bluuebunny/crossref_metadata_2025 huggingface dataset:
A Machine Learning Approach to Objective Identification of Dust in Satellite Imagery
Authors: Berndt E. B. , Elmer N. J. , Junod R. A. , Fuell K. K. , Harkema S. S. , Burke A. R. , Feemster C. M.
Published: May 2021

Airborne dust has broad adverse effects on human activity, including aviation, human health, and agriculture. Remote sensing observations are used to detect dust and aerosols in the atmosphere using long established techniques. False color Red‐Green‐Blue (RGB) imagery using band differences sensitive to dust absorption (Dust RGB) is currently used operationally to assist forecasters and decision‐makers in identifying dust at night, but there are still limitations, subjectivity, and nuances to image interpretation making night‐time dust identification difficult even for experts. This study applies machine learning to the problem of night‐time dust detection with a simple random forest (RF) model using Geostationary Operational Environmental Satellite‐16 (GOES‐16) Advanced Baseline Imager (ABI) infrared imagery, band differences sensitive to dust absorption, and Dust RGB color components as inputs to the model. The RF model achieves an Area‐Under‐Curve (AUC) of 0.97 with a standard deviation of 0.04 for dust cases. For images with dust present, the model correctly labels 85% of dust pixels and 99.96% of no‐dust pixels for all dust images in the validation data set. The addition of a single null case to the training data set drastically reduces error in labeling no‐dust pixels as dust from 45% to 14.5%. Application of the machine learning model to the April 13–14, 2019 dust event demonstrates the ability of the model to identify dust during night‐time hours when visual dust detection is limited by the cooling ground surface characteristics.
Controls Over Oxygen Isotope Fractionation in the Waters and Bivalves (Arthritica helmsi) of an Estuarine Lagoon System
Authors: Chamberlayne B. K. , Tyler J. J. , Gillanders B. M.
Published: May 2021

Oxygen isotope ratios in bivalve shells have long been used as a proxy for environmental change, reflecting both temperature and the oxygen isotope composition of host water. In estuarine systems, the oxygen isotope composition of water is complicated by variable mixing between river and seawater, as well as evaporative enrichment. In addition, due to species‐specific variation in temperature‐dependent fractionation into bivalve carbonate, modern calibrations are necessary prior to applications in paleoenvironmental studies. In this study, live specimens of the micromollusc Arthritica helmsi were collected from five sites in the Coorong Lagoon, an estuarine system at the mouth of the River Murray, Australia, on six occasions from November 2016 to May 2018. Whole shell oxygen and carbon isotope compositions (n = 131) were measured alongside monthly temperature and oxygen and hydrogen isotope analyses of waters from the Coorong and neighboring Lake Alexandrina (n = 137). Oxygen and hydrogen isotope ratios in water were mostly controlled by evaporation of source waters, though a period of high river water discharge was reflected in the isotopic values of the Coorong North Lagoon. A species‐specific temperature‐dependent oxygen isotope fractionation equation was calibrated for A. helmsi: T (°C) = (21.39 ± 0.45) − (4.43 ± 0.38) × (δ18Oshell − δ18Owater). This equation is similar to other published paleotemperature equations for biogenic carbonates. These contemporary observations of the isotope hydrology of the Coorong, coupled with our contemporary calibration of oxygen isotope fractionation, lay the foundation for paleoenvironmental studies using bivalves collected from the sediments of the Coorong.
Diffusion‐to‐Imbibition Transition in Water Sorption in Nanoporous Media: Theoretical Studies
Authors: Cihan Abdullah , Tokunaga Tetsu K. , Birkholzer Jens T.
Published: May 2021

The ability to predict multiphase fluid transport in nanoporous rocks such as shales is critical for many geoscience applications, for example unconventional hydrocarbon production, geologic carbon sequestration, and nuclear waste disposal. When the pore sizes approach nanoscales, the impact of the molecular interaction forces between fluids and solids becomes increasingly important. These forces can alter macroscopic fluid phase behavior and control transport. Recent experimental studies have shown that capillary condensation and subsequent imbibition of liquid water can occur in hydrophilic nanoporous media even if the vapor phase is at a critical relative humidity (rhcrit) well below vapor saturation. This study presents a theoretical investigation of the processes controlling adsorption, capillary condensation and imbibition in nanoporous media, using the square‐gradient classical density functional theory. The proposed theoretical model explicitly includes the relevant interaction forces among fluids and solids in macroscopic porous media. Application of the model to a relative‐humidity‐controlled water adsorption experiment is presented to demonstrate the impact of water‐pore wall attractive forces on multiphase water behavior in a hydrophilic silicon nanoporous medium. The model represents well the measured time‐dependent evolution of the water imbibition front inside the nanoporous medium and also explains the diffusion‐like water transport regimes observed at rh < rhcrit and the imbibition‐like flow regimes observed at rh > rhcrit. The study furthermore gives an insight on hysteresis phenomenon in adsorption and desorption isotherms.
IL-30† (IL-27A): a familiar stranger in immunity, inflammation, and cancer
Authors: Min Booki , Kim Dongkyun , Feige Matthias J.
Published: May 2021

