bluuebunny/crossref_metadata_2025 huggingface dataset:
Why Are There so Few Reports of High‐Energy Electron Drift Resonances? Role of Radial Phase Space Density Gradients
Authors: Hartinger M. D. , Reeves G. D. , Boyd A. , Henderson M. G. , Turner D. L. , Komar C. M. , Claudepierre S. G. , Mann I. R. , Breneman A. , Di Matteo S. , Zhang X.‐J.
Published: August 2020

Models of monochromatic Pc5 (2–7 mHz) ultralow frequency (ULF) wave interactions with high energy (greater than ∼1 MeV) electrons predict drift resonant interactions that can cause rapid radial transport and acceleration. There are few reports of electron drift resonance at energies greater than ∼1 MeV, in contrast to lower energies; moreover, all previous reports occur in the aftermath of interplanetary shocks. These two facts are difficult to reconcile with theory and numerical simulations predicting that greater than ∼1 MeV drift resonances should occur more often and in a wider variety of driving conditions. In this study, we show that a combination of observational sampling biases and nominal radial phase space density gradients is one explanation for this discrepancy between theory and observations. In particular, we examine electron dynamics in two case studies with very similar satellite coverage, solar wind conditions, and Pc5 wave properties, yet with different radial phase space density profiles. Using global wave and particle observations, we show that the events have vastly different particle responses despite having similar wave properties. Placing these results in context with past studies, we further show that nominal radial PSD gradients near geostationary orbit can mask the expected drift resonance particle response and explain (1) the small number of past greater than ∼1 MeV drift resonance reports and (2) the restriction of these reports to interplanetary shock events. We argue that future observational studies characterizing radial transport via drift resonance should examine global particle dynamics, including observations of the radial phase space density profile.
Equatorial North‐South Difference of Noontime Electron Density Bite‐Out in the F2 Layer
Authors: Chen Yiding , Liu Libo , Le Huijun , Zhang Hui
Published: August 2020

Noontime bite‐out (depletion) of NmF2 (peak electron density of the F2 layer) often occurs in the equatorial ionosphere; it is characterized by a noontime minimum sandwiched by a prenoon peak and a postnoon peak of NmF2. The fountain effect was suggested to be responsible for this abnormal diurnal variation pattern. Noontime bite‐out should occur not only at the dip equator but also concurrently at both equatorial north and south according to the fountain effect mechanism. In this study, ionosonde measurements in the equatorial ionization anomaly trough region were selected to investigate the climatology of noontime bite‐out. North‐south difference of noontime bite‐out was presented for the first time. Noontime bite‐out occurs near the dip equator in all months. However, NmF2 enhances continuously since early morning till late afternoon at equatorial north (south) in northern summer (winter) months; nevertheless, noontime bite‐out still occurs in other months. This cannot be understood only in terms of the fountain effect mechanism. We suggested the reason is seasonally dependent transequator plasma transport induced by neutral meridional winds. Transequator transport works since early morning to modulate NmF2 variation pattern in daytime. Plasma outflow induced by the transequator transport results in significant NmF2 depletion at equatorial north or south before the fountain effect induced bite‐out; thus, NmF2 prenoon peak is restrained and noontime bite‐out variation pattern is absent.
Subsidence‐Derived Volumetric Strain Models for Mapping Extensional Fissures and Constraining Rock Mechanical Properties in the San Joaquin Valley, California
Authors: Carlson Grace , Shirzaei Manoochehr , Ojha Chandrakanta , Werth Susanna
Published: August 2020

Large‐scale subsidence due to aquifer‐overdraft is an ongoing hazard in the San Joaquin Valley. Subsidence continues to cause damage to infrastructure and increases the risk of extensional fissures.Here, we use InSAR‐derived vertical land motion (VLM) to model the volumetric strain rate due to groundwater storage change during the 2007–2010 drought in the San Joaquin Valley, Central Valley, California. We then use this volumetric strain rate model to calculate surface tensile stress in order to predict regions that are at the highest risk for hazardous tensile surface fissures. We find a maximum volumetric strain rate of −232 microstrain/yr at a depth of 0 to 200 m in Tulare and Kings County, California. The highest risk of tensile fissure development occurs at the periphery of the largest subsiding zones, particularly in Tulare County and Merced County. Finally, we assume that subsidence is likely due to aquifer pressure change, which is calculated using groundwater level changes observed at 300 wells during this drought. We combine pressure data from selected wells with our volumetric strain maps to estimate the quasi‐static bulk modulus, K, a poroelastic parameter applicable when pressure change within the aquifer is inducing volumetric strain. This parameter is reflective of a slow deformation process and is one to two orders of magnitude lower than typical values for the bulk modulus found using seismic velocity data. The results of this study highlight the importance of large‐scale, high‐resolution VLM measurements in evaluating aquifer system dynamics, hazards associated with overdraft, and in estimating important poroelastic parameters.
A Semianalytical Method to Fast Delineate Seawater‐Freshwater Interface in Two‐Dimensional Heterogeneous Coastal Aquifers
Authors: Rathore Saubhagya Singh , Lu Chunhui , Luo Jian
Published: August 2020

