bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reconfigurable asymmetric protein assemblies through implicit negative design
Authors: Sahtoe Danny D. , Praetorius Florian , Courbet Alexis , Hsia Yang , Wicky Basile I.M. , Edman Natasha I. , Miller Lauren M. , Timmermans Bart J. R. , Morris Hana M. , Kang Alex , Bera Asim K. , Baker David 
Published: August 2021

AbstractAsymmetric multi-protein complexes that undergo subunit exchange play central roles in biology, but present a challenge for protein design. The individual components must contain interfaces enabling reversible addition to and dissociation from the complex, but be stable and well behaved in isolation. Here we employ a set of implicit negative design principles to generate beta sheet mediated heterodimers which enable the generation of a wide variety of structurally well defined asymmetric assemblies. Crystal structures of the heterodimers are very close to the design models, and unlike previously designed orthogonal heterodimer sets, the subunits are stable, folded and monomeric in isolation and rapidly assemble upon mixing. Rigid fusion of individual heterodimer halves to repeat proteins yields central assembly hubs that can bind two or three different proteins across different interfaces. We use these connectors to assemble linearly arranged hetero-oligomers with up to 6 unique components, branched hetero-oligomers, closed C4-symmetric two-component rings, and hetero-oligomers assembled on a cyclic homo-oligomeric central hub, and demonstrate such complexes can readily reconfigure through subunit exchange. Our approach provides a general route to designing asymmetric reconfigurable protein systems.
Structural basis for channel conduction in the pump-like channelrhodopsin ChRmine
Authors: Kishi Koichiro E. , Kim Yoon Seok , Fukuda Masahiro , Kusakizako Tsukasa , Thadhani Elina , Byrne Eamon F.X. , Paggi Joseph M. , Ramakrishnan Charu , Matsui Toshiki E. , Yamashita Keitaro , Nagata Takashi , Konno Masae , Wang Peter Y. , Inoue Masatoshi , Benster Tyler , Uemura Tomoko , Liu Kehong , Shibata Mikihiro , Nomura Norimichi , Iwata So , Nureki Osamu , Dror Ron O. , Inoue Keiichi , Deisseroth Karl , Kato Hideaki E. 
Published: August 2021

SummaryChRmine1, a recently-discovered bacteriorhodopsin-like cation-conducting channelrhodopsin1, 2, exhibits puzzling properties (unusually-large photocurrents, exceptional red-shift in action spectrum, and extreme light-sensitivity) that have opened up new opportunities in optogenetics1, 3–5. ChRmine and its homologs function as light-gated ion channels, but by primary sequence more closely resemble ion pump rhodopsins; the molecular mechanisms for passive channel conduction in this family of proteins, as well as the unusual properties of ChRmine itself, have remained mysterious. Here we present the cryo-electron microscopy structure of ChRmine at 2.0 Å resolution. The structure reveals striking architectural features never seen before in channelrhodopsins including trimeric assembly, a short transmembrane-helix 3 unwound in the middle of the membrane, a prominently-twisting extracellular-loop 1, remarkably-large intracellular cavities and extracellular vestibule, and an unprecedented hydrophilic pore that extends through the center of the trimer, separate from the three individual monomer pores. Electrophysiological, spectroscopic, and computational analyses provide insight into conduction and gating of light-gated channels with these distinct design features, and point the way toward structure-guided creation of novel channelrhodopsins for optogenetic applications in biology.
Hyperactive chemotaxis contributes to anti-TNFα treatment resistance in inflammatory bowel disease
Authors: Yau Tung On , Vadakekolathu Jayakumar , Foulds Gemma Ann , Du Guodong , Polytarchou Christos , Dickins Benjamin , Rutella Sergio 
Published: August 2021

