bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular-level insights into the electronic effects in platinum-catalyzed carbon monoxide oxidation
Authors: Chen Wenyao , Cao Junbo , Yang Jia , Cao Yueqiang , Zhang Hao , Jiang Zheng , Zhang Jing , Qian Gang , Zhou Xinggui , Chen De , Yuan Weikang , Duan Xuezhi 
Published: November 2021

AbstractA molecular-level understanding of how the electronic structure of metal center tunes the catalytic behaviors remains a grand challenge in heterogeneous catalysis. Herein, we report an unconventional kinetics strategy for bridging the microscopic metal electronic structure and the macroscopic steady-state rate for CO oxidation over Pt catalysts. X-ray absorption and photoelectron spectroscopy as well as electron paramagnetic resonance investigations unambiguously reveal the tunable Pt electronic structures with well-designed carbon support surface chemistry. Diminishing the electron density of Pt consolidates the CO-assisted O2 dissociation pathway via the O*-O-C*-O intermediate directly observed by isotopic labeling studies and rationalized by density-functional theory calculations. A combined steady-state isotopic transient kinetic and in situ electronic analyses identifies Pt charge as the kinetics indicators by being closely related to the frequency factor, site coverage, and activation energy. Further incorporation of catalyst structural parameters yields a novel model for quantifying the electronic effects and predicting the catalytic performance. These could serve as a benchmark of catalyst design by a comprehensive kinetics study at the molecular level.
NUDT2 initiates viral RNA degradation by removal of 5′-phosphates
Authors: Laudenbach Beatrice T. , Krey Karsten , Emslander Quirin , Andersen Line Lykke , Reim Alexander , Scaturro Pietro , Mundigl Sarah , Dächert Christopher , Manske Katrin , Moser Markus , Ludwig Janos , Wohlleber Dirk , Kröger Andrea , Binder Marco , Pichlmair Andreas 
Published: November 2021

AbstractWhile viral replication processes are largely understood, comparably little is known on cellular mechanisms degrading viral RNA. Some viral RNAs bear a 5′-triphosphate (PPP-) group that impairs degradation by the canonical 5′-3′ degradation pathway. Here we show that the Nudix hydrolase 2 (NUDT2) trims viral PPP-RNA into monophosphorylated (P)-RNA, which serves as a substrate for the 5′-3′ exonuclease XRN1. NUDT2 removes 5′-phosphates from PPP-RNA in an RNA sequence- and overhang-independent manner and its ablation in cells increases growth of PPP-RNA viruses, suggesting an involvement in antiviral immunity. NUDT2 is highly homologous to bacterial RNA pyrophosphatase H (RppH), a protein involved in the metabolism of bacterial mRNA, which is 5′-tri- or diphosphorylated. Our results show a conserved function between bacterial RppH and mammalian NUDT2, indicating that the function may have adapted from a protein responsible for RNA turnover in bacteria into a protein involved in the immune defense in mammals.
Dihydroxyacetone valorization with high atom efficiency via controlling radical oxidation pathways over natural mineral-inspired catalyst
Authors: Wang Jinling , Dai Xingchao , Wang Hualin , Liu Honglai , Rabeah Jabor , Brückner Angelika , Shi Feng , Gong Ming , Yang Xuejing 
Published: November 2021

AbstractDiminishing fossil fuel resources and calls for sustainability are driving the urgent need for efficient valorization of renewable resources with high atom efficiency. Inspired from the natural goethite mineral with Mn paragenesis, we develop cost-effective MnO2/goethite catalysts for the efficient valorization of dihydroxyacetone, an important biomass-based platform molecule, into value-added glycolic acid and formic acid with 83.2% and 93.4% yields. The DHA substrates first undergo C−C cleavage to selectively form glycolic acid and hydroxymethyl (·CH2OH) radicals, which are further oxidized into formic acid. The kinetic and isotopic labeling experiments reveal that the catalase-like activity of MnO2 turns the oxidative radicals into oxygen, which then switches towards a hydroxymethyl peroxide (HMOO) pathway for formic acid generation and prevents formic acid over-oxidation. This nature-inspired catalyst design not only significantly improves the carbon efficiency to 86.6%, but also enhances the oxygen atom utilization efficiency from 11.2% to 46.6%, indicating a promising biomass valorization process.
Learning neural network potentials from experimental data via Differentiable Trajectory Reweighting
Authors: Thaler Stephan , Zavadlav Julija 
Published: November 2021