The freshwater‐seawater interface is one of the most important regions in coastal aquifer systems, delineating the subsurface into zones with distinct fluid density and biogeochemical properties. Heterogeneity in hydraulic conductivity is inherent to geological formations, resulting in distinct interface profiles. Currently available analytical solutions are limited to homogeneous and stratified aquifers, and numerical simulations of variable‐density flow and transport are the only option to characterize the interface in a two‐ or three‐dimensional heterogeneous aquifer. This study presents a novel semianalytical method to fast delineate the steady seawater‐freshwater interface in a two‐dimensional, confined, heterogeneous aquifer with a constant flux inland boundary and indistinct seepage face at the vertical coastal boundary. The heterogeneous domain is conceptualized as a series of thin columns of stratified aquifers with the horizontal flow in each of them. The proposed approach is based on the concept of local transmissivity parameters and shows high accuracy in the interface delineation. Leveraging the ability to delineate the interface rapidly along with the Monte Carlo approach, we numerically investigate the stochastic behavior of the interface profile. The uncertainty in seawater intrusion is heavily influenced by the degree of heterogeneity and weakly influenced by the scale of heterogeneity. To homogenize the aquifer, we found that geometric mean generally underestimates the seawater intrusion and cannot be used as an effective parameter. We also showed that the near‐coast, near‐top region of the aquifer is the most influential region and should be characterized at a higher resolution to reduce uncertainties in estimating seawater intrusion.
Gynura divaricata exerts hypoglycemic effects by regulating the PI3K/AKT signaling pathway and fatty acid metabolism signaling pathway
Authors: Xu Wenjun , Lu Zhongxia , Wang Xin , Cheung Man Hei , Lin Meiai , Li Changyu , Dong Yu , Liang Chun , Chen Yitao
Published: August 2020

Objectives

The study aimed to examine the anti-diabetic effects ofGynura divaricata(GD) and the underlying mechanism.

Methods

Information about the chemical compositions of GD was obtained from extensive literature reports. Potential target genes were predicted using PharmMapper and analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). To validate the results from bioinformatics analyses, an aqueous extract of GD was administered to type 2 diabetic rats established by feeding a high-fat and high-sugar diet followed by STZ injection. Key proteins of the PI3K/AKT signaling pathway and fatty acid metabolism signaling pathway were investigated by immunoblotting.

Results

The blood glucose of the rats in the GD treatment group was significantly reduced compared with the model group without treatment. GD also showed activities in reducing the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine (CREA). The levels of urine sugar (U-GLU) and urine creatinine (U-CREA) were also lowered after treatment with GD. Bioinformatics analysis showed that some pathways including metabolic pathways, insulin resistance, insulin signaling pathway, PPAR signaling pathway, bile secretion, purine metabolism, etc. may be regulated by GD. Furthermore, GD significantly increased the protein expression levels of PKM1/2, p-AKT, PI3K p85, and GLUT4 in the rat liver. In addition, the expression levels of key proteins in the fatty acid metabolism signaling pathway including AMPK, p-AMPK, PPARα, and CPT1α were significantly upregulated. The anti-apoptotic protein BCL-2/BAX expression ratio in rats was significantly upregulated after GD intervention. These results were consistent with the bioinformatics analysis results.

Conclusions

Our study suggests that GD can exert hypoglycemic effects in vivo by regulating the genes at the key nodes of the PI3K/AKT signaling pathway and fatty acid metabolism signaling pathway.
New preclinical models for angioimmunoblastic T-cell lymphoma: filling the GAP
Authors: Mhaidly Rana , Krug Adrien , Gaulard Philippe , Lemonnier François , Ricci Jean-Ehrland , Verhoeyen Els
Published: August 2020

