bluuebunny/crossref_metadata_2025_split huggingface dataset:
The axonal sorting activity of pseudorabies virus Us9 protein depends on the state of neuronal maturation
Authors: Tanneti Nikhila S , Federspiel Joel D , Cristea Ileana M , Enquist Lynn W 
Published: August 2020

AbstractAlpha-herpesviruses establish a life-long infection in the nervous system of the affected host; while this infection is restricted to peripheral neurons in a healthy host, the reactivated virus can spread within the neuronal circuitry, such as to the brain, in compromised individuals and lead to adverse health outcomes. Pseudorabies virus (PRV), an alpha-herpesvirus, requires the viral protein Us9 to sort virus particles into axons and facilitate neuronal spread. Us9 sorts virus particles by mediating the interaction of virus particles with neuronal transport machinery. Here, we report that Us9-mediated regulation of axonal sorting also depends on the state of neuronal maturation. Specifically, the development of dendrites and axons is accompanied with proteomic changes that influence neuronal processes. Immature superior cervical ganglionic neurons (SCGs) have rudimentary neurites that lack markers of mature axons. Immature SCGs can be infected by PRV, but they show markedly reduced Us9-dependent regulation of sorting, and increased Us9-independent transport of particles into neurites. Mature SCGs have relatively higher abundances of proteins characteristic of vesicle-transport machinery. We also identify Us9-associated neuronal proteins that can contribute to axonal sorting and subsequent anterograde spread of virus particles in axons. We show that SMPD4/nsMase3, a sphingomyelinase abundant in lipid-rafts, associates with Us9 and is a negative regulator of PRV sorting into axons and neuronal spread, a potential antiviral function.Author SummaryViral pathogenesis often is age-dependent, with more severe outcomes for infected fetuses and neonates compared to adults. As neurons age and mature, dendrites and axons polarize with distinct functions that affect neurotropic virus replication and neuronal spread of infection. This study investigates how neuronal maturation of peripheral nervous system neurons, the site of alpha-herpesvirus life-long latency and reactivation, affects replication and neuronal spread of pseudorabies virus. Characterization of infected immature and mature primary cultures of superior cervical ganglionic neurons revealed significant differences in protein composition and cellular processes that affected the activity of Us9, a viral protein required for sorting virus particles into axons. We identified neuronal and viral proteins that interact with Us9 in immature and mature neurons. Among these, we demonstrate that SMPD4/nsMase3, a sphingomyelinase critical for membrane organization and neuronal function, regulates PRV neuronal spread by preventing capsid association with Us9-containing membranes, presenting a possible antiviral function.
Chromosomal instability by mutations in a novel specificity factor of the minor spliceosome
Authors: de Wolf Bas , Oghabian Ali , Akinyi Maureen V. , Hanks Sandra , Tromer Eelco C. , van Hooff Jolien , van Voorthuijsen Lisa , van Rooijen Laura E. , Verbeeren Jens , Uijttewaal Esther C.H. , Baltissen Marijke P.A. , Yost Shawn , Piloquet Philippe , Vermeulen Michiel , Snel Berend , Isidor Bertrand , Rahman Nazneen , Frilander Mikko J. , Kops Geert J.P.L. 
Published: August 2020

AbstractAneuploidy is the leading cause of miscarriage and congenital birth defects, and a hallmark of cancer. Despite this strong association with human disease, the genetic causes of aneuploidy remain largely unknown. Through exome sequencing of patients with constitutional mosaic aneuploidy, we identified biallelic truncating mutations inCENATAC(CCDC84). We show that CENATAC is a novel component of the minor (U12-dependent) spliceosome that promotes splicing of a specific, rare minor intron subtype. This subtype is characterized by AT-AN splice sites and relatively high basal levels of intron retention. CENATAC depletion or expression of disease mutants resulted in excessive retention of AT-AN minor introns in ~100 genes enriched for nucleocytoplasmic transport and cell cycle regulators, and caused chromosome segregation errors. Our findings reveal selectivity in minor intron splicing with a specific impact on the chromosome segregation process, and show how defects herein can cause constitutional aneuploidy.
Enhanced inflammatory response mediated by parenchymal cells associates with resistance towards mTOR inhibition
Authors: Jiao Long , Eickhoff Roman , Jumpertz Sandra , Roth Johanna , Erdem Merve , Kroh Andreas , Duimel Hans , López-Iglesias Carmen , Schmeding Maximilian , Heij Lara R. , Meierhofer David , Neumann Ulf P. , Cramer Thorsten 
Published: August 2020

