bluuebunny/crossref_metadata_2025_split huggingface dataset:
Necroptosis in head and neck squamous cell carcinoma: characterization of clinicopathological relevance and in vitro cell model
Authors: Li Jingyuan , Huang Sihui , Zeng Lijuan , Li Kan , Yang Le , Gao Siyong , Guan Chenyu , Zhang Sien , Lao Xiaomei , Liao Guiqing , Liang Yujie 
Published: May 2020

AbstractNecroptosis is a recently discovered form of programmed cell death (PCD) having necrotic-like morphology. However, its presence and potential impact with respect to head and neck squamous cell carcinoma (HNSCC) are still unknown. The aim of this study was to reveal the necroptosis status and its clinicopathological relevance in HNSCC and to establish an in vitro model. We first analyzed the level of p-MLKL, MLKL, and tumor necrosis in HNSCC patient tissues as well as their correlation with clinicopathological features. Results showed that approximately half of the tumor necrosis can be attributed to necroptosis, and the extent of necroptosis is an independent prognostic marker for patient’s overall survival and progression-free survival. Then we established and thoroughly verified an in vitro model of necroptosis in two HNSCC cell lines using combined treatment of TNF-α, Smac mimetic and zVAD-fmk (TSZ). At last, we adopted this model and demonstrated that necroptosis can promote migration and invasion of HNSCC cells by releasing damage-associated molecular patterns. In conclusion, our study unveiled the necroptotic status in HNSCC for the first time and provided a novel in vitro model of necroptosis in two HNSCC cell lines. In addition, our results indicated that necroptosis may be a potential cancer promoter in HNSCC. This study may serve as the foundation for future researches of necroptosis in HNSCC.
Sodium–glucose cotransporter 2 inhibition suppresses HIF-1α-mediated metabolic switch from lipid oxidation to glycolysis in kidney tubule cells of diabetic mice
Authors: Cai Ting , Ke Qingqing , Fang Yi , Wen Ping , Chen Hanzhi , Yuan Qi , Luo Jing , Zhang Yu , Sun Qi , Lv Yunhui , Zen Ke , Jiang Lei , Zhou Yang , Yang Junwei 
Published: May 2020

AbstractInhibition of sodium–glucose cotransporter 2 (SGLT2) in the proximal tubule of the kidney has emerged as an effective antihyperglycemic treatment. The potential protective role of SGLT2 inhibition on diabetic kidney disease (DKD) and underlying mechanism, however, remains unknown. In this study, metabolic switch was examined using kidney samples from human with diabetes and streptozocin (STZ)-induced experimental mouse model of diabetes treated with or without SGLT2 inhibitor dapagliflozin. Results were further validated using primarily cultured proximal tubule epithelial cells. We found that DKD development and progression to renal fibrosis entailed profound changes in proximal tubule metabolism, characterized by a switch from fatty acid utilization to glycolysis and lipid accumulation, which is associated with the increased expression of HIF-1α. Diabetes-induced tubulointerstitial damage, such as macrophage infiltration and fibrosis, was significantly improved by dapagliflozin. Consistent with the effects of these beneficial interventions, the metabolic disorder was almost completely eliminated by dapagliflozin. The increased level of HIF-1α in renal proximal tubule was nearly nullified by dapagliflozin. Moreover, dapagliflozin protects against glucose-induced metabolic shift in PTCs via inhibiting HIF-1α. It suggests that SGLT2 inhibition is efficient in rectifying the metabolic disorder and may be a novel prevention and treatment strategy for kidney tubule in DKD.
How to define and study structural proteins as biopolymer materials
Authors: Numata Keiji 
Published: May 2020

AbstractStructural proteins, including silk fibroins, play an important role in shaping the skeletons and structures of cells, tissues, and organisms. The amino acid sequences of structural proteins often show characteristic features, such as a repeating tandem motif, that are notably different from those of functional proteins such as enzymes and antibodies. In recent years, materials composed of or containing structural proteins have been studied and developed as biomedical, apparel, and structural materials. This review outlines the definition of structural proteins, methods for characterizing structural proteins as polymeric materials, and potential applications.
Single-cell analysis of murine fibroblasts identifies neonatal to adult switching that regulates cardiomyocyte maturation
Authors: Wang Yin , Yao Fang , Wang Lipeng , Li Zheng , Ren Zongna , Li Dandan , Zhang Mingzhi , Han Leng , Wang Shi-qiang , Zhou Bingying , Wang Li 
Published: May 2020

