bluuebunny/crossref_metadata_2025 huggingface dataset:
GATA6 promotes epithelial-mesenchymal transition and metastasis through MUC1/β-catenin pathway in cholangiocarcinoma
Authors: Deng Xiang , Jiang Peng , Chen Jian , Li Jianwei , Li Dajiang , He Yu , Jiang Yan , Zhang Yujun , Xu Shuangnian , Li Xi , Wang Shuguang , Tian Feng
Published: October 2020

GATA6 acts as an oncogene or tumour suppressor in different cancers. Previously, we found that aberrant expression of GATA6 promoted metastasis in cholangiocarcinoma (CCA). However, the mechanism by which GATA6 promotes metastasis in CCA is unclear. In the present study, we aimed to investigate the role of GATA6 in CCA cell epithelial–mesenchymal transition (EMT). Our results showed that GATA6 expression was positively associated with N-cadherin and vimentin expression but negatively associated with E-cadherin expression in 91 CCA samples. GATA6 promoted EMT and metastasis in CCA cells in vitro and in vivo based on knockdown and overexpression analyses. ChIP-sequencing data revealed that MUC1 is a novel downstream target of GATA6. GATA6 upregulated MUC1 expression through binding to both the 1584 and 1456 GATA-motifs in the promoter region and enhancing its transcription by luciferase reporter assays and point-mutant assays. MUC1 expression was positively associated with N-cadherin and vimentin expression but negatively associated with E-cadherin expression in 91 CCA samples. In addition, MUC1 promoted EMT in CCA cells based on knockdown and overexpression analyses. Moreover, MUC1 knockdown significantly abrogated the GATA6-induced EMT in CCA cells, indicating that MUC1 promoted EMT through upregulating MUC1 in CCA cells. β-Catenin is a putative transcriptional coactivator that regulates EMT in cancers. Our data showed that MUC1 expression was positively associated with nuclear β-catenin expression in 91 CCA samples. MUC1 upregulated nuclear β-catenin expression in CCA cells. Moreover, MUC1 bound to β-catenin in CCA cells based on protein immunoprecipitation analyses. MUC1 knockdown significantly decreased the binding of MUC1 to β-catenin, and thereby decreased nuclear β-catenin protein levels in CCA cells, indicating that MUC1 bound to β-catenin and increased its nuclear expression in CCA cells. Together, our results show that GATA6 promotes EMT through MUC1/β-catenin pathway in CCA, indicating potential implications for anti-metastatic therapy.
Correction: Stable isotopes: their use and safety in human nutrition studies
Authors: Davies Peter S. W.
Published: October 2020

This article was originally published under Nature Research’s License to Publish, but has now been made available under a CC BY 4.0 license. The PDF and HTML versions of the article have been modified accordingly.
Single crystalline quaternary sulfide nanobelts for efficient solar-to-hydrogen conversion
Authors: Wu Liang , Wang Qian , Zhuang Tao-Tao , Li Yi , Zhang Guozhen , Liu Guo-Qiang , Fan Feng-Jia , Shi Lei , Yu Shu-Hong
Published: October 2020

Although solar-driven water splitting on semiconductor photocatalysts is an attractive route for hydrogen generation, there is a lack of excellent photocatalysts with high visible light activity. Due to their tunable bandgaps suitable for superior visible-light absorption, copper-based quaternary sulfides have been the important candidates. Here, we first assessed the preferred facet of wurtzite Cu-Zn-In-S for photocatalytic hydrogen evolution reaction using the relevant Gibbs free energies determined by first principle calculation. We then developed a colloidal method to synthesize single crystalline wurtzite Cu-Zn-In-S nanobelts (NBs) exposing (0001) facet with the lowest reaction Gibbs energy, as well as Cu-Zn-Ga-S NBs exposing (0001) facet. The obtained single crystalline Cu-Zn-In-S and Cu-Zn-Ga-S NBs exhibit superior hydrogen production activities under visible-light irradiation, which is composition-dependent. Our protocol represents an alternative surface engineering approach to realize efficient solar-to-chemical conversion of single crystalline copper-based multinary chalcogenides.
Computational optical imaging with a photonic lantern
Authors: Choudhury Debaditya , McNicholl Duncan K. , Repetti Audrey , Gris-Sánchez Itandehui , Li Shuhui , Phillips David B. , Whyte Graeme , Birks Tim A. , Wiaux Yves , Thomson Robert R.
Published: October 2020

The thin and flexible nature of optical fibres often makes them the ideal technology to view biological processes in-vivo, but current microendoscopic approaches are limited in spatial resolution. Here, we demonstrate a route to high resolution microendoscopy using a multicore fibre (MCF) with an adiabatic multimode-to-single-mode “photonic lantern” transition formed at the distal end by tapering. We show that distinct multimode patterns of light can be projected from the output of the lantern by individually exciting the single-mode MCF cores, and that these patterns are highly stable to fibre movement. This capability is then exploited to demonstrate a form of single-pixel imaging, where a single pixel detector is used to detect the fraction of light transmitted through the object for each multimode pattern. A custom computational imaging algorithm we call SARA-COIL is used to reconstruct the object using only the pre-measured multimode patterns themselves and the detector signals.
Aberrant methylation underlies insulin gene expression in human insulinoma
Authors: Karakose Esra , Wang Huan , Inabnet William , Thakker Rajesh V. , Libutti Steven , Fernandez-Ranvier Gustavo , Suh Hyunsuk , Stevenson Mark , Kinoshita Yayoi , Donovan Michael , Antipin Yevgeniy , Li Yan , Liu Xiaoxiao , Jin Fulai , Wang Peng , Uzilov Andrew , Argmann Carmen , Schadt Eric E. , Stewart Andrew F. , Scott Donald K. , Lambertini Luca
Published: October 2020

