bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pathogenic and Indigenous Denitrifying Bacteria are Transcriptionally Active and Key Multi-Antibiotic Resistant Players in Wastewater Treatment Plants
Authors: Yuan Ling , Wang Yubo , Zhang Lu , Palomo Alejandro , Zhou Jizhong , Smets Barth F. , Bürgmann Helmut , Ju Feng 
Published: December 2020

ABSTRACTThe global rise and spread of antibiotic resistance greatly challenge the treatment of bacterial infections. Wastewater treatment plants (WWTPs) harbor and discharge antibiotic resistance genes (ARGs) as environmental contaminants. However, the knowledge gap on the host identity, activity and functionality of ARGs limits transmission and health risk assessment of WWTPs resistome. Hereby, a genome-centric quantitative metatranscriptomic approach was exploited to realize high-resolution qualitative and quantitative analyses of bacterial hosts of ARGs (i.e., multi-resistance, pathogenicity, activity and niches) throughout 12 urban WWTPs. We found that ∼45% of 248 recovered genomes expressed ARGs against multiple classes of antibiotics, among which bacitracin and aminoglycoside resistance genes inProteobacteriawas the most prevalent scenario. Both potential pathogens and indigenous denitrifying bacteria were transcriptionally active hosts of ARGs. The almost unchanged relative expression levels of ARGs in the most resistant populations (66.9%) and the surviving ARG hosts including globally emerging pathogens (e.g.,Aliarcobacter cryaerophilus) in treated WWTP effluent prioritizes future examination on the health risks related with resistance propagation and human exposure in the receiving environment.
Paracrine behaviors arbitrate parasite-like interactions between tumor subclones
Authors: Noble Robert J. , Walther Viola , Roumestand Christian , Hibner Urszula , Hochberg Michael E. , Lassus Patrice 
Published: December 2020

AbstractExplaining the emergence and maintenance of intratumor heterogeneity is an important question in cancer biology. Tumor cells can generate considerable subclonal diversity, which influences tumor growth rate, treatment resistance, and metastasis, yet we know remarkably little about how cells from different subclones interact. Here, we confronted two murine mammary cancer cell lines to determine both the nature and mechanisms of subclonal cellular interactionsin vitro.Surprisingly, we found that, compared to monoculture, growth of the ‘winner’ was enhanced by the presence of the ‘loser’ cell line, whereas growth of the latter was reduced. Mathematical modeling and laboratory assays indicated that these interactions are mediated by the production of paracrine metabolites resulting in the winner subclone effectively ‘farming’ the loser. Our findings add a new level of complexity to the mechanisms underlying subclonal growth dynamics.
Activity-dependent refinement of nasal retinal projections drives topographic map sharpening in the teleost visual system
Authors: Spead Olivia , Poulain Fabienne E. 
Published: December 2020

ABSTRACTTopographic maps in the brain are essential for processing information. Yet, our understanding of topographic mapping has remained limited by our inability to observe maps forming and refining directly in vivo. Here, we used Cre-mediated recombination of a new colorswitch reporter in zebrafish to generate the first transgenic model allowing the dynamic analysis of retinotopic mapping in vivo. We found that the antero-posterior retinotopic map forms early but remains dynamic, with nasal and temporal retinal axons expanding their projection domains over time. Nasal projections initially arborize in the anterior tectum but progressively refine their projection domain to the posterior tectum in an activity-dependent manner. This activity-dependent refinement drives retinotopic map sharpening along the antero-posterior axis. Altogether, our study provides the first analysis of a topographic map maturing in real-time in a live animal and opens new strategies for dissecting the intricate mechanisms of precise topographic mapping in vertebrates.
A cytokine network balance influences the fate ofLeishmania (Viannia) braziliensisinfection in a cutaneous leishmaniasis hamster model
Authors: Paiva MB , Ribeiro-Romão RP , Resende-Vieira L , Braga-Gomes T , Oliveira MP , Saavedra AF , Silva-Couto L , Albuquerque HG , Moreira OC , Pinto EF , Da-Cruz AM , Gomes-Silva A 
Published: December 2020

