bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial dysfunction induces radioresistance in colorectal cancer by activating [Ca2+]m-PDP1-PDH-histone acetylation retrograde signaling
Authors: Shi Yingying , Wang You , Jiang Huangang , Sun Xuehua , Xu Hui , Wei Xue , Wei Yan , Xiao Guohui , Song Zhiyin , Zhou Fuxiang 
Published: September 2021

AbstractMitochondrial retrograde signaling (mito-RTG) triggered by mitochondrial dysfunction plays a potential role in regulating tumor metabolic reprogramming and cellular sensitivity to radiation. Our previous studies showed phos-pyruvate dehydrogenase (p-PDH) and PDK1, which involved in aerobic glycolysis, were positively correlated with radioresistance, but how they initiate and work in the mito-RTG pathway is still unknown. Our further genomics analysis revealed that complex I components were widely downregulated in mitochondrial dysfunction model. In the present study, high expression of p-PDH was found in the complex I deficient cells and induced radioresistance. Mechanistically, complex I defects led to a decreased PDH both in cytoplasm and nucleus through [Ca2+]m-PDP1-PDH axis, and decreased PDH in nucleus promote DNA damage repair (DDR) response via reducing histone acetylation. Meanwhile, NDUFS1 (an important component of the complex I) overexpression could enhance the complex I activity, reverse glycolysis and resensitize cancer cells to radiation in vivo and in vitro. Furthermore, low NDUFS1 and PDH expression were validated to be correlated with poor tumor regression grading (TRG) in local advanced colorectal cancer (CRC) patients underwent neoadjuvant radiotherapy. Here, we propose that the [Ca2+]m-PDP1-PDH-histone acetylation retrograde signaling activated by mitochondrial complex I defects contribute to cancer cell radioresistance, which provides new insight in the understanding of the mito-RTG. For the first time, we reveal that NDUFS1 could be served as a promising predictor of radiosensitivity and modification of complex I function may improve clinical benefits of radiotherapy in CRC.
Inferring multilayer interactome networks shaping phenotypic plasticity and evolution
Authors: Yang Dengcheng , Jin Yi , He Xiaoqing , Dong Ang , Wang Jing , Wu Rongling 
Published: September 2021

AbstractPhenotypic plasticity represents a capacity by which the organism changes its phenotypes in response to environmental stimuli. Despite its pivotal role in adaptive evolution, how phenotypic plasticity is genetically controlled remains elusive. Here, we develop a unified framework for coalescing all single nucleotide polymorphisms (SNPs) from a genome-wide association study (GWAS) into a quantitative graph. This framework integrates functional genetic mapping, evolutionary game theory, and predator-prey theory to decompose the net genetic effect of each SNP into its independent and dependent components. The independent effect arises from the intrinsic capacity of a SNP, only expressed when it is in isolation, whereas the dependent effect results from the extrinsic influence of other SNPs. The dependent effect is conceptually beyond the traditional definition of epistasis by not only characterizing the strength of epistasis but also capturing the bi-causality of epistasis and the sign of the causality. We implement functional clustering and variable selection to infer multilayer, sparse, and multiplex interactome networks from any dimension of genetic data. We design and conduct two GWAS experiments usingStaphylococcus aureus, aimed to test the genetic mechanisms underlying the phenotypic plasticity of this species to vancomycin exposure andEscherichia colicoexistence. We reconstruct the two most comprehensive genetic networks for abiotic and biotic phenotypic plasticity. Pathway analysis shows that SNP-SNP epistasis for phenotypic plasticity can be annotated to protein-protein interactions through coding genes. Our model can unveil the regulatory mechanisms of significant loci and excavate missing heritability from some insignificant loci. Our multilayer genetic networks provide a systems tool for dissecting environment-induced evolution.
BMP8 and activated brown adipose tissue in human newborns
Authors: Urisarri Adela , González-García Ismael , Estévez-Salguero Ánxela , Pata María P. , Milbank Edward , López Noemi , Mandiá Natalia , Grijota-Martinez Carmen , Salgado Carlos A. , Nogueiras Rubén , Diéguez Carlos , Villarroya Francesc , Fernández-Real José-Manuel , Couce María L. , López Miguel 
Published: September 2021

