bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of two-drug combinations, amikacin/tigecycline/imipenem and amikacin/tigecycline/clarithromycin against Mycobacteroides abscessus subsp. abscessus using the in vitro time-kill assay
Authors: Portell-Buj Elena , Bonet-Rossinyol Queralt , López-Gavín Alexandre , Roman Angely , Fernández-Pittol Mariana , Tudó Griselda , Gonzalez-Martin Julian
Published: January 2021

Nontuberculous mycobacteria include 198 mycobacterial species. Among these, Mycobacteroides abscessus is a rapidly growing mycobacteria that causes lung and skin infections. M. abscessus lung infections are difficult to treat due to the high levels of resistance to several classes of antibiotics. The current treatment is based on combining at least two or three antibiotics. However, treatment outcomes remain very poor. The objective was to compare the in vitro activity of amikacin, tigecycline, imipenem, and clarithromycin, alone and in two different three-drug combinations (amikacin/tigecycline/imipenem and amikacin/tigecycline/clarithromycin) against seven M. abscessus subsp. abscessus clinical isolates using the time-kill assay. The two combinations showed greater activity than the antibiotics tested individually. Even though both combinations showed similar activity as well as no antagonistic activity, the combination including imipenem could not be an alternative treatment against M. abscessus subsp. abscessus lung infections caused by clarithromycin susceptible isolates. However, this combination could be considered against clarithromycin resistant isolates. Future studies are necessary to confirm this hypothesis.
Chromosome-scale genome assembly provides insights into the evolution and flavor synthesis of passion fruit (Passiflora edulis Sims)
Authors: Xia Zhiqiang , Huang Dongmei , Zhang Shengkui , Wang Wenquan , Ma Funing , Wu Bin , Xu Yi , Xu Bingqiang , Chen Di , Zou Meiling , Xu Huanyu , Zhou Xincheng , Zhan Rulin , Song Shun
Published: January 2021

Passion fruit (Passiflora edulis Sims) is an economically valuable fruit that is cultivated in tropical and subtropical regions of the world. Here, we report an ~1341.7 Mb chromosome-scale genome assembly of passion fruit, with 98.91% (~1327.18 Mb) of the assembly assigned to nine pseudochromosomes. The genome includes 23,171 protein-coding genes, and most of the assembled sequences are repetitive sequences, with long-terminal repeats (LTRs) being the most abundant. Phylogenetic analysis revealed that passion fruit diverged after Brassicaceae and before Euphorbiaceae. Ks analysis showed that two whole-genome duplication events occurred in passion fruit at 65 MYA and 12 MYA, which may have contributed to its large genome size. An integrated analysis of genomic, transcriptomic, and metabolomic data showed that ‘alpha-linolenic acid metabolism’, ‘metabolic pathways’, and ‘secondary metabolic pathways’ were the main pathways involved in the synthesis of important volatile organic compounds (VOCs) in passion fruit, and this analysis identified some candidate genes, including GDP-fucose Transporter 1-like, Tetratricopeptide repeat protein 33, protein NETWORKED 4B isoform X1, and Golgin Subfamily A member 6-like protein 22. In addition, we identified 13 important gene families in fatty acid pathways and eight important gene families in terpene pathways. Gene family analysis showed that the ACX, ADH, ALDH, and HPL gene families, especially ACX13/14/15/20, ADH13/26/33, ALDH1/4/21, and HPL4/6, were the key genes for ester synthesis, while the TPS gene family, especially PeTPS2/3/4/24, was the key gene family for terpene synthesis. This work provides insights into genome evolution and flavor trait biology and offers valuable resources for the improved cultivation of passion fruit.
Lossless integration of multiple electronic health records for identifying pleiotropy using summary statistics
Authors: Li Ruowang , Duan Rui , Zhang Xinyuan , Lumley Thomas , Pendergrass Sarah , Bauer Christopher , Hakonarson Hakon , Carrell David S. , Smoller Jordan W. , Wei Wei-Qi , Carroll Robert , Velez Edwards Digna R. , Wiesner Georgia , Sleiman Patrick , Denny Josh C. , Mosley Jonathan D. , Ritchie Marylyn D. , Chen Yong , Moore Jason H.
Published: January 2021

Increasingly, clinical phenotypes with matched genetic data from bio-bank linked electronic health records (EHRs) have been used for pleiotropy analyses. Thus far, pleiotropy analysis using individual-level EHR data has been limited to data from one site. However, it is desirable to integrate EHR data from multiple sites to improve the detection power and generalizability of the results. Due to privacy concerns, individual-level patients’ data are not easily shared across institutions. As a result, we introduce Sum-Share, a method designed to efficiently integrate EHR and genetic data from multiple sites to perform pleiotropy analysis. Sum-Share requires only summary-level data and one round of communication from each site, yet it produces identical test statistics compared with that of pooled individual-level data. Consequently, Sum-Share can achieve lossless integration of multiple datasets. Using real EHR data from eMERGE, Sum-Share is able to identify 1734 potential pleiotropic SNPs for five cardiovascular diseases.
Nanoscale coordination polymers induce immunogenic cell death by amplifying radiation therapy mediated oxidative stress
Authors: Huang Zhusheng , Wang Yuxiang , Yao Dan , Wu Jinhui , Hu Yiqiao , Yuan Ahu
Published: January 2021