AbstractBackground & AimsAnti-tumour necrosis factor-alpha (anti-TNFα) agents have been used for inflammatory bowel disease (IBD), however, it has up to 30% non-response rate. Identifying molecular pathways and finding reliable diagnostic biomarkers for patient response to anti-TNFα treatment are clearly needed.MethodsPublicly available transcriptomic data from IBD patients receiving anti-TNFα therapy was systemically collected and integrated.In silicoflow cytometry approaches and MetaScape were applied to evaluate immune cell populations and to perform gene enrichment analysis, respectively. Genes identified within enrichment pathways validated in neutrophils were tracked in an anti-TNFα-treated animal model (with lipopolysaccharide (LPS)-induced inflammation). The receiver operating characteristic (ROC) curve was applied to all genes to identify the best prediction biomarkers.ResultsA total of 449 samples were retrieved from control, baseline and after primary anti-TNFα therapy or placebo. No statistically significant differences were observed between anti-TNFα treatment responders and non-responders at baseline in immune microenvironment scores. Neutrophils, endothelial and B cell populations were higher in baseline non-responders and chemotaxis pathways may contribute to the treatment resistance. Genes related to chemotaxis pathways were significantly up-regulated in LPS-induced neutrophils but no statistically significant changes were observed in neutrophils treated with anti-TNFα. Interleukin 13 receptor subunit alpha 2 (IL13RA2) is the best predictor (ROC: 80.7%, 95% CI: 73.8% - 87.5%) with a sensitivity of 68.13% and specificity of 84.93%, and significantly higher in non-responders compared to responders (p< 0.0001).ConclusionsHyperactive chemotaxis influences responses to anti-TNFα treatment andIL13RA2is a potential biomarker to predict anti-TNFα treatment response.
Citrus Huanglongbing is an immune-mediated disease that can be treated by mitigating reactive oxygen species triggered cell death of the phloem tissues caused by Candidatus Liberibacter asiaticus
Authors: Ma Wenxiu , Pang Zhiqian , Huang Xiaoen , Pandey Sheo Shankar , Li Jinyun , Xu Jin , Achor Diann S. , Vasconcelos Fernanda N.C. , Hendrich Connor , Huang Yixiao , Wang Wenting , Lee Donghwan , Wang Nian 
Published: August 2021

AbstractThe immune system is critical for keeping animals and plants healthy from pathogens. However, immune-mediated diseases are also common for human. Immune-mediated diseases have not been reported for plants. Here, we present evidence that citrus Huanglongbing (HLB), caused by phloem-colonizing Candidatus Liberibacter asiaticus (CLas), is an immune-mediated disease. CLas infection of Citrus sinensis stimulated systemic and chronic immune response in the phloem tissues including reactive oxygen species (ROS) production as indicated by H2O2, callose deposition, and induction of immune related genes. Systemic cell death of companion and sieve element cells, but not surrounding parenchyma cells, was observed following ROS production triggered by CLas. ROS production triggered by CLas localized in phloem tissues. The H2O2 concentration in exudates extracted from phloem enriched bark tissue of CLas infected plants reached a threshold of killing citrus protoplast cells, which was suppressed by uric acid (a ROS scavenger) and gibberellin. Foliar spray of HLB positive citrus with antioxidants (uric acid and rutin) and gibberellin significantly reduced both H2O2 concentrations and cell death in phloem tissues induced by CLas and reduced HLB symptoms. RNA-seq analyses of CLas infected and health C. sinensis support that CLas causes oxidative stress. In sum, HLB is an immune-mediated disease and both mitigating ROS via antioxidants and promoting plant growth can reduce cell death of the phloem tissues caused by CLas, thus controlling HLB.
On the interpretation of transcriptome-wide association studies
Authors: de Leeuw Christiaan , Werme Josefin , Savage Jeanne E. , Peyrot Wouter J. , Posthuma Danielle 
Published: August 2021

AbstractTranscriptome-wide association studies (TWAS) aim to detect relationships between gene expression and a phenotype, and are commonly used for secondary analysis of genome-wide association study (GWAS) results. Results from TWAS analyses are often interpreted as indicating a geneticrelationship between gene expression and a phenotype, but this interpretation is not consistent with the null hypothesis that is evaluated in the traditional TWAS framework. In this study we provide a mathematical outline of this TWAS framework, and elucidate what interpretations are warrantedgiven the null hypothesis it actually tests. We then use both simulations and real data analysis to assess the implications of misinterpreting TWAS results as indicative of a genetic relationship between gene expression and the phenotype. Our simulation results show considerably inflated type 1 error rates for TWAS when interpreted this way, with 41% of significant TWAS associations detected in the real data analysis found to have insufficient statistical evidence to infer such a relationship. This demonstrates that in current implementations, TWAS cannot reliably be used to investigate genetic relationships between gene expression and a phenotype, but that local genetic correlation analysis can serve as a potential alternative.
Long-term effects of moderate concussive brain injury during adolescence on synaptic and tonic GABA currents in dentate projection neurons
Authors: Gupta Akshay , Proddutur Archana , Elgammal Fatima S. , Santhakumar Vijayalakshmi 
Published: August 2021