Human insulinomas are rare, benign, slowly proliferating, insulin-producing beta cell tumors that provide a molecular “recipe” or “roadmap” for pathways that control human beta cell regeneration. An earlier study revealed abnormal methylation in the imprinted p15.5-p15.4 region of chromosome 11, known to be abnormally methylated in another disorder of expanded beta cell mass and function: the focal variant of congenital hyperinsulinism. Here, we compare deep DNA methylome sequencing on 19 human insulinomas, and five sets of normal beta cells. We find a remarkably consistent, abnormal methylation pattern in insulinomas. The findings suggest that abnormal insulin (INS) promoter methylation and altered transcription factor expression create alternative drivers of INS expression, replacing canonical PDX1-driven beta cell specification with a pathological, looping, distal enhancer-based form of transcriptional regulation. Finally, NFaT transcription factors, rather than the canonical PDX1 enhancer complex, are predicted to drive INS transactivation.
Phase synchronization of fluid-fluid interfaces as hydrodynamically coupled oscillators
Authors: Um Eujin , Kim Minjun , Kim Hyoungsoo , Kang Joo H. , Stone Howard A. , Jeong Joonwoo
Published: October 2020

Hydrodynamic interactions play a role in synchronized motions of coupled oscillators in fluids, and understanding the mechanism will facilitate development of applications in fluid mechanics. For example, synchronization phenomenon in two-phase flow will benefit the design of future microfluidic devices, allowing spatiotemporal control of microdroplet generation without additional integration of control elements. In this work, utilizing a characteristic oscillation of adjacent interfaces between two immiscible fluids in a microfluidic platform, we discover that the system can act as a coupled oscillator, notably showing spontaneous in-phase synchronization of droplet breakup. With this observation of in-phase synchronization, the coupled droplet generator exhibits a complete set of modes of coupled oscillators, including out-of-phase synchronization and nonsynchronous modes. We present a theoretical model to elucidate how a negative feedback mechanism, tied to the distance between the interfaces, induces the in-phase synchronization. We also identify the criterion for the transition from in-phase to out-of-phase oscillations.
Topaz-Denoise: general deep denoising models for cryoEM and cryoET
Authors: Bepler Tristan , Kelley Kotaro , Noble Alex J. , Berger Bonnie
Published: October 2020

Cryo-electron microscopy (cryoEM) is becoming the preferred method for resolving protein structures. Low signal-to-noise ratio (SNR) in cryoEM images reduces the confidence and throughput of structure determination during several steps of data processing, resulting in impediments such as missing particle orientations. Denoising cryoEM images can not only improve downstream analysis but also accelerate the time-consuming data collection process by allowing lower electron dose micrographs to be used for analysis. Here, we present Topaz-Denoise, a deep learning method for reliably and rapidly increasing the SNR of cryoEM images and cryoET tomograms. By training on a dataset composed of thousands of micrographs collected across a wide range of imaging conditions, we are able to learn models capturing the complexity of the cryoEM image formation process. The general model we present is able to denoise new datasets without additional training. Denoising with this model improves micrograph interpretability and allows us to solve 3D single particle structures of clustered protocadherin, an elongated particle with previously elusive views. We then show that low dose collection, enabled by Topaz-Denoise, improves downstream analysis in addition to reducing data collection time. We also present a general 3D denoising model for cryoET. Topaz-Denoise and pre-trained general models are now included in Topaz. We expect that Topaz-Denoise will be of broad utility to the cryoEM community for improving micrograph and tomogram interpretability and accelerating analysis.
Stress-induced RNA–chromatin interactions promote endothelial dysfunction
Authors: Calandrelli Riccardo , Xu Lixia , Luo Yingjun , Wu Weixin , Fan Xiaochen , Nguyen Tri , Chen Chien-Ju , Sriram Kiran , Tang Xiaofang , Burns Andrew B. , Natarajan Rama , Chen Zhen Bouman , Zhong Sheng
Published: October 2020

Chromatin-associated RNA (caRNA) has been proposed as a type of epigenomic modifier. Here, we test whether environmental stress can induce cellular dysfunction through modulating RNA-chromatin interactions. We induce endothelial cell (EC) dysfunction with high glucose and TNFα (H + T), that mimic the common stress in diabetes mellitus. We characterize the H + T-induced changes in gene expression by single cell (sc)RNA-seq, DNA interactions by Hi-C, and RNA-chromatin interactions by iMARGI. H + T induce inter-chromosomal RNA-chromatin interactions, particularly among the super enhancers. To test the causal relationship between H + T-induced RNA-chromatin interactions and the expression of EC dysfunction-related genes, we suppress the LINC00607 RNA. This suppression attenuates the expression of SERPINE1, a critical pro-inflammatory and pro-fibrotic gene. Furthermore, the changes of the co-expression gene network between diabetic and healthy donor-derived ECs corroborate the H + T-induced RNA-chromatin interactions. Taken together, caRNA-mediated dysregulation of gene expression modulates EC dysfunction, a crucial mechanism underlying numerous diseases.
MYB61 is regulated by GRF4 and promotes nitrogen utilization and biomass production in rice
Authors: Gao Yihong , Xu Zuopeng , Zhang Lanjun , Li Shance , Wang Shaogan , Yang Hanlei , Liu Xiangling , Zeng Dali , Liu Qiaoquan , Qian Qian , Zhang Baocai , Zhou Yihua
Published: October 2020