Radiation therapy can potentially induce immunogenic cell death, thereby priming anti-tumor adaptive immune responses. However, radiation-induced systemic immune responses are very rare and insufficient to meet clinical needs. Here, we demonstrate a synergetic strategy for boosting radiation-induced immunogenic cell death by constructing gadolinium-hemin based nanoscale coordination polymers to simultaneously perform X-ray deposition and glutathione depletion. Subsequently, immunogenic cell death is induced by sensitized radiation to potentiate checkpoint blockade immunotherapies against primary and metastatic tumors. In conclusion, nanoscale coordination polymers-sensitized radiation therapy exhibits biocompatibility and therapeutic efficacy in preclinical cancer models, and has the potential for further application in cancer radio-immunotherapy.
Groundwater discharge impacts marine isotope budgets of Li, Mg, Ca, Sr, and Ba
Authors: Mayfield Kimberley K. , Eisenhauer Anton , Santiago Ramos Danielle P. , Higgins John A. , Horner Tristan J. , Auro Maureen , Magna Tomas , Moosdorf Nils , Charette Matthew A. , Gonneea Meagan Eagle , Brady Carolyn E. , Komar Nemanja , Peucker-Ehrenbrink Bernhard , Paytan Adina
Published: January 2021

Groundwater-derived solute fluxes to the ocean have long been assumed static and subordinate to riverine fluxes, if not neglected entirely, in marine isotope budgets. Here we present concentration and isotope data for Li, Mg, Ca, Sr, and Ba in coastal groundwaters to constrain the importance of groundwater discharge in mediating the magnitude and isotopic composition of terrestrially derived solute fluxes to the ocean. Data were extrapolated globally using three independent volumetric estimates of groundwater discharge to coastal waters, from which we estimate that groundwater-derived solute fluxes represent, at a minimum, 5% of riverine fluxes for Li, Mg, Ca, Sr, and Ba. The isotopic compositions of the groundwater-derived Mg, Ca, and Sr fluxes are distinct from global riverine averages, while Li and Ba fluxes are isotopically indistinguishable from rivers. These differences reflect a strong dependence on coastal lithology that should be considered a priority for parameterization in Earth-system models.
An efficient and stable solar flow battery enabled by a single-junction GaAs photoelectrode
Authors: Fu Hui-Chun , Li Wenjie , Yang Ying , Lin Chun-Ho , Veyssal Atilla , He Jr-Hau , Jin Song
Published: January 2021

Converting and storing solar energy and releasing it on demand by using solar flow batteries (SFBs) is a promising way to address the challenge of solar intermittency. Although high solar-to-output electricity efficiencies (SOEE) have been recently demonstrated in SFBs, the complex multi-junction photoelectrodes used are not desirable for practical applications. Here, we report an efficient and stable integrated SFB built with back-illuminated single-junction GaAs photoelectrode with an n-p-n sandwiched design. Rational potential matching simulation and operating condition optimization of this GaAs SFB lead to a record SOEE of 15.4% among single-junction SFB devices. Furthermore, the TiO2 protection layer and robust redox couples in neutral pH electrolyte enable the SFB to achieve stable cycling over 408 h (150 cycles). These results advance the utilization of more practical solar cells with higher photocurrent densities but lower photovoltages for high performance SFBs and pave the way for developing practical and efficient SFBs.
Van Hove singularity in the magnon spectrum of the antiferromagnetic quantum honeycomb lattice
Authors: Sala G. , Stone M. B. , Rai Binod K. , May A. F. , Laurell Pontus , Garlea V. O. , Butch N. P. , Lumsden M. D. , Ehlers G. , Pokharel G. , Podlesnyak A. , Mandrus D. , Parker D. S. , Okamoto S. , Halász Gábor B. , Christianson A. D.
Published: January 2021

In quantum magnets, magnetic moments fluctuate heavily and are strongly entangled with each other, a fundamental distinction from classical magnetism. Here, with inelastic neutron scattering measurements, we probe the spin correlations of the honeycomb lattice quantum magnet YbCl3. A linear spin wave theory with a single Heisenberg interaction on the honeycomb lattice, including both transverse and longitudinal channels of the neutron response, reproduces all of the key features in the spectrum. In particular, we identify a Van Hove singularity, a clearly observable sharp feature within a continuum response. The demonstration of such a Van Hove singularity in a two-magnon continuum is important as a confirmation of broadly held notions of continua in quantum magnetism and additionally because analogous features in two-spinon continua could be used to distinguish quantum spin liquids from merely disordered systems. These results establish YbCl3 as a benchmark material for quantum magnetism on the honeycomb lattice.
Bayesian genome scale modelling identifies thermal determinants of yeast metabolism
Authors: Li Gang , Hu Yating , Jan Zrimec  , Luo Hao , Wang Hao , Zelezniak Aleksej , Ji Boyang , Nielsen Jens
Published: January 2021

The molecular basis of how temperature affects cell metabolism has been a long-standing question in biology, where the main obstacles are the lack of high-quality data and methods to associate temperature effects on the function of individual proteins as well as to combine them at a systems level. Here we develop and apply a Bayesian modeling approach to resolve the temperature effects in genome scale metabolic models (GEM). The approach minimizes uncertainties in enzymatic thermal parameters and greatly improves the predictive strength of the GEMs. The resulting temperature constrained yeast GEM uncovers enzymes that limit growth at superoptimal temperatures, and squalene epoxidase (ERG1) is predicted to be the most rate limiting. By replacing this single key enzyme with an ortholog from a thermotolerant yeast strain, we obtain a thermotolerant strain that outgrows the wild type, demonstrating the critical role of sterol metabolism in yeast thermosensitivity. Therefore, apart from identifying thermal determinants of cell metabolism and enabling the design of thermotolerant strains, our Bayesian GEM approach facilitates modelling of complex biological systems in the absence of high-quality data and therefore shows promise for becoming a standard tool for genome scale modeling.
Constructing multifunctional solid electrolyte interface via in-situ polymerization for dendrite-free and low N/P ratio lithium metal batteries
Authors: Luo Dan , Zheng Lei , Zhang Zhen , Li Matthew , Chen Zhongwei , Cui Ruiguang , Shen Yanbin , Li Gaoran , Feng Renfei , Zhang Shaojian , Jiang Gaopeng , Chen Liwei , Yu Aiping , Wang Xin
Published: January 2021

