bluuebunny/crossref_metadata_2025_split huggingface dataset:
Similar time course of fast familiarity and slow recollection processes for recognition memory in humans and macaques
Authors: Wu Zhemeng , Kavanova Martina , Hickman Lydia , Lin Fiona , Buckley Mark J. 
Published: January 2020

AbstractAccording to dual-process theory, recognition memory performance draws upon two processes, familiarity and recollection. The relative contribution to recognition memory are commonly distinguished in humans by analyzing receiver-operating-characteristics (ROC) curves; analogous methods are more complex and very rare in animals but fast familiarity and slow recollective-like processes (FF/SR) have been detected in non-human primates (NHPs) based on analyzing recognition error response time profiles. The relative utility of these methods to investigate familiarity and recollection/recollection-like processes across species is uncertain; indeed, even how comparable the FF/SR measures are across humans and NHPs remains unclear. Therefore in this study a broadly similar recognition memory task was exploited in both humans and NHPs to investigate the time course of the two recognition processes. We first show that the FF/SR dissociation exists in this task in human participants and then we demonstrate a similar profile in NHPs which suggests that FF/SR processes are comparable across species. We then verified, using ROC-derived indices for each time-bin in the FF/SR profile, that the ROC and FF/DR measures are related. Hence we argue that the FF/SR approach, procedurally easier in animals, can be used as a decent proxy to investigate these two recognition processes in future animal studies, important given that scant data exists as to the neural basis underlying recollection yet many of the most informative techniques primarily exist in animal models.
The dynamic surface proteomes of allergenic fungal conidia
Authors: Blango Matthew G. , Pschibul Annica , Rivieccio Flora , Krüger Thomas , Rafiq Muhammad , Jia Lei-Jie , Zheng Tingting , Goldmann Marie , Voltersen Vera , Li Jun , Panagiotou Gianni , Kniemeyer Olaf , Brakhage Axel A. 
Published: January 2020

AbstractFungal spores and hyphal fragments play an important role as allergens in respiratory diseases. In this study, we performed trypsin shaving and secretome analyses to identify the surface-exposed proteins and secreted/shed proteins ofAspergillus fumigatusconidia, respectively. We investigated the surface proteome under different conditions, including temperature variation and germination. We found that the surface proteome of restingA. fumigatusconidia is not static, but instead unexpectedly dynamic, as evidenced by drastically different surface proteomes under different growth conditions. Knockouts of two abundantA. fumigatussurface proteins, ScwA and CweA, were found to function only in fine-tuning the cell wall stress response, implying that the conidial surface is very robust against perturbations. We then compared the surface proteome ofA. fumigatusto other allergy-inducing molds, includingAlternaria alternata, Penicillium rubens, andCladosporium herbarum, and performed comparative proteomics on resting and swollen conidia, as well as secreted proteins from germinating conidia. We detected 125 protein ortholog groups, including 80 with putative catalytic activity, in the extracellular region of all four molds, and 42 nonorthologous proteins produced solely byA. fumigatus. Ultimately, this study highlights the dynamic nature of theA. fumigatusconidial surface and provides targets for future diagnostics and immunotherapy.
Contrasting population genetics of cattle- and buffalo-derivedTheileria annulatacausing tropical theileriosis
Authors: Chaudhry Umer , Ali Qasim , Zheng Lynn , Rashid Imran , Shabbir Muhammad Zubair , Nauman Muhammad , Ashraf Kamran , Evans Mike , Rafiq Shahzad , Oneeb Muhammad , Morrison Ivan , Sargison Neil D. 
Published: January 2020

