bluuebunny/crossref_metadata_2025_split huggingface dataset:
Huntingtin fibrils with different toxicity, structure, and seeding potential can be reversibly interconverted
Authors: Isas J. Mario , Pandey Nitin K. , Teranishi Kazuki , Okada Alan K. , Applebaum Anise , Meier Franziska , Langen Ralf , Siemer Ansgar B. 
Published: July 2019

AbstractThe first exon of the huntingtin protein (HTTex1) important in Huntington’s Disease (HD) can form cross-β fibrils of varying toxicity. We find that the difference between these fibrils is the degree of entanglement and dynamics of the C-terminal proline-rich domain (PRD) in a mechanism analogous to polyproline film formation. In contrast to fibril strains found for other cross-β fibrils, these HTTex1 fibril types can be reversibly interconverted. This is because the structure of their polyQ fibril core remains unchanged. Further, we find that more toxic fibrils of low entanglement have higher affinities for protein interactors and are more effective seeds for recombinant HTTex1 and HTTex1 in cells. Together these data show how the structure of a framing sequence at the surface of a fibril can modulate seeding, protein-protein interactions, and thereby toxicity in neurodegenerative disease.
ASCL1-regulated DARPP-32 and t-DARPP stimulate small cell lung cancer growth and neuroendocrine tumor cell survival
Authors: Alam Sk. Kayum , Wang Li , Ren Yanan , Hernandez Christina E. , Kosari Farhad , Roden Anja C. , Yang Rendong , Hoeppner Luke H. 
Published: July 2019

AbstractSmall cell lung cancer (SCLC) is the most aggressive form of lung cancer, and new molecular insights are necessary for prognostic and therapeutic advances. Here we demonstrate in orthotopic mouse models that dopamine and cAMP-regulated phosphoprotein, Mr 32000 (DARPP-32) and its N-terminally truncated splice variant t-DARPP promote SCLC growth through increased proliferation, Akt/Erk-mediated survival and anti-apoptotic signaling. DARPP-32 and t-DARPP proteins are overexpressed in SCLC patient-derived tumor tissue, but virtually undetectable in physiologically normal lung. RNA sequencing analysis reveals a subset of SCLC patients with high tumoral t-DARPP expression and upregulated Notch signaling genes, including achaete-scute homologue 1 (ASCL1). We show that DARPP-32 isoforms are transcriptionally activated by ASCL1 in human SCLC cells. Taken together, we demonstrate new regulatory mechanisms of SCLC oncogenesis that suggest DARPP-32 isoforms may represent a negative prognostic indicator for SCLC and serve as a potential target for the development of new therapies.
Diffusion analysis of single particle trajectories in a Bayesian nonparametrics framework
Authors: Falcao Rebeca Cardim , Coombs Daniel 
Published: July 2019

AbstractSingle particle tracking (SPT), where individual molecules are fluorescently labelled and followed over time, is an important tool that allows the spatiotemporal dynamics of subcellular biological systems to be studied at very fine temporal and spatial resolution. Mathematical models of particle motion are typically based on Brownian diffusion, reflecting the noisy environment that biomolecules typically inhabit. In order to study changes in particle behaviour within individual tracks, Hidden Markov models (HMM) featuring multiple diffusive states have been used as a descriptive tool for SPT data. However, such models are typically specified with an a-priori defined number of particle states and it has not been clear how such assumptions have affected their outcomes. Here, we propose a method for simultaneously inferring the number of diffusive states alongside the dynamic parameters governing particle motion. Our method is an infinite HMM (iHMM) within the general framework of Bayesian non-parametric models. We directly extend previous applications of these concepts in molecular biophysics to the SPT framework and propose and test an additional constraint with the goal of accelerating convergence and reducing computational time. We test our iHMM using simulated data and apply it to a previously-analyzed large SPT dataset for B cell receptor motion on the plasma membrane of B cells of the immune system.
The Ciliary Lumen Accommodates Passive Diffusion and Vesicle Trafficking in Cytoplasmic-Ciliary Transport
Authors: Ruba Andrew , Luo Wangxi , Yu Jingjie , Takao Daisuke , Evangelou Athanasios , Higgins Rachel , Khim Saovleak , Verhey Kristen J. , Yang Weidong 
Published: July 2019