Nitrogen (N) is a macronutrient that boosts carbon (C) metabolism and plant growth leading to biomass accumulation. The molecular connection between nitrogen utilization efficiency (NUE) and biomass production remains unclear. Here, via quantitative trait loci analysis and map-based cloning, we reveal that natural variation at the MYB61 locus leads to differences in N use and cellulose biogenesis between indica and japonica subspecies of rice. MYB61, a transcriptional factor that regulates cellulose synthesis, is directly regulated by a known NUE regulator GROWTH-REGULATING FACTOR4 (GRF4), which coordinates cellulosic biomass production and N utilization. The variation at MYB61 has been selected during indica and japonica domestication. The indica allele of MYB61 displays robust transcription resulting in higher NUE and increased grain yield at reduced N supply than that of japonica. Our study hence unravels how C metabolism is linked to N uptake and may provide an opportunity to reduce N use for sustainable agriculture.
Structural analysis reveals TLR7 dynamics underlying antagonism
Authors: Tojo Shingo , Zhang Zhikuan , Matsui Hiroyuki , Tahara Masahiro , Ikeguchi Mitsunori , Kochi Mami , Kamada Mami , Shigematsu Hideki , Tsutsumi Akihisa , Adachi Naruhiko , Shibata Takuma , Yamamoto Masaki , Kikkawa Masahide , Senda Toshiya , Isobe Yoshiaki , Ohto Umeharu , Shimizu Toshiyuki
Published: October 2020

Toll-like receptor 7 (TLR7) recognizes both microbial and endogenous RNAs and nucleosides. Aberrant activation of TLR7 has been implicated in several autoimmune diseases including systemic lupus erythematosus (SLE). Here, by modifying potent TLR7 agonists, we develop a series of TLR7-specific antagonists as promising therapeutic agents for SLE. These compounds protect mice against lethal autoimmunity. Combining crystallography and cryo-electron microscopy, we identify the open conformation of the receptor and reveal the structural equilibrium between open and closed conformations that underlies TLR7 antagonism, as well as the detailed mechanism by which TLR7-specific antagonists bind to their binding pocket in TLR7. Our work provides small-molecule TLR7-specific antagonists and suggests the TLR7-targeting strategy for treating autoimmune diseases.
Highly efficient and air-stable Eu(II)-containing azacryptates ready for organic light-emitting diodes
Authors: Li Jiayi , Wang Liding , Zhao Zifeng , Sun Boxun , Zhan Ge , Liu Huanyu , Bian Zuqiang , Liu Zhiwei
Published: October 2020

Divalent europium 5d-4ftransition has aroused great attention in many fields, in a way of doping Eu2+ions into inorganic solids. However, molecular Eu2+complexes with 5d-4ftransition are thought to be too air-unstable to explore their applications. In this work, we synthesized four Eu2+-containing azacryptates EuX2-Nn(X = Br, I,n = 4, 8) and systematically studied the photophysical properties in crystalline samples and solutions. Intriguingly, the EuX2-N8complexes exhibit near-unity photoluminescence quantum yield, good air-/thermal-stability and mechanochromic property (X = I). Furthermore, we proved the application of Eu2+complexes in organic light-emitting diodes (OLEDs) with high efficiency and luminance. The optimized device employing EuI2-N8as emitter has the best performance as the maximum luminance, current efficiency, and external quantum efficiency up to 25470 cd m−2, 62.4 cd A−1, and 17.7%, respectively. Our work deepens the understanding of structure-property relationship in molecular Eu2+complexes and could inspire further research on application in OLEDs.
Long-range exciton diffusion in molecular non-fullerene acceptors
Authors: Firdaus Yuliar , Le Corre Vincent M. , Karuthedath Safakath , Liu Wenlan , Markina Anastasia , Huang Wentao , Chattopadhyay Shirsopratim , Nahid Masrur Morshed , Nugraha Mohamad I. , Lin Yuanbao , Seitkhan Akmaral , Basu Aniruddha , Zhang Weimin , McCulloch Iain , Ade Harald , Labram John , Laquai Frédéric , Andrienko Denis , Koster L. Jan Anton , Anthopoulos Thomas D.
Published: October 2020

The short exciton diffusion length associated with most classical organic semiconductors used in organic photovoltaics (5-20 nm) imposes severe limits on the maximum size of the donor and acceptor domains within the photoactive layer of the cell. Identifying materials that are able to transport excitons over longer distances can help advancing our understanding and lead to solar cells with higher efficiency. Here, we measure the exciton diffusion length in a wide range of nonfullerene acceptor molecules using two different experimental techniques based on photocurrent and ultrafast spectroscopy measurements. The acceptors exhibit balanced ambipolar charge transport and surprisingly long exciton diffusion lengths in the range of 20 to 47 nm. With the aid of quantum-chemical calculations, we are able to rationalize the exciton dynamics and draw basic chemical design rules, particularly on the importance of the end-group substituent on the crystal packing of nonfullerene acceptors.
21-nt phasiRNAs direct target mRNA cleavage in rice male germ cells
Authors: Jiang Pengfei , Lian Bi , Liu Changzhen , Fu Zeyu , Shen Yi , Cheng Zhukuan , Qi Yijun
Published: October 2020