AbstractCardiac maturation lays the foundation for postnatal heart development and disease, yet little is known about the contributions of the microenvironment to cardiomyocyte maturation. By integrating single-cell RNA-sequencing data of mouse hearts at multiple postnatal stages, we construct cellular interactomes and regulatory signaling networks. Here we report switching of fibroblast subtypes from a neonatal to adult state and this drives cardiomyocyte maturation. Molecular and functional maturation of neonatal mouse cardiomyocytes and human embryonic stem cell-derived cardiomyocytes are considerably enhanced upon co-culture with corresponding adult cardiac fibroblasts. Further, single-cell analysis of in vivo and in vitro cardiomyocyte maturation trajectories identify highly conserved signaling pathways, pharmacological targeting of which substantially delays cardiomyocyte maturation in postnatal hearts, and markedly enhances cardiomyocyte proliferation and improves cardiac function in infarcted hearts. Together, we identify cardiac fibroblasts as a key constituent in the microenvironment promoting cardiomyocyte maturation, providing insights into how the manipulation of cardiomyocyte maturity may impact on disease development and regeneration.
KAT3-dependent acetylation of cell type-specific genes maintains neuronal identity in the adult mouse brain
Authors: Lipinski Michal , Muñoz-Viana Rafael , del Blanco Beatriz , Marquez-Galera Angel , Medrano-Relinque Juan , Caramés José M. , Szczepankiewicz Andrzej A. , Fernandez-Albert Jordi , Navarrón Carmen M. , Olivares Roman , Wilczyński Grzegorz M. , Canals Santiago , Lopez-Atalaya Jose P. , Barco Angel 
Published: May 2020

AbstractThe lysine acetyltransferases type 3 (KAT3) family members CBP and p300 are important transcriptional co-activators, but their specific functions in adult post-mitotic neurons remain unclear. Here, we show that the combined elimination of both proteins in forebrain excitatory neurons of adult mice resulted in a rapidly progressing neurological phenotype associated with severe ataxia, dendritic retraction and reduced electrical activity. At the molecular level, we observed the downregulation of neuronal genes, as well as decreased H3K27 acetylation and pro-neural transcription factor binding at the promoters and enhancers of canonical neuronal genes. The combined deletion of CBP and p300 in hippocampal neurons resulted in the rapid loss of neuronal molecular identity without de- or transdifferentiation. Restoring CBP expression or lysine acetylation rescued neuronal-specific transcription in cultured neurons. Together, these experiments show that KAT3 proteins maintain the excitatory neuron identity through the regulation of histone acetylation at cell type-specific promoter and enhancer regions.
Ultra-dense optical data transmission over standard fibre with a single chip source
Authors: Corcoran Bill , Tan Mengxi , Xu Xingyuan , Boes Andreas , Wu Jiayang , Nguyen Thach G. , Chu Sai T. , Little Brent E. , Morandotti Roberto , Mitchell Arnan , Moss David J. 
Published: May 2020

AbstractMicro-combs - optical frequency combs generated by integrated micro-cavity resonators – offer the full potential of their bulk counterparts, but in an integrated footprint. They have enabled breakthroughs in many fields including spectroscopy, microwave photonics, frequency synthesis, optical ranging, quantum sources, metrology and ultrahigh capacity data transmission. Here, by using a powerful class of micro-comb called soliton crystals, we achieve ultra-high data transmission over 75 km of standard optical fibre using a single integrated chip source. We demonstrate a line rate of 44.2 Terabits s−1 using the telecommunications C-band at 1550 nm with a spectral efficiency of 10.4 bits s−1 Hz−1. Soliton crystals exhibit robust and stable generation and operation as well as a high intrinsic efficiency that, together with an extremely low soliton micro-comb spacing of 48.9 GHz enable the use of a very high coherent data modulation format (64 QAM - quadrature amplitude modulated). This work demonstrates the capability of optical micro-combs to perform in demanding and practical optical communications networks.
Tunable photo-responsive elastic metamaterials
Authors: Gliozzi Antonio S. , Miniaci Marco , Chiappone Annalisa , Bergamini Andrea , Morin Benjamin , Descrovi Emiliano 
Published: May 2020

