bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mobile RDoC: Using Smartphones to Understand the Relationship Between Auditory Verbal Hallucinations and Need for Care
Authors: Ben-Zeev Dror , Buck Benjamin , Chander Ayesha , Brian Rachel , Wang Weichen , Atkins David , Brenner Carolyn J , Cohen Trevor , Campbell Andrew , Munson Jeffrey 
Published: October 2020

Abstract

Objective
Auditory verbal hallucinations (AVH) are common in multiple clinical populations but also occur in individuals who are otherwise considered healthy. Adopting the National Institute of Mental Health’s Research Domain Criteria (RDoC) framework, the aim of the current study was to integrate a variety of measures to evaluate whether AVH experience varies across clinical and nonclinical individuals.

Methods
A total of 384 people with AVH from 41 US states participated in the study; 295 participants (77%) who received inpatient, outpatient, or combination treatments for AVH and 89 participants (23%) who never received care. Participants used a multi-modal smartphone data collection system to report on their AVH experiences and co-occurring psychological states multiple times daily, over 30 days. In parallel, smartphone sensors recorded their physical activity, geolocation, and calling and texting behavior continuously.

Results
The clinical sample experienced AVH more frequently than the nonclinical group and rated their AVH as significantly louder and more powerful. They experienced more co-occurring negative affect and were more socially withdrawn, spending significantly more time at home and significantly less time near other people. Participants with a history of inpatient care also rated their AVH as infused with significantly more negative content. The groups did not differ in their physical activity or use of their smartphones for digital communication.

Conclusion
Smartphone-assisted remote data collection revealed real-time/real-place phenomenological, affective, and behavioral differences between clinical and nonclinical samples of people who experience AVH. The study provided strong support for the application of RDoC-informed approaches in psychosis research.
Protective Effects of STI-2020 Antibody Delivered Post-Infection by the Intranasal or Intravenous Route in a Syrian Golden Hamster COVID-19 Model
Authors: Fu Yanwen , Maruyama Junki , Singh Alok , Lim Reyna , Ledesma Arthur , Lee Daniel , Rivero-Nava Laura , Ko Jamie , Rivera Ianne , Sattler Rachel A. , Manning John T. , Kerwin Lisa , Zhou Heyue , Brunswick Mark , Bresson Damien , Ji Henry , Paessler Slobodan , Allen Robert D. 
Published: October 2020

ABSTRACTWe have previously reported that the SARS-CoV-2 neutralizing antibody, STI-2020, potently inhibits cytopathic effects of infection by genetically diverse clinical SARS-CoV-2 pandemic isolates in vitro, and has demonstrated efficacy in a hamster model of COVID-19 when administered by the intravenous route immediately following infection. We now have extended our in vivo studies of STI-2020 to include disease treatment efficacy, profiling of biodistribution of STI-2020 in mice when antibody is delivered intranasally (IN) or intravenously (IV), as well as pharmacokinetics in mice following IN antibody administration. Importantly, SARS-CoV-2-infected hamsters were treated with STI-2020 using these routes, and treatment effects on severity and duration of COVID-19-like disease in this model were evaluated. In SARS-CoV-2 infected hamsters, treatment with STI-2020 12 hours post-infection using the IN route led to a decrease in severity of clinical disease signs and a more robust recovery during 9 days of infection as compared to animals treated with an isotype control antibody. Treatment via the IV route using the same dose and timing regimen resulted in a decrease in the average number of consecutive days that infected animals experienced weight loss, shortening the duration of disease and allowing recovery to begin more rapidly in STI-2020 treated animals. Following IN administration in mice, STI-2020 was detected within 10 minutes in both lung tissue and lung lavage. The half-life of STI-2020 in lung tissue is approximately 25 hours. We are currently investigating the minimum effective dose of IN-delivered STI-2020 in the hamster model as well as establishing the relative benefit of delivering neutralizing antibodies by both IV and IN routes.
GDV1 C-terminal truncation of 39 amino acids disrupts sexual commitment inPlasmodium falciparum
Authors: Tibúrcio Marta , Hitz Eva , Niederwieser Igor , Kelly Gavin , Davies Heledd , Doerig Christian , Billker Oliver , Voss Till S. , Treeck Moritz 
Published: October 2020

