bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival control of oligodendrocyte progenitor cells requires the transcription factor 4 during olfactory bulb development
Authors: Zhang Yilan , Cai Yuqun , Wang Yafei , Deng Xin , Zhao Yifan , Zhang Yubin , Xie Yunli 
Published: January 2021

AbstractA proper number of oligodendrocytes in the nerve system is essential for neuronal functions. In the olfactory bulb (OB), enriched oligodendrocytes are crucial for olfactory information processing. However, how the precise number of oligodendrocytes in the OB is regulated remains elusive. Here we identified that the transcription factor 4 (Tcf4)-mediated cell death is essential for generating an appropriate number of oligodendrocyte progenitor cells (OPCs) and thereby oligodendrocytes in the OB. We showed that Nkx2.1-positive progenitors in the medial ganglionic eminence (MGE) and anterior entopeduncular area (AEP) provide the first source of OPCs in the OB. Conditional depletion of Tcf4 leads to an increase of OPCs in the OB, which is mediated by the suppression of programmed cell death. Furthermore, we showed that Tcf4 mediated OPC survival is cell-autonomous by transplantation assay. Mechanistically, we identified Bax/Bak as a potential key pathway to promote OPC elimination during OB development. Depletion of Bax/Bak in Nkx2.1 lineage results in an increase of OPCs in the OB. Mutations in TCF4 causes Pitt-Hopkins syndrome, a severe neurodevelopmental disorder. Thus, our findings reveal an important intrinsic mechanism underlying the survival control of OPCs in the OB and provide new insights into the pathogenesis of Pitt–Hopkins syndrome.
Inhibition of Aurora Kinase B activity disrupts development and differentiation of salivary glands
Authors: Shaalan Abeer K. , Teshima Tathyane H. N. , Tucker Abigail S. , Proctor Gordon B. 
Published: January 2021

AbstractLittle is known about the key molecules that regulate cell division during organogenesis. Here we determine the role of the cell cycle promoter aurora kinase B (AURKB) during development, using embryonic salivary glands (E-SGs) as a model. AURKB is a serine/threonine kinase that regulates key events in mitosis, which makes it an attractive target for tailored anticancer therapy. Many reports have elaborated on the role of AURKB in neoplasia and cancer; however, no previous study has shown its role during organ development. Our previous experiments have highlighted the essential requirement for AURKB during adult exocrine regeneration. To investigate if AURKB is similarly required for progression during embryonic development, we pharmacologically inhibited AURKB in developing submandibular glands (SMGs) at embryonic day (E)13.5 and E16.5, using the highly potent and selective drug Barasertib. Inhibition of AURKB interfered with the expansion of the embryonic buds. Interestingly, this effect on SMG development was also seen when the mature explants (E16.5) were incubated for 24 h with another cell cycle inhibitor Aphidicolin. Barasertib prompted apoptosis, DNA damage and senescence, the markers of which (cleaved caspase 3, γH2AX, SA-βgal and p21, respectively), were predominantly seen in the developing buds. In addition to a reduction in cell cycling and proliferation of the epithelial cells in response to AURKB inhibition, Barasertib treatment led to an excessive generation of reactive oxygen species (ROS) that resulted in downregulation of the acinar differentiation marker Mist1. Importantly, inhibition of ROS was able to rescue this loss of identity, with Mist1 expression maintained despite loss of AURKB. Together, these data identify AURKB as a key molecule in supporting embryonic development and differentiation, while inhibiting senescence-inducing signals during organogenesis.
Pervasive distribution of polyester fibres in the Arctic Ocean is driven by Atlantic inputs
Authors: Ross Peter S. , Chastain Stephen , Vassilenko Ekaterina , Etemadifar Anahita , Zimmermann Sarah , Quesnel Sarah-Ann , Eert Jane , Solomon Eric , Patankar Shreyas , Posacka Anna M. , Williams Bill 
Published: January 2021

