bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upregulation of miR-382 contributes to renal fibrosis secondary to aristolochic acid-induced kidney injury via PTEN signaling pathway
Authors: Wang Xiaoyan , Xue Ning , Zhao Shuan , Shi Yiqin , Ding Xiaoqiang , Fang Yi 
Published: August 2020

AbstractAcute kidney injury (AKI) has a critical role in the development of chronic kidney disease (CKD). Building on our previous findings, we explored the role of miR-382 in facilitating the transition of AKI to CKD using the Aristolochic acid (AA) nephropathy model, which was induced by intraperitoneal injection of aristolochic acid I salt (10 or 20 mg/kg). The effects of genetic depletion, pharmacologic inhibition, or overexpression of miR-382 on the PTEN/AKT signaling pathway were examined in vivo and in vitro. Changes in renal pathology and renal epithelial polarity were evaluated. A luciferase reporter assay was performed to investigate the reciprocal suppression relationship between miR-382 andPTEN. Renal fibrosis developed 14 d after AA exposure in a dose- and time-dependent manner. Renal abundance of miR-382 was upregulated following AA treatment, while genetic depletion or pharmacological inhibition of miR-382 partially reversed renal tubulointerstitial fibrosis. Expression of PTEN, a target of miR-382, was downregulated and subsequently its downstream AKT signaling pathway was activated during AKI to CKD transition induced by AA. Inhibition of PTEN in vitro resulted in the acquisition of the EMT phenotypes. Furthermore, upregulation of miR-382 in renal epithelial cells was partially mediated by the activation of NF-kB signaling, with a substantial elevation of proinflammatory cytokines. An in vivo study revealed that either miR-382 knockdown or miR-382 knockout was pivotal for inflammatory suppression, while an in vitro experiment confirmed that upregulation of miR-382 in cultured MTEC cells under AA exposure was remarkably reversed by NF-kB siRNA. These data indicated a novel role for the NF-κB/miR-382/PTEN/AKT axis in the pathogenesis of tubulointerstitial fibrosis following AA-induced acute renal tubular epithelial injury. Targeting miR-382 may lead to a potential novel therapeutic approach for retarding the AKT to CKD transition.
Novel ginsenoside derivative 20(S)-Rh2E2 suppresses tumor growth and metastasis in vivo and in vitro via intervention of cancer cell energy metabolism
Authors: Huang Qi , Zhang Hui , Bai Li Ping , Law Betty Yuen Kwan , Xiong Haoming , Zhou Xiaobo , Xiao Riping , Qu Yuan Qing , Mok Simon Wing Fai , Liu Liang , Wong Vincent Kam Wai 
Published: August 2020

AbstractIncreased energy metabolism is responsible for supporting the abnormally upregulated proliferation and biosynthesis of cancer cells. The key cellular energy sensor AMP-activated protein kinase (AMPK) and the glycolytic enzyme alpha-enolase (α-enolase) have been identified as the targets for active components of ginseng. Accordingly, ginseng or ginsenosides have been demonstrated with their potential values for the treatment and/or prevention of cancerviathe regulation of energy balance. Notably, our previous study demonstrated that theR-form derivative of 20(R)-Rh2, 20(R)-Rh2E2 exhibits specific and potent anti-tumor effect via suppression of cancer energy metabolism. However, the uncertain pharmacological effect ofS-form derivative, 20(S)-Rh2E2, the by-product during the synthesis of 20(R)-Rh2E2 from parental compound 20(R/S)-Rh2 (with bothR- andS-form), retarded the industrialized production, research and development of this novel effective candidate drug. In this study, 20(S)-Rh2E2 was structurally modified from pure 20(S)-Rh2, and this novel compound was directly compared with 20(R)-Rh2E2 for their in vitro and in vivo antitumor efficacy. Results showed that 20(S)-Rh2E2 effectively inhibited tumor growth and metastasis in a lung xenograft mouse model. Most importantly, animal administrated with 20(S)-Rh2E2 up to 320 mg/kg/day survived with no significant body weight lost or observable toxicity upon 7-day treatment. In addition, we revealed that 20(S)-Rh2E2 specifically suppressed cancer cell energy metabolism via the downregulation of metabolic enzyme α-enolase, leading to the reduction of lactate, acetyl-coenzyme (acetyl CoA) and adenosine triphosphate (ATP) production in Lewis lung cancer cells (LLC-1), but not normal cells. These findings are consistent to the results obtained from previous studies using a similar isomer 20(R)-Rh2E2. Collectively, current results suggested that 20(R/S)-Rh2E2 isomers could be the new and safe anti-metabolic agents by acting as the tumor metabolic suppressors, which could be generated from 20(R/S)-Rh2 in industrialized scale with low cost.
Ethylene-independent signaling by the ethylene precursor ACC in Arabidopsis ovular pollen tube attraction
Authors: Mou Wangshu , Kao Yun-Ting , Michard Erwan , Simon Alexander A. , Li Dongdong , Wudick Michael M. , Lizzio Michael A. , Feijó José A. , Chang Caren 
Published: August 2020