AbstractMalaria is a mosquito-borne disease caused by apicomplexan parasites of the genusPlasmodium.Completion of the parasite’s life cycle depends on the transmission of sexual stages, the gametocytes, from an infected human host to the mosquito vector. Sexual commitment occurs in only a small fraction of asexual blood stage parasites and is initiated by external cues. The gametocyte development protein 1 (GDV1) has been described as a key facilitator to trigger sexual commitment. GDV1 interacts with the silencing factor heterochromatin protein 1 (HP1), leading to its dissociation from heterochromatic DNA at the genomic locus encoding AP2-G, the master transcription factor of gametocytogenesis. How this process is regulated is not known. In this study we have addressed the role of protein kinases implicated in gametocyte development. From a pool of available protein kinase KO lines, we identified two kinase knockout lines which fail to produce gametocytes. However, independent genetic verification revealed that both kinases are not required for gametocytogenesis but both lines harbour the same mutation that leads to a truncation in the extreme C-terminus of GDV1. Introduction of the identified nonsense mutation into the genome of wild type parasite lines replicates the observed phenotype. Using a GDV1 overexpression line we show that the truncation in the GDV1 C-terminus does neither interfere with the nuclear import of GDV1 nor its interaction with HP1in vitro, but appears important to sustain GDV1 protein levels and thereby sexual commitment.ImportanceTransmission of malaria causingPlasmodiumspecies by mosquitos requires the parasite to change from a continuously growing asexual parasite form growing in the blood, to a sexually differentiated form, the gametocyte. Only a small subset of asexual parasites differentiates into gametocytes that are taken up by the mosquito. Transmission represents a bottleneck in the lifecycle of the parasite, so a molecular understanding of the events that lead to stage conversion may identify novel intervention points. Here we screened a subset of kinases we hypothesized to play a role in this process. While we did not identify kinases required for sexual conversion, we identified a mutation in the C-terminus of the Gametocyte Development 1 protein (GDV1), which abrogates sexual development. The mutation destabilises the protein but not its interaction with its cognate binding partner HP1. This suggest an important role for the GDV1 C-terminus beyond trafficking and protein stability.
Real-Time Multi-Angle Projection Imaging of Biological Dynamics
Authors: Chang Bo-Jui , Sapoznik Etai , Pohlkamp Theresa , Terrones Tamara S. , Welf Erik S. , Manton James D. , Roudot Philippe , Hake Kayley , Whitehead Lachlan , York Andrew G. , Dean Kevin M. , Fiolka Reto 
Published: October 2020

AbstractWe introduce a cost-effective and easily implemented scan unit which enables any camera-based microscope to perform projection imaging from diverse viewing angles. We demonstrate this capability on Lattice Light-Sheet and Oblique Plane Microscopy by rapidly delivering projection images with an uncompromised lateral resolution and high optical contrast. By imaging the sample from one or multiple perspectives, our method enables visualization of rapid biological processes, real time stereoscopic imaging as well as three-dimensional particle localization throughout a cellular volume from just two images. Furthermore, because our projection imaging technique provides intuitive three-dimensional renderings in real-time, it improves microscope usability, allows users to more-readily optimize instrument performance and identify biological phenomena of interest on-the-fly, while also reducing data overhead by a factor of >100. We leverage our rapid projection method to image cancer cell morpho-dynamics and calcium signaling in cultured neurons, to perform three-dimensional localization of genetically encoded nanoparticles, as well as to image orthogonal views of an embryonic Zebrafish heart simultaneously.
How many and which species to plant? A multi-trait-based approach to select species to restore ecosystem services
Authors: Tsujii Paula Kiyomi , Coutinho André Ganem , Medina Anderson M. , Kraft Nathan J. B. , Gonzalez-Melo Andres , Higuchi Pedro , Müller Sandra Cristina , Niinemets Ülo , Pillar Valério D. , Sosinski Enio E. , Carlucci Marcos B. 
Published: October 2020