AbstractTransport of membrane and cytosolic proteins into the primary cilium is essential for its role in cellular signaling. Using single molecule microscopy, we mapped the movement of membrane and soluble proteins at the base of the primary cilium. In addition to the well-known intraflagellar transport (IFT) route, we identified two new pathways within the lumen of the primary cilium - passive diffusional and vesicle transport routes - that are adopted by proteins for cytoplasmic-cilium transport in live cells. Independent of the IFT path, approximately half of IFT motors (KIF3A) and cargo (α-tubulin) take the passive diffusion route and more than half of membrane-embedded G protein coupled receptors (SSTR3 and HTR6) use RAB8A-regulated vesicles to transport into and inside cilia. Furthermore, ciliary lumen transport is the preferred route for membrane proteins in the early stages of ciliogenesis and inhibition of SSTR3 vesicle transport completely blocks ciliogenesis. Furthermore, clathrin-mediated, signal-dependent internalization of SSTR3 also occurs through the ciliary lumen. These transport routes were also observed inChlamydomonas reinhardtiiflagella, suggesting their conserved roles in trafficking of ciliary proteins.
Instructor-learner brain coupling discriminates between instructional approaches and predicts learning
Authors: Pan Yafeng , Dikker Suzanne , Goldstein Pavel , Zhu Yi , Yang Cuirong , Hu Yi 
Published: July 2019

AbstractThe neural mechanisms that support naturalistic learning via effective pedagogical approaches remain elusive. Here we use functional near-infrared spectroscopy to measure brain activity from instructor-learner dyads simultaneously during dynamic conceptual learning. We report that brain-to-brain coupling is correlated with learning outcomes, and, crucially, appears to be driven by specific scaffolding behaviors on the part of the instructors (e.g., asking guiding questions or providing hints). Brain-to-brain coupling enhancement is absent when instructors use an explanation approach (e.g., providing definitions or clarifications). Finally, we find that machine-learning techniques are more successful when decoding instructional approaches (scaffolding vs. explanation) from brain-to-brain coupling data than when using a single-brain method. These findings suggest that brain-to-brain coupling as a pedagogically relevant measure tracks the naturalistic instructional process during instructor-learner interaction throughout constructive engagement, but not information clarification.
Single-cell sequencing reveals a clonal expansion of pro-inflammatory synovial CD8 T cells expressing tissue homing receptors in psoriatic arthritis
Authors: Penkava Frank , Del Castillo Velasco-Herrera Martin , Young Matthew D , Yager Nicole , Lara Alicia Lledo , Guzzo Charlotte , Maroof Ash , Mamanova Lira , Cole Suzanne , Efremova Mirjana , Simone Davide , Brown Chrysothemis C , Croxford Andrew L , Teichmann Sarah , Bowness Paul , Behjati Sam , Al-Mossawi M Hussein 
Published: July 2019

AbstractPsoriatic arthritis (PsA) is a debilitating immune-mediated inflammatory arthritis of unknown pathogenesis commonly affecting patients with skin psoriasis. We used three complementary single cell approaches to study leukocytes from PsA joints. Mass cytometry (CyTOF) demonstrated marked (>3 fold) expansion of memory CD8 T cells in the joints compared to matched blood. Further exploration of the memory CD8 compartment using both droplet and plate based single cell RNA sequencing of paired alpha and beta chain T cell receptor sequences identified pronounced CD8 T cell clonal expansions within the joints, strongly suggesting antigen driven expansion. These clonotypes exhibited distinct gene expression profiles including cycling, activation, tissue homing and tissue residency markers. Pseudotime analysis of these clonal CD8 populations identified trajectories in which tissue residency can represent an intermediate developmental state giving rise to activated, cycling and exhausted CD8 populations. Comparing T-cell clonality across patients further revealed specificity convergence of clones against a putative common antigen. We identify chemokine receptor CXCR3 as upregulated in expanded synovial clones, and elevation of two CXCR3 ligands, CXCL9 and CXCL10, in PsA synovial fluid.
Tetrad analysis without tetrad dissection: Meiotic recombination and genomic diversity in the yeast Komagataella phaffii (Pichia pastoris)
Authors: Braun-Galleani Stephanie , Dias Julie A. , Coughlan Aisling Y. , Ryan Adam P. , Byrne Kevin P. , Wolfe Kenneth H. 
Published: July 2019