Over the years, interleukin (IL)-27 has received much attention because of its highly divergent, sometimes even opposing, functions in immunity. IL-30, the p28 subunit that forms IL-27 together with Ebi3 and is also known as IL-27p28 or IL-27A, has been considered a surrogate to represent IL-27. However, it was later discovered that IL-30 can form complexes with other protein subunits, potentially leading to overlapping or discrete functions. Furthermore, there is emerging evidence that IL-30 itself may perform immunomodulatory functions independent of Ebi3 or other binding partners and that IL-30 production is strongly associated with certain cancers in humans. In this review, we will discuss the biology of IL-30 and other IL-30-associated cytokines and their functions in inflammation and cancer.
A critical role for Th17 cell-derived TGF-β1 in regulating the stability and pathogenicity of autoimmune Th17 cells
Authors: Choi Garam , Park Young-Jun , Cho Minkyoung , Moon Heesu , Kim Daehong , Kang Chang-Yuil , Chung Yeonseok , Kim Byung-Seok
Published: May 2021

Pathogenic conversion of Th17 cells into multifunctional helper T cells or Th1 cells contributes to the pathogenesis of autoimmune diseases; however, the mechanism regulating the plasticity of Th17 cells remains unclear. Here, we found that Th17 cells expressed latent TGF-β1 in a manner dependent on autocrine TGF-β1. By employing IL-17-producing cell-specific Tgfb1 conditional knockout and fate-mapping systems, we demonstrated that TGF-β1-deficient Th17 cells are relatively susceptible to becoming IFN-γ producers through IL-12Rβ2 and IL-27Rα upregulation. TGF-β1-deficient Th17 cells exacerbated tissue inflammation compared to TGF-β1-sufficient Th17 cells in adoptive transfer models of experimental autoimmune encephalomyelitis and colitis. Thus, TGF-β1 production by Th17 cells provides an essential autocrine signal for maintaining the stability and regulating the pathogenicity of Th17 cells in vivo.
Oncogenic long intervening noncoding RNA Linc00284 promotes c-Met expression by sponging miR-27a in colorectal cancer
Authors: You Jun , Li Jiayi , Ke Chunlin , Xiao Yanru , Lu Chuanhui , Huang Fakun , Mi Yanjun , Xia Rongmu , Li Qiyuan
Published: May 2021

Emerging evidences suggest that long noncoding RNA (lncRNA) plays a vital role in tumorigenesis and cancer progression. Here, the aim of this study is to investigate the biological function of long intervening noncoding RNA Linc00284 in colorectal cancer (CRC). The expression levels of Linc00284, miR-27a and c-Met were evaluated by qPCR and/or Western blotting. Immunohistochemistry was used to detect the expression of Ki67 and Phh3 in tumor tissues. The interaction between Linc00284, miR-27a and c-Met was validated by luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Cell function experiments, including CCK-8, wound-healing and transwell invasion assays, were conducted. The in vivo studies were performed with the subcutaneous tumor xenograft mouse models. Our findings reveal that Linc00284 is upregulated in CRC tissues and colorectal cancer cell lines HCT116 and SW480 in comparison with corresponding para-carcinoma tissues and human fetal colonic mucosa cells FHC. High expression of Linc00284 in tumor tissues is associated with tumor metastasis and predicts a poor clinical outcome in CRC patients. Serum Linc00284 is increased, while miR-27a is decreased in CRC patients compared to healthy controls. ROC curve analysis indicates that serum Linc00284 and miR-27a produce the area under the curve (AUC) value of at 0.8151 and 0.7316 in patients with colorectal cancer compared to healthy individuals, respectively. Additionally, results in vitro and in vivo experiments suggest that Linc00284 silencing significantly suppresses CRC cell proliferation and/or invasion. Mechanistically, Linc00284 promotes c-Met expression by acting as miR-27a sponge, leading to the activation of downstream signaling pathways, thereby causing malignant phenotypes of CRC cells. Taken together, Linc00284 exhibits oncogenic function and the disturbance of Linc00284/miR-27a/c-Met regulatory axis contributes to CRC progression, providing new insight into the pathogenesis of colorectal cancer. Importantly, the expression levels of serum Linc00284 and miR-27a may serve as clinical biomarkers for CRC diagnosis.
Dysregulation of post-transcriptional modification by copy number variable microRNAs in schizophrenia with enhanced glycation stress
Authors: Yoshikawa Akane , Kushima Itaru , Miyashita Mitsuhiro , Toriumi Kazuya , Suzuki Kazuhiro , Horiuchi Yasue , Kawaji Hideya , Takizawa Shunya , Ozaki Norio , Itokawa Masanari , Arai Makoto
Published: May 2021

Previously, we identified a subpopulation of schizophrenia (SCZ) showing increased levels of plasma pentosidine, a marker of glycation and oxidative stress. However, its causative genetic factors remain largely unknown. Recently, it has been suggested that dysregulated posttranslational modification by copy number variable microRNAs (CNV-miRNAs) may contribute to the etiology of SCZ. Here, an integrative genome-wide CNV-miRNA analysis was performed to investigate the etiology of SCZ with accumulated plasma pentosidine (PEN-SCZ). The number of CNV-miRNAs and the gene ontology (GO) in the context of miRNAs within CNVs were compared between PEN-SCZ and non-PEN-SCZ groups. Gene set enrichment analysis of miRNA target genes was further performed to evaluate the pathways affected in PEN-SCZ. We show that miRNAs were significantly enriched within CNVs in the PEN-SCZ versus non-PEN-SCZ groups (p = 0.032). Of note, as per GO analysis, the dysregulated neurodevelopmental events in the two groups may have different origins. Additionally, gene set enrichment analysis of miRNA target genes revealed that miRNAs involved in glycation/oxidative stress and synaptic neurotransmission, especially glutamate/GABA receptor signaling, were possibly affected in PEN-SCZ. To the best of our knowledge, this is the first genome-wide CNV-miRNA study suggesting the role of CNV-miRNAs in the etiology of PEN-SCZ, through effects on genes related to glycation/oxidative stress and synaptic function. Our findings provide supportive evidence that glycation/oxidative stress possibly caused by genetic defects related to the posttranscriptional modification may lead to synaptic dysfunction. Therefore, targeting miRNAs may be one of the promising approaches for the treatment of PEN-SCZ.
Genome information processing by the INO80 chromatin remodeler positions nucleosomes
Authors: Oberbeckmann Elisa , Krietenstein Nils , Niebauer Vanessa , Wang Yingfei , Schall Kevin , Moldt Manuela , Straub Tobias , Rohs Remo , Hopfner Karl-Peter , Korber Philipp , Eustermann Sebastian
Published: May 2021

