bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autophagy activated by silibinin contributes to glioma cell death via induction of oxidative stress-mediated BNIP3-dependent nuclear translocation of AIF
Authors: Wang Chongcheng , He Chuan , Lu Shan , Wang Xuanzhong , Wang Lei , Liang Shipeng , Wang Xinyu , Piao Meihua , Cui Jiayue , Chi Guangfan , Ge Pengfei 
Published: August 2020

AbstractInduction of lethal autophagy has become a strategy to eliminate glioma cells, but it remains elusive whether autophagy contributes to cell death via causing mitochondria damage and nuclear translocation of apoptosis inducing factor (AIF). In this study, we find that silibinin induces AIF translocation from mitochondria to nuclei in glioma cells in vitro and in vivo, which is accompanied with autophagy activation. In vitro studies reveal that blocking autophagy with 3MA, bafilomycin A1 or by knocking down ATG5 with SiRNA inhibits silibinin-induced mitochondrial accumulation of superoxide, AIF translocation from mitochondria to nuclei and glioma cell death. Mechanistically, silibinin activates autophagy through depleting ATP by suppressing glycolysis. Then, autophagy improves intracellular H2O2 via promoting p53-mediated depletion of GSH and cysteine and downregulation of xCT. The increased H2O2 promotes silibinin-induced BNIP3 upregulation and translocation to mitochondria. Knockdown of BNIP3 with SiRNA inhibits silibinin-induced mitochondrial depolarization, accumulation of mitochondrial superoxide, and AIF translocation from mitochondria to nuclei, as well as prevents glioma cell death. Furthermore, we find that the improved H2O2 reinforces silibinin-induced glycolysis dysfunction. Collectively, autophagy contributes to silibinin-induced glioma cell death via promotion of oxidative stress-mediated BNIP3-dependent nuclear translocation of AIF.
Overexposure to apoptosis via disrupted glial specification perturbs Drosophila macrophage function and reveals roles of the CNS during injury
Authors: Armitage Emma Louise , Roddie Hannah Grace , Evans Iwan Robert 
Published: August 2020

AbstractApoptotic cell clearance by phagocytes is a fundamental process during development, homeostasis and the resolution of inflammation. However, the demands placed on phagocytic cells such as macrophages by this process, and the limitations these interactions impose on subsequent cellular behaviours are not yet clear. Here, we seek to understand how apoptotic cells affect macrophage function in the context of a genetically tractable Drosophila model in which macrophages encounter excessive amounts of apoptotic cells. Loss of the glial-specific transcription factor Repo prevents glia from contributing to apoptotic cell clearance in the developing embryo. We show that this leads to the challenge of macrophages with large numbers of apoptotic cells in vivo. As a consequence, macrophages become highly vacuolated with cleared apoptotic cells, and their developmental dispersal and migration is perturbed. We also show that the requirement to deal with excess apoptosis caused by a loss of repo function leads to impaired inflammatory responses to injury. However, in contrast to migratory phenotypes, defects in wound responses cannot be rescued by preventing apoptosis from occurring within a repo mutant background. In investigating the underlying cause of these impaired inflammatory responses, we demonstrate that wound-induced calcium waves propagate into surrounding tissues, including neurons and glia of the ventral nerve cord, which exhibit striking calcium waves on wounding, revealing a previously unanticipated contribution of these cells during responses to injury. Taken together, these results demonstrate important insights into macrophage biology and how repo mutants can be used to study macrophage–apoptotic cell interactions in the fly embryo. Furthermore, this work shows how these multipurpose cells can be ‘overtasked’ to the detriment of their other functions, alongside providing new insights into which cells govern macrophage responses to injury in vivo.
Homoharringtonine suppresses tumor proliferation and migration by regulating EphB4-mediated β-catenin loss in hepatocellular carcinoma
Authors: Zhu Man , Gong Zhengyan , Wu Qing , Su Qi , Yang Tianfeng , Yu Runze , Xu Rui , Zhang Yanmin 
Published: August 2020