Mouse models are essential to study and comprehend normal and malignant hematopoiesis. The ideal preclinical model should mimic closely the human malignancy. This means that these mice should recapitulate the clinical behavior of the human diseases such as cancer and therapeutic responses with high reproducibility. In addition, the genetic mutational status, the cell phenotype, the microenvironment of the tumor and the time until tumor development occurs, should be mimicked in a preclinical model. This has been particularly challenging for human angioimmunoblastic lymphoma (AITL), one of the most prominent forms of peripheral T-cell lymphomas. A complex network of interactions between AITL tumor cells and the various cells of the tumor microenvironment has impeded the study of AITL pathogenesis in vitro. Very recently, new mouse models that recapitulate faithfully the major features of human AITL disease have been developed. Here, we provide a summary of the pathology, the transcriptional profile and genetic and immune-phenotypic features of human AITL. In addition, we give an overview of preclinical models that recapitulate more or less faithfully human AITL characteristics and pathology. These recently engineered mouse models were essential in the evaluation of novel therapeutic agents for possible treatment of AITL, a malignancy in urgent need of new treatment options.
Maternal immune conditions are increased in males with autism spectrum disorders and are associated with behavioural and emotional but not cognitive co-morbidity
Authors: Patel Shrujna , Dale Russell C. , Rose Destanie , Heath Brianna , Nordahl Christine W. , Rogers Sally , Guastella Adam J. , Ashwood Paul
Published: August 2020

Epidemiological and animal research shows that maternal immune activation increases the risk of autism spectrum disorders (ASD) in offspring. Emerging evidence suggests that maternal immune conditions may play a role in the phenotypic expression of neurodevelopmental difficulties in children with ASD and this may be moderated by offspring sex. This study aimed to investigate whether maternal immune conditions were associated with increased severity of adverse neurodevelopmental outcomes in children with ASD. Maternal immune conditions were examined as predictors of ASD severity, behavioural and emotional well-being, and cognitive functioning in a cohort of 363 children with ASD (n = 363; 252 males, 111 females; median age 3.07 [interquartile range 2.64–3.36 years]). We also explored whether these outcomes varied between male and female children. Results showed that maternal asthma was the most common immune condition reported in mothers of children with ASD. A history of maternal immune conditions (p = 0.009) was more common in male children with ASD, compared to female children. Maternal immune conditions were associated with increased behavioural and emotional problems in male and female children. By contrast, maternal immune conditions were not associated with decreased cognitive function. The findings demonstrate that MIA may influence the expression of symptoms in children with ASD and outcomes may vary between males and females.
MiR-93 suppresses tumorigenesis and enhances chemosensitivity of breast cancer via dual targeting E2F1 and CCND1
Authors: Bao Chang , Chen Jishun , Chen Danni , Lu Yunkun , Lou Weiyang , Ding Bisha , Xu Liang , Fan Weimin
Published: August 2020

Chemoresistance of tumors often leads to treatment failure in clinical practice, which underscores pivotal needs to uncover novel therapeutic strategies. Accumulating evidences show that microRNAs (miRNAs) are widely involved in carcinogenesis, but their function on chemoresistance remains largely unexplored. In this study, we found that miR-93-5p (miR-93) significantly inhibited cell proliferation, induced G1/S cell cycle arrest and increased chemosensitivity to paclitaxel (PTX) in vitro and in vivo. Moreover, two well-established oncogenes, E2F1 and CCND1, were identified as dual targets of miR-93. Knockdown of E2F1 and CCND1 reduced cell proliferation and PTX-sensitivity, whereas overexpression of them had the opposite effect. More importantly, overexpression of E2F1 and CCND1 antagonized miR-93-mediated cell cycle arrest and apoptosis. Further mechanistic study revealed that miR-93 exhibited its inhibitory role by directly targeting E2F1 and CCND1 to inactivate pRB/E2F1 pathway and AKT phosphorylation. Taken together, our findings suggested that miR-93 greatly improved chemosensitivity and potentially served as a novel therapeutic target for breast cancer treatment.
N-acetyl-D-glucosamine kinase binds dynein light chain roadblock 1 and promotes protein aggregate clearance
Authors: Ripon Md. Kamal Hossain , Lee HyunSook , Dash Raju , Choi Ho Jin , Oktaviani Diyah Fatimah , Moon Il Soo , Haque Md. Nazmul
Published: August 2020

