bluuebunny/crossref_metadata_2025_split huggingface dataset:
Construction of boron-stereogenic compounds via enantioselective Cu-catalyzed desymmetric B–H bond insertion reaction
Authors: Zhang Guan , Zhang Zhihan , Hou Mengyuan , Cai Xinping , Yang Kai , Yu Peiyuan , Song Qiuling 
Published: May 2022

AbstractCompared with the well-developed carbon-stereogenic chemistry, the construction of boron-stereogenic compounds remains undeveloped and challenging. Herein, the previously elusive catalytic enantioselective construction of boron-stereogenic compounds has been achieved through enantioselective desymmetric B–H bond insertion reaction. The B–H bond insertion reaction of 2-arylpyridine-boranes with versatile diazo compounds under chiral copper catalyst can afford boron-stereogenic compounds with good to excellent enantioselectivity. Moreover, the synthetic utility of this reaction is demonstrated by the scalability and downstream transformations. DFT calculations provide insights into the reaction mechanism and the origin of stereoselectivity.
Photo-thermo semi-hydrogenation of acetylene on Pd1/TiO2 single-atom catalyst
Authors: Guo Yalin , Huang Yike , Zeng Bin , Han Bing , AKRI Mohcin , Shi Ming , Zhao Yue , Li Qinghe , Su Yang , Li Lin , Jiang Qike , Cui Yi-Tao , Li Lei , Li Rengui , Qiao Botao , Zhang Tao 
Published: May 2022

AbstractSemi-hydrogenation of acetylene in excess ethylene is a key industrial process for ethylene purification. Supported Pd catalysts have attracted most attention due to their superior intrinsic activity but often suffer from low selectivity. Pd single-atom catalysts (SACs) are promising to significantly improve the selectivity, but the activity needs to be improved and the feasible preparation of Pd SACs remains a grand challenge. Here, we report a simple strategy to construct Pd1/TiO2 SACs by selectively encapsulating the co-existed small amount of Pd nanoclusters/nanoparticles based on their different strong metal-support interaction (SMSI) occurrence conditions. In addition, photo-thermo catalysis has been applied to this process where a much-improved catalytic activity was obtained. Detailed characterization combined with DFT calculation suggests that photo-induced electrons transferred from TiO2 to the adjacent Pd atoms facilitate the activation of acetylene. This work offers an opportunity to develop highly stable Pd SACs for efficient catalytic semi-hydrogenation process.
MRNIP condensates promote DNA double-strand break sensing and end resection
Authors: Wang Yun-Long , Zhao Wan-Wen , Bai Shao-Mei , Feng Li-Li , Bie Shu-Ying , Gong Li , Wang Fang , Wei Ming-Biao , Feng Wei-Xing , Pang Xiao-Lin , Qin Cao-Litao , Yin Xin-Ke , Wang Ying-Nai , Zhou Weihua , Wahl Daniel R. , Liu Quentin , Chen Ming , Hung Mien-Chie , Wan Xiang-Bo 
Published: May 2022

AbstractThe rapid recognition of DNA double-strand breaks (DSBs) by the MRE11/RAD50/NBS1 (MRN) complex is critical for the initiation of DNA damage response and DSB end resection. Here, we show that MRN complex interacting protein (MRNIP) forms liquid-like condensates to promote homologous recombination-mediated DSB repair. The intrinsically disordered region is essential for MRNIP condensate formation. Mechanically, the MRN complex is compartmentalized and concentrated into MRNIP condensates in the nucleus. After DSB formation, MRNIP condensates move to the damaged DNA rapidly to accelerate the binding of DSB by the concentrated MRN complex, therefore inducing the autophosphorylation of ATM and subsequent activation of DNA damage response signaling. Meanwhile, MRNIP condensates-enhanced MRN complex loading further promotes DSB end resection. In addition, data from xenograft models and clinical samples confirm a correlation between MRNIP and radioresistance. Together, these results reveal an important role of MRNIP phase separation in DSB response and the MRN complex-mediated DSB end resection.
Sensory adaptation mediates efficient and unambiguous encoding of natural stimuli by vestibular thalamocortical pathways
Authors: Carriot Jerome , McAllister Graham , Hooshangnejad Hamed , Mackrous Isabelle , Cullen Kathleen E. , Chacron Maurice J. 
Published: May 2022