The fundamental molecular determinants by which ATP-dependent chromatin remodelers organize nucleosomes across eukaryotic genomes remain largely elusive. Here, chromatin reconstitutions on physiological, whole-genome templates reveal how remodelers read and translate genomic information into nucleosome positions. Using the yeast genome and the multi-subunit INO80 remodeler as a paradigm, we identify DNA shape/mechanics encoded signature motifs as sufficient for nucleosome positioning and distinct from known DNA sequence preferences of histones. INO80 processes such information through an allosteric interplay between its core- and Arp8-modules that probes mechanical properties of nucleosomal and linker DNA. At promoters, INO80 integrates this readout of DNA shape/mechanics with a readout of co-evolved sequence motifs via interaction with general regulatory factors bound to these motifs. Our findings establish a molecular mechanism for robust and yet adjustable +1 nucleosome positioning and, more generally, remodelers as information processing hubs that enable active organization and allosteric regulation of the first level of chromatin.
Artificial dual solid-electrolyte interfaces based on in situ organothiol transformation in lithium sulfur battery
Authors: Guo Wei , Zhang Wanying , Si Yubing , Wang Donghai , Fu Yongzhu , Manthiram Arumugam
Published: May 2021

The interfacial instability of the lithium-metal anode and shuttling of lithium polysulfides in lithium-sulfur (Li-S) batteries hinder the commercial application. Herein, we report a bifunctional electrolyte additive, i.e., 1,3,5-benzenetrithiol (BTT), which is used to construct solid-electrolyte interfaces (SEIs) on both electrodes from in situ organothiol transformation. BTT reacts with lithium metal to form lithium 1,3,5-benzenetrithiolate depositing on the anode surface, enabling reversible lithium deposition/stripping. BTT also reacts with sulfur to form an oligomer/polymer SEI covering the cathode surface, reducing the dissolution and shuttling of lithium polysulfides. The Li–S cell with BTT delivers a specific discharge capacity of 1,239 mAh g−1 (based on sulfur), and high cycling stability of over 300 cycles at 1C rate. A Li–S pouch cell with BTT is also evaluated to prove the concept. This study constructs an ingenious interface reaction based on bond chemistry, aiming to solve the inherent problems of Li–S batteries.
CRISPR/Cas9 mediated deletion of the adenosine A2A receptor enhances CAR T cell efficacy
Authors: Giuffrida Lauren , Sek Kevin , Henderson Melissa A. , Lai Junyun , Chen Amanda X. Y. , Meyran Deborah , Todd Kirsten L. , Petley Emma V. , Mardiana Sherly , Mølck Christina , Stewart Gregory D. , Solomon Benjamin J. , Parish Ian A. , Neeson Paul J. , Harrison Simon J. , Kats Lev M. , House Imran G. , Darcy Phillip K. , Beavis Paul A.
Published: May 2021

Adenosine is an immunosuppressive factor that limits anti-tumor immunity through the suppression of multiple immune subsets including T cells via activation of the adenosine A2A receptor (A2AR). Using both murine and human chimeric antigen receptor (CAR) T cells, here we show that targeting A2AR with a clinically relevant CRISPR/Cas9 strategy significantly enhances their in vivo efficacy, leading to improved survival of mice. Effects evoked by CRISPR/Cas9 mediated gene deletion of A2AR are superior to shRNA mediated knockdown or pharmacological blockade of A2AR. Mechanistically, human A2AR-edited CAR T cells are significantly resistant to adenosine-mediated transcriptional changes, resulting in enhanced production of cytokines including IFNγ and TNF, and increased expression of JAK-STAT signaling pathway associated genes. A2AR deficient CAR T cells are well tolerated and do not induce overt pathologies in mice, supporting the use of CRISPR/Cas9 to target A2AR for the improvement of CAR T cell function in the clinic.
Small sinking particles control anammox rates in the Peruvian oxygen minimum zone
Authors: Karthäuser Clarissa , Ahmerkamp Soeren , Marchant Hannah K. , Bristow Laura A. , Hauss Helena , Iversen Morten H. , Kiko Rainer , Maerz Joeran , Lavik Gaute , Kuypers Marcel M. M.
Published: May 2021

Anaerobic oxidation of ammonium (anammox) in oxygen minimum zones (OMZs) is a major pathway of oceanic nitrogen loss. Ammonium released from sinking particles has been suggested to fuel this process. During cruises to the Peruvian OMZ in April–June 2017 we found that anammox rates are strongly correlated with the volume of small particles (128–512 µm), even though anammox bacteria were not directly associated with particles. This suggests that the relationship between anammox rates and particles is related to the ammonium released from particles by remineralization. To investigate this, ammonium release from particles was modelled and theoretical encounters of free-living anammox bacteria with ammonium in the particle boundary layer were calculated. These results indicated that small sinking particles could be responsible for ~75% of ammonium release in anoxic waters and that free-living anammox bacteria frequently encounter ammonium in the vicinity of smaller particles. This indicates a so far underestimated role of abundant, slow-sinking small particles in controlling oceanic nutrient budgets, and furthermore implies that observations of the volume of small particles could be used to estimate N-loss across large areas.
Laser-driven growth of structurally defined transition metal oxide nanocrystals on carbon nitride photoelectrodes in milliseconds
Authors: Zhang Junfang , Zou Yajun , Eickelmann Stephan , Njel Christian , Heil Tobias , Ronneberger Sebastian , Strauss Volker , Seeberger Peter H. , Savateev Aleksandr , Loeffler Felix F.
Published: May 2021