AbstractThe golden hamster is a suitable model for studying cutaneous leishmaniasis (CL) due toLeishmania (Viannia) braziliensis. Immunopathological mechanismsare wellstablished intheL. (L.) major-mousemodel, in which IL-4 instructs a Th2 response towards progressive infection. In the present study, we evaluatedthe natural history ofL. braziliensisinfection from its first stagesup to lesion establishment, with the aim ofidentifyingimmunological parameters associated with the disease outcome and parasitismfate. To this end, hamsters infected with 104, 105,or 106promastigoteswere monitored duringthe first hours (4h, 24h), early (15, 30 days) and late (50 days) post-infection (pi) phases. Cytokines, iNOS and arginasegene expression were quantified in the established lesions by RT-PCR. Compared to the 105or 106groups, 104animals presented lower lesions sizes, less tissue damage,and lower IgG levels. Basal gene expression in normal skin was high for TGF-β, and intermediary for TNF, IL-6, and IL-4.At 4hpi, no cytokine induction was observed in the 104group, while an upregulation of IL-6, IL-10, and IL-4 was observed in the 106group. At 15dpi, lesion appearance was accompanied byan increasedexpression of all assessed cytokines, markedly in the 105and 106groups. Upregulation of all investigated cytokines was observed in the late phase, although less expressive in the 104group. IFN-γ was the depending variable influencing tissue damage, while IL-6 was associatedto parasite load. The network correlating gene expression and clinical and laboratorial parameters indicated inoculum-independent associations at 15 and 30dpi.A strong positive network correlation was observed in the 104group, but not in the105or 106groups. In conclusion, IL-4, IL-6, IL-10, and TGF-β are linkedtoL. braziliensisprogression. However, a balanced cytokine network is the key for an immune response able to reduce the ongoing infection and reduce pathological damage.
Selective human tau protein expression in different clock circuits of theDrosophilabrain disrupts different aspects of sleep and circadian rhythms
Authors: Jaciuch David , Munns Jack , Chawla Sangeeta , Davis Seth J. , Juusola Mikko 
Published: December 2020

AbstractCircadian behavioural deficits, such as increased daytime naps and reduced night-time sleep, are common in Alzheimer’s disease and other tauopathies. But it has remained unclear whether these circadian abnormalities arise from tau pathology in either the master pacemaker or downstream neurons. Here we study this question by selectively expressing different human tau proteins in specificDrosophilabrain circuits and monitoring locomotor activity under light-dark (LD) and in “free-running” dark-dark (DD) conditions. We show that expressing human tau proteins in the fly brain recapitulates faithfully several behavioural changes found in tauopathies. We identify discrete neuronal subpopulations within the clock network as the primary target of distinct circadian behavioural disturbances in different environmental conditions. Specifically, we show that the PDF-positive pacemaker neurons are the main site for night-activity gain and -sleep loss, whereas the non-PDF clock-neurons are the main site of reduced intrinsic behavioural rhythmicity. Bioluminescence measurements revealed that the molecular clock is intact despite the behavioural arrhythmia. Our results establish that dysfunction in both the central clock- and afferent clock-neurons jointly contribute to the circadian locomotor activity rhythm disruption inDrosophilaexpressing human tau.Significance StatementThis study directly linksin vivohuman tau protein expression in region-specificDrosophilaclock-neurons with the resulting sleep and circadian rhythm deficits to extract new knowledge of how Alzheimer’s disease and other tauopathies perturb the balance of activity and sleep. We anticipate that this novel approach will provide a useful general template for other studies of neurodegeneration in model organisms, seeking to dissect the impact of neurodegenerative disease on circadian behaviour, and further deepening our understanding of how the clock-neuron network works.
Decomposing the sources of SARS-CoV-2 fitness variation in the United States
Authors: Kepler Lenora , Hamins-Puertolas Marco , Rasmussen David A. 
Published: December 2020

