bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comments on “EpiRank: Modeling Bidirectional Disease Spread in Asymmetric Commuting Networks” for Analyzing Emerging Coronavirus Epidemic Patterns
Authors: Benny Chin Wei Chien , Huang Chung-Yuan 
Published: April 2020

ABSTRACTHuang et al.1 used their EpiRank algorithm, which emphasizes forward-and-backward commuter flow between homes and workplaces, to analyze the distribution patterns of two infectious diseases in Taiwan: the 2009-H1N1 influenza virus and the widespread emergence of the 2000-2008 type 71 enterovirus (EV). As this article was being prepared, the spreading mechanism of the novel coronavirus disease now designated as COVID-19 had yet to be identified, but according to the American Centers for Disease Control, its spreading mechanism and patterns are likely more similar to influenza than to other coronaviruses such as Severe Acute Respiratory Syndrome (SARS-CoV-1) or Middle East Respiratory Syndrome (MERS-CoV). To consider potential COVID-19 spatial patterns, we applied EpiRank to the 2003 SARS outbreak in north Taiwan for comparison with H1N1 and EV. SARS was found to be less contagious than H1N1 or EV, but with a significantly higher fatality rate. The characteristics of these diseases determined their specific spatial spreading patterns, as reflected in the different effects of forward and backward commuting movement. Our motivation is to highlight these differences and to illustrate EpiRank spatial patterns for the 2003 SARS outbreak for comparison with EpiRank-determined distributions for the H1N1 and EV outbreaks. Our results indicate that the daytime parameter (i.e., forward movement effect) range was slightly higher (0.5-0.55) for the SARS outbreak than for either the influenza (0.4-0.5) or EV (0.3-0.5) outbreaks, suggesting that the forward-and-backward movements of individuals between residential and core urban areas with concentrated populations were equally important regarding the spread of SARS. While COVID-19 might resemble either SARS or H1N1 in terms of spatial spreading, its daytime parameter is likely somewhere in-between, with backward movement being dominant (similar to H1N1) or with forward and backward movement being equally important (similar to SARS). Building on Huang et al.’s paper, we present an estimated risk distribution pattern for the Taipei Metropolitan Area for a daytime parameter of 0.55.
Anti-biofilm efficacy of a medieval treatment for bacterial infection requires the combination of multiple ingredients
Authors: Furner-Pardoe Jessica , Anonye Blessing O , Cain Ricky , Moat John , Ortori Catherine A. , Lee Christina , Barrett David A. , Corre Christophe , Harrison Freya 
Published: April 2020

AbstractNovel antimicrobials are urgently needed to combat the increasing occurrence of drug-resistant bacteria and to overcome the inherent difficulties in treating biofilm-associated infections. Research into natural antimicrobials could provide candidates to fill the antibiotic discovery gap, and the study of plants and other natural materials used in historical infection remedies may enable further discoveries of natural products with useful antimicrobial activity. We previously reconstructed a 1,000-year-old remedy containing onion, garlic, wine, and bile salts, which is known as ‘Bald’s eyesalve’, and showed it to have promising antibacterial activity. In this paper, we have found this remedy has bactericidal activity against a range of Gram-negative and Gram-positive wound pathogens in planktonic culture and, crucially, that this activity is maintained againstAcinetobacter baumannii, Stenotrophomonas maltophilia, Staphylococcus aureus, Staphylococcus epidermidisandStreptococcus pyogenesin a model of soft-tissue wound biofilm. While the presence of garlic in the mixture is sufficient to explain activity against planktonic cultures, garlic alone has no activity against biofilms. We have found the potent anti-biofilm activity of Bald’s eyesalve cannot be attributed to a single ingredient and requires the combination of all ingredients to achieve full activity. Our work highlights the need to explore not only single compounds but also mixtures of natural products for treating biofilm infections. These results also underline the importance of working with biofilm models when exploring natural products for the anti-biofilm pipeline.ImportanceBacteria can live in two ways, as individual planktonic cells or as a multicellular biofilm. Biofilm helps protect bacteria from antibiotics and makes them much harder to treat. Both the biofilm lifestyle and the evolution of antibiotic resistance mean we urgently need new drugs to treat infections. Here, we show that a medieval remedy made from onion, garlic, wine, and bile can kill a range of problematic bacteria grown both planktonically and as biofilms. A single component of the remedy – allicin, derived from garlic – is sufficient to kill planktonic bacteria. However, garlic or allicin alone do nothing against bacteria when they form a biofilm. All four ingredients are needed to fully kill bacterial biofilm communities, hinting that these ingredients work together to kill the bacteria. This suggests that future discovery of antibiotics from natural products could be enhanced by studying combinations of ingredients, rather than single plants or compounds.
Naïve orangutans (Pongo abelii & Pongo pygmaeus) individually acquire nut-cracking using hammer tools
Authors: Bandini Elisa , Grossmann Johannes , Funk Martina , Serrano Anna Albiach , Tennie Claudio 
Published: April 2020

