bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allosteric control of Ubp6 and the proteasome via a bidirectional switch
Authors: Hung Ka Ying Sharon , Klumpe Sven , Eisele Markus R. , Elsasser Suzanne , Tian Geng , Sun Shuangwu , Moroco Jamie A. , Cheng Tat Cheung , Joshi Tapan , Seibel Timo , Van Dalen Duco , Feng Xin-Hua , Lu Ying , Ovaa Huib , Engen John R. , Lee Byung-Hoon , Rudack Till , Sakata Eri , Finley Daniel 
Published: February 2022

AbstractThe proteasome recognizes ubiquitinated proteins and can also edit ubiquitin marks, allowing substrates to be rejected based on ubiquitin chain topology. In yeast, editing is mediated by deubiquitinating enzyme Ubp6. The proteasome activates Ubp6, whereas Ubp6 inhibits the proteasome through deubiquitination and a noncatalytic effect. Here, we report cryo-EM structures of the proteasome bound to Ubp6, based on which we identify mutants in Ubp6 and proteasome subunit Rpt1 that abrogate Ubp6 activation. The Ubp6 mutations define a conserved region that we term the ILR element. The ILR is found within the BL1 loop, which obstructs the catalytic groove in free Ubp6. Rpt1-ILR interaction opens the groove by rearranging not only BL1 but also a previously undescribed network of three interconnected active-site-blocking loops. Ubp6 activation and noncatalytic proteasome inhibition are linked in that they are eliminated by the same mutations. Ubp6 and ubiquitin together drive proteasomes into a unique conformation associated with proteasome inhibition. Thus, a multicomponent allosteric switch exerts simultaneous control over both Ubp6 and the proteasome.
Analysis of vibronic coupling in a 4f molecular magnet with FIRMS
Authors: Kragskow Jon G. C. , Marbey Jonathan , Buch Christian D. , Nehrkorn Joscha , Ozerov Mykhaylo , Piligkos Stergios , Hill Stephen , Chilton Nicholas F. 
Published: February 2022

AbstractVibronic coupling, the interaction between molecular vibrations and electronic states, is a fundamental effect that profoundly affects chemical processes. In the case of molecular magnetic materials, vibronic, or spin-phonon, coupling leads to magnetic relaxation, which equates to loss of magnetic memory and loss of phase coherence in molecular magnets and qubits, respectively. The study of vibronic coupling is challenging, and most experimental evidence is indirect. Here we employ far-infrared magnetospectroscopy to directly probe vibronic transitions in [Yb(trensal)] (where H3trensal = 2,2,2-tris(salicylideneimino)trimethylamine). We find intense signals near electronic states, which we show arise due to an “envelope effect” in the vibronic coupling Hamiltonian, which we calculate fully ab initio to simulate the spectra. We subsequently show that vibronic coupling is strongest for vibrational modes that simultaneously distort the first coordination sphere and break the C3 symmetry of the molecule. With this knowledge, vibrational modes could be identified and engineered to shift their energy towards or away from particular electronic states to alter their impact. Hence, these findings provide new insights towards developing general guidelines for the control of vibronic coupling in molecules.
Decoding reactive structures in dilute alloy catalysts
Authors: Marcella Nicholas , Lim Jin Soo , Płonka Anna M. , Yan George , Owen Cameron J. , van der Hoeven Jessi E. S. , Foucher Alexandre C. , Ngan Hio Tong , Torrisi Steven B. , Marinkovic Nebojsa S. , Stach Eric A. , Weaver Jason F. , Aizenberg Joanna , Sautet Philippe , Kozinsky Boris , Frenkel Anatoly I. 
Published: February 2022