AbstractActivation of the mTOR pathway is frequently found in cancer, but mTOR inhibitors have thus far failed to demonstrate significant antiproliferative efficacy in the majority of cancer types. Besides cancer cell-intrinsic resistance mechanisms, it is conceivable that mTOR inhibitors impact on non-malignant host cells in a manner that ultimately supports resistance of cancer cells. Against this background, we sought to analyze the functional consequences of mTOR inhibition in hepatocytes for the growth of metastatic colon cancer. To this end, we established aliverepithelialcell (LEC)-specific knock-out (KO) of mTOR (mTORLECmice). We used these mice to characterize the growth of colorectal liver metastases with and without partial hepatectomy to model different clinical settings. While the LEC-specific loss of mTOR remained without effect on metastasis growth in intact liver, partial liver resection resulted in the formation of larger metastases in mTORLECmice compared to wildtype controls. This was accompanied by significantly enhanced inflammatory activity in LEC-specific mTOR KO livers after partial liver resection. Analysis of NF-κB target gene expression and immunohistochemistry of p65 displayed a significant activation of NF-κB in mTORLECmice, suggesting a functional importance of this pathway for the observed inflammatory phenotype. Taken together, we show an unexpected acceleration of liver metastases upon deletion of mTOR in liver epithelial cells. Our results support the notion that non-malignant host cells can contribute to resistance against mTOR inhibitors and encourage to test if anti-inflammatory drugs are able to improve the efficacy of mTOR inhibitor for cancer therapy.
A genome compendium reveals diverse metabolic adaptations of Antarctic soil microorganisms
Authors: Ortiz Maximiliano , Leung Pok Man , Shelley Guy , Van Goethem Marc W. , Bay Sean K. , Jordaan Karen , Vikram Surendra , Hogg Ian D. , Makhalanyane Thulani P. , Chown Steven L. , Grinter Rhys , Cowan Don A. , Greening Chris 
Published: August 2020

AbstractA surprising diversity and abundance of microorganisms resides in the cold desert soils of Antarctica. The metabolic processes that sustain them, however, are poorly understood. In this study, we used metagenomic and biogeochemical approaches to study the microbial communities in 16 physicochemically diverse mountainous and glacial soils from remote sites in South Victoria Land, north of the Mackay Glacier. We assembled 451 metagenome-assembled genomes from 18 bacterial and archaeal phyla, constituting the largest resource of Antarctic soil microbial genomes to date. The most abundant and prevalent microorganisms are metabolically versatile aerobes that use atmospheric hydrogen and carbon monoxide to meet energy, carbon, and, through metabolic water production, hydration needs. Phylogenetic analysis and structural modelling infer that bacteria from nine phyla can scavenge atmospheric hydrogen using a previously unreported enzyme family, the group 1l [NiFe]-hydrogenases. Consistently, gas chromatography measurements confirmed most soils rapidly consume atmospheric hydrogen and carbon monoxide, and provide the first experimental evidence of methane oxidation in non-maritime Antarctica. We also recovered genomes of microorganisms capable of oxidizing other inorganic compounds, including nitrogen, sulfur, and iron compounds, as well as harvesting solar energy via photosystems and novel microbial rhodopsins. Bacterial lineages defined by symbiotic lifestyles, including Patescibacteria, Chlamydiae, and predatory Bdellovibrionota, were also surprisingly abundant. We conclude that the dominant microorganisms in Antarctic soils adopt mixotrophic strategies for energy and sometimes carbon acquisition, though they co-exist with diverse bacteria and archaea that adopt more specialist lifestyles. These unprecedented insights and associated genome compendium will inform efforts to protect biodiversity in this continent.
Decoding Multivoxel Representations of Affective Scenes in Retinotopic Visual Cortex
Authors: Bo Ke , Yin Siyang , Liu Yuelu , Hu Zhenhong , Meyyapan Sreenivasan , Kim Sungkean , Keil Andreas , Ding Mingzhou 
Published: August 2020