AbstractNut-cracking using hammer tools has been argued to be one of the most complex tool-use behaviours observed in non-human animals (henceforth: animals). Recently, even the United Nations Convention on the Conservation of Migratory Species (CMS) recognised the unique nature of chimpanzee nut-cracking by making it the first animal behaviour to be awarded UN-protected status (Picheta, 2020). So far, only chimpanzees, capuchins and macaques have been observed using tools to crack nuts in the wild (Boesch & Boesch, 1990; Gumert, Kluck, & Malaivijitnond, 2009; Ottoni & Mannu, 2001). However, the learning mechanisms behind this behaviour, and the extent of nut-cracking in other primate species are still unknown. The aim of this study was two-fold. First, we aimed to examine whether other great ape species would develop nut-cracking when provided with all the tools and motivation to do so. Second, we wanted to examine the mechanisms behind the emergence of nut-cracking in a naïve sample. Orangutans (Pongo abelii; pygmaeus) have not been observed cracking nuts in the wild, despite having the second most extensive tool-use repertoire of the great apes (after chimpanzees), having the materials for the behaviour in the wild (albeit rarely) and possessing flexible problem-solving capacities. Therefore, orangutans are a valid candidate species for the investigation of the development of nut-cracking. Four nut-cracking-naïve orangutans at Leipzig zoo (Pongo abelii;Mage=16; age range=10-19; 4F; at time of testing) were provided with nuts and hammers but were not demonstrated the nut-cracking behavioural form, in order to control for the role of copying social learning in the acquisition of this behaviour. Additionally, we report data from a previously unpublished study by one of the authors (MF) with eight orangutans housed at Zürich zoo (10Pongo abeliiand twoPongo pygmaeus;Mage=14; age range =2-30; 5F; at time of testing) that followed a similar testing paradigm. Out of the twelve orangutans across both testing institutions, at least four individuals, one from Leipzig (Pongo abelii) and three from Zürich (Pongo abelii;pygmaeus), spontaneously expressed nut-cracking with a wooden hammer. These results suggest that the behavioural form of nut-cracking using hammer tools can emerge in orangutans when required through individual learning combined, in some cases, with non-copying social learning mechanisms.
Skipping a beat: heartbeat-evoked potentials reflect predictions during interoceptive-exteroceptive integration
Authors: Banellis Leah , Cruse Damian 
Published: April 2020

AbstractSeveral theories propose that emotions and self-awareness arise from the integration of internal and external signals and their respective precision-weighted expectations. Supporting these mechanisms, research indicates that the brain uses temporal cues from cardiac signals to predict auditory stimuli, and that these predictions and their prediction errors can be observed in the scalp heartbeat-evoked potential (HEP). We investigated the effect of precision modulations on these cross-modal predictive mechanisms, via attention and interoceptive ability. We presented auditory sequences at short (perceived synchronous) or long (perceived asynchronous) cardio-audio delays, with half of the trials including an omission. Participants attended to the cardio-audio synchronicity of the tones (internal attention) or the auditory stimuli alone (external attention). Comparing HEPs during omissions allowed for the observation of pure predictive signals, without contaminating auditory input. We observed an early effect of cardio-audio delay, reflecting a difference in heartbeat-driven expectations. We also observed a larger positivity to omissions of sounds perceived as synchronous than to omissions of sounds perceived as asynchronous when attending internally only, consistent with the role of attentional precision for enhancing predictions. These results provide support for attentionally-modulated cross-modal predictive coding, and suggest a potential tool for investigating its role in emotion and self-awareness.
Karyotype asymmetry shapes diversity within the physaloids (Physalidinae, Physalideae, Solanaceae)
Authors: Rodríguez Julieta , Deanna Rocío , Chiarini Franco 
Published: April 2020