AbstractThe classical dogma states that brown adipose tissue (BAT) plays a major role in the regulation of temperature in neonates. However, although BAT has been studied in infants for more than a century, the knowledge about its physiological features at this stage of life is rather limited. This has been mainly due to the lack of appropriate investigation methods, ethically suitable for neonates. Here, we have applied non-invasive infrared thermography (IRT) to investigate neonatal BAT activity. Our data show that BAT temperature correlates with body temperature and that mild cold stimulus promotes BAT activation in newborns. Notably, a single short-term cold stimulus during the first day of life improves the body temperature adaption to a subsequent cold event. Finally, we identify that bone morphogenic protein 8B (BMP8B) is associated with the BAT thermogenic response in neonates. Overall, our data uncover key features of the setup of BAT thermogenesis in newborns.
MEG source imaging detects optogenetically-induced activity in cortical and subcortical networks
Authors: Alberto Gregory E. , Stapleton-Kotloski Jennifer R. , Klorig David C. , Rogers Emily R. , Constantinidis Christos , Daunais James B. , Godwin Dwayne W. 
Published: September 2021

AbstractMagnetoencephalography measures neuromagnetic activity with high temporal, and theoretically, high spatial resolution. We developed an experimental platform combining MEG-compatible optogenetic techniques in nonhuman primates for use as a functional brain-mapping platform. Here we show localization of optogenetically evoked signals to known sources in the superficial arcuate sulcus of cortex and in CA3 of hippocampus at a resolution of 750 µm3. We detect activation in subcortical, thalamic, and extended temporal structures, conforming to known anatomical and functional brain networks associated with the respective sites of stimulation. This demonstrates that high-resolution localization of experimentally produced deep sources is possible within an intact brain. This approach is suitable for exploring causal relationships between discrete brain regions through precise optogenetic control and simultaneous whole brain MEG recording with high-resolution magnetic source imaging (MSI).
Evidence of a coupled electron-phonon liquid in NbGe2
Authors: Yang Hung-Yu , Yao Xiaohan , Plisson Vincent , Mozaffari Shirin , Scheifers Jan P. , Savvidou Aikaterini Flessa , Choi Eun Sang , McCandless Gregory T. , Padlewski Mathieu F. , Putzke Carsten , Moll Philip J. W. , Chan Julia Y. , Balicas Luis , Burch Kenneth S. , Tafti Fazel 
Published: September 2021

AbstractWhereas electron-phonon scattering relaxes the electron’s momentum in metals, a perpetual exchange of momentum between phonons and electrons may conserve total momentum and lead to a coupled electron-phonon liquid. Such a phase of matter could be a platform for observing electron hydrodynamics. Here we present evidence of an electron-phonon liquid in the transition metal ditetrelide, NbGe2, from three different experiments. First, quantum oscillations reveal an enhanced quasiparticle mass, which is unexpected in NbGe2 with weak electron-electron correlations, hence pointing at electron-phonon interactions. Second, resistivity measurements exhibit a discrepancy between the experimental data and standard Fermi liquid calculations. Third, Raman scattering shows anomalous temperature dependences of the phonon linewidths that fit an empirical model based on phonon-electron coupling. We discuss structural factors, such as chiral symmetry, short metallic bonds, and a low-symmetry coordination environment as potential design principles for materials with coupled electron-phonon liquid.
Genetically encoded cell-death indicators (GEDI) to detect an early irreversible commitment to neurodegeneration
Authors: Linsley Jeremy W. , Shah Kevan , Castello Nicholas , Chan Michelle , Haddad Dominik , Doric Zak , Wang Shijie , Leks Wiktoria , Mancini Jay , Oza Viral , Javaherian Ashkan , Nakamura Ken , Kokel David , Finkbeiner Steven 
Published: September 2021