AbstractThe fitness of a pathogen is a composite phenotype determined by many different factors influencing growth rates both within and between hosts. Determining what factors shape fitness at the host population-level is especially challenging because both intrinsic factors like pathogen genetics and extrinsic factors such as host behaviour influence between-host transmission potential. These challenges have been highlighted by controversy surrounding the population-level fitness effects of mutations in the SARS-CoV-2 genome and their relative importance when compared against non-genetic factors shaping transmission dynamics. Building upon phylodynamic birth-death models, we develop a new framework to learn how hundreds of genetic and non-genetic factors have shaped the fitness of SARS-CoV-2. We estimate the fitness effects of all amino acid variants and several structural variants that have circulated in the United States between February 2020 and March 2021 from viral phylogenies. We also estimate how much fitness variation among pathogen lineages is attributable to genetic versus non-genetic factors such as spatial heterogeneity in transmission rates. Before September 2020, most fitness variation between lineages can be explained by background spatial heterogeneity in transmission rates across geographic regions. Starting in late 2020, genetic variation in fitness increased dramatically with the emergence of several new lineages including B.1.1.7, B.1.427, B.1.429 and B.1.526. Our analysis also indicates that genetic variants in less well-explored genomic regions outside of Spike may be contributing significantly to overall fitness variation in the viral population.
Exploring the microbiome-wide lysine acetylation, succinylation and propionylation in human gut microbiota
Authors: Zhang Xu , Cheng Kai , Ning Zhibin , Mayne Janice , Walker Krystal , Chi Hao , Farnsworth Charles L. , Lee Kimberly , Figeys Daniel 
Published: December 2020

AbstractBackgroundLysine acylations are important post-translational modifications that are present in both eukaryotes and prokaryotes, regulating diverse cellular functions. Our knowledge of the microbiome lysine acylation remains limited due to the lack of efficient analytical and bioinformatics methods for complex microbial communities.ResultsWe show that serial enrichment using motif antibodies successfully captures peptides containing lysine acetylation, propionylation and succinylation from human gut microbiome samples. A new bioinformatic workflow consisting of unrestricted database search confidently identified >60,000 acetylated, and ~20,000 propionylated and succinylated gut microbial peptides. Characterization of these identified modification-specific metaproteomes, i.e. meta-PTMomes, demonstrates that lysine acylations are differentially distributed in microbial species with different metabolic capabilities.ConclusionThis study provides an analytical framework, consisting of a serial immunoaffinity enrichment and an open database search strategy, for the study of lysine acylations in microbiome, which enables functional microbiome studies at the post-translational level.
Soft sweeps predominate recent positive selection in bonobos (Pan paniscus) and chimpanzees (Pan troglodytes)
Authors: Brand Colin M. , White Frances J. , Ting Nelson , Webster Timothy H. 
Published: December 2020

AbstractTwo modes of positive selection have been recognized: 1) hard sweeps that result in the rapid fixation of a beneficial allele typically from ade novomutation and 2) soft sweeps that are characterized by intermediate frequencies of at least two haplotypes that stem from standing genetic variation or recurrentde novomutations. While many populations exhibit both hard and soft sweeps throughout the genome, there is increasing evidence that soft sweeps, rather than hard sweeps, are the predominant mode of adaptation in many species, including humans. Here, we use a supervised machine learning approach to assess the extent of completed hard and soft sweeps in the closest living relatives of humans: bonobos and chimpanzees (genusPan). We trained convolutional neural network classifiers using simulated data and applied these classifiers to population genomic data for 71 individuals representing all five extantPanlineages, of which we successfully analyzed 60 individuals from four lineages. We found that recent adaptation inPanis largely the result of soft sweeps, ranging from 73.1 to 97.7% of all identified sweeps. While few hard sweeps were shared among lineages, we found that between 19 and 267 soft sweep windows were shared by at least two lineages. We also identify novel candidate genes subject to recent positive selection. This study emphasizes the importance of shifts in the physical and social environment, rather than novel mutation, in shaping recent adaptations in bonobos and chimpanzees.
More than Words: Neurophysiological Correlates of Semantic Dissimilarity Depend on Comprehension of the Speech Narrative
Authors: Broderick Michael P. , Zuk Nathaniel J. , Anderson Andrew J. , Lalor Edmund C. 
Published: December 2020

