bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design and development of a vortex ring generator to study the impact of the ring as a gust
Authors: Gupta Dipendra , Sane Sanjay P. , Arakeri Jaywant H. 
Published: October 2020

ABSTRACTWe present a simple method to generate discrete aerodynamic gust under controlled laboratory condition in the form of a vortex ring which, unlike conventional methods of perturbation, is well studied and highly controllable. We characterized the flow properties of the vortex ring using flow visualization and novel light bead method. Reynolds number of the vortex ring, based on its average propagation velocity and nozzle exit diameter, was 16000. We demonstrate this method by studying the impact of head-on gust on freely flying soldier flies, Reynolds number of which, based on its wingtip velocity and mean wing chord, was 1100. We also present simple theoretical models to characterize the vortex ring based on generating conditions. The device can also be used to generate continuous gust in any direction and can be applied, in general, to study the gust response of natural fliers and swimmers, man-made micro aerial vehicles and aquatic plant lives.
Jurassic NLR: conserved and dynamic evolutionary features of the atypically ancient immune receptor ZAR1
Authors: Adachi Hiroaki , Sakai Toshiyuki , Kourelis Jiorgos , Pai Hsuan , Gonzalez Hernandez Jose L. , Maqbool Abbas , Kamoun Sophien 
Published: October 2020

ABSTRACTIn plants, NLR immune receptors generally exhibit hallmarks of rapid evolution even at the intraspecific level. We used iterative sequence similarity searches coupled with phylogenetic analyses to reconstruct the evolutionary history of ZAR1, an atypically conserved NLR that traces its origin to early flowering plant lineages ∼220 to 150 million years ago (Jurassic period). We discovered 120 ZAR1 orthologs in 88 species, including the monocotColacasia esculenta, the magnoliidCinnamomum micranthumand the majority of eudicots, notably the early diverging eudicot speciesAquilegia coerulea. Ortholog sequence analyses revealed highly conserved features of ZAR1, including regions for pathogen effector recognition, intramolecular interactions and cell death activation. We functionally reconstructed the cell death activity of ZAR1 and its partner receptor-like cytoplasmic kinase (RLCK) from distantly related plant species, experimentally validating the hypothesis that ZAR1 has evolved to be a partner with RLCKs early in its evolution. In addition, ZAR1 acquired novel features, such as a C-terminal integration of a thioredoxin-like domain. ZAR1 duplicated into two paralog families, which underwent distinct evolutionary paths. We conclude that ZAR1 stands out among angiosperm NLRs for having experienced relatively limited gene duplication and expansion throughout its deep evolutionary history. Nonetheless, ZAR1 did also give rise to non-canonical NLR proteins with integrated domains and degenerated molecular features.
Between-subject correlation of heart rate variability predicts movie preferences
Authors: So Tsz Yan , Li Man Yi Erica , Lau Hakwan 
Published: October 2020

AbstractWe introduce a novel and simple method for assessing audiences’ emotional responses to audiovisuals (e.g. films). Viewers (N=21) watched movies and TV commercials from different genres while wearing photoplethysmography (PPG) optic sensors on their wrists. Heart rate variability (HRV) synchrony was observed among the audience. Based on this between-subject synchrony measure, we identified emotionally arousing segments from the materials. New participants (N=24;N=16) were then invited to watch these identified segments along with some randomly selected segments as control; they reported that the former was more engaging (effect sizew=.67;w=.5). This finding was confirmed in an online study with a larger cohort (N=300). While some specific effects varied depending on movie genre or gender, HRV-based editing generally performed better than the control. These findings suggest that HRV synchrony can be used as a new tool for audience psychology, and potentially also for automatically creating short trailers out of movies in a principled manner while taking into account the human perspective.
Synapse-specific direction selectivity in retinal bipolar cell axon terminals
Authors: Matsumoto Akihiro , Agbariah Weaam , Nolte Stella Solveig , Andrawos Rawan , Levi Hadara , Sabbah Shai , Yonehara Keisuke 
Published: October 2020