AbstractIt has been increasingly argued that ecological restoration should focus more on targeting ecosystem services than on species composition of reference ecosystems. In this sense, the role that species play on community assembly and functioning through their functional traits is very relevant, because effect traits mediate ecosystem processes, ultimately resulting in provision of ecosystem services. One major challenge in ecological restoration is to know which species to use that will deliver the target ecosystem services. We developed an algorithm to select the minimum set of species that maximize the functional richness (FRic) and the functional redundancy (FR) of the restored community, a proxy for the provision of multiple ecosystem services and the resilience of the system to environmental changes, respectively. For this, we simulated the restoration of 24 riparian woody communities of the Brazilian Cerrado. Using the species pool of each original local community, we ran restoration simulations for gradually increasing species richness until reaching the total species richness of the original local community. We computed FRic and FR for each simulated restoration community using the traits specific leaf area, maximum plant height and seed mass. Our simulation results indicate that multiple ecosystem services could be restored with an average of 66% of the species of the original community. Moreover, an average of 59% of the species would be needed to restore communities resilient to environmental changes. Our approach contributes to solving one of the major challenges of ecological restoration, which is defining how many and which species should be used to achieve functional targets. We believe this approach can help in projects of restoration by enabling restoration practitioners to select minimum alternative sets of species that optimize the provision of multiple ecosystem services in a resilient restored ecosystem.
Synteny-based genome assembly for 16 species ofHeliconiusbutterflies, and an assessment of structural variation across the genus
Authors: Seixas Fernando A. , Edelman Nathaniel B. , Mallet James 
Published: October 2020

AbstractHeliconiusbutterflies (Lepidoptera: Nymphalidae) are a group of 48 neotropical species widely studied in evolutionary research. Despite the wealth of genomic data generated in past years, chromosomal level genome assemblies currently exist for only two species,Heliconius melpomeneandH. erato, each a representative of one of the two major clades of the genus. Here, we use these reference genomes to improve the contiguity of previously published draft genome assemblies of 16Heliconiusspecies. Using a reference-assisted scaffolding approach, we place and order the scaffolds of these genomes onto chromosomes, resulting in 95.7-99.9% of their genomes anchored to chromosomes. Genome sizes are somewhat variable among species (270-422 Mb) and in one small group of species (H. hecale,H. elevatusandH. pardalinus) differences in genome size are mainly driven by a few restricted repetitive regions. Genes within these repeat regions show an increase in exon copy number, an absence of internal stop codons, evidence of constraint on non-synonymous changes, and increased expression, all of which suggest that the extra copies are functional. Finally, we conducted a systematic search for inversions and identified five moderately large inversions fixed between the two majorHeliconiusclades. We infer that one of these inversions was transferred by introgression between the lineages leading to theerato/saraandburneyi/dorisclades. These reference-guided assemblies represent a major improvement inHeliconiusgenomic resources that should aid further genetic and evolutionary studies in this genus.
Metabolic flux signatures of the ER unfolded protein responsein vivoreveal decreased hepaticde novolipogenesis and mobilization of lipids from adipose tissue to liver
Authors: Schneider Catherine P. , Peng Lucy , Yuen Samuel , Chang Michael , Karapetyan Rozalina , Nyangau Edna , Mohammed Hussein , Palacios Hector , Ziari Naveed , Joe Larry K. , Frakes Ashley E. , Dillin Andrew , Hellerstein Marc K. 
Published: October 2020