AbstractThe metamaterial paradigm has allowed an unprecedented space-time control of various physical fields, including elastic and acoustic waves. Despite the wide variety of metamaterial configurations proposed so far, most of the existing solutions display a frequency response that cannot be tuned, once the structures are fabricated. Few exceptions include systems controlled by electric or magnetic fields, temperature, radio waves and mechanical stimuli, which may often be unpractical for real-world implementations. To overcome this limitation, we introduce here a polymeric 3D-printed elastic metamaterial whose transmission spectrum can be deterministically tuned by a light field. We demonstrate the reversible doubling of the width of an existing frequency band gap upon selective laser illumination. This feature is exploited to provide an elastic-switch functionality with a one-minute lag time, over one hundred cycles. In perspective, light-responsive components can bring substantial improvements to active devices for elastic wave control, such as beam-splitters, switches and filters.
A biochemically-interpretable machine learning classifier for microbial GWAS
Authors: Kavvas Erol S. , Yang Laurence , Monk Jonathan M. , Heckmann David , Palsson Bernhard O. 
Published: May 2020

AbstractCurrent machine learning classifiers have successfully been applied to whole-genome sequencing data to identify genetic determinants of antimicrobial resistance (AMR), but they lack causal interpretation. Here we present a metabolic model-based machine learning classifier, named Metabolic Allele Classifier (MAC), that uses flux balance analysis to estimate the biochemical effects of alleles. We apply the MAC to a dataset of 1595 drug-tested Mycobacterium tuberculosis strains and show that MACs predict AMR phenotypes with accuracy on par with mechanism-agnostic machine learning models (isoniazid AUC = 0.93) while enabling a biochemical interpretation of the genotype-phenotype map. Interpretation of MACs for three antibiotics (pyrazinamide, para-aminosalicylic acid, and isoniazid) recapitulates known AMR mechanisms and suggest a biochemical basis for how the identified alleles cause AMR. Extending flux balance analysis to identify accurate sequence classifiers thus contributes mechanistic insights to GWAS, a field thus far dominated by mechanism-agnostic results.
A cysteine selenosulfide redox switch for protein chemical synthesis
Authors: Diemer Vincent , Ollivier Nathalie , Leclercq Bérénice , Drobecq Hervé , Vicogne Jérôme , Agouridas Vangelis , Melnyk Oleg 
Published: May 2020

AbstractThe control of cysteine reactivity is of paramount importance for the synthesis of proteins using the native chemical ligation (NCL) reaction. We report that this goal can be achieved in a traceless manner during ligation by appending a simple N-selenoethyl group to cysteine. While in synthetic organic chemistry the cleavage of carbon-nitrogen bonds is notoriously difficult, we describe that N-selenoethyl cysteine (SetCys) loses its selenoethyl arm in water under mild conditions upon reduction of its selenosulfide bond. Detailed mechanistic investigations show that the cleavage of the selenoethyl arm proceeds through an anionic mechanism with assistance of the cysteine thiol group. The implementation of the SetCys unit in a process enabling the modular and straightforward assembly of linear or backbone cyclized polypeptides is illustrated by the synthesis of biologically active cyclic hepatocyte growth factor variants.
TNFAIP8 controls murine intestinal stem cell homeostasis and regeneration by regulating microbiome-induced Akt signaling
Authors: Goldsmith Jason R. , Spitofsky Nina , Zamani Ali , Hood Ryan , Boggs Amanda , Li Xinyuan , Li Mingyue , Reiner Elizabeth , Ayyaz Arshad , Etwebi Zienab , Lu Ling , Rivera Guzman Javier , Bou-Dargham Mayassa J. , Cathoupolis Terry , Hakonarson Hakon , Sun Honghong , Wrana Jeffrey L. , Gonzalez Michael V. , Chen Youhai H. 
Published: May 2020

AbstractThe intestine is a highly dynamic environment that requires tight control of the various inputs to maintain homeostasis and allow for proper responses to injury. It was recently found that the stem cell niche and epithelium is regenerated after injury by de-differentiated adult cells, through a process that gives rise to Sca1+ fetal-like cells and is driven by a transient population of Clu+ revival stem cells (revSCs). However, the molecular mechanisms that regulate this dynamic process have not been fully defined. Here we show that TNFAIP8 (also known as TIPE0) is a regulator of intestinal homeostasis that is vital for proper regeneration. TIPE0 functions through inhibiting basal Akt activation by the commensal microbiota via modulating membrane phospholipid abundance. Loss of TIPE0 in mice results in injury-resistant enterocytes, that are hyperproliferative, yet have regenerative deficits and are shifted towards a de-differentiated state. Tipe0−/− enterocytes show basal induction of the Clu+ regenerative program and a fetal gene expression signature marked by Sca1, but upon injury are unable to generate Sca-1+/Clu+ revSCs and could not regenerate the epithelium. This work demonstrates the role of TIPE0 in regulating the dynamic signaling that determines the injury response and enables intestinal epithelial cell regenerative plasticity.
Transcriptional activation during cell reprogramming correlates with the formation of 3D open chromatin hubs
Authors: Di Stefano Marco , Stadhouders Ralph , Farabella Irene , Castillo David , Serra François , Graf Thomas , Marti-Renom Marc A. 
Published: May 2020