Stable solid electrolyte interface (SEI) is highly sought after for lithium metal batteries (LMB) owing to its efficient electrolyte consumption suppression and Li dendrite growth inhibition. However, current design strategies can hardly endow a multifunctional SEI formation due to the non-uniform, low flexible film formation and limited capability to alter Li nucleation/growth orientation, which results in unconstrained dendrite growth and short cycling stability. Herein, we present a novel strategy to employ electrolyte additives containing catechol and acrylic groups to construct a stable multifunctional SEI by in-situ anionic polymerization. This self-smoothing and robust SEI offers multiple sites for Li adsorption and steric repulsion to constrain nucleation/growth process, leading to homogenized Li nanosphere formation. This isotropic nanosphere offers non-preferred Li growth orientation, rendering uniform Li deposition to achieve a dendrite-free anode. Attributed to these superiorities, a remarkable cycling performance can be obtained, i.e., high current density up to 10 mA cm−2, ultra-long cycle life over 8500 hrs operation, high cumulative capacity over 4.25 Ah cm−2 and stable cycling under 60 °C. A prolonged lifespan can also be achieved in Li-S and Li-LiFePO4 cells under lean electrolyte content, low N/P ratio or high temperature conditions. This facile strategy also promotes the practical application of LMB and enlightens the SEI design in related fields.
Longitudinal evaluation of fecal microbiota transplantation for ameliorating calf diarrhea and improving growth performance
Authors: Kim Hyun Sik , Whon Tae Woong , Sung Hojun , Jeong Yun-Seok , Jung Eun Sung , Shin Na-Ri , Hyun Dong-Wook , Kim Pil Soo , Lee June-Young , Lee Choong Hwan , Bae Jin-Woo
Published: January 2021

Calf diarrhea is associated with enteric infections, and also provokes the overuse of antibiotics. Therefore, proper treatment of diarrhea represents a therapeutic challenge in livestock production and public health concerns. Here, we describe the ability of a fecal microbiota transplantation (FMT), to ameliorate diarrhea and restore gut microbial composition in 57 growing calves. We conduct multi-omics analysis of 450 longitudinally collected fecal samples and find that FMT-induced alterations in the gut microbiota (an increase in the family Porphyromonadaceae) and metabolomic profile (a reduction in fecal amino acid concentration) strongly correlate with the remission of diarrhea. During the continuous follow-up study over 24 months, we find that FMT improves the growth performance of the cattle. This first FMT trial in ruminants suggest that FMT is capable of ameliorating diarrhea in pre-weaning calves with alterations in their gut microbiota, and that FMT may have a potential role in the improvement of growth performance.
Cryo-EM analysis of the HCoV-229E spike glycoprotein reveals dynamic prefusion conformational changes
Authors: Song Xiyong , Shi Yuejun , Ding Wei , Niu Tongxin , Sun Limeng , Tan Yubei , Chen Yong , Shi Jiale , Xiong Qiqi , Huang Xiaojun , Xiao Shaobo , Zhu Yanping , Cheng Chongyun , Fu Zhen F. , Liu Zhi-Jie , Peng Guiqing
Published: January 2021

Coronaviruses spike (S) glycoproteins mediate viral entry into host cells by binding to host receptors. However, how the S1 subunit undergoes conformational changes for receptor recognition has not been elucidated in Alphacoronavirus. Here, we report the cryo-EM structures of the HCoV-229E S trimer in prefusion state with two conformations. The activated conformation may pose the potential exposure of the S1-RBDs by decreasing of the interaction area between the S1-RBDs and the surrounding S1-NTDs and S1-RBDs compared to the closed conformation. Furthermore, structural comparison of our structures with the previously reported HCoV-229E S structure showed that the S trimers trended to open the S2 subunit from the closed conformation to open conformation, which could promote the transition from pre- to postfusion. Our results provide insights into the mechanisms involved in S glycoprotein-mediated Alphacoronavirus entry and have implications for vaccine and therapeutic antibody design.
Multi-scale characterisation of a ferroelectric polymer reveals the emergence of a morphological phase transition driven by temperature
Authors: Hafner Jonas , Benaglia Simone , Richheimer Filipe , Teuschel Marco , Maier Franz J. , Werner Artner , Wood Sebastian , Platz Daniel , Schneider Michael , Hradil Klaudia , Castro Fernando A. , Garcia Ricardo , Schmid Ulrich
Published: January 2021