AbstractThe present study was designed to improve understanding ofTheileria annulatain sympatric water buffalo and cattle in the Punjab province of Pakistan. The prevalence of tropical theileriosis is high, buparvaquone resistance is widespread, and vaccine protection is poor in the field. Better understanding is, therefore, needed of the factors that influence the genetics ofT. annulatapopulations both within its hosts and in its overall populations. Here we utilise a panel of six satellites and a mitochondrial cytochrome b marker to explore the multiplicity ofT. annulatainfection and patterns of emergence and spread of different parasite genotypes. Parasite materials were collected from infected animals in defined regions, where water buffalo and cattle are kept together. Our results show thatT. annulatais genetically more diverse in cattle- than in water buffalo-derived populations (the mean numbers of unique satellite alleles were 13.3 and 1.8 and numbers of unique cytochrome b locus alleles were 65 and 27 in cattle- and water buffalo-derived populations, respectively). The data show a high level of genetic diversity among the individual host-derived populations (the overall heterozygosity (He) indices were 0.912 and 0.931 in cattle, and 0.874 and 0.861 in buffalo, based on satellite and cytochrome b loci, respectively). When considered in the context of high parasite transmission rates and frequent animal movements between different regions, the predominance of multipleT. annulatagenotypes, with multiple introductions of infection in the hosts from which the parasite populations were derived, may have practical implications for the spread of parasite genetic adaptations; such as those conferring vaccine cross-protection against different strains affecting cattle and buffalo, or resistance to antiprotozoal drugs.
Cul3regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development
Authors: Morandell Jasmin , Schwarz Lena A. , Basilico Bernadette , Tasciyan Saren , Nicolas Armel , Sommer Christoph , Kreuzinger Caroline , Dotter Christoph P. , Knaus Lisa S. , Dobler Zoe , Cacci Emanuele , Danzl Johann G. , Novarino Gaia 
Published: January 2020

AbstractDe novoloss of function mutations in the ubiquitin ligase-encoding geneCullin3(CUL3)lead to autism spectrum disorder (ASD). Here, we usedCul3mouse models to evaluate the consequences ofCul3mutationsin vivo.Our results show thatCul3haploinsufficient mice exhibit deficits in motor coordination as well as ASD-relevant social and cognitive impairments.Cul3mutant brain displays cortical lamination abnormalities due to defective neuronal migration and reduced numbers of excitatory and inhibitory neurons. In line with the observed abnormal columnar organization,Cul3haploinsufficiency is associated with decreased spontaneous excitatory and inhibitory activity in the cortex. At the molecular level, employing a quantitative proteomic approach, we show thatCul3regulates cytoskeletal and adhesion protein abundance in mouse embryos. Abnormal regulation of cytoskeletal proteins inCul3mutant neuronal cells results in atypical organization of the actin mesh at the cell leading edge, likely causing the observed migration deficits. In contrast to these important functions early in development,Cul3deficiency appears less relevant at adult stages. In fact, induction ofCul3haploinsufficiency in adult mice does not result in the behavioral defects observed in constitutiveCul3haploinsufficient animals. Taken together, our data indicate thatCul3has a critical role in the regulation of cytoskeletal proteins and neuronal migration and that ASD-associated defects and behavioral abnormalities are primarily due toCul3functions at early developmental stages.
Using Natural Language Processing to Learn the Grammar of Glycans
Authors: Bojar Daniel , Camacho Diogo M. , Collins James J. 
Published: January 2020

AbstractWhile nucleic acids and proteins receive ample attention, progress on understanding the structural and functional roles of carbohydrates has lagged behind. Here, we develop a language model for glycans, SweetTalk, taking into account glycan connectivity and composition. We use this model to investigate motifs in glycan substructures, classify them according to their O-/N-linkage, and predict their immunogenicity with an accuracy of ∼92%, opening up the potential for rational glycoengineering.
Intestine-specific deletion of metal transporterZip14 (Slc39a14)causes brain manganese overload and locomotor defects of manganism
Authors: Aydemir Tolunay B. , Thorn Trista L. , Ruggiero Courtney H. , Pompilus Marjory , Febo Marcelo , Cousins Robert J. 
Published: January 2020