AbstractChromosome structure is a crucial regulatory factor for a wide range of nuclear processes. Chromosome conformation capture (3C)-based experiments combined with computational modelling are pivotal for unveiling 3D chromosome structure. Here, we introduce TADdyn, a tool that integrates time-course 3C data, restraint-based modelling, and molecular dynamics to simulate the structural rearrangements of genomic loci in a completely data-driven way. We apply TADdyn on in situ Hi-C time-course experiments studying the reprogramming of murine B cells to pluripotent cells, and characterize the structural rearrangements that take place upon changes in the transcriptional state of 21 genomic loci of diverse expression dynamics. By measuring various structural and dynamical properties, we find that during gene activation, the transcription starting site contacts with open and active regions in 3D chromatin domains. We propose that these 3D hubs of open and active chromatin may constitute a general feature to trigger and maintain gene transcription.
Molecular molds for regularizing Kondo states at atom/metal interfaces
Authors: Li Xiangyang , Zhu Liang , Li Bin , Li Jingcheng , Gao Pengfei , Yang Longqing , Zhao Aidi , Luo Yi , Hou Jianguo , Zheng Xiao , Wang Bing , Yang Jinlong 
Published: May 2020

AbstractAdsorption of magnetic transition metal atoms on a metal surface leads to the formation of Kondo states at the atom/metal interfaces. However, the significant influence of surrounding environment presents challenges for potential applications. In this work, we realize a novel strategy to regularize the Kondo states by moving a CoPc molecular mold on an Au(111) surface to capture the dispersed Co adatoms. The symmetric and ordered structures of the atom-mold complexes, as well as the strong dπ–π bonding between the Co adatoms and conjugated isoindole units, result in highly robust and uniform Kondo states at the Co/Au(111) interfaces. Even more remarkably, the CoPc further enables a fine tuning of Kondo states through the molecular-mold-mediated superexchange interactions between Co adatoms separated by more than 12 Å. Being highly precise, efficient and reproducible, the proposed molecular mold strategy may open a new horizon for the construction and control of nano-sized quantum devices.
Discrete populations of isotype-switched memory B lymphocytes are maintained in murine spleen and bone marrow
Authors: Riedel René , Addo Richard , Ferreira-Gomes Marta , Heinz Gitta Anne , Heinrich Frederik , Kummer Jannis , Greiff Victor , Schulz Daniel , Klaeden Cora , Cornelis Rebecca , Menzel Ulrike , Kröger Stefan , Stervbo Ulrik , Köhler Ralf , Haftmann Claudia , Kühnel Silvia , Lehmann Katrin , Maschmeyer Patrick , McGrath Mairi , Naundorf Sandra , Hahne Stefanie , Sercan-Alp Özen , Siracusa Francesco , Stefanowski Jonathan , Weber Melanie , Westendorf Kerstin , Zimmermann Jakob , Hauser Anja E. , Reddy Sai T. , Durek Pawel , Chang Hyun-Dong , Mashreghi Mir-Farzin , Radbruch Andreas 
Published: May 2020

AbstractAt present, it is not clear how memory B lymphocytes are maintained over time, and whether only as circulating cells or also residing in particular tissues. Here we describe distinct populations of isotype-switched memory B lymphocytes (Bsm) of murine spleen and bone marrow, identified according to individual transcriptional signature and B cell receptor repertoire. A population of marginal zone-like cells is located exclusively in the spleen, while a population of quiescent Bsm is found only in the bone marrow. Three further resident populations, present in spleen and bone marrow, represent transitional and follicular B cells and B1 cells, respectively. A population representing 10-20% of spleen and bone marrow memory B cells is the only one qualifying as circulating. In the bone marrow, all cells individually dock onto VCAM1+ stromal cells and, reminiscent of resident memory T and plasma cells, are void of activation, proliferation and mobility.
Continuously controllable photoconductance in freestanding BiFeO3 by the macroscopic flexoelectric effect
Authors: Guo Rui , You Lu , Lin Weinan , Abdelsamie Amr , Shu Xinyu , Zhou Guowei , Chen Shaohai , Liu Liang , Yan Xiaobing , Wang Junling , Chen Jingsheng 
Published: May 2020