AbstractMicroplastics are increasingly recognized as ubiquitous global contaminants, but questions linger regarding their source, transport and fate. We document the widespread distribution of microplastics in near-surface seawater from 71 stations across the European and North American Arctic - including the North Pole. We also characterize samples to a depth of 1,015 m in the Beaufort Sea. Particle abundance correlated with longitude, with almost three times more particles in the eastern Arctic compared to the west. Polyester comprised 73% of total synthetic fibres, with an east-to-west shift in infra-red signatures pointing to a potential weathering of fibres away from source. Here we suggest that relatively fresh polyester fibres are delivered to the eastern Arctic Ocean, via Atlantic Ocean inputs and/or atmospheric transport from the South. This raises further questions about the global reach of textile fibres in domestic wastewater, with our findings pointing to their widespread distribution in this remote region of the world.
Insights into genome recoding from the mechanism of a classic +1-frameshifting tRNA
Authors: Gamper Howard , Li Haixing , Masuda Isao , Miklos Robkis D. , Christian Thomas , Conn Adam B. , Blaha Gregor , Petersson E. James , Gonzalez Ruben L. , Hou Ya-Ming 
Published: January 2021

AbstractWhile genome recoding using quadruplet codons to incorporate non-proteinogenic amino acids is attractive for biotechnology and bioengineering purposes, the mechanism through which such codons are translated is poorly understood. Here we investigate translation of quadruplet codons by a +1-frameshifting tRNA, SufB2, that contains an extra nucleotide in its anticodon loop. Natural post-transcriptional modification of SufB2 in cells prevents it from frameshifting using a quadruplet-pairing mechanism such that it preferentially employs a triplet-slippage mechanism. We show that SufB2 uses triplet anticodon-codon pairing in the 0-frame to initially decode the quadruplet codon, but subsequently shifts to the +1-frame during tRNA-mRNA translocation. SufB2 frameshifting involves perturbation of an essential ribosome conformational change that facilitates tRNA-mRNA movements at a late stage of the translocation reaction. Our results provide a molecular mechanism for SufB2-induced +1 frameshifting and suggest that engineering of a specific ribosome conformational change can improve the efficiency of genome recoding.
Giant anomalous Hall effect from spin-chirality scattering in a chiral magnet
Authors: Fujishiro Yukako , Kanazawa Naoya , Kurihara Ryosuke , Ishizuka Hiroaki , Hori Tomohiro , Yasin Fehmi Sami , Yu Xiuzhen , Tsukazaki Atsushi , Ichikawa Masakazu , Kawasaki Masashi , Nagaosa Naoto , Tokunaga Masashi , Tokura Yoshinori 
Published: January 2021

AbstractThe electrical Hall effect can be significantly enhanced through the interplay of the conduction electrons with magnetism, which is known as the anomalous Hall effect (AHE). Whereas the mechanism related to band topology has been intensively studied towards energy efficient electronics, those related to electron scattering have received limited attention. Here we report the observation of giant AHE of electron-scattering origin in a chiral magnet MnGe thin film. The Hall conductivity and Hall angle, respectively, reach $$40,000$$
40
,
000
Ω−1 cm−1 and $$18$$
18
% in the ferromagnetic region, exceeding the conventional limits of AHE of intrinsic and extrinsic origins, respectively. A possible origin of the large AHE is attributed to a new type of skew-scattering via thermally excited spin-clusters with scalar spin chirality, which is corroborated by the temperature–magnetic-field profile of the AHE being sensitive to the film-thickness or magneto-crystalline anisotropy. Our results may open up a new platform to explore giant AHE responses in various systems, including frustrated magnets and thin-film heterostructures.
Pure non-local machine-learned density functional theory for electron correlation
Authors: Margraf Johannes T. , Reuter Karsten 
Published: January 2021

AbstractDensity-functional theory (DFT) is a rigorous and (in principle) exact framework for the description of the ground state properties of atoms, molecules and solids based on their electron density. While computationally efficient density-functional approximations (DFAs) have become essential tools in computational chemistry, their (semi-)local treatment of electron correlation has a number of well-known pathologies, e.g. related to electron self-interaction. Here, we present a type of machine-learning (ML) based DFA (termed Kernel Density Functional Approximation, KDFA) that is pure, non-local and transferable, and can be efficiently trained with fully quantitative reference methods. The functionals retain the mean-field computational cost of common DFAs and are shown to be applicable to non-covalent, ionic and covalent interactions, as well as across different system sizes. We demonstrate their remarkable possibilities by computing the free energy surface for the protonated water dimer at hitherto unfeasible gold-standard coupled cluster quality on a single commodity workstation.
Differential contribution of transcriptomic regulatory layers in the definition of neuronal identity
Authors: Ha Kevin C. H. , Sterne-Weiler Timothy , Morris Quaid , Weatheritt Robert J. , Blencowe Benjamin J. 
Published: January 2021