AbstractImpaired manganese (Mn) homeostasis can result in excess Mn accumulation in specific brain regions and neuropathology. Maintaining Mn homeostasis and detoxification is dependent on effective Mn elimination. Specific metal transporters control Mn homeostasis. Human carriers of mutations in the metal transporter ZIP14 and whole-bodyZip14KO (WB-KO) mice display similar phenotypes, including spontaneous systemic and brain Mn overload, and motor dysfunction. Initially, it was believed that Mn accumulation due toZIP14mutations caused by impaired hepatobiliary Mn elimination. However, liver-specificZip14KO mice (L-KO) did not show systemic Mn accumulation or motor deficits. ZIP14 is highly expressed in the small intestine and is localized to the basolateral surface of enterocytes. Thus we hypothesized that basolaterally-localized ZIP14 in enterocytes provides another route for elimination of Mn. Using wild type and intestine-specific ZIP14 KO (I-KO) mice, we have shown that ablation of intestinalZip14is sufficient to cause systemic and brain Mn accumulation. The lack of intestinal ZIP14- mediated Mn excretion was compensated for by the hepatobiliary system; however, it was not sufficient to maintain Mn homeostasis. When supplemented with extra dietary Mn, I-KO mice displayed some motor dysfunctions, brain Mn accumulation based on both MRI imaging and chemical analysis, thus demonstrating the importance of intestinal ZIP14 as a route of Mn excretion. A defect in intestinalZip14expresssion likely could contribute to the Parkinson-like Mn accumulation of manganism.New & NoteworthyMn-induced parkinsonism is recognized as rising in frequency due to both environmental factors and genetic vulnerability, yet currently, there is no cure. We provide evidence in an integrative animal model that basolaterally localized ZIP14 regulates Mn excretion and detoxification and that deletion of intestinal ZIP14 leads to systemic and brain Mn accumulation, providing robust evidence for the indispensable role of intestinal ZIP14 on Mn excretion.
Chemical-Genetic Interrogation of Nuclear Size Control Reveals Cancer-Specific Effects on Cell Migration and Invasion
Authors: Rizzotto Andrea , Tollis Sylvain , Pham Nhan T. , Wildenhain Jan , Zuleger Nikolaj , Keys Jeremy T. , Batrakou Dzmitry , Culley Jayne , Zheng Sarah , Lammerding Jan , Carragher Neil O. , Brunton Valerie G. , Auer Manfred , Tyers Mike , Schirmer Eric C. 
Published: January 2020

AbstractLower survival rates for many cancer types correlate with increases or decreases in nuclear size/scaling in a tumor-type/tissue-specific manner. Postulating that nuclear size changes confer a fitness advantage on tumor cells, we screened for FDA/EMA-approved compounds that reverse tumor nuclear size changes in cell lines from three such tumor types: prostate adenocarcinoma, colonic adenocarcinoma, and small-cell squamous lung cancer. We found distinct, largely non-overlapping sets of compounds that either rectify or exacerbate nuclear size changes for each tumor type. Nuclear size phenotypes across cell lines clustered particular classes of compounds including serotonin uptake inhibitors, cyclo-oxygenase inhibitors, beta-adrenergic receptor agonists, monoamine oxidase inhibitors, and Na+/K+ATPase inhibitors. Nearly all compounds selected for further investigation inhibited cell migration and/or invasion, suggesting that targeting nuclear size control pathways in chemotherapy regimens could improve patient survival.
Antigen responsive CD4+T cell clones contribute to the HIV-1 latent reservoir
Authors: Mendoza Pilar , Jackson Julia R. , Oliveira Thiago , Gaebler Christian , Ramos Victor , Caskey Marina , Jankovic Mila , Nussenzweig Michel C. , Cohn Lillian B. 
Published: January 2020

AbstractAntiretroviral therapy suppresses but does not cure HIV-1 infection due to the existence of a long-lived reservoir of latently infected cells. The reservoir has an estimated half-life of 44 months and is largely composed of clones of infected CD4+T cells. The long half-life appears to result in part from expansion and contraction of infected CD4+T cell clones. However, the mechanisms that govern this process are poorly understood. To determine whether the clones might result from, and be maintained by exposure to antigen, we measured responses of reservoir cells to a small subset of antigens from viruses that produce chronic or recurrent infections. Despite the limited panel of test antigens, clones of antigen responsive CD4+T cells containing defective or intact latent proviruses were found in 7 out of 8 individuals studied. Thus, chronic or repeated exposure to antigen may contribute to the longevity of the HIV-1 reservoir by stimulating the clonal expansion of latently infected CD4+T cells.
Efficient and accurate inference of microbial trajectories from longitudinal count data
Authors: Joseph Tyler A. , Pasarkar Amey P. , Pe’er Itsik 
Published: January 2020