AbstractKomagataella phaffii is a yeast widely used in the pharmaceutical and biotechnology industries, and is one of the two species that were formerly called Pichia pastoris. However, almost all laboratory work on K. phaffii has been done on strains derived from a single natural isolate, CBS7435. There is little information about the genetic properties of K. phaffii or its sequence diversity. Genetic analysis is difficult because, although K. phaffii makes asci with four spores, the spores are small and tend to clump together, making the asci hard to dissect. Here, we sequenced the genomes of all the known isolates of this species, and find that K. phaffii has only been isolated from nature four times. We analyzed the meiotic recombination landscape in a cross between auxotrophically marked strains derived from two isolates that differ at 44,000 single nucleotide polymorphism sites. We conducted tetrad analysis by making use of the property that haploids of this species do not mate in rich media, which enabled us to isolate and sequence the four types of haploid cell that are present in the colony that forms when a tetratype ascus germinates. We found that approximately 25 crossovers occur per meiosis, which is 3.5 times fewer than in Saccharomyces cerevisiae. Recombination is suppressed, and genetic diversity among natural isolates is low, in a region around centromeres that is much larger than the centromeres themselves. Our method of tetrad analysis without tetrad dissection will be applicable to other species whose spores do not mate spontaneously after germination.Author summaryTo better understand the basic genetics of the budding yeast Komagataella phaffii, which has many applications in biotechnology, we investigated its genetic diversity and its meiotic recombination landscape. We made a genetic cross between strains derived from two natural isolates, and developed a method for characterizing the genomes of the four spores resulting from meiosis, which were previously impossible to isolate. We found that K. phaffii has a lower recombination rate than Saccharomyces cerevisiae. It shows a large zone of suppressed recombination around its centromeres, which may be due to the structural differences between centromeres in K. phaffii and S. cerevisiae.
Biodiversity conservation in cities: Defining habitat analogs for plant species of conservation interest
Authors: Itani M , Al Zein M. , Nasralla N. , Talhouk S. N. 
Published: July 2019

AbstractUrban plant habitats have become primary drivers of species interactions. They consist of managed vegetation and spontaneous assemblages of native, naturalized, ornamental garden escapes, and invasive species. Our objective was to define urban habitat analogs for a plant species of conservation interest,Matthiola crassifolia,which has persisted in varying abundance in the Mediterranean city of Beirut.We adopted a stepwise method that integrates two vegetation assessments, floristics, and physiognomy. We placed seventy-eight quadrats (1m x 1m) in 12 study sites following a deliberate biased method to capture habitat diversity. In every quadrat, we performed taxonomic identification and recorded life form of each species. We pooled species that shared the same life form into categories and estimated area cover for each of these life forms. We performed TWINSPAN analysis on floristic data to identify species positively associated withM. crassifolia,and on life forms, to determine plant assemblages that promote optimalM. crassifoliarepresentation. We then combined findings from both analyses to generate a description of urban habitat analogs suitable forM. crassifolia.The results revealed that urban habitat analogs favorable toM. crassifoliainclude green spaces dominated by palms, low-lying succulents, or by shrubs with scale-like leaves. On the other hand, spaces dominated by turf grass, canopy trees, or vegetation that produces significant litter were not favorable toM. crassifolia’s persistence. Based on these findings, we generated a plant palette of native and non-native species to design urban habitat analogs favorable to the persistence ofM. crassifolia.Synthesis and applicationsThe application of this method can inform planting designs that yield suitable habitats for plants of conservation interest. It can also guide landscape management plans that seek to create or modify green spaces to optimize growing conditions for species of conservation interest. Depending on sites, and based on the information generated by the stepwise method, designers and managers may decide to exclude life forms of native or non-native species that do not support the growth of a species of conservation interest, or they may create an artificial habitat that is conducive to its persistence.
A Kinesin-3 Recruitment Complex Facilitates Axonal Sorting of Enveloped Alpha Herpesvirus Capsids
Authors: Scherer Julian , Hogue Ian B. , Yaffe Zachary A. , Tanneti Nikhila S. , Winer Benjamin Y. , Vershinin Michael , Enquist Lynn W. 
Published: July 2019