AbstractWithin the cosmopolitan family Solanaceae, Physalideae is the tribe with the highest generic diversity (30 genera and more than 200 species). This tribe embraces subtribe Physalidinae, in which positions of some genera are not entirely resolved. Chromosomes may help on this goal, by providing information on the processes underlying speciation. Thus, cytogenetic analyses were carried out in the subtribe in order to establish its chromosome number and morphology. Physalidinae is characterized by x = 12 and most species shows a highly asymmetric karyotype. These karyotype traits were mapped onto a molecular phylogeny to test the congruence between karyotype evolution and clade differentiation. A diploid ancestor was reconstructed for the subtribe, and five to six polyploidy independent events were estimated, plus one aneuploidy event (X = 11 in the monotypic genusQuincula). Comparative phylogenetic methods showed that asymmetry indices and chromosome arm ratio (r) have a high phylogenetic signal, whereas the number of telocentric and submetacentric chromosomes presented a conspicuous amount of changes. Karyotype asymmetry allow us to differentiate genera within the subtribe. Overall, our study suggests that Physalidineae diversification has been accompanied by karyotype changes, which can be applied to delimit genera within the group.
Customizable high-throughput platform for profiling cofactor recruitment to DNA to characterize cis-regulatory elements and screen non-coding single-nucleotide polymorphisms
Authors: Bray David , Hook Heather , Zhao Rose , Keenan Jessica L. , Penvose Ashley , Osayame Yemi , Mohaghegh Nima , Siggers Trevor 
Published: April 2020

AbstractDetermining how DNA variants affect the binding of regulatory complexes to cis-regulatory elements (CREs) and non-coding single-nucleotide polymorphisms (ncSNPs) is a challenge in genomics. To address this challenge, we have developed CASCADE (ComprehensiveASsessment ofComplexAssembly atDNAElements), which is a protein-binding microarray (PBM)-based approach that allows for the high-throughput profiling of cofactor (COF) recruitment to DNA sequence variants. The method also enables one to infer the identity of the transcription factor-cofactor (TF-COF) complexes involved in COF recruitment. We use CASCADE to characterize regulatory complexes binding to CREs and SNP quantitative trait loci (SNP-QTLs) in resting and stimulated human macrophages. By profiling the recruitment of the acetyltransferase p300 and MLL methyltransferase component RBBP5, we identify key regulators of the chemokine CXCL10, and by profiling a set of five functionally diverse COFs we identify a prevalence of ETS sites mediating COF recruitment at SNP-QTLs in macrophages. Our results demonstrate that CASCADE is a customizable, high-throughput platform to link DNA variants with the biophysical complexes that mediate functions such as chromatin modification or remodeling in a cell state-specific manner.
Localization of the Lens Intermediate Filament Switch by Imaging Mass Spectrometry
Authors: Wang Zhen , Ryan Daniel J. , Schey Kevin L 
Published: April 2020

AbstractImaging mass spectrometry (IMS) enables targeted and untargeted visualization of the spatial localization of molecules in tissues with great specificity. The lens is a unique tissue that contains fiber cells corresponding to various stages of differentiation that are packed in a highly spatial order. The application of IMS to lens tissue localizes molecular features that are spatially related to the fiber cell organization. Such spatially resolved molecular information assists our understanding of lens structure and physiology; however, protein IMS studies are typically limited to abundant, soluble, low molecular weight proteins. In this study, a method was developed for imaging low solubility cytoskeletal proteins in the lens; a tissue that is filled with high concentrations of soluble crystallins. Optimized tissue washes combined with on-tissue enzymatic digestion allowed successful imaging of peptides corresponding to known lens cytoskeletal proteins. The resulting peptide signals facilitated segmentation of the bovine lens into molecularly distinct regions. A sharp intermediate filament transition from vimentin to lens-specific beaded filament proteins was detected in the lens cortex. MALDI IMS also revealed the region where posttranslational myristoylation of filensin occurs and the results indicate that truncation and myristoylation of filensin starts soon after filensin expression increased in the inner cortex. From intermediate filament switch to filensin truncation and myristoylation, multiple remarkable changes occur in the narrow region of lens cortex. MALDI images delineated the boundaries of distinct lens regions that will guide further proteomic and interactomic studies.
Non-bursting non-rhythmic neurons of the ventral pallidum form cell assemblies and respond to reward and punishment during Pavlovian conditioning
Authors: Hegedüs Panna , Heckenast Julia , Hangya Balázs 
Published: April 2020