Emerging evidence indicates that neurodegenerative diseases (NDs) result from a failure to clear toxic protein aggregates rather than from their generation. We previously showedN-acetylglucosamine kinase (NAGK) promotes dynein functionality and suggested this might promote aggregate removal and effectively address proteinopathies. Here, we report NAGK interacts with dynein light chain roadblock type 1 (DYNLRB1) and efficiently suppresses mutant huntingtin (mHtt) (Q74) and α-synuclein (α-syn) A53T aggregation in mouse brain cells. A kinase-inactive NAGKD107Aalso efficiently cleared Q74 aggregates. Yeast two-hybrid selection and in silico protein–protein docking analysis showed the small domain of NAGK (NAGK-DS) binds to the C-terminal of DYNLRB1. Furthermore, a small peptide derived from NAGK-DSinterfered with Q74 clearance. We propose binding of NAGK-DSto DYNLRB1 ‘pushes up’ the tail of dynein light chain and confers momentum for inactive phi- to active open-dynein transition.
Circular noncoding RNA circMBOAT2 is a novel tumor marker and regulates proliferation/migration by sponging miR-519d-3p in colorectal cancer
Authors: Tang Xiaolong , Sun Guorui , He Qingsi , Wang Chao , Shi Jingbo , Gao Lei , Ye Jianhong , Liang Yahang , Qu Hui
Published: August 2020

Colorectal cancer (CRC) is a common malignant tumor with a poor prognosis. However, its pathogenesis has not been fully elucidated, accounting for poor overall survival. Circular RNA (circRNA) is a class of noncoding RNAs discovered many years ago. Only recently have they been re-evaluated for their important roles in the regulation of gene expression. Studies have confirmed that circRNAs have important biological functions in a variety of malignant tumors. This study aimed to characterize one circRNA derived from the MBOAT2 gene and termed it circMBOAT2, which has been reported to promote prostate cancer progression. CircMBOAT2 is highly expressed in both CRC tissues and serum samples, and has a correlation with tumor stage. The receiver-operating characteristic curves suggested that circMBOAT2 acted as a novel diagnostic tumor marker in CRC. Univariate and multivariate analyses showed that the levels of circMBOAT2 in tissues were independent prognostic markers of CRC. Further functional studies revealed that circMBOAT2 served as a microRNA (miRNA) sponge of miR-519d-3p and promoted the proliferation, migration, and invasion of CRC cells. Also, circMBOAT2 regulated cell proliferation and migration by competitively binding to miR-519d-3p and targeting troponin-associated protein (TROAP) in CRC cells. These results suggested that circMBOAT2 might be a novel potential biomarker of CRC.
FBX8 promotes metastatic dormancy of colorectal cancer in liver
Authors: Zhu Xiaohui , Wang Feifei , Wu Xuehui , Li Zhou , Wang Zhizhi , Ren Xiaoli , Zhou Yangshu , Song Fuyao , Liang Yunshi , Zeng Zhicheng , Liao Wangjun , Ding Yanqing , Liao Wenting , Liang Li
Published: August 2020

Patients with colorectal cancer (CRC) often develop malignant regrowth of metastatic dormant tumor cells in liver years after primary treatment. FBX8 is involved in suppressing tumor metastasis. Short-term chemotherapy experiments and liver metastasis mice model of orthotopic injection into the cecum were performed to construct the dormant models. GST-pull-down assay, Co-IP and immunofluorescence were used to confirm the bindings among FBX8 and its substrates. FBX8 upregulated the expression of epithelial and stemness markers, while downregulated the expression of mesenchymal and proliferative markers associated with tumor cell dormancy. FBX8 promoted the maintenance of metastatic dormancy of CRC cells. Mechanistically, FBX8 directly bound to HIF-1α, CDK4 and C-myc through its Sec7 domain and led to the ubiquitin degradation of these proteins, thereby inhibiting cell cycle progression, proliferation, angiogenesis, and metastasis. Clinically, FBX8 expression was negatively correlated with the HIF-1α, CDK4, and c-Myc in CRC tissues. Our study reveals a novel mechanism of FBX8 in regulating tumor metastatic dormancy in liver and provides new strategies for the treatment of CRC metastasis.
XJB-5-131 inhibited ferroptosis in tubular epithelial cells after ischemia−reperfusion injury
Authors: Zhao Zhi , Wu Jianliang , Xu Huzi , Zhou Cheng , Han Bicui , Zhu Han , Hu Zhizhi , Ma Zhimei , Ming Zhangyin , Yao Ying , Zeng Rui , Xu Gang
Published: August 2020

Regulated necrosis has been reported to exert an important role in the pathogenesis of various diseases, including renal ischemia-reperfusion (I/R) injury. Damage to renal tubular epithelial cells and subsequent cell death initiate the progression of acute kidney injury (AKI) and subsequent chronic kidney disease (CKD). We found that ferroptosis appeared in tubular epithelial cells (TECs) of various human kidney diseases and the upregulation of tubular proferroptotic gene ACSL4 was correlated with renal function in patients with acute kidney tubular injury. XJB-5-131, which showed high affinity for TECs, attenuated I/R-induced renal injury and inflammation in mice by specifically inhibiting ferroptosis rather than necroptosis and pyroptosis. Single-cell RNA sequencing (scRNA-seq) indicated that ferroptosis-related genes were mainly expressed in tubular epithelial cells after I/R injury, while few necroptosis- and pyroptosis-associated genes were identified to express in this cluster of cell. Taken together, ferroptosis plays an important role in renal tubular injury and the inhibition of ferroptosis by XJB-5-131 is a promising therapeutic strategy for protection against renal tubular cell injury in kidney diseases.
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