AbstractRational catalyst design is crucial toward achieving more energy-efficient and sustainable catalytic processes. Understanding and modeling catalytic reaction pathways and kinetics require atomic level knowledge of the active sites. These structures often change dynamically during reactions and are difficult to decipher. A prototypical example is the hydrogen-deuterium exchange reaction catalyzed by dilute Pd-in-Au alloy nanoparticles. From a combination of catalytic activity measurements, machine learning-enabled spectroscopic analysis, and first-principles based kinetic modeling, we demonstrate that the active species are surface Pd ensembles containing only a few (from 1 to 3) Pd atoms. These species simultaneously explain the observed X-ray spectra and equate the experimental and theoretical values of the apparent activation energy. Remarkably, we find that the catalytic activity can be tuned on demand by controlling the size of the Pd ensembles through catalyst pretreatment. Our data-driven multimodal approach enables decoding of reactive structures in complex and dynamic alloy catalysts.
Single-cell RNA sequencing reveals time- and sex-specific responses of mouse spinal cord microglia to peripheral nerve injury and links ApoE to chronic pain
Authors: Tansley Shannon , Uttam Sonali , Ureña Guzmán Alba , Yaqubi Moein , Pacis Alain , Parisien Marc , Deamond Haley , Wong Calvin , Rabau Oded , Brown Nicole , Haglund Lisbet , Ouellet Jean , Santaguida Carlo , Ribeiro-da-Silva Alfredo , Tahmasebi Soroush , Prager-Khoutorsky Masha , Ragoussis Jiannis , Zhang Ji , Salter Michael W. , Diatchenko Luda , Healy Luke M. , Mogil Jeffrey S. , Khoutorsky Arkady 
Published: February 2022

AbstractActivation of microglia in the spinal cord following peripheral nerve injury is critical for the development of long-lasting pain hypersensitivity. However, it remains unclear whether distinct microglia subpopulations or states contribute to different stages of pain development and maintenance. Using single-cell RNA-sequencing, we show that peripheral nerve injury induces the generation of a male-specific inflammatory microglia subtype, and demonstrate increased proliferation of microglia in male as compared to female mice. We also show time- and sex-specific transcriptional changes in different microglial subpopulations following peripheral nerve injury. Apolipoprotein E (Apoe) is the top upregulated gene in spinal cord microglia at chronic time points after peripheral nerve injury in mice. Furthermore, polymorphisms in the APOE gene in humans are associated with chronic pain. Single-cell RNA sequencing analysis of human spinal cord microglia reveals a subpopulation with a disease-related transcriptional signature. Our data provide a detailed analysis of transcriptional states of mouse and human spinal cord microglia, and identify a link between ApoE and chronic pain in humans.
High content screening and proteomic analysis identify a kinase inhibitor that rescues pathological phenotypes in a patient-derived model of Parkinson’s disease
Authors: Antoniou Nasia , Prodromidou Kanella , Kouroupi Georgia , Boumpoureka Ioanna , Samiotaki Martina , Panayotou George , Xilouri Maria , Kloukina Ismini , Stefanis Leonidas , Grailhe Regis , Taoufik Era , Matsas Rebecca 
Published: February 2022

AbstractCombining high throughput screening approaches with induced pluripotent stem cell (iPSC)-based disease modeling represents a promising unbiased strategy to identify therapies for neurodegenerative disorders. Here we applied high content imaging on iPSC-derived neurons from patients with familial Parkinson’s disease bearing the G209A (p.A53T) α-synuclein (αSyn) mutation and launched a screening campaign on a small kinase inhibitor library. We thus identified the multi-kinase inhibitor BX795 that at a single dose effectively restores disease-associated neurodegenerative phenotypes. Proteomics profiling mapped the molecular pathways underlying the protective effects of BX795, comprising a cohort of 118 protein-mediators of the core biological processes of RNA metabolism, protein synthesis, modification and clearance, and stress response, all linked to the mTORC1 signaling hub. In agreement, expression of human p.A53T-αSyn in neuronal cells affected key components of the mTORC1 pathway resulting in aberrant protein synthesis that was restored in the presence of BX795 with concurrent facilitation of autophagy. Taken together, we have identified a promising small molecule with neuroprotective actions as candidate therapeutic for PD and other protein conformational disorders.
Dual-comb cavity ring-down spectroscopy
Authors: Lisak Daniel , Charczun Dominik , Nishiyama Akiko , Voumard Thibault , Wildi Thibault , Kowzan Grzegorz , Brasch Victor , Herr Tobias , Fleisher Adam J. , Hodges Joseph T. , Ciuryło Roman , Cygan Agata , Masłowski Piotr 
Published: February 2022

AbstractCavity ring-down spectroscopy is a ubiquitous optical method used to study light-matter interactions with high resolution, sensitivity and accuracy. However, it has never been performed with the multiplexing advantages of direct frequency comb spectroscopy without significantly compromising spectral resolution. We present dual-comb cavity ring-down spectroscopy (DC-CRDS) based on the parallel heterodyne detection of ring-down signals with a local oscillator comb to yield absorption and dispersion spectra. These spectra are obtained from widths and positions of cavity modes. We present two approaches which leverage the dynamic cavity response to coherently or randomly driven changes in the amplitude or frequency of the probe field. Both techniques yield accurate spectra of methane—an important greenhouse gas and breath biomarker. When combined with broadband frequency combs, the high sensitivity, spectral resolution and accuracy of our DC-CRDS technique shows promise for applications like studies of the structure and dynamics of large molecules, multispecies trace gas detection and isotopic composition.
Immediate voluntary activation deficits following submaximal eccentric contractions of knee extensors are associated with alterations of the sense of movement
Authors: Da Silva Flavio , Colson Serge S. , Zghal Firas , Chorin Frédéric , Guérin Olivier , Monjo Florian 
Published: February 2022