AbstractThe perception of opportunities and threats in complex scenes represents one of the main functions of the human visual system. In the laboratory, its neurophysiological basis is often studied by having observers view pictures varying in affective content. This body of work has consistently shown that viewing emotionally engaging, compared to neutral, pictures (1) heightens blood flow in limbic structures and frontoparietal cortex, as well as in anterior ventral and dorsal visual cortex, and (2) prompts an increase in the late positive event-related potential (LPP), a scalp-recorded and time-sensitive index of engagement within the network of aforementioned neural structures. The role of retinotopic visual cortex in this process has, however, been contentious, with competing theoretical notions predicting the presence versus absence of emotion-specific signals in retinotopic visual areas. The present study used multimodal neuroimaging and machine learning to address this question by examining the large-scale neural representations of affective pictures. Recording EEG and fMRI simultaneously while observers viewed pleasant, unpleasant, and neutral affective pictures, and applying multivariate pattern analysis to single-trial BOLD activities in retinotopic visual cortex, we identified three robust findings: First, unpleasant-versus-neutral decoding accuracy, as well as pleasant-versus-neutral decoding accuracy, were well above chance level in all retinotopic visual areas, including primary visual cortex. Second, the decoding accuracy in ventral visual cortex, but not in early visual cortex or dorsal visual cortex, was significantly correlated with LPP amplitude. Third, effective connectivity from amygdala to ventral visual cortex predicted unpleasant-versus-neutral decoding accuracy, and effective connectivity from ventral frontal cortex to ventral visual cortex predicted pleasant-versus-neutral decoding accuracy. These results suggest that affective pictures evoked valence-specific multivoxel neural representations in retinotopic visual cortex and that these multivoxel representations were influenced by reentry signals from limbic and frontal brain regions.
PARIETAL CONTRIBUTIONS TO ABSTRACT NUMEROSITY MEASURED WITH STEADY STATE VISUAL EVOKED POTENTIALS
Authors: Kohler Peter J. , Barzegaran Elham , Norcia Anthony M. , McCandliss Bruce D. 
Published: August 2020

AbstractNon-symbolic number changes produce transient Event Related Potentials over parietal electrodes, while numerosity effects measured with Steady-State Visual Evoked Potentials (SSVEPs) appear to originate in occipital cortex. We hypothesized that the stimulation rates used in previous SSVEP studies may be too rapid to drive parietal numerosity mechanisms. Here we recorded SSVEPs and behavioral reports over a slower range of temporal frequencies than previously used. Isoluminant dot stimuli updated at a consistent “carrier” frequency (3-6 Hz) while periodic changes in numerosity (e.g. 8→5) formed an even slower “oddball” frequency (0.5-1 Hz). Each numerosity oddball condition had a matched control condition where the number of dots did not change. Carrier frequencies induced SSVEPs with midline occipital topographies that did not differentiate the presence or absence of numerosity oddballs. By contrast, SSVEPs at oddball frequencies had parietal topographies and responded more strongly when oddballs were present. Consistent with our hypothesis, numerosity effects were stronger at slower stimulation rates. In a second study, the numerosity change was either supra-threshold (e.g. 8→5 dots) or near the threshold required for detecting numerosity changes (e.g. 8→9 dots). We found robust parietal responses for the supra-threshold case only, indicating anumerical distance effect. A third study replicated the parietal oddball SSVEP effect across four distinct suprathreshold numerosity-change conditions and showed that number change direction does not influence the effect. These findings show that SSVEP oddball paradigms can probe parietal computations of abstract numerosity, and may provide a rapid, portable approach to quantifying number sense within educational settings.
Newly discovered cichlid fish biodiversity threatened by hybridization with non-native species
Authors: Blackwell Tabitha , Ford Antonia G.P. , Ciezarek Adam G. , Bradbeer Stephanie J. , Juarez Carlos A. Gracida , Ngatunga Benjamin P. , Shechonge Asilatu H. , Tamatamah Rashid , Etherington Graham , Haerty Wilfried , Di Palma Federica , Turner George F. , Genner Martin J. 
Published: August 2020