AbstractIn molecular dynamics (MD), neural network (NN) potentials trained bottom-up on quantum mechanical data have seen tremendous success recently. Top-down approaches that learn NN potentials directly from experimental data have received less attention, typically facing numerical and computational challenges when backpropagating through MD simulations. We present the Differentiable Trajectory Reweighting (DiffTRe) method, which bypasses differentiation through the MD simulation for time-independent observables. Leveraging thermodynamic perturbation theory, we avoid exploding gradients and achieve around 2 orders of magnitude speed-up in gradient computation for top-down learning. We show effectiveness of DiffTRe in learning NN potentials for an atomistic model of diamond and a coarse-grained model of water based on diverse experimental observables including thermodynamic, structural and mechanical properties. Importantly, DiffTRe also generalizes bottom-up structural coarse-graining methods such as iterative Boltzmann inversion to arbitrary potentials. The presented method constitutes an important milestone towards enriching NN potentials with experimental data, particularly when accurate bottom-up data is unavailable.
Experimental observation of localized interfacial phonon modes
Authors: Cheng Zhe , Li Ruiyang , Yan Xingxu , Jernigan Glenn , Shi Jingjing , Liao Michael E. , Hines Nicholas J. , Gadre Chaitanya A. , Idrobo Juan Carlos , Lee Eungkyu , Hobart Karl D. , Goorsky Mark S. , Pan Xiaoqing , Luo Tengfei , Graham Samuel 
Published: November 2021

AbstractInterfaces impede heat flow in micro/nanostructured systems. Conventional theories for interfacial thermal transport were derived based on bulk phonon properties of the materials making up the interface without explicitly considering the atomistic interfacial details, which are found critical to correctly describing thermal boundary conductance. Recent theoretical studies predicted the existence of localized phonon modes at the interface which can play an important role in understanding interfacial thermal transport. However, experimental validation is still lacking. Through a combination of Raman spectroscopy and high-energy-resolution electron energy-loss spectroscopy in a scanning transmission electron microscope, we report the experimental observation of localized interfacial phonon modes at ~12 THz at a high-quality epitaxial Si-Ge interface. These modes are further confirmed using molecular dynamics simulations with a high-fidelity neural network interatomic potential, which also yield thermal boundary conductance agreeing well with that measured in time-domain thermoreflectance experiments. Simulations find that the interfacial phonon modes have an obvious contribution to the total thermal boundary conductance. Our findings significantly contribute to the understanding of interfacial thermal transport physics and have impact on engineering thermal boundary conductance at interfaces in applications such as electronics thermal management and thermoelectric energy conversion.
Versatile selective evolutionary pressure using synthetic defect in universal metabolism
Authors: Sellés Vidal Lara , Murray James W. , Heap John T. 
Published: November 2021

AbstractThe non-natural needs of industrial applications often require new or improved enzymes. The structures and properties of enzymes are difficult to predict or design de novo. Instead, semi-rational approaches mimicking evolution entail diversification of parent enzymes followed by evaluation of isolated variants. Artificial selection pressures coupling desired enzyme properties to cell growth could overcome this key bottleneck, but are usually narrow in scope. Here we show diverse enzymes using the ubiquitous cofactors nicotinamide adenine dinucleotide (NAD) or nicotinamide adenine dinucleotide phosphate (NADP) can substitute for defective NAD regeneration, representing a very broadly-applicable artificial selection. Inactivation of Escherichia coli genes required for anaerobic NAD regeneration causes a conditional growth defect. Cells are rescued by foreign enzymes connected to the metabolic network only via NAD or NADP, but only when their substrates are supplied. Using this principle, alcohol dehydrogenase, imine reductase and nitroreductase variants with desired selectivity modifications, and a high-performing isopropanol metabolic pathway, are isolated from libraries of millions of variants in single-round experiments with typical limited information to guide design.
A human fetal liver-derived infant MLL-AF4 acute lymphoblastic leukemia model reveals a distinct fetal gene expression program
Authors: Rice Siobhan , Jackson Thomas , Crump Nicholas T. , Fordham Nicholas , Elliott Natalina , O’Byrne Sorcha , Fanego Maria del Mar Lara , Addy Dilys , Crabb Trisevgeni , Dryden Carryl , Inglott Sarah , Ladon Dariusz , Wright Gary , Bartram Jack , Ancliff Philip , Mead Adam J. , Halsey Christina , Roberts Irene , Milne Thomas A. , Roy Anindita 
Published: November 2021