AbstractProgressive physiological changes in the hippocampal dentate gyrus circuits following traumatic brain injury contribute to temporal evolution of neurological sequelae. Although early posttraumatic changes in dentate synaptic and extrasynaptic GABA currents have been reported, whether they evolve over time and remain distinct between the two projection neuron classes, granule cells and semilunar granule cells, has not been evaluated. We examined changes in tonic GABA currents and spontaneous inhibitory postsynaptic currents (sIPSCs) and in dentate projection neurons one and three month after moderate concussive fluid percussion injury (FPI) in adolescent rats. Granule cell tonic GABA current amplitude remained elevated up to one month after FPI, but decreased to levels comparable to age-matched controls by three months postinjury. Granule cell sIPSC frequency, which we previously reported to be increased one week after FPI, remained higher than in age-matched controls at one month and was significantly reduced three months after FPI. In contrast to the early decrease, tonic GABA current amplitude and sIPSC frequency in semilunar granule cell was not different from controls three months after FPI. The switch in granule cell inhibitory inputs from early increase to subsequent decrease could contribute to the delayed emergence of cognitive deficits and seizure susceptibility after brain injury.
Nos2-/-mice infected withM. tuberculosisdevelop neurobehavioral changes and immunopathology mimicking human central nervous system tuberculosis
Authors: Poh Xuan Ying , Hong Jia Mei , Bai Chen , Miow Qing Hao , Thong Pei Min , Wang Yu , Rajarethinam Ravisankar , Ding Cristine S.L. , Ong Catherine W.M. 
Published: August 2021

ABSTRACTBackgroundUnderstanding the pathophysiology of central nervous system tuberculosis (CNS-TB) is hampered by the lack of a good pre-clinical model that mirrors the human CNS-TB infection. We developed a murine CNS-TB model that demonstrates neurobehavioral changes with similar immunopathology with human CNS-TB.MethodsWe injected twoMycobacterium tuberculosis(M.tb) strains, H37Rv and CDC1551, respectively, into two mouse strains, C3HeB/FeJ andNos2-/-mice, either into the third ventricle or intravenous. We compared the neurological symptoms, histopathological changes and levels of adhesion molecules, chemokines, and inflammatory cytokines in the brain induced by the infections through different routes in different strains.ResultsIntra-cerebroventricular infection ofNos2-/-mice withM.tbled to development of neurological signs and more severe brain granulomas compared to C3HeB/FeJ mice. Compared with CDC1551M.tb, H37RvM.tbinfection resulted in a higher neurobehavioral score and earlier mortality. Intra-cerebroventricular infection caused necrotic neutrophil-dominated pyogranulomas in the brain relative to intravenous infection which resulted in disseminated granulomas and mycobacteraemia. Histologically, intra-cerebroventricular infection ofNos2-/-mice withM.tbresembled human CNS-TB brain biopsy specimens. H37Rv intra-cerebroventricular infected mice demonstrated higher brain concentrations of inflammatory cytokines, chemokines and adhesion molecule ICAM-1 than H37Rv intravenous-infected mice.ConclusionsIntra-cerebroventricular infection ofNos2-/-mice with H37Rv creates a murine CNS-TB model that resembled human CNS-TB immunopathology, exhibiting the worst neurobehavioral score with a high and early mortality reflecting disease severity and its associated neurological morbidity. Our murine CNS-TB model serves as a pre-clinical platform to dissect host-pathogen interactions and evaluate therapeutic agents for CNS-TB.
Orchestrated Restructuring Events During Secretory Granule Maturation Mediate Intragranular Cargo Segregation
Authors: Syed Zulfeqhar A. , Zhang Liping , Tran Duy T. , Bleck Christopher K. E. , Ten Hagen Kelly G. 
Published: August 2021