AbstractCell death is a critical process that occurs normally in health and disease. However, its study is limited due to available technologies that only detect very late stages in the process or specific death mechanisms. Here, we report the development of a family of fluorescent biosensors called genetically encoded death indicators (GEDIs). GEDIs specifically detect an intracellular Ca2+ level that cells achieve early in the cell death process and that marks a stage at which cells are irreversibly committed to die. The time-resolved nature of a GEDI delineates a binary demarcation of cell life and death in real time, reformulating the definition of cell death. We demonstrate that GEDIs acutely and accurately report death of rodent and human neurons in vitro, and show that GEDIs enable an automated imaging platform for single cell detection of neuronal death in vivo in zebrafish larvae. With a quantitative pseudo-ratiometric signal, GEDIs facilitate high-throughput analysis of cell death in time-lapse imaging analysis, providing the necessary resolution and scale to identify early factors leading to cell death in studies of neurodegeneration.
Comparative genomic analysis reveals metabolic flexibility of Woesearchaeota
Authors: Huang Wen-Cong , Liu Yang , Zhang Xinxu , Zhang Cui-Jing , Zou Dayu , Zheng Shiling , Xu Wei , Luo Zhuhua , Liu Fanghua , Li Meng 
Published: September 2021

AbstractThe archaeal phylum Woesearchaeota, within the DPANN superphylum, includes phylogenetically diverse microorganisms that inhabit various environments. Their biology is poorly understood due to the lack of cultured isolates. Here, we analyze datasets of Woesearchaeota 16S rRNA gene sequences and metagenome-assembled genomes to infer global distribution patterns, ecological preferences and metabolic capabilities. Phylogenomic analyses indicate that the phylum can be classified into ten subgroups, termed A–J. While a symbiotic lifestyle is predicted for most, some members of subgroup J might be host-independent. The genomes of several Woesearchaeota, including subgroup J, encode putative [FeFe] hydrogenases (known to be important for fermentation in other organisms), suggesting that these archaea might be anaerobic fermentative heterotrophs.
A concise access to bridged [2,2,1] bicyclic lactones with a quaternary stereocenter via stereospecific hydroformylation
Authors: Li Shuailong , Li Zhuangxing , Li Mingzheng , He Lin , Zhang Xumu , Lv Hui 
Published: September 2021

AbstractChiral bridged [2,2,1] bicyclic lactones are privileged structural units in pharmaceutics and bioactive nature products. However, the synthetic methods for these compounds are rare. Here we report an efficient method for enantioselective construction of bridged [2,2,1] bicyclic lactones bearing a quaternary stereocenter via Rh-catalyzed asymmetric hydroformylation/intramolecular cyclization/pyridium chlorochromate (PCC) oxidation. By employing a hybrid phosphine-phosphite chiral ligand, a series of cyclopent-3-en-1-ols are transformed into corresponding γ-hydroxyl aldehydes with specific syn-selectivity. Then, hemiacetals form in situ and oxidation with PCC in one-pot affords bridged [2,2,1] bicyclic lactones in high yields and excellent enantiomeric excess. Replacing the hydroxyl group by an ester group, cyclopentanecarbaldehydes with a chiral all-carbon quaternary stereocenter in the γ-position can be generated efficiently.
Structure and efflux mechanism of the yeast pleiotropic drug resistance transporter Pdr5
Authors: Harris Andrzej , Wagner Manuel , Du Dijun , Raschka Stefanie , Nentwig Lea-Marie , Gohlke Holger , Smits Sander H. J. , Luisi Ben F. , Schmitt Lutz 
Published: September 2021

AbstractPdr5, a member of the extensive ABC transporter superfamily, is representative of a clinically relevant subgroup involved in pleiotropic drug resistance. Pdr5 and its homologues drive drug efflux through uncoupled hydrolysis of nucleotides, enabling organisms such as baker’s yeast and pathogenic fungi to survive in the presence of chemically diverse antifungal agents. Here, we present the molecular structure of Pdr5 solved with single particle cryo-EM, revealing details of an ATP-driven conformational cycle, which mechanically drives drug translocation through an amphipathic channel, and a clamping switch within a conserved linker loop that acts as a nucleotide sensor. One half of the transporter remains nearly invariant throughout the cycle, while its partner undergoes changes that are transmitted across inter-domain interfaces to support a peristaltic motion of the pumped molecule. The efflux model proposed here rationalises the pleiotropic impact of Pdr5 and opens new avenues for the development of effective antifungal compounds.
Multistep nucleation of anisotropic molecules
Authors: Takahashi Kazuaki Z. , Aoyagi Takeshi , Fukuda Jun-ichi 
Published: September 2021