AbstractAlthough 90% of children with acute lymphoblastic leukemia (ALL) are now cured, the prognosis for infant-ALL remains dismal. Infant-ALL is usually caused by a single genetic hit that arises in utero: an MLL/KMT2A gene rearrangement (MLL-r). This is sufficient to induce a uniquely aggressive and treatment-refractory leukemia compared to older children. The reasons for disparate outcomes in patients of different ages with identical driver mutations are unknown. Using the most common MLL-r in infant-ALL, MLL-AF4, as a disease model, we show that fetal-specific gene expression programs are maintained in MLL-AF4 infant-ALL but not in MLL-AF4 childhood-ALL. We use CRISPR-Cas9 gene editing of primary human fetal liver hematopoietic cells to produce a t(4;11)/MLL-AF4 translocation, which replicates the clinical features of infant-ALL and drives infant-ALL-specific and fetal-specific gene expression programs. These data support the hypothesis that fetal-specific gene expression programs cooperate with MLL-AF4 to initiate and maintain the distinct biology of infant-ALL.
STAT3 is critical for skeletal development and bone homeostasis by regulating osteogenesis
Authors: Zhou Siru , Dai Qinggang , Huang Xiangru , Jin Anting , Yang Yiling , Gong Xinyi , Xu Hongyuan , Gao Xin , Jiang Lingyong 
Published: November 2021

AbstractSkeletal deformities are typical AD-HIES manifestations, which are mainly caused by heterozygous and loss-of-function mutations in Signal transducer and activator of transcription 3 (STAT3). However, the mechanism is still unclear and the treatment strategy is limited. Herein, we reported that the mice with Stat3 deletion in osteoblasts, but not in osteoclasts, induced AD-HIES-like skeletal defects, including craniofacial malformation, osteoporosis, and spontaneous bone fracture. Mechanistic analyses revealed that STAT3 in cooperation with Msh homeobox 1(MSX1) drove osteoblast differentiation by promoting Distal-less homeobox 5(Dlx5) transcription. Furthermore, pharmacological activation of STAT3 partially rescued skeletal deformities in heterozygous knockout mice, while inhibition of STAT3 aggravated bone loss. Taken together, these data show that STAT3 is critical for modulating skeletal development and maintaining bone homeostasis through STAT3-indcued osteogenesis and suggest it may be a potential target for treatments.
Structures of tweety homolog proteins TTYH2 and TTYH3 reveal a Ca2+-dependent switch from intra- to intermembrane dimerization
Authors: Li Baobin , Hoel Christopher M. , Brohawn Stephen G. 
Published: November 2021

AbstractTweety homologs (TTYHs) comprise a conserved family of transmembrane proteins found in eukaryotes with three members (TTYH1-3) in vertebrates. They are widely expressed in mammals including at high levels in the nervous system and have been implicated in cancers and other diseases including epilepsy, chronic pain, and viral infections. TTYHs have been reported to form Ca2+- and cell volume-regulated anion channels structurally distinct from any characterized protein family with potential roles in cell adhesion, migration, and developmental signaling. To provide insight into TTYH family structure and function, we determined cryo-EM structures of Mus musculus TTYH2 and TTYH3 in lipid nanodiscs. TTYH2 and TTYH3 adopt a previously unobserved fold which includes an extended extracellular domain with a partially solvent exposed pocket that may be an interaction site for hydrophobic molecules. In the presence of Ca2+, TTYH2 and TTYH3 form homomeric cis-dimers bridged by extracellularly coordinated Ca2+. Strikingly, in the absence of Ca2+, TTYH2 forms trans-dimers that span opposing membranes across a ~130 Å intermembrane space as well as a monomeric state. All TTYH structures lack ion conducting pathways and we do not observe TTYH2-dependent channel activity in cells. We conclude TTYHs are not pore forming subunits of anion channels and their function may involve Ca2+-dependent changes in quaternary structure, interactions with hydrophobic molecules near the extracellular membrane surface, and/or association with additional protein partners.
Current progress of rehabilitative strategies in stem cell therapy for spinal cord injury: a review
Authors: Tashiro Syoichi , Tsuji Osahiko , Shinozaki Munehisa , Shibata Takahiro , Yoshida Takashi , Tomioka Yohei , Unai Kei , Kondo Takahiro , Itakura Go , Kobayashi Yoshiomi , Yasuda Akimasa , Nori Satoshi , Fujiyoshi Kanehiro , Nagoshi Narihito , Kawakami Michiyuki , Uemura Osamu , Yamada Shin , Tsuji Tetsuya , Okano Hideyuki , Nakamura Masaya 
Published: November 2021