AbstractThe ability to encode the direction of image motion is fundamental to our sense of vision. Direction selectivity along the four cardinal directions is thought to originate in direction-selective ganglion cells (DSGCs), due to directionally-tuned GABAergic suppression by starburst cells. Here, by utilizing two-photon glutamate imaging to measure synaptic release, we reveal that direction selectivity along all four directions arises earlier than expected, at bipolar cell outputs. Thus, DSGCs receive directionally-aligned glutamatergic inputs from bipolar cell boutons. We further show that this bouton-specific tuning relies on cholinergic excitation and GABAergic inhibition from starburst cells. In this way, starburst cells are able to refine directional tuning in the excitatory visual pathway by modulating the activity of DSGC dendrites and their axonal inputs using two different neurotransmitters.
Development of an orally-administrable tumor vasculature-targeting therapeutic using annexin A1-binding D-peptides
Authors: Nonaka Motohiro , Mabashi-Asazuma Hideaki , Jarvis Donald L. , Yamasaki Kazuhiko , Akama Tomoya O. , Nagaoka Masato , Sasai Toshio , Kimura-Takagi Itsuko , Suwa Yoichi , Yaegashi Takashi , Huang Chun-Ten , Nishizawa-Harada Chizuko , Fukuda Michiko N. 
Published: October 2020

ABSTRACTIF7 peptide, which binds to the annexin A1 (ANXA1) N-terminal domain, functions as a tumor vasculature-targeted drug delivery vehicle after intravenous injection. To enhance IF7 stability in vivo, we undertook mirror-image peptide phage display using a synthetic D-peptide representing the Anxa1 N-terminus as target. Peptide sequences were identified, synthesized as D-amino acids, and designated as dTIT7, which was shown to bind the ANXA1 N-terminus. Whole body imaging of mouse brain tumors modeled with near infrared fluorescent IRDye-conjugated dTIT7 showed fluorescent signals in brain and kidney. Furthermore, orally-administered geldanamycin (GA)-conjugated dTIT7 suppressed brain tumor growth. Ours is a proof-of-concept experiment showing that Anxa1-binding D-peptide could be developed as an orally-administrable, tumor vasculature-targeted therapeutic.Role of each author: MN designed and performed experiments, analyzed data, and wrote the manuscript; HMA and DLJ produced recombinant ANXA1 protein; KY conducted NMR analysis and data analysis; TOA designed, performed and analyzed LC-MS/MS data; MN, TS, IKT, YS, and TY analyzed peptide-binding assays and performed in silico structural analysis; CTU produced lentivirus for luciferase expression; CNH performed peptide binding assays, tissue culture and animal experiments; and MNF supervised the project and wrote the manuscript.
A protease protection assay for the detection of internalized alpha-synuclein pre-formed fibrils
Authors: Jarvela Timothy S. , Chaplot Kriti , Lindberg Iris 
Published: October 2020

ABSTRACTAlpha-synuclein pre-formed fibrils (PFFs) represent a promising model system for the study of cellular processes underlying cell-to-cell transmission of alpha-synuclein proteopathic aggregates. However, the ability to differentiate the fate of internalized PFFs from those which remain in the extracellular environment remains limited due to the propensity for PFFs to adhere to the cell surface. Removal of PFFs requires repeated washing and/or specific quenching of extracellular fluorescent PFF signals. In this paper we present a new method for analyzing the fate of internalized alpha-synuclein. We inserted a tobacco etch virus (TEV) protease cleavage site between alpha-synuclein and green fluorescent protein and subjected cells to brief treatment with TEV protease after incubation with tagged PFFs. As the TEV protease is highly specific, non-toxic, and active under physiological conditions, protection from TEV cleavage can be used to distinguish internalized PFFs from those which remain attached to the cell surface. Using this experimental paradigm, downstream intracellular events can be analyzed via live or fixed cell microscopy as well as by Western blotting. We suggest that this method will be useful for understanding the fate of PFFs after endocytosis under various experimental manipulations.
Relationship between personality and cognitive traits in domestic rabbits (Oryctolagus cuniculus)
Authors: GomezdelaTorre Clavel Macarena G. , Youngblood Mason , Lahti David 
Published: October 2020