AbstractPhase transition of anisotropic materials is ubiquitously observed in physics, biology, materials science, and engineering. Nevertheless, how anisotropy of constituent molecules affects the phase transition dynamics is still poorly understood. Here we investigate numerically the phase transition of a simple model system composed of anisotropic molecules, and report on our discovery of multistep nucleation of nuclei with layered positional ordering (smectic ordering), from a fluid-like nematic phase with orientational order only (no positional order). A trinity of molecular dynamics simulation, machine learning, and molecular cluster analysis yielding free energy landscapes unambiguously demonstrates the dynamics of multistep nucleation process involving characteristic metastable clusters that precede supercritical smectic nuclei and cannot be accounted for by the classical nucleation theory. Our work suggests that molecules of simple shape can exhibit rich and complex nucleation processes, and our numerical approach will provide deeper understanding of phase transitions and resulting structures in anisotropic materials such as biological systems and functional materials.
Construction of Pd-Zn dual sites to enhance the performance for ethanol electro-oxidation reaction
Authors: Qiu Yajun , Zhang Jian , Jin Jing , Sun Jiaqiang , Tang Haolin , Chen Qingqing , Zhang Zedong , Sun Wenming , Meng Ge , Xu Qi , Zhu Youqi , Han Aijuan , Gu Lin , Wang Dingsheng , Li Yadong 
Published: September 2021

AbstractRational design and synthesis of superior electrocatalysts for ethanol oxidation is crucial to practical applications of direct ethanol fuel cells. Here, we report that the construction of Pd-Zn dual sites with well exposure and uniformity can significantly improve the efficiency of ethanol electro-oxidation. Through synthetic method control, Pd-Zn dual sites on intermetallic PdZn nanoparticles, Pd-Pd sites on Pd nanoparticles and individual Pd sites are respectively obtained on the same N-doped carbon coated ZnO support. Compared with Pd-Pd sites and individual Pd sites, Pd-Zn dual sites display much higher activity for ethanol electro-oxidation, exceeding that of commercial Pd/C by a factor of ~24. Further computational studies disclose that Pd-Zn dual sites promote the adsorption of ethanol and hydroxide ion to optimize the electro-oxidation pathway with dramatically reduced energy barriers, leading to the superior activity. This work provides valuable clues for developing high-performance ethanol electro-oxidation catalysts for fuel cells.
The regulatory light chain mediates inactivation of myosin motors during active shortening of cardiac muscle
Authors: Kampourakis Thomas , Irving Malcolm 
Published: September 2021

AbstractThe normal function of heart muscle depends on its ability to contract more strongly at longer length. Increased venous filling stretches relaxed heart muscle cells, triggering a stronger contraction in the next beat- the Frank-Starling relation. Conversely, heart muscle cells are inactivated when they shorten during ejection, accelerating relaxation to facilitate refilling before the next beat. Although both effects are essential for the efficient function of the heart, the underlying mechanisms were unknown. Using bifunctional fluorescent probes on the regulatory light chain of the myosin motor we show that its N-terminal domain may be captured in the folded OFF state of the myosin dimer at the end of the working-stroke of the actin-attached motor, whilst its C-terminal domain joins the OFF state only after motor detachment from actin. We propose that sequential folding of myosin motors onto the filament backbone may be responsible for shortening-induced de-activation in the heart.
Single-cell ATAC and RNA sequencing reveal pre-existing and persistent cells associated with prostate cancer relapse
Authors: Taavitsainen S. , Engedal N. , Cao S. , Handle F. , Erickson A. , Prekovic S. , Wetterskog D. , Tolonen T. , Vuorinen E. M. , Kiviaho A. , Nätkin R. , Häkkinen T. , Devlies W. , Henttinen S. , Kaarijärvi R. , Lahnalampi M. , Kaljunen H. , Nowakowska K. , Syvälä H. , Bläuer M. , Cremaschi P. , Claessens F. , Visakorpi T. , Tammela T. L. J. , Murtola T. , Granberg K. J. , Lamb A. D. , Ketola K. , Mills I. G. , Attard G. , Wang W. , Nykter M. , Urbanucci A. 
Published: September 2021