Ferroelectric materials exhibit a phase transition to a paraelectric state driven by temperature - called the Curie transition. In conventional ferroelectrics, the Curie transition is caused by a change in crystal symmetry, while the material itself remains a continuous three-dimensional solid crystal. However, ferroelectric polymers behave differently. Polymeric materials are typically of semi-crystalline nature, meaning that they are an intermixture of crystalline and amorphous regions. Here, we demonstrate that the semi-crystalline morphology of the ferroelectric copolymer of vinylidene fluoride and trifluoroethylene (P(VDF-TrFE)) strongly affects its Curie transition, as not only a change in crystal symmetry but also in morphology occurs. We demonstrate, by high-resolution nanomechanical measurements, that the semi-crystalline microstructure in the paraelectric state is formed by crystalline domains embedded into a softer amorphous phase. Using in situ X-ray diffraction measurements, we show that the local electromechanical response of the crystalline domains is counterbalanced by the amorphous phase, effectively masking its macroscopic effect. Our quantitative multi-scale characterisations unite the nano- and macroscopic material properties of the ferroelectric polymer P(VDF-TrFE) through its semi-crystalline nature.
Spread spectrum SERS allows label-free detection of attomolar neurotransmitters
Authors: Lee Wonkyoung , Kang Byoung-Hoon , Yang Hyunwoo , Park Moonseong , Kwak Ji Hyun , Chung Taerin , Jeong Yong , Kim Bong Kyu , Jeong Ki-Hun
Published: January 2021

The quantitative label-free detection of neurotransmitters provides critical clues in understanding neurological functions or disorders. However, the identification of neurotransmitters remains challenging for surface-enhanced Raman spectroscopy (SERS) due to the presence of noise. Here, we report spread spectrum SERS (ss-SERS) detection for the rapid quantification of neurotransmitters at the attomolar level by encoding excited light and decoding SERS signals with peak autocorrelation and near-zero cross-correlation. Compared to conventional SERS measurements, the experimental result of ss-SERS shows an exceptional improvement in the signal-to-noise ratio of more than three orders of magnitude, thus achieving a high temporal resolution of over one hundred times. The ss-SERS measurement further allows the attomolar SERS detection of dopamine, serotonin, acetylcholine, γ-aminobutyric acid, and glutamate without Raman reporters. This approach opens up opportunities not only for investigating the early diagnostics of neurological disorders or highly sensitive biomedical SERS applications but also for developing low-cost spectroscopic biosensing applications.
Thioesterase-mediated side chain transesterification generates potent Gq signaling inhibitor FR900359
Authors: Hermes Cornelia , Richarz René , Wirtz Daniel A. , Patt Julian , Hanke Wiebke , Kehraus Stefan , Voß Jan Hendrik , Küppers Jim , Ohbayashi Tsubasa , Namasivayam Vigneshwaran , Alenfelder Judith , Inoue Asuka , Mergaert Peter , Gütschow Michael , Müller Christa E. , Kostenis Evi , König Gabriele M. , Crüsemann Max
Published: January 2021

The potent and selective Gq protein inhibitor depsipeptide FR900359 (FR), originally discovered as the product of an uncultivable plant endosymbiont, is synthesized by a complex biosynthetic system comprising two nonribosomal peptide synthetase (NRPS) assembly lines. Here we characterize a cultivable bacterial FR producer, enabling detailed investigations into biosynthesis and attachment of the functionally important FR side chain. We reconstitute side chain assembly by the monomodular NRPS FrsA and the non-heme monooxygenase FrsH, and characterize intermolecular side chain transesterification to the final macrocyclic intermediate FR-Core, mediated by the FrsA thioesterase domain. We harness FrsA substrate promiscuity to generate FR analogs with altered side chains and demonstrate indispensability of the FR side chain for efficient Gq inhibition by comparative bioactivity, toxicity and docking studies. Finally, evolution of FR and side chain biosynthesis is discussed based on bioinformatics analyses. Side chain transesterification boosts potency and target affinity of selective Gq inhibitor natural products.
Thermocatalytic hydrogen peroxide generation and environmental disinfection by Bi2Te3 nanoplates
Authors: Lin Yu-Jiung , Khan Imran , Saha Subhajit , Wu Chih-Cheng , Barman Snigdha Roy , Kao Fu-Cheng , Lin Zong-Hong
Published: January 2021

The highly reactive nature of reactive oxygen species (ROS) is the basis for widespread use in environmental and health-related fields. Conventionally, there are only two kinds of catalysts used for ROS generation: photocatalysts and piezocatalysts. However, their usage has been limited due to various environmental and physical factors. To address this problem, herein, we report thermoelectric materials, such as Bi2Te3, Sb2Te3, and PbTe, as thermocatalysts which can produce hydrogen peroxide (H2O2) under a small surrounding temperature difference. Being the most prevalent environmental factors in daily life, temperature and related thermal effects have tremendous potential for practical applications. To increase the practicality in everyday life, bismuth telluride nanoplates (Bi2Te3NPs), serving as an efficient thermocatalyst, are coated on a carbon fiber fabric (Bi2Te3@CFF) to develop a thermocatalytic filter with antibacterial function. Temperature difference induced H2O2generation by thermocatalysts results in the oxidative damage of bacteria, which makes thermocatalysts highly promising for disinfection applications. Antibacterial activity as high as 95% is achieved only by the treatment of low-temperature difference cycles. The current work highlights the horizon-shifting impacts of thermoelectric materials for real-time purification and antibacterial applications.
Identification of a subset of immunosuppressive P2RX1-negative neutrophils in pancreatic cancer liver metastasis
Authors: Wang Xu , Hu Li-Peng , Qin Wei-Ting , Yang Qin , Chen De-Yu , Li Qing , Zhou Kai-Xia , Huang Pei-Qi , Xu Chun-Jie , Li Jun , Yao Lin-Li , Wang Ya-Hui , Tian Guang-Ang , Yang Jian-Yu , Yang Min-Wei , Liu De-Jun , Sun Yong-Wei , Jiang Shu-Heng , Zhang Xue-Li , Zhang Zhi-Gang
Published: January 2021