AbstractDomestication is the process by which species adapt to, and are artificially selected for, human-made environments. Few studies have explored how the process of domestication has affected the connection between behavioral traits and cognitive abilities in animals. This study investigated the relationship between personality and cognitive traits in domestic rabbits (Oryctolagus cuniculus). Fifteen individuals kept in a rabbit rescue facility were tested over a period of two months. We measured the linkage between behavioral traits (response to a novel object and exploration time) and cognitive performance. Our results suggest that there is no relationship between personality traits and problem solving abilities in domestic rabbits. In addition, our results suggest that exploration time is significantly repeatable at the individual level while latency to approach a novel object is not. Thus further research is needed to explore the relationship between cognitive and personality traits in domestic rabbits.
Using Machine Learning To Develop A Fully Automated Soybean Nodule Acquisition Pipeline (SNAP)
Authors: Jubery Talukder Zaki , Carley Clayton N. , Singh Arti , Sarkar Soumik , Ganapathysubramanian Baskar , Singh Asheesh K. 
Published: October 2020

AbstractNodules form on plant roots through the symbiotic relationship between soybean (Glycine maxL. Merr.) roots and bacteria (Bradyrhizobium japonicum), and are an important structure where atmospheric nitrogen (N2) is fixed into bio-available ammonia (NH3) for plant growth and developmental. Nodule quantification on soybean roots is a laborious and tedious task; therefore, assessment is done on a less informative qualitative scale. We report the Soybean Nodule Acquisition Pipeline (SNAP) for nodule quantification that combines RetinaNet and UNet deep learning architectures for object (i.e., nodule) detection and segmentation. SNAP was built using data from 691 unique roots from diverse soybean genotypes, vegetative growth stages, and field locations; and has a prediction accuracy of 99%. SNAP reduces the human labor and inconsistencies of counting nodules, while acquiring quantifiable traits related to nodule growth, location and distribution on roots. The ability of SNAP to phenotype nodules on soybean roots at a higher throughput enables researchers to assess the genetic and environmental factors, and their interactions on nodulation from an early development stage. The application of SNAP in research and breeding pipelines may lead to more nitrogen use efficient soybean and other legume species cultivars, as well as enhanced insight into the plant-Bradyrhizobiumrelationship.
Sustained nitrogen loss in a symbiotic association of ComammoxNitrospiraand Anammox bacteria
Authors: Gottshall Ekaterina Y. , Bryson Sam J. , Cogert Kathryn I. , Landreau Matthieu , Sedlacek Christopher J. , Stahl David A. , Daims Holger , Winkler Mari 
Published: October 2020

ABSTRACTThe discovery of complete aerobic and anaerobic ammonia-oxidizing bacteria (Comammox and Anammox) significantly altered our understanding of the global nitrogen cycle. A high affinity for ammonia (Km(app),NH3≈ 63nM) and oxygen place the first described isolate, ComammoxNitrospira inopinatain the same trophic category as organisms such as some ammonia-oxidizing archaea. However,N. inopinatahas a relatively low affinity for nitrite (Km,NO2≈ 449.2μM) suggesting it would be less competitive for nitrite than other nitrite-consuming aerobes and anaerobes. We examined the ecological relevance of the disparate substrate affinities by coupling it with Anammox (Nitrospira inopinataandBrocadia anammoxidans, respectively). Synthetic communities were established in hydrogel granules in which Comammox grew in the aerobic outer layer to provide Anammox with nitrite in the inner anoxic core to form dinitrogen gas. This spatial organization was confirmed with FISH imaging, supporting a mutualistic or commensal relationship. Successful co-habitation of ComammoxN. inopinataand Anammox in synthetic granules broadens our limited understanding of the interplay between these two species and offers potential biotechnological applications to study any type of bacterial pairings in a systematic and reproducible manner.
Post-transcriptional regulation of redox homeostasis by the small RNA SHOxi in haloarchaea
Authors: Gelsinger Diego Rivera , Reddy Rahul , Whittington Kathleen , Debic Sara , DiRuggiero Jocelyne 
Published: October 2020