AbstractInvasive freshwater fish systems are known to readily hybridize with indigenous congeneric species, driving loss of unique and irreplaceable genetic resources. Here we reveal that newly discovered (2013-2016) evolutionarily significant populations of Korogwe tilapia (Oreochromis korogwe) from southern Tanzania are threatened by hybridization with the larger invasive Nile tilapia (Oreochromis niloticus). We use a combination of morphology, microsatellite allele frequencies and whole genome sequences to show thatO. korogwefrom southern lakes (Nambawala, Rutamba and Mitupa) are distinct from geographically-disjunct populations in northern Tanzania (Zigi River and Mlingano Dam). We also provide genetic evidence ofO. korogwexniloticushybrids in three lakes and demonstrate heterogeneity in the extent of admixture across the genome. Finally, using the least admixed genomic regions we estimate that the northern and southernO. korogwepopulations most plausibly diverged approximately 140,000 years ago, suggesting that the geographical separation of the northern and southern groups is not a result of a recent translocation, and instead these populations represent independent evolutionarily significant units. We conclude that these newly-discovered and phenotypically unique cichlid populations are already threatened by hybridization with an invasive species, and propose that these irreplaceable genetic resources would benefit from conservation interventions.
Radiolabelled Bacterial Metallophores as Targeted PET Imaging Contrast Agents for Accurate Identification of Bacteria and Outer Membrane Vesiclesin vivo
Authors: Siddiqui Nabil A. , Houson Hailey A. , Thomas Shindu C. , Blanco Jose R. , O’Donnell Robert E. , Hassett Daniel J. , Lapi Suzanne E. , Kotagiri Nalinikanth 
Published: August 2020

AbstractModern technologies such as 16s DNA sequencing capable of identifying microbes and provide taxonomic resolution at species and strain-specific levels is destined to be transformative1. Likewise, there is an emerging need to accurately identify both infectious and non-infectious microbes non-invasively in the body at the genus and species level to guide diagnosis and treatment strategies. Here, we report development of radiometal-labelled bacterial chelators, knowns as metallophores that allow non-invasive and selective imaging of bacteria and bacterial productsin vivo. We show that these novel contrast agents are able to identifyE. coliwith strain level specificity and other bacteria, such asK. pneumoniae, based on expression of distinct cognate transporters on the bacterial surface. The probe is also capable of tracking probiotic, engineered bacteria and bacterial products, outer membrane vesicles (OMVs), in unique niches such as tumours. Moreover, we report that this novel targeted imaging approach has impactful applicability in monitoring antibiotic treatment outcomes in patients with pulmonary infections, thereby providing the ability to optimize individualized therapeutic approaches. Compared to traditional techniques used to manufacture probes, this strategy simplifies the process considerably by combining the function of metal attachment and cell recognition into a single molecule. Thus, we anticipate that these probes will be widely used in both clinical and investigative settings in living systems for non-invasive imaging of infectious and non-infectious organisms.
Eocene origin, Miocene diversification and intercontinental dispersal of the genusDrosera(Droseraceae)
Authors: Sen Sandeep , Tiwari Neha , Ganesan R 
Published: August 2020