Fabrication of hybrid photoelectrodes on a subsecond timescale with low energy consumption and possessing high photocurrent densities remains a centerpiece for successful implementation of photoelectrocatalytic synthesis of fuels and value-added chemicals. Here, we introduce a laser-driven technology to print sensitizers with desired morphologies and layer thickness onto different substrates, such as glass, carbon, or carbon nitride (CN). The specially designed process uses a thin polymer reactor impregnated with transition metal salts, confining the growth of transition metal oxide (TMO) nanostructures on the interface in milliseconds, while their morphology can be tuned by the laser. Multiple nano-p-n junctions at the interface increase the electron/hole lifetime by efficient charge trapping. A hybrid copper oxide/CN photoanode with optimal architecture reaches 10 times higher photocurrents than the pristine CN photoanode. This technology provides a modular approach to build a library of TMO-based composite films, enabling the creation of materials for diverse applications.
A single m6A modification in U6 snRNA diversifies exon sequence at the 5’ splice site
Authors: Ishigami Yuma , Ohira Takayuki , Isokawa Yui , Suzuki Yutaka , Suzuki Tsutomu
Published: May 2021

N6-methyladenosine (m6A) is a modification that plays pivotal roles in RNA metabolism and function, although its functions in spliceosomal U6 snRNA remain unknown. To elucidate its role, we conduct a large-scale transcriptome analysis of a Schizosaccharomyces pombe strain lacking this modification and found a global change of pre-mRNA splicing. The most significantly impacted introns are enriched for adenosine at the fourth position pairing the m6A in U6 snRNA, and exon sequences weakly recognized by U5 snRNA. This suggests cooperative recognition of 5’ splice site by U6 and U5 snRNPs, and also a role of m6A facilitating efficient recognition of the splice sites weakly interacting with U5 snRNA, indicating that U6 snRNA m6A relaxes the 5’ exon constraint and allows protein sequence diversity along with explosively increasing number of introns over the course of eukaryotic evolution.
Automated annotation and visualisation of high-resolution spatial proteomic mass spectrometry imaging data using HIT-MAP
Authors: Guo G. , Papanicolaou M. , Demarais N. J. , Wang Z. , Schey K. L. , Timpson P. , Cox T. R. , Grey A. C.
Published: May 2021

Spatial proteomics has the potential to significantly advance our understanding of biology, physiology and medicine. Matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) is a powerful tool in the spatial proteomics field, enabling direct detection and registration of protein abundance and distribution across tissues. MALDI-MSI preserves spatial distribution and histology allowing unbiased analysis of complex, heterogeneous tissues. However, MALDI-MSI faces the challenge of simultaneous peptide quantification and identification. To overcome this, we develop and validate HIT-MAP (High-resolution Informatics Toolbox in MALDI-MSI Proteomics), an open-source bioinformatics workflow using peptide mass fingerprint analysis and a dual scoring system to computationally assign peptide and protein annotations to high mass resolution MSI datasets and generate customisable spatial distribution maps. HIT-MAP will be a valuable resource for the spatial proteomics community for analysing newly generated and retrospective datasets, enabling robust peptide and protein annotation and visualisation in a wide array of normal and disease contexts.
Three-body correlations in nonlinear response of correlated quantum liquid
Authors: Hata Tokuro , Teratani Yoshimichi , Arakawa Tomonori , Lee Sanghyun , Ferrier Meydi , Deblock Richard , Sakano Rui , Oguri Akira , Kobayashi Kensuke
Published: May 2021

Behavior of quantum liquids is a fascinating topic in physics. Even in a strongly correlated case, the linear response of a given system to an external field is described by the fluctuation-dissipation relations based on the two-body correlations in the equilibrium. However, to explore nonlinear non-equilibrium behaviors of the system beyond this well-established regime, the role of higher order correlations starting from the three-body correlations must be revealed. In this work, we experimentally investigate a controllable quantum liquid realized in a Kondo-correlated quantum dot and prove the relevance of the three-body correlations in the nonlinear conductance at finite magnetic field, which validates the recent Fermi liquid theory extended to the non-equilibrium regime.
Identifying genetic modifiers of age-associated penetrance in X-linked dystonia-parkinsonism
Authors: Laabs Björn-Hergen , Klein Christine , Pozojevic Jelena , Domingo Aloysius , Brüggemann Norbert , Grütz Karen , Rosales Raymond L. , Jamora Roland Dominic , Saranza Gerard , Diesta Cid Czarina E. , Wittig Michael , Schaake Susen , Dulovic-Mahlow Marija , Quismundo Jana , Otto Pia , Acuna Patrick , Go Criscely , Sharma Nutan , Multhaupt-Buell Trisha , Müller Ulrich , Hanssen Henrike , Kilpert Fabian , Franke Andre , Rolfs Arndt , Bauer Peter , Dobričić Valerija , Lohmann Katja , Ozelius Laurie J. , Kaiser Frank J. , König Inke R. , Westenberger Ana
Published: May 2021