AbstractPrevious transcriptomic profiling studies have typically focused on separately analyzing mRNA expression, alternative splicing and alternative polyadenylation differences between cell and tissue types. However, the relative contribution of these three transcriptomic regulatory layers to cell type specification is poorly understood. This question is particularly relevant to neurons, given their extensive heterogeneity associated with brain location, morphology and function. In the present study, we generated profiles for the three regulatory layers from developmentally and regionally distinct subpopulations of neurons from the mouse hippocampus and broader nervous system. Multi-omics factor analyses revealed differing contributions of each transcriptomic layer in the discrimination of neurons based on their stage of development, region, and function. Importantly, profiles of differential alternative splicing and polyadenylation better discriminated specific neuronal subtype populations than gene expression patterns. These results provide evidence for differential relative contributions of coordinated gene regulatory layers in the specification of neuronal subtypes.
Structural basis for the multi-activity factor Rad5 in replication stress tolerance
Authors: Shen Miaomiao , Dhingra Nalini , Wang Quan , Cheng Chen , Zhu Songbiao , Tian Xiaolin , Yu Jun , Gong Xiaoxin , Li Xuzhichao , Zhang Hongwei , Xu Xin , Zhai Liting , Xie Min , Gao Ying , Deng Haiteng , He Yongning , Niu Hengyao , Zhao Xiaolan , Xiang Song 
Published: January 2021

AbstractThe yeast protein Rad5 and its orthologs in other eukaryotes promote replication stress tolerance and cell survival using their multiple activities, including ubiquitin ligase, replication fork remodeling and DNA lesion targeting activities. Here, we present the crystal structure of a nearly full-length Rad5 protein. The structure shows three distinct, but well-connected, domains required for Rad5’s activities. The spatial arrangement of these domains suggest that different domains can have autonomous activities but also undergo intrinsic coordination. Moreover, our structural, biochemical and cellular studies demonstrate that Rad5’s HIRAN domain mediates interactions with the DNA metabolism maestro factor PCNA and contributes to its poly-ubiquitination, binds to DNA and contributes to the Rad5-catalyzed replication fork regression, defining a new type of HIRAN domains with multiple activities. Our work provides a framework to understand how Rad5 integrates its various activities in replication stress tolerance.
Time-frequency super-resolution with superlets
Authors: Moca Vasile V. , Bârzan Harald , Nagy-Dăbâcan Adriana , Mureșan Raul C. 
Published: January 2021

AbstractDue to the Heisenberg–Gabor uncertainty principle, finite oscillation transients are difficult to localize simultaneously in both time and frequency. Classical estimators, like the short-time Fourier transform or the continuous-wavelet transform optimize either temporal or frequency resolution, or find a suboptimal tradeoff. Here, we introduce a spectral estimator enabling time-frequency super-resolution, called superlet, that uses sets of wavelets with increasingly constrained bandwidth. These are combined geometrically in order to maintain the good temporal resolution of single wavelets and gain frequency resolution in upper bands. The normalization of wavelets in the set facilitates exploration of data with scale-free, fractal nature, containing oscillation packets that are self-similar across frequencies. Superlets perform well on synthetic data and brain signals recorded in humans and rodents, resolving high frequency bursts with excellent precision. Importantly, they can reveal fast transient oscillation events in single trials that may be hidden in the averaged time-frequency spectrum by other methods.
Functional cooperativity between the trigger factor chaperone and the ClpXP proteolytic complex
Authors: Rizzolo Kamran , Yu Angela Yeou Hsiung , Ologbenla Adedeji , Kim Sa Rang , Zhu Haojie , Ishimori Koichiro , Thibault Guillaume , Leung Elisa , Zhang Yi Wen , Teng Mona , Haniszewski Marta , Miah Noha , Phanse Sadhna , Minic Zoran , Lee Sukyeong , Caballero Julio Diaz , Babu Mohan , Tsai Francis T. F. , Saio Tomohide , Houry Walid A. 
Published: January 2021