AbstractSpeech comprehension relies on the ability to understand the meaning of words within a coherent context. Recent studies have attempted to obtain electrophysiological indices of this process by modelling how brain activity is affected by a word’s semantic dissimilarity to preceding words. While the resulting indices appear robust and are strongly modulated by attention, it remains possible that, rather than capturing the contextual understanding of words, they may actually reflect word-to-word changes in semantic content without the need for a narrative-level understanding on the part of the listener. To test this possibility, we recorded EEG from subjects who listened to speech presented in either its original, narrative form, or after scrambling the word order by varying amounts. This manipulation affected the ability of subjects to comprehend the narrative content of the speech, but not the ability to recognize the individual words. Neural indices of semantic understanding and low-level acoustic processing were derived for each scrambling condition using the temporal response function (TRF) approach. Signatures of semantic processing were observed for conditions where speech was unscrambled or minimally scrambled and subjects were able to understand the speech. The same markers were absent for higher levels of scrambling when speech comprehension dropped below chance. In contrast, word recognition remained high and neural measures related to envelope tracking did not vary significantly across the different scrambling conditions. This supports the previous claim that electrophysiological indices based on the semantic dissimilarity of words to their context reflect a listener’s understanding of those words relative to that context. It also highlights the relative insensitivity of neural measures of low-level speech processing to speech comprehension.
ImuA participates in SOS mutagenesis by interacting with RecA1 and ImuB inMyxococcus xanthus
Authors: Sheng Duohong , Wang Ye , Jiang Zhiwei , Liu Dongkai , Li Yuezhong 
Published: December 2020

AbstractBacteria have two pathways to restart stalled replication forks caused by environmental stresses, error-prone translesion DNA synthesis (TLS) catalyzed by TLS polymerase and error-free template switching catalyzed by RecA, and their competition on the arrested fork affects bacterial SOS mutagenesis. DnaE2 is an error-prone TLS polymerase, and its functions require ImuA and ImuB. Here we investigated the function ofimuA,imuBanddnaE2inMyxococcus xanthusand found thatimuAshowed differences fromimuBanddnaE2in bacterial growth, resistance and mutation frequency. Transcriptomics analysis found that ImuA were associated with bacterial SOS response. Yeast-two-hybrid scanning revealed that ImuA interacted with RecA1 besides ImuB. Protein activity analysis proved that ImuA had no DNA binding activity, but inhibited the DNA binding and recombinase activity of RecA1. These findings highlight that ImuA not only participates in TLS by binding ImuB, but also inhibits the recombinase activity of RecA1 inM. xanthus, suggesting a role of ImuA in the two replication restart pathways.ImportanceDnaE2 is responsible for bacterial SOS mutagenesis in nearly one third of sequenced bacterial strains. However, its mechanism, especially the function of its accessory protein ImuA, is still unclear. Here we reported thatM. xanthusImuA might facilitate DnaE2 TLS by inhibiting the recombinase activity of RecA1, which helps to explain the mechanism of DnaE2-dependent TLS and the scientific problem of choosing one of the two restart pathways to repair the stalled replication fork.
Increased connectivity among sensory and motor regions during visual and audiovisual speech perception
Authors: Peelle Jonathan E. , Spehar Brent , Jones Michael S. , McConkey Sarah , Myerson Joel , Hale Sandra , Sommers Mitchell S. , Tye-Murray Nancy 
Published: December 2020