AbstractOverexpressed EphB4 conduce to tumor development and is regarded as a potential anticancer target. Homoharringtonine (HHT) has been approved for hematologic malignancies treatment, but its effect on hepatocellular carcinoma (HCC) has not been studied. This study elucidated HHT could restrain the proliferation and migration of HCC via an EphB4/β-catenin-dependent manner. We found that the antiproliferative activity of HHT in HCC cells and tumor xenograft was closely related to EphB4 expression. In HepG2, Hep3B and SMMC-7721 cells, EphB4 overexpression or EphrinB2 Fc stimulation augmented HHT-induced inhibitory effect on cell growth and migration ability, and such effect was abrogated when EphB4 was knocked down. The similar growth inhibitory effect of HHT was observed in SMMC-7721 and EphB4+/SMMC-7721 cells xenograft in vivo. Preliminary mechanistic investigation indicated that HHT directly bound to EphB4 and suppressed its expression. Data obtained from HCC patients revealed increased β-catenin expression and a positive correlation between EphB4 expression and β-catenin levels. HHT-induced EphB4 suppression promoted the phosphorylation and loss of β-catenin, which triggered regulation of β-catenin downstream signaling related to migration, resulting in the reversion of EMT in TGF-β-induced HepG2 cells. Collectively, this study provided a groundwork for HHT as an effective antitumor agent for HCC in an EphB4/β-catenin-dependent manner.
Dynamic spatiotemporal beams that combine two independent and controllable orbital-angular-momenta using multiple optical-frequency-comb lines
Authors: Zhao Zhe , Song Hao , Zhang Runzhou , Pang Kai , Liu Cong , Song Haoqian , Almaiman Ahmed , Manukyan Karapet , Zhou Huibin , Lynn Brittany , Boyd Robert W. , Tur Moshe , Willner Alan E. 
Published: August 2020

AbstractNovel forms of beam generation and propagation based on orbital angular momentum (OAM) have recently gained significant interest. In terms of changes in time, OAM can be manifest at a given distance in different forms, including: (1) a Gaussian-like beam dot that revolves around a central axis, and (2) a Laguerre-Gaussian ($$LG_{\ell ,p}$$
L

G

ℓ
,
p

) beam with a helical phasefront rotating around its own beam center. Here we explore the generation of dynamic spatiotemporal beams that combine these two forms of orbital-angular-momenta by coherently adding multiple frequency comb lines. Each line carries a superposition of multiple $$LG_{\ell ,p}$$
L

G

ℓ
,
p

modes such that each line is composed of a different $$\ell$$
ℓ
value and multiple p values. We simulate the generated beams and find that the following can be achieved: (a) mode purity up to 99%, and (b) control of the helical phasefront from 2π-6π and the revolving speed from 0.2–0.6 THz. This approach might be useful for generating spatiotemporal beams with even more sophisticated dynamic properties.
Biomimetic design of iridescent insect cuticles with tailored, self-organized cholesteric patterns
Authors: Scarangella Adriana , Soldan Vanessa , Mitov Michel 
Published: August 2020

AbstractReplicating biological patterns is promising for designing materials with multifaceted properties. Twisted cholesteric liquid crystal patterns are found in the iridescent tessellated cuticles of many insects and a few fruits. Their accurate replication is extremely difficult since discontinuous patterns and colors must coexist in a single layer without discontinuity of the structures. Here, a solution is demonstrated by addressing striped insect cuticles with a complex twisted organization. Geometric constraints are met by controlling the thermal diffusion in a cholesteric oligomer bilayer subjected to local changes in the molecular anchoring conditions. A multicriterion comparison reveals a very high level of biomimicry. Proof-of-concept prototypes of anti-counterfeiting tags are presented. The present design involves an economy of resources and a high versatility of chiral patterns unreached by the current manufacturing techniques such as metallic layer vacuum deposition, template embossing and various forms of lithography which are limited and often prohibitively expensive.
Untangling the seasonal dynamics of plant-pollinator communities
Authors: Bramon Mora Bernat , Shin Eura , CaraDonna Paul J. , Stouffer Daniel B. 
Published: August 2020

AbstractEcological communities often show changes in populations and their interactions over time. To date, however, it has been challenging to effectively untangle the mechanisms shaping such dynamics. One approach that has yet to be fully explored is to treat the varying structure of empirical communities—i.e. their network of interactions—as time series. Here, we follow this approach by applying a network-comparison technique to study the seasonal dynamics of plant-pollinator networks. We find that the structure of these networks is extremely variable, where species constantly change how they interact with each other within seasons. Most importantly, we find the holistic dynamic of plants and pollinators to be remarkably coherent across years, allowing us to reveal general rules by which species first enter, then change their roles, and finally leave the networks. Overall, our results disentangle key aspects of species’ interaction turnover, phenology, and seasonal assembly/disassembly processes in empirical plant-pollinator communities.
Single-cell TCR sequencing reveals phenotypically diverse clonally expanded cells harboring inducible HIV proviruses during ART
Authors: Gantner Pierre , Pagliuzza Amélie , Pardons Marion , Ramgopal Moti , Routy Jean-Pierre , Fromentin Rémi , Chomont Nicolas 
Published: August 2020