AbstractA functional association is uncovered between the ribosome-associated trigger factor (TF) chaperone and the ClpXP degradation complex. Bioinformatic analyses demonstrate conservation of the close proximity of tig, the gene coding for TF, and genes coding for ClpXP, suggesting a functional interaction. The effect of TF on ClpXP-dependent degradation varies based on the nature of substrate. While degradation of some substrates are slowed down or are unaffected by TF, surprisingly, TF increases the degradation rate of a third class of substrates. These include λ phage replication protein λO, master regulator of stationary phase RpoS, and SsrA-tagged proteins. Globally, TF acts to enhance the degradation of about 2% of newly synthesized proteins. TF is found to interact through multiple sites with ClpX in a highly dynamic fashion to promote protein degradation. This chaperone–protease cooperation constitutes a unique and likely ancestral aspect of cellular protein homeostasis in which TF acts as an adaptor for ClpXP.
Targeting adaptor protein SLP76 of RAGE as a therapeutic approach for lethal sepsis
Authors: Yan Zhengzheng , Luo Haihua , Xie Bingyao , Tian Tian , Li Shan , Chen Zhixia , Liu Jinghua , Zhao Xuwen , Zhang Liyong , Deng Yongqiang , Billiar Timothy R. , Jiang Yong 
Published: January 2021

AbstractAccumulating evidence shows that RAGE has an important function in the pathogenesis of sepsis. However, the mechanisms by which RAGE transduces signals to downstream kinase cascades during septic shock are not clear. Here, we identify SLP76 as a binding partner for the cytosolic tail of RAGE both in vitro and in vivo and demonstrate that SLP76 binds RAGE through its sterile α motif (SAM) to mediate downstream signaling. Genetic deficiency of RAGE or SLP76 reduces AGE-induced phosphorylation of p38 MAPK, ERK1/2 and IKKα/β, as well as cytokine release. Delivery of the SAM domain into macrophages via the TAT cell-penetrating peptide blocks proinflammatory cytokine production. Furthermore, administration of TAT-SAM attenuates inflammatory cytokine release and tissue damage in mice subjected to cecal ligation and puncture (CLP) and protects these mice from the lethality of sepsis. These findings reveal an important function for SLP76 in RAGE-mediated pro-inflammatory signaling and shed light on the development of SLP76-targeted therapeutics for sepsis.
Metal-free atom transfer radical polymerization with ppm catalyst loading under sunlight
Authors: Ma Qiang , Song Jinshuai , Zhang Xun , Jiang Yu , Ji Li , Liao Saihu 
Published: January 2021

AbstractOrganocatalytic atom transfer radical polymerization (O-ATRP) is recently emerging as an appealing method for the synthesis of metal-free polymer materials with well-defined microstructures and architectures. However, the development of highly effective catalysts that can be employed at a practical low loading are still a challenging task. Herein, we introduce a catalyst design logic based on heteroatom-doping of polycyclic arenes, which leads to the discovery of oxygen-doped anthanthrene (ODA) as highly effective organic photoredox catalysts for O-ATRP. In comparison with known organocatalysts, ODAs feature strong visible-light absorption together with high molar extinction coefficient (ε455nm up to 23,950 M–1 cm–1), which allow for the establishment of a controlled polymerization under sunlight at low ppm levels of catalyst loading.
DsbA-L deficiency in T cells promotes diet-induced thermogenesis through suppressing IFN-γ production
Authors: Zhou Haiyan , Peng Xinyi , Hu Jie , Wang Liwen , Luo Hairong , Zhang Junyan , Zhang Yacheng , Li Guobao , Ji Yujiao , Zhang Jingjing , Bai Juli , Liu Meilian , Zhou Zhiguang , Liu Feng 
Published: January 2021

AbstractAdipose tissue-resident T cells have been recognized as a critical regulator of thermogenesis and energy expenditure, yet the underlying mechanisms remain unclear. Here, we show that high-fat diet (HFD) feeding greatly suppresses the expression of disulfide-bond A oxidoreductase-like protein (DsbA-L), a mitochondria-localized chaperone protein, in adipose-resident T cells, which correlates with reduced T cell mitochondrial function. T cell-specific knockout of DsbA-L enhances diet-induced thermogenesis in brown adipose tissue (BAT) and protects mice from HFD-induced obesity, hepatosteatosis, and insulin resistance. Mechanistically, DsbA-L deficiency in T cells reduces IFN-γ production and activates protein kinase A by reducing phosphodiesterase-4D expression, leading to increased BAT thermogenesis. Taken together, our study uncovers a mechanism by which T cells communicate with brown adipocytes to regulate BAT thermogenesis and whole-body energy homeostasis. Our findings highlight a therapeutic potential of targeting T cells for the treatment of over nutrition-induced obesity and its associated metabolic diseases.
Selective hydrogenolysis of catechyl lignin into propenylcatechol over an atomically dispersed ruthenium catalyst
Authors: Wang Shuizhong , Zhang Kaili , Li Helong , Xiao Ling-Ping , Song Guoyong 
Published: January 2021

