to learn is critical for flexible behavior. Learning about the consequences of actions should be slow in stable environments, but accelerate when that environment changes. Recognizing stability and detecting change is difficult in environments with noisy relationships between actions and outcomes. Under these conditions, theories propose that uncertainty can be used to modulate learning rates (“meta-learning”). We show that mice behaving in a dynamic foraging task exhibit choice behavior that varied as a function of two forms of uncertainty estimated from a meta-learning model. The activity of dorsal raphe serotonin neurons tracked both types of uncertainty in the foraging task, as well as in a dynamic Pavlovian task. Reversible inhibition of serotonin neurons in the foraging task reproduced changes in learning predicted by a simulated lesion of meta-learning in the model. We thus provide a quantitative link between serotonin neuron activity, learning, and decision making.
Trade-Offs Between Antibacterial Resistance and Fitness Cost in the Production of Metallo-β-Lactamase by Enteric Bacteria Manifest as Sporadic Emergence of Carbapenem Resistance in a Clinical Setting
Authors: Cheung Ching Hei Phoebe , Alorabi Mohammed , Hamilton Fergus , Takebayashi Yuiko , Mounsey Oliver , Heesom Kate J. , Williams Philip B. , Williams O. Martin , Albur Maha , MacGowan Alasdair P. , Avison Matthew B.
Published: October 2020

Meropenem is a clinically important antibacterial reserved for treatment of multi-resistant infections. In meropenem-resistant bacteria of the family Enterobacteriales, NDM-1 is considerably more common than IMP-1, despite both metallo-β-lactamases (MBLs) hydrolysing meropenem with almost identical kinetics. We show thatblaNDM-1consistently confers meropenem resistance in wild-type Enterobacteriales, butblaIMP-1does not. The reason is higherblaNDM-1expression because of its stronger promoter. However, the cost of meropenem resistance is reduced fitness ofblaNDM-1positive Enterobacteriales because of amino acid starvation. In parallel, from a clinical case, we identified multipleEnterobacterspp. isolates carrying a plasmid-encodedblaNDM-1having a modified promoter region. This modification lowered MBL production to a level associated with zero fitness cost but, consequently, the isolates were not meropenem resistant. However, we identified aKlebsiella pneumoniaeisolate from this same clinical case carrying the sameblaNDM-1plasmid. This isolate was meropenem resistant despite low-level NDM-1 production because of aramRmutation, reducing envelope permeability. Overall, therefore, we show how the resistance/fitness trade-off for MBL carriage can be resolved. The result is sporadic emergence of meropenem resistance in a clinical setting.
Decoding subjective emotional arousal from EEG during an immersive Virtual Reality experience
Authors: Hofmann Simon M. , Klotzsche Felix , Mariola Alberto , Nikulin Vadim V. , Villringer Arno , Gaebler Michael
Published: October 2020

Immersive virtual reality (VR) enables naturalistic neuroscientific studies while maintaining experimental control, but dynamic and interactive stimuli pose methodological challenges. We here probed the link between emotional arousal, a fundamental property of affective experience, and parieto-occipital alpha power under naturalistic stimulation: 37 young healthy adults completed an immersive VR experience, which included rollercoaster rides, while their EEG was recorded. They then continuously rated their subjective emotional arousal while viewing a replay of their experience. The association between emotional arousal and parieto-occipital alpha power was tested and confirmed by (1) decomposing the continuous EEG signal while maximizing the comodulation between alpha power and arousal ratings and by (2) decoding periods of high and low arousal with discriminative common spatial patterns and a Long Short-Term Memory recurrent neural network.

We successfully combine EEG and a naturalistic immersive VR experience to extend previous findings on the neurophysiology of emotional arousal towards real-world neuroscience.
Endpoint PCR coupled with capillary electrophoresis (celPCR) provides sensitive and quantitative measures of environmental DNA in singleplex and multiplex reactions
Authors: Thalinger Bettina , Pütz Yannick , Traugott Michael
Published: October 2020

The use of sensitive methods is key for the detection of target taxa, from trace amounts of environmental DNA (eDNA) in a sample. In this context, digital PCR (dPCR) enables direct quantification and is commonly perceived as more sensitive than endpoint PCR. However, endpoint PCR coupled with capillary electrophoresis (celPCR) potentially embodies a viable alternative as it quantitatively measures signal strength in Relative Fluorescence Units (RFU). Provided comparable levels of sensitivity are reached, celPCR permits the development of cost-efficient multiplex PCRs, enabling the simultaneous detection of several target taxa.