AbstractThe mechanisms underlying movement sense alterations following repeated eccentric contractions remain unclear. This study concomitantly investigated the effects of unilateral eccentric contractions on movement sense and on neuromuscular function at the knee before, immediately after (POST), 24 (POST24) and 48 (POST48) h after the exercise. Twelve participants performed sets of submaximal knee extensors (KE) eccentric contractions until a 20% decrease in maximal voluntary isometric contraction (MVIC) torque was reached. Threshold to detect passive movement (TTDPM) tasks were used to assess movement sense during both knee flexion (TTDPMFLEX) and extension (TTDPMEXT). KE fatigability was assessed using the interpolated twitch technique. TTDPM values expressed in seconds and the percentage of unsuccessful trials only increased at POST during TTDPMFLEX and TTDPMEXT. The 20%-MVIC decrease was associated with significant decreases in voluntary activation level (− 12.7%, p < 0.01) and potentiated doublet torque at 100 Hz (− 18.1%, p < 0.001). At POST24, despite persistent reductions of maximal voluntary and electrically evoked torques associated with increased perceived muscle soreness, TTDPM values and the percentage of unsuccessful trials returned to baseline values. Consequently, movement sense alterations were only observed in the presence of voluntary activation deficits, suggesting that some exercise-induced central alterations may affect the somatosensory function.
RYBP regulates Pax6 during in vitro neural differentiation of mouse embryonic stem cells
Authors: Sutus Enikő , Henry Surya , Adorján Lili , Kovács Gergő , Pirity Melinda Katalin 
Published: February 2022

AbstractWe have previously reported that RING1 and YY1 binding protein (RYBP) is important for central nervous system development in mice and that Rybp null mutant (Rybp−/−) mouse embryonic stem (ES) cells form more progenitors and less terminally differentiated neural cells than the wild type cells in vitro. Accelerated progenitor formation coincided with a high level of Pax6 expression in the Rybp−/− neural cultures. Since Pax6 is a retinoic acid (RA) inducible gene, we have analyzed whether altered RA signaling contributes to the accelerated progenitor formation and impaired differentiation ability of the Rybp−/− cells. Results suggested that elevated Pax6 expression was driven by the increased activity of the RA signaling pathway in the Rybp−/− neural cultures. RYBP was able to repress Pax6 through its P1 promoter. The repression was further attenuated when RING1, a core member of ncPRC1s was also present. According to this, RYBP and PAX6 were rarely localized in the same wild type cells during in vitro neural differentiation. These results suggest polycomb dependent regulation of Pax6 by RYBP during in vitro neural differentiation. Our results thus provide novel insights on the dynamic regulation of Pax6 and RA signaling by RYBP during mouse neural development.
ASCL1 phosphorylation and ID2 upregulation are roadblocks to glioblastoma stem cell differentiation
Authors: Azzarelli Roberta , McNally Aoibheann , Dell’Amico Claudia , Onorati Marco , Simons Benjamin , Philpott Anna 
Published: February 2022

AbstractThe growth of glioblastoma (GBM), one of the deadliest adult cancers, is fuelled by a subpopulation of stem/progenitor cells, which are thought to be the source of resistance and relapse after treatment. Re-engagement of a latent capacity of these cells to re-enter a trajectory resulting in cell differentiation is a potential new therapeutic approach for this devastating disease. ASCL1, a proneural transcription factor, plays a key role in normal brain development and is also expressed in a subset of GBM cells, but fails to engage a full differentiation programme in this context. Here, we investigated the barriers to ASCL1-driven differentiation in GBM stem cells. We see that ASCL1 is highly phosphorylated in GBM stem cells where its expression is compatible with cell proliferation. However, overexpression of a form of ASCL1 that cannot be phosphorylated on Serine–Proline sites drives GBM cells down a neuronal lineage and out of cell cycle more efficiently than its wild-type counterpart, an effect further enhanced by deletion of the inhibitor of differentiation ID2, indicating mechanisms to reverse the block to GBM cell differentiation.
Formation and function of OmpG or OmpA-incorporated liposomes using an in vitro translation system
Authors: Kamiya Koki 
Published: February 2022