AbstractSensory systems must continuously adapt to optimally encode stimuli encountered within the natural environment. The prevailing view is that such optimal coding comes at the cost of increased ambiguity, yet to date, prior studies have focused on artificial stimuli. Accordingly, here we investigated whether such a trade-off between optimality and ambiguity exists in the encoding of natural stimuli in the vestibular system. We recorded vestibular nuclei and their target vestibular thalamocortical neurons during naturalistic and artificial self-motion stimulation. Surprisingly, we found no trade-off between optimality and ambiguity. Using computational methods, we demonstrate that thalamocortical neural adaptation in the form of contrast gain control actually reduces coding ambiguity without compromising the optimality of coding under naturalistic but not artificial stimulation. Thus, taken together, our results challenge the common wisdom that adaptation leads to ambiguity and instead suggest an essential role in underlying unambiguous optimized encoding of natural stimuli.
Tailored modular assembly derived self-healing polythioureas with largely tunable properties covering plastics, elastomers and fibers
Authors: Li Yan Mei , Zhang Ze Ping , Rong Min Zhi , Zhang Ming Qiu 
Published: May 2022

AbstractTo impart self-healing polymers largely adjustable dynamicity and mechanical performance, here we develop libraries of catalyst-free reversible polythioureas directly from commodity 1,4-phenylene diisothiocyanate and amines via facile click chemistry based modular assembly. By using the amine modules with various steric hindrances and flexibilities, the reversible thiourea units acquire triggering temperatures from room temperature to 120 °C. Accordingly, the derived self-healable, recyclable and controlled degradable dynamically crosslinked polythioureas can take effect within wide temperature range. Moreover, mechanical properties of the materials can be tuned covering plastics, elastomers and fibers using (i) different assemble modules or (ii) solid-state stretching. Particularly, unidirectional stretching leads to the record-high tensile strength of 266 MPa, while bidirectional stretching provides the materials with biaxial strengths up to over 120 MPa. The molecular mechanism and technological innovations discussed in this work may benefit promotion and application of self-healing polymers towards greatly diverse demands and scenarios.
Substrate recognition and cryo-EM structure of the ribosome-bound TAC toxin of Mycobacterium tuberculosis
Authors: Mansour Moise , Giudice Emmanuel , Xu Xibing , Akarsu Hatice , Bordes Patricia , Guillet Valérie , Bigot Donna-Joe , Slama Nawel , D’urso Gaetano , Chat Sophie , Redder Peter , Falquet Laurent , Mourey Lionel , Gillet Reynald , Genevaux Pierre 
Published: May 2022

AbstractToxins of toxin-antitoxin systems use diverse mechanisms to control bacterial growth. Here, we focus on the deleterious toxin of the atypical tripartite toxin-antitoxin-chaperone (TAC) system of Mycobacterium tuberculosis, whose inhibition requires the concerted action of the antitoxin and its dedicated SecB-like chaperone. We show that the TAC toxin is a bona fide ribonuclease and identify exact cleavage sites in mRNA targets on a transcriptome-wide scale in vivo. mRNA cleavage by the toxin occurs after the second nucleotide of the ribosomal A-site codon during translation, with a strong preference for CCA codons in vivo. Finally, we report the cryo-EM structure of the ribosome-bound TAC toxin in the presence of native M. tuberculosis cspA mRNA, revealing the specific mechanism by which the TAC toxin interacts with the ribosome and the tRNA in the P-site to cleave its mRNA target.
CDK12 promotes tumorigenesis but induces vulnerability to therapies inhibiting folate one-carbon metabolism in breast cancer
Authors: Filippone M. G. , Gaglio D. , Bonfanti R. , Tucci F. A. , Ceccacci E. , Pennisi R. , Bonanomi M. , Jodice G. , Tillhon M. , Montani F. , Bertalot G. , Freddi S. , Vecchi M. , Taglialatela A. , Romanenghi M. , Romeo F. , Bianco N. , Munzone E. , Sanguedolce F. , Vago G. , Viale G. , Di Fiore P. P. , Minucci S. , Alberghina L. , Colleoni M. , Veronesi P. , Tosoni D. , Pece S. 
Published: May 2022