AbstractProstate cancer is heterogeneous and patients would benefit from methods that stratify those who are likely to respond to systemic therapy. Here, we employ single-cell assays for transposase-accessible chromatin (ATAC) and RNA sequencing in models of early treatment response and resistance to enzalutamide. In doing so, we identify pre-existing and treatment-persistent cell subpopulations that possess regenerative potential when subjected to treatment. We find distinct chromatin landscapes associated with enzalutamide treatment and resistance that are linked to alternative transcriptional programs. Transcriptional profiles characteristic of persistent cells are able to stratify the treatment response of patients. Ultimately, we show that defining changes in chromatin and gene expression in single-cell populations from pre-clinical models can reveal as yet unrecognized molecular predictors of treatment response. This suggests that the application of single-cell methods with high analytical resolution in pre-clinical models may powerfully inform clinical decision-making.
Quantized classical response from spectral winding topology
Authors: Li Linhu , Mu Sen , Lee Ching Hua , Gong Jiangbin 
Published: September 2021

AbstractTopologically quantized response is one of the focal points of contemporary condensed matter physics. While it directly results in quantized response coefficients in quantum systems, there has been no notion of quantized response in classical systems thus far. This is because quantized response has always been connected to topology via linear response theory that assumes a quantum mechanical ground state. Yet, classical systems can carry arbitrarily amounts of energy in each mode, even while possessing the same number of measurable edge states as their topological winding. In this work, we discover the totally new paradigm of quantized classical response, which is based on the spectral winding number in the complex spectral plane, rather than the winding of eigenstates in momentum space. Such quantized response is classical insofar as it applies to phenomenological non-Hermitian setting, arises from fundamental mathematical properties of the Green’s function, and shows up in steady-state response, without invoking a conventional linear response theory. Specifically, the ratio of the change in one quantity depicting signal amplification to the variation in one imaginary flux-like parameter is found to display fascinating plateaus, with their quantized values given by the spectral winding numbers as the topological invariants.
Infusing theory into deep learning for interpretable reactivity prediction
Authors: Wang Shih-Han , Pillai Hemanth Somarajan , Wang Siwen , Achenie Luke E. K. , Xin Hongliang 
Published: September 2021

AbstractDespite recent advances of data acquisition and algorithms development, machine learning (ML) faces tremendous challenges to being adopted in practical catalyst design, largely due to its limited generalizability and poor explainability. Herein, we develop a theory-infused neural network (TinNet) approach that integrates deep learning algorithms with the well-established d-band theory of chemisorption for reactivity prediction of transition-metal surfaces. With simple adsorbates (e.g., *OH, *O, and *N) at active site ensembles as representative descriptor species, we demonstrate that the TinNet is on par with purely data-driven ML methods in prediction performance while being inherently interpretable. Incorporation of scientific knowledge of physical interactions into learning from data sheds further light on the nature of chemical bonding and opens up new avenues for ML discovery of novel motifs with desired catalytic properties.
Interfacial electronic structure engineering on molybdenum sulfide for robust dual-pH hydrogen evolution
Authors: Liu Mingqiang , Wang Jia-Ao , Klysubun Wantana , Wang Gui-Gen , Sattayaporn Suchinda , Li Fei , Cai Ya-Wei , Zhang Fuchun , Yu Jie , Yang Ya 
Published: September 2021

AbstractMolybdenum disulfide, as an electronic highly-adjustable catalysts material, tuning its electronic structure is crucial to enhance its intrinsic hydrogen evolution reaction (HER) activity. Nevertheless, there are yet huge challenges to the understanding and regulation of the surface electronic structure of molybdenum disulfide-based catalysts. Here we address these challenges by tuning its electronic structure of phase modulation synergistic with interfacial chemistry and defects from phosphorus or sulfur implantation, and we then successfully design and synthesize electrocatalysts with the multi-heterojunction interfaces (e.g., 1T0.81-MoS2@Ni2P), demonstrating superior HER activities and good stabilities with a small overpotentials of 38.9 and 95 mV at 10 mA/cm2, a low Tafel slopes of 41 and 42 mV/dec in acidic as well as alkaline surroundings, outperforming commercial Pt/C catalyst and other reported Mo-based catalysts. Theoretical calculation verified that the incorporation of metallic-phase and intrinsic HER-active Ni-based materials into molybdenum disulfide could effectively regulate its electronic structure for making the bandgap narrower. Additionally, X-ray absorption spectroscopy indicate that reduced nickel possesses empty orbitals, which is helpful for additional H binding ability. All these factors can decrease Mo-H bond strength, greatly improving the HER catalytic activity of these materials.