In grasses, phased small interfering RNAs (phasiRNAs), 21- or 24-nucleotide (nt) in length, are predominantly expressed in anthers and play a role in regulating male fertility. However, their targets and mode of action on the targets remain unknown. Here we profile phasiRNA expression in premeiotic and meiotic spikelets as well as in purified male meiocytes at early prophase I, tetrads and microspores in rice. We show that 21-nt phasiRNAs are most abundant in meiocytes at early prophase I while 24-nt phasiRNAs are more abundant in tetrads and microspores. By performing highly sensitive degradome sequencing, we find that 21-nt phasiRNAs direct target mRNA cleavage in male germ cells, especially in meiocytes at early prophase I. These targets include 435 protein-coding genes and 71 transposons that show an enrichment for carbohydrate biosynthetic and metabolic pathways. Our study provides strong evidence that 21-nt phasiRNAs act in a target-cleavage mode and may facilitate the progression of meiosis by fine-tuning carbohydrate biosynthesis and metabolism in male germ cells.
Greenhouse gas consequences of the China dual credit policy
Authors: He Xin , Ou Shiqi , Gan Yu , Lu Zifeng , Przesmitzki Steven Victor , Bouchard Jessey Lee , Sui Lang , Amer Amer Ahmad , Lin Zhenhong , Yu Rujie , Zhou Yan , Wang Michael
Published: October 2020

For over ten years, China has been the largest vehicle market in the world. In order to address energy security and air quality concerns, China issued the Dual Credit policy to improve vehicle efficiency and accelerate New Energy Vehicle adoption. In this paper, a market-penetration model is combined with a vehicle fleet model to assess implications on greenhouse gas (GHG) emissions and energy demand. Here we use this integrated modeling framework to study several scenarios, including hypothetical policy tweaks, oil price, battery cost and charging infrastructure for the Chinese passenger vehicle fleet. The model shows that the total GHGs of the Chinese passenger vehicle fleet are expected to peak in 2032 under the Dual Credit policy. A significant reduction in GHG emissions is possible if more efficient internal combustion engines continue to be part of the technology mix in the short term with more New Energy Vehicle penetration in the long term.
Transplantation of hPSC-derived pericyte-like cells promotes functional recovery in ischemic stroke mice
Authors: Sun Jiaqi , Huang Yinong , Gong Jin , Wang Jiancheng , Fan Yubao , Cai Jianye , Wang Yi , Qiu Yuan , Wei Yili , Xiong Chuanfeng , Chen Jierui , Wang Bin , Ma Yuanchen , Huang Lihua , Chen Xiaoyong , Zheng Shuwei , Huang Weijun , Ke Qiong , Wang Tao , Li Xiaoping , Zhang Wei , Xiang Andy Peng , Li Weiqiang
Published: October 2020

Pericytes play essential roles in blood–brain barrier (BBB) integrity and dysfunction or degeneration of pericytes is implicated in a set of neurological disorders although the underlying mechanism remains largely unknown. However, the scarcity of material sources hinders the application of BBB models in vitro for pathophysiological studies. Additionally, whether pericytes can be used to treat neurological disorders remains to be elucidated. Here, we generate pericyte-like cells (PCs) from human pluripotent stem cells (hPSCs) through the intermediate stage of the cranial neural crest (CNC) and reveal that the cranial neural crest-derived pericyte-like cells (hPSC-CNC PCs) express typical pericyte markers including PDGFRβ, CD146, NG2, CD13, Caldesmon, and Vimentin, and display distinct contractile properties, vasculogenic potential and endothelial barrier function. More importantly, when transplanted into a murine model of transient middle cerebral artery occlusion (tMCAO) with BBB disruption, hPSC-CNC PCs efficiently promote neurological functional recovery in tMCAO mice by reconstructing the BBB integrity and preventing of neuronal apoptosis. Our results indicate that hPSC-CNC PCs may represent an ideal cell source for the treatment of BBB dysfunction-related disorders and help to model the human BBB in vitro for the study of the pathogenesis of such neurological diseases.
Experimental study on the mechanical properties of Guiyang red clay considering the meso micro damage mechanism and stress path
Authors: Zhang Yanzhao , Zuo Shuangying , Li Rita Yi Man , Mo Yunchuan , Yang Guosheng , Zhang Min
Published: October 2020

This study investigated the macroscopic physical and mechanical properties of Guiyang red clay during surcharge loading, lateral excavation and lateral unloading with axial loading, and clarified the failure mechanism of microstructure before and after shear under different stress paths of CTC, RTC and TC. Consolidated undrained triaxial shear permeability, SEM scanning, XRF fluorescence spectrum analysis and XRD diffraction tests were conducted to simulate the actual engineering conditions. The stress–strain curve, shear strength, pore water pressure variation rule and macroscopic failure mode of soil samples under different stress paths were analysed. In addition, Image Pro Plus 6.0 and PCAS were used to study the relationship between the macro mechanical properties and micro microstructure failure under different stress paths. The stress–strain curves from CTC, RTC and TC in CU tests were different, with the peak values of shear stress under the three stress paths being P-increasing, equal P-path and P-decreasing path. Moreover, the internal friction angle and cohesion of the increasing P path were higher than those of equal P path and decreasing P path, hence, the influence of stress paths on the cohesion is greater than that of internal friction angle. The pore water pressure is strongly dependent on the stress path, and the variation characteristics of pore water pressure are consistent with the change in the law of the stress–strain curve. Under the same confining pressure in the P-increasing path, the shear failure zone runs through the whole soil sample, and the shear failure zone is significant, whereas under the condition of the P-reducing path, the shear failure angle of soil sample is about 65°, 55° and 45°, and in the equal P path, the soil sample is dominated by the confining pressure, with no obvious microcrack on the surface of the soil sample. The difference is that the distribution of pores in the path of increasing P and equal P is directional, and the anisotropy rate is small, while the distribution of pores in soil samples with shear failure and before shear is random and the anisotropy rate is high.
Exposure to the natural alkaloid Berberine affects cardiovascular system morphogenesis and functionality during zebrafish development
Authors: Martini Davide , Pucci Cecilia , Gabellini Chiara , Pellegrino Mario , Andreazzoli Massimiliano
Published: October 2020

