bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor
Authors: Herguedas Beatriz , Kohegyi Bianka K. , Dohrke Jan-Niklas , Watson Jake F. , Zhang Danyang , Ho Hinze , Shaikh Saher A. , Lape Remigijus , Krieger James M. , Greger Ingo H. 
Published: February 2022

AbstractAMPA-type glutamate receptors (AMPARs) mediate rapid signal transmission at excitatory synapses in the brain. Glutamate binding to the receptor’s ligand-binding domains (LBDs) leads to ion channel activation and desensitization. Gating kinetics shape synaptic transmission and are strongly modulated by transmembrane AMPAR regulatory proteins (TARPs) through currently incompletely resolved mechanisms. Here, electron cryo-microscopy structures of the GluA1/2 TARP-γ8 complex, in both open and desensitized states (at 3.5 Å), reveal state-selective engagement of the LBDs by the large TARP-γ8 loop (‘β1’), elucidating how this TARP stabilizes specific gating states. We further show how TARPs alter channel rectification, by interacting with the pore helix of the selectivity filter. Lastly, we reveal that the Q/R-editing site couples the channel constriction at the filter entrance to the gate, and forms the major cation binding site in the conduction path. Our results provide a mechanistic framework of how TARPs modulate AMPAR gating and conductance.
Tousled-like kinase 2 targets ASF1 histone chaperones through client mimicry
Authors: Simon Bertrand , Lou Hua Jane , Huet-Calderwood Clotilde , Shi Guangda , Boggon Titus J. , Turk Benjamin E. , Calderwood David A. 
Published: February 2022

AbstractTousled-like kinases (TLKs) are nuclear serine-threonine kinases essential for genome maintenance and proper cell division in animals and plants. A major function of TLKs is to phosphorylate the histone chaperone proteins ASF1a and ASF1b to facilitate DNA replication-coupled nucleosome assembly, but how TLKs selectively target these critical substrates is unknown. Here, we show that TLK2 selectivity towards ASF1 substrates is achieved in two ways. First, the TLK2 catalytic domain recognizes consensus phosphorylation site motifs in the ASF1 C-terminal tail. Second, a short sequence at the TLK2 N-terminus docks onto the ASF1a globular N-terminal domain in a manner that mimics its histone H3 client. Disrupting either catalytic or non-catalytic interactions through mutagenesis hampers ASF1 phosphorylation by TLK2 and cell growth. Our results suggest that the stringent selectivity of TLKs for ASF1 is enforced by an unusual interaction mode involving mutual recognition of a short sequence motifs by both kinase and substrate.
RNA-seq profiling of white and brown adipocyte differentiation treated with epigallocatechin gallate
Authors: Zhang Pengpeng , Wu Wei , Du Chunyu , Ji Xiang , Wang Yaling , Han Qiu , Xu Hiaxia , Li Cencen , Xu Yongjie 
Published: February 2022

AbstractDue to serious adverse effects, many of the approved anti-obesity medicines have been withdrawn, and the selection of safer natural ingredients is of great interest. Epigallocatechin gallate (EGCG) is one of the major green tea catechins, and has been demonstrated to possess an anti-obesity function by regulating both white and brown adipose tissue activity. However, there are currently no publicly available studies describing the effects of EGCG on the two distinct adipose tissue transcriptomes. The stromal vascular fraction (SVF) cell derived from adipose tissue is a classic cell model for studying adipogenesis and fat accumulation. In the current study, primary WAT and BAT SVF cells were isolated and induced to adipogenic differentiation in the presence or absence of EGCG. RNA-seq was used to determine genes regulated by EGCG and identify the key differences between the two functionally distinct adipose tissues. Taken together, we provide detailed stage- and tissue-specific gene expression profiles affected by EGCG. These data will be valuable for obesity-related clinical/basic research.
In situ vaccination using unique TLR9 ligand K3-SPG induces long-lasting systemic immune response and synergizes with systemic and local immunotherapy
Authors: Okada Hirokazu , Takahashi Ken , Yaku Hiroaki , Kobiyama Kouji , Iwaisako Keiko , Zhao Xiangdong , Shiokawa Masahiro , Uza Norimitsu , Kodama Yuzo , Ishii Ken J. , Seno Hiroshi 
Published: February 2022