The immunosuppressive microenvironment that is shaped by hepatic metastatic pancreatic ductal adenocarcinoma (PDAC) is essential for tumor cell evasion of immune destruction. Neutrophils are important components of the metastatic tumor microenvironment and exhibit heterogeneity. However, the specific phenotypes, functions and regulatory mechanisms of neutrophils in PDAC liver metastases remain unknown. Here, we show that a subset of P2RX1-negative neutrophils accumulate in clinical and murine PDAC liver metastases. RNA sequencing of murine PDAC liver metastasis-infiltrated neutrophils show that P2RX1-deficient neutrophils express increased levels of immunosuppressive molecules, including PD-L1, and have enhanced mitochondrial metabolism. Mechanistically, the transcription factor Nrf2 is upregulated in P2RX1-deficient neutrophils and associated with PD-L1 expression and metabolic reprogramming. An anti-PD-1 neutralizing antibody is sufficient to compromise the immunosuppressive effects of P2RX1-deficient neutrophils on OVA-activated OT1 CD8+ T cells. Therefore, our study uncovers a mechanism by which metastatic PDAC tumors evade antitumor immunity by accumulating a subset of immunosuppressive P2RX1-negative neutrophils.
Northern preference for terrestrial electromagnetic energy input from space weather
Authors: Pakhotin I. P. , Mann I. R. , Xie K. , Burchill J. K. , Knudsen D. J.
Published: January 2021

Terrestrial space weather involves the transfer of energy and momentum from the solar wind into geospace. Despite recently discovered seasonal asymmetries between auroral forms and the intensity of emissions between northern and southern hemispheres, seasonally averaged energy input into the ionosphere is still generally considered to be symmetric. Here we show, using Swarm satellite data, a preference for electromagnetic energy input at 450 km altitude into the northern hemisphere, on both the dayside and the nightside, when averaged over season. We propose that this is explained by the offset of the magnetic dipole away from Earth’s center. This introduces a larger separation between the magnetic pole and rotation axis in the south, creating different relative solar illumination of northern and southern auroral zones, resulting in changes to the strength of reflection of incident Alfvén waves from the ionosphere. Our study reveals an important asymmetry in seasonally averaged electromagnetic energy input to the atmosphere. Based on observed lower Poynting flux on the nightside this asymmetry may also exist for auroral emissions. Similar offsets may drive asymmetric energy input, and potentially aurora, on other planets.
An autophagy enhancer ameliorates diabetes of human IAPP-transgenic mice through clearance of amyloidogenic oligomer
Authors: Kim Jinyoung , Park Kihyoun , Kim Min Jung , Lim Hyejin , Kim Kook Hwan , Kim Sun-Woo , Lee Eun-Seo , Kim Hyongbum , Kim Sung Joo , Hur Kyu Yeon , Kim Jae Hyeon , Ahn Jin Hee , Yoon Kun-Ho , Kim Ji-Won , Lee Myung-Shik
Published: January 2021

We have reported that autophagy is crucial for clearance of amyloidogenic human IAPP (hIAPP) oligomer, suggesting that an autophagy enhancer could be a therapeutic modality against human diabetes with amyloid accumulation. Here, we show that a recently identified autophagy enhancer (MSL-7) reduces hIAPP oligomer accumulation in human induced pluripotent stem cell-derived β-cells (hiPSC-β-cells) and diminishes oligomer-mediated apoptosis of β-cells. Protective effects of MSL-7 against hIAPP oligomer accumulation and hIAPP oligomer-mediated β-cell death are significantly reduced in cells with knockout of MiTF/TFE family members such as Tfeb or Tfe3. MSL-7 improves glucose tolerance and β-cell function of hIAPP+ mice on high-fat diet, accompanied by reduced hIAPP oligomer/amyloid accumulation and β-cell apoptosis. Protective effects of MSL-7 against hIAPP oligomer-mediated β-cell death and the development of diabetes are also significantly reduced by β-cell-specific knockout of Tfeb. These results suggest that an autophagy enhancer could have therapeutic potential against human diabetes characterized by islet amyloid accumulation.
A flexible electron-blocking interfacial shield for dendrite-free solid lithium metal batteries
Authors: Huo Hanyu , Gao Jian , Zhao Ning , Zhang Dongxing , Holmes Nathaniel Graham , Li Xiaona , Sun Yipeng , Fu Jiamin , Li Ruying , Guo Xiangxin , Sun Xueliang
Published: January 2021

Solid-state batteries (SSBs) are considered to be the next-generation lithium-ion battery technology due to their enhanced energy density and safety. However, the high electronic conductivity of solid-state electrolytes (SSEs) leads to Li dendrite nucleation and proliferation. Uneven electric-field distribution resulting from poor interfacial contact can further promote dendritic deposition and lead to rapid short circuiting of SSBs. Herein, we propose a flexible electron-blocking interfacial shield (EBS) to protect garnet electrolytes from the electronic degradation. The EBS formed by an in-situ substitution reaction can not only increase lithiophilicity but also stabilize the Li volume change, maintaining the integrity of the interface during repeated cycling. Density functional theory calculations show a high electron-tunneling energy barrier from Li metal to the EBS, indicating an excellent capacity for electron-blocking. EBS protected cells exhibit an improved critical current density of 1.2 mA cm−2 and stable cycling for over 400 h at 1 mA cm−2 (1 mAh cm−2) at room temperature. These results demonstrate an effective strategy for the suppression of Li dendrites and present fresh insight into the rational design of the SSE and Li metal interface.
Function-oriented design of robust metal cocatalyst for photocatalytic hydrogen evolution on metal/titania composites
Authors: Wang Dong , Gong Xue-Qing
Published: January 2021