AbstractResolving the evolutionary history of plant carnivory is of great interest to biologists throughout the world. Among the carnivorous plants, GenusDrosera(Droseraceae) is highly diverse with a wide pantropical distribution. Despite being a group of interest for evolutionary biology studies since the time of Charles Darwin, the historical biogeography of this group remains poorly understood. In this study, with an improved species sampling from Genbank, we present a reanalyzed phylogenetic hypothesis of the genusDrosera. We developed a dated molecular phylogeny ofDroserafrom DNA sequences of nuclear ITS and chloroplast rbcL genes. Divergence times were estimated on the combined dataset using an uncorrelated lognormal relaxed clock model and a known fossil calibration implemented in BEAST. The maximum clade credibility tree was then used for ancestral range estimations using DEC+J model implemented in BioGeoBEARS. Our analysis suggests thatDroseraevolved during the Mid Eocene 36 Ma [95% HPD: 49.5-26] and have diversified and dispersed from the late Miocene onwards. Ancestral areas estimated using the DEC+J models suggest an African origin followed major radiation within Australia. Diversification inDroserais temporally congruent with the prevailing drier conditions during the Miocene. From Miocene, grasslands and open habitats dominated across continents and might have provided ecological opportunities for their dispersal and diversification. Several long-distance dispersals and range extensions and in situ radiations coinciding with the evolution of drier conditions can explain their extant distribution across continents. Overall our data set provides fresh insights into the biogeographic factors that shaped the origin and evolution of the genusDrosera.
CorRelator: An interactive and flexible toolkit for high-precision cryo-correlative light and electron microscopy
Authors: Yang Jie E. , Larson Matthew R. , Sibert Bryan S. , Shrum Samantha , Wright Elizabeth R. 
Published: August 2020

AbstractCryo-correlative light and electron microscopy (CLEM) is a technique that uses the spatiotemporal cues from fluorescence light microscopy (FLM) to investigate the high-resolution ultrastructure of biological samples by cryo-electron microscopy (cryo-EM). Cryo-CLEM provides advantages for identifying and distinguishing fluorescently labeled proteins, macromolecular complexes, and organelles from the cellular environment. Challenges remain on how correlation workflows and software tools are implemented on different microscope platforms to support microscopy-driven structural studies. Here, we present an open-source desktop application tool, CorRelator, to bridge between cryo-FLM and cryo-EM/ET data collection instruments. CorRelator was designed to be flexible for both on-the-fly and post-acquisition correlation schemes. The CorRelator workflow is easily adapted to any fluorescence and transmission electron microscope (TEM) system configuration. CorRelator was benchmarked under cryogenic and ambient temperature conditions using several FLM and TEM instruments, demonstrating that CorRelator is a rapid and efficient application for image and position registration in CLEM studies. CorRelator is a cross-platform software featuring an intuitive Graphical User Interface (GUI) that guides the user through the correlation process. CorRelator source code is available at:https://github.com/wright-cemrc-projects/corr.
Dissociation of Medial Frontal β-Bursts and Executive Control
Authors: Errington Steven P. , Woodman Geoffrey F. , Schall Jeffrey D. 
Published: August 2020

ABSTRACTThe neural mechanisms of executive and motor control concern both basic researchers and clinicians. In human studies, preparation and cancellation of movements are accompanied by changes in the β-frequency band (15–29 Hz) of EEG. Previous studies with human participants performing stop signal (countermanding) tasks have described reduced frequency of transient β-bursts over sensorimotor cortical areas before movement initiation and increased β-bursting over medial frontal areas with movement cancellation. This modulation has been interpreted as contributing to the trial-by-trial control of behavior. We performed identical analyses of EEG recorded over the frontal lobe of macaque monkeys performing a saccade countermanding task. Whilst, we replicate the occurrence and modulation of β-bursts associated with initiation and cancellation of saccades, we found that β-bursts occur too infrequently to account for the observed stopping behavior. We also found β-bursts were more common after errors, but their incidence was unrelated to response time adaptation. These results demonstrate the homology of this EEG signature between humans and macaques but raise questions about the current interpretation of β-band functional significance.SIGNIFICANCE STATEMENTThe finding of increased β-bursting over medial frontal cortex with movement cancellation in humans is difficult to reconcile with the finding of modulation too late to contribute to movement cancellation in medial frontal cortex of macaque monkeys. To obtain comparable measurement scales, we recorded EEG over medial frontal cortex of macaques performing a stop signal (countermanding) task. We replicated the occurrence and modulation of β-bursts associated with the cancellation of movements, but we found that β-bursts occur too infrequently to account for observed stopping behavior. Unfortunately, this finding raises doubts whether β-bursts can be a causal mechanism of response inhibition, which impacts future applications in devices such as brain-machine interfaces.