ABSTRACTRegulated secretion is an essential process where proteins are packaged into membranous secretory vesicles. However, the details of cargo packaging and secretory granule maturation are largely unknown. Here, we demonstrate that multiple distinct proteins undergo intragranular restructuring during secretory granule maturation in vivo, resulting in spatial segregation of distinct protein components within the same granule. Furthermore, through a combination of genetics and multimodality imaging, we demonstrate the molecular identity of each distinct intragranular structure. We further identify temporally-regulated genes that are essential for the restructuring events, including those controlling pH (Vha16-1), Cl− ions (Clic and ClC-c) and Ca2+ ions (fwe). Finally, we show that altered cargo glycosylation influences dimensions of these structures, thereby affecting secretory granule morphology. This study elucidates key steps and factors involved in intragranular, rather than intergranular segregation of cargo through regulated restructuring events during secretory granule maturation. Understanding how multiple distinct proteins are efficiently packaged into and secreted from the same secretory granule may provide insight into diseases resulting from defects in secretion.
A time irreversible model of nucleotide substitution for the SARS-CoV-2 evolution
Authors: Misawa Kazuharu 
Published: August 2021

AbstractSARS-CoV-2 is the cause of the worldwide epidemic of severe acute respiratory syndrome. Evolutionary studies of the virus genome will provide a predictor of the fate of COVID-19 in the near future. Recent studies of the virus genomes have shown that C to U substitutions are overrepresented in the genome sequences of SARS-CoV-2. Traditional time-reversible substitution models cannot be applied to the evolution of SARS-CoV-2 sequences. Therefore, in this study, I propose a new time-irreversible model and a new method for estimating the nucleotide substitution rate of SARS-CoV-2. Computer simulations showed that that the new method gives good estimates. I applied the new method to estimate nucleotide substitution rates of SARS-CoV-2 sequences. The result suggests that the rate of C to U substitution of SARS-Cov-2 is ten times higher than other types of substitutions.
Velocity-free distributed geometric formation control for underactuated UAVs
Authors: Chen Yanjie , Zhan Weiwei , Huang Yibin , Miao Zhiqiang , Wang Yaonan 
Published: August 2021

Purpose
This paper aims to investigate the distributed formation control problem for a multi-quadrotor unmanned aerial vehicle system without linear velocity feedbacks.

Design/methodology/approach
A nonlinear controller is proposed based on the orthogonal group SE(3) to obviate singularities and ambiguities of the traditional parameterized attitude representations. A cascade structure is applied in the distributed controller design. The inner loop is responsible for attitude control, and the outer loop is responsible for translational dynamics. To ensure a linear-velocity-free characteristic, some auxiliary variables are introduced to construct virtual signals in distributed controller design. The stability analysis of the proposed distributed control method by the Lyapunov function is provided as well.

Findings
A group of four quadrotors with constant reference linear velocity and a group of six quadrotors with varying reference linear velocity are adopted to verify the effectiveness of the proposed strategy.

Originality/value
This is a new innovation for multi-robot formation control method to improve assembly automation.
Analysis on corrosion of aluminum-based micro-arc oxidation coating
Authors: Yang Yuanhang , Feng Gang , Gu Yanhong , Zhao Jie , Liang Jian 
Published: August 2021

Purpose
Aluminum alloy is susceptible to chloride ion attack in sea water, resulting in pitting damage and hence serious security risks for the related applications. To improve the corrosion resistance of Al alloy, micro-arc oxidation (MAO) technology has been developed to produce a protective dense oxide layer on top of Al alloy. However, the mechanism of MAO-induced corrosion resistance is still not fully understood, particularly on local corrosion issue. This paper aims to focus on comprehensively studying the corrosion-resistance mechanism by a series of technologies.

Design/methodology/approach
The corrosion behavior of samples was studied by open circuit potential (OCP), potentiodynamic polarization (PDP), electrode impedance spectroscopy (EIS) and localized electrode impedance spectroscopy (LEIS) tests in NaCl solution.