AbstractThe unfolded protein response in the endoplasmic reticulum (UPRER) is involved in a number of metabolic diseases, including non-alcoholic fatty liver disease. Here, we characterize the UPRERinduced metabolic changes in mouse liver throughin vivometabolic labeling and mass spectrometric analysis of proteome and lipid fluxes. We induced ER stressin vivovia tunicamycin treatment and measured rates of proteome-wide protein synthesis,de novolipogenesis and cholesterol synthesis serially over a three-day period, thereby generating a metabolic “signature” of the UPRERover time. Synthesis of most proteins was suppressed under ER stress conditions, including proteins involved in lipogenesis, consistent with reducedde novolipogenesis at 48 and 72 hours. Electron microscopy revealed striking morphological changes to ER and H&E staining showed lipid droplet enriched livers under ER stress. Pre-labeling of adipose tissue prior to ER stress induction revealed mobilization of lipids from adipose to the liver. Interestingly, the source of these lipids was uptake of free fatty acids, not whole triglycerides or phospholipids from lipoproteins, as demonstrated by replacement of the triglyceride-glycerol moiety in liver concurrently with increased incorporation of labeled palmitate from adipose. We also induced ER stress by a high-fat diet and observed similar metabolic flux signatures, suggesting that this mechanism may play a role in the progression of fatty liver disease. This flux-based approach provides a powerful tool to identify novel regulators of ER stress and potential targets for pharmacological intervention.
Sex-biasedZRSR2mutations in myeloid malignancies impair plasmacytoid dendritic cell activation and apoptosis
Authors: Togami Katsuhiro , Chung Sun Sook , Madan Vikas , Kenyon Christopher M. , Cabal-Hierro Lucia , Taylor Justin , Kim Sunhee S. , Griffin Gabriel K. , Ghandi Mahmoud , Li Jia , Li Yvonne Y. , Angelot-Delettre Fanny , Biichle Sabeha , Seiler Michael , Buonamici Silvia , Lovitch Scott B. , Louissaint Abner , Morgan Elizabeth A. , Jardin Fabrice , Piccaluga Pier Paolo , Weinstock David M. , Hammerman Peter S. , Yang Henry , Konopleva Marina , Pemmaraju Naveen , Garnache-Ottou Francine , Abdel-Wahab Omar , Koeffler H. Phillip , Lane Andrew A. 
Published: October 2020

ABSTRACTBlastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive leukemia of plasmacytoid dendritic cells (pDCs). BPDCN occurs at least three times more frequently in men than women, but the reasons for this sex bias are unknown. Here, studying genomics of primary BPDCN and modeling disease-associated mutations, we link acquired alterations in RNA splicing to abnormal pDC development and inflammatory response through Toll-like receptors. Loss-of-function mutations inZRSR2,an X chromosome gene encoding a splicing factor, are enriched in BPDCN and nearly all mutations occur in males.ZRSR2mutation impairs pDC activation and apoptosis after inflammatory stimuli, associated with intron retention and inability to upregulate the transcription factor IRF7. In vivo, BPDCN-associated mutations promote pDC expansion and signatures of decreased activation. These data support a model in which male-biased mutations in hematopoietic progenitors alter pDC function and confer protection from apoptosis, which may impair immunity and predispose to leukemic transformation.STATEMENT OF SIGNIFICANCESex bias in cancer is well recognized but the underlying mechanisms are incompletely defined. We connect X chromosome mutations inZRSR2to an extremely male-predominant leukemia. Aberrant RNA splicing induced byZRSR2mutation impairs dendritic cell inflammatory signaling, interferon production, and apoptosis, revealing a sex- and lineage-related tumor suppressor pathway.
SurfStamp: 3D Printer Compatible Molecular Surface Representation
Authors: Oda Toshiyuki 
Published: October 2020

AbstractSurfStamp is an application that is used to generate textures for surface models of proteins. The textures contain information about surface residues and the information is drawn directly on the 3D object of the models. This approach is more intuitive than the labeling functions that most three-dimensional (3D) structure viewers use to show residue information. Therefore, the use of this application enables researchers, readers, or audiences to easily determine which residues are contributing the surface they are focusing on.AvailabilityThe application is provided under the open-source Apache License Version 2.0 (http://www.apache.org/licenses/LICENSE-2.0). The application and source code are available fromhttps://github.com/yamule/SurfStamp-public/releases. The application is also available as a plugin for the recent versions of PyMOL (Schrodinger, 2015,https://github.com/schrodinger/pymol-open-source) fromhttps://github.com/yamule/SurfStamp-pymol-plugin.
Nonsense mediated decay and a novel protein Period-2 regulatecasein kinase Iin an opposing manner to control circadian period inNeurospora crassa
Authors: Kelliher Christina M. , Lambreghts Randy , Xiang Qijun , Baker Christopher L. , Loros Jennifer J. , Dunlap Jay C. 
Published: October 2020