AbstractAlthough checkpoint inhibitors (CPIs) have changed the paradigm of cancer therapy, low response rates and serious systemic adverse events remain challenging. In situ vaccine (ISV), intratumoral injection of immunomodulators that stimulate innate immunity at the tumor site, allows for the development of vaccines in patients themselves. K3-SPG, a second-generation nanoparticulate Toll-like receptor 9 (TLR9) ligand consisting of K-type CpG oligodeoxynucleotide (ODN) wrapped with SPG (schizophyllan), integrates the best of conventional CpG ODNs, making it an ideal cancer immunotherapy adjuvant. Focusing on clinical feasibility for pancreaticobiliary and gastrointestinal cancers, we investigated the antitumor activity of K3-SPG-ISV in preclinical models of pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC). K3-SPG-ISV suppressed tumor growth more potently than K3-ISV or K3-SPG intravenous injections, prolonged survival, and enhanced the antitumor effect of CPIs. Notably, in PDAC model, K3-SPG-ISV alone induced systemic antitumor effect and immunological memory. ISV combination of K3-SPG and agonistic CD40 antibody further enhanced the antitumor effect. Our results imply that K3-SPG-based ISV can be applied as monotherapy or combined with CPIs to improve their response rate or, conversely, with CPI-free local immunotherapy to avoid CPI-related adverse events. In either strategy, the potency of K3-SPG-based ISV would provide the rationale for its clinical application to puncturable pancreaticobiliary and gastrointestinal malignancies.
Sample-efficient parameter exploration of the powder film drying process using experiment-based Bayesian optimization
Authors: Nagai Kohei , Osa Takayuki , Inoue Gen , Tsujiguchi Takuya , Araki Takuto , Kuroda Yoshiyuki , Tomizawa Morio , Nagato Keisuke 
Published: February 2022

AbstractParameter optimization is a long-standing challenge in various production processes. Particularly, powder film forming processes entail multiscale and multiphysical phenomena, each of which is usually controlled by a combination of several parameters. Therefore, it is difficult to optimize the parameters either by numerical-model-based analysis or by “brute force” experiment-based exploration. In this study, we focus on a Bayesian optimization method that has led to breakthroughs in materials informatics. Specifically, we apply this method to exploration of production-process-parameter for the powder film forming process. To this end, a slurry containing a powder, polymer, and solvent was dropped, the drying temperature and time were controlled as parameters to be explored, and the uniformity of the fabricated film was evaluated. Using this experiment-based Bayesian optimization system, we searched for the optimal parameters among 32,768 (85) parameter sets to minimize defects. This optimization converged at 40 experiments, which is a substantially smaller number than that observed in brute-force exploration and traditional design-of-experiments methods. Furthermore, we inferred the mechanism corresponding to the unknown drying conditions discovered in the parameter exploration that resulted in uniform film formation. This demonstrates that a data-driven approach leads to high-throughput exploration and the discovery of novel parameters, which inspire further research.
Automatic real-time occupational posture evaluation and select corresponding ergonomic assessments
Authors: Lin Po-Chieh , Chen Yu-Jung , Chen Wei-Shin , Lee Yun-Ju 
Published: February 2022

AbstractThe objective is to develop a system to automatically select the corresponding assessment scales and calculate the score of the risk based on the joint angle information obtained from the imaged process (OpenPose) via image-based motion capture technology. Current occupational assessments, for example, REBA, RULA, and OWAS were used to evaluate the risk of musculoskeletal disorders. However, the assessment result would not be reported immediately. Introducing real-time occupational assessments in different working environments will be helpful for occupational injury prevention. In this study, the decision tree was developed to select the most appropriate assessment method according to the joint angles derived by OpenPose image process. Fifteen operation videos were tested and these videos can be classified into six types including maintenance, handling, assembly, cleaning, office work, and driving. The selected ergonomic assessment method by our developed decision tree in each condition are consistent with the recommendation of the Labour Research Institute. Moreover, the high-risk posture could be identified immediately and provide to the inspector for further evaluation on this posture rather than the whole operation period. This approach provides a quick inspection of the operation movements to prevent musculoskeletal injuries and enhances the application of the scale assessment method in different industrial environments.
Characterization and phylogeny of fungi isolated from industrial wastewater using multiple genes
Authors: Ezeonuegbu Blessing Amaka , Abdullahi Machido Dauda , Whong Clement M. Z. , Sohunago Japhet Wisdom , Kassem Hazem S. , Yaro Clement Ameh , Hetta Helal F. , Mostafa-Hedeab Gomaa , Zouganelis George D. , Batiha Gaber El-Saber 
Published: February 2022