AbstractCyclin-dependent kinase 12 (CDK12) overexpression is implicated in breast cancer, but whether it has a primary or only a cooperative tumorigenic role is unclear. Here, we show that transgenic CDK12 overexpression in the mouse mammary gland per se is sufficient to drive the emergence of multiple and multifocal tumors, while, in cooperation with known oncogenes, it promotes earlier tumor onset and metastasis. Integrative transcriptomic, metabolomic and functional data reveal that hyperactivation of the serine-glycine-one-carbon network is a metabolic hallmark inherent to CDK12-induced tumorigenesis. Consistently, in retrospective patient cohort studies and in patient-derived xenografts, CDK12-overexpressing breast tumors show positive response to methotrexate-based chemotherapy targeting CDK12-induced metabolic alterations, while being intrinsically refractory to other types of chemotherapy. In a retrospective analysis of hormone receptor-negative and lymph node-positive breast cancer patients randomized in an adjuvant phase III trial to 1-year low-dose metronomic methotrexate-based chemotherapy or no maintenance chemotherapy, a high CDK12 status predicts a dramatic reduction in distant metastasis rate in the chemotherapy-treated vs. not-treated arm. Thus, by coupling tumor progression with metabolic reprogramming, CDK12 creates an actionable vulnerability for breast cancer therapy and might represent a suitable companion biomarker for targeted antimetabolite therapies in human breast cancers.
Ketamine activates adult-born immature granule neurons to rapidly alleviate depression-like behaviors in mice
Authors: Rawat Radhika , Tunc-Ozcan Elif , McGuire Tammy L. , Peng Chian-Yu , Kessler John A. 
Published: May 2022

AbstractKetamine treatment decreases depressive symptoms within hours, but the mechanisms mediating these rapid antidepressant effects are unclear. Here, we demonstrate that activity of adult-born immature granule neurons (ABINs) in the mouse hippocampal dentate gyrus is both necessary and sufficient for the rapid antidepressant effects of ketamine. Ketamine treatment activates ABINs in parallel with its behavioral effects in both stressed and unstressed mice. Chemogenetic inhibition of ABIN activity blocks the antidepressant effects of ketamine, indicating that this activity is necessary for the behavioral effects. Conversely, chemogenetic activation of ABINs without any change in neuron numbers mimics both the cellular and the behavioral effects of ketamine, indicating that increased activity of ABINs is sufficient for rapid antidepressant effects. These findings thus identify a specific cell population that mediates the antidepressant actions of ketamine, indicating that ABINs can potentially be targeted to limit ketamine’s side effects while preserving its therapeutic efficacy.
Structure and mechanism of NALCN-FAM155A-UNC79-UNC80 channel complex
Authors: Kang Yunlu , Chen Lei 
Published: May 2022

AbstractNALCN channel mediates sodium leak currents and is important for maintaining proper resting membrane potential. NALCN and FAM155A form the core complex of the channel, the activity of which essentially depends on the presence of both UNC79 and UNC80, two auxiliary proteins. NALCN, FAM155A, UNC79, and UNC80 co-assemble into a large hetero-tetrameric channel complex. Genetic mutations of NALCN channel components lead to neurodevelopmental diseases. However, the structure and mechanism of the intact channel complex remain elusive. Here, we present the cryo-EM structure of the mammalian NALCN-FAM155A-UNC79-UNC80 quaternary complex. The structure shows that UNC79-UNC80 form a large piler-shaped heterodimer which was tethered to the intracellular side of the NALCN channel through tripartite interactions with the cytoplasmic loops of NALCN. Two interactions are essential for proper cell surface localization of NALCN. The other interaction relieves the self-inhibition of NALCN by pulling the auto-inhibitory CTD Interacting Helix (CIH) out of its binding site. Our work defines the structural mechanism of NALCN modulation by UNC79 and UNC80.
Structural basis of ion – substrate coupling in the Na+-dependent dicarboxylate transporter VcINDY
Authors: Sauer David B. , Marden Jennifer J. , Sudar Joseph C. , Song Jinmei , Mulligan Christopher , Wang Da-Neng 
Published: May 2022