While the precise design of catalysts is one of ultimate goals in catalysis, practical strategies often fall short, especially for complicated photocatalytic processes. Here, taking the hydrogen evolution reaction (HER) as an example, we introduce a theoretical approach for designing robust metal cocatalysts supported on TiO2 using density functional theory calculations adopting on-site Coulomb correction and/or hybrid functionals. The approach starts with clarifying the individual function of each metal layer of metal/TiO2 composites in photocatalytic HER, covering both the electron transfer and surface catalysis aspects, followed by conducting a function-oriented optimization via exploring competent candidates. With this approach, we successfully determine and verify bimetallic Pt/Rh/TiO2 and Pt/Cu/TiO2 catalysts to be robust substitutes for conventional Pt/TiO2. The right metal type as well as the proper stacking sequence are demonstrated to be key to boosting performance. Moreover, we tentatively identify the tunneling barrier height as an effective descriptor for the important electron transfer process in photocatalysis on metal/oxide catalysts. We believe that this study pushes forward the frontier of photocatalyst design towards higher water splitting efficiency.
Around one third of current Arctic Ocean primary production sustained by rivers and coastal erosion
Authors: Terhaar Jens , Lauerwald Ronny , Regnier Pierre , Gruber Nicolas , Bopp Laurent
Published: January 2021

Net primary production (NPP) is the foundation of the oceans’ ecosystems and the fisheries they support. In the Arctic Ocean, NPP is controlled by a complex interplay of light and nutrients supplied by upwelling as well as lateral inflows from adjacent oceans and land. But so far, the role of the input from land by rivers and coastal erosion has not been given much attention. Here, by upscaling observations from the six largest rivers and using measured coastal erosion rates, we construct a pan-Arctic, spatio-temporally resolved estimate of the land input of carbon and nutrients to the Arctic Ocean. Using an ocean-biogeochemical model, we estimate that this input fuels 28–51% of the current annual Arctic Ocean NPP. This strong enhancement of NPP is a consequence of efficient recycling of the land-derived nutrients on the vast Arctic shelves. Our results thus suggest that nutrient input from the land is a key process that will affect the future evolution of Arctic Ocean NPP.
Integrated analysis of telomerase enzymatic activity unravels an association with cancer stemness and proliferation
Authors: Noureen Nighat , Wu Shaofang , Lv Yingli , Yang Juechen , Alfred Yung W. K. , Gelfond Jonathan , Wang Xiaojing , Koul Dimpy , Ludlow Andrew , Zheng Siyuan
Published: January 2021

Active telomerase is essential for stem cells and most cancers to maintain telomeres. The enzymatic activity of telomerase is related but not equivalent to the expression of TERT, the catalytic subunit of the complex. Here we show that telomerase enzymatic activity can be robustly estimated from the expression of a 13-gene signature. We demonstrate the validity of the expression-based approach, named EXTEND, using cell lines, cancer samples, and non-neoplastic samples. When applied to over 9,000 tumors and single cells, we find a strong correlation between telomerase activity and cancer stemness. This correlation is largely driven by a small population of proliferating cancer cells that exhibits both high telomerase activity and cancer stemness. This study establishes a computational framework for quantifying telomerase enzymatic activity and provides new insights into the relationships among telomerase, cancer proliferation, and stemness.
Thermoelectric current in a graphene Cooper pair splitter
Authors: Tan Z. B. , Laitinen A. , Kirsanov N. S. , Galda A. , Vinokur V. M. , Haque M. , Savin A. , Golubev D. S. , Lesovik G. B. , Hakonen P. J.
Published: January 2021

Generation of electric voltage in a conductor by applying a temperature gradient is a fundamental phenomenon called the Seebeck effect. This effect and its inverse is widely exploited in diverse applications ranging from thermoelectric power generators to temperature sensing. Recently, a possibility of thermoelectricity arising from the interplay of the non-local Cooper pair splitting and the elastic co-tunneling in the hybrid normal metal-superconductor-normal metal structures was predicted. Here, we report the observation of the non-local Seebeck effect in a graphene-based Cooper pair splitting device comprising two quantum dots connected to an aluminum superconductor and present a theoretical description of this phenomenon. The observed non-local Seebeck effect offers an efficient tool for producing entangled electrons.
Electric-field-driven octahedral rotation in perovskite
Authors: Kyung Wonshik , Kim Choong H. , Kim Yeong Kwan , Kim Beomyoung , Kim Chul , Jung Woobin , Kwon Junyoung , Kim Minsoo , Bostwick Aaron , Denlinger Jonathan D. , Yoshida Yoshiyuki , Kim Changyoung
Published: January 2021

Rotation of MO6 (M = transition metal) octahedra is a key determinant of the physical properties of perovskite materials. Therefore, tuning physical properties, one of the most important goals in condensed matter research, may be accomplished by controlling octahedral rotation (OR). In this study, it is demonstrated that OR can be driven by an electric field in Sr2RuO4. Rotated octahedra in the surface layer of Sr2RuO4 are restored to the unrotated bulk structure upon dosing the surface with K. Theoretical investigation shows that OR in Sr2RuO4 originates from the surface electric field, which can be tuned via the screening effect of the overlaid K layer. This work establishes not only that variation in the OR angle can be induced by an electric field, but also provides a way to control OR, which is an important step toward in situ control of the physical properties of perovskite oxides.
Nurture might be nature: cautionary tales and proposed solutions
Authors: Hart Sara A. , Little Callie , van Bergen Elsje
Published: January 2021