AbstractThe aim of this study was the isolation and molecular characterization of fungi from untreated refinery effluent by using multiple conserved genes. The Fungi isolated were characterized based on PCR amplification and genomic sequencing of the internal transcribed spacer region (ITS), partial β-tubulin (BenA), calmodulin (CaM), and RNA polymerase second large subunit (RPB2) genes, along with morphological characterization. The obtained sequences were subjected to BLAST analysis and the corresponding fungal isolates were assigned species names after comparison with representative sequences available in GenBank. Fifteen (15) Fungi species belonging to four genera of Aspergillus, Penicillium, Fusarium, and Trichoderma with Aspergillus as the predominant genus were identified. Therefore these genes should be used as molecular markers for species level identification of fungi (especially Aspergillus and Penicillium as proven in this study.
Molecular diameters of rarefied gases
Authors: Kunze S. , Groll R. , Besser B. , Thöming J. 
Published: February 2022

AbstractMolecular diameters are an important property of gases for numerous scientific and technical disciplines. Different measurement techniques for these diameters exist, each delivering a characteristic value. Their reliability in describing the flow of rarefied gases, however, has not yet been discussed, especially the case for the transitional range between continuum and ballistic flow. Here, we present a method to describe gas flows in straight channels with arbitrary cross sections for the whole Knudsen range by using a superposition model based on molecular diameters. This model allows us to determine a transition diameter from flow measurement data that paves the way for generalized calculations of gas behaviour under rarefied conditions linking continuum and free molecular regime.
Dual-color dynamic anti-counterfeiting labels with persistent emission after visible excitation allowing smartphone authentication
Authors: Katumo Ngei , Li Kai , Richards Bryce S. , Howard Ian A. 
Published: February 2022

AbstractA significant impediment to the deployment of anti-counterfeiting technologies is the reliance on specialized hardware. Here, anti-counterfeiting labels are developed that are both excited and detected using a smartphone. The persistent luminescence pattern and color changes on the timescale of hundreds of milliseconds to seconds. The labels can be authenticated by comparing still images from the red and green channels of video acquired at known times after flashlight excitation against expected reference patterns. The labels are based on a green-emitting SrAl2O4: Eu2+,Dy3+ (SAED), and red-emitting CaS:Eu2+ phosphors whose lifetimes are varied: (i) for SAED from 0.5 to 11.7 s by annealing the commercial material in air; and (ii) CaS:Eu2+ from 0.1 to 0.6 s by varying the dopant concentration. Examples of anti-counterfeiting labels exhibiting changing emission patterns and colors on a seven-segment display, barcode, and emoji are demonstrated. These results demonstrate that phosphors with visible absorption and tunable persistent luminescence lifetimes on the order of hundreds of milliseconds to seconds are attractive for anti-counterfeiting applications as they allow authentication to be performed using only a smartphone. Further development should allow richer color shifts and enhancement of security by embedding further covert anti-counterfeiting features.
Molecular characterization of methicillin-resistant Staphylococcus aureus genotype ST764-SCCmec type II in Thailand
Authors: Kondo Sumalee , Phokhaphan Pimonwan , Tongsima Sissades , Ngamphiw Chumpol , Phornsiricharoenphant Worawich , Ruangchai Wuthiwat , Disratthakit Areeya , Tingpej Pholawat , Mahasirimongkol Surakameth , Lulitanond Aroonlug , Apisarnthanarak Anucha , Palittapongarnpim Prasit 
Published: February 2022