X-linked dystonia-parkinsonism is a neurodegenerative disorder caused by a founder retrotransposon insertion, in which a polymorphic hexanucleotide repeat accounts for ~50% of age at onset variability. Employing a genome-wide association study to identify additional factors modifying age at onset, we establish that three independent loci are significantly associated with age at onset (p < 5 × 10−8). The lead single nucleotide polymorphisms collectively account for 25.6% of the remaining variance not explained by the hexanucleotide repeat and 13.0% of the overall variance in age at onset in X-linked dystonia-parkinsonism with the protective alleles delaying disease onset by seven years. These regions harbor or lie adjacent to MSH3 and PMS2, the genes that were recently implicated in modifying age at onset in Huntington’s disease, likely through a common pathway influencing repeat instability. Our work indicates the existence of three modifiers of age at onset in X-linked dystonia-parkinsonism that likely affect the DNA mismatch repair pathway.
Open fire exposure increases the risk of pregnancy loss in South Asia
Authors: Xue Tao , Geng Guannan , Han Yiqun , Wang Huiyu , Li Jiajianghui , Li Hong-tian , Zhou Yubo , Zhu Tong
Published: May 2021

Interactions between climate change and anthropogenic activities result in increasing numbers of open fires, which have been shown to harm maternal health. However, few studies have examined the association between open fire and pregnancy loss. We conduct a self-comparison case-control study including 24,876 mothers from South Asia, the region with the heaviest pregnancy-loss burden in the world. Exposure is assessed using a chemical transport model as the concentrations of fire-sourced PM2.5(i.e., fire PM2.5). The adjusted odds ratio (OR) of pregnancy loss for a 1-μg/m3increment in averaged concentration of fire PM2.5during pregnancy is estimated as 1.051 (95% confidence intervals [CI]: 1.035, 1.067). Because fire PM2.5is more strongly linked with pregnancy loss than non-fire PM2.5(OR: 1.014; 95% CI: 1.011, 1.016), it contributes to a non-neglectable fraction (13%) of PM2.5-associated pregnancy loss. Here, we show maternal health is threaten by gestational exposure to fire smoke in South Asia.
Extreme parsimony in ATP consumption by 20S complexes in the global disassembly of single SNARE complexes
Authors: Kim Changwon , Shon Min Ju , Kim Sung Hyun , Eun Gee Sung , Ryu Je-Kyung , Hyeon Changbong , Jahn Reinhard , Yoon Tae-Young
Published: May 2021

Fueled by ATP hydrolysis in N-ethylmaleimide sensitive factor (NSF), the 20S complex disassembles rigid SNARE (soluble NSF attachment protein receptor) complexes in single unraveling step. This global disassembly distinguishes NSF from other molecular motors that make incremental and processive motions, but the molecular underpinnings of its remarkable energy efficiency remain largely unknown. Using multiple single-molecule methods, we found remarkable cooperativity in mechanical connection between NSF and the SNARE complex, which prevents dysfunctional 20S complexes that consume ATP without productive disassembly. We also constructed ATP hydrolysis cycle of the 20S complex, in which NSF largely shows randomness in ATP binding but switches to perfect ATP hydrolysis synchronization to induce global SNARE disassembly, minimizing ATP hydrolysis by non-20S complex-forming NSF molecules. These two mechanisms work in concert to concentrate ATP consumption into functional 20S complexes, suggesting evolutionary adaptations by the 20S complex to the energetically expensive mechanical task of SNARE complex disassembly.
Phototunable self-oscillating system driven by a self-winding fiber actuator
Authors: Hu Zhiming , Li Yunlong , Lv Jiu-an
Published: May 2021

Self-oscillating systems that enable autonomous, continuous motions driven by an unchanging, constant stimulus would have significant applications in intelligent machines, advanced robotics, and biomedical devices. Despite efforts to gain self-oscillations have been made through artificial systems using responsive soft materials of gels or liquid crystal polymers, these systems are plagued with problems that restrict their practical applicability: few available oscillation modes due to limited degrees of freedom, inability to control the evolution between different modes, and failure under loading. Here we create a phototunable self-oscillating system that possesses a broad range of oscillation modes, controllable evolution between diverse modes, and loading capability. This self-oscillating system is driven by a photoactive self-winding fiber actuator designed and prepared through a twistless strategy inspired by the helix formation of plant-tendrils, which endows the system with high degrees of freedom. It enables not only controllable generation of three basic self-oscillations but also production of diverse complex oscillatory motions. Moreover, it can work continuously over 1270000 cycles without obvious fatigue, exhibiting high robustness. We envision that this system with controllable self-oscillations, loading capability, and mechanical robustness will be useful in autonomous, self-sustained machines and devices with the core feature of photo-mechanical transduction.
Entropy engineering promotes thermoelectric performance in p-type chalcogenides
Authors: Jiang Binbin , Yu Yong , Chen Hongyi , Cui Juan , Liu Xixi , Xie Lin , He Jiaqing
Published: May 2021