Across a wide range of studies, researchers often conclude that the home environment and children’s outcomes are causally linked. In contrast, behavioral genetic studies show that parents influence their children by providing them with both environment and genes, meaning the environment that parents provide should not be considered in the absence of genetic influences, because that can lead to erroneous conclusions on causation. This article seeks to provide behavioral scientists with a synopsis of numerous methods to estimate the direct effect of the environment, controlling for the potential of genetic confounding. Ideally, using genetically sensitive designs can fully disentangle this genetic confound, but these require specialized samples. In the near future, researchers will likely have access to measured DNA variants (summarized in a polygenic scores), which could serve as a partial genetic control, but that is currently not an option that is ideal or widely available. We also propose a work around for when genetically sensitive data are not readily available: the Familial Control Method. In this method, one measures the same trait in the parents as the child, and the parents’ trait is then used as a covariate (e.g., a genetic proxy). When these options are all not possible, we plead with our colleagues to clearly mention genetic confound as a limitation, and to be cautious with any environmental causal statements which could lead to unnecessary parent blaming.
Suppression of mucosal Th17 memory responses by acellular pertussis vaccines enhances nasal Bordetella pertussis carriage
Authors: Dubois Violaine , Chatagnon Jonathan , Thiriard Anaïs , Bauderlique-Le Roy Hélène , Debrie Anne-Sophie , Coutte Loïc , Locht Camille
Published: January 2021

Pertussis has made a spectacular rebound in countries that have switched from whole-cell (wPV) to acellular pertussis vaccines (aPV). Here, we show that, unlike wPV, aPV, while protective against lung colonization byBordetella pertussis(Bp), did not protect BALB/c mice from nasal colonization, but instead substantially prolonged nasal carriage. aPV prevented the natural induction of nasal interleukin-17 (IL-17)-producing and interferon-γ (IFN-γ)-producing CD103+CD44+CD69+CD4+-resident memory T (TRM) cells. IL-17-deficient, but not IFN-γ-deficient, mice failed to clear nasal Bp, indicating a key role of IL-17+TRMcells in the control of nasal infection. These cells appeared essential for neutrophil recruitment, crucial for clearance of Bp tightly bound to the nasal epithelium. Transfer of IL-17+TRMcells from Bp-infected mice to IL-17-deficient mice resulted in neutrophil recruitment and protection against nasal colonization. Thus, aPV may have augmented the Bp reservoir by inhibiting natural TRMcell induction and neutrophil recruitment, thereby contributing to the pertussis resurgence.
Deregulation of extracellular matrix modeling with molecular prognostic markers revealed by transcriptome sequencing and validations in Oral Tongue squamous cell carcinoma
Authors: Thangaraj Soundara Viveka , Shyamsundar Vidyarani , Krishnamurthy Arvind , Ramshankar Vijayalakshmi
Published: January 2021

Oral Tongue Squamous Cell Carcinoma (OTSCC), a distinct sub-group of head and neck cancers, is characteristically aggressive in nature with a higher incidence of recurrence and metastasis. Recent advances in therapeutics have not improved patient survival. The phenomenon of occult node metastasis, even among the purportedly good prognosis group of early-stage and node-negative tongue tumors, leads to a high incidence of locoregional failure in OTSCC which needs to be addressed. In the current study, transcriptome analysis of OTSCC patients identified the key genes and deregulated pathways. A panel of 26 marker genes was shortlisted and validated using real-time PCR in a prospective cohort of 100 patients. The gene expression was correlated with clinicopathological features including occult node metastasis, survival, and therapeutic outcome. The up-regulation of a panel of 6 genes namely, matrix metalloproteinase 9 (MMP9), Laminin subunit Gamma 2 (LAMC2), Desmoglein 2 (DSG2), Plasminogen Activator Urokinase (PLAU), Forkhead Box M1 (FOXM1), and Myosin 1B (MYO1B) was associated with failure of treatment in the early stage (T1, T2). Up-regulation of Tenacin C (TNC) and Podoplanin (PDPN) was significantly correlated with occult node positivity. Immunohistochemical analysis of LAMC2, MMP9, and E-Cadherin (ECAD) confirmed these markers to be indicators of poor prognosis. We propose this panel of valuable prognostic markers can be clinically useful to identify poor prognosis and occult node metastasis in OTSCC patients.
Spatiotemporal analysis of soluble aggregates and autophagy markers in the R6/2 mouse model
Authors: Kumar M. J. Vijay , Shah Devanshi , Giridharan Mridhula , Yadav Niraj , Manjithaya Ravi , Clement James P.
Published: January 2021

Maintenance of cellular proteostasis is vital for post-mitotic cells like neurons to sustain normal physiological function and homeostasis, defects in which are established hallmarks of several age-related conditions like AD, PD, HD, and ALS. The Spatio-temporal accumulation of aggregated proteins in the form of inclusion bodies/plaques is one of the major characteristics of many neurodegenerative diseases, including Huntington’s disease (HD). Toxic accumulation of HUNTINGTIN (HTT) aggregates in neurons bring about the aberrant phenotypes of HD, including severe motor dysfunction, dementia, and cognitive impairment at the organismal level, in an age-dependent manner. In several cellular and animal models, aggrephagy induction has been shown to clear aggregate-prone proteins like HTT and ameliorate disease pathology by conferring neuroprotection. In this study, we used the mouse model of HD, R6/2, to understand the pathogenicity of mHTT aggregates, primarily focusing on autophagy dysfunction. We report that basal autophagy is not altered in R6/2 mice, whilst being functional at a steady-state level in neurons. Moreover, we tested the efficacy of a known autophagy modulator, Nilotinib (Tasigna™), presently in clinical trials for PD, and HD, in curbing mHTT aggregate growth and their potential clearance, which was ineffective in both inducing autophagy and rescuing the pathological phenotypes in R6/2 mice.
An interactive holographic projection system that uses a hand-drawn interface with a consumer CPU
Authors: Nishitsuji Takashi , Kakue Takashi , Blinder David , Shimobaba Tomoyoshi , Ito Tomoyoshi
Published: January 2021