The plant-derived natural alkaloid berberine displays therapeutic potential to treat several pathological conditions, including dyslipidemias, diabetes and cardiovascular disorders. However, data on berberine effects during embryonic development are scarce and in part controversial. In this study, using zebrafish embryos as vertebrate experimental model, we address the effects of berberine treatment on cardiovascular system development and functionality. Starting from the observation that berberine induces developmental toxicity and pericardial edema in a time- and concentration-dependent manner, we found that treated embryos display cardiac looping defects and, at later stages, present an abnormal heart characterized by a stretched morphology and atrial endocardial/myocardial detachment. Furthermore, berberine affected cardiac functionality of the embryos, promoting bradycardia and reducing the cardiac output, the atrial shortening fraction percentage and the atrial stroke volume. We also found that, during development, berberine interferes with the angiogenic process, without altering vascular permeability. These alterations are associated with increased levels of vascular endothelial growth factor aa (vegfaa) mRNA, suggesting an important role for Vegfaa as mediator of berberine-induced cardiovascular defects. Altogether, these data indicate that berberine treatment during vertebrate development leads to an impairment of cardiovascular system morphogenesis and functionality, suggesting a note of caution in its use during pregnancy and lactation.
Author Correction: Global Disease Outbreaks Associated with the 2015–2016 El Niño Event
Authors: Anyamba Assaf , Chretien Jean-Paul , Britch Seth C. , Soebiyanto Radina P. , Small Jennifer L. , Jepsen Rikke , Forshey Brett M. , Sanchez Jose L. , Smith Ryan D. , Harris Ryan , Tucker Compton J. , Karesh William B. , Linthicum Kenneth J.
Published: October 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
PGC-1β-expressing POMC neurons mediate the effect of leptin on thermoregulation in the mouse
Authors: Delezie Julien , Gill Jonathan F. , Santos Gesa , Karrer-Cardel Bettina , Handschin Christoph
Published: October 2020

The arcuate nucleus (ARC) of the hypothalamus is a key regulator of food intake, brown adipose tissue (BAT) thermogenesis, and locomotor activity. Whole-body deficiency of the transcriptional coactivator peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1β (PGC-1β) disrupts mouse circadian locomotor activity and BAT-regulated thermogenesis, in association with altered gene expression at the central level. We examined whether PGC-1β expression in the ARC is required for proper energy balance and locomotor behavior by generating mice lacking the PGC-1β gene specifically in pro-opiomelanocortin (POMC) neurons. POMC neuron-specific deletion of PGC-1β did not impact locomotor behavior, food intake, body composition, energy fuel utilization and metabolic rate in fed, 24-h fasted and 24-h refed conditions. In contrast, in the fed state, deletion of PGC-1β in POMC cells elevated core body temperature during the nighttime period. Importantly, this higher body temperature is not associated with changes in BAT function and gene expression. Conversely, we provide evidence that mice lacking PGC-1β in POMC neurons are more sensitive to the effect of leptin on heat dissipation. Our data indicate that PGC-1β-expressing POMC neurons are part of a circuit controlling body temperature homeostasis and that PGC-1β function in these neurons is involved in the thermoregulatory effect of leptin.
Non-junctional role of Cadherin3 in cell migration and contact inhibition of locomotion via domain-dependent, opposing regulation of Rac1
Authors: Ichikawa Takehiko , Stuckenholz Carsten , Davidson Lance A.
Published: October 2020

Classical cadherins are well-known adhesion molecules responsible for physically connecting neighboring cells and signaling this cell–cell contact. Recent studies have suggested novel signaling roles for “non-junctional” cadherins (NJCads); however, the function of cadherin signaling independent of cell–cell contacts remains unknown. In this study, mesendodermal cells and tissues from gastrula stage Xenopus laevis embryos demonstrate that deletion of extracellular domains of Cadherin3 (Cdh3; formerly C-cadherin in Xenopus) disrupts contact inhibition of locomotion. In both bulk Rac1 activity assays and spatio-temporal FRET image analysis, the extracellular and cytoplasmic Cdh3 domains disrupt NJCad signaling and regulate Rac1 activity in opposing directions. Stabilization of the cytoskeleton counteracted this regulation in single cell migration assays. Our study provides novel insights into adhesion-independent signaling by Cadherin3 and its role in regulating single and collective cell migration.
Improvement of light penetration in biological tissue using an ultrasound-induced heating tunnel
Authors: Hsieh Zong-Han , Fan Ching-Hsiang , Ho Yi-Ju , Li Meng-Lin , Yeh Chih-Kuang
Published: October 2020

The major obstacles of optical imaging and photothermal therapy in biomedical applications is the strong scattering of light within biological tissues resulting in light defocusing and limited penetration. In this study, we propose high intensity focused ultrasound (HIFU)-induced heating tunnel to reduce the photon scattering. To verify our idea, Monte Carlo simulation and intralipid-phantom experiments were conducted. The results show that the thermal effect created by HIFU could improve the light fluence at the targeted region by 3% in both simulation and phantom experiments. Owing to the fluence increase, similar results can also be found in the photoacoustic experiments. In conclusion, our proposed method shows a noninvasive way to increase the light delivery efficiency in turbid medium. It is expected that our finding has a potential for improving the focal light delivery in photoacoustic imaging and photothermal therapy.
Characterization and properties of hybrid foams from nanocellulose and kaolin-microfibrillated cellulose composite
Authors: González-Ugarte Alina S. , Hafez Islam , Tajvidi Mehdi
Published: October 2020