AbstractMethicillin-resistant Staphylococcus aureus (MRSA) is a significant causative agent of hospital-acquired infections. We characterized MRSA isolated from August 2012 to July 2015 from Thammasat University Hospital. Genotypic characterization of MRSA SCCmec type II and III isolates were scrutinized by whole genome sequencing (WGS). The WGS data revealed that the MRSA SCCmec type II isolates belonged to ST764 previously reported mainly in Japan. All of tested isolates contained ACME Type II′, SaPIn2, SaPIn3, seb, interrupted SA1320, and had a virulence gene profile similar to Japan MRSA ST764. Rigorous surveillance of MRSA strains is imperative in Thailand to arrest its potential spread.
Optimizing intact skull intrinsic signal imaging for subsequent targeted electrophysiology across mouse visual cortex
Authors: Nsiangani Armel , Del Rosario Joseph , Yeh Alan C. , Shin Donghoon , Wells Shea , Lev-Ari Tidhar , Williams Brice , Haider Bilal 
Published: February 2022

AbstractUnderstanding brain function requires repeatable measurements of neural activity across multiple scales and multiple brain areas. In mice, large scale cortical neural activity evokes hemodynamic changes readily observable with intrinsic signal imaging (ISI). Pairing ISI with visual stimulation allows identification of primary visual cortex (V1) and higher visual areas (HVAs), typically through cranial windows that thin or remove the skull. These procedures can diminish long-term mechanical and physiological stability required for delicate electrophysiological measurements made weeks to months after imaging (e.g., in subjects undergoing behavioral training). Here, we optimized and directly validated an intact skull ISI system in mice. We first assessed how imaging quality and duration affect reliability of retinotopic maps in V1 and HVAs. We then verified ISI map retinotopy in V1 and HVAs with targeted, multi-site electrophysiology several weeks after imaging. Reliable ISI maps of V1 and multiple HVAs emerged with ~ 60 trials of imaging (65 ± 6 min), and these showed strong correlation to local field potential (LFP) retinotopy in superficial cortical layers (r2 = 0.74–0.82). This system is thus well-suited for targeted, multi-area electrophysiology weeks to months after imaging. We provide detailed instructions and code for other researchers to implement this system.
Forecasting global and multi-level thermospheric neutral density and ionospheric electron content by tuning models against satellite-based accelerometer measurements
Authors: Forootan Ehsan , Kosary Mona , Farzaneh Saeed , Kodikara Timothy , Vielberg Kristin , Fernandez-Gomez Isabel , Borries Claudia , Schumacher Maike 
Published: February 2022

AbstractGlobal estimation of thermospheric neutral density (TND) on various altitudes is important for geodetic and space weather applications. This is typically provided by models, however, the quality of these models is limited due to their imperfect structure and the sensitivity of their parameters to the calibration period. Here, we present an ensemble Kalman filter (EnKF)-based calibration and data assimilation (C/DA) technique that updates the model’s states and simultaneously calibrates its key parameters. Its application is demonstrated using the TND estimates from on-board accelerometer measurements, e.g., those of the Gravity Recovery and Climate Experiment (GRACE) mission (at $$\sim 410$$

∼
410

km altitude), as observation, and the frequently used empirical model NRLMSISE-00. The C/DA is applied here to re-calibrate the model parameters including those controlling the influence of solar radiation and geomagnetic activity as well as those related to the calculation of exospheric temperature. The resulting model, called here ‘C/DA-NRLMSISE-00’, is then used to now-cast TNDs and individual neutral mass compositions for 3 h, where the model with calibrated parameters is run again during the assimilation period. C/DA-NRLMSISE-00 is also used to forecast the next 21 h, where no new observations are introduced. These forecasts are unique because they are available globally and on various altitudes (300–600 km). To introduce the impact of the thermosphere on estimating ionospheric parameters, the coupled physics-based model TIE-GCM is run by replacing the O2, O1, He and neutral temperature estimates of the C/DA-NRLMSISE-00. Then, the non-assimilated outputs of electron density (Ne) and total electron content (TEC) are validated against independent measurements. Assessing the forecasts of TNDs with those along the Swarm-A ($$\sim 467$$

∼
467

km), -B ($$\sim 521$$

∼
521

km), and -C ($$\sim 467$$

∼
467

km) orbits shows that the root-mean-square error (RMSE) is considerably reduced by 51, 57 and 54%, respectively. We find improvement of 30.92% for forecasting Ne and 26.48% for TEC compared to the radio occulation and global ionosphere maps (GIM), respectively. The presented C/DA approach is recommended for the short-term global multi-level thermosphere and enhanced ionosphere forecasting applications.
Banknote authenticity is signalled by rapid neural responses
Authors: Dodgson Daniel B. , Raymond Jane E. 
Published: February 2022