We demonstrate that the thermoelectric properties of p-type chalcogenides can be effectively improved by band convergence and hierarchical structure based on a high-entropy-stabilized matrix. The band convergence is due to the decreased light and heavy band energy offsets by alloying Cd for an enhanced Seebeck coefficient and electric transport property. Moreover, the hierarchical structure manipulated by entropy engineering introduces all-scale scattering sources for heat-carrying phonons resulting in a very low lattice thermal conductivity. Consequently, a peak zT of 2.0 at 900 K for p-type chalcogenides and a high experimental conversion efficiency of 12% at ΔT = 506 K for the fabricated segmented modules are achieved. This work provides an entropy strategy to form all-scale hierarchical structures employing high-entropy-stabilized matrix. This work will promote real applications of low-cost thermoelectric materials.
Breast cancer dormancy: need for clinically relevant models to address current gaps in knowledge
Authors: Bushnell Grace G. , Deshmukh Abhijeet P. , den Hollander Petra , Luo Ming , Soundararajan Rama , Jia Dongya , Levine Herbert , Mani Sendurai A. , Wicha Max S.
Published: May 2021

Breast cancer is the most commonly diagnosed cancer in the USA. Although advances in treatment over the past several decades have significantly improved the outlook for this disease, most women who are diagnosed with estrogen receptor positive disease remain at risk of metastatic relapse for the remainder of their life. The cellular source of late relapse in these patients is thought to be disseminated tumor cells that reactivate after a long period of dormancy. The biology of these dormant cells and their natural history over a patient’s lifetime is largely unclear. We posit that research on tumor dormancy has been significantly limited by the lack of clinically relevant models. This review will discuss existing dormancy models, gaps in biological understanding, and propose criteria for future models to enhance their clinical relevance.
Dietary calcium, magnesium, and phosphorus intakes and risk of stroke in Chinese adults
Authors: Zhu Hai-Lu , Liu Yan , Zhang Jian , Wang Ming-Xu , Jiang Hong , Guo Fang , Li Ming , Qi Fei-Fei , Liu Xiao-Hong , Ma Le
Published: May 2021

Controversial results have been reported about the association of calcium, magnesium, and phosphorus and stroke risk, but none in China. To investigate the association between dietary calcium, magnesium, phosphorus, and stroke incidence in Chinese adults, we collected data from the China Health and Nutrition Survey (CHNS) from 2004 to 2011, including 6411 participants aged 45–79 years and free of stroke at baseline. Diet was assessed by interviews combining 3-d 24-h food recalls and household food inventory weighing at each survey round. The stroke incident was identified based on the validated self-report. Multivariate Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). For 32,024 person-years of follow-up, 179 stroke cases were documented. After adjustment for major lifestyle and dietary risk factors, calcium intake was positively associated with reduced stroke risk, and the HR of stroke comparing extreme quartiles was 0.53 (95% CI 0.29–0.96, Ptrend = 0.03). In further stratified analyses, significant heterogeneity across sex strata was found (Pinteraction = 0.03). Dietary calcium intake among men was more inversely related to stroke, with HRs being 0.33 (95% CI 0.15–0.76, Ptrend = 0.02), compared to 1.24 (95% CI 0.46–3.35, Ptrend = 0.89) among women. However, no significant association between stroke and magnesium or phosphorus was revealed. Our findings suggest that higher dietary calcium intake was associated with a lower risk of stroke in Chinese adults, particularly in men.
Identification of coronary calcifications in optical coherence tomography imaging using deep learning
Authors: Avital Yarden , Madar Akiva , Arnon Shlomi , Koifman Edward
Published: May 2021

Coronary calcifications are an obstacle for successful percutaneous treatment of coronary artery disease patients. The optimal method for delineating calcifications extent is coronary optical coherence tomography (OCT). To identify calcification on OCT and subsequently tailor the appropriate treatment, requires expertise in both image acquisition and interpretation. Image acquisition consists from system calibration, blood clearance by a contrast agent along with synchronization of the pullback process. Accurate interpretation demands careful review by the operator of a segment of 50–75 mm of the coronary vessel at steps of 5–10 frames per mm accounting for 375–540 images in each OCT run, which is time consuming and necessitates some expertise in OCT analysis. In this paper we developed a new deep learning algorithm to assist the physician to identify and quantify coronary calcifications promptly, efficiently and accurately. Our algorithm achieves an accuracy of 0.9903 ± 0.009 over the test set at size of 1500 frames and even managed to find calcifications that were not recognized manually by the physician. For the best knowledge of the authors our algorithm achieves high accuracy which was never achieved in the past.
Pronounced proliferation of non-beta cells in response to beta-cell mitogens in isolated human islets of Langerhans
Authors: Maachi Hasna , Ghislain Julien , Tremblay Caroline , Poitout Vincent
Published: May 2021

The potential to treat diabetes by increasing beta-cell mass is driving a major effort to identify beta-cell mitogens. Demonstration of mitogen activity in human beta cells is frequently performed in ex vivo assays. However, reported disparities in the efficacy of beta-cell mitogens led us to investigate the sources of this variability. We studied 35 male (23) and female (12) human islet batches covering a range of donor ages and BMI. Islets were kept intact or dispersed into single cells and cultured in the presence of harmine, glucose, or heparin-binding epidermal growth factor-like growth factor (HB-EGF), and subsequently analyzed by immunohistochemistry or flow cytometry. Proliferating cells were identified by double labeling with EdU and Ki67 and glucagon, c-peptide or Nkx6.1, and cytokeratin-19 to respectively label alpha, beta, and ductal cells. Harmine and HB-EGF stimulated human beta-cell proliferation, but the effect of glucose was dependent on the assay and the donor. Harmine potently stimulated alpha-cell proliferation and both harmine and HB-EGF increased proliferation of insulin- and glucagon-negative cells, including cytokeratin 19-positive cells. Given the abundance of non-beta cells in human islet preparations, our results suggest that assessment of beta-cell mitogens requires complementary approaches and rigorous identification of cell identity using multiple markers.
Analysis of methods for quantifying yeast cell concentration in complex lignocellulosic fermentation processes
Authors: Wang Ruifei , Lorantfy Bettina , Fusco Salvatore , Olsson Lisbeth , Franzén Carl Johan
Published: May 2021