AbstractIn everyday conversation, we usually process the talker’s face as well as the sound of their voice. Access to visual speech information is particularly useful when the auditory signal is degraded. Here we used fMRI to monitor brain activity while adult humans (n = 60) were presented with visual-only, auditory-only, and audiovisual words. The audiovisual words were presented in quiet and several signal-to-noise ratios. As expected, audiovisual speech perception recruited both auditory and visual cortex, with some evidence for increased recruitment of premotor cortex in some conditions (including in substantial background noise). We then investigated neural connectivity using psychophysiological interaction (PPI) analysis with seed regions in both primary auditory cortex and primary visual cortex. Connectivity between auditory and visual cortices was stronger in audiovisual conditions than in unimodal conditions, including a wide network of regions in posterior temporal cortex and prefrontal cortex. In addition to whole-brain analyses, we also conducted a region-of-interest analysis on the left posterior superior temporal sulcus (pSTS), implicated in many previous studies of audiovisual speech perception. We found evidence for both activity and effective connectivity in pSTS for visual-only and audiovisual speech, although these were not significant in whole-brain analyses. Taken together, our results suggest a prominent role for cross-region synchronization in understanding both visual-only and audiovisual speech that complements activity in “integrative” brain regions like pSTS.
Ranked Choice Voting for Representative Transcripts with TRaCE
Authors: Olson Andrew J. , Ware Doreen 
Published: December 2020

AbstractSummaryGenome sequencing projects annotate protein-coding gene models with multiple transcripts, aiming to represent all of the available transcript evidence. However, downstream analyses often operate on only one representative transcript per gene locus, sometimes known as the canonical transcript. To choose canonical transcripts, TRaCE (Transcript Ranking and Canonical Election) holds an ‘election’ in which a set of RNA-seq samples rank transcripts by annotation edit distance. These sample-specific votes are tallied along with other criteria such as protein length and InterPro domain coverage. The winner is selected as the canonical transcript, but the election proceeds through multiple rounds of voting to order all the transcripts by relevance. Based on the set of expression data provided, TRaCE can identify the most common isoforms from a broad expression atlas or prioritize alternative transcripts expressed in specific contexts.Availability and ImplementationTranscript ranking code can be found on GitHub at {{https://github.com/warelab/TRaCE}}Contactolson@cshl.edu,ware@cshl.eduSupplementary informationAdditional data are available in the github repository.
Experiencing surprise: the temporal dynamics of its impact on memory
Authors: Frank Darya , Kafkas Alex , Montaldi Daniela 
Published: December 2020

AbstractTo efficiently process information, the brain shifts between encoding and retrieval states, prioritising bottom-up or top-down processing accordingly. Expectation violation before or during learning has been shown to trigger an adaptive encoding mechanism, resulting in better memory for unexpected events. Using fMRI we explored (1) whether this encoding mechanism is also triggered during retrieval, and if so, (2) what the temporal dynamics of its mnemonic consequences are. Male and female participants studied object images, then, with new objects, they learned a contingency between a cue and a semantic category. Rule-abiding (expected) and violating (unexpected) targets and similar foils were used at test. We found interactions between previous and current similar events’ expectation, such that when an expected event followed a similar but unexpected event, its performance was boosted, underpinned by activation in the hippocampus, midbrain, and occipital cortex. In contrast, a sequence of two unexpected similar events also triggered occipital engagement, however, this did not enhance memory performance. Taken together, our findings suggest that when the goal is to retrieve, encountering surprising events engages an encoding mechanism, supported by bottom-up processing, that may enhance memory for future related events.Significance statementOptimising the balance between new learning and the retrieval of existing knowledge is an ongoing process, at the core of human cognition. Previous research into memory encoding suggests experiencing surprise leads to the prioritisation of the leaning of new memories, forming an adaptive encoding mechanism. We examined whether this mechanism is also engaged when the current goal is to retrieve information. Our results demonstrate that an expectation-driven shift towards an encoding state, supported by enhanced perceptual processing, is beneficial for the correct identification of subsequent expected similar events. These findings have important implications for our understanding of the temporal dynamics of the adaptive encoding of information into memory.