AbstractAuthenticating valuable objects is widely assumed to involve protracted scrutiny for detection of reproduction flaws. Yet, accurate authentication of banknotes is possible within one second of viewing, suggesting that rapid neural processes may underpin counterfeit detection. To investigate, we measured event-related brain potentials (ERPs) in response to briefly viewed genuine or forensically recovered counterfeit banknotes presented in a visual oddball counterfeit detection task. Three ERP components, P1, P3, and extended P3, were assessed for each combination of banknote type (genuine, counterfeit) and overt response (“real”, “fake”). P1 amplitude was greater for oddballs, demonstrating that the initial feedforward sweep of visual processing yields the essential information for differentiating genuine from counterfeit. A similar oddball effect was found for P3. The magnitude of this P3 effect was positively correlated with behavioural counterfeit sensitivity, although the corresponding correlation for P1 was not. For the extended P3, amplitude was greatest for correctly detected counterfeits and similarly small for missed counterfeits, incorrectly and correctly categorised genuine banknotes. These results show that authentication of complex stimuli involves a cascade of neural processes that unfolds in under a second, beginning with a very rapid sensory analysis, followed by a later decision stage requiring higher level processing.
Computed tomography with segmentation and quantification of individual organs in a D. melanogaster tumor model
Authors: Holland Petter , Quintana Eduardo Martin , Khezri Rojyar , Schoborg Todd Andrew , Rusten Tor Erik 
Published: February 2022

AbstractDrosophila melanogaster tumor models are growing in popularity, driven by the high degree of genetic as well as functional conservation to humans. The most common method to measure the effects of a tumor on distant organs of a human cancer patient is to use computed tomography (CT), often used in diagnosing cachexia, a debilitating cancer-induced syndrome most visibly characterized by loss of muscle mass. Successful application of high resolution micro-CT scanning of D. melanogaster was recently reported and we here present the segmentation of all visible larval organs at several stages of tumor development. We previously showed the strong expected reduction in muscle mass as the tumor develops, and we here report a surprisingly strong reduction also in gut and Malpighian tubules (kidney) volume. Time-point of tumor development was found to have a stronger correlation to cachectic organ volume loss than tumor volume, giving support to the previously proposed idea that tumor size does not directly determine degree of cachexia.
3D pCASL-perfusion in preoperative assessment of brain gliomas in large cohort of patients
Authors: Batalov A. I. , Zakharova N. E. , Pronin I. N. , Belyaev A. Yu. , Pogosbekyan E. L. , Goryaynov S. A. , Bykanov A. E. , Tyurina A. N. , Shevchenko A. M. , Solozhentseva K. D. , Nikitin P. V. , Potapov A. A. 
Published: February 2022

AbstractThe aim of the study was to evaluate the role of pseudocontinuous arterial spin labeling perfusion (pCASL-perfusion) in preoperative assessment of cerebral glioma grades. The study group consisted of 253 patients, aged 7–78 years with supratentorial gliomas (65 low-grade gliomas (LGG), 188 high-grade gliomas (HGG)). We used 3D pCASL-perfusion for each patient in order to calculate the tumor blood flow (TBF). We obtained maximal tumor blood flow (maxTBF) in small regions of interest (30 ± 10 mm2) and then normalized absolute maximum tumor blood flow (nTBF) to that of the contralateral normal-appearing white matter of the centrum semiovale. MaxTBF and nTBF values significantly differed between HGG and LGG groups (p < 0.001), as well as between patient groups separated by the grades (grade II vs. grade III) (p < 0.001). Moreover, we performed ROC-analysis which demonstrated high sensitivity and specificity in differentiating between HGG and LGG. We found significant differences for maxTBF and nTBF between grade III and IV gliomas, however, ROC-analysis showed low sensitivity and specificity. We did not observe a significant difference in TBF for astrocytomas and oligodendrogliomas. Our study demonstrates that 3D pCASL-perfusion as an effective diagnostic tool for preoperative differentiation of glioma grades.