AbstractClonal expansions occur in the persistent HIV reservoir as shown by the duplication of proviral integration sites. However, the source of the proliferation of HIV-infected cells remains unclear. Here, we analyze the TCR repertoire of single HIV-infected cells harboring translation-competent proviruses in longitudinal samples from eight individuals on antiretroviral therapy (ART). When compared to uninfected cells, the TCR repertoire of reservoir cells is heavily biased: expanded clonotypes are present in all individuals, account for the majority of reservoir cells and are often maintained over time on ART. Infected T cell clones are detected at low frequencies in the long-lived central memory compartment and overrepresented in the most differentiated memory subsets. Our results indicate that clonal expansions highly contribute to the persistence of the HIV reservoir and suggest that reservoir cells displaying a differentiated phenotype are the progeny of infected central memory cells undergoing antigen-driven clonal expansion during ART.
Genomic characterization of malignant progression in neoplastic pancreatic cysts
Authors: Noë Michaël , Niknafs Noushin , Fischer Catherine G. , Hackeng Wenzel M. , Beleva Guthrie Violeta , Hosoda Waki , Debeljak Marija , Papp Eniko , Adleff Vilmos , White James R. , Luchini Claudio , Pea Antonio , Scarpa Aldo , Butturini Giovanni , Zamboni Giuseppe , Castelli Paola , Hong Seung-Mo , Yachida Shinichi , Hiraoka Nobuyoshi , Gill Anthony J. , Samra Jaswinder S. , Offerhaus G. Johan A. , Hoorens Anne , Verheij Joanne , Jansen Casper , Adsay N. Volkan , Jiang Wei , Winter Jordan , Albores-Saavedra Jorge , Terris Benoit , Thompson Elizabeth D. , Roberts Nicholas J. , Hruban Ralph H. , Karchin Rachel , Scharpf Robert B. , Brosens Lodewijk A. A. , Velculescu Victor E. , Wood Laura D. 
Published: August 2020

AbstractIntraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) are non-invasive neoplasms that are often observed in association with invasive pancreatic cancers, but their origins and evolutionary relationships are poorly understood. In this study, we analyze 148 samples from IPMNs, MCNs, and small associated invasive carcinomas from 18 patients using whole exome or targeted sequencing. Using evolutionary analyses, we establish that both IPMNs and MCNs are direct precursors to pancreatic cancer. Mutations in SMAD4 and TGFBR2 are frequently restricted to invasive carcinoma, while RNF43 alterations are largely in non-invasive lesions. Genomic analyses suggest an average window of over three years between the development of high-grade dysplasia and pancreatic cancer. Taken together, these data establish non-invasive IPMNs and MCNs as origins of invasive pancreatic cancer, identifying potential drivers of invasion, highlighting the complex clonal dynamics prior to malignant transformation, and providing opportunities for early detection and intervention.
Ultrafast coupled charge and spin dynamics in strongly correlated NiO
Authors: Gillmeister Konrad , Golež Denis , Chiang Cheng-Tien , Bittner Nikolaj , Pavlyukh Yaroslav , Berakdar Jamal , Werner Philipp , Widdra Wolf 
Published: August 2020

AbstractCharge excitations across an electronic band gap play an important role in opto-electronics and light harvesting. In contrast to conventional semiconductors, studies of above-band-gap photoexcitations in strongly correlated materials are still in their infancy. Here we reveal the ultrafast dynamics controlled by Hund’s physics in strongly correlated photoexcited NiO. By combining time-resolved two-photon photoemission experiments with state-of-the-art numerical calculations, an ultrafast (≲10 fs) relaxation due to Hund excitations and related photo-induced in-gap states are identified. Remarkably, the weight of these in-gap states displays long-lived coherent THz oscillations up to 2 ps at low temperature. The frequency of these oscillations corresponds to the strength of the antiferromagnetic superexchange interaction in NiO and their lifetime vanishes slightly above the Néel temperature. Numerical simulations of a two-bandt-Jmodel reveal that the THz oscillations originate from the interplay between local many-body excitations and antiferromagnetic spin correlations.
Uncertainty quantification in molecular simulations with dropout neural network potentials
Authors: Wen Mingjian , Tadmor Ellad B. 
Published: August 2020