AbstractStem cell-based regenerative therapy has opened an avenue for functional recovery of patients with spinal cord injury (SCI). Regenerative rehabilitation is attracting wide attention owing to its synergistic effects, feasibility, non-invasiveness, and diverse and systemic properties. In this review article, we summarize the features of rehabilitation, describe the mechanism of combinatorial treatment, and discuss regenerative rehabilitation in the context of SCI. Although conventional rehabilitative methods have commonly been implemented alone, especially in studies of acute-to-subacute SCI, the combinatorial effects of intensive and advanced methods, including various neurorehabilitative approaches, have also been reported. Separating the concept of combined rehabilitation from regenerative rehabilitation, we suggest that the main roles of regenerative rehabilitation can be categorized as conditioning/reconditioning, functional training, and physical exercise, all of which are indispensable for enhancing functional recovery achieved using stem cell therapies.
MCMICRO: a scalable, modular image-processing pipeline for multiplexed tissue imaging
Authors: Schapiro Denis , Sokolov Artem , Yapp Clarence , Chen Yu-An , Muhlich Jeremy L. , Hess Joshua , Creason Allison L. , Nirmal Ajit J. , Baker Gregory J. , Nariya Maulik K. , Lin Jia-Ren , Maliga Zoltan , Jacobson Connor A. , Hodgman Matthew W. , Ruokonen Juha , Farhi Samouil L. , Abbondanza Domenic , McKinley Eliot T. , Persson Daniel , Betts Courtney , Sivagnanam Shamilene , Regev Aviv , Goecks Jeremy , Coffey Robert J. , Coussens Lisa M. , Santagata Sandro , Sorger Peter K. 
Published: November 2021

AbstractHighly multiplexed tissue imaging makes detailed molecular analysis of single cells possible in a preserved spatial context. However, reproducible analysis of large multichannel images poses a substantial computational challenge. Here, we describe a modular and open-source computational pipeline, MCMICRO, for performing the sequential steps needed to transform whole-slide images into single-cell data. We demonstrate the use of MCMICRO on tissue and tumor images acquired using multiple imaging platforms, thereby providing a solid foundation for the continued development of tissue imaging software.
SDG partnerships may perpetuate the global North–South divide
Authors: Blicharska Malgorzata , Teutschbein Claudia , Smithers Richard J. 
Published: November 2021

AbstractThe 2030 Agenda for Sustainable Development gives equal emphasis to developed (“Northern”) countries and developing (“Southern”) countries. Thus, implementation of the Sustainable Development Goals (SDGs) demands coherent collaboration to transform society across all countries. Yet, there has been little research published on SDG partnerships and this is the first study to explore the extent to which partners from Northern and Southern countries are involved in them and their focus. It identifies that involvement is unequally distributed and may perpetuate the North–South divide in countries’ resources, including access to data and scientific capacities. Most notably, partners from low-income countries are involved in far fewer partnerships than partners from countries in all other World Bank income categories, although the former are least able to develop sustainably. As such, all those promoting sustainable development from governmental, private and third-sector organisations need to address global inequalities in establishing and implementing SDG partnerships if, collectively, they are to facilitate delivery of Agenda 2030.
Pax5 mediates the transcriptional activation of the CD81 gene
Authors: Hosokawa Kohei , Ishimaru Hanako , Watanabe Tadashi , Fujimuro Masahiro 
Published: November 2021