Cell mass and viability are tightly linked to the productivity of fermentation processes. In 2nd generation lignocellulose-based media quantitative measurement of cell concentration is challenging because of particles, auto-fluorescence, and intrinsic colour and turbidity of the media. We systematically evaluated several methods for quantifying total and viable yeast cell concentrations to validate their use in lignocellulosic media. Several automated cell counting systems and stain-based viability tests had very limited applicability in such samples. In contrast, manual cell enumeration in a hemocytometer, plating and enumeration of colony forming units, qPCR, and in situ﻿ dielectric spectroscopy were further investigated. Parameter optimization to measurements in synthetic lignocellulosic media, which mimicked typical lignocellulosic fermentation conditions, resulted in statistically significant calibration models with good predictive capacity for these four methods. Manual enumeration of cells in a hemocytometer and of CFU were further validated for quantitative assessment of cell numbers in simultaneous saccharification and fermentation experiments on steam-exploded wheat straw. Furthermore, quantitative correlations could be established between these variables and in situ permittivity. In contrast, qPCR quantification suffered from inconsistent DNA extraction from the lignocellulosic slurries. Development of reliable and validated cell quantification methods and understanding their strengths and limitations in lignocellulosic contexts, will enable further development, optimization, and control of lignocellulose-based fermentation processes.
Accurate detection and quantification of seasonal abundance of American bullfrog (Lithobates catesbeianus) using ddPCR eDNA assays
Authors: Everts Teun , Halfmaerten David , Neyrinck Sabrina , De Regge Nico , Jacquemyn Hans , Brys Rein
Published: May 2021

The invasive American bullfrog (Lithobates catesbeianus) imperils freshwater biodiversity worldwide. Effective management hinges on early detection of incipient invasions and subsequent rapid response, as established populations are extremely difficult to eradicate. Although environmental DNA (eDNA) detection methods provide a highly sensitive alternative to conventional surveillance techniques, extensive testing is imperative to generate reliable output. Here, we tested and compared the performance of two primer/probe assays to detect and quantify the abundance of bullfrogs in Western Europe in silico and in situ using digital droplet PCR (ddPCR). Although both assays proved to be equally target-specific and sensitive, one outperformed the other in ddPCR detection resolution (i.e., distinguishing groups of target-positive and target-negative droplets), and hence was selected for further analyses. Mesocosm experiments revealed that tadpole abundance and biomass explained 99% of the variation in eDNA concentration. Because per individual eDNA emission rates did not differ significantly among tadpoles and juveniles, and adults mostly reside out of the water, eDNA concentration can be used as an approximation of local bullfrog abundance in natural populations. Seasonal eDNA patterns in three colonized ponds showed parallel fluctuations in bullfrog eDNA concentration. An increase in eDNA concentration was detected in spring, followed by a strong peak coinciding with the breeding season (August, September or October), and continuously low eDNA concentrations during winter. With this study, we report the validation process required for appropriately implementing eDNA barcoding analyses in lentic systems. We demonstrate that this technique can serve as a solid and reliable tool to detect the early stages of bullfrog invasions and to quantify temporal changes in abundance that will be useful in coordinating large-scale bullfrog eradication programs and evaluating their efficiency.
Transcriptome analysis of MBD5-associated neurodevelopmental disorder (MAND) neural progenitor cells reveals dysregulation of autism-associated genes
Authors: Mullegama Sureni V. , Klein Steven D. , Williams Stephen R. , Innis Jeffrey W. , Probst Frank J. , Haldeman-Englert Chad , Martinez-Agosto Julian A. , Yang Ying , Tian Yuchen , Elsea Sarah H. , Ezashi Toshihiko
Published: May 2021

MBD5-associated neurodevelopmental disorder (MAND) is an autism spectrum disorder (ASD) characterized by intellectual disability, motor delay, speech impairment and behavioral problems; however, the biological role of methyl-CpG-binding domain 5, MBD5, in neurodevelopment and ASD remains largely undefined. Hence, we created neural progenitor cells (NPC) derived from individuals with chromosome 2q23.1 deletion and conducted RNA-seq to identify differentially expressed genes (DEGs) and the biological processes and pathways altered in MAND. Primary skin fibroblasts from three unrelated individuals with MAND and four unrelated controls were converted into induced pluripotent stem cell (iPSC) lines, followed by directed differentiation of iPSC to NPC. Transcriptome analysis of MAND NPC revealed 468 DEGs (q < 0.05), including 20 ASD-associated genes. Comparison of DEGs in MAND with SFARI syndromic autism genes revealed a striking significant overlap in biological processes commonly altered in neurodevelopmental phenotypes, with TGFβ, Hippo signaling, DNA replication, and cell cycle among the top enriched pathways. Overall, these transcriptome deviations provide potential connections to the overlapping neurocognitive and neuropsychiatric phenotypes associated with key high-risk ASD genes, including chromatin modifiers and epigenetic modulators, that play significant roles in these disease states.
Nitric oxide down-regulates voltage-gated Na+ channel in cardiomyocytes possibly through S-nitrosylation-mediated signaling
Authors: Wang Pu , Wei Mengyan , Zhu Xiufang , Liu Yangong , Yoshimura Kenshi , Zheng Mingqi , Liu Gang , Kume Shinichiro , Morishima Masaki , Kurokawa Tatsuki , Ono Katsushige
Published: May 2021