AbstractThe Na+-dependent dicarboxylate transporter from Vibrio cholerae (VcINDY) is a prototype for the divalent anion sodium symporter (DASS) family. While the utilization of an electrochemical Na+ gradient to power substrate transport is well established for VcINDY, the structural basis of this coupling between sodium and substrate binding is not currently understood. Here, using a combination of cryo-EM structure determination, succinate binding and site-directed cysteine alkylation assays, we demonstrate that the VcINDY protein couples sodium- and substrate-binding via a previously unseen cooperative mechanism by conformational selection. In the absence of sodium, substrate binding is abolished, with the succinate binding regions exhibiting increased flexibility, including HPinb, TM10b and the substrate clamshell motifs. Upon sodium binding, these regions become structurally ordered and create a proper binding site for the substrate. Taken together, these results provide strong evidence that VcINDY’s conformational selection mechanism is a result of the sodium-dependent formation of the substrate binding site.
Rapid meniscus-guided printing of stable semi-solid-state liquid metal microgranular-particle for soft electronics
Authors: Lee Gun-Hee , Lee Ye Rim , Kim Hanul , Kwon Do A , Kim Hyeonji , Yang Congqi , Choi Siyoung Q. , Park Seongjun , Jeong Jae-Woong , Park Steve 
Published: May 2022

AbstractLiquid metal is being regarded as a promising material for soft electronics owing to its distinct combination of high electrical conductivity comparable to that of metals and exceptional deformability derived from its liquid state. However, the applicability of liquid metal is still limited due to the difficulty in simultaneously achieving its mechanical stability and initial conductivity. Furthermore, reliable and rapid patterning of stable liquid metal directly on various soft substrates at high-resolution remains a formidable challenge. In this work, meniscus-guided printing of ink containing polyelectrolyte-attached liquid metal microgranular-particle in an aqueous solvent to generate semi-solid-state liquid metal is presented. Liquid metal microgranular-particle printed in the evaporative regime is mechanically stable, initially conductive, and patternable down to 50 μm on various substrates. Demonstrations of the ultrastretchable (~500% strain) electrical circuit, customized e-skin, and zero-waste ECG sensor validate the simplicity, versatility, and reliability of this manufacturing strategy, enabling broad utility in the development of advanced soft electronics.
Sox2 levels regulate the chromatin occupancy of WNT mediators in epiblast progenitors responsible for vertebrate body formation
Authors: Blassberg Robert , Patel Harshil , Watson Thomas , Gouti Mina , Metzis Vicki , Delás M. Joaquina , Briscoe James 
Published: May 2022

AbstractWNT signalling has multiple roles. It maintains pluripotency of embryonic stem cells, assigns posterior identity in the epiblast and induces mesodermal tissue. Here we provide evidence that these distinct functions are conducted by the transcription factor SOX2, which adopts different modes of chromatin interaction and regulatory element selection depending on its level of expression. At high levels, SOX2 displaces nucleosomes from regulatory elements with high-affinity SOX2 binding sites, recruiting the WNT effector TCF/β-catenin and maintaining pluripotent gene expression. Reducing SOX2 levels destabilizes pluripotency and reconfigures SOX2/TCF/β-catenin occupancy to caudal epiblast expressed genes. These contain low-affinity SOX2 sites and are co-occupied by T/Bra and CDX. The loss of SOX2 allows WNT-induced mesodermal differentiation. These findings define a role for Sox2 levels in dictating the chromatin occupancy of TCF/β-catenin and reveal how context-specific responses to a signal are configured by the level of a transcription factor.
Depression symptoms 6 years after stroke are associated with higher perceived impact of stroke, limitations in ADL and restricted participation
Authors: Ytterberg Charlotte , Cegrell Linda , von Koch Lena , Wiklander Maria 
Published: May 2022