AbstractThe phytohormone ethylene has numerous effects on plant growth and development. Its immediate precursor, 1-aminocyclopropane-1-carboxylic acid (ACC), is a non-proteinogenic amino acid produced by ACC SYNTHASE (ACS). ACC is often used to induce ethylene responses. Here, we demonstrate that ACC exhibits ethylene-independent signaling in Arabidopsis thaliana reproduction. By analyzing an acs octuple mutant with reduced seed set, we find that ACC signaling in ovular sporophytic tissue is involved in pollen tube attraction, and promotes secretion of the pollen tube chemoattractant LURE1.2. ACC activates Ca2+-containing ion currents via GLUTAMATE RECEPTOR-LIKE (GLR) channels in root protoplasts. In COS-7 cells expressing moss PpGLR1, ACC induces the highest cytosolic Ca2+ elevation compared to all twenty proteinogenic amino acids. In ovules, ACC stimulates transient Ca2+ elevation, and Ca2+ influx in octuple mutant ovules rescues LURE1.2 secretion. These findings uncover a novel ACC function and provide insights for unraveling new physiological implications of ACC in plants.
Giant photothermal nonlinearity in a single silicon nanostructure
Authors: Duh Yi-Shiou , Nagasaki Yusuke , Tang Yu-Lung , Wu Pang-Han , Cheng Hao-Yu , Yen Te-Hsin , Ding Hou-Xian , Nishida Kentaro , Hotta Ikuto , Yang Jhen-Hong , Lo Yu-Ping , Chen Kuo-Ping , Fujita Katsumasa , Chang Chih-Wei , Lin Kung-Hsuan , Takahara Junichi , Chu Shi-Wei 
Published: August 2020

AbstractSilicon photonics have attracted significant interest because of their potential in integrated photonics components and all-dielectric meta-optics elements. One major challenge is to achieve active control via strong photon–photon interactions, i.e. optical nonlinearity, which is intrinsically weak in silicon. To boost the nonlinear response, practical applications rely on resonant structures such as microring resonators or photonic crystals. Nevertheless, their typical footprints are larger than 10 μm. Here, we show that 100 nm silicon nano-resonators exhibit a giant photothermal nonlinearity, yielding 90% reversible and repeatable modulation from linear scattering response at low excitation intensities. The equivalent nonlinear index is five-orders larger compared with bulk, based on Mie resonance enhanced absorption and high-efficiency heating in thermally isolated nanostructures. Furthermore, the nanoscale thermal relaxation time reaches nanosecond. This large and fast nonlinearity leads to potential applications for GHz all-optical control at the nanoscale and super-resolution imaging of silicon.
Triacylglycerol synthesis enhances macrophage inflammatory function
Authors: Castoldi Angela , Monteiro Lauar B. , van Teijlingen Bakker Nikki , Sanin David E. , Rana Nisha , Corrado Mauro , Cameron Alanna M. , Hässler Fabian , Matsushita Mai , Caputa George , Klein Geltink Ramon I. , Büscher Jörg , Edwards-Hicks Joy , Pearce Erika L. , Pearce Edward J. 
Published: August 2020

AbstractFoamy macrophages, which have prominent lipid droplets (LDs), are found in a variety of disease states. Toll-like receptor agonists drive triacylglycerol (TG)-rich LD development in macrophages. Here we explore the basis and significance of this process. Our findings indicate that LD development is the result of metabolic commitment to TG synthesis on a background of decreased fatty acid oxidation. TG synthesis is essential for optimal inflammatory macrophage activation as its inhibition, which prevents LD development, has marked effects on the production of inflammatory mediators, including IL-1β, IL-6 and PGE2, and on phagocytic capacity. The failure of inflammatory macrophages to make PGE2 when TG-synthesis is inhibited is critical for this phenotype, as addition of exogenous PGE2 is able to reverse the anti-inflammatory effects of TG synthesis inhibition. These findings place LDs in a position of central importance in inflammatory macrophage activation.
Disease-associated KIF3A variants alter gene methylation and expression impacting skin barrier and atopic dermatitis risk
Authors: Stevens Mariana L. , Zhang Zhonghua , Johansson Elisabet , Ray Samriddha , Jagpal Amrita , Ruff Brandy P. , Kothari Arjun , He Hua , Martin Lisa J. , Ji Hong , Wikenheiser-Brokamp Kathryn , Weirauch Matthew T. , Supp Dorothy M. , Biagini Myers Jocelyn M. , Khurana Hershey Gurjit K. 
Published: August 2020