ABSTRACTHaloarchaea are highly resistant to oxidative stress, however, a comprehensive understanding of the processes regulating this remarkable response is lacking. Oxidative stress-responsive small non-coding RNAs (sRNAs) have been reported in the model archaeon,Haloferax volcanii, but targets and mechanisms have not been elucidated. Using a combination of high throughput and reverse molecular genetic approaches, we elucidated the functional role of the most up-regulated intergenic sRNA during oxidative stress inH. volcanii, namedSmall RNA inHaloferaxOxidative Stress (SHOxi). SHOxi was predicted to form a stable secondary structure with a conserved stem-loop region as the potential binding site for trans-targets. NAD-dependent malic enzyme mRNA, identified as a putative target of SHOxi, interacted directly with a putative “seed” region within the predicted stem loop of SHOxi. Malic enzyme is an enzyme of the tricarboxylic acid cycle that catalyzes the oxidative decarboxylation of malate into pyruvate using NAD+as a cofactor. The destabilization of malic enzyme mRNA, and the decrease in the NAD+/NADH ratio, resulting from the direct RNA-RNA interaction between SHOxi and its trans-target was essential for the survival ofH. volcaniito oxidative stress. These findings indicate that SHOxi likely regulates redox homeostasis during oxidative stress by the post-transcriptional destabilization of malic enzyme mRNA. SHOxi-mediated regulation provides evidence that the fine-tuning of metabolic cofactors could be a core strategy to mitigate damage from oxidative stress and confer resistance. This study is the first to establish the regulatory effects of sRNAs on mRNAs during the oxidative stress response in Archaea.
Expansion and transformation of the minor spliceosomal system in the slime moldPhysarum polycephalum
Authors: Larue Graham E. , Eliáš Marek , Roy Scott W. 
Published: October 2020

AbstractSpliceosomal introns interrupt nuclear genes and are removed from RNA transcripts (“spliced”) by machinery called spliceosomes. While the vast majority of spliceosomal introns are removed by the so-called major spliceosome, diverse eukaryotes also contain a mysterious second form, the minor spliceosome, and associated introns [1–3]. In all characterized species, minor introns are distinguished by several features, including being rare in the genome (∼0.5% of all introns) [4–6], containing extended evolutionary-conserved splicing sites [4,5,7,8], being generally ancient [9,10] and being inefficiently spliced [11–13]. Here, we report a remarkable exception in the slime moldPhysarum polycephalum. TheP. polycephalumgenome contains > 20,000 minor introns—25 times more than any other species—with transformed splicing signals that have co-evolved with the spliceosome due to massive gain of efficiently spliced minor introns. These results reveal an unappreciated dynamism of minor spliceosomal introns and spliceosomal introns in general.
A dominant-negative variant in the dopamine transporter PDZ-binding motif is linked to parkinsonism and neuropsychiatric disease
Authors: Herborg Freja , Jensen Kathrine L. , Tolstoy Sasha , Arends Natascha V. , Posselt Leonie P. , Shekar Aparna , Aguilar Jenny , Lund Viktor K. , Erreger Kevin , Rickhag Mattias , Lykas Matthew D. , Lonsdale Markus N. , Rahbek-Clemmensen Troels , Sørensen Andreas T. , Newman Amy H. , Løkkegaard Annemette , Kjærulff Ole , Werge Thomas , Møller Lisbeth B. , Matthies Heinrich JG , Galli Aurelio , Hjermind Lena E. , Gether Ulrik 
Published: October 2020

AbstractDopaminergic dysfunction is central to movement disorders and mental diseases. The dopamine transporter (DAT) is essential for the regulation of extracellular dopamine but the genetic and mechanistic link between DAT function and dopamine-related pathologies remains elusive. Particularly, the pathophysiological significance of monoallelic missense mutations in DAT is unknown. Here we identify a novel coding DAT variant, DAT-K619N, in a patient with early-onset parkinsonism and comorbid neuropsychiatric disease and in 22 individuals from exome-sequenced samples of neuropsychiatric patients. The variant localizes to the critical C-terminal PDZ-binding motif of DAT and causes reduced uptake capacity, decreased surface expression, and accelerated turnover of DATin vitro.In vivo, we demonstrate that expression of DAT-K619N in mice anddropsophilaimposes impairments in dopamine transmission with accompanying changes in dopamine-directed behaviors. Importantly, both cellular studies and viral overexpression of DAT-K619N in mice show that DAT-K619N has a dominant-negative effect which collectively implies that a single dominant-negative genetic DAT variant can confer risk for neuropsychiatric disease and neurodegenerative early-onset parkinsonism.
Viral protein engagement of GBF1 induces host cell vulnerability through synthetic lethality
Authors: Navare Arti T , Mast Fred D , Olivier Jean Paul , Bertomeu Thierry , Neal Maxwell , Carpp Lindsay N , Kaushansky Alexis , Coulombe-Huntington Jasmin , Tyers Mike , Aitchison John D 
Published: October 2020