Here, we compared the sensitivity of singleplex and multiplex celPCR to dPCR for species-specific primer pairs amplifying mitochondrial DNA (COI) of fish species occurring in European freshwaters by analysing dilution series of DNA extracts and field-collected water samples. Both singleplex and multiplex celPCR and dPCR displayed comparable sensitivity with reliable positive amplifications starting at two to 10 target DNA copies per µl DNA extract. celPCR was suitable for quantifying target DNA and direct inference of DNA concentrations from RFU was possible after accounting for primer effects. Furthermore, multiplex celPCRs and dPCRs were successfully used for the detection and quantification of fish-eDNA in field-collected water samples, confirming the results of the dilution series experiment and exemplifying the high sensitivity of the two approaches.

The possibility of detection and quantification via multiplex celPCR is appealing for the cost-efficient screening of high sample numbers. The present results confirm the sensitivity of this approach thus enabling its application for future eDNA-based monitoring efforts.
Microglial synaptic pruning on axon initial segment of dentate granule cells: sexually dimorphic effects on fear response of adult rats subjected to early life stress
Authors: Zetter Mario A. , Roque Angélica , Hernández Vito S. , Hernández-Pérez Oscar R. , Gómora María J. , Ruiz-Velasco Silvia , Eiden Lee E. , Zhang Limei
Published: October 2020

Axon initial segments (AIS) of dentate granule cells (GC) in hippocampus exhibit prominent spines during early development that are associated with microglial contacts. Here, we asked if developmental changes in axon initial segment spines (AISS) could be modified by neonatal maternal separation through stress hormones and microglial activation and examined the potential behavioral consequences. We examined AISS densities at postnatal day (PND) 15 and 50, using Golgi-Cox staining and anatomical analysis. Neuron-microglial interaction was assessed using antibodies against ankyrinG, PSD95 and Iba1, for AIS, AISS and microglia, respectively, in normally reared and neonatal maternally separated (MS) male and female rats. We observed a higher density of AISS in MS groups at both PND15 and PND50 compared to control. Effects were more pronounced in female than in male rats. AIS-associated microglia showed a hyper-ramified morphology and less co-localization with PSD95 in MS compared to normally reared animals at PND 15. An MS-like alteration in microglial morphology and synaptic pruning could be produced ex vivo by vasopressin application in acute hippocampal slices from normally reared animals. MS rats exhibited increased freezing behavior during auditory fear memory testing which, like effects on AISS density, was more pronounced in females than males. Freezing behavior was associated with Fos expression in dorsal and ventral dentate GC. In summary, AIS associated microglial activity is altered by MS. Sex differences in the long-term effects of MS on AISS density are penetrant to a behavioral phenotype of increased stimulus reactivity in adult female subjects.
Identification ofAcinetobacter baumanniiand detection of ß - lactam antibiotic resistance genes in clinical samples by multiplex PCR
Authors: Phan-Canh Trinh , Le-Thi-Thanh Thao , Ngo-Thi-Bich Thuy , Nguyen-Thi-Thanh Thanh , Ho-Le-Truc Linh , Nguyen Tu-Anh
Published: October 2020

Acinetobacter baumanniiis the leading cause of hospital-acquired infection in Vietnam. Of note, antibiotic resistance genes are significantly popular in clinical isolates ofA. baumannii. Therefore, rapid identification ofA. baumanniiand determination of antibiotic resistance genes will help to make effective clinical decisions related to antibiotic use. This paper proposes a multiplex PCR to identifyAcinetobacter baumanniiand detect their ß-lactam antibiotic resistance genes in clinical isolates. Multiplex PCR was applied to amplifiedrecA gene and region ITS 16S - 23S rDNA for Rapid detection ofA. baumannii.The two antibiotic resistance genes -blaOXA-51-like,ampC gene - were detected by multiplex PCR and three genes coding Extended-spectrum beta-lactamases -blaCTX-M,blaTEM,blaSHVgenes - were subjected to PCR. 49 bacteria strains were subjected to colony PCR. The result showed that 46 strains wereA. baumanniiand 3 strains belonged to the genusAcinetobacter.The multiplex PCR showed that all of 46A. baumanniicontaining theblaOXA-51-likegene and theAmpC gene; 34 strains possess the geneblaTEMand none of them hasblaCTX-MandblaSHVgenes. The results of the multiplex PCR are the same as those of thein vitroantibiotic sensitivity testing ofA. baumannii. However, applying the multiplex PCR directly from the bacteria colony, we can proceed simultaneously with the bacterial identification and the antibiotic resistance gene detection.