AbstractMachine learning interatomic potentials (IPs) can provide accuracy close to that of first-principles methods, such as density functional theory (DFT), at a fraction of the computational cost. This greatly extends the scope of accurate molecular simulations, providing opportunities for quantitative design of materials and devices on scales hitherto unreachable by DFT methods. However, machine learning IPs have a basic limitation in that they lack a physical model for the phenomena being predicted and therefore have unknown accuracy when extrapolating outside their training set. In this paper, we propose a class of Dropout Uncertainty Neural Network (DUNN) potentials that provide rigorous uncertainty estimates that can be understood from both Bayesian and frequentist statistics perspectives. As an example, we develop a DUNN potential for carbon and show how it can be used to predict uncertainty for static and dynamical properties, including stress and phonon dispersion in graphene. We demonstrate two approaches to propagate uncertainty in the potential energy and atomic forces to predicted properties. In addition, we show that DUNN uncertainty estimates can be used to detect configurations outside the training set, and in some cases, can serve as a predictor for the accuracy of a calculation.
High-temperature oxidation behaviour of AlxFeCrCoNi and AlTiVCr compositionally complex alloys
Authors: Esmaily Mohsen , Qiu Yao , Bigdeli Sedigheh , Venkataraman Mahesh B. , Allanore Antoine , Birbilis Nick 
Published: August 2020

AbstractCompositionally complex alloys (CCAs), also termed as high entropy alloys (HEAs) or multi-principal element alloys (MPEAs), are being considered as a potential solution for many energy-related applications comprising extreme environments and temperatures. Herein, a review of the pertinent literature is performed in conjunction with original works characterising the oxidation behaviour of two diverse Al-containing alloys; namely a lightweight (5.06 g/cm3) single-phase AlTiVCr CCA and a multiple-phase Al0.9FeCrCoNi CCA (6.9 g/cm3). The thermogravimetric results obtained during oxidation of the alloys at 700 and 900 °C revealed that both alloys tended to obey the desired parabolic rate law. Post-exposure analysis by means of electron microscopy indicated that while the oxide scale formed on the AlTiVCr is adherent to the substrate, the scale developed on the Al0.9FeCrCoNi displays a notable spalling propensity. This study highlights the need for tailoring the protective properties of the oxide scale formed on the surface of the CCAs.
Autophagy protein ATG7 is a critical regulator of endothelial cell inflammation and permeability
Authors: Shadab Mohammad , Millar Michelle Warren , Slavin Spencer A. , Leonard Antony , Fazal Fabeha , Rahman Arshad 
Published: August 2020

AbstractEndothelial cell (EC) inflammation and permeability are critical pathogenic mechanisms in many inflammatory conditions including acute lung injury. In this study, we investigated the role of ATG7, an essential autophagy regulator with no autophagy-unrelated functions, in the mechanism of EC inflammation and permeability. Knockdown of ATG7 using si-RNA significantly attenuated thrombin-induced expression of proinflammatory molecules such as IL-6, MCP-1, ICAM-1 and VCAM-1. Mechanistic study implicated reduced NF-κB activity in the inhibition of EC inflammation in ATG7-silenced cells. Moreover, depletion of ATG7 markedly reduced the binding of RelA/p65 to DNA in the nucleus. Surprisingly, the thrombin-induced degradation of IκBα in the cytosol was not affected in ATG7-depleted cells, suggesting a defect in the translocation of released RelA/p65 to the nucleus in these cells. This is likely due to suppression of thrombin-induced phosphorylation and thereby inactivation of Cofilin1, an actin-depolymerizing protein, in ATG7-depleted cells. Actin stress fiber dynamics are required for thrombin-induced translocation of RelA/p65 to the nucleus, and indeed our results showed that ATG7 silencing inhibited this response via inactivation of Cofilin1. ATG7 silencing also reduced thrombin-mediated EC permeability by inhibiting the disassembly of VE-cadherin at adherens junctions. Together, these data uncover a novel function of ATG7 in mediating EC inflammation and permeability, and provide a mechanistic basis for the linkage between autophagy and EC dysfunction.
Molecular evolution of coxsackievirus A24v in Cuba over 23-years, 1986–2009
Authors: Fonseca Magilé C. , Pupo-Meriño Mario , García-González Luis A. , Resik Sonia , Hung Lai Heng , Muné Mayra , Rodríguez Hermis , Morier Luis , Norder Heléne , Sarmiento Luis 
Published: August 2020