Acute 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

Increased 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

The 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

Silicon 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

Foamy 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

Single 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

DNA 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

Chest 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

Recurrence 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

Notarchirico (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

Ex 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

CD4+ 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

Most 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

Biodegradable 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.
Increased likelihood of heat-induced large wildfires in the Mediterranean Basin
Authors: Ruffault Julien , Curt Thomas , Moron Vincent , Trigo Ricardo M. , Mouillot Florent , Koutsias Nikos , Pimont François , Martin-StPaul Nicolas , Barbero Renaud , Dupuy Jean-Luc , Russo Ana , Belhadj-Khedher Chiraz
Published: August 2020

Wildfire activity is expected to increase across the Mediterranean Basin because of climate change. However, the effects of future climate change on the combinations of atmospheric conditions that promote wildfire activity remain largely unknown. Using a fire-weather based classification of wildfires, we show that future climate scenarios point to an increase in the frequency of two heat-induced fire-weather types that have been related to the largest wildfires in recent years. Heat-induced fire-weather types are characterized by compound dry and warm conditions occurring during summer heatwaves, either under moderate (heatwave type) or intense (hot drought type) drought. The frequency of heat-induced fire-weather is projected to increase by 14% by the end of the century (2071–2100) under the RCP4.5 scenario, and by 30% under the RCP8.5, suggesting that the frequency and extent of large wildfires will increase throughout the Mediterranean Basin.
RLP23 is required for Arabidopsis immunity against the grey mould pathogen Botrytis cinerea
Authors: Ono Erika , Mise Kazuyuki , Takano Yoshitaka
Published: August 2020

Necrosis- and ethylene-inducing-like proteins (NLPs) are secreted by fungi, oomycetes and bacteria. Conserved nlp peptides derived from NLPs are recognized as pathogen-associated molecular patterns (PAMPs), leading to PAMP-triggered immune responses. RLP23 is the receptor of the nlp peptides in Arabidopsis thaliana; however, its actual contribution to plant immunity is unclear. Here, we report that RLP23 is required for Arabidopsis immunity against the necrotrophic fungal pathogen Botrytis cinerea. Arabidopsis rlp23 mutants exhibited enhanced susceptibility to B. cinerea compared with the wild-type plants. Notably, microscopic observation of the B. cinerea infection behaviour indicated the involvement of RLP23 in pre-invasive resistance to the pathogen. B. cinerea carried two NLP genes, BcNEP1 and BcNEP2; BcNEP1 was expressed preferentially before/during invasion into Arabidopsis, whereas BcNEP2 was expressed at the late phase of infection. Importantly, the nlp peptides derived from both BcNEP1 and BcNEP2 induced the production of reactive oxygen species in an RLP23-dependent manner. In contrast, another necrotrophic fungus Alternaria brassicicola did not express the NLP gene in the early infection phase and exhibited no enhanced virulence in the rlp23 mutants. Collectively, these results strongly suggest that RLP23 contributes to Arabidopsis pre-invasive resistance to B. cinerea via NLP recognition at the early infection phase.
Netting and pan traps fail to identify the pollinator guild of an agricultural crop
Authors: Boyer K. J. , Fragoso F. P. , Dieterich Mabin M. E. , Brunet J.
Published: August 2020

Pollinator decline is expected to cause significant reductions in food production and plant reproduction. Quantifying the impact of pollinator decline on food production requires survey methods that can identify insect and bee species responsible for pollination of specific crops. To address this issue, we compared the effectiveness of two survey methods, netting and pan traps, at capturing the pollinators of alfalfa, Medicago sativa. Alfalfa is a major component of forage for cows and an important ingredient in chicken feed. We also examined bee species richness and diversity with these two survey methods, and compared these measures among three different colors of pan traps. Netting was more effective at capturing known pollinators of alfalfa, especially those belonging to the Bombus and Apis genera. Pan traps captured a higher bee diversity relative to netting and, like previous studies, each survey method and each trap color was more efficient at capturing certain bee genera. However, without a priori knowledge of pollinators, neither survey method could identify which of the bee species captured could pollinate alfalfa. We therefore recommend direct observations when the goal of a study is to identify pollinators or link pollinator decline to food production.