Hybrid nanocellulose-based foams are a desirable class of low-density and porous materials for their potential in many applications. This study aims at characterizing and understanding the structure-properties relationship of four foam formulations prepared from combinations of cellulose nanofibrils (CNF), cellulose nanocrystals (CNC), and kaolin-microfibrillated cellulose composite. All the foams were crosslinked with a polyamide-epichlorohydrin crosslinker (Polycup) to impart stability under wet conditions without additional functionalization. Foams containing 25 wt% kaolin exhibited excellent shape recovery promoted by a higher load of crosslinker (5 wt%), and superior compressive properties. The addition of CNC at 33.3 wt% and 50 wt% did not seem to enhance the properties of the foam and also reduced the specific surface area. A preliminary comparative study between the four tested formulations was conducted to assess the feasibility of the foam as an adsorbent of methylene blue dye.
Association of cancer screening and residing in a coal-polluted East Asian region with overall survival of lung cancer patients: a retrospective cohort study
Authors: Yang Runxiang , He Ming , Wang Dongmei , Ye Rongrong , Li Lu , Deng Rouyu , Shah Mohsin , Yeung Sai-Ching Jim
Published: October 2020

Lung cancer is the leading cause of cancer death worldwide. The Xuanwei-Fuyuan (XF) region of Yunnan, China has a high incidence of lung cancer from coal-related pollution. Effort to raise public awareness screening for lung cancer has been ongoing. We retrospectively analyzed overall survival (OS) of lung cancer patients of a tertiary cancer center in Yunnan to investigate screening and regional residential status as predictive factors. Consecutive cases of newly diagnosed lung cancer were reviewed. The lung cancer cases diagnosed by screening were more likely to be early-staged and treated by surgery than those diagnosed not by screening. In patients diagnosed not by screening, XF residential status was a significant predictor of improved OS. Frailty model detected significant heterogeneity associated with region of residence in unscreened patients. Potential biases associated with screening were examined by Monte Carlo simulations and sensitivity analyses. Focused effort in cancer screening and increased public awareness of pollution-related lung cancer in XF might have led to early diagnosis and improved OS, and increased investment in health care resources in high risk areas may have produced additional unobserved factors that underlay the association of XF residential status with improved OS in patients diagnosed not by screening.
In vitro plant regeneration and Agrobacterium-mediated genetic transformation of a carnivorous plant, Nepenthes mirabilis
Authors: Miguel Sissi , Michel Cindy , Biteau Flore , Hehn Alain , Bourgaud Frédéric
Published: October 2020

In nutrient-poor habitats, carnivorous plants have developed novel feeding strategies based on the capture and digestion of prey and the assimilation of prey-derived nutrients by specialized traps. The Nepenthes genus, comprising nearly 160 species, presents a remarkable pitcher-shaped trap, leading to great interest among biologists, but the species of this genus are listed as threatened. In this work, we developed a protocol for reproducing Nepenthes mirabilis through shoot regeneration from calli. The cultivation of stem segments of N. mirabilis on MS medium containing thidiazuron induced organogenic calli after 10 weeks. Subcultured calli exposed to 6-benzylaminopurine showed shoot regeneration in 3 weeks with considerable yields (143 shoots/g of calli). Excised shoots transferred to medium with indole-3-butyric acid allowed rooting in 4 weeks, and rooted plantlets had a 100% survival rate. Based on this method, we also developed an Agrobacterium-mediated genetic transformation protocol using calli as explants and ipt as a positive method of selection. Twelve weeks post infection, regenerated shoots were observed at the surface of calli. Their transgenic status was confirmed by PCR and RT-PCR. In conclusion, this study provides an efficient method for regenerating Nepenthes and the first protocol for its stable genetic transformation, a new tool for studying carnivory.
A reconfigurable sandwich structure switchable DNA-based metamaterial
Authors: Zhong Min
Published: October 2020

In this paper, a tunable DNA-based metamaterial is designed and simulated in 170–340 THz range. This metamaterial can be transformed from an ON mode with a low resistance state of the DNA strip to its OFF mode with a high resistance state. Three Structures with containing different combinations metal layers are designed and simulated. Structure 1 with Ag/DNA/Ag and Au/DNA/Au strategies achieves field enhancement factors (FEF) 2.18 and 2.07, respectively. Structure 2 (Au/DNA/Dirac, Dirac/DNA/Au, Ag/DNA/Dirac, or Dirac/DNA/Ag) achieves the FEF values 14.11, 10.70, 13.75, or 9.62, respectively, while the FEF value of Structure 3 with Dirac/DNA/Dirac reaches 59.8. The FEF value of Structure 3 can be modulated from 59.8 to 91.96 as Fermi energy increasing from 0 to 60 meV. Moreover, the FEF value is also enhanced through increasing the magnetic field strength. The Structure 3 exhibits convertibility and sustainable modulation lines between two opposing patterns. The proposed structure reveals a switchable feature based on the resistance characteristics of DNA strips, which can be revealed as an ON/OFF switch sensor. Moreover, the switching performance of Structures 3 and 2 is significantly higher than Structure 1. Therefore, Structures 3 and 2 can be set to be an optical memristor or optical gate.
Anatomical MRI and [18F]FDG PET/CT imaging of Schistosoma mansoni in a NMRI mouse model
Authors: Lindner Tobias , Stenzel Jan , Koslowski Nicole , Hohn Alexander , Glass Änne , Schwarzenböck Sarah M. , Krause Bernd J. , Vollmar Brigitte , Reisinger Emil C. , Sombetzki Martina
Published: October 2020