Highlights

100% of isolates ofA. baumanniicontains theblaOXA-51-likegene and theAmpC gene.

34/46 isolates possess the geneblaTEM, however, do not containblaCTX-MandblaSHVgenes.

Combined disc test with cefotaxime/clavulanic acid/boronic acid is an excellent method to analyse ESBL phenotype.
Mechanically Induced Integrin Ligation Mediates Intracellular Calcium Signaling with Single Pulsating Cavitation Bubbles
Authors: Li Fenfang , Park Tae Hyun , Sankin George , Gilchrist Christopher , Liao Defei , Chan Chon U , Mao Zheng , Hoffman Brenton D. , Zhong Pei
Published: October 2020

Ultrasound or shockwave-induced cavitation is used therapeutically to stimulate neural and muscle tissue, but the mechanisms underlying this mechanotransduction are unclear. Intracellular Ca2+signaling is one of the earliest events in mechanotransduction. In this study, we investigate the mechanism of Ca2+signaling in individual HEK293T cells stimulated by single cavitation bubbles. Ca2+responses are rare at cell-bubble distance that avoids membrane poration, even with overexpression of the mechanosensitive ion channel Piezo1, but could be increased in frequency to 42% of cells by attaching RGD beads to the apical surface of the cells. By using Piezo1 knockout and Piezo1-expressing cells, integrin-blocking antibodies, and inhibitors of P2X ion channels, key molecular players are identified in the RGD bead-enhanced Ca2+response: increased integrin ligation by substrate ECM triggers ATP release and activation of P2X—but not Piezo1—ion channels. These molecular players have not been examined previously in cavitation-induced Ca2+signaling. The resultant Ca2+influx causes dynamic changes in cell spread area. This approach to eliciting a Ca2+response with cavitation microbubbles without cell injury, and the uncovered mechanotransduction mechanism by which increased integrin-ligation mediates ATP release and Ca2+signaling will inform new strategies to stimulate tissues with ultrasound and shockwaves.
Diffusion-Informed Spatial Smoothing of fMRI Data in White Matter Using Spectral Graph Filters
Authors: Abramian David , Larsson Martin , Eklund Anders , Aganj Iman , Westin Carl-Fredrik , Behjat Hamid
Published: October 2020

Brain activation mapping using functional magnetic resonance imaging (fMRI) has been extensively studied in brain gray matter (GM), whereas in large disregarded for probing white matter (WM). This unbalanced treatment has been in part due to controversies in relation to the nature of the blood oxygenation level-dependent (BOLD) contrast in WM and its detachability. However, an accumulating body of studies has provided solid evidence of the functional significance of the BOLD signal in WM and has revealed that it exhibits anisotropic spatio-temporal correlations and structure-specific fluctuations concomitant with those of the cortical BOLD signal. In this work, we present an anisotropic spatial filtering scheme for smoothing fMRI data in WM that accounts for known spatial constraints on the BOLD signal in WM. In particular, the spatial correlation structure of the BOLD signal in WM is highly anisotropic and closely linked to local axonal structure in terms of shape and orientation, suggesting that isotropic Gaussian filters conventionally used for smoothing fMRI data are inadequate for denoising the BOLD signal in WM. The fundamental element in the proposed method is a graph-based description of WM that encodes the underlying anisotropy observed across WM, derived from diffusion-weighted MRI data. Based on this representation, and leveraging graph signal processing principles, we design subject-specific spatial filters that adapt to a subject’s unique WM structure at each position in the WM that they are applied at. We use the proposed filters to spatially smooth fMRI data in WM, as an alternative to the conventional practice of using isotropic Gaussian filters. We test the proposed filtering approach on two sets of simulated phantoms, showcasing its greater sensitivity and specificity for the detection of slender anisotropic activations, compared to that achieved with isotropic Gaussian filters. We also present WM activation mapping results on the Human Connectome Project’s 100-unrelated subject dataset, across seven functional tasks, showing that the proposed method enables the detection of streamline-like activations within axonal bundles.
AP-4 mediates vesicular transport of the 2-AG endocannabinoid producing enzyme DAGLB
Authors: Davies Alexandra K. , Ziegler Marvin , Jumo Hellen , Saber Wardiya Afshar , Ebrahimi-Fakhari Darius , Borner Georg H. H.
Published: October 2020