Findings
The MAO-coated Al alloy shows a more positive corrosion potential and a higher corrosion current density compared to the untreated counterpart, indicating a significantly enhanced corrosion-resistance. The study of surface morphology and structure also suggest significantly enhanced corrosion-resistance due to the MAO treatment.

Originality/value
Based on the results, a new corrosion model was proposed to describe the influence of MAO treatment on the corrosion process and corrosion mechanism of Al alloy, providing insights on the design of the corrosion-resistance coating for metallic alloys in marine applications.
Holistic approaches and advanced technologies in aviation product recycling
Authors: Yakovlieva Anna , Boichenko Sergii , Kale Utku , Nagy András 
Published: August 2021

Purpose
The purpose of this study is to analyze existing policies, methods and technologies, which are aimed at the rational and proper handling of decommissioned aviation transport means, determination of the world trends and substantiation of the prospects for implementation of utilization and recycling programs in the aviation industry. This research is devoted to problems of utilization and recycling of decommissioned aircraft and its components: features of proper handling of aviation industry vehicles are considered; the analysis of existing methods and technologies aimed at the rational and correct handling of the end-of-life aircraft is carried out; the necessity of the introduction of the system of complex utilization of aviation equipment is substantiated; the ecological and economic problems connected with the utilization and recycling of aviation vehicles, their units and units are considered; and the relevance and feasibility of introducing recycling programs in the field of aviation industry waste management are substantiated.

Design/methodology/approach
Problems of utilization and recycling of decommissioned aircraft and its components are considered in this research. The analysis of existing methods and technologies aimed at the rational and correct handling of the end-of-life aircraft is carried out. In addition to this, the ecological and economic problems connected with the utilization and recycling of aviation vehicles, their units and parts are considered. Moreover, the relevance and feasibility of introducing recycling programs in the field of aviation industry waste management are substantiated.

Findings
In this study, the life cycle of aircraft is carried out and analyzed. The existing methodologies and approaches to end-of-life aircraft recycling and utilization are presented in this paper. The experience of the leading organizations in the sphere of decommissioned aircraft recycling, such as Aircraft Fleet Recycling Association and Process for Advanced Management of End-of-Life Aircraft, are considered as well. Environmental and economical benefits to aviation and neighbor industries, arising from the introduction of aircraft recycling systems, are shown.

Originality/value
The existing experience of leading companies in the aviation and aircraft recycling industry is accumulated and analyzed to show and propose the general methodology for the development and implementation methodology of end-of-life aircraft recycling and utilization.
Plasma actuation effect on a NACA 4412 airfoil
Authors: Karadag Burak , Kolbakir Cem , Durna Ahmet Selim 
Published: August 2021

Purpose
This paper aims to investigate the effects of a dielectric barrier discharge (DBD) plasma actuator (PA) qualitatively on aerodynamic characteristics of a 3 D-printed NACA 4412 airfoil model.

Design/methodology/approach
Airflow visualization study was performed at a Reynolds number of 35,000 in a small-scale open-loop wind tunnel. The effect of plasma actuation on flow separation was compared for the DBD PA with four different electrode configurations at 10°, 20° and 30° angles of attack.

Findings
Plasma activation may delay the onset of flow separation up to 6° and decreases the boundary layer thickness. The effects of plasma diminish as the angle of attack increases. Streamwise electrode configuration, in which electric wind is produced in a direction perpendicular to the freestream, is more effective in the reattachment of the airflow compared to the spanwise electrode configuration, in which the electric wind and the free stream are in the same direction.

Practical implications
The Reynolds number is much smaller than that in cruise aircraft conditions; however, the results are promising for low-velocity subsonic airflows such as improving control capabilities of unmanned aerial vehicles.

Originality/value
Superior efficacy of spanwise-generated electric wind over streamwise-generated one is demonstrated at a very low Reynolds number. The results in the plasma aerodynamics literature can be reproduced using ultra-low-cost off-the-shelf components. This is important because high voltage power amplifiers that are frequently encountered in the literature may be prohibitively expensive especially for resource-limited university aerodynamics laboratories.