AbstractAxonal sorting, the controlled passage of specific cargoes from the cell soma into the axon compartment, is critical for establishing and maintaining the polarity of mature neurons. To delineate axonal sorting events, we took advantage of two neuroinvasive alpha-herpesviruses. Human herpes simplex virus 1 (HSV-1) and pseudorabies virus of swine (PRV; suid herpesvirus 1) have evolved as robust cargo of axonal sorting and transport mechanisms. For efficient axonal sorting and subsequent egress from axons and presynaptic termini, progeny capsids depend on three viral membrane proteins (Us7 (gI), Us8 (gE), and Us9), which engage axon-directed kinesin motors. We present evidence that Us7-9 of the veterinary pathogen pseudorabies virus (PRV) form a tripartite complex to recruit Kif1a, a kinesin-3 motor. Based on multi-channel super-resolution and live TIRF microscopy, complex formation and motor recruitment occurs at the trans-Golgi network. Subsequently, progeny virus particles enter axons as enveloped capsids in a transport vesicle. Artificial recruitment of Kif1a using a drug-inducible heterodimerization system was sufficient to rescue axonal sorting and anterograde spread of PRV mutants devoid of Us7-9. Importantly, biophysical evidence suggests that Us9 is able to increase the velocity of Kif1a, a previously undescribed phenomenon. In addition to elucidating mechanisms governing axonal sorting, our results provide further insight into the composition of neuronal transport systems used by alpha-herpesviruses, which will be critical for both inhibiting the spread of infection and the safety of herpesvirus-based oncolytic therapies.Author SummaryAlpha-herpesviruses represent a group of large, enveloped DNA viruses that are capable to establish a quiescent (also called latent) but reactivatable form of infection in the peripheral nervous system of their hosts. Following reactivation of latent genomes, virus progeny are formed in the soma of neuronal cells and depend on sorting into the axon for anterograde spread of infection to mucosal sites and potentially new host. We studied two alpha-herpesviruses (the veterinary pathogen pseudorabies virus (PRV) and human herpes simplex virus 1 (HSV-1)) and found viral membrane proteins Us7, Us8, and Us9 to form a complex, which is able to recruit kinsin-3 motors. Motor recruitment facilitates axonal sorting and subsequent transport to distal egress sites. Complex formation occurs at the trans-Golgi network and mediates efficiency of axonal sorting and motility characteristics of egressing capsids. We also used an artificial kinesin-3 recruitment system, which allows controlled induction of axonal sorting and transport for virus mutants lacking Us7, Us8, and Us9. Overall, these data contribute to our understanding of anterograde alpha-herpesvirus spread and kinesin-mediated sorting of vesicular axonal cargoes.
CD8+ T-cell-mediated immunoediting influences genomic evolution and immune evasion in murine gliomas
Authors: Kane J. Robert , Zhao Junfei , Tsujiuchi Takashi , Laffleur Brice , Mahajan Aayushi , Rao Ganesh , Mela Angeliki , Dmello Crismita , Arrieta Víctor A. , Chen Li , Zhang Daniel Y. , Gonzalez-Buendia Edgar , Lee-Chang Catalina , Xiao Ting , Rothschild Gerson , Basu Uttiya , Horbinski Craig , Lesniak Maciej S. , Heimberger Amy B. , Rabadan Raul , Canoll Peter D. , Sonabend Adam M. 
Published: July 2019