The adaptor protein complex AP-4 mediates anterograde axonal transport and is essential for axon health. AP-4-deficient patients suffer from a severe neurological disorder, which encompasses neurodevelopmental and neurodegenerative features. While impaired autophagy has been suggested to account for axon degeneration in AP-4 deficiency, axon growth defects occur through an unknown mechanism. Here we use orthogonal proteomic and imaging methods to identify DAGLB (diacylglycerol lipase-beta) as a cargo of AP-4 vesicles. DAGLB is a key enzyme for the generation of 2-AG (2-arachidonoylglycerol), the most abundant endocannabinoid in brain. During normal development, DAGLB is targeted to the axon, where 2-AG signalling drives axonal growth. We show that DAGLB accumulates at the TGN of AP-4-deficient cells, including in iPSC-derived neurons from a patient with AP-4 deficiency syndrome. Our data thus support that AP-4 mediates axonal targeting of DAGLB, and we propose that axon growth defects in AP-4 deficiency may arise through spatial dysregulation of endocannabinoid signalling.
Trip duration drives shift in travel network structure with implications for the predictability of spatial disease spread
Authors: Giles John R , Cummings Derek AT , Grenfell Bryan T , Tatem Andrew J , Erbach-Schoenberg Elisabeth zu , Metcalf CJE , Wesolowski Amy
Published: October 2020

Human travel is one of the primary drivers of infectious disease spread. Models of travel are often used that assume the amount of travel to a specific destination decays as cost of travel increases and higher travel volumes to more populated destinations. Trip duration, the length of time spent in a destination, can also impact travel patterns. We investigated the spatial distribution of travel conditioned on trip duration and find distinct differences between short and long duration trips. In short-trip duration travel networks, trips are skewed towards urban destinations, compared with long-trip duration networks where travel is more evenly spread among locations. Using gravity models imbedded in simulations of disease transmission, we show that pathogens with shorter generation times exhibit initial patterns of spatial propagation that are more predictable among urban locations, whereas longer generation time pathogens have more diffusive patterns of spatial spread reflecting more unpredictable disease dynamics.
The psychological impact of coronavirus on university students and its socio-economic determinants in Malaysia
Authors: Irfan Muhammad , Shahudin Faizah , Hooper Vincent James , Akram Waqar , Abdul Ghani Rosmaiza Binti
Published: October 2020

This article examines the impact of coronavirus disease 2019 (COVID-19) upon university students’ anxiety level and finds the factors associated with the anxiety disorder in Malaysia. We collected data from 958 students from 16 different universities using an originally designed questionnaire. The Generalized Anxiety Disorder Scale 7-item (GAD-7) was used to estimate the anxiety. We find that 12.3% students were normal, whereas 30.5% were experiencing mild, 31.1% moderate, and 26.1% severe anxiety. Surprisingly, only 37.2% of students were aware of mental health support which was provided by their universities. Moreover, it was found that gender as male (Odds Ratio (OR= 0.798, 95% Confidence Interval (CI)= 0.61 - 1.04)) and having internet access (OR = 0.44, 95% CI= 0.24 - 0.80) were alleviating factors for the anxiety. Whereas, age above than 20 years (OR= 1.30, 95% CI= 0.96 - 1.75), ethnicity Chinese (OR=1.72, 95% CI= 0.95 - 3.1), any other disease (OR=2.0, 95% CI=1.44 - 2.79), decreased family income (OR=1.71, 95% CI=1.34 - 2.17), more time spent on watching COVID-19 related news (OR=1.52, 95% CI=1.17 - 1.97), and infected relative or friends (OR=1.62, 95% CI=1.06 - 2.50) were risk factors for anxiety among students. We suggest that the government of Malaysia should monitor the mental health of the universities’ students more closely and universities should open online mental health support clinics to avoid the adverse impacts of the anxiety disorder.