AbstractC-lignin is a homo-biopolymer, being made up of caffeyl alcohol exclusively. There is significant interest in developing efficient and selective catalyst for depolymerization of C-lignin, as it represents an ideal feedstock for producing catechol derivatives. Here we report an atomically dispersed Ru catalyst, which can serve as an efficient catalyst for the hydrogenolysis of C-lignin via the cleavage of C−O bonds in benzodioxane linkages, giving catechols in high yields with TONs up to 345. A unique selectivity to propenylcatechol (77%) is obtained, which is otherwise hard to achieve, because this catalyst is capable of hydrogenolysis rather than hydrogenation. This catalyst also demonstrates good reusability in C-lignin depolymerization. Detailed investigations by model compounds concluded that the pathways involving dehydration and/or dehydrogenation reactions are incompatible routes; we deduced that caffeyl alcohol generated via concurrent C−O bonds cleavage of benzodioxane unit may act as an intermediate in the C-lignin hydrogenolysis. Current demonstration validates that atomically dispersed metals can not only catalyze small molecules reactions, but also drive the transformation of abundant and renewable biopolymer.
Targeting aberrant DNA methylation in mesenchymal stromal cells as a treatment for myeloma bone disease
Authors: Garcia-Gomez Antonio , Li Tianlu , de la Calle-Fabregat Carlos , Rodríguez-Ubreva Javier , Ciudad Laura , Català-Moll Francesc , Godoy-Tena Gerard , Martín-Sánchez Montserrat , San-Segundo Laura , Muntión Sandra , Morales Xabier , Ortiz-de-Solórzano Carlos , Oyarzabal Julen , San José-Enériz Edurne , Esteller Manel , Agirre Xabier , Prosper Felipe , Garayoa Mercedes , Ballestar Esteban 
Published: January 2021

AbstractMultiple myeloma (MM) progression and myeloma-associated bone disease (MBD) are highly dependent on bone marrow mesenchymal stromal cells (MSCs). MM-MSCs exhibit abnormal transcriptomes, suggesting the involvement of epigenetic mechanisms governing their tumor-promoting functions and prolonged osteoblast suppression. Here, we identify widespread DNA methylation alterations of bone marrow-isolated MSCs from distinct MM stages, particularly in Homeobox genes involved in osteogenic differentiation that associate with their aberrant expression. Moreover, these DNA methylation changes are recapitulated in vitro by exposing MSCs from healthy individuals to MM cells. Pharmacological targeting of DNMTs and G9a with dual inhibitor CM-272 reverts the expression of hypermethylated osteogenic regulators and promotes osteoblast differentiation of myeloma MSCs. Most importantly, CM-272 treatment prevents tumor-associated bone loss and reduces tumor burden in a murine myeloma model. Our results demonstrate that epigenetic aberrancies mediate the impairment of bone formation in MM, and its targeting by CM-272 is able to reverse MBD.
Modelling the global burden of drug-resistant tuberculosis avertable by a post-exposure vaccine
Authors: Fu Han , Lewnard Joseph A. , Frost Isabel , Laxminarayan Ramanan , Arinaminpathy Nimalan 
Published: January 2021

AbstractThere have been notable advances in the development of vaccines against active tuberculosis (TB) disease for adults and adolescents. Using mathematical models, we seek to estimate the potential impact of a post-exposure TB vaccine, having 50% efficacy in reducing active disease, on global rifampicin-resistant (RR-) TB burden. In 30 countries that together accounted for 90% of global RR-TB incidence in 2018, a future TB vaccine could avert 10% (95% credible interval: 9.7–11%) of RR-TB cases and 7.3% (6.6–8.1%) of deaths over 2020–2035, with India, China, Indonesia, Pakistan, and the Russian Federation having the greatest contribution. This impact would increase to 14% (12–16%) and 31% (29–33%) respectively, when combined with improvements in RR-TB diagnosis and treatment relative to a scenario of no vaccine and no such improvements. A future TB vaccine could have important implications for the global control of RR-TB, especially if implemented alongside enhancements in management of drug resistance.