AbstractCancer immunoediting shapes tumor progression by the selection of tumor cell variants that can evade immune recognition. Given the immune evasion and intra-tumor heterogeneity intrinsic to gliomas, we hypothesized that CD8+ T-cells mediate immunoediting in these tumors. We evaluated glioma progression in the absence of CD8+ T-cells by depleting this immune cell population in transgenic murine gliomas. Upon transplantation, gliomas that developed in the absence of CD8+ T-cells engrafted poorly in recipients with intact immunity but engrafted well in those with CD8+ T-cell depletion. Gliomas developed in absence of CD8+ T-cells exhibited increased chromosomal instability, MAPK signaling, gene fusions, and macrophage/microglial infiltration. MAPK activation correlated with macrophage/microglial recruitment in this model and in the human disease. Our results indicate that CD8+ T-cells mediate immunoediting during gliomagenesis, influencing the genomic stability of glioma and its microenvironment, leading to immune evasion.SignificanceImmune evasion renders cancer resistant to anti-tumoral immunity. Therapeutic intervention often fails for gliomas because of the plasticity of tumor cell variants that resist immune surveillance. Our results demonstrate a mechanism of immune evasion in gliomas that derives from CD8+ T-cells during the development and progression of this disease.
Review of augmented reality in aerospace industry
Authors: Safi Maryam , Chung Joon , Pradhan Pratik 
Published: July 2019

PurposeThe purpose of this paper is to assess and determine the potential of augmented reality (AR) in aerospace applications through a survey of published sources.Design/methodology/approachThis paper reviews a database of AR applications developed for the aerospace sector in academic research or industrial training and operations. The review process begins with the classification of these applications, followed by a brief discussion on the implications of AR technology in each category.FindingsAR is abundantly applied in engineering, navigation, training and simulation. There is potential for application in in-flight entertainment and communication, crew support and airport operations monitoring.Originality/valueThis paper is a general review introducing existing and potential AR applications in various fields of the aerospace industry. Unlike previous publications, this article summarizes existing and emerging applications to familiarize readers with AR use in all of aerospace. The paper outlines example projects and creates a single comprehensive reference of AR advancements and its use in the aerospace industry. The paper provides individuals with a quick guide to available and emerging technology.
Derivation of knockdown factors for grid-stiffened cylinders considering various shell thickness ratios
Authors: Sim Chang-Hoon , Kim Han-Il , Park Jae-Sang , Lee Keejoo 
Published: July 2019

PurposeThe purpose of this paper is to derive knockdown factor functions in terms of a shell thickness ratio (i.e. the ratio of radius to thickness) for conventional orthogrid and hybrid-grid stiffened cylinders for the lightweight design of space launch vehicles.

Design/methodology/approachThe shell knockdown factors of grid-stiffened cylinders under axial compressive loads are derived numerically considering various shell thickness ratios. Two grid systems using stiffeners – conventional orthogrid and hybrid-grid systems – are used for the grid-stiffened cylinders. The hybrid-grid stiffened cylinder uses major and minor stiffeners having two different cross-sectional areas. For modeling grid-stiffened cylinders with various thickness ratios, the effective thickness (teff) of the cylinders is kept constant, and the radius of the cylinder is varied. Thickness ratios of 100, 192 and 300 are considered for the orthogrid stiffened cylinder, and 100, 160, 200 and 300 for the hybrid-grid stiffened cylinder. Postbuckling analyses of grid-stiffened cylinders are conducted using a commercial nonlinear finite element analysis code, ABAQUS, to derive the shell knockdown factor. The single perturbation load approach is applied to represent the geometrical initial imperfection of a cylinder. Knockdown factors are derived for both the conventional orthogrid and hybrid-grid stiffened cylinders for different shell thickness ratios. Knockdown factor functions in terms of shell thickness ratio are obtained by curve fitting with the derived shell knockdown factors for the two grid-stiffened cylinders.

FindingsFor the two grid-stiffened cylinders, the derived shell knockdown factors are all higher than the previous NASA’s shell knockdown factors for various shell thickness ratios, ranging from 100 to 400. Therefore, the shell knockdown factors derived in this study may facilitate in the development of lightweight structures of space launch vehicles from the aspect of buckling design. For different shell thickness ratios of up to 500, the knockdown factor of the hybrid-grid stiffened cylinder is higher than that of the conventional orthogrid stiffened cylinder. Therefore, it is concluded that the hybrid-grid stiffened cylinder is more efficient than the conventional orthogrid-stiffened cylinder from the perspective of buckling design.

Practical implicationsThe obtained knockdown factor functions may provide the design criteria for lightweight cylindrical structures of space launch vehicles.

Originality/valueDerivation of shell knockdown factors of hybrid-grid stiffened cylinders considering various shell thickness ratios is attempted for the first time in this study.