Abstract
Flexoelectricity induced by the strain gradient is attracting much attention due to its potential applications in electronic devices. Here, by combining a tunable flexoelectric effect and the ferroelectric photovoltaic effect, we demonstrate the continuous tunability of photoconductance in BiFeO3 films. The BiFeO3 film epitaxially grown on SrTiO3 is transferred to a flexible substrate by dissolving a sacrificing layer. The tunable flexoelectricity is achieved by bending the flexible substrate which induces a nonuniform lattice distortion in BiFeO3 and thus influences the inversion asymmetry of the film. Multilevel conductance is thus realized through the coupling between flexoelectric and ferroelectric photovoltaic effect in freestanding BiFeO3. The strain gradient induced multilevel photoconductance shows very good reproducibility by bending the flexible BiFeO3 device. This control strategy offers an alternative degree of freedom to tailor the physical properties of flexible devices and thus provides a compelling toolbox for flexible materials in a wide range of applications.
Integrated redox-active reagents for photoinduced regio- and stereoselective fluorocarboborylation
Authors: Zhang Weigang , Zou Zhenlei , Zhao Wenxuan , Lu Shuo , Wu Zhengguang , Huang Mengjun , Wang Xiaochen , Wang Yi , Liang Yong , Zhu Yi , Zheng Youxuan , Pan Yi 
Published: May 2020

AbstractVinylboronates and alkylboronates are key components in variegated transformations in all facets of chemical science. The synthesis of vinylboronates and alkylboronates suffers from step-tedious and poor stereoselective procedures. We have developed a regulated radical difunctionalization strategy for the construction of fluorine-containing vinylboronates and alkylboronates with an integrated redox-active reagent IMDN-SO2RF. This bench-stable imidazolium sulfonate cationic salt offers a scalable and operational protocol for the fluoroalkylation-borylation of unsaturated hydrocarbons in a high regio- and stereoselective manner. The products can be further transformed into valuable fluorinated building blocks.
Genome-scale metabolic reconstruction of the symbiosis between a leguminous plant and a nitrogen-fixing bacterium
Authors: diCenzo George C. , Tesi Michelangelo , Pfau Thomas , Mengoni Alessio , Fondi Marco 
Published: May 2020

AbstractThe mutualistic association between leguminous plants and endosymbiotic rhizobial bacteria is a paradigmatic example of a symbiosis driven by metabolic exchanges. Here, we report the reconstruction and modelling of a genome-scale metabolic network ofMedicago truncatula(plant) nodulated bySinorhizobium meliloti(bacterium). The reconstructed nodule tissue contains five spatially distinct developmental zones and encompasses the metabolism of both the plant and the bacterium. Flux balance analysis (FBA) suggests that the metabolic costs associated with symbiotic nitrogen fixation are primarily related to supporting nitrogenase activity, and increasing N2-fixation efficiency is associated with diminishing returns in terms of plant growth. Our analyses support that differentiating bacteroids have access to sugars as major carbon sources, ammonium is the main nitrogen export product of N2-fixing bacteria, and N2fixation depends on proton transfer from the plant cytoplasm to the bacteria through acidification of the peribacteroid space. We expect that our model, called ‘Virtual Nodule Environment’ (ViNE), will contribute to a better understanding of the functioning of legume nodules, and may guide experimental studies and engineering of symbiotic nitrogen fixation.
Magnetic mechanism for the biological functioning of hemoglobin
Authors: Mayda Selma , Kandemir Zafer , Bulut Nejat , Maekawa Sadamichi 
Published: May 2020

AbstractThe role of magnetism in the biological functioning of hemoglobin has been debated since its discovery by Pauling and Coryell in 1936. The hemoglobin molecule contains four heme groups each having a porphyrin layer with a Fe ion at the center. Here, we present combined density-functional theory and quantum Monte Carlo calculations for an effective model of Fe in a heme cluster. In comparison with these calculations, we analyze the experimental data on human adult hemoglobin (HbA) from the magnetic susceptibility, Mössbauer and magnetic circular dichroism (MCD) measurements. In both the deoxygenated (deoxy) and the oxygenated (oxy) cases, we show that local magnetic moments develop in the porphyrin layer with antiferromagnetic coupling to the Fe moment. Our calculations reproduce the magnetic susceptibility measurements on deoxy and oxy-HbA. For deoxy-HbA, we show that the anomalous MCD signal in the UV region is an experimental evidence for the presence of antiferromagnetic Fe-porphyrin correlations. The functional properties of hemoglobin such as the binding of O2, the Bohr effect and the cooperativity are explained based on the magnetic correlations. This analysis suggests that magnetism could be involved in the functioning of hemoglobin.