Schistosomiasis represents one of the most devastating worm parasitosis in the world. Current diagnostic methods are insufficient to determine the infection grade and the disease related organ damage. We herein investigated whether discrimination of infection grade and its correlation to liver damage could be accurately performed by multimodal imaging in a mouse model ofSchistosoma mansoniinfection. Therefore, groups of uninfected and infected mice underwent MRI and [18F]FDG PET/CT imaging. Anatomical MRI images were used for liver volumetry and for quantification of hepatic granulomas. For PET/CT images a volume of interest based analyses were employed to calculate the [18F]FDG uptake in liver, portal vein, spleen and abdomen. Herein, we demonstrate that the combined use of [18F]FDG-PET/CT and MRI represents an appropriate diagnostic tool forSchistosoma mansoniinfection, but fails to discriminate the infection grade and the linked organ damage. Only the splenic [18F]FDG uptake in the 25 cercariae group (5.68 ± 0.90%ID/cc) and 50 cercariae group (4.98 ± 1.43%ID/cc) was significantly higher compared to the control group (2.13 ± 0.69%ID/cc). Nevertheless, future multimodal imaging studies with new radiopharmaceuticals could build a highly sensitive and specific basis for the diagnosis and evaluation of organ damage of schistosomiasis.
The constraint of ignoring the subtidal water climatology in evaluating the changes of coralligenous reefs due to heating events
Authors: Ceccherelli Giulia , Pinna Federico , Pansini Arianna , Piazzi Luigi , La Manna Gabriella
Published: October 2020

Predicting community-level responses to seawater warming is a pressing goal of global change ecologists. How far such predictions can be derived from a fine gradient of thermal environments needs to be explored, even if ignoring water climatology does not allow estimating subtidal marine heat waves. In this study insights about the influence of the thermal environment on the coralligenous community structure were gained by considering sites (Sardinia, Italy) at different temperature conditions. Heating events were measured (by loggers at 18 m, 23 m, 28 m, 33 m and 38 m deep) and proxies for their duration (the maximum duration of events warmer than the 90th percentile temperature), intensity (the median temperature) and variability (the number of daily ΔT larger than the mean daily ΔT, and the number of heating events larger in ΔT than the 90th percentile ΔT) were selected by GAM models. Reliable predictions of decrease in coralligenous richness of taxa/morphological groups, with relevant increment in turfs and encrusting coralline algae abundance at the expenses of bryozoans were made. Associations to the different types of heating descriptor have highlighted the aspect (intensity, duration or variability) of the heating events and the threshold for each of them responsible for the trajectories of change.
The genetic diversity and differentiation of mussels with complex life cycles and relations to host fish migratory traits and densities
Authors: Österling Martin , Lopes-Lima Manuel , Froufe Elsa , Hadzihalilovic Amra H. , Arvidsson Björn
Published: October 2020

Many landscape and biotic processes shape the genetic structure of populations. The genetic structure of species with parasitic stages may also depend on the life history and ecology of their host. We investigated population genetic structure of the musselMargaritifera margaritiferain Southern Sweden, and in relation to the population size and life history of its hosts,Salmo truttaandS. salar. Mussel populations were genetically differentiated into two clusters, further subdivided into four clusters and distinct conservation units. Regardless of host species, the genetic differentiation was lower among mussel populations sustained by sea-migrating than by resident hosts, while the genetic diversity was higher in mussel populations sustained by sea-migrating than by resident hosts. Genetic diversity of mussel populations was positively related to host abundance. Mussel population size was positively related to high genetic diversity of mussels sustained by resident hosts, while low mussel population size sustained by sea-migrating hosts had a high genetic diversity. The results of our study suggest a combined influence of mussels and host fish on genetic structure of unionoid mussels. We suggest to conserve not only mussel population sizes and host fish species, but also consider host migratory/resident behaviour and abundance when designing conservation programs.
Clinical characteristics of “re-positive” discharged COVID-19 pneumonia patients in Wuhan, China
Authors: He Shengyang , Zhou Kefu , Hu Mengyun , Liu Chun , Xie Lihua , Sun Shenghua , Sun Wenwu , Chen Liangkai
Published: October 2020

To analyze the clinical characteristics of re-positive discharged COVID-19 patients and find distinguishing markers. The demographic features, clinical symptoms, laboratory results, comorbidities, co-infections, treatments, illness severities and chest CT scan results of 267 patients were collected from 1st January to 15th February 2020. COVID-19 was diagnosed by RT-PCR. Clinical symptoms and nucleic acid test results were collected during the 14 days post-hospitalization quarantine. 30 out of 267 COVID-19 patients were detected re-positive during the post-hospitalization quarantine. Re-positive patients could not be distinguished by demographic features, clinical symptoms, laboratory results, comorbidities, co-infections, treatments, chest CT scan results or subsequent clinical symptoms. However, re-positive rate was found to be correlated to illness severity, according the Acute Physiology and Chronic Health Evaluation II (APACHE II) severity-of-disease classification system, and the confusion, urea, respiratory rate and blood pressure (CURB-65) score. Common clinical characteristics were not able to distinguish re-positive patients. However, severe and critical cases classified high according APACHE II and CURB-65 scores, were more likely to become re-positive after discharge.
Cell-free DNA in plasma as an essential immune system regulator
Authors: Korabecna M. , Zinkova A. , Brynychova I. , Chylikova B. , Prikryl P. , Sedova L. , Neuzil P. , Seda O.
Published: October 2020