AbstractOuter membrane proteins (OMPs), located on the outer membrane of gram-negative bacteria, have a β-strand structure and form nanopores, which allow passage of ions, sugars, and small molecules. Recently, OMPs have been used as sensing elements to detect biological molecules. OMPs are normally expressed and purified from Escherichia coli (E. coli). Although the cell-free synthesis of OMPs, such as OmpA and OmpG, is achieved in the presence of liposomes and periplasmic chaperones, the amount of OmpA and OmpG incorporated into the nano-sized liposomes is not clear. In this study, after in vitro translation, the incorporation of OmpG into purified nano-sized liposomes with various lipid compositions was investigated. Liposomes containing the synthesized OmpG were purified using a stepwise sucrose density gradient. We report that liposomes prepared with the E. coli lipid extract (PE/PG) had the highest amount of OmpG incorporated compared to liposomes with other lipid compositions, as detected by recording the current across the OmpG containing liposomes using the patch clamp technique. This study reveals some of the requirements for the insertion and refolding of OMPs synthesized by the in vitro translation system into lipid membranes, which plays a role in the biological sensing of various molecules.
A disintegrin derivative as a case study for PHIP labeling of disulfide bridged biomolecules
Authors: Fleckenstein Max , Herr Kevin , Theiß Franziska , Knecht Stephan , Wienands Laura , Brodrecht Martin , Reggelin Michael , Buntkowsky Gerd 
Published: February 2022

AbstractA specific labeling strategy for bioactive molecules is presented for eptifibatide (integrilin) an antiplatelet aggregation inhibitor, which derives from the disintegrin protein barbourin in the venom of certain rattlesnakes. By specifically labeling the disulfide bridge this molecule becomes accessible for the nuclear spin hyperpolarization method of parahydrogen induced polarization (PHIP). The PHIP-label was synthesized and inserted into the disulfide bridge of eptifibatide via reduction of the peptide and insertion by a double Michael addition under physiological conditions. This procedure is universally applicable for disulfide-containing biomolecules and preserves their tertiary structure with a minimum of change. HPLC and MS spectra prove the successful insertion of the label.1H-PHIP-NMR experiments yield a factor of over 1000 as lower limit for the enhancement factor. These results demonstrate the high potential of the labeling strategy for the introduction of site selective PHIP-labels into biomolecules’ disulfide bonds.
Quality of life score as a prognosticator for pharyngeal cancer patients treated with radiotherapy
Authors: Ishiyama Hiromichi , Kawakami Shogo , Sekiguchi Akane , Kainuma Takuro , Miyamoto Shunsuke , Yamashita Taku , Nakano Masahiro 
Published: February 2022

AbstractThe purpose of this study was to evaluate the prognostic value of quality of life (QOL) scores acquired not only pre-treatment, but also 1 month after treatment for locoregional control (LRC), distant metastasis-free survival (DMFS), and overall survival (OS) in patients with pharyngeal cancer treated using radiotherapy. Data for 102 patients with naso-, oro-, or hypo-pharyngeal cancer treated between December 2008 and September 2017 were retrospectively analyzed. About 90% of the patients were male. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) was used for QOL assessments. Associations between QLQ-C30 scores before and 1 month after treatment and outcomes including LRC, DMFS, and OS were analyzed using Cox proportional hazard models. Median follow-up was 37 months (range, 5–117 months). Three-year LRC, DMFS, and OS rates were 77.8%, 60.0%, and 66.5%, respectively. Pre-treatment emotional functioning and diarrhea at 1 month after treatment were identified as significant predictors of LRC. Pre-treatment global QOL and diarrhea at 1 month after treatment were detected as significant predictors of DMFS. Pre-treatment emotional functioning, pre-treatment appetite loss, and diarrhea at 1 month after treatment were detected as significant predictors of OS. Diarrhea at 1 month after treatment was the most powerful QOL variable for predicting LRC, DMFS and OS. Our study revealed that several QOL scores not only before treatment but also 1 month after treatment correlated with LRC, DMFS and OS. In particular, the diarrhea domain of QOL at 1 month after treatment offered the most powerful prognosticator for pharyngeal cancer patients treated with radiotherapy.
Putative variants, genetic diversity and population structure among Soybean cultivars bred at different ages in Huang-Huai-Hai region
Authors: Liu Jialin , Xie Huimin , Lin Ting , Tie Congxiao , Luo Huolin , Yang Boyun , Xiong Dongjin 
Published: February 2022