AbstractThe ventral pallidum (VP) is a major hub interfacing striatopallidal and limbic circuits, conveying information about salience and valence crucial to adjusting behavior. However, how neuron populations of the VP with different firing properties represent these variables is not fully understood. Therefore, we trained mice on auditory Pavlovian conditioning and recorded the activity of VP neurons while mice were performing the task. Many VP neurons responded to punishment (51%) and reward (44%), either by firing rate increase or decrease. Additionally, 20% of cells responded to outcome-predicting auditory stimuli, showing larger responses to reward-predicting cues compared to those that signaled likely punishment. We found that a large subset of VP neurons showed burst firing based on their auto-correlograms, while a small population exhibited fast rhythmic discharge in the beta/gamma frequency range. Some bursting neurons exhibited distinct response properties of their bursts and single spikes, suggesting a multiplexed coding scheme in the VP. However, non-bursting, non-rhythmic neurons were the most sensitive to reward and punishment. Finally, we demonstrate the presence of synchronously firing neuron assemblies in the VP. Neurons participating in such assemblies were particularly responsive to reinforcing stimuli. This suggests that a synchronous, non-bursting, non-rhythmic neuron population of the VP is responsible for the lion’s share of ventral pallidal salience representation, likely important for reinforcement learning.Significance statementThe ventral pallidum (VP) is a subcortical brain area that participates in regulating motion and emotion by processing information related to appetitive and aversive stimuli. However, how these stimuli are represented by VP neural circuits is not well understood. Therefore, we investigated how VP neuron populations defined by their firing properties respond to reward and punishment during Pavlovian conditioning. We found that a distinct, non-bursting-non-rhythmic group of neurons was responsible for most responses to reward and punishment in the VP. Neurons of this group formed co-active cell assemblies and multiplexed different types of information via different firing patterns, revealing flexible and plastic neuronal representation strategies in the VP during associative learning.
An opaque cell-specific expression program of secreted proteases and transporters allows cell-type cooperation inCandida albicans
Authors: Lohse Matthew B. , Brenes Lucas R. , Ziv Naomi , Winter Michael B. , Craik Charles S. , Johnson Alexander D. 
Published: April 2020

AbstractAn unusual feature of the opportunistic pathogenC. albicansis its ability to stochastically switch between two distinct, heritable cell types called white and opaque. Here, we show that only opaque cells, in response to environmental signals, massively up-regulate a specific group of secreted proteases and peptide transporters, allowing exceptionally efficient use of proteins as sources of nitrogen. We identify the specific proteases (members of the secreted aspartyl protease (SAP) family) needed for opaque cells to proliferate under these conditions, and we identify four transcriptional regulators of this specialized proteolysis and uptake program. We also show that, in mixed cultures, opaque cells enable white cells to also proliferate efficiently when proteins are the sole nitrogen source. Based on these observations, we suggest that one role of white-opaque switching is to create mixed populations where the different phenotypes derived from a single genome are shared between two distinct cell types.SummaryThe opportunistic human fungal pathogenCandida albicansswitches between two distinct, heritable cell types, named “white” and “opaque.” We show that opaque cells, in response to proteins as the sole nitrogen source, up-regulate a specialized program, including specific secreted aspartyl proteases and peptide transporters. We demonstrate that, in mixed cultures, opaque cells enable white cells to respond and proliferate more efficiently under these conditions. These observations suggest that white-opaque switching creates mixtures of cells where the population characteristics - which derive from a single genome - reflect the contributions of two distinct cell types.Dataset Reference NumbersThe .RAW files for both sets of Mass Spectrometry experiments have been deposited at the ProteoSAFe resource (https://proteomics.ucsd.edu/ProteoSAFe/).MSP-MS experiment reference number: MSV000085279. For reviewer access use login “MSV000085279_reviewer” and password “candidamspms”.Proteomics experiment reference number: MSV000085283. For reviewer access use login “MSV000085283_reviewer” and password “candidaprot”.
Glycomic analysis of host-response reveals high mannose as a key mediator of influenza severity
Authors: Heindel Daniel W. , Koppolu Sujeethraj , Zhang Yue , Kasper Brian , Meche Lawrence , Vaiana Christopher , Bissel Stephanie J. , Carter Chalise E. , Kelvin Alyson A. , Zhang Bin , Zhou Bin , Chou Tsui-Wen , Lashua Lauren , Ross Ted M. , Ghedin Elodie , Mahal Lara K. 
Published: April 2020