AbstractThe recently completed second phase of the Human Microbiome Project has highlighted the relationship between dynamic changes in the microbiome and disease, motivating new microbiome study designs based on longitudinal sampling. Yet, analysis of such data is hindered by presence of technical noise, high dimensionality, and data sparsity. To address these challenges, we propose LUMINATE (LongitUdinal Microbiome INference And zero deTEction), a fast and accurate method for inferring relative abundances from noisy read count data. We demonstrate on synthetic data that LUMINATE is orders of magnitude faster than current approaches, with better or similar accuracy. This translates to feasibility of analyzing data at the requisite dimensionality for current studies. We further show that LUMINATE can accurately distinguish biological zeros, when a taxon is absent from the community, from technical zeros, when a taxon is below the detection threshold. We conclude by demonstrating the utility of LUMINATE for downstream analysis by using estimates of latent relative abundances to fit the parameters of a dynamical system, leading to more accurate predictions of community dynamics.Code availabilityhttps://github.com/tyjo/luminate
Music-selective neural populations arise without musical training
Authors: Boebinger Dana , Norman-Haignere Sam , McDermott Josh , Kanwisher Nancy 
Published: January 2020

ABSTRACTRecent work has shown that human auditory cortex contains neural populations anterior and posterior to primary auditory cortex that respond selectively to music. However, it is unknown how this selectivity for music arises. To test whether musical training is necessary, we measured fMRI responses to 192 natural sounds in 10 people with almost no musical training. When voxel responses were decomposed into underlying components, this group exhibited a music-selective component that was very similar in response profile and anatomical distribution to that previously seen in individuals with moderate musical training. We also found that musical genres that were less familiar to our participants (e.g., Balinesegamelan) produced strong responses within the music component, as did drum clips with rhythm but little melody, suggesting that these neural populations are broadly responsive to music as a whole. Our findings demonstrate that the signature properties of neural music selectivity do not require musical training to develop, showing that the music-selective neural populations are a fundamental and widespread property of the human brain.NEW & NOTEWORTHYWe show that music-selective neural populations are clearly present in people without musical training, demonstrating that they are a fundamental and widespread property of the human brain. Additionally, we show music-selective neural populations respond strongly to music from unfamiliar genres as well as music with rhythm but little pitch information, suggesting that they are broadly responsive to music as a whole.
An amygdalo-parabrachial pathway regulates pain perception and chronic pain
Authors: Raver Charles , Uddin Olivia , Ji Yadong , Li Ying , Cramer Nathan , Jenne Carleigh , Morales Marisela , Masri Radi , Keller Asaf 
Published: January 2020

AbstractThe parabrachial (PB) complex mediates both ascending nociceptive signaling and descending pain modulatory information in the affective/emotional pain pathway. We have recently reported that chronic pain is associated with amplified activity of PB neurons in a rat model of neuropathic pain. Here we demonstrate that similar activity amplification occurs in mice, and that this is related to suppressed inhibition to PB neurons from the central nucleus of the amygdala (CeA). Animals with pain after chronic constriction injury of the infraorbital nerve (CCI-Pain) displayed higher spontaneous and evoked activity in PB neurons, and a dramatic increase in after-discharges—responses that far outlast the stimulus—compared to controls. PB neurons in CCI-Pain animals showed a reduction in inhibitory, GABAergic inputs. We show that—in both rats and mice—PB contains few GABAergic neurons, and that most of its GABAergic inputs arise from CeA. These CeA GABA neurons express dynorphin, somatostatin and/or corticotropin releasing hormone. We find that the efficacy of this CeA-LPB pathway is suppressed in chronic pain. Further, optogenetically stimulating this pathway suppresses acute pain, and inhibiting it, in naïve animals, evokes pain behaviors. These findings demonstrate that the CeA-LPB pathway is critically involved in pain regulation, and in the pathogenesis of chronic pain.Significance StatementWe describe a novel pathway, consisting of inhibition by dynorphin, somatostatin and corticotropin-releasing hormone expressing neurons in the central nucleus of the amygdala that project to the parabrachial nucleus (PB). We show that this pathway regulates the activity of pain-related neurons in PB, and that, in chronic pain, this inhibitory pathway is suppressed, and that this suppression is causally related to pain perception. We propose that this amygdalo-parabrachial pathway is a key regulator of both chronic and acute pain, and a novel target for pain relief.
CRL5-dependent regulation of Arl4c and Arf6 controls hippocampal morphogenesis
Authors: Han Jisoo S. , Hino Keiko , Reyes Raenier V. , Canales Cesar P. , Miltner Adam M. , Haddadi Yasmin , Sun Junqing , Chen Chao-Yin , La Torre Anna , Simó Sergi 
Published: January 2020