AbstractLate post-stroke depression symptoms are understudied. This study aimed to investigate depression symptoms 6 years after stroke, and associations with perceived impact of stroke, activities of daily living (ADL), and participation in social and everyday activities. Data was collected in a 6-year follow-up in a longitudinal study of stroke. Assessments included Hospital Anxiety and Depression Scale (HADS) for depression symptoms, Stroke Impact Scale 3.0. for perceived impact of stroke,
Barthel Index for ADL, Frenchay Activities Index for participation in social and everyday activities. The research questions were addressed by bivariate analyses (with HADS-D ≥ 4 as cut-off), and hierarchical multiple regression
analyses using continuous HADS-D scores. Forty percent of the 105 participants (57% men, age 30–91) showed depression symptoms (HADS-D ≥ 4). Depression symptoms were associated with higher perceived impact of
stroke, more dependence in ADL, and more restrictions in participation in social and everyday activities. Most of those with depression symptoms had low scores on HADS, indicating that even mild depression symptoms might
be relevant to identify and target in treatment and rehabilitation of long-term consequences of stroke.
First biphotochromic fluorescent protein moxSAASoti stabilized for oxidizing environment
Authors: Marynich N. K. , Khrenova M. G. , Gavshina A. V. , Solovyev I. D. , Savitsky A. P. 
Published: May 2022

AbstractBiphotochromic proteins simultaneously possess reversible photoswitching (on-to-off) and irreversible photoconversion (green-to-red). High photochemical reactivity of cysteine residues is one of the reasons for the development of “mox”-monomeric and oxidation resistant proteins. Based on site-saturated simultaneous two-point C105 and C117 mutagenesis, we chose C21N/C71G/C105G/C117T/C175A as the moxSAASoti variant. Since its on-to-off photoswitching rate is higher, off-to-on recovery is more complete and photoconversion rates are higher than those of mSAASoti. We analyzed the conformational behavior of the F177 side chain by classical MD simulations. The conformational flexibility of the F177 side chain is mainly responsible for the off-to-on conversion rate changes and can be further utilized as a measure of the conversion rate. Point mutations in mSAASoti mainly affect the pKavalues of the red form and off-to-on switching. We demonstrate that the microscopic measure of the observed pKavalue is the C–O bond length in the phenyl fragment of the neutral chromophore. According to molecular dynamics simulations with QM/MM potentials, larger C–O bond lengths are found for proteins with larger pKa. This feature can be utilized for prediction of the pKavalues of red fluorescent proteins.
High-speed X-ray ptychographic tomography
Authors: Batey Darren , Rau Christoph , Cipiccia Silvia 
Published: May 2022

AbstractX-ray ptychography is a coherent scanning imaging technique widely used at synchrotron facilities for producing quantitative phase images beyond the resolution limit of conventional x-ray optics. The scanning nature of the technique introduces an inherent overhead to the collection at every scan position and limits the acquisition time of each 2D projection. The overhead associated with motion can be minimised with a continuous-scanning approach. Here we present an acquisition architecture based on continuous-scanning and up-triggering which allows to record ptychographic datasets at up to 9 kHz. We demonstrate the method by applying it to record 2D scans at up to 273 µm2/s and 3D scans of a (20 µm)3 volume in less than three hours. We discuss the current limitations and the outlook toward the development of sub-second 2D acquisition and minutes-long 3D ptychographic tomograms.
Preyssler-type phosphotungstate is a new family of negative-staining reagents for the TEM observation of viruses
Authors: Sahiro Koichi , Kawato Yasuhiko , Koike Kanae , Sano Tsuneji , Nakai Toshihiro , Sadakane Masahiro 
Published: May 2022

AbstractTransmission electron microscopy (TEM) is an essential method in virology because it allows for direct visualization of virus morphology at a nanometer scale. Negative staining to coat virions with heavy metal ions must be performed before TEM observations to achieve sufficient contrast. Herein, we report that potassium salts of Preyssler-type phosphotungstates (K(15-n)[P5W30O110Mn+], M = Na+, Ca2+, Ce3+, Eu3+, Bi3+, or Y3+) are high-performance negative staining reagents. Additionally, we compare the staining abilities of these salts to those of uranyl acetate and Keggin-type phosphotungstate. The potassium salt of Preyssler-type phosphotungstates has the advantage of not requiring prior neutralization because it is a neutral compound. Moreover, the potassium counter-cation can be protonated by a reaction with H+-resin, allowing easy exchange of protons with other cations by acid–base reaction. Therefore, the counter-cations can be changed. Encapsulated cations can also be exchanged, and clear TEM images were obtained using Preyssler-type compounds with different encapsulated cations. Preyssler-type phosphotungstates may be superior negative staining reagents for observing virus. Polyoxotungstates (tungsten-oxide molecules with diverse molecular structures and properties) are thus promising tools to develop negative staining reagents for TEM observations.