ABSTRACTInfluenza virus infections cause a wide variety of outcomes, from mild disease to 3-5 million cases of severe illness and ~290,000-645,000 deaths annually worldwide. The molecular mechanisms underlying these disparate outcomes are currently unknown. Glycosylation within the human host plays a critical role in influenza virus biology. However, the impact these modifications have on the severity of influenza disease has not been examined. Herein, we profile the glycomic host responses to influenza virus infection as a function of disease severity using a ferret model and our lectin microarray technology. We identify the glycan epitope high mannose as a marker of influenza virus-induced pathogenesis and severity of disease outcome. Induction of high mannose is dependent upon the unfolded protein response (UPR) pathway, a pathway previously shown to associate with lung damage and severity of influenza virus infection. Also, the mannan-binding lectin (MBL2), an innate immune lectin that negatively impacts influenza outcomes, recognizes influenza virus-infected cells in a high mannose dependent manner. Together, our data argue that the high mannose motif is an infection-associated molecular pattern on host cells that may guide immune responses leading to the concomitant damage associated with severity.SIGNIFICANCEInfluenza virus infection causes a range of outcomes from mild illness to death. The molecular mechanisms leading to these differential host responses are currently unknown. Herein, we identify the induction of high mannose, a glycan epitope, as a key mediator of severe disease outcome. We propose a mechanism in which activation of the unfolded protein response (UPR) upon influenza virus infection turns on expression of high mannose, which is then recognized by the innate immune lectin MBL2, activating the complement cascade and leading to subsequent inflammation. This work is the first to systematically study host glycomic changes in response to influenza virus infection, identifying high mannose as a key feature of differential host response.
Genes adapt to outsmart gene targeting strategies in mutant mouse strains by skipping exons to reinitiate transcription and translation
Authors: Hosur Vishnu , Low Benjamin E. , Li Daniel , Stafford Grace A. , Kohar Vivek , Shultz Leonard D. , Wiles Michael V. 
Published: April 2020

AbstractGene disruption in mouse embryonic stem cells or zygotes is a conventional genetics approach to identify gene functionin vivo. However, because different gene-disruption strategies use different mechanisms to disrupt genes, the strategies can result in diverse phenotypes in the resulting mouse model. To determine whether different gene-disruption strategies affect the phenotype of resulting mutant mice, we characterizedRhbdf1mouse mutant strains generated by three commonly used strategies—definitive-null, targeted knockout (KO)-first, and CRISPR/Cas9. We find thatRhbdf1responds differently to distinct KO strategies, for example, by skipping exons and reinitiating translation to potentially yield gain-of-function alleles rather than the expected null or severe hypomorphic alleles. Our analysis also revealed that at least 4% of mice generated using the KO-first strategy show conflicting phenotypes, suggesting that exon skipping is a widespread phenomenon occurring across the genome. Additionally, our study emphasizes that at least 35% of mouse and 45% of human protein-coding genes could be predisposed to targeted KO-first- and CRISPR/Cas9-mediated unexpected translation. Our findings have significant implications for the application of genome editing in both basic research and clinical practice.