The cell-free DNA (cfDNA) is always present in plasma, and it is biomarker of growing interest in prenatal diagnostics as well as in oncology and transplantology for therapy efficiency monitoring. But does this cfDNA have a physiological role? Here we show that cfDNA presence and clearance in plasma of healthy individuals plays an indispensable role in immune system regulation. We exposed THP1 cells to healthy individuals’ plasma with (NP) and without (TP) cfDNA. In cells treated with NP, we found elevated expression of genes whose products maintain immune system homeostasis. Exposure of cells to TP triggered an innate immune response (IIR), documented particularly by elevated expression of pro-inflammatory interleukin 8. The results of mass spectrometry showed a higher abundance of proteins associated with IIR activation due to the regulation of complement cascade in cells cultivated with TP. These expression profiles provide evidence that the presence of cfDNA and its clearance in plasma of healthy individuals regulate fundamental mechanisms of the inflammation process and tissue homeostasis. The detailed understanding how neutrophil extracellular traps and their naturally occurring degradation products affect the performance of immune system is of crucial interest for future medical applications.
ATP synthase modulation leads to an increase of spare respiratory capacity in HPV associated cancers
Authors: Kirschberg Matthias , Heuser Sandra , Marcuzzi Gian Paolo , Hufbauer Martin , Seeger Jens Michael , Đukić Anamaria , Tomaić Vjekoslav , Majewski Slawomir , Wagner Steffen , Wittekindt Claus , Würdemann Nora , Klussmann Jens Peter , Quaas Alexander , Kashkar Hamid , Akgül Baki
Published: October 2020

Mucosal and skin cancers are associated with infections by human papillomaviruses (HPV). The manner how viral oncoproteins hijack the host cell metabolism to meet their own energy demands and how this may contribute to tumorigenesis is poorly understood. We now show that the HPV oncoprotein E7 of HPV8, HPV11 and HPV16 directly interact with the beta subunit of the mitochondrial ATP-synthase (ATP5B), which may therefore represent a conserved feature across different HPV genera. By measuring both glycolytic and mitochondrial activity we observed that the association of E7 with ATP5B was accompanied by reduction of glycolytic activity. Interestingly, there was a drastic increase in spare mitochondrial respiratory capacity in HPV8-E7 and an even more profound increase in HPV16-E7 expressing cells. In addition, we could show that ATP5B levels were unchanged in betaHPV positive skin cancers. However, comparing HPV-positive and HPV-negative oropharyngeal squamous cell carcinomas (OPSCC) we noticed that, while ATP5B expression levels did not correlate with patient overall survival in HPV-negative OPSCC, there was a strong correlation within the HPV16-positive OPSCC patient group. These novel findings provide evidence that HPV targets the host cell energy metabolism important for viral life cycle and HPV-mediated tumorigenesis.
β-SNAP activity in the outer segment growth period is critical for preventing BNip1-dependent apoptosis in zebrafish photoreceptors
Authors: Nishiwaki Yuko , Masai Ichiro
Published: October 2020

BNip1, which functions as a t-SNARE component of the syntaxin18 complex, is localized on the ER membrane and regulates retrograde transport from Golgi to the ER. BNip1 also has a BH3 domain, which generally releases pro-apoptotic proteins from Bcl2-mediated inhibition. Previously we reported that retinal photoreceptors undergo BNip1-dependent apoptosis in zebrafish β-snap1 mutants. Here, we investigated physiological roles of BNip1-dependent photoreceptor apoptosis. First, we examined the spatio-temporal profile of photoreceptor apoptosis in β-snap1 mutants, and found that apoptosis occurs only during a small developmental window, 2–4 days-post-fertilization (dpf), in which an apical photoreceptive membrane structure, called the outer segment (OS), grows rapidly. Transient expression of β-SNAP1 during this OS growing period prevents photoreceptor apoptosis in β-snap1 mutants, enabling cone to survive until at least 21 dpf. These observations suggest that BNip1-mediated apoptosis is linked to excessive activation of vesicular transport associated with rapid growth of the OS. Consistently, knockdown of Ift88 and Kif3b, which inhibits protein transport to the OS, rescued photoreceptor apoptosis in β-snap1 mutants. Treatment with rapamycin, which inhibits protein synthesis via the mTOR pathway, also rescued photoreceptor apoptosis in β-snap1 mutants. These data suggest that BNip1 performs risk assessment to detect excessive vesicular transport in photoreceptors.
Cathodoluminescence of green fluorescent protein exhibits the redshifted spectrum and the robustness
Authors: Akiba Keiichirou , Tamehiro Katsuyuki , Matsui Koki , Ikegami Hayata , Minoda Hiroki
Published: October 2020

Green fluorescent protein (GFP) and its variants are an essential tool for visualizing functional units in biomaterials. This is achieved by the fascinating optical properties of them. Here, we report novel optical properties of enhanced GFP (EGFP), which is one of widely used engineered variants of the wild-type GFP. We study the electron-beam-induced luminescence, which is known as cathodoluminescence (CL), using the hybrid light and transmission electron microscope. Surprisingly, even from the same specimen, we observe a completely different dependences of the fluorescence and CL on the electron beam irradiation. Since light emission is normally independent of whether an electron is excited to the upper level by light or by electron beam, this difference is quite peculiar. We conclude that the electron beam irradiation causes the local generation of a new redshifted form of EGFP and CL is preferentially emitted from it. In addition, we also find that the redshifted form is rather robust to electron bombardment. These remarkable properties can be utilized for three-dimensional reconstruction without electron staining in focused ion beam/scanning electron microscopy technology and provide significant potential for simultaneously observing the functional information specified by super-resolution CL imaging and the structural information at the molecular level obtained by electron microscope.