AbstractCD81 is an integral membrane protein of the tetraspanin family and forms complexes with a variety of other cell surface membrane proteins. CD81 is involved in cell migration and B cell activation. However, the mechanism of the transcriptional regulation of the CD81 gene remains unclear. Here, we revealed that CD81 transcriptional activation was required for binding of the transcription factor Pax5 at the Pax5-binding sequence (-54)GCGGGAC(-48) located upstream of the transcriptional start site (TSS) of the CD81 gene. The reporter assay showed that the DNA sequence between − 130 and − 39 bp upstream of the TSS of the CD81 gene had promoter activity for CD81 transcription. The DNA sequence between − 130 and − 39 bp upstream of TSS of CD81 harbors two potential Pax5-binding sequences (-87)GCGTGAG(-81) and (-54)GCGGGAC(-48). Reporter, electrophoresis mobility shift, and chromatin immunoprecipitation (ChIP) assays disclosed that Pax5 bound to the (-54)GCGGGAC(-48) in the promoter region of the CD81 gene in order to activate CD81 transcription. Pax5 overexpression increased the expression level of CD81 protein, while the Pax5-knockdown by shRNA decreased CD81 expression. Moreover, we found that the expression level of CD81 was positively correlated with Pax5 expression in human tumor cell lines. Because CD81 was reported to be involved in cell migration, we evaluated the effects of Pax5 overexpression by wound healing and transwell assays. The data showed that overexpression of either Pax5 or CD81 promoted the epithelial cell migration. Thus, our findings provide insights into the transcriptional mechanism of the CD81 gene through transcription factor Pax5.
A new p65 isoform that bind the glucocorticoid hormone and is expressed in inflammation liver diseases and COVID-19
Authors: Spinelli Gaetano , Biddeci Giuseppa , Artale Anna , Valentino Francesca , Tarantino Giuseppe , Gallo Giuseppe , Gianguzza Fabrizio , Conaldi Pier Giulio , Corrao Salvatore , Gervasi Francesco , Aronica Tommaso Silvano , Di Leonardo Aldo , Duro Giovanni , Di Blasi Francesco 
Published: November 2021

AbstractInflammation is a physiological process whose deregulation causes some diseases including cancer. Nuclear Factor kB (NF-kB) is a family of ubiquitous and inducible transcription factors, in which the p65/p50 heterodimer is the most abundant complex, that play critical roles mainly in inflammation. Glucocorticoid Receptor (GR) is a ligand-activated transcription factor and acts as an anti-inflammatory agent and immunosuppressant. Thus, NF-kB and GR are physiological antagonists in the inflammation process. Here we show that in mice and humans there is a spliced variant of p65, named p65 iso5, which binds the corticosteroid hormone dexamethasone amplifying the effect of the glucocorticoid receptor and is expressed in the liver of patients with hepatic cirrhosis and hepatocellular carcinoma (HCC). Furthermore, we have quantified the gene expression level of p65 and p65 iso5 in the PBMC of patients affected by SARS-CoV-2 disease. The results showed that in these patients the p65 and p65 iso5 mRNA levels are higher than in healthy subjects. The ability of p65 iso5 to bind dexamethasone and the regulation of the glucocorticoid (GC) response in the opposite way of the wild type improves our knowledge and understanding of the anti-inflammatory response and identifies it as a new therapeutic target to control inflammation and related diseases.
Gut microbiota depletion from early adolescence alters anxiety and depression-related behaviours in male mice with Alzheimer-like disease
Authors: Mosaferi Belal , Jand Yahya , Salari Ali-Akbar 
Published: November 2021

AbstractThe gut-microbiota–brain axis plays an important role in stress-related disorders, and dysfunction of this complex bidirectional system is associated with Alzheimer’s disease. This study aimed to assess the idea that whether gut microbiota depletion from early adolescence can alter anxiety- and depression-related behaviours in adult mice with or without Alzheimer-like disease. Male C57BL/6 mice were treated with an antibiotic cocktail from weaning to adulthood. Adult mice received an intracerebroventricular injection of amyloid-beta (Aβ)1–42, and were subjected to anxiety and depression tests. We measured, brain malondialdehyde and glutathione following anxiety tests, and assessed brain oxytocin and the hypothalamic–pituitary–adrenal (HPA) axis function by measuring adrenocorticotrophic hormone (ACTH) and corticosterone following depression tests. Healthy antibiotic-treated mice displayed significant decreases in anxiety-like behaviours, whereas they did not show any alterations in depression-like behaviours and HPA axis function. Antibiotic treatment from early adolescence prevented the development of anxiety- and depression-related behaviours, oxidative stress and HPA axis dysregulation in Alzheimer-induced mice. Antibiotic treatment increased oxytocin in the brain of healthy but not Alzheimer-induced mice. Taken together, these findings suggest that gut microbiota depletion following antibiotic treatment from early adolescence might profoundly affect anxiety- and depression-related behaviours, and HPA axis function in adult mice with Alzheimer-like disease.