SummaryThe small GTPase Arl4c participates in the regulation of cell migration, cytoskeletal rearrangements, and vesicular trafficking in epithelial cells. The Arl4c signaling cascade starts by the recruitment of the Arf-GEF cytohesins to the plasma membrane, which in turn engage the small GTPase Arf6. In the nervous system, Arf6 regulates dendrite outgrowth in vitro and neuronal migration in the developing cortex. However, the role of Arl4c-cytohesin-Arf6 signaling during brain development and particularly during hippocampal development remain elusive. Here, we report that the E3 ubiquitin ligase Cullin 5/Rbx2 (CRL5) controls the stability of Arl4c and its signaling effectors to regulate hippocampal morphogenesis. Rbx2 knock out causes hippocampal pyramidal neuron mislocalization and formation of multiple apical dendrites. The same phenotypes were observed when Cullin 5 was knocked down in pyramidal neurons by in utero electroporation. We used quantitative mass spectrometry to show that Arl4c, Cytohesin-1/3, and Arf6 accumulate in the telencephalon when Rbx2 is absent. Arl4c expression is post-transcriptionally regulated, with a peak in expression at early postnatal stages, and is localized at the plasma membrane and on intracellular vesicles in hippocampal pyramidal neurons. Furthermore, we show that depletion of Arl4c rescues the phenotypes caused by Cullin 5 knock down in the hippocampus, whereas depletion of Arf6 exacerbates over-migration. Finally, we show that Arl4c and Arf6 are necessary for the dendritic outgrowth of pyramidal neurons to the most superficial strata of the hippocampus. Overall, we identified CRL5 as a key regulator of hippocampal development and uncovered Arl4c and Arf6 as novel CRL5-regulated signaling effectors that control pyramidal neuron migration and dendritogenesis.
Advantages and limits of metagenomic assembly and binning of a giant virus
Authors: Schulz Frederik , Andreani Julien , Francis Rania , Khalil Jacques Yaacoub Bou , Lee Janey , La Scola Bernard , Woyke Tanja 
Published: January 2020

AbstractGiant viruses have large genomes, often within the size range of cellular organisms. This distinguishes them from most other viruses and demands additional effort for the successful recovery of their genomes from environmental sequence data. Here we tested the performance of genome-resolved metagenomics on a recently isolated giant virus, Fadolivirus, by spiking it into an environmental sample from which two other giant viruses were isolated. At high spike-in levels, metagenome assembly and binning led to the successful genomic recovery of Fadolivirus from the sample. A complementary survey of viral hallmark genes indicated the presence of other giant viruses in the sample matrix, but did not detect the two isolated from this sample. Our results indicate that genome-resolved metagenomics is a valid approach for the recovery of near-complete giant virus genomes given that sufficient clonal particles are present. Our data also underline that a vast majority of giant viruses remain currently undetected, even in an era of terabase-scale metagenomics.
Modulation of the canonical Wnt activity by androgen signaling in prostate epithelial basal stem cells
Authors: Liu Yueli , Wang Jiawen , Horton Corrigan , Katzman Sol , Cai Tao , Wang Zhu A. 
Published: January 2020

AbstractBoth the canonical Wnt signaling and androgen signaling are important factors regulating prostate organogenesis. How these two pathways crosstalk to regulate prostate stem cell functions remain unclear. Here, we show that while canonical Wnt activity is required for prostate basal stem cell multipotency in vivo, ectopic Wnt activity does not promote basal-to-luminal cell differentiation. We provide evidence that androgen signaling may keep Wnt activity in check. In prostate organoid culture from basal cells, dihydrotestosterone (DHT) antagonizes R-spondin-stimulated organoid growth in a concentration-dependent manner. Molecular analyses of organoids under different treatment conditions showed that androgen signaling down-regulated the expressions of a Wnt reporter as well as many Wnt target genes. Pathway analysis and gene set enrichment analysis of organoid RNA-seq data also revealed the canonical Wnt signaling as a key pathway distinguishing organoids treated with or without DHT. Notably, DHT treatment enhanced AR and β–catenin binding in the nuclei of prostate organoids, providing possible mechanistic clues. Our results reveal a critical role of AR signaling in modulating canonical Wnt activity in prostate basal cells to regulate their multipotency.