AbstractSingle nucleotide polymorphisms (SNPs) in the gene encoding kinesin family member 3A, KIF3A, have been associated with atopic dermatitis (AD), a chronic inflammatory skin disorder. We find that KIF3A SNP rs11740584 and rs2299007 risk alleles create cytosine-phosphate-guanine sites, which are highly methylated and result in lower KIF3A expression, and this methylation is associated with increased transepidermal water loss (TEWL) in risk allele carriers. Kif3aK14∆/∆ mice have increased TEWL, disrupted junctional proteins, and increased susceptibility to develop AD. Thus, KIF3A is required for skin barrier homeostasis whereby decreased KIF3A skin expression causes disrupted skin barrier function and promotes development of AD.
DNA methylation is reconfigured at the onset of reproduction in rice shoot apical meristem
Authors: Higo Asuka , Saihara Noriko , Miura Fumihito , Higashi Yoko , Yamada Megumi , Tamaki Shojiro , Ito Tasuku , Tarutani Yoshiaki , Sakamoto Tomoaki , Fujiwara Masayuki , Kurata Tetsuya , Fukao Yoichiro , Moritoh Satoru , Terada Rie , Kinoshita Toshinori , Ito Takashi , Kakutani Tetsuji , Shimamoto Ko , Tsuji Hiroyuki 
Published: August 2020

AbstractDNA methylation is an epigenetic modification that specifies the basic state of pluripotent stem cells and regulates the developmental transition from stem cells to various cell types. In flowering plants, the shoot apical meristem (SAM) contains a pluripotent stem cell population which generates the aerial part of plants including the germ cells. Under appropriate conditions, the SAM undergoes a developmental transition from a leaf-forming vegetative SAM to an inflorescence- and flower-forming reproductive SAM. While SAM characteristics are largely altered in this transition, the complete picture of DNA methylation remains elusive. Here, by analyzing whole-genome DNA methylation of isolated rice SAMs in the vegetative and reproductive stages, we show that methylation at CHH sites is kept high, particularly at transposable elements (TEs), in the vegetative SAM relative to the differentiated leaf, and increases in the reproductive SAM via the RNA-dependent DNA methylation pathway. We also show that half of the TEs that were highly methylated in gametes had already undergone CHH hypermethylation in the SAM. Our results indicate that changes in DNA methylation begin in the SAM long before germ cell differentiation to protect the genome from harmful TEs.
Artificial intelligence for the detection of COVID-19 pneumonia on chest CT using multinational datasets
Authors: Harmon Stephanie A. , Sanford Thomas H. , Xu Sheng , Turkbey Evrim B. , Roth Holger , Xu Ziyue , Yang Dong , Myronenko Andriy , Anderson Victoria , Amalou Amel , Blain Maxime , Kassin Michael , Long Dilara , Varble Nicole , Walker Stephanie M. , Bagci Ulas , Ierardi Anna Maria , Stellato Elvira , Plensich Guido Giovanni , Franceschelli Giuseppe , Girlando Cristiano , Irmici Giovanni , Labella Dominic , Hammoud Dima , Malayeri Ashkan , Jones Elizabeth , Summers Ronald M. , Choyke Peter L. , Xu Daguang , Flores Mona , Tamura Kaku , Obinata Hirofumi , Mori Hitoshi , Patella Francesca , Cariati Maurizio , Carrafiello Gianpaolo , An Peng , Wood Bradford J. , Turkbey Baris 
Published: August 2020

AbstractChest CT is emerging as a valuable diagnostic tool for clinical management of COVID-19 associated lung disease. Artificial intelligence (AI) has the potential to aid in rapid evaluation of CT scans for differentiation of COVID-19 findings from other clinical entities. Here we show that a series of deep learning algorithms, trained in a diverse multinational cohort of 1280 patients to localize parietal pleura/lung parenchyma followed by classification of COVID-19 pneumonia, can achieve up to 90.8% accuracy, with 84% sensitivity and 93% specificity, as evaluated in an independent test set (not included in training and validation) of 1337 patients. Normal controls included chest CTs from oncology, emergency, and pneumonia-related indications. The false positive rate in 140 patients with laboratory confirmed other (non COVID-19) pneumonias was 10%. AI-based algorithms can readily identify CT scans with COVID-19 associated pneumonia, as well as distinguish non-COVID related pneumonias with high specificity in diverse patient populations.
DAXX-inducing phytoestrogens inhibit ER+ tumor initiating cells and delay tumor development
Authors: Peiffer Daniel S. , Ma Emily , Wyatt Debra , Albain Kathy S. , Osipo Clodia 
Published: August 2020