AbstractSoybean cultivars bred in the Huang-Huai-Hai region (HR) are rich in pedigree information. To date, few reports have exposed the genetic variants, population structure and genetic diversity of cultivars in this region by making use of genome-wide resequencing data. To depict genetic variation, population structure and composition characteristics of genetic diversity, a sample of soybean population composed all by cultivars was constructed. We re-sequenced 181 soybean cultivar genomes with an average depth of 10.38×. In total, 11,185,589 single nucleotide polymorphisms (SNPs) and 2,520,208 insertion-deletions (InDels) were identified on all 20 chromosomes. A considerable number of putative variants existed in important genome regions that may have an incalculable influence on genes, which participated in momentous biological processes. All 181 varieties were divided into five subpopulations according to their breeding years, SA (1963–1980), SB (1983–1988), SC (1991–2000), SD (2001–2011), SE (2012–2017). PCA and population structure figured out that there was no obvious grouping trend. The LD semi-decay distances of sub-population D and E were 182 kb, and 227 kb, respectively. Sub-population A (SA) had the highest value of nucleotide polymorphism (π). With the passage of time, the nucleotide polymorphism of SB and SC decreased gradually, however that of SD and SE, opposite to SB and SC, gave a rapid up-climbing trend, which meant a sharp increase in genetic diversity during the latest 20 years, hinting that breeders may have different breeding goals in different breeding periods in HR. Analysis of the PIC statistics exhibited very similar results with π. The current study is to analyze the genetic variants and characterize the structure and genetic diversity of soybean cultivars bred in different decades in HR, and to provide a theoretical reference for other identical studies.
Single-particle spectroscopic investigation on the scattering spectrum of Au@MoS2 core–shell nanosphere heterostructure
Authors: You Jian , Xie Hao , Yang Yanhe , Ni Weihai , Ye Weixiang 
Published: February 2022

QSA theory can predict scattering spectra of Au@MoS2 core−shell nanoparticles. The A and B exciton absorption peaks do not rely on the local refractive index change while the particle plasmon resonance position does, which is a helpful internal reference against defocusing.
Deep learning‐based substation remote construction management and AI automatic violation detection system
Authors: Yan Kai , Li Quanjing , Li Hao , Wang Haifeng , Fang Yuping , Xing Lin , Yang Yang , Bai Haicheng , Zhou Chengjiang 
Published: February 2022

AbstractWorkplace video surveillance and timely response to operational violations are critical to avoid operator injuries at power construction sites. Here, a system that combines remote substation construction management and artificial intelligence object detection techniques to intellectualize the power construction management process and identify violations during construction in real time is proposed. To improve the detection accuracy, a data augmentation method, including three operations: (1) object segmentation and background fusion; (2) partial erasing; and (3) other basic transformations, is also proposed. Six variants of the You Only Look Once (YOLO) model are trained as detectors for comparative experiments on a dataset collected at the practical construction site. The experimental results show that the detection precision and recall of the YOLOv5‐s model are 0.852 and 0.922, with high accuracy and low miss rate, which meet the requirements of robustness and accuracy in detecting realistic power construction violations.
Evaluation of the turn‐off transient controllability for high‐power IGBT modules
Authors: Tan Kun , Ji Bing , Wang Jun , Deng Wenjuan , Li Daohui , Wang Zhiqiang , Liu Zheng , Cao Wenping 
Published: February 2022

AbstractThe efficient and flexible conversion of electrical energy is increasingly accomplished by megawatt insulated gate bipolar transistor (IGBT) modules. Their dynamic performance is influenced by the gate driver control, operating points and the switching loop parasitics, which are crucial to their optimized operational behaviours, efficiency and field reliability. This paper investigates the controllability of the transient voltage and current slopes of megawatt IGBT modules during their turn‐off transitions and proposes an efficient assessment method accordingly. Firstly, the causal relationship of transient characteristic variations and controllability is investigated analytically. Then, major factors impacting the controllability are analysed and validated, including the charge carrier profile, the operating points (i.e. the load voltage, the load current, and the junction temperature), and the gate resistance. Finally, an efficient method using the MOS‐channel turn‐off point on calibrated gate voltage waveform is proposed for the controllability evaluation, which can guide the IGBT, gate driver, and converter design.