AbstractCircadian clocks in fungi and animals are driven by a functionally conserved transcription-translation feedback loop. InNeurospora crassa, negative feedback is executed by a complex of Frequency (FRQ), FRQ-interacting RNA helicase (FRH), and Casein Kinase I (CKI), which inhibits the activity of the clock’s positive arm, the White Collar Complex (WCC). Here, we show that theperiod-2gene, whose mutation is characterized by recessive inheritance of a long 26-hour period phenotype, encodes an RNA-binding protein that stabilizes theck-1atranscript, resulting in CKI protein levels sufficient for normal rhythmicity. Moreover, by examining the molecular basis for the short circadian period ofperiod-6mutants, we uncovered a strong influence of the Nonsense Mediated Decay pathway on CKI levels. The finding that circadian period defects in two classically-derivedNeurosporaclock mutants each arise from disruption ofck-1aregulation is consistent with circadian period being exquisitely sensitive to levels ofcasein kinase I.
Purinergic P2Y1 and P2Y2/4 receptors elicit distinct Ca2+signaling patterns in hepatocytes via differential feedback regulation by Protein Kinase C
Authors: Corrêa-Velloso Juliana C. , Bartlett Paula J. , Brumer Robert , Gaspers Lawrence , Ulrich Henning , Thomas Andrew P. 
Published: October 2020

AbstractExtracellular nucleotides are key regulators of liver physiology. In primary rat hepatocytes, P2Y1 receptor (P2Y1R) activation by ADP generates cytosolic calcium ([Ca2+]c) oscillations with narrow spikes, whereas P2Y2/4R activation by UTP led to more complex broad [Ca2+]coscillations. Both [Ca2+]coscillation signatures were observed with the common agonist ATP. Inhibition of Gαqsignaling with YM-254890 abolished ATP-induced [Ca2+]coscillations, indicating that they depend on inositol 1,4,5-trisphosphate (IP3), and are not mediated by P2X receptors. The narrow P2Y1-linked [Ca2+]cspikes and the broad P2Y2/4-linked [Ca2+]cspikes are shaped by differential and complex PKC-mediated feedback mechanisms. Downregulation of PKC broadened both ADP- and UTP-induced [Ca2+]coscillations, with a more pronounced effect on the former. PKC downregulation also selectively elicited a more robust response to ADP stimulation, enhancing oscillatory and sustained [Ca2+]cresponses. Acute PKC modulation confirmed the importance of the negative PKC feedback regulation of P2Y1R-linked [Ca2+]csignals; such that PKC activation decreased [Ca2+]coscillation frequency and PKC inhibition increased [Ca2+]cspike width. However, both PKC activation and inhibition decreased the spike width of P2Y2/4R-induced [Ca2+]coscillations, suggesting that multiple opposing PKC feedback mechanisms shape P2Y2/4R responses. Significantly, plasma membrane Ca2+entry was required for negative PKC feedback on P2Y1R-linked [Ca2+]coscillations, whereas P2Y2/4R-linked [Ca2+]coscillations were less sensitive to negative regulation by PKC and independent of Ca2+influx. Thus, differential feedback regulation by PKC gives rise to receptor-specific [Ca2+]coscillation profiles, which can encode the diverse physiological and pathophysiological responses to distinct agonists that all act through the IP3signaling cascade.
Epitope profiling reveals binding signatures of SARS-CoV-2 immune response and cross-reactivity with endemic HCoVs
Authors: Stoddard Caitlin I. , Galloway Jared , Chu Helen Y. , Shipley Mackenzie M. , Itell Hannah L. , Wolf Caitlin R. , Logue Jennifer K. , Magedson Ariana , Sung Kevin , Garrett Meghan , Crawford Katharine H.D. , Laserson Uri , Matsen Frederick A. , Overbaugh Julie 
Published: October 2020

AbstractA major goal of current SARS-CoV-2 vaccine efforts is to elicit antibody responses that confer protection. Mapping the epitope targets of the SARS-CoV-2 antibody response is critical for innovative vaccine design, diagnostics, and development of therapeutics. Here, we developed a phage display library to map antibody binding sites at high resolution within the complete viral proteomes of all human-infecting coronaviruses in patients with mild or moderate/severe COVID-19. The dominant immune responses to SARS-CoV-2 were targeted to regions spanning the Spike protein, Nucleocapsid, and ORF1ab. Some epitopes were identified in the majority of samples while others were rare, and we found variation in the number of epitopes targeted by different individuals. We also identified a set of cross-reactive sequences that were bound by antibodies in SARS-CoV-2 unexposed individuals. Finally, we uncovered a subset of enriched epitopes from commonly circulating human coronaviruses with significant homology to highly reactive SARS-CoV-2 sequences.