Holography is a promising technology for photo-realistic three-dimensional (3D) displays because of its ability to replay the light reflected from an object using a spatial light modulator (SLM). However, the enormous computational requirements for calculating computer-generated holograms (CGHs)—which are displayed on an SLM as a diffraction pattern—are a significant problem for practical uses (e.g., for interactive 3D displays for remote navigation systems). Here, we demonstrate an interactive 3D display system using electro-holography that can operate with a consumer’s CPU. The proposed system integrates an efficient and fast CGH computation algorithm for line-drawn 3D objects with inter-frame differencing, so that the trajectory of a line-drawn object that is handwritten on a drawing tablet can be played back interactively using only the CPU. In this system, we used an SLM with 1,920 $$\times $$
×
1,080 pixels and a pixel pitch of 8 μm × 8 μm, a drawing tablet as an interface, and an Intel Core i9–9900K 3.60 GHz CPU. Numerical and optical experiments using a dataset of handwritten inputs show that the proposed system is capable of reproducing handwritten 3D images in real time with sufficient interactivity and image quality.
Gene diversity explains variation in biological features of insect killing fungus, Beauveria bassiana
Authors: Gasmi Laila , Baek Sehyeon , Kim Jong Cheol , Kim Sihyeon , Lee Mi Rong , Park So Eun , Shin Tae Young , Lee Se Jin , Parker Bruce L. , Kim Jae Su
Published: January 2021

Beauveria bassianais a species complex whose isolates show considerable natural genetic variability. However, little is known about how this genetic diversity affects the fungus performance. Herein, we characterized the diversity of genes involved in various mechanisms of the infective cycle of 42 isolates that have different growth rates, thermotolerance and virulence. The analysed genes showed general genetic diversity measured as non-synonymous changes (NSC) and copy number variation (CNV), with most of them being subjected to positive episodic diversifying selection. Correlation analyses between NSC or CNV and the isolate virulence, thermotolerance and growth rate revealed that various genes shaped the biological features of the fungus. Lectin-like, mucin signalling, Biotrophy associated and chitinase genes NSCs correlated with the three biological features ofB. bassiana. In addition, other genes (i.e.DNA photolyaseandcyclophilin B) that had relatively conserved sequences, had variable CNs across the isolates which were correlated with the variability of either virulence or thermotolerance ofB. bassianaisolates. The data obtained is important for a better understanding of population structure, ecological and potential impact when isolates are used as mycoinsecticides and can justify industrialization of new isolates.
A 3D-CNN model with CT-based parametric response mapping for classifying COPD subjects
Authors: Ho Thao Thi , Kim Taewoo , Kim Woo Jin , Lee Chang Hyun , Chae Kum Ju , Bak So Hyeon , Kwon Sung Ok , Jin Gong Yong , Park Eun-Kee , Choi Sanghun
Published: January 2021

Chronic obstructive pulmonary disease (COPD) is a respiratory disorder involving abnormalities of lung parenchymal morphology with different severities. COPD is assessed by pulmonary-function tests and computed tomography-based approaches. We introduce a new classification method for COPD grouping based on deep learning and a parametric-response mapping (PRM) method. We extracted parenchymal functional variables of functional small airway disease percentage (fSAD%) and emphysema percentage (Emph%) with an image registration technique, being provided as input parameters of 3D convolutional neural network (CNN). The integrated 3D-CNN and PRM (3D-cPRM) achieved a classification accuracy of 89.3% and a sensitivity of 88.3% in five-fold cross-validation. The prediction accuracy of the proposed 3D-cPRM exceeded those of the 2D model and traditional 3D CNNs with the same neural network, and was comparable to that of 2D pretrained PRM models. We then applied a gradient-weighted class activation mapping (Grad-CAM) that highlights the key features in the CNN learning process. Most of the class-discriminative regions appeared in the upper and middle lobes of the lung, consistent with the regions of elevated fSAD% and Emph% in COPD subjects. The 3D-cPRM successfully represented the parenchymal abnormalities in COPD and matched the CT-based diagnosis of COPD.
Prognostic gene expression signatures of breast cancer are lacking a sensible biological meaning
Authors: Manjang Kalifa , Tripathi Shailesh , Yli-Harja Olli , Dehmer Matthias , Glazko Galina , Emmert-Streib Frank
Published: January 2021

The identification of prognostic biomarkers for predicting cancer progression is an important problem for two reasons. First, such biomarkers find practical application in a clinical context for the treatment of patients. Second, interrogation of the biomarkers themselves is assumed to lead to novel insights of disease mechanisms and the underlying molecular processes that cause the pathological behavior. For breast cancer, many signatures based on gene expression values have been reported to be associated with overall survival. Consequently, such signatures have been used for suggesting biological explanations of breast cancer and drug mechanisms. In this paper, we demonstrate for a large number of breast cancer signatures that such an implication is not justified. Our approach eliminates systematically all traces of biological meaning of signature genes and shows that among the remaining genes, surrogate gene sets can be formed with indistinguishable prognostic prediction capabilities and opposite biological meaning. Hence, our results demonstrate that none of the studied signatures has a sensible biological interpretation or meaning with respect to disease etiology. Overall, this shows that prognostic signatures are black-box models with sensible predictions of breast cancer outcome but no value for revealing causal connections. Furthermore, we show that the number of such surrogate gene sets is not small but very large.