AbstractViruses co-opt host proteins to carry out their lifecycle. Repurposed host proteins may thus become functionally compromised; a situation analogous to a loss-of-function mutation. We term such host proteins viral-induced hypomorphs. Cells bearing cancer driver loss-of-function mutations have successfully been targeted with drugs perturbing proteins encoded by the synthetic lethal partners of cancer-specific mutations. Synthetic lethal interactions of viral-induced hypomorphs have the potential to be similarly targeted for the development of host-based antiviral therapeutics. Here, we use GBF1, which supports the infection of many RNA viruses, as a proof-of-concept. GBF1 becomes a hypomorph upon interaction with the poliovirus protein 3A. Screening for synthetic lethal partners of GBF1 revealed ARF1 as the top hit, disruption of which, selectively killed cells that synthesize poliovirus 3A. Thus, viral protein interactions can induce hypomorphs that render host cells vulnerable to perturbations that leave uninfected cells intact. Exploiting viral-induced vulnerabilities could lead to broad-spectrum antivirals for many viruses, including SARS-CoV-2.SummaryUsing a viral-induced hypomorph of GBF1, Navare et al., demonstrate that the principle of synthetic lethality is a mechanism to selectively kill virus-infected cells.
Targeted Degradation of Transcription Factors by TRAFTACs: Transcription Factor Targeting Chimeras
Authors: Samarasinghe Kusal T. G. , Jaime-Figueroa Saul , Dai Katherine , Hu Zhenyi , Crews Craig M. 
Published: October 2020

AbstractMany diseases, including cancer, stem from aberrant activation and overexpression of oncoproteins that are associated with multiple signaling pathways. Although proteins with catalytic activity are able to be successfully drugged, the majority of other protein families, such as transcription factors, remain intractable due to their lack of ligandable sites. In this study, we report the development of TRAnscription Factor TArgeting Chimeras (TRAFTACs) as a generalizable strategy for targeted transcription-factor degradation. Herein, we show that TRAFTACs, which consist of a chimeric oligonucleotide that simultaneously binds to the transcription-factor of interest (TOI) and to HaloTag fused dCas9 protein, can induce degradation of the former via the proteasomal pathway. Application of TRAFTACs to two oncogenic TOIs, NF-κB and brachyury, suggests that TRAFTACs can be successfully employed for the targeted degradation of other DNA-binding proteins with minor changes to the chimeric oligonucleotide.
Brain-Restricted mTOR Inhibition with Binary Pharmacology
Authors: Zhang Ziyang , Fan Qiwen , Luo Xujun , Lou Kevin J. , Weiss William A. , Shokat Kevan M. 
Published: October 2020

AbstractOn-target-off-tissue drug engagement is an important source of adverse effects that constrains the therapeutic window of drug candidates. In diseases of the central nervous system, drugs with brain-restricted pharmacology are highly desirable. Here we report a strategy to achieve inhibition of mTOR while sparing mTOR activity elsewhere through the use of a brain-permeable mTOR inhibitor RapaLink-1 and brain-impermeable FKBP12 ligand RapaBlock. We show that this drug combination mitigates the systemic effects of mTOR inhibitors but retains the efficacy of RapaLink-1 in glioblastoma xenografts. We further present a general method to design cell-permeable, FKBP12-dependent kinase inhibitors from known drug scaffolds. These inhibitors are sensitive to deactivation by RapaBlock enabling the brain-restricted inhibition of their respective kinase targets.