AbstractRecurrence of estrogen receptor (ER)-positive breast tumors despite curative-intent adjuvant therapy is thought to be due to enrichment of tumor initiating cells (TIC) during endocrine therapy (ET). Recently, it was identified that by antagonizing the ER, ET promotes rapid degradation of the death-associated factor 6 (DAXX) protein, which is necessary and sufficient to potently inhibit TICs. Thus, the goal of the current study was to identify a DAXX-inducing agent to inhibit TICs and prevent proliferation of the tumor. Phytoestrogens (naringenin, resveratrol, genistein, apigenin, and quercetin) were screened for DAXX protein expression, anti-TIC and anti-proliferative efficacy in vitro and in vivo. Specific DAXX-inducing phytoestrogens were tested to assess selectivity towards ERα and/or ERβ. Results showed that phytoestrogens tested induced DAXX protein expression and inhibited survival of TICs from ER+ MCF-7 and T47D cells. Only naringenin, resveratrol, and quercetin did not stimulate total cell proliferation. Naringenin, resveratrol, but not quercetin inhibited survival of TICs in vitro and in vivo in a DAXX-dependent manner. Naringenin-induced DAXX protein expression and inhibition of TICs seemed to be more selective towards ERβ while resveratrol was more selective through ERα. Naringenin or resveratrol inhibited the rate of tumor initiation and rate of tumor growth in a DAXX-dependent manner. These results suggest that a therapeutic approach using a phytoestrogen to induce DAXX protein expression could potently inhibit TICs within a tumor to delay or prevent tumor initiation. Therefore, a DAXX-promoting phytoestrogen should be explored for prevention of tumor progression in advanced disease and relapse in the adjuvant setting.
The origin of early Acheulean expansion in Europe 700 ka ago: new findings at Notarchirico (Italy)
Authors: Moncel Marie-Hélène , Santagata Carmen , Pereira Alison , Nomade Sébastien , Voinchet Pierre , Bahain Jean-Jacques , Daujeard Camille , Curci Antonio , Lemorini Cristina , Hardy Bruce , Eramo Giacomo , Berto Claudio , Raynal Jean-Paul , Arzarello Marta , Mecozzi Beniamino , Iannucci Alessio , Sardella Raffaele , Allegretta Ignazio , Delluniversità Emanuela , Terzano Roberto , Dugas Pauline , Jouanic Gwenolé , Queffelec Alain , d’Andrea Andrea , Valentini Rosario , Minucci Eleonora , Carpentiero Laura , Piperno Marcello 
Published: August 2020

AbstractNotarchirico (Southern Italy) has yielded the earliest evidence of Acheulean settlement in Italy and four older occupation levels have recently been unearthed, including one with bifaces, extending the roots of the Acheulean in Italy even further back in time. New40Ar/39Ar on tephras and ESR dates on bleached quartz securely and accurately place these occupations between 695 and 670 ka (MIS 17), penecontemporaneous with the Moulin-Quignon and la Noira sites (France). These new data demonstrate a very rapid expansion of shared traditions over Western Europe during a period of highly variable climatic conditions, including interglacial and glacial episodes, between 670 and 650 (i.e., MIS17/MIS16 transition). The diversity of tools and activities observed in these three sites shows that Western Europe was populated by adaptable hominins during this time. These conclusions question the existence of refuge areas during intense glacial stages and raise questions concerning understudied migration pathways, such as the Sicilian route.
A multimodal computational pipeline for 3D histology of the human brain
Authors: Mancini Matteo , Casamitjana Adrià , Peter Loic , Robinson Eleanor , Crampsie Shauna , Thomas David L. , Holton Janice L. , Jaunmuktane Zane , Iglesias Juan Eugenio 
Published: August 2020