Nitric oxide (NO) is produced from endothelial cells and cardiomyocytes composing the myocardium and benefits cardiac function through both vascular-dependent and—independent effects. This study was purposed to investigate the possible adverse effect of NO focusing on the voltage-gated Na+ channel in cardiomyocytes. We carried out patch-clamp experiments on rat neonatal cardiomyocytes demonstrating that NOC-18, an NO donor, significantly reduced Na+ channel current in a dose-dependent manner by a long-term application for 24 h, accompanied by a reduction of Nav1.5-mRNA and the protein, and an increase of a transcription factor forkhead box protein O1 (FOXO1) in the nucleus. The effect of NOC-18 on the Na+ channel was blocked by an inhibitor of thiol oxidation N-ethylmaleimide, a disulfide reducing agent disulfide 1,4-Dithioerythritol, or a FOXO1 activator paclitaxel, suggesting that NO is a negative regulator of the voltage-gated Na+ channel through thiols in regulatory protein(s) for the channel transcription.
Ixodiphagus hookeri wasps (Hymenoptera: Encyrtidae) in two sympatric tick species Ixodes ricinus and Haemaphysalis concinna (Ixodida: Ixodidae) in the Slovak Karst (Slovakia): ecological and biological considerations
Authors: Buczek Alicja , Buczek Weronika , Bartosik Katarzyna , Kulisz Joanna , Stanko Michał
Published: May 2021

Ixodiphagusendoparasitoid wasps are natural tick enemies that can reduce their abundance. In this study, we investigated the presence ofIxodiphagus hookeriinHaemaphysalis concinnaandIxodes ricinusticks in the Slovak Karst (southern Slovakia) and analysed the ecological and physiological relationships in the parasitoid-host system. UnfedH. concinnaandI. ricinusnymphs harvested from vegetation were fed on rabbits. The engorged specimens were kept at 25 °C and 75% RH until the emergence of the adult wasps. For the first time in Europe, we found the presence ofI. hookeriin two species of ticks collected in the same locality and compared their development in these tick species. The prevalence of wasps inH. concinnaandI. ricinusduring their spring activity was estimated at 10.64% and 27.78%, respectively. The presence of the wasps did not affect the duration of nymph feeding. Engorged wasp-infected ticks achieved higher body mass than non-infected specimens. In both tick species, there were no differences in the length of the development period and the number and sex ratio of adultI. hookeri. The analysed indicators and characteristics of theI. hookeriwasp-tick system can be used in research on tick control.
Identification and functional analysis of cadmium-binding protein in the visceral mass of Crassostrea gigas
Authors: Zheng Zehua , Kawakami Kazuhiro , Zhang Dingkun , Negishi Lumi , Abomosallam Mohamed , Asakura Tomiko , Nagata Koji , Suzuki Michio
Published: May 2021

The Pacific oyster, Crassostrea gigas, is a traditional food worldwide. The soft body of the oyster can easily accumulate heavy metals such as cadmium (Cd). To clarify the molecular mechanism of Cd accumulation in the viscera of C. gigas, we identified Cd-binding proteins. 5,10,15,20-Tetraphenyl-21H,23H-porphinetetrasulfonic acid, disulfuric acid, tetrahydrate, and Cd-binding competition experiments using immobilized metal ion affinity chromatography revealed the binding of water-soluble high molecular weight proteins to Cd, including C. gigas protein disulfide isomerase (cgPDI). Liquid chromatography–tandem mass spectrometry (LC–MS/MS) analyses revealed two CGHC motifs in cgPDI. The binding between Cd and rcgPDI was confirmed through a Cd-binding experiment using the TPPS method. Isothermal titration calorimetry (ITC) revealed the binding of two Cd ions to one molecule of rcgPDI. Circular dichroism (CD) spectrum and tryptophan fluorescence analyses demonstrated that the rcgPDI bound to Cd. The binding markedly changed the two-dimensional or three-dimensional structures. The activity of rcgPDI measured by a PDI Activity Assay Kit was more affected by the addition of Cd than by human PDI. Immunological analyses indicated that C. gigas contained cgPDI at a concentration of 1.0 nmol/g (viscera wet weight). The combination of ITC and quantification results revealed that Cd-binding to cgPDI accounted for 20% of the total bound Cd in the visceral mass. The findings provide new insights into the defense mechanisms of invertebrates against Cd.
Cartilage structure increases swimming efficiency of underwater robots
Authors: Yurugi Masaki , Shimanokami Makoto , Nagai Toshiaki , Shintake Jun , Ikemoto Yusuke
Published: May 2021

Underwater robots are useful for exploring valuable resources and marine life. Traditional underwater robots use screw propellers, which may be harmful to marine life. In contrast, robots that incorporate the swimming principles, morphologies, and softness of aquatic animals are expected to be more adaptable to the surrounding environment. Rajiform is one of the swimming forms observed in nature, which swims by generating the traveling waves on flat large pectoral fins. From an anatomical point of view, Rajiform fins consist of cartilage structures encapsulated in soft tissue, thereby realizing anisotropic stiffness. We hypothesized that such anisotropy is responsible for the generation of traveling waves that enable a highly efficient swimming. We validate our hypothesis through the development of a stingray robot made of silicone-based cartilages and soft tissue. For comparison, we fabricate a robot without cartilages, as well as the one combining soft tissue and cartilage materials. The fabricated robots are tested to clarify their stiffness and swimming performance. The results show that inclusion of cartilage structure in the robot fins increases the swimming efficiency. It is suggested that arrangement and distribution of soft and hard areas inside the body structure is a key factor to realize high-performance soft underwater robots.