AbstractCoxsackievirus A24 variant (CVA24v) is a major causative agent of acute hemorrhagic conjunctivitis outbreaks worldwide, yet the evolutionary and transmission dynamics of the virus remain unclear. To address this, we analyzed and compared the 3C and partial VP1 gene regions of CVA24v isolates obtained from five outbreaks in Cuba between 1986 and 2009 and strains isolated worldwide. Here we show that Cuban strains were homologous to those isolated in Africa, the Americas and Asia during the same time period. Two genotypes of CVA24v (GIII and GIV) were repeatedly introduced into Cuba and they arose about two years before the epidemic was detected. The two genotypes co-evolved with a population size that is stable over time. However, nucleotide substitution rates peaked during pandemics with 4.39 × 10−3 and 5.80 × 10−3 substitutions per site per year for the 3C and VP1 region, respectively. The phylogeographic analysis identified 25 and 19 viral transmission routes based on 3C and VP1 regions, respectively. Pandemic viruses usually originated in Asia, and both China and Brazil were the major hub for the global dispersal of the virus. Together, these data provide novel insight into the epidemiological dynamics of this virus and possibly other pandemic viruses.
Outbreak investigation of foot and mouth disease in Nangarhar province of war-torn Afghanistan, 2014
Authors: Wajid Abdul , Chaudhry Mamoona , Rashid Hamad Bin , Gill Shakera Sadiq , Halim Sayed Rafiullah 
Published: August 2020

AbstractAfghanistan has long history of ongoing conflicts, resulting in massive destruction of the country’s infrastructure. Illegal trade of livestock between Afghanistan and Pakistan boosted the spread of Foot & Mouth Disease (FMD). Current study was conducted to investigate outbreaks of FMD occurred between April-August 2014 in Nangarhar, Afghanistan. Descriptive data about suspected FMD cases were collected from the Civil Veterinary Hospital, Nangarhar to analyze spatio-temporal pattern of FMD. Case farms (n = 137) were selected from list of clinically confirmed FMD outbreaks available in the hospital. Control farms (n = 137) were enrolled from neighboring premises of case farms. The epidemic curve showed that the virus is continuously circulating among susceptible population. The mean age of the oldest lesion was 2.8 days. Foot & Mouth Disease was more likely to occur in female animals compared to male animals (p < 0.001). Farmers having no ability to clinically recognize FMD (OR 5.8, 95% CI 1.4–23.8); previously having any FMD case in herd (OR 11.8, 95% CI 3.0–45.8), farms where animals leave shed during day (OR 15.4, 95% CI 5.6–42.0), and farms, where neighboring farmers used to visit the premises (OR 3.5, 95% CI 1.2–9.9) were identified as risk factors. Current findings may be used to create awareness of concerned veterinary health authorities about FMD control.
Serum phosphate levels modify the impact of parathyroid hormone levels on renal outcomes in kidney transplant recipients
Authors: Doi Yohei , Hamano Takayuki , Ichimaru Naotsugu , Tomida Kodo , Obi Yoshitsugu , Fujii Naohiko , Yamaguchi Satoshi , Oka Tatsufumi , Sakaguchi Yusuke , Matsui Isao , Kaimori Jun-ya , Abe Toyofumi , Imamura Ryoichi , Takahara Shiro , Tsubakihara Yoshiharu , Nonomura Norio , Isaka Yoshitaka 
Published: August 2020

AbstractSeparate assessment of mineral bone disorder (MBD) parameters including calcium, phosphate, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D (1,25D) predict renal outcomes in kidney transplant recipients (KTRs), with conflicting results. To date, data simultaneously evaluating these parameters and interwoven relations on renal outcomes are scarce. We conducted a prospective long-term follow-up cohort study included 263 KTRs with grafts functioning at least 1 year after transplantation. The outcome was a composite of estimated GFR halving and graft loss. Cox regression analyses were employed to evaluate associations between a panel of six MBD parameters and renal outcomes. The outcome occurred in 98 KTRs during a median follow-up of 10.7 years. In a multivariate Cox analysis, intact PTH (iPTH), phosphate, and 1,25D levels were associated with the outcome (hazard ratio, 1.60 per log scale; 95% confidence interval, 1.19–2.14, 1.60 per mg/dL; 1.14–2.23 and 0.82 per 10 pg/mL; 0.68–0.99, respectively). Competing risk analysis with death as a competing event yielded a similar result. After stratification into four groups by iPTH and phosphate medians, high risks associated with high iPTH was not observed in KTRs with low phosphate levels (P-interaction < 0.1). Only KTRs not receiving active vitamin D, poor 1,25D status predicted the worse outcome (P-interaction < 0.1). High iPTH, phosphate, and low 1,25D, but not FGF23, levels predicted poor renal outcomes. Simultaneous evaluation of PTH and phosphate levels may provide additional information regarding renal allograft prognosis.