AbstractEx vivo imaging enables analysis of the human brain at a level of detail that is not possible in vivo with MRI. In particular, histology can be used to study brain tissue at the microscopic level, using a wide array of different stains that highlight different microanatomical features. Complementing MRI with histology has important applications in ex vivo atlas building and in modeling the link between microstructure and macroscopic MR signal. However, histology requires sectioning tissue, hence distorting its 3D structure, particularly in larger human samples. Here, we present an open-source computational pipeline to produce 3D consistent histology reconstructions of the human brain. The pipeline relies on a volumetric MRI scan that serves as undistorted reference, and on an intermediate imaging modality (blockface photography) that bridges the gap between MRI and histology. We present results on 3D histology reconstruction of whole human hemispheres from two donors.
Kinetics of T lymphocyte subsets and B lymphocytes in response to immunostimulants in flounder (Paralichthys olivaceus): implications for CD4+ T lymphocyte differentiation
Authors: Xing Jing , Tian Hong-fei , Tang Xiao-qian , Sheng Xiu-zhen , Zhan Wen-bin 
Published: August 2020

AbstractCD4+ T lymphocytes play crucial roles in the adaptive immune system. CD4, as the most effective marker to delineate the T-helper subsets, was identified in many fish species. Two CD4 homologs, CD4-1 and CD4-2, have been reported in flounder (Paralichthys olivaceus). In this study, monoclonal antibodies (mAbs) against CD4-1 and CD4-2 of flounder were produced, CD4+ T lymphocytes were isolated and identified, and the variations in CD4+ and CD8+ T lymphocytes and IgM+ B lymphocytes after Poly I:C, PMA or β-glucan stimulation were investigated. Then, the expression of transcription factors and cytokines in sorted CD4+ T lymphocytes was analyzed. The results showed that the mAbs were specific to flounder CD4-1+ and CD4-2+ T cells. CD4-1+ and CD4-2+ cells responded to all three stimulants, while CD8+ T lymphocytes only give a strong response to Poly I:C, and the percentages of IgM+ B lymphocytes showed a tendency to increase. After stimulation, the expression of transcription factors and cytokines of Th1, Th2 and Th17 cells varied in CD4+ T cells. These results will provide crucial foundations for the differentiation and function of teleost CD4+ T lymphocytes.
Temperature and salinity, not acidification, predict near-future larval growth and larval habitat suitability of Olympia oysters in the Salish Sea
Authors: Lawlor Jake A. , Arellano Shawn M. 
Published: August 2020

AbstractMost invertebrates in the ocean begin their lives with planktonic larval phases that are critical for dispersal and distribution of these species. Larvae are particularly vulnerable to environmental change, so understanding interactive effects of environmental stressors on larval life is essential in predicting population persistence and vulnerability of species. Here, we use a novel experimental approach to rear larvae under interacting gradients of temperature, salinity, and ocean acidification, then model growth rate and duration of Olympia oyster larvae and predict the suitability of habitats for larval survival. We find that temperature and salinity are closely linked to larval growth and larval habitat suitability, but larvae are tolerant to acidification at this scale. We discover that present conditions in the Salish Sea are actually suboptimal for Olympia oyster larvae from populations in the region, and that larvae from these populations might actually benefit from some degree of global ocean change. Our models predict a vast decrease in mean pelagic larval duration by the year 2095, which has the potential to alter population dynamics for this species in future oceans. Additionally, we find that larval tolerance can explain large-scale biogeographic patterns for this species across its range.
Systemically-delivered biodegradable PLGA alters gut microbiota and induces transcriptomic reprogramming in the liver in an obesity mouse model
Authors: Chaplin Alice , Gao Huiyun , Asase Courteney , Rengasamy Palanivel , Park Bongsoo , Skander Danielle , Bebek Gürkan , Rajagopalan Sanjay , Maiseyeu Andrei 
Published: August 2020

AbstractBiodegradable materials, including the widely used poly (lactic-co-glycolic acid) (PLGA) nanoparticles contained in slow-release drug formulations, scaffolds and implants, are ubiquitous in modern biomedicine and are considered inert or capable of being metabolized through intermediates such as lactate. However, in the presence of metabolic stress, such as in obesity, the resulting degradation products may play a detrimental role, which is still not well understood. We evaluated the effect of intravenously-administered PLGA nanoparticles on the gut-liver axis under conditions of caloric excess in C57BL/6 mice. Our results show that PLGA nanoparticles accumulate and cause gut acidification in the cecum, accompanied by significant changes in the microbiome, with a marked decrease of Firmicutes and Bacteroidetes. This was associated with transcriptomic reprogramming in the liver, with a downregulation of mitochondrial function, and an increase in key enzymatic, inflammation and cell activation pathways. No changes were observed in systemic inflammation. Metagenome analysis coupled with publicly available microarray data suggested a mechanism of impaired PLGA degradation and intestinal acidification confirming an important enterohepatic axis of metabolite-microbiome interaction resulting in maintenance of metabolic homeostasis. Thus, our results have important implications for the investigation of PLGA use in metabolically-compromised clinical and experimental settings.